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Sample records for humans lack igb3

  1. Crystal Structures of Mouse CD1d-IGb3 Complex And Its Cognate Valpha14 T Cell Receptor Suggest a Model for Dual Recognition of Foreign And Self Glycolipids

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    Zajonc, D.M.; Saveage, P.B.; Bendelac, A.; Wilson, I.A.; Teyton, L.

    2009-05-28

    The semi-invariant Valpha14Jalpha18 T cell receptor (TCR) is expressed by regulatory NKT cells and has the unique ability to recognize chemically diverse ligands presented by CD1d. The crystal structure of CD1d complexed to a natural, endogenous ligand, isoglobotrihexosylceramide (iGb3), illustrates the extent of this diversity when compared to the binding of potent, exogenous ligands, such as alpha-galactosylceramide (alpha-GalCer). A single mode of recognition for these two classes of ligands would then appear problematic for a single T cell receptor. However, the Valpha14 TCR adopts two different conformations in the crystal where, in one configuration, the presence of a larger cavity between the two CDR3 regions could accommodate iGb3 and, in the other, a smaller cavity fits alpha-GalCer more snugly. Alternatively, the extended iGb3 headgroup could be 'squashed' upon docking of the TCR and accommodated between the CD1 and TCR surfaces. Thus, the same TCR may adopt alternative modes of recognition for these foreign and self-ligands for NKT cell activation.

  2. Characteristics of Adolescents Lacking Provider-Recommended Human Papillomavirus Vaccination.

    Science.gov (United States)

    Krakow, Melinda; Beavis, Anna; Cosides, Olivia; Rositch, Anne F

    2017-05-01

    To characterize subgroups of teens in the United States for whom provider recommendation is less likely to impact human papillomavirus (HPV) vaccine initiation. We analyzed provider-verified vaccination data from the Centers for Disease Control and Prevention's 2014 National Immunization Survey-Teen. Poisson regression models identified characteristics associated with the lack of HPV vaccine initiation among teens who received a provider recommendation (n = 12,742). Top qualitative reasons for nonvaccination among teens who received a provider recommendation were summarized (n = 1,688). Among teens with provider recommendations, males, younger teens, and white teens were less likely to initiate vaccination, compared to peers. Believing the vaccine was unnecessary, concerns about safety and lack of vaccine knowledge were common reasons parents did not initiate the vaccine, despite receiving provider recommendations. These key subgroups and barriers to HPV vaccination should be targeted with interventions that complement provider recommendation to achieve broad vaccine uptake in the United States. Published by Elsevier Inc.

  3. 34 CFR 97.118 - Applications and proposals lacking definite plans for involvement of human subjects.

    Science.gov (United States)

    2010-07-01

    ... Education PROTECTION OF HUMAN SUBJECTS Federal Policy for the Protection of Human Subjects (Basic ED Policy for Protection of Human Research Subjects) § 97.118 Applications and proposals lacking definite plans..., or contracts are submitted to departments or agencies with the knowledge that subjects may be...

  4. Antigenicity of Leishmania-Activated C-Kinase Antigen (LACK in Human Peripheral Blood Mononuclear Cells, and Protective Effect of Prime-Boost Vaccination With pCI-neo-LACK Plus Attenuated LACK-Expressing Vaccinia Viruses in Hamsters

    Directory of Open Access Journals (Sweden)

    Laura Fernández

    2018-04-01

    Full Text Available Leishmania-activated C-kinase antigen (LACK is a highly conserved protein among Leishmania species and is considered a viable vaccine candidate for human leishmaniasis. In animal models, prime-boost vaccination with LACK-expressing plasmids plus attenuated vaccinia viruses (modified vaccinia Ankara [MVA] and mutant M65 expressing LACK, has been shown to protect against cutaneous leishmaniasis (CL. Further, LACK demonstrated to induce the production of protective cytokines in patients with active CL or cured visceral leishmaniasis, as well as in asymptomatic individuals from endemic areas. However, whether LACK is capable to trigger cytokine release by peripheral blood mononuclear cells from patients cured of CL due to Leishmania infantum (L. infantum or induce protection in L. infantum-infected hamsters [visceral leishmaniasis (VL model], has not yet been analyzed. The present work examines the ex vivo immunogenicity of LACK in cured VL and CL patients, and asymptomatic subjects from an L. infantum area. It also evaluates the vaccine potential of LACK against L. infantum infection in hamsters, in a protocol of priming with plasmid pCI-neo-LACK (DNA-LACK followed by a booster with the poxvirus vectors MVA-LACK or M65-LACK. LACK-stimulated PBMC from both asymptomatic and cured subjects responded by producing IFN-γ, TNF-α, and granzyme B (Th1-type response. Further, 78% of PBMC samples that responded to soluble Leishmania antigen showed IFN-γ secretion following stimulation with LACK. In hamsters, the protocol of DNA-LACK prime/MVA-LACK or M65-LACK virus boost vaccination significantly reduced the amount of Leishmania DNA in the liver and bone marrow, with no differences recorded between the use of MVA or M65 virus vector options. In summary, the Th1-type and cytotoxic responses elicited by LACK in PBMC from human subjects infected with L. infantum, and the parasite protective effect of prime/boost vaccination in hamsters with DNA-LACK/MVA-LACK

  5. Lack of school requirements and clinician recommendations for human papillomavirus vaccination

    Directory of Open Access Journals (Sweden)

    Linda M. Niccolai

    2018-04-01

    Full Text Available Background: A strong recommendation from a clinician is one of the best predictors of human papillomavirus (HPV vaccination among adolescents, yet many clinicians do not provide effective recommendations. The objective of this study was to understand how the lack of school entry requirements for HPV vaccination influences clinicians’ recommendations. Design and Methods: Semi-structured interviews with a purposive sample of 32 clinicians were conducted in 2015 in Connecticut USA. Data were analysed using an iterative thematic approach in 2016-2017. Results: Many clinicians described presenting HPV vaccination as optional or non-urgent because it is not required for school entry. This was noted to be different from how other required vaccines were discussed. Even strong recommendations were often qualified by statements about the lack of requirements. Furthermore, lack of requirements was often raised initially by clinicians and not by parents. Many clinicians agreed that requirements would simplify the recommendation, but that parents may not agree with requirements. Personal opinions about school entry requirements were mixed. Conclusions: The current lack of school entry requirements for HPV vaccination is an important influence on clinicians’ recommendations that are often framed as optional or non-urgent. Efforts are needed to strengthen the quality of clinicians’ recommendations in a way that remains strong and focused on disease prevention yet uncoupled from the lack of requirements that may encourage delays. Additionally, greater support for requirements among clinicians may be needed to successfully enact requirements in the future.

  6. Lack of adaptation to human tetherin in HIV-1 Group O and P

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    Haworth Kevin G

    2011-09-01

    Full Text Available Abstract Background HIV-1 viruses are categorized into four distinct groups: M, N, O and P. Despite the same genomic organization, only the group M viruses are responsible for the world-wide pandemic of AIDS, suggesting better adaptation to human hosts. Previously, it has been reported that the group M Vpu protein is capable of both down-modulating CD4 and counteracting BST-2/tetherin restriction, while the group O Vpu cannot antagonize tetherin. This led us to investigate if group O, and the related group P viruses, possess functional anti-tetherin activities in Vpu or another viral protein, and to further map the residues required for group M Vpu to counteract human tetherin. Results We found a lack of activity against human tetherin for both the Vpu and Nef proteins from group O and P viruses. Furthermore, we found no evidence of anti-human tetherin activity in a fully infectious group O proviral clone, ruling out the possibility of an alternative anti-tetherin factor in this virus. Interestingly, an activity against primate tetherins was retained in the Nef proteins from both a group O and a group P virus. By making chimeras between a functional group M and non-functional group O Vpu protein, we were able to map the first 18 amino acids of group M Vpu as playing an essential role in the ability of the protein to antagonize human tetherin. We further demonstrated the importance of residue alanine-18 for the group M Vpu activity. This residue lies on a diagonal face of conserved alanines in the TM domain of the protein, and is necessary for specific Vpu-tetherin interactions. Conclusions The absence of human specific anti-tetherin activities in HIV-1 group O and P suggests a failure of these viruses to adapt to human hosts, which may have limited their spread.

  7. Lack of adaptation to human tetherin in HIV-1 Group O and P

    Science.gov (United States)

    2011-01-01

    Background HIV-1 viruses are categorized into four distinct groups: M, N, O and P. Despite the same genomic organization, only the group M viruses are responsible for the world-wide pandemic of AIDS, suggesting better adaptation to human hosts. Previously, it has been reported that the group M Vpu protein is capable of both down-modulating CD4 and counteracting BST-2/tetherin restriction, while the group O Vpu cannot antagonize tetherin. This led us to investigate if group O, and the related group P viruses, possess functional anti-tetherin activities in Vpu or another viral protein, and to further map the residues required for group M Vpu to counteract human tetherin. Results We found a lack of activity against human tetherin for both the Vpu and Nef proteins from group O and P viruses. Furthermore, we found no evidence of anti-human tetherin activity in a fully infectious group O proviral clone, ruling out the possibility of an alternative anti-tetherin factor in this virus. Interestingly, an activity against primate tetherins was retained in the Nef proteins from both a group O and a group P virus. By making chimeras between a functional group M and non-functional group O Vpu protein, we were able to map the first 18 amino acids of group M Vpu as playing an essential role in the ability of the protein to antagonize human tetherin. We further demonstrated the importance of residue alanine-18 for the group M Vpu activity. This residue lies on a diagonal face of conserved alanines in the TM domain of the protein, and is necessary for specific Vpu-tetherin interactions. Conclusions The absence of human specific anti-tetherin activities in HIV-1 group O and P suggests a failure of these viruses to adapt to human hosts, which may have limited their spread. PMID:21955466

  8. Lack of evidence for metabolism of p-phenylenediamine by human hepatic cytochrome P450 enzymes

    International Nuclear Information System (INIS)

    Stanley, Lesley A.; Skare, Julie A.; Doyle, Edward; Powrie, Robert; D'Angelo, Diane; Elcombe, Clifford R.

    2005-01-01

    p-Phenylenediamine (PPD) is a widely used ingredient in permanent hair dyes; however, little has been published on its metabolism, especially with respect to hepatic cytochrome P450 (CYP)-mediated oxidation. This is regarded as a key step in the activation of carcinogenic arylamines that ultimately leads to the development of bladder cancer. Most epidemiology studies show no significant association between personal use of hair dyes and bladder cancer, but one recent study reported an increased risk of bladder cancer in women who were frequent users of permanent hair dyes. The aim of the present study was to use intact human hepatocytes, human liver microsomes, and heterologously expressed human CYPs to determine whether PPD is metabolised by hepatic CYPs to form an N-hydroxylamine. p-Phenylenediamine was N-acetylated by human hepatocytes to form N-acetylated metabolites, but there was no evidence for the formation of mono-oxygenated metabolites or for enzyme-mediated covalent binding of 14 C-PPD to microsomal protein. In contrast, 2-aminofluorene underwent CYP-mediated metabolism to ≥4 different hydroxylated metabolites. The lack of evidence for hepatic CYP-mediated metabolism of PPD is inconsistent with the hypothesis that this compound plays a causal role in the development of bladder cancer via a mode of action involving hepatic metabolism to an N-hydroxyarylamine

  9. Lack of tissue renewal in human adult Achilles tendon is revealed by nuclear bomb 14C

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    Heinemeier, Katja Maria; Schjerling, Peter; Heinemeier, Jan; Magnusson, Stig Peter; Kjaer, Michael

    2013-01-01

    Tendons are often injured and heal poorly. Whether this is caused by a slow tissue turnover is unknown, since existing data provide diverging estimates of tendon protein half-life that range from 2 mo to 200 yr. With the purpose of determining life-long turnover of human tendon tissue, we used the 14C bomb-pulse method. This method takes advantage of the dramatic increase in atmospheric levels of 14C, produced by nuclear bomb tests in 1955–1963, which is reflected in all living organisms. Levels of 14C were measured in 28 forensic samples of Achilles tendon core and 4 skeletal muscle samples (donor birth years 1945–1983) with accelerator mass spectrometry (AMS) and compared to known atmospheric levels to estimate tissue turnover. We found that Achilles tendon tissue retained levels of 14C corresponding to atmospheric levels several decades before tissue sampling, demonstrating a very limited tissue turnover. The tendon concentrations of 14C approximately reflected the atmospheric levels present during the first 17 yr of life, indicating that the tendon core is formed during height growth and is essentially not renewed thereafter. In contrast, 14C levels in muscle indicated continuous turnover. Our observation provides a fundamental premise for understanding tendon function and pathology, and likely explains the poor regenerative capacity of tendon tissue.—Heinemeier, K. M., Schjerling, P., Heinemeier, J., Magnusson, S. P., Kjaer, M. Lack of tissue renewal in human adult Achilles tendon is revealed by nuclear bomb 14C. PMID:23401563

  10. Some remarks on the effects of drugs, lack of sleep and loud noise on human performance.

    NARCIS (Netherlands)

    Sanders, A.F. & A.A. Bunt.

    1971-01-01

    Some literature is reviewed on the effect of some drugs, (amphetamine, hypnotics, alcohol), loud noise and sleep loss in test of time estimation, decision making, long term performance and short term memory. Results are most clear with respect to amphetamine, hypnotics and lack of sleep, in that

  11. Low calorie sweeteners: Evidence remains lacking for effects on human gut function.

    Science.gov (United States)

    Bryant, Charlotte; Mclaughlin, John

    2016-10-01

    The importance of nutrient induced gut-brain signalling in the regulation of human food intake has become an increasing focus of research. Much of the caloric excess consumed comes from dietary sugars, but our knowledge about the mechanisms mediating the physiological and appetitive effects of sweet tastants in the human gut and gut-brain axis is far from complete. The comparative effects of natural sugars vs low calorie sweeteners are also poorly understood. Research in animal and cellular models has suggested a key functional role in gut endocrine cells for the sweet taste receptors previously well described in oral taste. However human studies to date have very consistently failed to show that activation of the sweet taste receptor by low calorie sweeteners placed in the human gut fails to replicate any of the effects on gastric motility, gut hormones or appetitive responses evoked by caloric sugars. Copyright © 2016. Published by Elsevier Inc.

  12. Atypical scrapie prions from sheep and lack of disease in transgenic mice overexpressing human prion protein.

    Science.gov (United States)

    Wadsworth, Jonathan D F; Joiner, Susan; Linehan, Jacqueline M; Balkema-Buschmann, Anne; Spiropoulos, John; Simmons, Marion M; Griffiths, Peter C; Groschup, Martin H; Hope, James; Brandner, Sebastian; Asante, Emmanuel A; Collinge, John

    2013-11-01

    Public and animal health controls to limit human exposure to animal prions are focused on bovine spongiform encephalopathy (BSE), but other prion strains in ruminants may also have zoonotic potential. One example is atypical/Nor98 scrapie, which evaded statutory diagnostic methods worldwide until the early 2000s. To investigate whether sheep infected with scrapie prions could be another source of infection, we inoculated transgenic mice that overexpressed human prion protein with brain tissue from sheep with natural field cases of classical and atypical scrapie, sheep with experimental BSE, and cattle with BSE. We found that these mice were susceptible to BSE prions, but disease did not develop after prolonged postinoculation periods when mice were inoculated with classical or atypical scrapie prions. These data are consistent with the conclusion that prion disease is less likely to develop in humans after exposure to naturally occurring prions of sheep than after exposure to epizootic BSE prions of ruminants.

  13. Lack of association between human plasma oxytocin and interpersonal trust in a Prisoner's Dilemma paradigm.

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    James C Christensen

    Full Text Available Expanding interest in oxytocin, particularly the role of endogenous oxytocin in human social behavior, has created a pressing need for replication of results and verification of assay methods. In this study, we sought to replicate and extend previous results correlating plasma oxytocin with trust and trustworthy behavior. As a necessary first step, the two most commonly used commercial assays were compared in human plasma via the addition of a known quantity of exogenous oxytocin, with and without sample extraction. Plasma sample extraction was found to be critical in obtaining repeatable concentrations of oxytocin. In the subsequent trust experiment, twelve samples in duplicate, from each of 82 participants, were collected over approximately six hours during the performance of a Prisoner's Dilemma task paradigm that stressed human interpersonal trust. We found no significant relationship between plasma oxytocin concentrations and trusting or trustworthy behavior. In light of these findings, previous published work that used oxytocin immunoassays without sample extraction should be reexamined and future research exploring links between endogenous human oxytocin and trust or social behavior should proceed with careful consideration of methods and appropriate biofluids for analysis.

  14. Lack of evidence for integration of Trypanosoma cruzi minicircle DNA in South American human genomes

    Czech Academy of Sciences Publication Activity Database

    Flegontova, Olga; Lukeš, Julius; Flegontov, Pavel

    2012-01-01

    Roč. 42, č. 5 (2012), s. 437-441 ISSN 0020-7519 Grant - others:GA MŠk(CZ) LM2010005 Institutional support: RVO:60077344 Keywords : Trypanosoma cruzi * Kinetoplast minicircle * Chagas disease * Horizontal gene transfer * Human genome Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.637, year: 2012 http://www.sciencedirect.com/science/article/pii/S0020751912000781

  15. Lack of Association between Human Plasma Oxytocin and Interpersonal Trust in a Prisoners Dilemma Paradigm

    Science.gov (United States)

    2014-12-30

    from data using rodent models. Zhang et al. [17] used two- dimensional liquid chromatography -tandem mass spectrometry (2D LC-MS/MS) to demonstrate that...DM, Lin Z, Steenwyk R (2011) Ultra sensitive quantitation of endogenous oxytocin in rat and human plasma using a two-dimensional liquid chromatography ... Handbook of motivation and cognition: Foundations of social behavior, 1, 96–121. 42. Feldman R, Weller A, Zagoory-Sharon O, Levine A (2007) Evidence for

  16. Lack of association between human herpesvirus and vestibular schwannoma: analysis of 121 cases.

    Science.gov (United States)

    Bhimrao, Sanjiv K; Maguire, John; Garnis, Cathie; Tang, Patrick; Lea, Jane; Akagami, Ryojo; Westerberg, Brian D

    2015-03-01

    To assess for the presence of human herpesvirus (HHV) using immunohistochemical and polymerase chain reaction (PCR) assay in surgically excised vestibular schwannoma (VS) samples. Cross-sectional study. A retrospective laboratory-based study of tumors from patients with vestibular schwannoma. Tissue microarrays (TMAs) representing sporadic and NF2-associated VS from 121 patients, as well as appropriate positive and negative controls, were studied. TMA sections were immunostained using antibodies directed against HHV-1, HHV-2, HHV-3, HHV-4, HHV-5, and HHV-8. PCR was used for the detection of all 8 known human herpesviruses. There was no detectable HHV (HHV-1, HHV-2, HHV-3, HHV-4, HHV-5, HHV-8) by immunohistochemistry in any of the 121 cases of sporadic and NF2 cases analyzed. These data were further validated by DNA sequence analyses using PCR in a subset of the VS samples, all of which were found to be negative for all HHV. The data offer no support for an association between HHV and the development of sporadic or NF2-associated VS in humans. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

  17. Phenylbutyrate Sensitizes Human Glioblastoma Cells Lacking Wild-Type P53 Function to Ionizing Radiation

    International Nuclear Information System (INIS)

    Lopez, Carlos A.; Feng, Felix Y.; Herman, Joseph M.; Nyati, Mukesh K.; Lawrence, Theodore S.; Ljungman, Mats

    2007-01-01

    Purpose: Histone deacetylase (HDAC) inhibitors induce growth arrest, differentiation, and apoptosis in cancer cells. Phenylbutyrate (PB) is a HDAC inhibitor used clinically for treatment of urea cycle disorders. Because of its low cytotoxicity, cerebrospinal fluid penetration, and high oral bioavailability, we investigated PB as a potential radiation sensitizer in human glioblastoma cell lines. Methods and Materials: Four glioblastoma cell lines were selected for this study. Phenylbutyrate was used at a concentration of 2 mM, which is achievable in humans. Western blots were used to assess levels of acetylated histone H3 in tumor cells after treatment with PB. Flow cytometry was used for cell cycle analysis. Clonogenic assays were performed to assess the effect of PB on radiation sensitivity. We used shRNA against p53 to study the role of p53 in radiosensitization. Results: Treatment with PB alone resulted in hyperacetylation of histones, confirmed by Western blot analysis. The PB alone resulted in cytostatic effects in three cell lines. There was no evidence of G 1 arrest, increase in sub-G 1 fraction or p21 protein induction. Clonogenic assays showed radiosensitization in two lines harboring p53 mutations, with enhancement ratios (± SE) of 1.5 (± 0.2) and 1.3 (± 0.1), respectively. There was no radiopotentiating effect in two cell lines with wild-type p53, but knockdown of wild-type p53 resulted in radiosensitization by PB. Conclusions: Phenylbutyrate can produce p21-independent cytostasis, and enhances radiation sensitivity in p53 mutant human glioblastoma cells in vitro. This suggests the potential application of combined PB and radiotherapy in glioblastoma harboring mutant p53

  18. Meta-analysis reveals a lack of sexual dimorphism in human amygdala volume.

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    Marwha, Dhruv; Halari, Meha; Eliot, Lise

    2017-02-15

    The amygdala plays a key role in many affective behaviors and psychiatric disorders that differ between men and women. To test whether human amygdala volume (AV) differs reliably between the sexes, we performed a systematic review and meta-analysis of AVs reported in MRI studies of age-matched healthy male and female groups. Using four search strategies, we identified 46 total studies (58 matched samples) from which we extracted effect sizes for the sex difference in AV. All data were converted to Hedges g values and pooled effect sizes were calculated using a random-effects model. Each dataset was further meta-regressed against study year and average participant age. We found that uncorrected amygdala volume is about 10% larger in males, with pooled sex difference effect sizes of g=0.581 for right amygdala (κ=28, n=2022), 0.666 for left amygdala (κ=28, n=2006), and 0.876 for bilateral amygdala (κ=16, n=1585) volumes (all p values brain volume (TBV; g=1.278, pbrain size in males. Among studies reporting AVs normalized for ICV or TBV, sex difference effect sizes were small and not statistically significant: g=0.171 for the right amygdala (p=0.206, κ=13, n=1560); 0.233 for the left amygdala (p=0.092, κ=12, n=1512); and 0.257 for bilateral volume (p=0.131, κ=5, n=1629). These values correspond to less than 0.1% larger corrected right AV and 2.5% larger corrected left AV in males compared to females. In summary, AV is not selectively enhanced in human males, as often claimed. Although we cannot rule out subtle male-female group differences, it is not accurate to refer to the human amygdala as "sexually dimorphic." Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Lack of FasL expression in cultured human retinal pigment epithelial cells

    DEFF Research Database (Denmark)

    Kaestel, C G; Madsen, H O; Prause, J U

    2001-01-01

    Retinal pigment epithelial (RPE) cells have been proposed to play a part in maintaining the eye as an immune privileged organ. However, our knowledge of the implicated mechanism is still sparse. Fas ligand (FasL) expression of RPE cells is generally recognized to be essential for the immune...... privilege of the eye, but due to contradictory published results, it is unclear whether RPE cells express this molecule. The purpose of this study was to investigate the expression of FasL in RPE cells in vitro and in vivo. Cultured human fetal and adult RPE cells were examined by flow cytometry, Western...... blotting, RT-PCR and RNase Protection assay for FasL expression. Additionally, sections of ocular tissue were stained for FasL by immunohistochemistry. None of the used methods indicated FasL expression in cultured fetal or adult RPE cells of various passages. However, RPE cells in vivo, as judged from...

  20. Lack of influence of GTP cyclohydrolase gene (GCH1 variations on pain sensitivity in humans

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    Dionne Raymond A

    2007-03-01

    Full Text Available Abstract Objectives To assess the effect of variations in GTP cyclohydrolase gene (GCH1 on pain sensitivity in humans. Methods Thermal and cold pain sensitivity were evaluated in a cohort of 735 healthy volunteers. Among this cohort, the clinical pain responses of 221 subjects after the surgical removal of impacted third molars were evaluated. Genotyping was done for 38 single nucleotide polymorphisms (SNPs whose heterozygosity > 0.2 in GCH1. Influence of the genetic variations including SNPs and haplotypes on pain sensitivity were analyzed. Results Minor allele frequencies and linkage disequilibrium show significant differences in European Americans, African Americans, Hispanic Americans and Asian Americans. Association analyses in European Americans do not replicate the previously reported important influence of GCH1 variations on pain sensitivity. Conclusion Considering population stratification, previously reported associations between GCH1 genetic variations and pain sensitivity appear weak or negligible in this well characterized model of pain.

  1. Lack of detection of human papillomavirus infection by hybridization test in prostatic biopsies

    International Nuclear Information System (INIS)

    Gazzaz, Faten S; Mosli, Hisham A

    2009-01-01

    To explore the possibility of finding human papillomavirus (HPV) infection in the prostate tissue of a cohort of Saudi men presenting with benign prostatic hyperplasia (BPH) or prostate cancer. A cohort study on prospectively collected tissue samples was conducted at King Abdulaziz University Hospital (KAUH), Jeddah, Kingdom of Saudi Arabia from March 2007 to December 2008 on a total of 56 male patients, age range 50-93 years (average 68), diagnosed as having BPH or prostate cancer. The HPV DNA hybridization by hybrid capture 2 technology was performed on prostate biopsies of these patients to detect 18 types of HPV infection, and differentiate between 2 HPV DNA groups, the low-risk types, and the high/intermediate risk types.The tissues of all the prostatic biopsies were negative for HPV DNA. Our results, using the hybridization test, indicate that it is unlikely that HPV-16 or HPV-18, or the other tested subtypes, enhance the risk of prostate cancer. (author)

  2. Lack of close relationship between three strains of human rhinoviruses as determined by their RNA sequences.

    Science.gov (United States)

    Yin, F H; Lonberg-Holm, K; Chan, S P

    1973-07-01

    The possible genomic homologies between three serotypes of human rhinoviruses (HRV 1A, HRV 2, and HRV 14) were investigated. First we confirmed that these viruses were unrelated by the criterion of the absence of common antigenic determinants on the surfaces of the native virions, as detected by cross-neutralization of complementfixation. RNA-RNA hybridization was then examined with purified, highly radioactive, double-stranded, replicative-form RNA and excess single-stranded virion RNA. Single-stranded RNA showed 100% homology with the minus strand from the replicative-form RNA of the same type of virus. HRV 1A, HRV 2, and HRV 14 showed low intertypic homologies; these were not significantly greater than those found between the rhinoviruses and polivirus, which were used as a negative control. The immunological relationship and the RNA homology between HRV 1A and HRV 1B were also examined by the above techniques. It was confirmed that HRV 1A and HRV 1B share some surface determinants and it was also found that HRV 1B RNA shares 70% homology with HRV 1A RNA.

  3. Lack of cilia and differentiation defects in the liver of human foetuses with the Meckel syndrome.

    Science.gov (United States)

    Clotman, Frédéric; Libbrecht, Louis; Killingsworth, Murray C; Loo, Christine C K; Roskams, Tania; Lemaigre, Frédéric P

    2008-03-01

    Meckel syndrome is an autosomal-recessive disease characterized by a combination of renal cysts, anomalies of the central nervous system, polydactyly and ductal plate malformations (DPM), which are hepatic anomalies consisting of excessive and abnormal foetal biliary structures. Among the genomic loci associated with Meckel syndrome, mutations in four genes were recently identified. These genes code for proteins associated with primary cilia and are possibly involved in cell differentiation. The aim of the present work was to investigate the formation of the primary cilia and the differentiation of the hepatic cells in foetuses with Meckel syndrome. Sections of livers from human foetuses with Meckel syndrome were analysed by immunofluorescence, immunohistochemistry and electron microscopy. The primary cilia of the biliary cells were absent in some Meckel foetuses, but were present in others. In addition, defects in hepatic differentiation were observed in Meckel livers, as evidenced by the presence of hybrid cells co-expressing hepatocytic and biliary markers. Defects in cilia formation occur in some Meckel livers, and most cases show DPM associated with abnormal hepatic cell differentiation. Because differentiation precedes the formation of the cilia during liver development, we propose that defective differentiation may constitute the initial defect in the liver of Meckel syndrome foetuses.

  4. Lack of oxygen effect in glutathione-deficient human cells in culture

    International Nuclear Information System (INIS)

    Edgren, M.; Larsson, A.; Nilsson, K.; Revesz, L.; Scott, O.C.A.

    1980-01-01

    The frequency of X-ray-induced DNA breaks was determined in human cell lines which are deficient in glutathione synthetase and have a greatly reduced glutathione content. Hydroxyapatite chromatography was used for the estimation of the DNA breaks in cell cultures, which were derived either from lymphoblasts transformed by infection with EB virus or from fibroblasts. The dose-effect relationship for the induction of breaks when radiation exposure was made in argon, was similar to that found when exposure was made in air. In control cultures with normal glutathione content, the induction of breaks was enhanced when irradiation was made under aerobic, instead of anaerobic, conditions. Treatment of the glutathione-deficient cells with the hypoxic radiosensitizer misonidazole did not enhance the induction of breaks by radiation delivered either in air or in argon. In control cultures, radiation induction of breaks was enhanced by misonidazole under anaerobic but not under aerobic conditions. When the glutathione-deficient cells were pretreated with cysteamine however, irradiation in the absence of oxygen resulted in a decreased frequency of DNA breaks. (author)

  5. Lack of support for the association between GAD2 polymorphisms and severe human obesity.

    Directory of Open Access Journals (Sweden)

    Michael M Swarbrick

    2005-09-01

    Full Text Available The demonstration of association between common genetic variants and chronic human diseases such as obesity could have profound implications for the prediction, prevention, and treatment of these conditions. Unequivocal proof of such an association, however, requires independent replication of initial positive findings. Recently, three (-243 A>G, +61450 C>A, and +83897 T>A single nucleotide polymorphisms (SNPs within glutamate decarboxylase 2 (GAD2 were found to be associated with class III obesity (body mass index > 40 kg/m2. The association was observed among 188 families (612 individuals segregating the condition, and a case-control study of 575 cases and 646 lean controls. Functional data supporting a pathophysiological role for one of the SNPs (-243 A>G were also presented. The gene GAD2 encodes the 65-kDa subunit of glutamic acid decarboxylase-GAD65. In the present study, we attempted to replicate this association in larger groups of individuals, and to extend the functional studies of the -243 A>G SNP. Among 2,359 individuals comprising 693 German nuclear families with severe, early-onset obesity, we found no evidence for a relationship between the three GAD2 SNPs and obesity, whether SNPs were studied individually or as haplotypes. In two independent case-control studies (a total of 680 class III obesity cases and 1,186 lean controls, there was no significant relationship between the -243 A>G SNP and obesity (OR = 0.99, 95% CI 0.83-1.18, p = 0.89 in the pooled sample. These negative findings were recapitulated in a meta-analysis, incorporating all published data for the association between the -243G allele and class III obesity, which yielded an OR of 1.11 (95% CI 0.90-1.36, p = 0.28 in a total sample of 1,252 class III obese cases and 1,800 lean controls. Moreover, analysis of common haplotypes encompassing the GAD2 locus revealed no association with severe obesity in families with the condition. We also obtained functional data for the

  6. Lack of Support for the Association Between GAD2 Polymorphisms andSevere Human Obesity

    Energy Technology Data Exchange (ETDEWEB)

    Swarbrick, Michael M.; Waldenmaier, Bjorn; Pennacchio, Len A.; Lind,Denise L.; Cavazos, Martha M.; Geller, Frank; Merriman, Raphael; Ustaszewska, Anna; Malloy, Mary; Scherag, Andre; Hsueh, Wen-Chi; Rief,Winfried; Mauvais-Jarvis, Franck; Pullinger, Clive R.; Kane, John P.; Dent, Robert; McPherson, Ruth; Kwok, Pui-Yan; Hinney, Anke; Hebebrand,Johannes; Vaisse, Christian

    2004-11-17

    Demonstration of association between common genetic variants and chronic human diseases such as obesity could have profound implications for the prediction, prevention and treatment of these conditions. Unequivocal proof of such an association, however, requires adherence to established methodological guidelines, which include independent replication of initial positive findings. Recently, single nucleotide polymorphisms (SNPs) within GAD2 were found to be associated with class III obesity (BMI > 40 kg/m2) in 188 families (612 individuals) segregating the condition and a case-control study of 575 cases and 646 lean controls. Functional data supporting a pathophysiological role for one of the SNPs (-243A>G) were also presented. In the present study, we attempted to replicate this association in larger groups of subjects, and to extend the functional studies of the -243A>G SNP. In 2,327 subjects comprising 692 German nuclear families with severe, early-onset obesity, we found no evidence for a relationship between the three GAD2 SNPs and obesity, whether SNPs were studied individually or as haplotypes. In two independent case-control studies (a total of 680 class III obesity cases and 1,186 lean controls), there was no significant relationship between the -243A>G SNP and obesity (odds ratio (OR) = 0.99, 95% CI 0.83 - 1.18,in the pooled sample). These negative findings were reinforced by a meta-analysis for the association between the 243G allele and class III obesity, which yielded an OR of 1.11 (95% CI 0.90 - 1.36) in a total sample of 1,252 class III obese cases and 1,800 lean controls. Finally,we were unable to confirm or extend the functional data pertaining to the -243A>G variant. Potential confounding variables in association studies involving common variants and complex diseases (low power to detect modest genetic effects, over-interpretation of marginal data, population stratification and biological plausibility) are also discussed in the context of GAD2 and

  7. Human NKCC2 cation–Cl– co-transporter complements lack of Vhc1 transporter in yeast vacuolar membranes.

    Science.gov (United States)

    Petrezselyova, Silvia; Dominguez, Angel; Herynkova, Pavla; Macias, Juan F; Sychrova, Hana

    2013-10-01

    Cation–chloride co-transporters serve to transport Cl– and alkali metal cations. Whereas a large family of these exists in higher eukaryotes, yeasts only possess one cation–chloride co-transporter, Vhc1, localized to the vacuolar membrane. In this study, the human cation–chloride co-transporter NKCC2 complemented the phenotype of VHC1 deletion in Saccharomyces cerevisiae and its activity controlled the growth of salt-sensitive yeast cells in the presence of high KCl, NaCl and LiCl. A S. cerevisiae mutant lacking plasma-membrane alkali–metal cation exporters Nha1 and Ena1-5 and the vacuolar cation–chloride co-transporter Vhc1 is highly sensitive to increased concentrations of alkali–metal cations, and it proved to be a suitable model for characterizing the substrate specificity and transport activity of human wild-type and mutated cation–chloride co-transporters. Copyright © 2013 John Wiley & Sons, Ltd.

  8. Expression and characterization of recombinant human factor V and a mutant lacking a major portion of the connecting region

    International Nuclear Information System (INIS)

    Kane, W.H.; Devore-Carter, D.; Ortel, T.L.

    1990-01-01

    Human coagulation factor V is a protein cofactor that is an essential component of the prothrombinase complex. A full-length factor V cDNA has been subcloned into the mammalian expression vector pDX and used to transfect COS cells. Approximately 95 ± 4% of the recombinant human factor V (rHFV) synthesized in COS cells is secreted into the culture medium. Factor V activity determined by fibrometer assay increased approximately 5-fold from 0.027 ± 0.012 to 0.124 ± 0.044 unit/mL following activation by the factor V activating enzyme from Russell's viper venom (RVV-V). A chromogenic assay specific for factor Va indicated that recombinant factor V had 3.8 ± 1.3% of the activity of the activated protein. The estimated specific activity of the recombinant factor Va was approximately 1,800 ± 500 units/mg, which is similar to the specific activity of purified plasma factor Va of 1,700-2,000 units/mg. Immunoprecipitation of [ 35 S]methionine-labeled rHFV revealed a single high molecular mass component. Treatment of rHFV with thrombin or RVV-V resulted in the formation of proteolytic products that were similar to those seen with plasma factor V. The authors have also expressed a mutant, rHFV-des-B 811-1441 , that lacks a large portion of the highly glycosylated connecting region that is present in factor V. This mutant constitutively expressed 38 ± 7% of the activity of the RVV-V-activated protein. These results suggest that one of the functions of the large connecting region in factor V is to inhibit constitutive procoagulant activity

  9. Oral human papillomavirus (HPV) infection in men who have sex with men: prevalence and lack of anogenital concordance

    Science.gov (United States)

    King, Eleanor M; Gilson, Richard; Beddows, Simon; Soldan, Kate; Panwar, Kavita; Young, Carmel; Jit, Mark; Edmunds, W John; Sonnenberg, Pam

    2015-01-01

    Objectives To estimate the prevalence of oral detectable human papillomavirus (HPV) DNA in HIV-negative men who have sex with men (MSM) attending a sexual health clinic in London and concordance with anogenital HPV infection. Such data are important to improve our understanding of the epidemiology of oral HPV and the potential use of vaccines to prevent oropharyngeal cancers. Methods Paired oral rinse samples and anogenital samples were available from 151 HIV-negative MSM within a larger cross-sectional survey. All samples were tested in parallel for 21 types of HPV DNA using an in-house assay. Results The median age of participants was 30 (IQR 25–35). The prevalence of any oral HPV and of high-risk HPV (HR-HPV) was 13.7% (n=21; 95% CI 8.7 to 20.2) and 5.9% (n=9; 95% CI 2.7 to 10.9) compared with 64.9% (n=98; 95% CI 56.7 to 72.5) and 34.4% (n=52; 95% CI 26.9 to 42.6) in any anogenital sample, respectively. The prevalence of types prevented by the bivalent (HPV16/18), quadrivalent (HPV6/11/16/18) and nonavalent (HPV6/11/16/18/31/33/45/52/58) vaccines was 1.3% (95% CI 0.2 to 4.7), 2.6% (95% CI 0.7 to 6.6) and 4.6% (95% CI 1.9 to 9.3), respectively. There was no concordance between HPV genotypes detected in oral and anogenital sites. Conclusions HR-HPV DNA, including HPV 16/18, was detected in oral specimens from HIV-negative MSM attending sexual health clinics, suggesting a potential role for vaccination, but is far less common than anogenital infection. How this relates to the risk and natural history of HPV-related head and neck cancers warrants further study. Lack of concordance with anogenital infection also suggests that oral HPV infection should be considered separately when estimating potential vaccine impact. PMID:25887283

  10. Lack of immunogenicity of ice structuring protein type III HPLC12 preparation administered by the oral route to human volunteers

    DEFF Research Database (Denmark)

    Crevel, R W R; Cooper, K J; Poulsen, Lars K.

    2007-01-01

    Before a novel protein can be used in foods, its potential allergenicity must be assessed. In this study, healthy volunteers consumed ice structuring protein (ISP) Type III preparation or a control material 5 days a week for a total of 8 weeks. General measures of health were recorded during...... background against which to interpret the results. Nevertheless, the absence of an immune response using a protocol which could have been expected to result in a response with a strongly immunogenic protein, confirms the conclusions of earlier published work, and attests to the lack of allergenicity of ISP...

  11. Once again about surrogacy, because human rights violations are increasing as a consequence of the lack of legal framework

    Directory of Open Access Journals (Sweden)

    Eleonora LAMM

    2016-07-01

    Full Text Available This paper seeks to highlight the ever more eloquent, frequent and manifest reality of surrogacy and how the strategies that are being used to remedy or avoid the legal prohibition violate fundamental human rights. It is based on the premisse that the legal prohibition does not prevent the practice, but makes a complex technique even more contentious, violating rights.

  12. Mice lacking lipid droplet-associated hydrolase, a gene linked to human prostate cancer, have normal cholesterol ester metabolism

    DEFF Research Database (Denmark)

    Kory, Nora; Grond, Susanne; Kamat, Siddhesh S

    2017-01-01

    Variations in the gene LDAH (C2ORF43), which encodes lipid droplet-associated hydrolase (LDAH), are among few loci associated with human prostate cancer. Homologs of LDAH have been identified as proteins of lipid droplets (LDs). LDs are cellular organelles that store neutral lipids...

  13. Human IgG lacking effector functions demonstrate lower FcRn-binding and reduced transplacental transport

    NARCIS (Netherlands)

    Stapleton, Nigel M.; Armstrong-Fisher, Sylvia S.; Andersen, Jan Terje; van der Schoot, C. Ellen; Porter, Charlene; Page, Kenneth R.; Falconer, Donald; de Haas, Masja; Williamson, Lorna M.; Clark, Michael R.; Vidarsson, Gestur; Armour, Kathryn L.

    2018-01-01

    We have previously generated human IgG1 antibodies that were engineered for reduced binding to the classical Fcγ receptors (FcγRI-III) and C1q, thereby eliminating their destructive effector functions (constant region G1Δnab). In their potential use as blocking agents, favorable binding to the

  14. Human IgG lacking effector functions demonstrate lower FcRn-binding and reduced transplacental transport.

    Science.gov (United States)

    Stapleton, Nigel M; Armstrong-Fisher, Sylvia S; Andersen, Jan Terje; van der Schoot, C Ellen; Porter, Charlene; Page, Kenneth R; Falconer, Donald; de Haas, Masja; Williamson, Lorna M; Clark, Michael R; Vidarsson, Gestur; Armour, Kathryn L

    2018-03-01

    We have previously generated human IgG1 antibodies that were engineered for reduced binding to the classical Fcγ receptors (FcγRI-III) and C1q, thereby eliminating their destructive effector functions (constant region G1Δnab). In their potential use as blocking agents, favorable binding to the neonatal Fc receptor (FcRn) is important to preserve the long half-life typical of IgG. An ability to cross the placenta, which is also mediated, at least in part, by FcRn is desirable in some indications, such as feto-maternal alloimmune disorders. Here, we show that G1Δnab mutants retain pH-dependent binding to human FcRn but that the amino acid alterations reduce the affinity of the IgG1:FcRn interaction by 2.0-fold and 1.6-fold for the two antibodies investigated. The transport of the modified G1Δnab mutants across monolayers of human cell lines expressing FcRn was approximately 75% of the wild-type, except that no difference was observed with human umbilical vein endothelial cells. G1Δnab mutation also reduced transport in an ex vivo placenta model. In conclusion, we demonstrate that, although the G1Δnab mutations are away from the FcRn-binding site, they have long-distance effects, modulating FcRn binding and transcellular transport. Our findings have implications for the design of therapeutic human IgG with tailored effector functions. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Lack of evidence from HPLC 32P-post-labelling for tamoxifen-DNA adducts in the human endometrium.

    Science.gov (United States)

    Carmichael, P L; Sardar, S; Crooks, N; Neven, P; Van Hoof, I; Ugwumadu, A; Bourne, T; Tomas, E; Hellberg, P; Hewer, A J; Phillips, D H

    1999-02-01

    Tamoxifen is associated with an increased incidence of endometrial cancer in women. It is also a potent carcinogen in rat liver and forms covalent DNA adducts in this tissue. A previous study exploring DNA adducts in human endometria, utilizing thin layer chromatography 32P-postlabelling, found no evidence for adducts in tamoxifen-treated women [Carmichael,P.L., Ugwumadu,A.H.N., Neven,P., Hewer,A.J., Poon,G.K. and Phillips,D.H. (1996) Cancer Res., 56, 1475-1479]. However, subsequent work utilizing HPLC 32P-post-labelling [Hemminki,K., Ranjaniemi,H., Lindahl,B. and Moberger,B. (1996) Cancer Res., 56, 4374-4377] suggested that very low levels could be detected. We have sought to investigate this question further by reproducing the HPLC methodology at two centres, and analysing endometrial DNA from 20 patients treated with 20 mg/day tamoxifen for between 22 and 65 months. Liver DNA isolated from tamoxifen-treated rats was used as a positive control. We found no convincing evidence for tamoxifen-derived DNA adducts in human endometrium. HPLC elution profiles of post-labelled DNA from tamoxifen-treated women were indistinguishable from those obtained with DNA from 14 untreated women and from six women taking toremifene, an analogue of tamoxifen.

  16. Lack of an association of miR-938 SNP in IDDM10 with human type 1 diabetes

    Directory of Open Access Journals (Sweden)

    Mi Xiaofan

    2011-10-01

    Full Text Available Abstract MicroRNAs (miRNAs are a newly discovered type of small non-protein coding RNA that function in the inhibition of effective mRNA translation, and may serve as susceptibility genes for various disease developments. The SNP rs12416605, located in human type 1 diabetes IDDM10 locus, changes the seeding sequence (UGU[G/A]CCC of miRNA miR-938 and potentially alters miR-938 targets, including IL-16 and IL-17A. In an attempt to test whether miR-938 may be a susceptibility gene for IDDM10, we assessed the possible association of the miR-938 SNP with T1D in an American Caucasian cohort of 622 patients and 723 healthy controls by TaqMan assay. Our current data do not support the association between the SNP in miR-938 and type 1 diabetes.

  17. Between Shame and Lack of Responsibility: The Articulation of Emotions among Female Returnees of Human Trafficking in Northern Vietnam

    Directory of Open Access Journals (Sweden)

    Runa Lazzarino

    2014-11-01

    Full Text Available Drawing on qualitative research conducted with some female residents of a shelter for victims of trafficking located in Lào Cai, an urban centre on the Northern Vietnamese border with China, the intention, in this article, is to explore some of their expressed feelings and emotions. These seem to oscillate between a sense of shame and guilt, and a sense of self-pity and victimization. Such oscillation finds significant correspondence at two broader levels, that of Vietnamese society and of the international ideological discourse of human trafficking, which both present a stigmatizing, yet compassionate, approach to the returnees of trafficking. In this way, the aim is to show how emotions are embedded within socio-political power relations and gender inequalities.

  18. Relationship between osteosarcoma and ionizing radiation hypersensitive human B lymphocyte cells lacking RecQL4 helicase

    International Nuclear Information System (INIS)

    Kohzaki, Masaoki; Moritake, Takashi; Okazaki, Ryuji; Ootsuyama, Akira

    2015-01-01

    Japanese society is now facing a transition period from aging society to super aging society. Concomitant with this situation, it is estimated that number of cancer patients and the requirement of less invasive Radiation Therapy (RT) for cancers will increase. Therefore, understanding of mechanisms without delay on second cancers caused by RT is indispensable. Osteosarcoma, an aggressive bone tumor frequently occurring 5% of cancers in young adult and children, increase statistically after RT for cancers. Although, mutation in p53, Rb and RecQL4 genes statistically relate with osteosarcoma incidence, precise mechanisms of osteosarcoma development by ionizing Radiation (IR) remain to be elucidated. Genome instability is one of the tumor promoting factors and we focused on RecQL4 in RecQ helicase family, which is involved in aging and cancer. We established RecQL4 knock-in human B lymphocyte Nalm-6 cells and found their hypersensitivity to IR, replication fork stall/collapses after IR. In this review, we summarize recently published studies on genetic cancer-predisposing syndrome and possible origins of bone cancers induced by IR. Then, we discuss what and how we address molecular mechanisms on osteosarcoma induced by IR in the future. (author)

  19. Lack of a Close Relationship Between Three Strains of Human Rhinoviruses as Determined by Their RNA Sequences 1

    Science.gov (United States)

    Yin, Fay H.; Lonberg-Holm, K.; Chan, S. P.

    1973-01-01

    The possible genomic homologies between three serotypes of human rhinoviruses (HRV 1A, HRV 2, and HRV 14) were investigated. First we confirmed that these viruses were unrelated by the criterion of the absence of common antigenic determinants on the surfaces of the native virions, as detected by cross-neutralization of complementfixation. RNA-RNA hybridization was then examined with purified, highly radioactive, double-stranded, replicative-form RNA and excess single-stranded virion RNA. Single-stranded RNA showed 100% homology with the minus strand from the replicative-form RNA of the same type of virus. HRV 1A, HRV 2, and HRV 14 showed low intertypic homologies; these were not significantly greater than those found between the rhinoviruses and polivirus, which were used as a negative control. The immunological relationship and the RNA homology between HRV 1A and HRV 1B were also examined by the above techniques. It was confirmed that HRV 1A and HRV 1B share some surface determinants and it was also found that HRV 1B RNA shares 70% homology with HRV 1A RNA. PMID:4126194

  20. Efficient CRISPR-Cas9-mediated generation of knockin human pluripotent stem cells lacking undesired mutations at the targeted locus.

    Science.gov (United States)

    Merkle, Florian T; Neuhausser, Werner M; Santos, David; Valen, Eivind; Gagnon, James A; Maas, Kristi; Sandoe, Jackson; Schier, Alexander F; Eggan, Kevin

    2015-05-12

    The CRISPR-Cas9 system has the potential to revolutionize genome editing in human pluripotent stem cells (hPSCs), but its advantages and pitfalls are still poorly understood. We systematically tested the ability of CRISPR-Cas9 to mediate reporter gene knockin at 16 distinct genomic sites in hPSCs. We observed efficient gene targeting but found that targeted clones carried an unexpectedly high frequency of insertion and deletion (indel) mutations at both alleles of the targeted gene. These indels were induced by Cas9 nuclease, as well as Cas9-D10A single or dual nickases, and often disrupted gene function. To overcome this problem, we designed strategies to physically destroy or separate CRISPR target sites at the targeted allele and developed a bioinformatic pipeline to identify and eliminate clones harboring deleterious indels at the other allele. This two-pronged approach enables the reliable generation of knockin hPSC reporter cell lines free of unwanted mutations at the targeted locus. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Lack of Evidence for a Relationship between High Risk Human Papillomaviruses and Breast Cancer in Iranian Patients.

    Science.gov (United States)

    Doosti, Masoud; Bakhshesh, Mehran; Zahir, Shokouh Taghipour; Shayestehpour, Mohammad; Karimi-Zarchi, Mojgan

    2016-01-01

    Whether there is any relationship between human papilloma virus (HPV) and breast carcinoma is not clear. Some previous studies have indicated a possible role in oncogenesis in the breast. In this study, we therefore analyzed the presence of HPV infection in breast tissues of Iranian women from Yazd city. In a cross-sectional study, formalin-fixed paraffin-embedded tissues from 87 patients with breast cancer and 84 cases with breast fibrocystic lesions (control group) were selected from a tissue archive. Grade of tumors and fibrocystic tissues were determined by two pathologists. The nested-PCR method was performed for detection of HPVs in samples. HPV genotypes were determined by sequencing and the phylogenetic tree depicted by MEGA software. Of the 87 women with breast cancer, 22.9% (20 isolates) had positive results for HPV DNA. In the control group no HPV was detected. The HPV genotypes in positive samples were HPV-16 (35%) HPV-18 (15%), HPV-6 (45%) and HPV-11 (5%). The data did not approved a significant correlation between tissue pathology of breast cancer and the HPV genotype frequency. The data did not provide any evidence for a role of high risk HPV types in oncogenesis in the breast.

  2. Elevated glucocorticoid receptor binding in cultured human lymphoblasts following hydroxyurea treatment: lack of effect on steroid responsiveness

    International Nuclear Information System (INIS)

    Littlefield, B.A.; Hoagland, H.C.; Greipp, P.R.

    1986-01-01

    While studying the effects of chemotherapy on glucocorticoid receptor (GR) binding levels in hematological malignancies, we observed a sizable increase in nuclear GR binding of [ 3 H]dexamethasone in peripheral leukocytes from a chronic basophilic leukemia patient following treatment with hydroxyurea plus prednisone, but not after prednisone alone. This apparent clinical effect of hydroxyurea led to an examination of hydroxyurea effects on GR binding and sensitivity in the glucocorticoid-sensitive human lymphoblast cell line GM4672A. GR binding levels in GM4672A cells were measured following a 3-day exposure to 50 microM hydroxyurea, a concentration chosen to have a minimal but measurable effect on cellular growth rates with little or no effect on cellular viability. Under these conditions, nuclear [ 3 H]dexamethasone receptor binding measured by Scatchard analysis using a whole-cell assay was elevated 2.4-fold over control values (P less than 0.05), while cytosolic residual receptor binding (measured at 37 0 C) remained unchanged. Thus, the total cellular content of measurable GR was increased, and this increase was totally accounted for by GR capable of nuclear binding. Hydroxyurea treatment of GM4672A cells had no effect on the affinity of nuclear or cytosolic GR for [ 3 H]dexamethasone. The increase in measurable nuclear-bound receptors occurred in a time-dependent manner over a period of 3 days and was fully reversible within 3 days following removal of hydroxyurea. The increase in receptor binding could not be explained by the slight alterations in cell cycle kinetics which occur at this low level of hydroxyurea. Despite increased receptor binding, cellular glucocorticoid responsiveness was unaltered as assessed by dexamethasone inhibition of cell growth and dexamethasone inhibition of a urokinase-like plasminogen activator

  3. β-lipotropin is the major opioid-like peptide of human pituitary and rat pars distalis: lack of significant β-endorphin

    International Nuclear Information System (INIS)

    Liotta, A.S.; Suda, T.; Krieger, D.T.

    1978-01-01

    β-Lipotropin is the predominant opioid peptide of the human pituitary and rat pars distalis and is present in concentrations essentially equimolar with corticotropin. When freshly obtained nonfrozen rat anterior pituitaries were homogenized with 0.2 M HCl, approximately 98% of the immunoreactivity detected utilizing an antiserum that crossreacts equally with β-lipotropin and β-endorphin coeluted with 125 I-labeled human β-lipotropin upon molecular sieve chromatography. The remainder of the activity eluted with synthetic human β-endorphin. Similar results were obtained for human pituitary. HCl homogenization of thawed tissue or homogenization of fresh tissue with acetic acid yielded substantially greater concentrations of β-endorphin and decreased concentrations of β-lipotropin. In human subjects, acute anterior pituitary stimulation using either insulin-induced hypoglycemia or vasopressin administration was associated with increased plasma β-lipotropin and corticotropin levels. At the time of peak concentrations, no significant levels of β-endorphin were detectable. These data indicate the lack of significant amounts of β-endorphin in human pituitary. Additionally, there appears to be no specific intrapituitary conversion of β-lipotropin to β-endorphin

  4. A human Polycomb isoform lacking the Pc box does not participate to PRC1 complexes but forms protein assemblies and represses transcription

    DEFF Research Database (Denmark)

    Völkel, Pamela; Le Faou, Perrine; Vandamme, Julien

    2012-01-01

    site for the PRC1 protein complex. Drosophila core PRC1 is composed of four subunits: Polycomb (Pc), Posterior sex combs (Psc), Polyhomeotic (Ph) and Sex combs extra (Sce). Each of these proteins has multiple orthologs in vertebrates, thus generating an enormous scope for potential combinatorial...... diversity. In particular, mammalian genomes encode five Pc family members: CBX2, CBX4, CBX6, CBX7 and CBX8. To complicate matters further, distinct isoforms might arise from single genes. Here, we address the functional role of the two human CBX2 isoforms. Owing to different polyadenylation sites...... and alternative splicing events, the human CBX2 locus produces two transcripts: a 5-exon transcript that encodes the 532-amino acid CBX2-1 isoform that contains the conserved chromodomain and Pc box and a 4-exon transcript encoding a shorter isoform, CBX2-2, lacking the Pc box but still possessing a chromodomain...

  5. R5 strains of human immunodeficiency virus type 1 from rapid progressors lacking X4 strains do not possess X4-type pathogenicity in human thymus

    NARCIS (Netherlands)

    Berkowitz, R. D.; van't Wout, A. B.; Kootstra, N. A.; Moreno, M. E.; Linquist-Stepps, V. D.; Bare, C.; Stoddart, C. A.; Schuitemaker, H.; McCune, J. M.

    1999-01-01

    Some individuals infected with only R5 strains of human immunodeficiency virus type 1 progress to AIDS as quickly as individuals harboring X4 strains. We determined that three R5 viruses were much less pathogenic than an X4 virus in SCID-hu Thy/Liv mice, suggesting that R5 virus-mediated rapid

  6. A human Polycomb isoform lacking the Pc box does not participate to PRC1 complexes but forms protein assemblies and represses transcription.

    Science.gov (United States)

    Völkel, Pamela; Le Faou, Perrine; Vandamme, Julien; Pira, Dorcas; Angrand, Pierre-Olivier

    2012-05-01

    Polycomb repression controls the expression of hundreds of genes involved in development and is mediated by essentially two classes of chromatin-associated protein complexes. The Polycomb repressive complex 2 (PRC2) trimethylates histone H3 at lysine 27, an epigenetic mark that serves as a docking site for the PRC1 protein complex. Drosophila core PRC1 is composed of four subunits: Polycomb (Pc), Posterior sex combs (Psc), Polyhomeotic (Ph) and Sex combs extra (Sce). Each of these proteins has multiple orthologs in vertebrates, thus generating an enormous scope for potential combinatorial diversity. In particular, mammalian genomes encode five Pc family members: CBX2, CBX4, CBX6, CBX7 and CBX8. To complicate matters further, distinct isoforms might arise from single genes. Here, we address the functional role of the two human CBX2 isoforms. Owing to different polyadenylation sites and alternative splicing events, the human CBX2 locus produces two transcripts: a 5-exon transcript that encodes the 532-amino acid CBX2-1 isoform that contains the conserved chromodomain and Pc box and a 4-exon transcript encoding a shorter isoform, CBX2-2, lacking the Pc box but still possessing a chromodomain. Using biochemical approaches and a novel in vivo imaging assay, we show that the short CBX2-2 isoform lacking the Pc box, does not participate in PRC1 protein complexes, but self-associates in vivo and forms complexes of high molecular weight. Furthermore, the CBX2 short isoform is still able to repress transcription, suggesting that Polycomb repression might occur in the absence of PRC1 formation.

  7. Quality Improvement to Demonstrate the Lack of Reliability of the Human Papillomavirus mRNA Assay to Identify Women With Latent Human Papillomavirus Infections.

    Science.gov (United States)

    Cotton, Sarah; Brown, Robert E; Nugent, Elizabeth K; Robazetti, Sonia C; Berens, Pamela D; Smith, Judith A

    2018-04-01

    To assess the consistency between human papillomavirus (HPV) mRNA testing in women with a history of previous HPV infections diagnosed by HPV DNA assay and the potential effects on follow-up HPV screening. This was a quality improvement study that used data from a pathology laboratory software database reviewed from November 2014 to June 2016 to identify female patients aged 30 years or older with greater than one HPV-positive result, including one or more HPV mRNA assay results and one or more documented HPV DNA assay results for comparison. Previous correlative cytology and colposcopic histopathology were also documented. American College of Obstetricians and Gynecologists' cervical cancer screening guidelines were used to compare potential differences in follow-up recommendations. Four hundred twenty-five charts for female patients 30 years of age or older were identified with one or more prior high-risk HPV infections by DNA assay. There was a 69.3% difference in HPV mRNA results compared with previous HPV DNA-positive results. There was a potential change in follow-up for 71.7% of patients with one prior high-risk-HPV-positive result and 60.0% of patients with two or more prior high-risk HPV-positive results. There were 231 colposcopy reports evaluated in this study. Of these, 62 (26.8%) were abnormal colposcopy reports, including 45 low-grade squamous intraepithelial lesions, 15 high-grade squamous intraepithelial lesions, and two cancers. Twenty-five (40.3%) abnormal colposcopy findings were in patients with a history of at least than two prior HPV DNA-positive results and a report of currently being HPV-negative with the mRNA assay. The HPV mRNA assays are less sensitive for detection of latent HPV infections compared with HPV DNA assays. Based on these data and the potential change in follow-up care, the HPV mRNA assay should not be used for a primary screening tool for cervical cancer. Many pathology laboratories have shifted to using the HPV mRNA assay

  8. Lack of T cell dysfunction and programmed cell death in human immunodeficiency virus type 1-infected chimpanzees correlates with absence of monocytotropic variants

    NARCIS (Netherlands)

    Schuitemaker, H.; Meyaard, L.; Kootstra, N. A.; Dubbes, R.; Otto, S. A.; Tersmette, M.; Heeney, J. L.; Miedema, F.

    1993-01-01

    In asymptomatic human immunodeficiency virus (HIV) infection in humans, disturbed T cell functions such as anergy and programmed cell death, thought to result from inappropriate signaling by antigen-presenting cells due to HIV infection, precede increase in virus load, decline in CD4+ T cell

  9. Verification of the lack of correlation between age and longitudinal chromatic aberrations of the human eye from the visible to the infrared

    Science.gov (United States)

    Nakajima, Masashi; Hiraoka, Takahiro; Hirohara, Yoko; Oshika, Tetsuro; Mihashi, Toshifumi

    2015-01-01

    Several researchers studied the longitudinal chromatic aberration (LCA) of the human eye and observed that it does not change due to age. We measured the LCA of 45 subjects’ normal right eyes at three distinct wavelengths (561, 690, and 840 nm) using a Hartmann–Shack wavefront aberrometer (HSWA) while consecutively switching between three light sources for wavefront sensing. We confirmed that the LCA of the human eye does not change due to age between 22 and 57 years. PMID:26203391

  10. Continuous Lymphoid Cell Lines with Characteristics of B Cells (Bone-Marrow-Derived), Lacking the Epstein-Barr Virus Genome and Derived from Three Human Lymphomas

    Science.gov (United States)

    Klein, George; Lindahl, Tomas; Jondal, Mikael; Leibold, Wolfgang; Menézes, José; Nilsson, Kenneth; Sundström, Christer

    1974-01-01

    Three exceptional cell lines have been tested for the presence of the Epstein-Barr virus genome by nucleic acid hybridization (complementary RNA·DNA) and Epstein-Barr virus-determined nuclear antigen tests. Two lines were derived from Swedish lymphoma cases and one from an African Burkitt-like lymphoma biopsy that was negative for Epstein-Barr virus DNA and the virus-determined nuclear antigen. All three lines apparently lacked the viral genome. Two of the three lines clearly had characteristics of B-cells (bone-marrow-derived). PMID:4369887

  11. Lack of association between infection with a novel human coronavirus (HCoV), HCoV-NH, and Kawasaki disease in Taiwan

    NARCIS (Netherlands)

    Chang, Luan-Yin; Chiang, Bor-Luen; Kao, Chuan-Liang; Wu, Mei-Hwan; Chen, Pei-Jer; Berkhout, Ben; Yang, Hui-Ching; Huang, Li-Min

    2006-01-01

    We investigated whether infection with a novel human coronavirus (HCoV), called "New Haven coronavirus" (HCoV-NH)--which is similar to and likely represents the same species as another novel HCoV, HCoV-NL63--is associated with Kawasaki disease (KD) in Taiwan. Fifty-three patients with KD were

  12. Domestic sheep show average Coxiella burnetii seropositivity generations after a sheep-associated human Q fever outbreak and lack detectable shedding by placental, vaginal, and fecal routes

    Science.gov (United States)

    Oliveira, Ryan D.; Mousel, Michelle R.; Pabilonia, Kristy L.; Highland, Margaret A.; Taylor, J. Bret; Knowles, Donald P.

    2017-01-01

    Coxiella burnetii is a globally distributed zoonotic bacterial pathogen that causes abortions in ruminant livestock. In humans, an influenza-like illness results with the potential for hospitalization, chronic infection, abortion, and fatal endocarditis. Ruminant livestock, particularly small ruminants, are hypothesized to be the primary transmission source to humans. A recent Netherlands outbreak from 2007–2010 traced to dairy goats resulted in over 4,100 human cases with estimated costs of more than 300 million euros. Smaller human Q fever outbreaks of small ruminant origin have occurred in the United States, and characterizing shedding is important to understand the risk of future outbreaks. In this study, we assessed bacterial shedding and seroprevalence in 100 sheep from an Idaho location associated with a 1984 human Q fever outbreak. We observed 5% seropositivity, which was not significantly different from the national average of 2.7% for the U.S. (P>0.05). Furthermore, C. burnetii was not detected by quantitative PCR from placentas, vaginal swabs, or fecal samples. Specifically, a three-target quantitative PCR of placenta identified 0.0% shedding (exact 95% confidence interval: 0.0%-2.9%). While presence of seropositive individuals demonstrates some historical C. burnetii exposure, the placental sample confidence interval suggests 2016 shedding events were rare or absent. The location maintained the flock with little or no depopulation in 1984 and without C. burnetii vaccination during or since 1984. It is not clear how a zero-shedding rate was achieved in these sheep beyond natural immunity, and more work is required to discover and assess possible factors that may contribute towards achieving zero-shedding status. We provide the first U.S. sheep placental C. burnetii shedding update in over 60 years and demonstrate potential for C. burnetii shedding to reach undetectable levels after an outbreak event even in the absence of targeted interventions, such

  13. Endogenous acute phase serum amyloid A lacks pro-inflammatory activity, contrasting the two recombinant variants that activate human neutrophils through different receptors

    Directory of Open Access Journals (Sweden)

    Karin eChristenson

    2013-04-01

    Full Text Available Most notable among the acute phase proteins is serum amyloid A (SAA, levels of which can increase 1000-fold during infections, aseptic inflammation, and/or trauma. Chronically elevated SAA levels are associated with a wide variety of pathological conditions, including obesity and rheumatic diseases. Using a recombinant hybrid of the two human SAA isoforms (SAA1 and 2 that does not exist in vivo, numerous in vitro studies have given rise to the notion that acute phase SAA is a pro-inflammatory molecule with cytokine-like properties. It is however unclear whether endogenous acute phase SAA per se mediates pro-inflammatory effects. We tested this in samples from patients with inflammatory arthritis and in a transgenic mouse model that expresses human SAA1. Endogenous human SAA did not drive production of pro-inflammatory IL-8/KC in either of these settings. Human neutrophils derived from arthritis patients displayed no signs of activation, despite being exposed to severely elevated SAA levels in circulation, and SAA-rich sera also failed to activate cells in vitro. In contrast, two recombinant SAA variants (the hybrid SAA and SAA1 both activated human neutrophils, inducing L-selectin shedding, production of reactive oxygen species, and production of IL-8. The hybrid SAA was approximately 100-fold more potent than recombinant SAA1. Recombinant hybrid SAA and SAA1 activated neutrophils through different receptors, with recombinant SAA1 being a ligand for formyl peptide receptor 2 (FPR2. We conclude that even though recombinant SAAs can be valuable tools for studying neutrophil activation, they do not reflect the nature of the endogenous protein.

  14. Domestic sheep show average Coxiella burnetii seropositivity generations after a sheep-associated human Q fever outbreak and lack detectable shedding by placental, vaginal, and fecal routes.

    Directory of Open Access Journals (Sweden)

    Ryan D Oliveira

    Full Text Available Coxiella burnetii is a globally distributed zoonotic bacterial pathogen that causes abortions in ruminant livestock. In humans, an influenza-like illness results with the potential for hospitalization, chronic infection, abortion, and fatal endocarditis. Ruminant livestock, particularly small ruminants, are hypothesized to be the primary transmission source to humans. A recent Netherlands outbreak from 2007-2010 traced to dairy goats resulted in over 4,100 human cases with estimated costs of more than 300 million euros. Smaller human Q fever outbreaks of small ruminant origin have occurred in the United States, and characterizing shedding is important to understand the risk of future outbreaks. In this study, we assessed bacterial shedding and seroprevalence in 100 sheep from an Idaho location associated with a 1984 human Q fever outbreak. We observed 5% seropositivity, which was not significantly different from the national average of 2.7% for the U.S. (P>0.05. Furthermore, C. burnetii was not detected by quantitative PCR from placentas, vaginal swabs, or fecal samples. Specifically, a three-target quantitative PCR of placenta identified 0.0% shedding (exact 95% confidence interval: 0.0%-2.9%. While presence of seropositive individuals demonstrates some historical C. burnetii exposure, the placental sample confidence interval suggests 2016 shedding events were rare or absent. The location maintained the flock with little or no depopulation in 1984 and without C. burnetii vaccination during or since 1984. It is not clear how a zero-shedding rate was achieved in these sheep beyond natural immunity, and more work is required to discover and assess possible factors that may contribute towards achieving zero-shedding status. We provide the first U.S. sheep placental C. burnetii shedding update in over 60 years and demonstrate potential for C. burnetii shedding to reach undetectable levels after an outbreak event even in the absence of targeted

  15. A lack of Birbeck granules in Langerhans cells is associated with a naturally occurring point mutation in the human Langerin gene.

    Science.gov (United States)

    Verdijk, Pauline; Dijkman, Remco; Plasmeijer, Elsemieke I; Mulder, Aat A; Zoutman, Willem H; Mieke Mommaas, A; Tensen, Cornelis P

    2005-04-01

    A heterozygous mutation in the Langerin gene corresponding to position 837 in the Langerin mRNA was identified in a person deficient in Birbeck granules (BG). This mutation results in an amino acid replacement of tryptophan by arginine at position 264 in the carbohydrate recognition domain of the Langerine protein. Expression of mutated Langerin in human fibroblasts induces tubular-like structures that are negative for BG-specific antibodies and do not resemble the characteristic structural features of BG.

  16. Energy brands lack vitality

    International Nuclear Information System (INIS)

    Godri, S.; Wilders, E.

    2004-01-01

    The three Dutch energy companies (Nuon, Essent and Eneco Energie) have relatively little brand strength. The brands are not perceived to be sufficiently different from one another and are not valued by consumers. With liberalisation imminent, this is hardly a strong starting point. How can you win over consumers if it is not clear what is on offer? In the business market, decision-makers are better placed to distinguish between brands. However, the brands lack vitality in this sector of the market too. The only consolation is that the situation is by no means exclusive to the Netherlands [nl

  17. Hypermethylation pattern of ESR and PgR genes and lacking estrogen and progesterone receptors in human breast cancer tumors: ER/PR subtypes.

    Science.gov (United States)

    Pirouzpanah, Saeed; Taleban, Forough-Azam; Mehdipour, Parvin; Sabour, Siamak; Atri, Morteza

    2018-02-14

    The option of endocrine therapy in breast cancer remains conventionally promising. We aimed to investigate how accurately the pattern of hypermethylation at estrogen receptor (ESR) and progesterone receptor (PgR) genes may associate with relative expression and protein status of ER, PR and the combinative phenotype of ER/PR. In this consecutive case-series, we enrolled 139 primary diagnosed breast cancer. Methylation specific PCR was used to assess the methylation status (individual test). Tumor mRNA expression levels were evaluated using real-time RT-PCR. Immunohistochemistry data was used to present hormonal receptor status of a tumor (as test reference). Methylation at ESR1 was comparably frequent in ER-breast tumors (83.0%, PPR- conditions (Cramer's V= 0.44, PPR (77.1%, PPR expressions (55.6%, PPR- (64.4%, PPR-, the hypermethylation of PgRb seem another epigenetic signalling variable actively associate with methylated ESR1 to show lack of ER+/PR+ tumors in breast cancer.

  18. Patterns of Human Respiratory Viruses and Lack of MERS-Coronavirus in Patients with Acute Upper Respiratory Tract Infections in Southwestern Province of Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Ahmed A. Abdulhaq

    2017-01-01

    Full Text Available We undertook enhanced surveillance of those presenting with respiratory symptoms at five healthcare centers by testing all symptomatic outpatients between November 2013 and January 2014 (winter time. Nasal swabs were collected from 182 patients and screened for MERS-CoV as well as other respiratory viruses using RT-PCR and multiplex microarray. A total of 75 (41.2% of these patients had positive viral infection. MERS-CoV was not detected in any of the samples. Human rhinovirus (hRV was the most detected pathogen (40.9% followed by non-MERS-CoV human coronaviruses (19.3%, influenza (Flu viruses (15.9%, and human respiratory syncytial virus (hRSV (13.6%. Viruses differed markedly depending on age in which hRV, Flu A, and hCoV-OC43 were more prevalent in adults and RSV, hCoV-HKU1, and hCoV-NL63 were mostly restricted to children under the age of 15. Moreover, coinfection was not uncommon in this study, in which 17.3% of the infected patients had dual infections due to several combinations of viruses. Dual infections decreased with age and completely disappeared in people older than 45 years. Our study confirms that MERS-CoV is not common in the southwestern region of Saudi Arabia and shows high diversity and prevalence of other common respiratory viruses. This study also highlights the importance and contribution of enhanced surveillance systems for better infection control.

  19. Identification of a novel splice variant of human PD-L1 mRNA encoding an isoform-lacking Igv-like domain.

    Science.gov (United States)

    He, Xian-hui; Xu, Li-hui; Liu, Yi

    2005-04-01

    To investigate the expression and regulation of PD-1 ligand 1 (PD-L1) in peripheral blood mononuclear cells (PBMC). The cDNA encoding human PD-L1 precursor was cloned from the total RNA extracted from the resting and phorbol dibutyrate plus ionomycin- or phytohemagglutinin-activated PBMC, by reverse transcription polymerase chain reaction (RT-PCR), and independent clones were sequenced and analyzed. The expression and subcellular localization were examined in transiently transfected cells. The PD-L1 gene expression in different PBMC was also analyzed by RT-PCR. A novel human PD-L1 splice variant was identified from the activated PBMC. It was generated by splicing out exon? encoding an immunoglobulin variable domain (Igv)-like domain but retaining all other exons without a frame-shift. Consequently, the putative translated protein contained all other domains including the transmembrane region except for the Igv-like domain. Furthermore, the conventional isoform was expressed on the plasma surface whereas the novel isoform showed a pattern of intracellular membrane distribution in transiently transfected K562 cells. In addition, the expression pattern of the PD-L1 splice variant was variable in different individuals and in different cellular status. PD-L1 expression may be regulated at the posttranscriptional level through alternative splicing, and modulation of the PD-L1 isoform expression may influence the outcome of specific immune responses in the peripheral tissues.

  20. Increased copper toxicity in Saccharomyces cerevisiae lacking VPS35, a component of the retromer and monogenic Parkinson disease gene in humans.

    Science.gov (United States)

    Sowada, Nadine; Stiller, Barbara; Kubisch, Christian

    2016-08-05

    The Saccharomyces cerevisiae gene VPS35 encodes a component of the retromer complex which is involved in vesicle transport from endosomes to the trans-Golgi network. Yeast and human VPS35 orthologs are highly conserved and mutations in human VPS35 cause an autosomal dominant form of late-onset Parkinson disease (PD). We now show that deletion of VPS35 in yeast (vps35Δ) leads to a dose-dependent growth defect towards copper. This increased sensitivity could be rescued by transformation with yeast wild-type VPS35 but not by the expression of a construct harboring the yeast equivalent (i.e. D686N) of the most commonly identified VPS35-associated PD mutation, p.D620N. In addition, we show that expression of one copy of α-synuclein, which is known to directly interact with copper, leads to a pronounced aggravation of copper toxicity in vps35Δ cells, thereby linking the regulation of copper homeostasis by Vps35p in yeast to one of the key molecules in PD pathophysiology. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. In vitro radiosensitivity of primary human fibroblasts. Lack of correlation with acute radiation toxicity in patients with head and neck cancer

    International Nuclear Information System (INIS)

    Rudat, Volker; Dietz, Andreas; Conradt, Christian; Weber, Klaus-Josef; Flentje, Michael

    1997-01-01

    Background and purpose: There is a considerable hope among clinicians and radiobiologists to detect genetically radiosensitive patients prior to radiotherapy. A predictive assay would enable adjustment of the total irradiation dose to the individual at a constant risk of normal tissue complications. In this prospective study, the clonogenic survival assay for primary human fibroblasts to determine radiosensitivity in vitro was evaluated and then correlated with clinically observed acute radiation reactions. Materials and methods: One hundred twenty-five independent survival experiments with primary fibroblasts derived from 63 biopsies from 55 cancer and non-cancer patients were performed. Results: A wide variation of cell survival between biopsies was detected. Statistical analysis revealed a highly significantly larger interindividual than intraindividual variation of SF2 values. However, a considerable scatter of SF2 values in repeated experiments was observed in individual cases. Age, gender, disease status (cancer patient, non-cancer patient) and origin of fibroblasts (skin, periodontal tissue) were demonstrated not to be statistically significant confounding factors on the intrinsic radiosensitivity in vitro. In a prospective study, no correlation of the SF2 and acute reactions in 25 patients with head and neck cancer treated with a primary accelerated radiochemotherapy was detected. Conclusion: Our data show that the clonogenic assay is able to distinguish between intrinsic radiosensitivities of primary human fibroblasts if a statistical approach is used but does not predict acute radiation toxicity

  2. Cd2+, Mn2+, Ni2+ and Se2+ toxicity to Saccharomyces cerevisiae lacking YPK9p the orthologue of human ATP13A2

    International Nuclear Information System (INIS)

    Schmidt, Karyn; Wolfe, Devin M.; Stiller, Barbara; Pearce, David A.

    2009-01-01

    The Saccharomyces cerevisiae gene YPK9 encodes a putative integral membrane protein which is 58% similar and 38% identical in amino acid sequence to the human lysosomal P 5B ATPase ATP13A2. Mutations in ATP13A2 have been found in patients with Kufor-Rakeb syndrome, a form of juvenile Parkinsonism. We report that Ypk9p localizes to the yeast vacuole and that deletion of YPK9 confers sensitivity for growth for cadmium, manganese, nickel or selenium. These results suggest that Ypk9p may play a role in sequestration of divalent heavy metal ions. Further studies on the function of Ypk9p/ATP13A2 may help to define the molecular basis of Kufor-Rakeb syndrome and provide a potential link to environmental factors such as heavy metals contributing to some forms of Parkinsonism.

  3. Transcranial alternating current stimulation at beta frequency: lack of immediate effects on excitation and interhemispheric inhibition of the human motor cortex

    Directory of Open Access Journals (Sweden)

    Viola Rjosk

    2016-11-01

    Full Text Available Transcranial alternating current stimulation (tACS is a form of noninvasive brain stimulation and is capable of influencing brain oscillations and cortical networks. In humans, the endogenous oscillation frequency in sensorimotor areas peaks at 20 Hz. This beta-band typically occurs during maintenance of tonic motor output and seems to play a role in interhemispheric coordination of movements. Previous studies showed that tACS applied in specific frequency bands over primary motor cortex (M1 or the visual cortex modulates cortical excitability within the stimulated hemisphere. However, the particular impact remains controversial because effects of tACS were shown to be frequency, duration and location specific. Furthermore, the potential of tACS to modulate cortical interhemispheric processing, like interhemispheric inhibition (IHI, remains elusive. Transcranial magnetic stimulation (TMS is a noninvasive and well-tolerated method of directly activating neurons in superficial areas of the human brain and thereby a useful tool for evaluating the functional state of motor pathways. The aim of the present study was to elucidate the immediate effect of 10 min tACS in the β-frequency band (20 Hz over left M1 on IHI between M1s in 19 young, healthy, right-handed participants. A series of TMS measurements (MEP size, RMT, IHI from left to right M1 and vice versa was performed before and immediately after tACS or sham using a double-blinded, cross-over design. We did not find any significant tACS-induced modulations of intracortical excitation (as assessed by MEP size and RMT and/or interhemispheric inhibition (IHI. These results indicate that 10 min of 20 Hz tACS over left M1 seems incapable of modulating immediate brain activity or inhibition. Further studies are needed to elucidate potential aftereffects of 20 Hz tACS as well as frequency-specific effects of tACS on intracortical excitation and interhemispheric inhibition.

  4. Cryopreservation does not alter main characteristics of Good Manufacturing Process-grade human multipotent mesenchymal stromal cells including immunomodulating potential and lack of malignant transformation.

    Science.gov (United States)

    Luetzkendorf, Jana; Nerger, Katrin; Hering, Julian; Moegel, Angelika; Hoffmann, Katrin; Hoefers, Christiane; Mueller-Tidow, Carsten; Mueller, Lutz P

    2015-02-01

    The immunomodulating capacity of multipotent mesenchymal stromal cells (MSCs) qualifies them as a therapeutic tool in several diseases. However, repeated transplantation with products of reproducible characteristics may be required. This could be achieved with cryopreserved aliquots of Good Manufacturing Practice (GMP)-grade MSCs. However, the impact of cryopreservation on the characteristics of GMP-MSCs is ill defined. We produced fresh and cryopreserved MSCs from human donors with a xenogen-free GMP protocol. Immunogenicity and immunomodulating capacity were tested in co-culture with putative recipient-specific peripheral blood mononuclear cells (PBMCs). Risk of malignant transformation was assessed in vitro and in vivo. Cryopreservation had no impact on viability and consensus criteria of MSCs. In co-culture with PBMCs, MSCs showed low immunogenicity and suppressed mitogen-stimulated proliferation of PBMC irrespective of cryopreservation. Cytogenetic aberrations were not observed consistently in fresh and cryopreserved products, and no signs of malignant transformation occurred in functional assays. MSC products from an elderly pretreated donor showed reduced functional quality, but imminent failure of functional criteria could be detected by an increased population doubling time in early passages. This study is the first systematic analysis on cryopreservation of xenogen-free human bone marrow-derived GMP-MSCs. The data support that cryopreservation does not alter the characteristics of the cells and thus may allow the generation of products for serial transplantation. In addition, the protocol allowed early detection of MSC products with low functional capacity. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  5. Neutrophilia, gelatinase release and microvascular leakage induced by human mast cell tryptase in a mouse model: Lack of a role of protease-activated receptor 2 (PAR2).

    Science.gov (United States)

    Khedr, M E M S; Abdelmotelb, A M; Pender, S L F; Zhou, X; Walls, A F

    2018-05-01

    Tryptase, the most abundant protease of the human mast cell, has been implicated as a key mediator of allergic inflammation that acts through activation of PAR2. To investigate the contribution of PAR2 in the pro-inflammatory actions mediated by tryptase in a mice model. We have injected recombinant human βII-tryptase into the peritoneum of PAR2-deficient and wild-type C57BL/6 mice. After 6, 12 and 24 hours, mice were killed, peritoneal lavage performed and inflammatory changes investigated. Tryptase stimulated an increase in neutrophil numbers in the peritoneum, but responses did not differ between PAR2-deficient and wild-type mice. Heat inactivation of tryptase or pre-incubation with a selective tryptase inhibitor reduced neutrophilia, but neutrophil accumulation was not elicited with a peptide agonist of PAR2 (SLIGRL-NH 2 ). Zymography indicated that tryptase stimulated the release of matrix metalloproteinases (MMP) 2 and 9 in the peritoneum of both mouse strains. Studies involving immunomagnetic isolation of neutrophils suggested that neutrophils represent the major cellular source of tryptase-induced MMP2 and MMP9. At 24 hours after tryptase injection, there was increased microvascular leakage as indicated by high levels of albumin in peritoneal lavage fluid, and this appeared to be partially abolished by heat-inactivating tryptase or addition of a protease inhibitor. There was no corresponding increase in levels of histamine or total protein. The extent of tryptase-induced microvascular leakage or gelatinase release into the peritoneum did not differ between PAR2-deficient and wild-type mice. Our findings indicate that tryptase is a potent stimulus for neutrophil accumulation, MMP release and microvascular leakage. Although these actions required an intact catalytic site, the primary mechanism of tryptase in vivo would appear to involve processes independent of PAR2. © 2018 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.

  6. Lack of viral selection in human immunodeficiency virus type 1 mother-to-child transmission with primary infection during late pregnancy and/or breastfeeding.

    Science.gov (United States)

    Ceballos, Ana; Andreani, Guadalupe; Ripamonti, Chiara; Dilernia, Dario; Mendez, Ramiro; Rabinovich, Roberto D; Cárdenas, Patricia Coll; Zala, Carlos; Cahn, Pedro; Scarlatti, Gabriella; Martínez Peralta, Liliana

    2008-11-01

    Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) as described for women with an established infection is, in most cases, associated with the transmission of few maternal variants. This study analysed virus variability in four cases of maternal primary infection occurring during pregnancy and/or breastfeeding. Estimated time of seroconversion was at 4 months of pregnancy for one woman (early seroconversion) and during the last months of pregnancy and/or breastfeeding for the remaining three (late seroconversion). The C2V3 envelope region was analysed in samples of mother-child pairs by molecular cloning and sequencing. Comparisons of nucleotide and amino acid sequences as well as phylogenetic analysis were performed. The results showed low variability in the virus population of both mother and child. Maximum-likelihood analysis showed that, in the early pregnancy seroconversion case, a minor viral variant with further evolution in the child was transmitted, which could indicate a selection event in MTCT or a stochastic event, whereas in the late seroconversion cases, the mother's and child's sequences were intermingled, which is compatible with the transmission of multiple viral variants from the mother's major population. These results could be explained by the less pronounced selective pressure exerted by the immune system in the early stages of the mother's infection, which could play a role in MTCT of HIV-1.

  7. Formyl Met-Leu-Phe-Stimulated FPR1 Phosphorylation in Plate-Adherent Human Neutrophils: Enhanced Proteolysis but Lack of Inhibition by Platelet-Activating Factor

    Directory of Open Access Journals (Sweden)

    Algirdas J. Jesaitis

    2018-01-01

    Full Text Available N-formyl-Met-Leu-Phe (fMLF is a model PAMP/DAMP driving human PMN to sites of injury/infection utilizing the GPCR, FPR1. We examined a microtiter plate format for measurement of FPR1 phosphorylation in adherent PMN at high densities and found that a new phosphosensitive FPR1 fragment, 25K-FPR1, accumulates in SDS-PAGE extracts. 25K-FPR1 is fully inhibited by diisopropylfluorophosphate PMN pretreatment but is not physiologic, as its formation failed to be significantly perturbed by ATP depletion, time and temperature of adherence, or adherence mechanism. 25K-FPR1 was minimized by extracting fMLF-exposed PMN in lithium dodecylsulfate at 4°C prior to reduction/alkylation. After exposure of adherent PMN to a 5 log range of PAF before or after fMLF, unlike in suspension PMN, no inhibition of fMLF-induced FPR1 phosphorylation was observed. However, PAF induced the release of 40% of PMN lactate dehydrogenase, implying significant cell lysis. We infer that PAF-induced inhibition of fMLF-dependent FPR1 phosphorylation observed in suspension PMN does not occur in the unlysed adherent PMN. We speculate that although the conditions of the assay may induce PAF-stimulated necrosis, the cell densities on the plates may approach levels observed in inflamed tissues and provide for an explanation of PAF’s divergent effects on FPR1 phosphorylation as well as PMN function.

  8. Lack of parvalbumin in mice leads to behavioral deficits relevant to all human autism core symptoms and related neural morphofunctional abnormalities.

    Science.gov (United States)

    Wöhr, M; Orduz, D; Gregory, P; Moreno, H; Khan, U; Vörckel, K J; Wolfer, D P; Welzl, H; Gall, D; Schiffmann, S N; Schwaller, B

    2015-03-10

    Gene mutations and gene copy number variants are associated with autism spectrum disorders (ASDs). Affected gene products are often part of signaling networks implicated in synapse formation and/or function leading to alterations in the excitation/inhibition (E/I) balance. Although the network of parvalbumin (PV)-expressing interneurons has gained particular attention in ASD, little is known on PV's putative role with respect to ASD. Genetic mouse models represent powerful translational tools for studying the role of genetic and neurobiological factors underlying ASD. Here, we report that PV knockout mice (PV(-/-)) display behavioral phenotypes with relevance to all three core symptoms present in human ASD patients: abnormal reciprocal social interactions, impairments in communication and repetitive and stereotyped patterns of behavior. PV-depleted mice also showed several signs of ASD-associated comorbidities, such as reduced pain sensitivity and startle responses yet increased seizure susceptibility, whereas no evidence for behavioral phenotypes with relevance to anxiety, depression and schizophrenia was obtained. Reduced social interactions and communication were also observed in heterozygous (PV(+/-)) mice characterized by lower PV expression levels, indicating that merely a decrease in PV levels might be sufficient to elicit core ASD-like deficits. Structural magnetic resonance imaging measurements in PV(-/-) and PV(+/-) mice further revealed ASD-associated developmental neuroanatomical changes, including transient cortical hypertrophy and cerebellar hypoplasia. Electrophysiological experiments finally demonstrated that the E/I balance in these mice is altered by modification of both inhibitory and excitatory synaptic transmission. On the basis of the reported changes in PV expression patterns in several, mostly genetic rodent models of ASD, we propose that in these models downregulation of PV might represent one of the points of convergence, thus providing a

  9. Lack of WDR36 leads to preimplantation embryonic lethality in mice and delays the formation of small subunit ribosomal RNA in human cells in vitro.

    Science.gov (United States)

    Gallenberger, Martin; Meinel, Dominik M; Kroeber, Markus; Wegner, Michael; Milkereit, Philipp; Bösl, Michael R; Tamm, Ernst R

    2011-02-01

    Mutations in WD repeat domain 36 gene (WDR36) play a causative role in some forms of primary open-angle glaucoma, a leading cause of blindness worldwide. WDR36 is characterized by the presence of multiple WD40 repeats and shows homology to Utp21, an essential protein component of the yeast small subunit (SSU) processome required for maturation of 18S rRNA. To clarify the functional role of WDR36 in the mammalian organism, we generated and investigated mutant mice with a targeted deletion of Wdr36. In parallel experiments, we used RNA interference to deplete WDR36 mRNA in mouse embryos and cultured human trabecular meshwork (HTM-N) cells. Deletion of Wdr36 in the mouse caused preimplantation embryonic lethality, and essentially similar effects were observed when WDR36 mRNA was depleted in mouse embryos by RNA interference. Depletion of WDR36 mRNA in HTM-N cells caused apoptotic cell death and upregulation of mRNA for BAX, TP53 and CDKN1A. By immunocytochemistry, staining for WDR36 was observed in the nucleolus of cells, which co-localized with that of nucleolar proteins such as nucleophosmin and PWP2. In addition, recombinant and epitope-tagged WDR36 localized to the nucleolus of HTM-N cells. By northern blot analysis, a substantial decrease in 21S rRNA, the precursor of 18S rRNA, was observed following knockdown of WDR36. In addition, metabolic-labeling experiments consistently showed a delay of 18S rRNA maturation in WDR36-depleted cells. Our results provide evidence that WDR36 is an essential protein in mammalian cells which is involved in the nucleolar processing of SSU 18S rRNA.

  10. Lack of Obvious Influence of PLLA Nanofibers on the Gene Expression of BMP-2 and VEGF during Growth and Differentiation of Human Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Markus D. Schofer

    2009-01-01

    Full Text Available Growth factors like bone morphogenetic protein 2 (BMP-2 and vascular endothelial growth factor (VEGF play an important role in bone remodeling and fracture repair. Therefore, with respect to tissue engineering, an artificial graft should have no negative impact on the expression of these factors. In this context, the aim of this study was to analyze the impact of poly(L-lactic acid (PLLA nanofibers on VEGF and BMP-2 gene expression during the time course of human mesenchymal stem cell (hMSC differentiation towards osteoblasts. PLLA matrices were seeded with hMSCs and cultivated over a period of 22 days under growth and osteoinductive conditions, and analyzed during the course of culture, with respect to gene expression of VEGF and BMP-2. Furthermore, BMP-2–enwoven PLLA nanofibers were used in order to elucidate whether initial down-regulation of growth factor expression could be compensated. Although there was a great interpatient variability with respect to the expression of VEGF and BMP-2, PLLA nanofibers tend to result in a down-regulation in BMP-2 expression during the early phase of cultivation. This effect was diminished in the case of VEGF gene expression. The initial down-regulation was overcome when BMP-2 was directly incorporated into the PLLA nanofibers by electrospinning. Furthermore, the incorporation of BMP-2 into the PLLA nanofibers resulted in an increase in VEGF gene expression. Summarized, the results indicate that the PLLA nanofibers have little effect on growth factor production. An enhancement in gene expression of BMP-2 and VEGF can be achieved by an incorporation of BMP-2 into the PLLA nanofibers.

  11. Lack of Obvious Influence of PLLA Nanofibers on the Gene Expression of BMP-2 and VEGF during Growth and Differentiation of Human Mesenchymal Stem Cells

    Science.gov (United States)

    Schofer, Markus D.; Fuchs-Winkelmann, S.; Wack, C.; Rudisile, M.; Dersch, R.; Leifeld, I.; Wendorff, J.; Greiner, A.; Paletta, J. R. J.; Boudriot, U.

    2009-01-01

    Growth factors like bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor (VEGF) play an important role in bone remodeling and fracture repair. Therefore, with respect to tissue engineering, an artificial graft should have no negative impact on the expression of these factors. In this context, the aim of this study was to analyze the impact of poly(L-lactic acid) (PLLA) nanofibers on VEGF and BMP-2 gene expression during the time course of human mesenchymal stem cell (hMSC) differentiation towards osteoblasts. PLLA matrices were seeded with hMSCs and cultivated over a period of 22 days under growth and osteoinductive conditions, and analyzed during the course of culture, with respect to gene expression of VEGF and BMP-2. Furthermore, BMP-2–enwoven PLLA nanofibers were used in order to elucidate whether initial down-regulation of growth factor expression could be compensated. Although there was a great interpatient variability with respect to the expression of VEGF and BMP-2, PLLA nanofibers tend to result in a down-regulation in BMP-2 expression during the early phase of cultivation. This effect was diminished in the case of VEGF gene expression. The initial down-regulation was overcome when BMP-2 was directly incorporated into the PLLA nanofibers by electrospinning. Furthermore, the incorporation of BMP-2 into the PLLA nanofibers resulted in an increase in VEGF gene expression. Summarized, the results indicate that the PLLA nanofibers have little effect on growth factor production. An enhancement in gene expression of BMP-2 and VEGF can be achieved by an incorporation of BMP-2 into the PLLA nanofibers. PMID:19412560

  12. Lack of negative autocorrelations of daily food intake on successive days challenges the concept of the regulation of body weight in humans.

    Science.gov (United States)

    Levitsky, David A; Raea Limb, Ji Eun; Wilkinson, Lua; Sewall, Anna; Zhong, Yingyi; Olabi, Ammar; Hunter, Jean

    2017-09-01

    According to most theories, the amount of food consumed on one day should be negatively related to intake on subsequent days. Several studies have observed such a negative correlation between the amount consumed on one day and the amount consumed two to four days later. The present study attempted to replicate this observation by re-examining data from a previous study where all food ingested over a 30-day observation period was measured. Nine male and seven female participants received a vegan diet prepared, dispensed, and measured in a metabolic unit. Autocorrelations were performed on total food intake consume on one day and that consumed one to five days later. A significant positive correlation was detected between the weight of food eaten on one day and on the amount consumed on the following day (r = 0.29, 95% CI [0.37, 0.20]). No correlation was found between weights of food consumed on one day and up to twelve days later (r = 0.09, 95% CI [0.24, -0.06]), (r = 0.11, 95% CI [0.26, -0.0.26]) (r = 0.02, 95% CI [0.15, -0.7]) (r = -0.08, 95% CI [0.11, -0.09]). The same positive correlation with the previous day's intake was observed at the succeeding breakfast but not at either lunch or dinner. However, the participants underestimated their daily energy need resulting in a small, but statistically significant weight loss. Daily food intake increased slightly (13 g/day), but significantly, across the 30-day period. An analysis of the previous studies revealed that the negative correlations observed by others was caused by a statistical artifact resulting from normalizing data before testing for the correlations. These results, when combined with the published literature, indicate that there is little evidence that humans precisely compensate for the previous day's intake by altering the amount consumed on subsequent days. Moreover, the small but persistent increase in food intake suggests that physiological mechanisms that affect food intake

  13. Peritubular dentin lacks piezoelectricity.

    Science.gov (United States)

    Habelitz, S; Rodriguez, B J; Marshall, S J; Marshall, G W; Kalinin, S V; Gruverman, A

    2007-09-01

    Dentin is a mesenchymal tissue, and, as such, is based on a collagenous matrix that is reinforced by apatite mineral. Collagen fibrils show piezoelectricity, a phenomenon that is used by piezoresponse force microscopy (PFM) to obtain high-resolution images. We applied PFM to image human dentin with 10-nm resolution, and to test the hypothesis that zones of piezoactivity, indicating the presence of collagen fibrils, can be distinguished in dentin. Piezoelectricity was observed by PFM in the dentin intertubular matrix, while the peritubular dentin remained without response. High-resolution imaging of chemically treated intertubular dentin attributed the piezoelectric effect to individual collagen fibrils that differed in the signal strength, depending on the fibril orientation. This study supports the hypothesis that peritubular dentin is a non-collagenous tissue and is thus an exception among mineralized tissues that derive from the mesenchyme.

  14. Human Clade 2.3.4.4 A/H5N6 Influenza Virus Lacks Mammalian Adaptation Markers and Does Not Transmit via the Airborne Route between Ferrets.

    Science.gov (United States)

    Herfst, Sander; Mok, Chris K P; van den Brand, Judith M A; van der Vliet, Stefan; Rosu, Miruna E; Spronken, Monique I; Yang, Zifeng; de Meulder, Dennis; Lexmond, Pascal; Bestebroer, Theo M; Peiris, J S Malik; Fouchier, Ron A M; Richard, Mathilde

    2018-01-01

    Since their emergence in 1997, A/H5N1 influenza viruses of the A/goose/Guangdong/1/96 lineage have diversified in multiple genetic and antigenic clades upon continued circulation in poultry in several countries in Eurasia and Africa. Since 2009, reassortant viruses carrying clade 2.3.4.4 hemagglutinin (HA) and internal and neuraminidase (NA) genes of influenza A viruses of different avian origin have been detected, yielding various HA-NA combinations, such as A/H5N1, A/H5N2, A/H5N3, A/H5N5, A/H5N6, and A/H5N8. Previous studies reported on the low pathogenicity and lack of airborne transmission of A/H5N2 and A/H5N8 viruses in the ferret model. However, although A/H5N6 viruses are the only clade 2.3.4.4 viruses that crossed the species barrier and infected humans, the risk they pose for human health remains poorly characterized. Here, the characterization of A/H5N6 A/Guangzhou/39715/2014 virus in vitro and in ferrets is described. This A/H5N6 virus possessed high polymerase activity, mediated by the E627K substitution in the PB2 protein, which corresponds to only one biological trait out of the three that were previously shown to confer airborne transmissibility to A/H5N1 viruses between ferrets. This might explain its lack of airborne transmission between ferrets. After intranasal inoculation, A/H5N6 virus replicated to high titers in the respiratory tracts of ferrets and was excreted for at least 6 days. Moreover, A/H5N6 virus caused severe pneumonia in ferrets upon intratracheal inoculation. Thus, A/H5N6 virus causes a more severe disease in ferrets than previously investigated clade 2.3.4.4 viruses, but our results demonstrate that the risk from airborne spread is currently low. IMPORTANCE Avian influenza A viruses are a threat to human health, as they cross the species barrier and infect humans occasionally, often with severe outcome. The antigenic and genetic diversity of A/H5 viruses from the A/goose/Guangdong/1/96 lineage is increasing, due to continued

  15. Lack of effect of synthetic human gastric inhibitory polypeptide and glucagon-like peptide 1 [7-36 amide] infused at near-physiological concentrations on pentagastrin-stimulated gastric acid secretion in normal human subjects

    DEFF Research Database (Denmark)

    Nauck, M A; Bartels, E; Orskov, C

    1992-01-01

    -stimulated (0.1 micrograms/kg/h from -90 to 120 min) gastric volume, acid and chloride output, on separate occasions, synthetic human GIP (1 pmol/kg/min) and/or GLP-1 [7-36 amide] (0.3 pmol/kg/min) or placebo (0.9% NaCl with 1% albumin) were infused intravenously (from -30 to 120 min) in 9 healthy volunteers...... secretion). In conclusion, (penta)gastrin-stimulated gastric acid secretion is not inhibited by physiological circulating concentrations of GIP or GLP-1 [7-36 amide]. Therefore, the insulinotropic action of these intestinal hormones is physiologically more important than their possible role...

  16. Recombinant Cyclophilins Lack Nuclease Activity

    OpenAIRE

    Manteca, Angel; Sanchez, Jesus

    2004-01-01

    Several single-domain prokaryotic and eukaryotic cyclophilins have been identified as also being unspecific nucleases with a role in DNA degradation during the lytic processes that accompany bacterial cell death and eukaryotic apoptosis. Evidence is provided here that the supposed nuclease activity of human and bacterial recombinant cyclophilins is due to contamination of the proteins by the host Escherichia coli endonuclease and is not an intrinsic property of these proteins.

  17. Lack of Exposure in a First-in-Man Study Due to Aldehyde Oxidase Metabolism: Investigated by Use of 14C-microdose, Humanized Mice, Monkey Pharmacokinetics, and In Vitro Methods.

    Science.gov (United States)

    Jensen, Klaus Gjervig; Jacobsen, Anne-Marie; Bundgaard, Christoffer; Nilausen, Dorrit Østergaard; Thale, Zia; Chandrasena, Gamini; Jørgensen, Martin

    2017-01-01

    Inclusion of a microdose of 14 C-labeled drug in the first-in-man study of new investigational drugs and subsequent analysis by accelerator mass spectrometry has become an integrated part of drug development at Lundbeck. It has been found to be highly informative with regard to investigations of the routes and rates of excretion of the drug and the human metabolite profiles according to metabolites in safety testing guidance and also when additional metabolism-related issues needed to be addressed. In the first-in-man study with the NCE Lu AF09535, contrary to anticipated, surprisingly low exposure was observed when measuring the parent compound using conventional bioanalysis. Parallel accelerator mass spectrometry analysis revealed that the low exposure was almost exclusively attributable to extensive metabolism. The metabolism observed in humans was mediated via a human specific metabolic pathway, whereas an equivalent extent of metabolism was not observed in preclinical species. In vitro, incubation studies in human liver cytosol revealed involvement of aldehyde oxidase (AO) in the biotransformation of Lu AF09535. In vivo, substantially lower plasma exposure of Lu AF09535 was observed in chimeric mice with humanized livers compared with control animals. In addition, Lu AF09535 exhibited very low oral bioavailability in monkeys despite relatively low clearance after intravenous administration in contrast to the pharmacokinetics in rats and dogs, both showing low clearance and high bioavailability. The in vitro and in vivo methods applied were proved useful for identifying and evaluating AO-dependent metabolism. Different strategies to integrate these methods for prediction of in vivo human clearance of AO substrates were evaluated. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  18. Development of ADA Against Recombinant Human Interferon Beta in Immune Tolerant Mice Requires Rapid Recruitment of CD4(+) T Cells, Induces Formation of Germinal Centers but Lacks Susceptibility for (Most) Adjuvants

    NARCIS (Netherlands)

    Kijanka, Grzegorz; Sauerborn, Melody; Boon, Louis; Schellekens, Huub; Brinks, Vera

    Immunological processes leading to formation of antidrug antibodies (Abs) against recombinant human proteins remain poorly understood. Animal and clinical studies revealed that immunogenicity shares both T-cell-dependent (requirement of CD4(+) T cells, isotype switching) and T-cell-independent

  19. Lack of correlation between virus barosensitivity and the presence of a viral envelope during inactivation of human rotavirus, vesicular stomatitis virus, and avian metapneumovirus by high-pressure processing.

    Science.gov (United States)

    Lou, Fangfei; Neetoo, Hudaa; Li, Junan; Chen, Haiqiang; Li, Jianrong

    2011-12-01

    High-pressure processing (HPP) is a nonthermal technology that has been shown to effectively inactivate a wide range of microorganisms. However, the effectiveness of HPP on inactivation of viruses is relatively less well understood. We systematically investigated the effects of intrinsic (pH) and processing (pressure, time, and temperature) parameters on the pressure inactivation of a nonenveloped virus (human rotavirus [HRV]) and two enveloped viruses (vesicular stomatitis virus [VSV] and avian metapneumovirus [aMPV]). We demonstrated that HPP can efficiently inactivate all tested viruses under optimal conditions, although the pressure susceptibilities and the roles of temperature and pH substantially varied among these viruses regardless of the presence of a viral envelope. We found that VSV was much more stable than most food-borne viruses, whereas aMPV was highly susceptible to HPP. When viruses were held for 2 min under 350 MPa at 4°C, 1.1-log, 3.9-log, and 5.0-log virus reductions were achieved for VSV, HRV, and aMPV, respectively. Both VSV and aMPV were more susceptible to HPP at higher temperature and lower pH. In contrast, HRV was more easily inactivated at higher pH, although temperature did not have a significant impact on inactivation. Furthermore, we demonstrated that the damage of virion structure by disruption of the viral envelope and/or capsid is the primary mechanism underlying HPP-induced viral inactivation. In addition, VSV glycoprotein remained antigenic although VSV was completely inactivated. Taken together, our findings suggest that HPP is a promising technology to eliminate viral contaminants in high-risk foods, water, and other fomites.

  20. Mouse Models Recapitulating Human Adrenocortical Tumors: What is lacking?

    Directory of Open Access Journals (Sweden)

    Felicia Leccia

    2016-07-01

    Full Text Available Adrenal cortex tumors are divided into benign forms such as primary hyperplasias and adrenocortical adenomas (ACAs, and malignant forms or adrenocortical carcinomas (ACCs. Primary hyperplasias are rare causes of ACTH-independent hypercortisolism. ACAs are the most common type of adrenal gland tumors and they are rarely functional, i.e producing steroids. When functional, adenomas result in endocrine disorders such as Cushing’s syndrome (hypercortisolism or Conn’s syndrome (hyperaldosteronism. In contrast, ACCs are extremely rare but highly aggressive tumors that may also lead to hypersecreting syndromes. Genetic analyses of patients with sporadic or familial forms of adrenocortical tumors led to the identification of potentially causative genes, most of them being involved in PKA, Wnt/β-catenin and P53 signaling pathways. Development of mouse models is a crucial step to firmly establish the functional significance of candidate genes, to dissect mechanisms leading to tumors and endocrine disorders and in fine to provide in vivo tools for therapeutic screens. In this article we will provide an overview on the existing mouse models (xenografted and genetically engineered of adrenocortical tumors by focusing on the role of PKA and Wnt/β-catenin pathways in this context. We will discuss the advantages and limitations of models that have been developed heretofore and we will point out necessary improvements in the development of next generation mouse models of adrenal diseases.

  1. A Phenomenological Study on Lack of Motivation

    Science.gov (United States)

    Educational Research and Reviews, 2013

    2013-01-01

    The aim of this research is to point out the underlying reasons about the lack of motivation at academic activities concerning Attribution Theory. Attribution Theory trys to understand how the people answer "why" question and how they do casual explanations. This research is a qualitative based research. It used the phenomenological…

  2. Conceptualising the lack of health insurance coverage.

    Science.gov (United States)

    Davis, J B

    2000-01-01

    This paper examines the lack of health insurance coverage in the US as a public policy issue. It first compares the problem of health insurance coverage to the problem of unemployment to show that in terms of the numbers of individuals affected lack of health insurance is a problem comparable in importance to the problem of unemployment. Secondly, the paper discusses the methodology involved in measuring health insurance coverage, and argues that the current method of estimation of the uninsured underestimates the extent that individuals go without health insurance. Third, the paper briefly introduces Amartya Sen's functioning and capabilities framework to suggest a way of representing the extent to which individuals are uninsured. Fourth, the paper sketches a means of operationalizing the Sen representation of the uninsured in terms of the disability-adjusted life year (DALY) measure.

  3. Laura: Soybean variety lacking Kunitz trypsin inhibitor

    Directory of Open Access Journals (Sweden)

    Srebrić Mirjana

    2010-01-01

    Full Text Available Grain of conventional soybean varieties requires heat processing to break down trypsin inhibitor's activity before using as food or animal feed. At the same time, protein denaturation and other qualitative changes occur in soybean grain, especially if the temperature of heating is not controlled. Two types of trypsin inhibitor were found in soybean grain the Kunitz trypsin inhibitor and the Bowman-Birk inhibitor. Mature grain of soybean Laura is lacking Kunitz trypsin inhibitor. Grain yield of variety Laura is equal to high yielding varieties from the maturity group I, where it belongs. Lacking of Kunitz-trypsin inhibitor makes soybean grain suitable for direct feeding in adult non ruminant animals without previous thermal processing. Grain of variety Laura can be processed for a shorter period of time than conventional soybeans. This way we save energy, and preserve valuable nutritional composition of soybean grain, which is of interest in industrial processing.

  4. Molecular Evolution of the Glycosyltransferase 6 Gene Family in Primates

    Directory of Open Access Journals (Sweden)

    Eliane Evanovich

    2016-01-01

    Full Text Available Glycosyltransferase 6 gene family includes ABO, Ggta1, iGb3S, and GBGT1 genes and by three putative genes restricted to mammals, GT6m6, GTm6, and GT6m7, only the latter is found in primates. GT6 genes may encode functional and nonfunctional proteins. Ggta1 and GBGT1 genes, for instance, are pseudogenes in catarrhine primates, while iGb3S gene is only inactive in human, bonobo, and chimpanzee. Even inactivated, these genes tend to be conversed in primates. As some of the GT6 genes are related to the susceptibility or resistance to parasites, we investigated (i the selective pressure on the GT6 paralogs genes in primates; (ii the basis of the conservation of iGb3S in human, chimpanzee, and bonobo; and (iii the functional potential of the GBGT1 and GT6m7 in catarrhines. We observed that the purifying selection is prevalent and these genes have a low diversity, though ABO and Ggta1 genes have some sites under positive selection. GT6m7, a putative gene associated with aggressive periodontitis, may have regulatory function, but experimental studies are needed to assess its function. The evolutionary conservation of iGb3S in humans, chimpanzee, and bonobo seems to be the result of proximity to genes with important biological functions.

  5. Lack of centrioles and primary cilia in STIL(-/-) mouse embryos.

    Science.gov (United States)

    David, Ahuvit; Liu, Fengying; Tibelius, Alexandra; Vulprecht, Julia; Wald, Diana; Rothermel, Ulrike; Ohana, Reut; Seitel, Alexander; Metzger, Jasmin; Ashery-Padan, Ruth; Meinzer, Hans-Peter; Gröne, Hermann-Josef; Izraeli, Shai; Krämer, Alwin

    2014-01-01

    Although most animal cells contain centrosomes, consisting of a pair of centrioles, their precise contribution to cell division and embryonic development is unclear. Genetic ablation of STIL, an essential component of the centriole replication machinery in mammalian cells, causes embryonic lethality in mice around mid gestation associated with defective Hedgehog signaling. Here, we describe, by focused ion beam scanning electron microscopy, that STIL(-/-) mouse embryos do not contain centrioles or primary cilia, suggesting that these organelles are not essential for mammalian development until mid gestation. We further show that the lack of primary cilia explains the absence of Hedgehog signaling in STIL(-/-) cells. Exogenous re-expression of STIL or STIL microcephaly mutants compatible with human survival, induced non-templated, de novo generation of centrioles in STIL(-/-) cells. Thus, while the abscence of centrioles is compatible with mammalian gastrulation, lack of centrioles and primary cilia impairs Hedgehog signaling and further embryonic development.

  6. Accidents in radiotherapy: Lack of quality assurance?

    International Nuclear Information System (INIS)

    Novotny, J.

    1997-01-01

    About 150 radiological accidents, involving more than 3000 patients with adverse effects, 15 patient's fatalities and about 5000 staff and public exposures have been collected and analysed. Out of 67 analysed accidents in external beam therapy 22% has been caused by wrong calculation of the exposure time or monitor units, 13% by inadequate review of patient's chart, 12% by mistakes in the anatomical area to be treated. The remaining 35% can be attributed to 17 different causes. The most common mistakes in brachytherapy were wrong activities of sources used for treatment (20%), inadequate procedures for placement of sources applicators (14%), mistakes in calculating the treatment time (12%), etc. The direct and contributing causes of radiological accidents have been deduced from each event, when it was possible and categorized into 9 categories: mistakes in procedures (30%), professional mistakes (17%), communication mistakes (15%), lack of training (8.5%), interpretation mistakes (7%), lack of supervision (6%), mistakes in judgement (6%), hardware failures (5%), software and other mistakes (5.5%). Three types of direct and contributing causes responsible for almost 62% of all accidents are directly connected to the quality assurance of treatment. The lessons learnt from the accidents are related to frequencies of direct and contributing factors and show that most of the accident are caused by lack, non-application of quality assurance (QA) procedures or by underestimating of QA procedures. The international system for collection of accidents and dissemination of lessons learnt from the different accidents, proposed by IAEA, can contribute to better practice in many radiotherapy departments. Most of the accidents could have been avoided, had a comprehensive QA programme been established and properly applied in all radiotherapy departments, whatever the size. (author)

  7. Why does Colombia lack agricultural commodity futures?

    Directory of Open Access Journals (Sweden)

    Pablo Moreno-Alemay

    2015-11-01

    Full Text Available This article explores the reasons why futures contracts are not traded as an alternative to price hedging for agricultural goods in Colombia. Based on surveys, interviews and statistical analysis, this study identified that conceptual gaps in contract negotiation, lack of consensus in the agricultural sector regarding the use of financial mechanisms and the sector’s infrequent contact with Colombia’s financial institutions, are the main reasons why a futures contracts market has not emerged.

  8. Reduced alcohol consumption in mice lacking preprodynorphin.

    Science.gov (United States)

    Blednov, Yuri A; Walker, Danielle; Martinez, Marni; Harris, R Adron

    2006-10-01

    Many studies suggest a role for endogenous opioid peptides and their receptors in regulation of ethanol intake. It is commonly accepted that the kappa-opioid receptors and their endogenous ligands, dynorphins, produce a dysphoric state and therefore may be responsible for avoidance of alcohol. We used mutant mice lacking preprodynorphin in a variety of behavioral tests of alcohol actions. Null mutant female, but not male, mice showed significantly lower preference for alcohol and consumed lower amounts of alcohol in a two-bottle choice test as compared with wild-type littermates. In the same test, knockout mice of both sexes showed a strong reduction of preference for saccharin compared to control mice. In contrast, under conditions of limited (4 h) access (light phase of the light/dark cycle), null mutant mice did not show any differences in consumption of saccharin, but they showed significantly reduced intake of sucrose. To determine the possible cause for reduction of ethanol preference and intake, we studied other ethanol-related behaviors in mice lacking the preprodynorphin gene. There were no differences between null mutant and wild-type mice in ethanol-induced loss of righting reflex, acute ethanol withdrawal, ethanol-induced conditioned place preference, or conditioned taste aversion to ethanol. These results indicate that deletion of preprodynorphin leads to substantial reduction of alcohol intake in female mice, and suggest that this is caused by decreased orosensory reward of alcohol (sweet taste and/or palatability).

  9. Lack of consensus in social systems

    Science.gov (United States)

    Benczik, I. J.; Benczik, S. Z.; Schmittmann, B.; Zia, R. K. P.

    2008-05-01

    We propose an exactly solvable model for the dynamics of voters in a two-party system. The opinion formation process is modeled on a random network of agents. The dynamical nature of interpersonal relations is also reflected in the model, as the connections in the network evolve with the dynamics of the voters. In the infinite time limit, an exact solution predicts the emergence of consensus, for arbitrary initial conditions. However, before consensus is reached, two different metastable states can persist for exponentially long times. One state reflects a perfect balancing of opinions, the other reflects a completely static situation. An estimate of the associated lifetimes suggests that lack of consensus is typical for large systems.

  10. Lack of RNase L attenuates macrophage functions.

    Directory of Open Access Journals (Sweden)

    Xin Yi

    Full Text Available Macrophages are one of the major cell types in innate immunity against microbial infection. It is believed that the expression of proinflammatory genes such as tumor necrosis factor-α (TNF-α, interleukin (IL-1β, IL-6, and cyclooxygenase-2 (Cox-2 by macrophages is also crucial for activation of both innate and adaptive immunities. RNase L is an interferon (IFN inducible enzyme which is highly expressed in macrophages. It has been demonstrated that RNase L regulates the expression of certain inflammatory genes. However, its role in macrophage function is largely unknown.Bone marrow-derived macrophages (BMMs were generated from RNase L(+/+and (-/- mice. The migration of BMMs was analyzed by using Transwell migration assays. Endocytosis and phagocytosis of macrophages were assessed by using fluorescein isothiocyanate (FITC-Dextran 40,000 and FITC-E. coli bacteria, respectively. The expression of inflammatory genes was determined by Western Blot and ELISA. The promoter activity of Cox-2 was measured by luciferase reporter assays.Lack of RNase L significantly decreased the migration of BMMs induced by M-CSF, but at a less extent by GM-CSF and chemokine C-C motif ligand-2 (CCL2. Interestingly, RNase L deficient BMMs showed a significant reduction of endocytic activity to FITC-Dextran 40,000, but no any obvious effect on their phagocytic activity to FITC-bacteria under the same condition. RNase L impacts the expression of certain genes related to cell migration and inflammation such as transforming growth factor (TGF-β, IL-1β, IL-10, CCL2 and Cox-2. Furthermore, the functional analysis of the Cox-2 promoter revealed that RNase L regulated the expression of Cox-2 in macrophages at its transcriptional level. Taken together, our findings provide direct evidence showing that RNase L contributes to innate immunity through regulating macrophage functions.

  11. Lack of efficacy of ergocalciferol repletion

    Directory of Open Access Journals (Sweden)

    Thomas Wasser

    2012-04-01

    Full Text Available Introduction: Vitamin D has become an area of intensive scrutiny, both in medical and lay literature. However, there are limited data to suggest proper repletion regimens for those patients who have hypovitaminosis D. Consequently, various methods are used in clinical practice. The aim of this study was to assess the efficacy of various treatment strategies for hypovitaminosis D in an ambulatory internal medicine practice. Methods: A retrospective chart review between October 2005 and June 2010 of a suburban internal medicine practice was performed via query of the electronic medical record (Centricity, General Electric Healthcare, UK. Patients with a 25-hydroxyvitamin D concentration less than 32 mg/dl were identified and treated. Treatment success was defined as 25-hydroxyvitamin D concentrations greater than 32 mg/dl. Statistical analysis to assess changes in vitamin D level controlling for season, comorbidities, and demographics were used. Results: A total of 607 treatment episodes were identified, with 395 excluded due to lack of follow-up vitamin D level within 16 weeks, no treatment documented, topical treatment, doxercalciferol treatment, or non-compliance. Of the remaining patients, there were 212 treatment instances on 178 patients. Ergocalciferol 50,000 international units (IU was used most frequently (71.4% of the time.. A higher initial vitamin D level was positively associated with treatment success (adjusted odds ratio = 1.11, p=0.002. Increased doses of ergocalciferol increased the likelihood of treatment success (p=0.0011. Seasonal variation was related to posttreatment 25-hydroxyvitamin D concentration as was body mass index (BMI (p=0.003 and p=0.044. Conclusion: Pretreatment levels of 25-hydroxyvitamin D, BMI, season, and vitamin D dose are predictors of successful hypovitaminosis D treatment. Our data suggest that patients with initial 25-hydroxyvitamin D concentrations of <20 should be treated with a higher total dose of

  12. Editor's Highlight: Complete Attenuation of Mouse Lung Cell Proliferation and Tumorigenicity in CYP2F2 Knockout and CYP2F1 Humanized Mice Exposed to Inhaled Styrene for up to 2 Years Supports a Lack of Human Relevance.

    Science.gov (United States)

    Cruzan, George; Bus, James S; Banton, Marcy I; Sarang, Satinder S; Waites, Robbie; Layko, Debra B; Raymond, James; Dodd, Darol; Andersen, Melvin E

    2017-10-01

    Styrene is a mouse-specific lung carcinogen, and short-term mode of action studies have demonstrated that cytotoxicity and/or cell proliferation, and genomic changes are dependent on CYP2F2 metabolism. The current study examined histopathology, cell proliferation, and genomic changes in CD-1, C57BL/6 (WT), CYP2F2(-/-) (KO), and CYP2F2(-/-) (CYP2F1, 2B6, 2A13-transgene) (TG; humanized) mice following exposure for up to 104 weeks to 0- or 120-ppm styrene vapor. Five mice per treatment group were sacrificed at 1, 26, 52, and 78 weeks. Additional 50 mice per treatment group were followed until death or 104 weeks of exposure. Cytotoxicity was present in the terminal bronchioles of some CD-1 and WT mice exposed to styrene, but not in KO or TG mice. Hyperplasia in the terminal bronchioles was present in CD-1 and WT mice exposed to styrene, but not in KO or TG mice. Increased cell proliferation, measured by KI-67 staining, occurred in CD-1 and WT mice exposed to styrene for 1 week, but not after 26, 52, or 78 weeks, nor in KO or TG mice. Styrene increased the incidence of bronchioloalveolar adenomas and carcinomas in CD-1 mice. No increase in lung tumors was found in WT despite clear evidence of lung toxicity, or, KO or TG mice. The absence of preneoplastic lesions and tumorigenicity in KO and TG mice indicates that mouse-specific CYP2F2 metabolism is responsible for both the short-term and chronic toxicity and tumorigenicity of styrene, and activation of styrene by CYP2F2 is a rodent MOA that is neither quantitatively or qualitatively relevant to humans. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Motor hypertonia and lack of locomotor coordination in mutant mice lacking DSCAM.

    Science.gov (United States)

    Lemieux, Maxime; Laflamme, Olivier D; Thiry, Louise; Boulanger-Piette, Antoine; Frenette, Jérôme; Bretzner, Frédéric

    2016-03-01

    Down syndrome cell adherence molecule (DSCAM) contributes to the normal establishment and maintenance of neural circuits. Whereas there is abundant literature regarding the role of DSCAM in the neural patterning of the mammalian retina, less is known about motor circuits. Recently, DSCAM mutation has been shown to impair bilateral motor coordination during respiration, thus causing death at birth. DSCAM mutants that survive through adulthood display a lack of locomotor endurance and coordination in the rotarod test, thus suggesting that the DSCAM mutation impairs motor control. We investigated the motor and locomotor functions of DSCAM(2J) mutant mice through a combination of anatomical, kinematic, force, and electromyographic recordings. With respect to wild-type mice, DSCAM(2J) mice displayed a longer swing phase with a limb hyperflexion at the expense of a shorter stance phase during locomotion. Furthermore, electromyographic activity in the flexor and extensor muscles was increased and coactivated over 20% of the step cycle over a wide range of walking speeds. In contrast to wild-type mice, which used lateral walk and trot at walking speed, DSCAM(2J) mice used preferentially less coordinated gaits, such as out-of-phase walk and pace. The neuromuscular junction and the contractile properties of muscles, as well as their muscle spindles, were normal, and no signs of motor rigidity or spasticity were observed during passive limb movements. Our study demonstrates that the DSCAM mutation induces dystonic hypertonia and a disruption of locomotor gaits. Copyright © 2016 the American Physiological Society.

  14. Mutant Mice Lacking the p53 C-Terminal Domain Model Telomere Syndromes

    NARCIS (Netherlands)

    Simeonova, I.; Jaber, S.; Draskovic, I.; Bardot, B.; Fang, M.; Bouarich-Bourimi, R.; Lejour, V.; Charbonnier, L.; Soudais, C.; Bourdon, J.C.; Huerre, M.; Londono-Vallejo, A.; Toledo, F.

    2013-01-01

    Mutations in p53, although frequent in human cancers, have not been implicated in telomere-related syndromes. Here, we show that homozygous mutant mice expressing p53(Delta31), a p53 lacking the C-terminal domain, exhibit increased p53 activity and suffer from aplastic anemia and pulmonary fibrosis,

  15. A Comparison between Administration of First Nations Education in Canada and Peru: Divestments, Losses and Lacks.

    Science.gov (United States)

    Young-Ing, Greg

    1988-01-01

    Points out similarities in the histories of Canadian and Peruvian government policies on the formal schooling of Native peoples. Discusses the divestment of Native cultural capital, loss of human potential, and lack of recognition of a fundamental Aboriginal right in both countries. Contains 20 references. (SV)

  16. 10 CFR 503.21 - Lack of alternate fuel supply.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Lack of alternate fuel supply. 503.21 Section 503.21 Energy DEPARTMENT OF ENERGY (CONTINUED) ALTERNATE FUELS NEW FACILITIES Temporary Exemptions for New Facilities § 503.21 Lack of alternate fuel supply. (a) Eligibility. Section 211(a)(1) of the Act provides for...

  17. Lack of consent for mediation between companies and its reasons

    OpenAIRE

    Karpińska-Królikowska, Iwona

    2011-01-01

    This article discusses commercial mediation, presenting its principles and procedure. It shows the reason why I became interested in the topic of companies’ lack of willingness to solve problems through mediation. It presents empirical statistics from mediation in commercial cases, including those on lack of consents or settlements. The figures are shown against the background of court statistics. On the basis of research conducted in the form of case studies, it presents...

  18. Lack of dust in quasar absorption line systems

    International Nuclear Information System (INIS)

    Jura, M.

    1977-01-01

    It is stated that the origin of absorption line systems in quasars is still uncertain. Most such systems apparently have atomic hydrogen column densities of the order of 10 19 /cm 2 , but at least two quasars, 1331 + 170 and PHL957, have such strong Lyman α absorption lines that atomic hydrogen column densities of the order of 10 21 /cm 2 are indicated. It should be possible to observe the dust produced 2,200 A extinction feature as it is red shifted into the visible, and to determine whether absorption line systems are produced in spiral galaxies where the dust content is similar to that in the interstellar medium. It has been argued that the emission line regions of quasars generally lack dust and that towards PHL957 the 2,200 A feature is absent. The present author argues that dust similar to that found in the interstellar medium is not found towards the quasars 1331 + 170 and PHL957. This could explain why H 2 is not found towards PHL957, and it indicates that the absorption line systems in quasars are not produced in spiral galaxies similar to our own. It seems from the analysis presented that the dust-to-gas ratio towards 1331 + 170 is at least a factor of 20 less than in the interstellar medium, and there is no reason to suppose that this lack of dust results from a lack of metals It is concluded that there seems to be a lack of normal dust towards PHL957 by at least a factor of two; and that the absorption region towards 1331 + 170 and probably the region towards PHL957 are lacking dust similar to that in our own galaxy. This can explain the lack of H 2 in these systems. (U.K.)

  19. Effect of lack of later support in the masseter muscle

    International Nuclear Information System (INIS)

    Fernandez Lopez, Otton

    2007-01-01

    One of the main complaints during dental consultation has been pain in the zone of the masseter muscle, especially a lack of rear support. None research has published that reveals what has been the relationship between the rear support and histological alterations in muscle mass. Both topics have treated to relate through a process of tooth wear in laboratory animals and produce a lack of rear support. Cuts of the masseter muscles and specimens were subjected to microscopic study of light and electronic. The conclusion has been that by removing the rear support are produced important changes to histological level. (author) [es

  20. [Lack of neonatologists: vocational crisis or mistaken policies?].

    Science.gov (United States)

    Justich, Pablo R

    2012-10-01

    In Argentina, the difficulty in covering neonatologist's positions represent an increasing problem. The absence of a coordinated and organized health system on one hand, and the lack of adaptation of the neonatologist's role to the current situation of the maternal and child care on the other, prevent the correct assistential coverage. The inadequate work conditions, the professional risks, the wide amount of time devoted to formation and studying, and the lack of knowledge of the professionals necessities and difficulties have a negative impact when it comes to incorporate new specialists. A global approach of the problem is essential to reach enduring answers.

  1. Children's Lack of Playtime Seen as Troubling Health, School Issue

    Science.gov (United States)

    Jacobson, Linda

    2008-01-01

    Teachers and parents are frequently warned that students in the United States are lacking the academic skills they need for the 21st century. But a growing contingent of educators, psychologists, and other professionals are voicing worries that today's children are also growing up without the chance to play. Test preparation in kindergarten,…

  2. Lack of competition in Italian natural gas market

    International Nuclear Information System (INIS)

    Bozzetto, Fabrizio

    2007-01-01

    This article analyses the reasons for an evident lack of competition in the Italian natural gas market, after the 2003 full liberalisation of the market. In particular, analysis focuses on dynamics which probably marks mass market and small office segments [it

  3. Kidney failure in mice lacking the tetraspanin CD151

    NARCIS (Netherlands)

    Sachs, Norman; Kreft, Maaike; van den Bergh Weerman, Marius A.; Beynon, Andy J.; Peters, Theo A.; Weening, Jan J.; Sonnenberg, Arnoud

    2006-01-01

    The tetraspanin CD151 is a cell-surface molecule known for its strong lateral interaction with the laminin-binding integrin alpha3beta1. Patients with a nonsense mutation in CD151 display end-stage kidney failure associated with regional skin blistering and sensorineural deafness, and mice lacking

  4. Kidney failure in mice lacking the tetraspanin CD151.

    NARCIS (Netherlands)

    Sachs, N.; Kreft, M.; Bergh Weerman, M. van der; Beynon, A.J.; Peters, T.A.; Weening, J.J.; Sonnenberg, A.

    2006-01-01

    The tetraspanin CD151 is a cell-surface molecule known for its strong lateral interaction with the laminin-binding integrin alpha3beta1. Patients with a nonsense mutation in CD151 display end-stage kidney failure associated with regional skin blistering and sensorineural deafness, and mice lacking

  5. Siim Nestor soovitab : lack of Eoins / Siim Nestor

    Index Scriptorium Estoniae

    Nestor, Siim, 1974-

    2008-01-01

    Väikefirma Seksound annab sel nädalavahetusel välja Viljandi indiebändi Lack of Eoins esikplaadi "Echo Group" (plaadiesitlused 11. dets. Tallinnas Von Krahlis ja 12. dets. Tartus Genialistide klubis, esinevad ka Ans. Andur ja Popidiot, plaate keerutavad Hannes Praks ja Taavi Laatsit)

  6. Lack of a safety culture destroyed the reactor

    International Nuclear Information System (INIS)

    Vuori, A.

    1996-01-01

    The importance of good safety culture in the operation of nuclear power plants is discussed. The modern safety culture emphasizes responsibility and preventive maintenance that can eliminate or minimize faults in advance. In the article the accident of Chernobyl is used as an example of the lack of safety culture. (1 fig.)

  7. Special Relativity in Week One: 4) Lack of Simultaneity

    Science.gov (United States)

    Huggins, Elisha

    2011-01-01

    This is our final article on teaching special relativity in the first week of an introductory physics course. One of the profound changes in our view of the world was Einstein's discovery of the lack of simultaneity. He illustrated this result with a thought experiment in which we observe a railroad car passing by us. We see the two ends of the…

  8. Lack of pre-antiretroviral care and competition from traditional ...

    African Journals Online (AJOL)

    Lack of family support tripled the risk of initiating ART very late (AOR 3.3, 95% CI: 1.6-6.6). Conclusion: Policy makers should prevent ARV stock-outs though effective ARV procurement and supply chain management. New HIV clients should seek pre-ARV care for routine monitoring and determination of ART eligibility.

  9. Economy may be harmed by lack of LLW disposal

    International Nuclear Information System (INIS)

    Anon.

    1994-01-01

    A study released by Organizations United for Responsible Low-Level Radioactive Waste Solutions warns that the substantial benefits of using radioactive materials are threatened by the lack of a low-level waste (LLW) disposal facility. The main point of the study is the threat to the American economy posed by insufficient facilities for disposal of the 1.7 billion ft 3 of LLW produced by the use of radioactive materials every year only 34.8 percent of which comes from nuclear power plants. open-quotes Thirty years of experience have provided the technical knowledge to design waste disposal facilities that protect the public and environment. But an impending lack of adequate disposal facilities jeopardizes our continued use of radioactive materials,close quotes according to the study

  10. Lack of diversity in behavioral healthcare leadership reflected in services.

    Science.gov (United States)

    Rosenberg, Linda

    2008-04-01

    America's rapidly changing demographics present an enormous challenge for today's healthcare leaders to redesign the organization and delivery of care to accommodate people who now represent every language, culture and religious belief in the world. So will mental health and addictions services in this country be ready to address the unique needs of these multicultural patients? A survey of the present landscape in 2008 tells us that we have a long, long way to go. Not only are mental health and addictions fields lacking in cultural competency, but there is little diversity in our leadership ranks. Top administrators and executives in behavioral health today are overwhelmingly non-Hispanic whites. This lack of cultural diversity among our leaders will lead to an ever-widening gap in the current chasm of racial and ethnic disparities in healthcare.

  11. Law tightened to protect adults who lack capacity.

    Science.gov (United States)

    2009-05-21

    VULNERABLE OLDER people will be better protected from abuse and poor care after new legislation came into force last month. Under the Mental Capacity Act Deprivation of Liberty Safeguards, a care home or hospital wanting to deprive a person who lacks capacity of their liberty, for their own safety or wellbeing, must now apply for permission. A rigorous, standardised assessment and authorisation process must then be completed.

  12. Return voltage: reproductibility of lack in isolated plastics

    International Nuclear Information System (INIS)

    Frutos, F.; Acedo, M.; Jimenez, A.; Perez, J.A.

    1998-01-01

    Return voltage measures from plane-plane and point-plane experimental test objects of polyethylene are presented. Even though a lack of reproducibility is observed, all the experimental voltage curves can be modellized as the sum of two exponential functions: a first one with a long time period and a second one with a quite shorter time parameter. This analytical behaviour could be theoretically explained by considering an exponential dielectric function response. (Author) 7 refs

  13. The subjetivacion of the lack: between Lacan and Hegel

    Directory of Open Access Journals (Sweden)

    Lorena Souyris Oportot

    2014-05-01

    Full Text Available The present article develops a reflection concerning the figure of the subjectivation and the statute of the lack  in relation to Jacques Lacan y Hegel's thought . The analysis will be addressed from a philosophical approach as and with a psychoanalytic perspective, to show the need to understand the subjectivity, not already as a "work" of duel, but ligature to the loss and the split. The idea is that the above mentioned significances make possible deconstruir and to rethink the duel in lack, that he structures to the subject in an experience "escripturaire" (escriptural and, for the same thing, of dispossession. So that the figure of the subjetivación "in" lack  will allow to grant an important place to the non-place while I spread where the unthinkable thing and the "Autre" registers.  Once exposed this, the reflection will focus on the tragic exigences behind experience “escripturaire” expressed in the image of Antigone

  14. REPROBATION AND LACK OF INTEREST IN MECHATRONICS ENGINEERING STUDENTS

    Directory of Open Access Journals (Sweden)

    César Humberto Guzmán Valdivia

    2013-07-01

    Full Text Available Engineering education in mechatronics is an attractive field of research because it is a new multidisciplinary career. However, a potential problem is the reprobation rate. In the period from January to April 2012 at the Universidad Politécnica de Zacatecas a 53% regular students of a total of 197 were registered. To find the causes of this problem, a survey was conducted to determine the causes of reprobation, lack of motivation and interest to a population of 96 students, of which 40 were the first training cycle, 32 the second and 24 the third. The surveys yielded three main results. The first indicates that the lack of interest is proportional to the time spent in college. The second shows that the reprobation rate is linked to the laziness and the excess of courses. And the last shows a lack of motivation and low expectations of student due to the monotony of the theoretical courses. In conclusion, more research is needed to have a motivated student in an engineering career in mechatronics.

  15. Lack of centrioles and primary cilia in STIL−/− mouse embryos

    Science.gov (United States)

    David, Ahuvit; Liu, Fengying; Tibelius, Alexandra; Vulprecht, Julia; Wald, Diana; Rothermel, Ulrike; Ohana, Reut; Seitel, Alexander; Metzger, Jasmin; Ashery-Padan, Ruth; Meinzer, Hans-Peter; Gröne, Hermann-Josef; Izraeli, Shai; Krämer, Alwin

    2014-01-01

    Although most animal cells contain centrosomes, consisting of a pair of centrioles, their precise contribution to cell division and embryonic development is unclear. Genetic ablation of STIL, an essential component of the centriole replication machinery in mammalian cells, causes embryonic lethality in mice around mid gestation associated with defective Hedgehog signaling. Here, we describe, by focused ion beam scanning electron microscopy, that STIL−/− mouse embryos do not contain centrioles or primary cilia, suggesting that these organelles are not essential for mammalian development until mid gestation. We further show that the lack of primary cilia explains the absence of Hedgehog signaling in STIL−/− cells. Exogenous re-expression of STIL or STIL microcephaly mutants compatible with human survival, induced non-templated, de novo generation of centrioles in STIL−/− cells. Thus, while the abscence of centrioles is compatible with mammalian gastrulation, lack of centrioles and primary cilia impairs Hedgehog signaling and further embryonic development. PMID:25486474

  16. Nuclear Energy is the Answer to Cope with the Lack of Energy and Global Warming

    International Nuclear Information System (INIS)

    Wisnu Arya Wardhana

    2009-01-01

    This paper of nuclear energy is the answer to cope with the lack of energy and global warming based on the analysis of energy demand which is increasing rapidly, meanwhile the energy reserve is limited and decreased. Mostly world′s energy is generated by fossil fuel energy, mainly oil and coal. Fossil fuel energy and industrial activities produce green house gases (GHG) such as : COx, CH 4 , N 2 O, and CFC which cause of global warming. Global warming gives bad impact to environment and to human being. Every country in the world needs sufficient energy, but the energy resources is limited and decreased. The answer for this solution must be an energy source which does not produce green house gases. Why nuclear energy is chosen to cope with the lack of energy and global warming will be explained briefly in this paper. (author)

  17. UK Citizens Lack Simple, Objective Knowledge of the European Union

    DEFF Research Database (Denmark)

    Manners, Ian James

    2017-01-01

    214); ‘A direct European tax will be created’ (EBS 214); ‘National citizenship will disappear’ (EBS 214); and ‘Most of the European budget is spent on administrative and personnel costs’ (EB65) UK respondents were far more likely to answer incorrectly that these were true. This is likely the result...... of disinformation in UK politics and media. The data suggests that not only are UK respondents unable to answer simple questions about the EU, but that they are relatively more likely to answer incorrectly rather than admit they did not know, reflecting disinformation about the EU in the UK. This lack of simple...

  18. Reincarnation and the Lack of Imagination in Philosophy

    Directory of Open Access Journals (Sweden)

    Mikel Burley

    2015-12-01

    Full Text Available It has been observed, by D. Z. Phillips among others, that philosophy suffers from a “lack of imagination”. That is, philosophers often fail to see possibilities of sense in forms of life and discourse due to narrow habits of thinking. This is especially problematic in the philosophy of religion, not least when cross-cultural modes of inquiry are called for. This article examines the problem in relation to the philosophical investigation of reincarnation beliefs in particular. As a remedial strategy, I argue for increased attention both to ethnographic sources and to the articulation of distinctively religious moral visions that reincarnation-talk facilitates.

  19. Lack of tissue renewal in human adult Achilles tendon is revealed by nuclear bomb C

    DEFF Research Database (Denmark)

    Heinemeier, Katja Maria; Schjerling, Peter; Heinemeier, J.

    2013-01-01

    the 14C bomb-pulse method. This method takes advantage of the dramatic increase in atmospheric levels of 14C, produced by nuclear bomb tests in 1955-1963, which is reflected in all living organisms. Levels of 14C were measured in 28 forensic samples of Achilles tendon core and 4 skeletal muscle samples...... is revealed by nuclear bomb 14C....

  20. Lack of mitochondrial trifunctional protein in mice causes neonatal hypoglycemia and sudden death

    OpenAIRE

    Ibdah, Jamal A.; Paul, Hyacinth; Zhao, Yiwen; Binford, Scott; Salleng, Ken; Cline, Mark; Matern, Dietrich; Bennett, Michael J.; Rinaldo, Piero; Strauss, Arnold W.

    2001-01-01

    Mitochondrial trifunctional protein (MTP) is a hetero-octamer of four α and four β subunits that catalyzes the final three steps of mitochondrial long chain fatty acid β-oxidation. Human MTP deficiency causes Reye-like syndrome, cardiomyopathy, or sudden unexpected death. We used gene targeting to generate an MTP α subunit null allele and to produce mice that lack MTP α and β subunits. The Mtpa–/– fetuses accumulate long chain fatty acid metabolites and have low birth weight compared with the...

  1. Lack of the RNA chaperone Hfq attenuates pathogenicity of several Escherichia coli pathotypes towards Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Bojer, Martin Saxtorph; Jakobsen, Henrik; Struve, Carsten

    2012-01-01

    as a model for virulence characterization and screening for novel antimicrobial entities. Several E. coli human pathotypes are also pathogenic towards C. elegans, and we show here that lack of the RNA chaperone Hfq significantly reduces pathogenicity of VTEC, EAEC, and UPEC in the nematode model. Thus, Hfq...... is intrinsically essential to pathogenic E. coli for survival and virulence exerted in the C. elegans host.......Escherichia coli is an important agent of Gram-negative bacterial infections worldwide, being one of the leading causes of diarrhoea and urinary tract infections. Strategies to understand pathogenesis and develop therapeutic compounds include the use of the nematode Caenorhabditis elegans...

  2. Efficient lighting in buildings: The lack of legislation in Portugal

    International Nuclear Information System (INIS)

    Almeida, António Manuel; Martins, António Gomes

    2014-01-01

    The behavior of building designers is conditioned by the existing legislation and regulations in the national context in which they operate. However, in the Portuguese legislation there are no rules concerning the use of daylight, and therefore, designers are not stimulated to adopt solutions that make use of the existing potential of sunlight availability. In the same way, it is difficult to understand the lack of specific regulation, with quantified targets, limiting power density of artificial lighting installed inside buildings. The present opportunity, generated by the need to carry out the revision of Portuguese building energy systems regulation, should be used to fill the existing gap in national legislation regarding those matters. In this paper the authors present some proposals for future legislation that will have as central purpose the utilization of efficient lighting systems and the promotion of architectural solutions that optimize the use of daylighting. It is possible, and desirable, to add new directives to national legislation that contribute to the improvement of Portuguese buildings, characterized by its good performance in terms of daylight availability, and at the same time, increasing the energy efficiency and reducing the energy consumption of lighting systems installed in those buildings. - Highlights: • In the Portuguese legislation there are no rules concerning the use of daylight. • Lack of specific regulation limiting power density of artificial lighting. • Revision of Portuguese building energy systems regulation. • Some proposals for future legislation. • Improvement of Portuguese buildings promoting energy efficiency

  3. [Lack of assertiveness in patients with eating disorders].

    Science.gov (United States)

    Behar A, Rosa; Manzo G, Rodrigo; Casanova Z, Dunny

    2006-03-01

    Low self-assertion has been noted as an important feature among patients with eating disorders. To verify, in a female population, if assertiveness is related or has a predictive capacity for the development of eating disorders. An structured clinical interview, the Eating Attitudes Test (EAT-40) and the Rathus Assertiveness Scale (RAS) were administered to 62 patients that fulfilled the DSM-IV diagnostic criteria for eating disorders and to 120 female students without eating problems. Patients with eating disorders ranked significantly higher on the EAT-40 and its factors (p assertiveness on the RAS (p Assertiveness measured by RAS and its factors was inversely related to EAT-40 and its items (r= -0.21). The predictive capability of the lack of self-assertion in the development of an eating disorder reached 53%, when patients with eating disorders and subjects at risk were considered together and compared to students without such disorder. Lack of assertiveness is a significant trait in patients with eating disorders; it may worsen its outcome and even perpetuate symptoms. Low self-assertion may be considered a predictive factor in the development of an eating disorder and must be managed from a preventive or therapeutic point of view.

  4. Individuals With OCD Lack Unrealistic Optimism Bias in Threat Estimation.

    Science.gov (United States)

    Zetsche, Ulrike; Rief, Winfried; Exner, Cornelia

    2015-07-01

    Overestimating the occurrence of threatening events has been highlighted as a central cognitive factor in the maintenance of obsessive-compulsive disorder (OCD). The present study examined the different facets of this cognitive bias, its underlying mechanisms, and its specificity to OCD. For this purpose, threat estimation, probabilistic classification learning (PCL) and psychopathological measures were assessed in 23 participants with OCD, 30 participants with social phobia, and 31 healthy controls. Whereas healthy participants showed an optimistic expectation bias regarding positive and negative future events, OCD participants lacked such a bias. This lack of an optimistic expectation bias was not specific to OCD. Compared to healthy controls, OCD participants overestimated their personal risk for experiencing negative events, but did not differ from controls in their risk estimation regarding other people. Finally, OCD participants' biases in the prediction of checking-related events were associated with their impairments in learning probabilistic cue-outcome associations in a disorder-relevant context. In sum, the present results add to a growing body of research demonstrating that cognitive biases in OCD are context-dependent. Copyright © 2015. Published by Elsevier Ltd.

  5. LACK OF EFFECT OF AGE AND ANTIOXIDANT DEPLETION ON RESPIRATORY RESPONSES TO CONCENTRATED AMBIENT PARTICULATES (CAPS) IN RATS

    Science.gov (United States)

    2003 AAR PM MeetingParticulate Matter: Atmospheric Sciences,Exposure and the Fourth Colloquium on PM and Human HealthLACK OF EFFECT OF AGE AND ANTIOXIDANT DEPLETION ON RESPIRATORY RESPONSES TO CONCENTRATED AMBIENT PARTICULATES (CAPs) IN RATS. JA Dye, LC Walsh, C...

  6. Lack of production sharing laws slows joint ventures in Russia

    International Nuclear Information System (INIS)

    Knott, D.

    1995-01-01

    When Russia opened its doors to foreign oil companies in 1990, there was a rush to secure a piece of the country's potentially vast oil wealth. Since then, many of the ventures between Russian and non-Russian partners have become bogged down with operational problems and an ever changing tax and legal regime. There is a stockpile of massive developments building, while government grinds with seeming reluctance toward passing laws that will allow outside firms to do big business. For major development projects the main stumbling block is the lack of production sharing contract legislation. The paper describes the problems, the current legislation, and operating problems, then highlights several joint ventures that have been successful and several that have ended in pullouts of the foreign investor

  7. [Lack of donor organs as an argument for living donors?].

    Science.gov (United States)

    Kirste, G

    2010-09-01

    In Germany more than 12,000 patients are presently waiting for an organ donation. Living donation makes sense for the long waiting time for a kidney, but it is not a permanent solution for the lack of organ donations. In the future topics which should be discussed are intensified public relations, a better family care and the allocation of rights and duties at the German coordinating agency. For all the prospects of success after a living donation the high standards of quality and security, which are targeted by the German donor organization in recipient protection, responsible evaluation of the expanded donor criteria and immunosuppressive therapy are all in favor of post-mortem organ donation. For all the phenomenal chance of success the priority of the post-mortem organ donation is regulated by law. The living donation remains an individual decision of the donor and the personal situation of life.

  8. Impaired intestinal proglucagon processing in mice lacking prohormone convertase 1

    DEFF Research Database (Denmark)

    Ugleholdt, Randi; Zhu, Xiaorong; Deacon, Carolyn F

    2003-01-01

    proglucagon processing showed marked defects. Tissue proglucagon levels in null mice were elevated, and proglucagon processing to glicentin, oxyntomodulin, and glucagon-like peptide-1 and -2 (GLP-1 and GLP-2) was markedly decreased, indicating that PC1 is essential for the processing of all the intestinal...... proglucagon cleavage sites. This includes the monobasic site R(77) and, thereby, production of mature, biologically active GLP-1. We also found elevated glucagon levels, suggesting that factors other than PC1 that are capable of processing to mature glucagon are present in the secretory granules of the L cell......The neuroendocrine prohormone convertases 1 and 2 (PC1 and PC2) are expressed in endocrine intestinal L cells and pancreatic A cells, respectively, and colocalize with proglucagon in secretory granules. Mice lacking PC2 have multiple endocrinopathies and cannot process proglucagon to mature...

  9. Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart

    Directory of Open Access Journals (Sweden)

    Wenjing Xu

    2015-10-01

    Full Text Available Both iron overload and iron deficiency have been associated with cardiomyopathy and heart failure, but cardiac iron utilization is incompletely understood. We hypothesized that the transferrin receptor (Tfr1 might play a role in cardiac iron uptake and used gene targeting to examine the role of Tfr1 in vivo. Surprisingly, we found that decreased iron, due to inactivation of Tfr1, was associated with severe cardiac consequences. Mice lacking Tfr1 in the heart died in the second week of life and had cardiomegaly, poor cardiac function, failure of mitochondrial respiration, and ineffective mitophagy. The phenotype could only be rescued by aggressive iron therapy, but it was ameliorated by administration of nicotinamide riboside, an NAD precursor. Our findings underscore the importance of both Tfr1 and iron in the heart, and may inform therapy for patients with heart failure.

  10. Problems caused by regulatory delays and lack of regulation

    Science.gov (United States)

    Reamer, Lynne A.

    1994-12-01

    An FDA perspective on some of the problems encountered during the device review process is described. Emphasis is placed on the need for communication and teamwork among all parties to make the system work. Manufacturers are encouraged to `Do it right the first time.' Pertinent questions are asked of the manufacturers and proposed solutions are presented. Day to day reality at FDA is described and document workload is revealed. Lack of regulation, or more appropriately, when less regulation is appropriate is discussed. FDA has distributed to manufacturers a new draft guidance document to help in the decisionmaking process and when to submit a 510(k) when modifications are made to a device. This and other mechanisms are in place at the FDA to streamline the review process. Manufacturers are cautioned about their decisions and to seek advice from qualified persons. FDA emphasizes that help is available and that when in doubt, call.

  11. Lack of Glycogenin Causes Glycogen Accumulation and Muscle Function Impairment.

    Science.gov (United States)

    Testoni, Giorgia; Duran, Jordi; García-Rocha, Mar; Vilaplana, Francisco; Serrano, Antonio L; Sebastián, David; López-Soldado, Iliana; Sullivan, Mitchell A; Slebe, Felipe; Vilaseca, Marta; Muñoz-Cánoves, Pura; Guinovart, Joan J

    2017-07-05

    Glycogenin is considered essential for glycogen synthesis, as it acts as a primer for the initiation of the polysaccharide chain. Against expectations, glycogenin-deficient mice (Gyg KO) accumulate high amounts of glycogen in striated muscle. Furthermore, this glycogen contains no covalently bound protein, thereby demonstrating that a protein primer is not strictly necessary for the synthesis of the polysaccharide in vivo. Strikingly, in spite of the higher glycogen content, Gyg KO mice showed lower resting energy expenditure and less resistance than control animals when subjected to endurance exercise. These observations can be attributed to a switch of oxidative myofibers toward glycolytic metabolism. Mice overexpressing glycogen synthase in the muscle showed similar alterations, thus indicating that this switch is caused by the excess of glycogen. These results may explain the muscular defects of GSD XV patients, who lack glycogenin-1 and show high glycogen accumulation in muscle. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Lack of time management as a psychosocial work risk

    Directory of Open Access Journals (Sweden)

    Ramon Cladellas

    2008-10-01

    Full Text Available This paper is aimed to explore the possible relationship between workers' lack of time management and several psychosocial risks. The psychosocial risks were assessed by means of the ISTAS21 Questionnaire, the Spanish version of the CoPsoQ (Copenhagen Psychological Questionnaire. More specifically, nine dimensions, which are directly related with time management, satisfaction, health and stress, were selected for evaluation. Time management was measured through the following variables: quantitative demands, influences and control of the time. Drawing on a sample of 142 workers from four departments (development, implantation, support and administration, the research results show that the employees who belong to a department that offers few opportunities for individual time management are less satisfied, have worse general and mental health, and experience more behavioral, symptomatic and cognitive stress than those who can manage their work schedule.

  13. Nonadherence is Associated with Lack of HIV-Related Knowledge

    DEFF Research Database (Denmark)

    Dyrehave, Charlotte; Rasmussen, Dlama Nggida; Hønge, Bo Langhoff

    2016-01-01

    -sectional study included 494 HIV-infected individuals from the Bissau HIV Cohort in Guinea-Bissau. They completed a questionnaire designed for assessment of adherence and HIV-related knowledge. RESULTS: A majority were female, 41% were illiterate, 25% did not take the medicine during the last 4 days, and 23......BACKGROUND: Poor treatment adherence is a main barrier for effective antiretroviral therapy (ART) globally. HIV-related knowledge may affect understanding and utilization of HIV medical information, hence limited health literacy is a known barrier to treatment adherence. DESIGN AND METHODS: A cross......% skipped their medicine during weekends. The most frequent reasons for not taking medicine were simply forgetting, side effects, lack of food, and being too ill to attend the clinic. Nonadherent patients had a lower level of HIV-related knowledge. CONCLUSION: Main barriers for nonadherence were side...

  14. Lack of sleep is associated with internet use for leisure.

    Science.gov (United States)

    Kim, So Young; Kim, Min-Su; Park, Bumjung; Kim, Jin-Hwan; Choi, Hyo Geun

    2018-01-01

    Previous studies have suggested that excessive internet use may cause lack of sleep. However, recent studies have hypothesized that lack of sleep may instigate internet use for leisure. To elucidate the potential effects of sleep time on internet use, we explored the different associations between sleep time and internet use according to its purpose. The population-based, cross-sectional study group from the Korea Youth Risk Behavior Web-based Survey (KYRBWS) collected data from 57,425 middle school students in 2014 and 2015. Sleep time over the past 7 days was classified into the following groups: Internet use time per day was separately surveyed for leisure and for study and categorized as follows: 0 h; > 0 h, ≤ 1 h (1 h); > 1 h, ≤ 2 h (2 h); and > 2 h (2+ h) per day. Information on age, sex, region of residence, body mass index (BMI), economic level, parental education level, stress level, school performance level, and sleep satisfaction were retrieved. The relationships between sleep time and internet use time for leisure/study were analyzed using multinomial logistic regression with complex sampling. In the subgroup analysis according to sleep satisfaction (good, normal, and poor), the associations of sleep time with internet use for leisure were analyzed using the same methods. Compared to 9+ h of sleep, less sleep was related to a long internet use time (2+ h) for leisure (adjusted odds ratio, AOR [95% confidence interval, CI] of sleep: 8 h = 1.23 [1.14-1.32]; 7 h = 1.42 [1.31-1.54]; and 6 h = 1.56 [1.44-1.70]; P internet use time (2+ h) for study was evident only for 6 h of sleep (AOR of sleep: 8 h = 0.84 [0.84-1.04]; 7 h = 1.05 [0.94-1.17]; and 6 h = 1.32 [1.27-1.59]; P internet use time for leisure in all sleep satisfaction groups, although the relationship was more significant in the lower sleep satisfaction group. Less sleep was significantly related to long-term use of the internet for leisure, whereas this association was not definite for internet

  15. Standardized education and parental awareness are lacking for testicular torsion.

    Science.gov (United States)

    Friedman, Ariella A; Ahmed, Haris; Gitlin, Jordan S; Palmer, Lane S

    2016-06-01

    Testicular torsion leads to orchiectomy in 30-50% of cases, which may cause psychological upset and parental guilt over a potentially avertable outcome. Presentation delay is an important modifiable cause of orchiectomy; yet, families are not routinely educated about torsion or its urgency. The present study assessed parental knowledge regarding acute scrotal pain. An anonymous survey was distributed to parents in Urology and ENT offices, asking about their children's gender and scrotal pain history, urgency of response to a child's acute scrotal pain, and familiarity with testicular torsion. Surveys of 479 urology and 59 ENT parents were analyzed. The results between the two were not statistically different. Among the urology parents, 34% had heard of testicular twisting/torsion, most commonly through friends, relatives or knowing someone with torsion (35%); only 17% were informed by pediatricians (Summary Figure). Parents presenting for a child's scrotal pain were significantly more likely to have heard of torsion (69%) than those presenting for other reasons (30%, OR 5.24, P parents of boys had spoken with their children about torsion. Roughly three quarters of them would seek emergent medical attention - by day (75%) or night (82%) - for acute scrotal pain. However, urgency was no more likely among those who knew about torsion. This was the first study to assess parental knowledge of the emergent nature of acute scrotal pain in a non-urgent setting, and most closely approximating their level of knowledge at the time of pain onset. It also assessed parents' hypothetical responses to the scenario, which was markedly different than documented presentation times, highlighting a potential area for improvement in presentation times. Potential limitations included lack of respondent demographic data, potential sampling bias of a population with greater healthcare knowledge or involvement, and assessment of parents only. Parental knowledge of testicular torsion was

  16. Lack of Aquaporin 3 in bovine erythrocyte membranes correlates with low glycerol permeation.

    Science.gov (United States)

    Campos, Elisa; Moura, Teresa F; Oliva, Abel; Leandro, Paula; Soveral, Graça

    2011-05-13

    In general, erythrocytes are highly permeable to water, urea and glycerol. However, expression of aquaporin isoforms in erythrocytes appears to be species characteristic. In the present study, human (hRBC) and bovine (bRBC) erythrocytes were chosen for comparative studies due to their significant difference in membrane glycerol permeability. Osmotic water permeability (P(f)) at 23°C was (2.89 ± 0.37) × 10(-2) and (5.12 ± 0.61) × 10(-2)cms(-1) for human and bovine cells, respectively, with similar activation energies for water transport. Glycerol permeability (P(gly)) for human ((1.37 ± 0.26) × 10(-5)cms(-1)) differed in three orders of magnitude from bovine erythrocytes ((5.82 ± 0.37) × 10(-8)cms(-1)) that also showed higher activation energy for glycerol transport. When compared to human, bovine erythrocytes showed a similar expression pattern of AQP1 glycosylated forms on immunoblot analysis, though in slight higher levels, which could be correlated with the 1.5-fold larger P(f) found. However, AQP3 expression was not detectable. Immunofluorescence analysis confirmed the absence of AQP3 expression in bovine erythrocyte membranes. In conclusion, lack of AQP3 in bovine erythrocytes points to the lipid pathway as responsible for glycerol permeation and explains the low glycerol permeability and high E(a) for transport observed in ruminants. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Post-exposure vaccination with MP-12 lacking NSs protects mice against lethal Rift Valley fever virus challenge.

    Science.gov (United States)

    Gowen, Brian B; Bailey, Kevin W; Scharton, Dionna; Vest, Zachery; Westover, Jonna B; Skirpstunas, Ramona; Ikegami, Tetsuro

    2013-05-01

    Rift Valley fever virus (RVFV) causes severe disease in humans and livestock. There are currently no approved antivirals or vaccines for the treatment or prevention of RVF disease in humans. A major virulence factor of RVFV is the NSs protein, which inhibits host transcription including the interferon (IFN)-β gene and promotes the degradation of dsRNA-dependent protein kinase, PKR. We analyzed the efficacy of the live-attenuated MP-12 vaccine strain and MP-12 variants that lack the NSs protein as post-exposure vaccinations. Although parental MP-12 failed to elicit a protective effect in mice challenged with wild-type (wt) RVFV by the intranasal route, significant protection was demonstrated by vaccination with MP-12 strains lacking NSs when they were administered at 20-30 min post-exposure. Viremia and virus replication in liver, spleen and brain were also inhibited by post-exposure vaccination with MP-12 lacking NSs. The protective effect was mostly lost when vaccination was delayed 6 or 24 h after intranasal RVFV challenge. When mice were challenged subcutaneously, efficacy of MP-12 lacking NSs was diminished, most likely due to more rapid dissemination of wt RVFV. Our findings suggest that post-exposure vaccination with MP-12 lacking NSs may be developed as a novel post-exposure treatment to prevent RVF. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Sucrose fermentation by Saccharomyces cerevisiae lacking hexose transport.

    Science.gov (United States)

    Batista, Anderson S; Miletti, Luiz C; Stambuk, Boris U

    2004-01-01

    Sucrose is the major carbon source used by Saccharomyces cerevisiae during production of baker's yeast, fuel ethanol and several distilled beverages. It is generally accepted that sucrose fermentation proceeds through extracellular hydrolysis of the sugar, mediated by the periplasmic invertase, producing glucose and fructose that are transported into the cells and metabolized. In the present work we analyzed the contribution to sucrose fermentation of a poorly characterized pathway of sucrose utilization by S. cerevisiae cells, the active transport of the sugar through the plasma membrane and its intracellular hydrolysis. A yeast strain that lacks the major hexose transporters (hxt1-hxt7 and gal2) is incapable of growing on or fermenting glucose or fructose. Our results show that this hxt-null strain is still able to ferment sucrose due to direct uptake of the sugar into the cells. Deletion of the AGT1 gene, which encodes a high-affinity sucrose-H(+) symporter, rendered cells incapable of sucrose fermentation. Since sucrose is not an inducer of the permease, expression of the AGT1 must be constitutive in order to allow growth of the hxt-null strain on sucrose. The molecular characterization of active sucrose transport and fermentation by S. cerevisiae cells opens new opportunities to optimize yeasts for sugarcane-based industrial processes.

  19. Impaired cardiac energy metabolism in embryos lacking adrenergic stimulation

    Science.gov (United States)

    Baker, Candice N.; Gidus, Sarah A.; Price, George F.; Peoples, Jessica N. R.

    2014-01-01

    As development proceeds from the embryonic to fetal stages, cardiac energy demands increase substantially, and oxidative phosphorylation of ADP to ATP in mitochondria becomes vital. Relatively little, however, is known about the signaling mechanisms regulating the transition from anaerobic to aerobic metabolism that occurs during the embryonic period. The main objective of this study was to test the hypothesis that adrenergic hormones provide critical stimulation of energy metabolism during embryonic/fetal development. We examined ATP and ADP concentrations in mouse embryos lacking adrenergic hormones due to targeted disruption of the essential dopamine β-hydroxylase (Dbh) gene. Embryonic ATP concentrations decreased dramatically, whereas ADP concentrations rose such that the ATP/ADP ratio in the adrenergic-deficient group was nearly 50-fold less than that found in littermate controls by embryonic day 11.5. We also found that cardiac extracellular acidification and oxygen consumption rates were significantly decreased, and mitochondria were significantly larger and more branched in adrenergic-deficient hearts. Notably, however, the mitochondria were intact with well-formed cristae, and there was no significant difference observed in mitochondrial membrane potential. Maternal administration of the adrenergic receptor agonists isoproterenol or l-phenylephrine significantly ameliorated the decreases in ATP observed in Dbh−/− embryos, suggesting that α- and β-adrenergic receptors were effective modulators of ATP concentrations in mouse embryos in vivo. These data demonstrate that adrenergic hormones stimulate cardiac energy metabolism during a critical period of embryonic development. PMID:25516547

  20. Impaired cardiac energy metabolism in embryos lacking adrenergic stimulation.

    Science.gov (United States)

    Baker, Candice N; Gidus, Sarah A; Price, George F; Peoples, Jessica N R; Ebert, Steven N

    2015-03-01

    As development proceeds from the embryonic to fetal stages, cardiac energy demands increase substantially, and oxidative phosphorylation of ADP to ATP in mitochondria becomes vital. Relatively little, however, is known about the signaling mechanisms regulating the transition from anaerobic to aerobic metabolism that occurs during the embryonic period. The main objective of this study was to test the hypothesis that adrenergic hormones provide critical stimulation of energy metabolism during embryonic/fetal development. We examined ATP and ADP concentrations in mouse embryos lacking adrenergic hormones due to targeted disruption of the essential dopamine β-hydroxylase (Dbh) gene. Embryonic ATP concentrations decreased dramatically, whereas ADP concentrations rose such that the ATP/ADP ratio in the adrenergic-deficient group was nearly 50-fold less than that found in littermate controls by embryonic day 11.5. We also found that cardiac extracellular acidification and oxygen consumption rates were significantly decreased, and mitochondria were significantly larger and more branched in adrenergic-deficient hearts. Notably, however, the mitochondria were intact with well-formed cristae, and there was no significant difference observed in mitochondrial membrane potential. Maternal administration of the adrenergic receptor agonists isoproterenol or l-phenylephrine significantly ameliorated the decreases in ATP observed in Dbh-/- embryos, suggesting that α- and β-adrenergic receptors were effective modulators of ATP concentrations in mouse embryos in vivo. These data demonstrate that adrenergic hormones stimulate cardiac energy metabolism during a critical period of embryonic development. Copyright © 2015 the American Physiological Society.

  1. Application of 133Xe encephalography in lack blood diseases

    International Nuclear Information System (INIS)

    Xie Zhiyuan; Guo Huiying

    1993-01-01

    The determination of local blood flow in brain gray matter (rCBF) using the type CGEM 2000 133 Xe encephalography is a reliable indication for judging the degree of lack blood disease. For all the inspected patients the scalp analogy localization is used. 28 probes are applied to some regions of the forehead, the vertex, the temporal folium and the occipital folium. The localization is accurate and repeatable. The result of rCBF determination is similar to XCT, but its range is rather wider than XCT. Therefore, the rCBF determination in clinic diagnosis is reliable and can give the rCBF value qualitatively. It can be used not only for diagnosing the decease in brain, but also for the predication before apoplexy, especially for vertigo disease to be inspected. For the vertigo disease of middle age and old man, the first consideration should be the decreasing of rCBF value. For the inspection of thrombus of neck artery system, it can reflect the real range of pathological changes correctly. The method is superior to XCT for treatment planning, estimating the results, supervising the effect treatment, and the diagnosis of acute cerebral embolism. In China, the morbidity rate, the sickness rate, the disability rate and recurrent rate of cerebrovascular disease are very high, especially for the old man. Satisfactory results for 1010 cases altogether are obtained by using type CGEM 2000 cerebral angiography technique for the screening

  2. Lack of international consensus in low-risk drinking guidelines.

    Science.gov (United States)

    Furtwaengler, Nina A F F; de Visser, Richard O

    2013-01-01

    To encourage moderate alcohol consumption, many governments have developed guidelines for alcohol intake, guidelines for alcohol consumption during pregnancy and legislation relating to blood alcohol limits when driving. The aim of this study was to determine the degree of international consensus within such guidelines. Official definitions of standard drinks and consumption guidelines were searched for on government websites, including all 27 European Union Member States and countries from all global geographic regions. There was a remarkable lack of agreement about what constitutes harmful or excessive alcohol consumption on a daily basis, a weekly basis and when driving, with no consensus about the ratios of consumption guidelines for men and women. International consensus in low-risk drinking guidelines is an important--and achievable--goal. Such agreement would facilitate consistent labelling of packaged products and could help to promote moderate alcohol consumption. However, there are some paradoxes related to alcohol content labelling and people's use of such information: although clearer information could increase people's capacity to monitor and regulate their alcohol consumption, not all drinkers are motivated to drink moderately or sensibly, and drinkers who intend to get drunk may use alcohol content labelling to select more alcoholic products. © 2012 Australasian Professional Society on Alcohol and other Drugs.

  3. LACK OF AWARENESS ABOUT SAFE BLOOD IN PAKISTANI POPULATION

    Directory of Open Access Journals (Sweden)

    Muhammad Usman

    2014-12-01

    Full Text Available Blood transfusion is a life saving procedure in various transfusion-dependent life threatening conditions and donation of safe blood is a prerequisite for achieving this goal. This study was designed to evaluate the awareness regarding “safe blood” in Pakistani population. This study was conducted at a large scale through a population survey. The test population was divided into two groups i.e. general population and students. The Performa was designed for a general and student population and included 20 questions related to awareness of safe blood. A total of 4900 individuals belonging to different ethnic groups were included in this population survey. Results of social survey were analyzed by using Usman and Moin awareness chart. Results of this study revealed profound unawareness about safe blood in Pakistani population. This study found lack of awareness about safe blood as a major factor that is playing a vital role in the propagation of blood borne diseases in Pakistan. To secure the recipients from blood borne complications through blood donation, it is necessary to create effective awareness about safe blood in Pakistani population.

  4. Prefrontal glucose deficits in murderers lacking psychosocial deprivation.

    Science.gov (United States)

    Raine, A; Phil, D; Stoddard, J; Bihrle, S; Buchsbaum, M

    1998-01-01

    Previous research has suggested that links between autonomic nervous system functioning and violence are strongest in those who come from benign home backgrounds, but there appears to be no similar research using brain-imaging measures of central nervous system functioning. It was hypothesized that murderers who had no early psychosocial deprivation (e.g., no childhood abuse, family neglect) would demonstrate lower prefrontal glucose metabolism than murderers with early psychosocial deprivation and a group of normal controls. Murderers from a previous study, which showed prefrontal deficits in murderers, were assessed for psychosocial deprivation and divided into those with and without deprivation. Murderers without any clear psychosocial deficits were significantly lower on prefrontal glucose metabolism than murderers with psychosocial deficits and controls. These results suggest that murderers lacking psychosocial deficits are characterized by prefrontal deficits. It is argued that among violent offenders without deprived home backgrounds, the "social push" to violence is minimized, and consequently, brain abnormalities provide a relatively stronger predisposition to violence in this group.

  5. Lack of empathy in patients with narcissistic personality disorder.

    Science.gov (United States)

    Ritter, Kathrin; Dziobek, Isabel; Preissler, Sandra; Rüter, Anke; Vater, Aline; Fydrich, Thomas; Lammers, Claas-Hinrich; Heekeren, Hauke R; Roepke, Stefan

    2011-05-15

    The study's objective was to empirically assess cognitive and emotional empathy in patients with narcissistic personality disorder (NPD). To date, "lack of empathy" is a core feature of NPD solely based on clinical observation. The study's method was that forty-seven patients with NPD, 53 healthy controls, and 27 clinical controls with borderline personality disorder (BPD) were included in the study. Emotional and cognitive empathy were assessed with traditional questionnaire measures, the newly developed Multifaceted Empathy Test (MET), and the Movie for the Assessment of Social Cognition (MASC). The study's results were that individuals with NPD displayed significant impairments in emotional empathy on the MET. Furthermore, relative to BPD patients and healthy controls, NPD patients did not show deficits in cognitive empathy on the MET or MASC. Crucially, this empathic profile of NPD is not captured by the Structured Clinical Interview for DSM-IV for Axis II Disorders (SCID-II). The study's conclusions were that while NPD involves deficits in emotional empathy, cognitive empathy seems grossly unaffected. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. THE LACK OF RECOGNITION OF OTHERS, AFFECTS SCHOOL LIFE

    Directory of Open Access Journals (Sweden)

    Apolinar López-Miguel

    2016-01-01

    Full Text Available The school is the ideal place to teach to live in ness (ie, work sameness and otherness because we are different but equal in dignity and human rights, also the importance of "peace education" takes place before the deterioration of coexistence, the result of discrimination. We invite the reader to re-think the role of the school as a driving space of peace, being vital interaction school-family-community; promoting in areas: dialogue, tolerance, respect for differences, to build a Peace Education.

  7. [The lack of information on genetically modified organisms in Brazil].

    Science.gov (United States)

    Ribeiro, Isabelle Geoffroy; Marin, Victor Augustus

    2012-02-01

    This article presents a review about the labeling of products that have Genetically Modified Organisms (GMO), also called transgenic elements in their composition. It addresses the conventions, laws and regulations relating to such products currently governing the market, the adequacy of these existing standards and their acceptance by society. It also examines the importance of the cautionary principle when assessing the application of new technologies or technologies where little is known or where there is no relevant scientific knowledge about the potential risks to the environment, human health and society.

  8. Lack of interaction between the peptidomimetic substrates captopril and cephradine.

    Science.gov (United States)

    Foster, David R; Yee, Shiyin; Bleske, Barry E; Carver, Peggy L; Shea, Michael J; Menon, Sujatha S; Ramachandran, Chandrasekharan; Welage, Lynda S; Amidon, Gordon L

    2009-03-01

    Intestinal peptide transporters, including hPEPT1, facilitate the absorption of cephalosporins and angiotensin-converting enzyme inhibitors, and have been investigated as a means to improve oral drug absorption. Renal peptide transporters including hPEPT2, may also facilitate renal reabsorption of such compounds. In vitro and animal studies suggest that co-administration of peptidomimetic compounds may alter oral pharmacokinetics, although this has not been well studied in humans. The purpose of this study was to determine whether co-administration of the hPEPT substrates captopril and cephradine alters the oral pharmacokinetics of either agent. Nine healthy male volunteers received a single oral 25-mg dose of captopril, a single oral 500-mg dose of cephradine, or concurrent ingestion of captopril and cephradine in a cross-over manner. Venous blood samples were taken and captopril and cephradine pharmacokinetics were determined using noncompartmental analyses. No significant differences were observed in captopril or cephradine pharmacokinetics when administered together as compared to each agent alone (a marginal decrease in C(max) was observed for both captopril and cephradine during co-administration [5-15%]; however, differences were not statistically significant). The results of our study suggest that hPEPT1 and hPEPT2 are unlikely to contribute to clinically important drug interactions in humans.

  9. Lack of Cholesterol Awareness among Physicians Who Smoke

    Directory of Open Access Journals (Sweden)

    Richard E. Scranton

    2009-02-01

    Full Text Available Cigarette use is a known risk factor for the development of coronary artery disease (CAD as it adversely affects HDL cholesterol levels and promotes thrombogenesis. Smoking may also be associated with behavioral characteristics that potentiate the risk of CAD. A lack of cholesterol knowledge would indicate an aversion to a prevention-oriented lifestyle. Thus, our goal was to determine the association between tobacco use and knowledge of self-reported cholesterol among male physicians. Using the 1982 and follow-up questionnaires from the physician health study, we report the changes in the frequencies of awareness of self-reported total cholesterol and cardiovascular risk factors among the 22,067 participants. We classified physicians as being aware of their cholesterol if they reported a cholesterol level and unaware if the question was left unanswered. In 1997, 207 physicians were excluded, as the recorded cholesterol was not interpretable, leaving 21,860 for our follow up analyses. Using unadjusted logistic models, we determined the odds ratios (OR and 95% confidence intervals (CI of not reporting a cholesterol level in either 1982 or 1997 for each specified risk factor. We then evaluated whether the lack of cholesterol awareness at both time points was associated with the use of tobacco throughout the study. After 14-years of follow up, cholesterol awareness increased from 35.9 to 58.6 percent. During this period, the frequency of hypertension and hyperlipidemia treatment increased (13.5 to 40.5% and 0.57% to 19.6% respectively, as did the diagnosis of diabetes (2.40 to 7.79%. Behavioral characteristics such as a sedentary lifestyle and obesity also increased (27.8 to 42% and 43.5 to 53.5%, respectively, however the proportion of current smokers deceased from 11.1 to 4.05%. The percentages of individuals being unaware of their cholesterol decreased in all risk factor groups. However, individuals were likely to be unaware of their cholesterol

  10. On the Lack of Circumbinary Planets Orbiting Isolated Binary Stars

    Science.gov (United States)

    Fleming, David P.; Barnes, Rory; Graham, David E.; Luger, Rodrigo; Quinn, Thomas R.

    2018-05-01

    We outline a mechanism that explains the observed lack of circumbinary planets (CBPs) via coupled stellar–tidal evolution of isolated binary stars. Tidal forces between low-mass, short-period binary stars on the pre-main sequence slow the stellar rotations transferring rotational angular momentum to the orbit as the stars approach the tidally locked state. This transfer increases the binary orbital period, expanding the region of dynamical instability around the binary, and destabilizing CBPs that tend to preferentially orbit just beyond the initial dynamical stability limit. After the stars tidally lock, we find that angular momentum loss due to magnetic braking can significantly shrink the binary orbit, and hence the region of dynamical stability, over time, impacting where surviving CBPs are observed relative to the boundary. We perform simulations over a wide range of parameter space and find that the expansion of the instability region occurs for most plausible initial conditions and that, in some cases, the stability semimajor axis doubles from its initial value. We examine the dynamical and observable consequences of a CBP falling within the dynamical instability limit by running N-body simulations of circumbinary planetary systems and find that, typically, at least one planet is ejected from the system. We apply our theory to the shortest-period Kepler binary that possesses a CBP, Kepler-47, and find that its existence is consistent with our model. Under conservative assumptions, we find that coupled stellar–tidal evolution of pre-main sequence binary stars removes at least one close-in CBP in 87% of multi-planet circumbinary systems.

  11. (Lack of) Corticospinal facilitation in association with hand laterality judgments.

    Science.gov (United States)

    Ferron, Lucas; Tremblay, François

    2017-07-01

    In recent years, mental practice strategies have drawn much interest in the field of rehabilitation. One form of mental practice particularly advocated involves judging the laterality of images depicting body parts. Such laterality judgments are thought to rely on implicit motor imagery via mental rotation of one own's limb. In this study, we sought to further characterize the involvement of the primary motor cortex (M1) in hand laterality judgments (HLJ) as performed in the context of an application designed for rehabilitation. To this end, we measured variations in corticospinal excitability in both hemispheres with motor evoked potentials (MEPs) while participants (n = 18, young adults) performed either HLJ or a mental counting task. A third condition (foot observation) provided additional control. We hypothesized that HLJ would lead to a selective MEP facilitation when compared to the other tasks and that this facilitation would be greater on the right than the left hemisphere. Contrary to our predictions, we found no evidence of task effects and hemispheric effects for the HLJ task. Significant task-related MEP facilitation was detected only for the mental counting task. A secondary experiment performed in a subset of participants (n = 6) to further test modulation during HLJ yielded the same results. We interpret the lack of facilitation with HLJ in the light of evidence that participants may rely on alternative strategies when asked to judge laterality when viewing depictions of body parts. The use of visual strategies notably would reduce the need to engage in mental rotation, thus reducing M1 involvement. These results have implications for applications of laterality tasks in the context of the rehabilitation program.

  12. Multiple sleep alterations in mice lacking cannabinoid type 1 receptors.

    Directory of Open Access Journals (Sweden)

    Alessandro Silvani

    Full Text Available Cannabinoid type 1 (CB1 receptors are highly expressed in the brain and play a role in behavior control. Endogenous cannabinoid signaling is modulated by high-fat diet (HFD. We investigated the consequences of congenital lack of CB1 receptors on sleep in mice fed standard diet (SD and HFD. CB1 cannabinoid receptor knock-out (KO and wild-type (WT mice were fed SD or HFD for 4 months (n = 9-10 per group. Mice were instrumented with electroencephalographic (EEG and electromyographic electrodes. Recordings were performed during baseline (48 hours, sleep deprivation (gentle handling, 6 hours, sleep recovery (18 hours, and after cage switch (insomnia model paradigm, 6 hours. We found multiple significant effects of genotype on sleep. In particular, KO spent more time awake and less time in non-rapid-eye-movement sleep (NREMS and rapid-eye-movement sleep (REMS than WT during the dark (active period but not during the light (rest period, enhancing the day-night variation of wake-sleep amounts. KO had slower EEG theta rhythm during REMS. REMS homeostasis after sleep deprivation was less effective in KO than in WT. Finally, KO habituated more rapidly to the arousing effect of the cage-switch test than WT. We did not find any significant effects of diet or of diet x genotype interaction on sleep. The occurrence of multiple sleep alterations in KO indicates important roles of CB1 cannabinoid receptors in limiting arousal during the active period of the day, in sleep regulation, and in sleep EEG in mice.

  13. Lack of awareness for spatial and verbal constructive apraxia.

    Science.gov (United States)

    Rinaldi, Maria Cristina; Piras, Federica; Pizzamiglio, Luigi

    2010-05-01

    It is still a matter of debate whether constructive apraxia (CA) should be considered a form of apraxia or, rather, the motor expression of a more pervasive impairment in visuo-spatial processing. Constructive disorders were linked to visuo-spatial disorders and to deficits in appreciating spatial relations among component sub-parts or problems in reproducing three-dimensionality. We screened a large population of brain-damaged patients for CA. Only patients with constructive disorders and no signs of neglect and/or aphasia were selected. Five apractic subjects were tested with both visuo-spatial and verbal tasks requiring constructive abilities. The former ones were tests such as design copying, while the latter were experimental tasks built to transpose into the linguistic domain the constructive process as phrasing by arranging paper scraps into a sentence. A first result showed a constructive impairment in both the visuo-spatial and the linguistic domain; this finding challenges the idea that CA is confined to the visuo-spatial domain. A second result showed a systematic association between CA and unawareness for constructive disorders. Third, lack of awareness was always associated with a lesion in the right dorsolateral prefrontal cortex, a region deemed as involved in managing a conflict between intentions and sensory feed-back. Anosognosia for constructive disorders and the potential role of the right prefrontal cortex in generating the impairment, are discussed in the light of current models of action control. The core of CA could be the inability to detect any inconsistency between intended and executed action rather than a deficit in reproducing spatial relationship. 2010 Elsevier Ltd. All rights reserved.

  14. Lack of plasma kallikrein-kinin system cascade in teleosts.

    Directory of Open Access Journals (Sweden)

    Marty Kwok-Shing Wong

    Full Text Available The kallikrein-kinin system (KKS consists of two major cascades in mammals: "plasma KKS" consisting of high molecular-weight (HMW kininogen (KNG, plasma kallikrein (KLKB1, and bradykinin (BK; and "tissue KKS" consisting of low molecular-weight (LMW KNG, tissue kallikreins (KLKs, and [Lys(0]-BK. Some components of the KKS have been identified in the fishes, but systematic analyses have not been performed, thus this study aims to define the KKS components in teleosts and pave a way for future physiological and evolutionary studies. Through a combination of genomics, molecular, and biochemical methods, we showed that the entire plasma KKS cascade is absent in teleosts. Instead of two KNGs as found in mammals, a single molecular weight KNG was found in various teleosts, which is homologous to the mammalian LMW KNG. Results of molecular phylogenetic and synteny analyses indicated that the all current teleost genomes lack KLKB1, and its unique protein structure, four apple domains and one trypsin domain, could not be identified in any genome or nucleotide databases. We identified some KLK-like proteins in teleost genomes by synteny and conserved domain analyses, which could be the orthologs of tetrapod KLKs. A radioimmunoassay system was established to measure the teleost BK and we found that [Arg(0]-BK is the major circulating form instead of BK, which supports that the teleost KKS is similar to the mammalian tissue KKS. Coincidently, coelacanths are the earliest vertebrate that possess both HMW KNG and KLKB1, which implies that the plasma KKS could have evolved in the early lobe-finned fish and descended to the tetrapod lineage. The co-evolution of HMW KNG and KLKB1 in lobe-finned fish and early tetrapods may mark the emergence of the plasma KKS and a contact activation system in blood coagulation, while teleosts may have retained a single KKS cascade.

  15. Triclosan Lacks (Anti-Estrogenic Effects in Zebrafish Cells but Modulates Estrogen Response in Zebrafish Embryos

    Directory of Open Access Journals (Sweden)

    Hélène Serra

    2018-04-01

    Full Text Available Triclosan (TCS, an antimicrobial agent widely found in the aquatic environment, is suspected to act as an endocrine disrupting compound, however mechanistic information is lacking in regards to aquatic species. This study assessed the ability of TCS to interfere with estrogen receptor (ER transcriptional activity, in zebrafish-specific in vitro and in vivo reporter gene assays. We report that TCS exhibits a lack of either agonistic or antagonistic effects on a panel of ER-expressing zebrafish (ZELH-zfERα and -zfERβ and human (MELN cell lines. At the organism level, TCS at concentrations of up to 0.3 µM had no effect on ER-regulated brain aromatase gene expression in transgenic cyp19a1b-GFP zebrafish embryos. At a concentration of 1 µM, TCS interfered with the E2 response in an ambivalent manner by potentializing a low E2 response (0.625 nM, but decreasing a high E2 response (10 nM. Altogether, our study suggests that while modulation of ER-regulated genes by TCS may occur in zebrafish, it does so irrespective of a direct binding and activation of zfERs.

  16. Globular Clusters Shine in a Galaxy Lacking Dark Matter

    Science.gov (United States)

    Kohler, Susanna

    2018-04-01

    You may have seen recent news about NGC 1052DF2, a galaxy that was discovered to have little or no dark matter. Now, a new study explores what NGC 1052DF2 does have: an enigmatic population of unusually large and luminous globular clusters.Keck/LRIS spectra (left and right) and HST images (center) of the 11 clusters associated with NGC 1052DF2. The color images each span 1 1. [van Dokkum et al. 2018]An Unusual DwarfThe ultra-diffuse galaxy NGC 1052DF2, originally identified with the Dragonfly Telescope Array, has puzzled astronomers since the discovery that its dynamical mass determined by the motions of globular-cluster-like objects spotted within it is essentially the same as its stellar mass. This equivalence implies that the galaxy is strangely lacking dark matter; the upper limit set on its dark matter halo is 400 times smaller than what we would expect for such a dwarf galaxy.Led by Pieter van Dokkum (Yale University), the team that made this discovery has now followed up with detailed Hubble Space Telescope imaging and Keck spectroscopy. Their goal? To explore the objects that allowed them to make the dynamical-mass measurement: the oddly bright globular clusters of NGC 1052DF2.Sizes (circularized half-light radii) vs. absolute magnitudes for globular clusters in NGC1052DF2 (black) and the Milky Way (red). [Adapted from van Dokkum et al. 2018]Whats Up with the Globular Clusters?Van Dokkum and collaborators spectroscopically confirmed 11 compact objects associated with the faint galaxy. These objects are globular-cluster-like in their appearance, but the peak of their luminosity distribution is offset by a factor of four from globular clusters of other galaxies; these globular clusters are significantly brighter than is typical.Using the Hubble imaging, the authors determined that NGC 1052DF2s globular clusters are more than twice the size of the Milky Ways globular clusters in the same luminosity range. As is typical for globular clusters, they are an old

  17. Mice lacking liver-specific β-catenin develop steatohepatitis and fibrosis after iron overload.

    Science.gov (United States)

    Preziosi, Morgan E; Singh, Sucha; Valore, Erika V; Jung, Grace; Popovic, Branimir; Poddar, Minakshi; Nagarajan, Shanmugam; Ganz, Tomas; Monga, Satdarshan P

    2017-08-01

    Iron overload disorders such as hereditary hemochromatosis and iron loading anemias are a common cause of morbidity from liver diseases and increase risk of hepatic fibrosis and hepatocellular carcinoma (HCC). Treatment options for iron-induced damage are limited, partly because there is lack of animal models of human disease. Therefore, we investigated the effect of iron overload in liver-specific β-catenin knockout mice (KO), which are susceptible to injury, fibrosis and tumorigenesis following chemical carcinogen exposure. Iron overload diet was administered to KO and littermate control (CON) mice for various times. To ameliorate an oxidant-mediated component of tissue injury, N-Acetyl-L-(+)-cysteine (NAC) was added to drinking water of mice on iron overload diet. KO on iron diet (KO +Fe) exhibited remarkable inflammation, followed by steatosis, oxidative stress, fibrosis, regenerating nodules and occurrence of occasional HCC. Increased injury in KO +Fe was associated with activated protein kinase B (AKT), ERK, and NF-κB, along with reappearance of β-catenin and target gene Cyp2e1, which promoted lipid peroxidation and hepatic damage. Addition of NAC to drinking water protected KO +Fe from hepatic steatosis, injury and fibrosis, and prevented activation of AKT, ERK, NF-κB and reappearance of β-catenin. The absence of hepatic β-catenin predisposes mice to hepatic injury and fibrosis following iron overload, which was reminiscent of hemochromatosis and associated with enhanced steatohepatitis and fibrosis. Disease progression was notably alleviated by antioxidant therapy, which supports its chemopreventive role in the management of chronic iron overload disorders. Lack of animal models for iron overload disorders makes it hard to study the disease process for improving therapies. Feeding high iron diet to mice that lack the β-catenin gene in liver cells led to increased inflammation followed by fat accumulation, cell death and wound healing that mimicked

  18. Recombinant vesicular stomatitis virus vaccine vectors expressing filovirus glycoproteins lack neurovirulence in nonhuman primates.

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    Chad E Mire

    Full Text Available The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV that expresses an individual filovirus glycoprotein (GP in place of the VSV glycoprotein (G. The main concern with all replication-competent vaccines, including the rVSV filovirus GP vectors, is their safety. To address this concern, we performed a neurovirulence study using 21 cynomolgus macaques where the vaccines were administered intrathalamically. Seven animals received a rVSV vector expressing the Zaire ebolavirus (ZEBOV GP; seven animals received a rVSV vector expressing the Lake Victoria marburgvirus (MARV GP; three animals received rVSV-wild type (wt vector, and four animals received vehicle control. Two of three animals given rVSV-wt showed severe neurological symptoms whereas animals receiving vehicle control, rVSV-ZEBOV-GP, or rVSV-MARV-GP did not develop these symptoms. Histological analysis revealed major lesions in neural tissues of all three rVSV-wt animals; however, no significant lesions were observed in any animals from the filovirus vaccine or vehicle control groups. These data strongly suggest that rVSV filovirus GP vaccine vectors lack the neurovirulence properties associated with the rVSV-wt parent vector and support their further development as a vaccine platform for human use.

  19. Generation of Recombinant Oropouche Viruses Lacking the Nonstructural Protein NSm or NSs.

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    Tilston-Lunel, Natasha L; Acrani, Gustavo Olszanski; Randall, Richard E; Elliott, Richard M

    2015-12-23

    Oropouche virus (OROV) is a midge-borne human pathogen with a geographic distribution in South America. OROV was first isolated in 1955, and since then, it has been known to cause recurring outbreaks of a dengue-like illness in the Amazonian regions of Brazil. OROV, however, remains one of the most poorly understood emerging viral zoonoses. Here we describe the successful recovery of infectious OROV entirely from cDNA copies of its genome and generation of OROV mutant viruses lacking either the NSm or the NSs coding region. Characterization of the recombinant viruses carried out in vitro demonstrated that the NSs protein of OROV is an interferon (IFN) antagonist as in other NSs-encoding bunyaviruses. Additionally, we demonstrate the importance of the nine C-terminal amino acids of OROV NSs in IFN antagonistic activity. OROV was also found to be sensitive to IFN-α when cells were pretreated; however, the virus was still capable of replicating at doses as high as 10,000 U/ml of IFN-α, in contrast to the family prototype BUNV. We found that OROV lacking the NSm protein displayed characteristics similar to those of the wild-type virus, suggesting that the NSm protein is dispensable for virus replication in the mammalian and mosquito cell lines that were tested. Oropouche virus (OROV) is a public health threat in Central and South America, where it causes periodic outbreaks of dengue-like illness. In Brazil, OROV is the second most frequent cause of arboviral febrile illness after dengue virus, and with the current rates of urban expansion, more cases of this emerging viral zoonosis could occur. To better understand the molecular biology of OROV, we have successfully rescued the virus along with mutants. We have established that the C terminus of the NSs protein is important in interferon antagonism and that the NSm protein is dispensable for virus replication in cell culture. The tools described in this paper are important in terms of understanding this important yet

  20. High Blood Caffeine Levels in MCI Linked to Lack of Progression to Dementia

    Science.gov (United States)

    Cao, Chuanhai; Loewenstein, David A.; Lin, Xiaoyang; Zhang, Chi; Wang, Li; Duara, Ranjan; Wu, Yougui; Giannini, Alessandra; Bai, Ge; Cai, Jianfeng; Greig, Maria; Schofield, Elizabeth; Ashok, Raj; Small, Brent; Potter, Huntington; Arendash, Gary W.

    2017-01-01

    Although both human epidemiologic and animal model studies have suggested that caffeine/coffee protects against Alzheimer’s disease, direct human evidence for this premise has been lacking. In the present case-control study, two separate cohorts consisting of 124 total individuals (65–88 years old) were cognitively assessed and a blood sample taken for caffeine/biomarker analysis. Subjects were then monitored for cognitive status over the ensuing 2–4 year period to determine the extent to which initial plasma caffeine/biomarkers levels would be predictive of changes in cognitive status. Plasma caffeine levels at study onset were substantially lower (−51%) in mild cognitive impairment (MCI) subjects who later progressed to dementia (MCI→DEM) compared to levels in stable MCI subjects (MCI→MCI). Moreover, none of the MCI→DEM subjects had initial blood caffeine levels that were above a critical level of 1200 ng/ml, while half of stable MCI→MCI subjects had blood caffeine levels higher than that critical level. Thus, plasma caffeine levels greater than 1200 ng/ml (≈6 µM) in MCI subjects were associated with no conversion to dementia during the ensuing 2–4 year follow-up period. Among the 11 cytokines measured in plasma, three of them (GCSF, IL-10, and IL-6) were decreased in MCI→DEM subjects, but not in stable MCI→MCI subjects with high plasma caffeine levels. Coffee would appear to be the major or perhaps only source of caffeine for such stable MCI patients. This case-control study provides the first direct evidence that caffeine/coffee intake is associated with a reduced risk of dementia or delayed onset, particularly for those who already have MCI. PMID:22430531

  1. Differentially expressed genes in embryonic cardiac tissues of mice lacking Folr1 gene activity

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    Schwartz Robert J

    2007-11-01

    Full Text Available Abstract Background Heart anomalies are the most frequently observed among all human congenital defects. As with the situation for neural tube defects (NTDs, it has been demonstrated that women who use multivitamins containing folic acid peri-conceptionally have a reduced risk for delivering offspring with conotruncal heart defects 123. Cellular folate transport is mediated by a receptor or binding protein and by an anionic transporter protein system. Defective function of the Folr1 (also known as Folbp1; homologue of human FRα gene in mice results in inadequate transport, accumulation, or metabolism of folate during cardiovascular morphogenesis. Results We have observed cardiovascular abnormalities including outflow tract and aortic arch arterial defects in genetically compromised Folr1 knockout mice. In order to investigate the molecular mechanisms underlying the failure to complete development of outflow tract and aortic arch arteries in the Folr1 knockout mouse model, we examined tissue-specific gene expression difference between Folr1 nullizygous embryos and morphologically normal heterozygous embryos during early cardiac development (14-somite stage, heart tube looping (28-somite stage, and outflow track septation (38-somite stage. Microarray analysis was performed as a primary screening, followed by investigation using quantitative real-time PCR assays. Gene ontology analysis highlighted the following ontology groups: cell migration, cell motility and localization of cells, structural constituent of cytoskeleton, cell-cell adhesion, oxidoreductase, protein folding and mRNA processing. This study provided preliminary data and suggested potential candidate genes for further description and investigation. Conclusion The results suggested that Folr1 gene ablation and abnormal folate homeostasis altered gene expression in developing heart and conotruncal tissues. These changes affected normal cytoskeleton structures, cell migration and

  2. Lack of evidence of rotavirus-dependent molecular mimicry as a trigger of coeliac disease.

    Science.gov (United States)

    Ziberna, F; De Lorenzo, G; Schiavon, V; Arnoldi, F; Quaglia, S; De Leo, L; Vatta, S; Martelossi, S; Burrone, O R; Ventura, A; Not, T

    2016-12-01

    New data suggest the involvement of rotavirus (RV) in triggering autoimmunity in coeliac disease (CD) by molecular mimicry between the human-transglutaminase protein and the dodecapeptide (260-271 aa) of the RV protein VP7 (pVP7). To assess the role of RV in the onset of CD, we measured anti-pVP7 antibodies in the sera of children with CD and of control groups. We analysed serum samples of 118 biopsy-proven CD patients and 46 patients with potential CD; 32 children with other gastrointestinal diseases; 107 no-CD children and 107 blood donors. Using enzyme-linked immunosorbent assay (ELISA) assay, we measured immunoglobulin (Ig)A-IgG antibodies against the synthetic peptides pVP7, the human transglutaminase-derived peptide (476-487 aa) which shows a homology with VP7 protein and a control peptide. The triple-layered RV particles (TLPs) containing the VP7 protein and the double-layered RV-particles (DLPs) lacking the VP7 protein were also used as antigens in ELISA assay. Antibody reactivity to the RV-TLPs was positive in 22 of 118 (18%) CD patients and in both paediatric (17 of 107, 16%) and adult (29 of 107, 27%) control groups, without showing a statistically significant difference among them (P = 0·6, P = 0·1). Biopsy-proven CD patients as well as the adult control group demonstrated a high positive antibody reactivity against both pVP7 (34 of 118, 29% CD patients; 66 of 107, 62% adult controls) and control synthetic peptides (35 of 118, 30% CD patients; 56 of 107, 52% adult controls), suggesting a non-specific response against RV pVP7. We show that children with CD do not have higher immune reactivity to RV, thus questioning the molecular mimicry mechanism as a triggering factor of CD. © 2016 British Society for Immunology.

  3. Mice lacking inositol 1,4,5-trisphosphate receptors exhibit dry eye.

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    Takaaki Inaba

    Full Text Available Tear secretion is important as it supplies water to the ocular surface and keeps eyes moist. Both the parasympathetic and sympathetic pathways contribute to tear secretion. Although intracellular Ca2+ elevation in the acinar cells of lacrimal glands is a crucial event for tear secretion in both the pathways, the Ca2+ channel, which is responsible for the Ca2+ elevation in the sympathetic pathway, has not been sufficiently analyzed. In this study, we examined tear secretion in mice lacking the inositol 1,4,5-trisphosphate receptor (IP3R types 2 and 3 (Itpr2-/-;Itpr3-/-double-knockout mice. We found that tear secretion in both the parasympathetic and sympathetic pathways was abolished in Itpr2-/-;Itpr3-/- mice. Intracellular Ca2+ elevation in lacrimal acinar cells after acetylcholine and epinephrine stimulation was abolished in Itpr2-/-;Itpr3-/- mice. Consequently, Itpr2-/-;Itpr3-/- mice exhibited keratoconjunctival alteration and corneal epithelial barrier disruption. Inflammatory cell infiltration into the lacrimal glands and elevation of serum autoantibodies, a representative marker for Sjögren's syndrome (SS in humans, were also detected in older Itpr2-/-;Itpr3-/- mice. These results suggested that IP3Rs are essential for tear secretion in both parasympathetic and sympathetic pathways and that Itpr2-/-;Itpr3-/- mice could be a new dry eye mouse model with symptoms that mimic those of SS.

  4. Lack of Evidence for Molecular Mimicry in HIV-Infected Subjects.

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    Peter D Burbelo

    Full Text Available Previous studies in HIV patients have reported autoantibodies to several human proteins, including erythropoietin (EPO, interferon-α (IFN-α, interleukin-2 (IL-2, and HLA-DR, as potential mediators of anemia or immunosuppression. The etiology of these autoantibodies has been attributed to molecular mimicry between HIV epitopes and self-proteins. Here, the Luciferase Immunoprecipitation System (LIPS was used to investigate the presence of such autoantibodies in HIV-infected adults. High levels of antibodies to HIV proteins such as capsid (p24, matrix (p17, envelope (gp41, and reverse transcriptase (RT were detected using LIPS in both untreated and anti-retroviral-treated HIV-infected individuals but not in uninfected controls. LIPS readily detected anti-EPO autoantibodies in serum samples from subjects with presumptive pure red cell aplasia but not in any of the samples from HIV-infected or uninfected individuals. Similarly, subjects with HIV lacked autoantibodies to IFN-α, IL-2, HLA-DR and the immunoglobulin lambda light chain; all purported targets of molecular mimicry. While molecular mimicry between pathogen proteins and self-proteins is a commonly proposed mechanism for autoantibody production, the findings presented here indicate such a process is not common in HIV disease.

  5. Mutant Mice Lacking the p53 C-Terminal Domain Model Telomere Syndromes

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    Iva Simeonova

    2013-06-01

    Full Text Available Mutations in p53, although frequent in human cancers, have not been implicated in telomere-related syndromes. Here, we show that homozygous mutant mice expressing p53Δ31, a p53 lacking the C-terminal domain, exhibit increased p53 activity and suffer from aplastic anemia and pulmonary fibrosis, hallmarks of syndromes caused by short telomeres. Indeed, p53Δ31/Δ31 mice had short telomeres and other phenotypic traits associated with the telomere disease dyskeratosis congenita and its severe variant the Hoyeraal-Hreidarsson syndrome. Heterozygous p53+/Δ31 mice were only mildly affected, but decreased levels of Mdm4, a negative regulator of p53, led to a dramatic aggravation of their symptoms. Importantly, several genes involved in telomere metabolism were downregulated in p53Δ31/Δ31 cells, including Dyskerin, Rtel1, and Tinf2, which are mutated in dyskeratosis congenita, and Terf1, which is implicated in aplastic anemia. Together, these data reveal that a truncating mutation can activate p53 and that p53 plays a major role in the regulation of telomere metabolism.

  6. Prophylactic platelets in dengue: survey responses highlight lack of an evidence base.

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    James Whitehorn

    Full Text Available Dengue is the most important arboviral infection of humans. Thrombocytopenia is frequently observed in the course of infection and haemorrhage may occur in severe disease. The degree of thrombocytopenia correlates with the severity of infection, and may contribute to the risk of haemorrhage. As a result of this prophylactic platelet transfusions are sometimes advocated for the prevention of haemorrhage. There is currently no evidence to support this practice, and platelet transfusions are costly and sometimes harmful. We conducted a global survey to assess the different approaches to the use of platelets in dengue. Respondents were all physicians involved with the treatment of patients with dengue. Respondents were asked that their answers reflected what they would do if they were the treating physician. We received responses from 306 physicians from 20 different countries. The heterogeneity of the responses highlights the variation in clinical practice and lack of an evidence base in this area and underscores the importance of prospective clinical trials to address this key question in the clinical management of patients with dengue.

  7. Acinetobacter baumannii and A. pittii clinical isolates lack adherence and cytotoxicity to lung epithelial cells in vitro.

    Science.gov (United States)

    Lázaro-Díez, María; Navascués-Lejarza, Teresa; Remuzgo-Martínez, Sara; Navas, Jesús; Icardo, José Manuel; Acosta, Felix; Martínez-Martínez, Luis; Ramos-Vivas, José

    2016-09-01

    The molecular and genetic basis of Acinetobacter baumannii and Acinetobacter pittii virulence remains poorly understood, and there is still lack of knowledge in host cell response to these bacteria. In this study, we have used eleven clinical Acinetobacter strains (A. baumannii n = 5; A. pittii n = 6) to unravel bacterial adherence, invasion and cytotoxicity to human lung epithelial cells. Our results showed that adherence to epithelial cells by Acinetobacter strains is scarce and cellular invasion was not truly detected. In addition, all Acinetobacter strains failed to induce any cytotoxic effect on A549 cells. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  8. Immunization against Leishmania major infection using LACK- and IL-12-expressing Lactococcus lactis induces delay in footpad swelling.

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    Felix Hugentobler

    Full Text Available BACKGROUND: Leishmania is a mammalian parasite affecting over 12 million individuals worldwide. Current treatments are expensive, cause severe side effects, and emerging drug resistance has been reported. Vaccination is the most cost-effective means to control infectious disease but currently there is no vaccine available against Leishmaniasis. Lactococcus lactis is a non-pathogenic, non-colonizing Gram-positive lactic acid bacterium commonly used in the dairy industry. Recently, L. lactis was used to express biologically active molecules including vaccine antigens and cytokines. METHODOLOGY/PRINCIPAL FINDINGS: We report the generation of L. lactis strains expressing the protective Leishmania antigen, LACK, in the cytoplasm, secreted or anchored to the bacterial cell wall. L. lactis was also engineered to secrete biologically active single chain mouse IL-12. Subcutaneous immunization with live L. lactis expressing LACK anchored to the cell wall and L. lactis secreting IL-12 significantly delayed footpad swelling in Leishmania major infected BALB/c mice. The delay in footpad swelling correlated with a significant reduction of parasite burden in immunized animals compared to control groups. Immunization with these two L. lactis strains induced antigen-specific multifunctional T(H1 CD4(+ and CD8(+ T cells and a systemic LACK-specific T(H1 immune response. Further, protection in immunized animals correlated with a Leishmania-specific T(H1 immune response post-challenge. L. lactis secreting mouse IL-12 was essential for directing immune responses to LACK towards a protective T(H1 response. CONCLUSIONS/SIGNIFICANCE: This report demonstrates the use of L. lactis as a live vaccine against L. major infection in BALB/c mice. The strains generated in this study provide the basis for the development of an inexpensive and safe vaccine against the human parasite Leishmania.

  9. Immunization against Leishmania major Infection Using LACK- and IL-12-Expressing Lactococcus lactis Induces Delay in Footpad Swelling

    Science.gov (United States)

    Hugentobler, Felix; Yam, Karen K.; Gillard, Joshua; Mahbuba, Raya; Olivier, Martin; Cousineau, Benoit

    2012-01-01

    Background Leishmania is a mammalian parasite affecting over 12 million individuals worldwide. Current treatments are expensive, cause severe side effects, and emerging drug resistance has been reported. Vaccination is the most cost-effective means to control infectious disease but currently there is no vaccine available against Leishmaniasis. Lactococcus lactis is a non-pathogenic, non-colonizing Gram-positive lactic acid bacterium commonly used in the dairy industry. Recently, L. lactis was used to express biologically active molecules including vaccine antigens and cytokines. Methodology/Principal findings We report the generation of L. lactis strains expressing the protective Leishmania antigen, LACK, in the cytoplasm, secreted or anchored to the bacterial cell wall. L. lactis was also engineered to secrete biologically active single chain mouse IL-12. Subcutaneous immunization with live L. lactis expressing LACK anchored to the cell wall and L. lactis secreting IL-12 significantly delayed footpad swelling in Leishmania major infected BALB/c mice. The delay in footpad swelling correlated with a significant reduction of parasite burden in immunized animals compared to control groups. Immunization with these two L. lactis strains induced antigen-specific multifunctional TH1 CD4+ and CD8+ T cells and a systemic LACK-specific TH1 immune response. Further, protection in immunized animals correlated with a Leishmania-specific TH1 immune response post-challenge. L. lactis secreting mouse IL-12 was essential for directing immune responses to LACK towards a protective TH1 response. Conclusions/Significance This report demonstrates the use of L. lactis as a live vaccine against L. major infection in BALB/c mice. The strains generated in this study provide the basis for the development of an inexpensive and safe vaccine against the human parasite Leishmania. PMID:22348031

  10. Sociability Deficits and Altered Amygdala Circuits in Mice Lacking Pcdh10, an Autism Associated Gene.

    Science.gov (United States)

    Schoch, Hannah; Kreibich, Arati S; Ferri, Sarah L; White, Rachel S; Bohorquez, Dominique; Banerjee, Anamika; Port, Russell G; Dow, Holly C; Cordero, Lucero; Pallathra, Ashley A; Kim, Hyong; Li, Hongzhe; Bilker, Warren B; Hirano, Shinji; Schultz, Robert T; Borgmann-Winter, Karin; Hahn, Chang-Gyu; Feldmeyer, Dirk; Carlson, Gregory C; Abel, Ted; Brodkin, Edward S

    2017-02-01

    Behavioral symptoms in individuals with autism spectrum disorder (ASD) have been attributed to abnormal neuronal connectivity, but the molecular bases of these behavioral and brain phenotypes are largely unknown. Human genetic studies have implicated PCDH10, a member of the δ2 subfamily of nonclustered protocadherin genes, in ASD. PCDH10 expression is enriched in the basolateral amygdala, a brain region implicated in the social deficits of ASD. Previous reports indicate that Pcdh10 plays a role in axon outgrowth and glutamatergic synapse elimination, but its roles in social behaviors and amygdala neuronal connectivity are unknown. We hypothesized that haploinsufficiency of Pcdh10 would reduce social approach behavior and alter the structure and function of amygdala circuits. Mice lacking one copy of Pcdh10 (Pcdh10 +/- ) and wild-type littermates were assessed for social approach and other behaviors. The lateral/basolateral amygdala was assessed for dendritic spine number and morphology, and amygdala circuit function was studied using voltage-sensitive dye imaging. Expression of Pcdh10 and N-methyl-D-aspartate receptor (NMDAR) subunits was assessed in postsynaptic density fractions of the amygdala. Male Pcdh10 +/- mice have reduced social approach behavior, as well as impaired gamma synchronization, abnormal spine morphology, and reduced levels of NMDAR subunits in the amygdala. Social approach deficits in Pcdh10 +/- male mice were rescued with acute treatment with the NMDAR partial agonist d-cycloserine. Our studies reveal that male Pcdh10 +/- mice have synaptic and behavioral deficits, and establish Pcdh10 +/- mice as a novel genetic model for investigating neural circuitry and behavioral changes relevant to ASD. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. Lack of miRNA misregulation at early pathological stages in Drosophila neurodegenerative disease models

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    Anita eReinhardt

    2012-10-01

    Full Text Available Late onset neurodegenerative diseases represent a major public health concern as the population in many countries ages. Both frequent diseases such as Alzheimer disease (AD, 14% incidence for 80-84 year old Europeans or Parkinson disease (PD, 1.4% prevalence for > 55 years old share, with other low-incidence neurodegenerative pathologies such as spinocerebellar ataxias (SCAs, 0.01% prevalence and frontotemporal lobar degeneration (FTLD, 0.02% prevalence, a lack of efficient treatment in spite of important research efforts. Besides significant progress, studies with animal models have revealed unexpected complexities in the degenerative process, emphasizing a need to better understand the underlying pathological mechanisms. Recently, microRNAs, a class of small regulatory non-coding RNAs, have been implicated in some neurodegenerative diseases. The current data supporting a role of miRNAs in PD, tauopathies, dominant ataxias and FTLD will first be discussed to emphasize the different levels of the pathological processes which may be affected by miRNAs. To investigate a potential involvement of miRNA dysregulation in the early stages of these neurodegenerative diseases we have used Drosophila models for 7 diseases (PD, 3 FTLD, 3 dominant ataxias that recapitulate many features of the human diseases. We performed deep sequencing of head small RNAs after 3 days of pathological protein expression in the fly head neurons. We found no evidence for a statistically significant difference in miRNA expression in this early stage of the pathological process. In addition, we could not identify small non coding CAG repeat RNAs (sCAG in polyQ disease models. Thus our data suggest that transcriptional deregulation of miRNAs or sCAG is unlikely to play a significant role in the initial stages of neurodegenerative diseases.

  12. Increased anxiety and fear memory in adult mice lacking type 2 deiodinase.

    Science.gov (United States)

    Bárez-López, Soledad; Montero-Pedrazuela, Ana; Bosch-García, Daniel; Venero, César; Guadaño-Ferraz, Ana

    2017-10-01

    A euthyroid state in the brain is crucial for its adequate development and function. Impairments in thyroid hormones (THs; T3 or 3,5,3'-triiodothyronine and T4 or thyroxine) levels and availability in brain can lead to neurological alterations and to psychiatric disorders, particularly mood disorders. The thyroid gland synthetizes mainly T4, which is secreted to circulating blood, however, most actions of THs are mediated by T3, the transcriptionally active form. In the brain, intracellular concentrations of T3 are modulated by the activity of type 2 (D2) and type 3 (D3) deiodinases. In the present work, we evaluated learning and memory capabilities and anxiety-like behavior at adult stages in mice lacking D2 (D2KO) and we analyzed the impact of D2-deficiency on TH content and on the expression of T3-dependent genes in the amygdala and the hippocampus. We found that D2KO mice do not present impairments in spatial learning and memory, but they display emotional alterations with increased anxiety-like behavior as well as enhanced auditory-cued fear memory and spontaneous recovery of fear memory following extinction. D2KO mice also presented reduced T3 content in the hippocampus and decreased expression of the T3-dependent gene Dio3 in the amygdala suggesting a hypothyroid status in this structure. We propose that the emotional dysfunctions found in D2KO mice can arise from the reduced T3 content in their brain, which consequently leads to alterations in gene expression with functional consequences. We found a downregulation in the gene encoding for the calcium-binding protein calretinin (Calb2) in the amygdala of D2KO mice that could affect the GABAergic transmission. The current findings in D2KO mice can provide insight into emotional disorders present in humans with DIO2 polymorphisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Lack of dependence of 5-fluorodeoxyuridine-mediated radiosensitization on cytotoxicity

    International Nuclear Information System (INIS)

    Lawrence, T.S.; Davis, M.A.; Chang, E.Y.

    1995-01-01

    It has been proposed that fluoropyrimidine-mediated cytotoxicity and radiosensitization are closely correlated. We have shown that HT29 human colon cancer cells transfected with the E. coli dUTPase gene are resistant to 5-fluorodeoxyuridine (FdUrd)-mediated cytotoxicity, presumably through more effective elimination of dUTP. We used these cells to assess the association between radiosensitization and cytotoxicity produced by FdUrd. The radiation sensitivities of the clones expressing elevated dUTPase activity (dutE clones) were similar to those of untransfected HT29 cells or HT29 cells which has been transfected with only the expression vector for the E. coli gene (con clones). We found that FdUrd produced similar increases in radiation sensitivity regardless of dUTPase activity. Levels of dUTPase in the dutE clones remained elevated during the entire period of FdUrd exposure, demonstrating that the lack of difference between dutE and Con clones was not a reflection of down-regulation of dUTPase activity by FdUrd, Flow cytometry showed that all clones progressed past the G 1 /S-phase boundary and into early S phase during FdUrd treatment. These data suggest that the mechanisms of FdUrd-mediated cytotoxicity and radiosensitization are not closely linked. These findings, combined with our previous investigations, are consistent with the hypothesis that radiosensitization occurs in cells which progress past the G 1 /S-phase boundary in the presence of FdUrd. 24 refs., 2 figs., 2 tabs

  14. Immature rats show ovulatory defects similar to those in adult rats lacking prostaglandin and progesterone actions

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    Sanchez-Criado Jose E

    2004-09-01

    Full Text Available Abstract Gonadotropin-primed immature rats (GPIR constitute a widely used model for the study of ovulation. Although the equivalence between the ovulatory process in immature and adult rats is generally assumed, the morphological and functional characteristics of ovulation in immature rats have been scarcely considered. We describe herein the morphological aspects of the ovulatory process in GPIR and their response to classical ovulation inhibitors, such as the inhibitor of prostaglandin (PG synthesis indomethacin (INDO and a progesterone (P receptor (PR antagonist (RU486. Immature Wistar rats were primed with equine chorionic gonadotropin (eCG at 21, 23 or 25 days of age, injected with human chorionic gonadotropin (hCG 48 h later, and sacrificed 16 h after hCG treatment, to assess follicle rupture and ovulation. Surprisingly, GPIR showed age-related ovulatory defects close similar to those in adult rats lacking P and PG actions. Rats primed with eCG at 21 or 23 days of age showed abnormally ruptured corpora lutea in which the cumulus-oocyte complex (COC was trapped or had been released to the ovarian interstitum, invading the ovarian stroma and blood and lymphatic vessels. Supplementation of immature rats with exogenous P and/or PG of the E series did not significantly inhibit abnormal follicle rupture. Otherwise, ovulatory defects were practically absent in rats primed with eCG at 25 days of age. GPIR treated with INDO showed the same ovulatory alterations than vehicle-treated ones, although affecting to a higher proportion of follicles. Blocking P actions with RU486 increased the number of COC trapped inside corpora lutea and decreased ovulation. The presence of ovulatory defects in GPIR, suggests that the capacity of the immature ovary to undergo the coordinate changes leading to effective ovulation is not fully established in Wistar rats primed with eCG before 25 days of age.

  15. ENU mutagenesis reveals a novel phenotype of reduced limb strength in mice lacking fibrillin 2.

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    Gaynor Miller

    2010-02-01

    Full Text Available Fibrillins 1 (FBN1 and 2 (FBN2 are components of microfibrils, microfilaments that are present in many connective tissues, either alone or in association with elastin. Marfan's syndrome and congenital contractural arachnodactyly (CCA result from dominant mutations in the genes FBN1 and FBN2 respectively. Patients with both conditions often present with specific muscle atrophy or weakness, yet this has not been reported in the mouse models. In the case of Fbn1, this is due to perinatal lethality of the homozygous null mice making measurements of strength difficult. In the case of Fbn2, four different mutant alleles have been described in the mouse and in all cases syndactyly was reported as the defining phenotypic feature of homozygotes.As part of a large-scale N-ethyl-N-nitrosourea (ENU mutagenesis screen, we identified a mouse mutant, Mariusz, which exhibited muscle weakness along with hindlimb syndactyly. We identified an amber nonsense mutation in Fbn2 in this mouse mutant. Examination of a previously characterised Fbn2-null mutant, Fbn2(fp, identified a similar muscle weakness phenotype. The two Fbn2 mutant alleles complement each other confirming that the weakness is the result of a lack of Fbn2 activity. Skeletal muscle from mutants proved to be abnormal with higher than average numbers of fibres with centrally placed nuclei, an indicator that there are some regenerating muscle fibres. Physiological tests indicated that the mutant muscle produces significantly less maximal force, possibly as a result of the muscles being relatively smaller in Mariusz mice.These findings indicate that Fbn2 is involved in integrity of structures required for strength in limb movement. As human patients with mutations in the fibrillin genes FBN1 and FBN2 often present with muscle weakness and atrophy as a symptom, Fbn2-null mice will be a useful model for examining this aspect of the disease process further.

  16. Tyrosinase degradation is prevented when EDEM1 lacks the intrinsically disordered region.

    Directory of Open Access Journals (Sweden)

    Marioara B Marin

    Full Text Available EDEM1 is a mannosidase-like protein that recruits misfolded glycoproteins from the calnexin/calreticulin folding cycle to downstream endoplasmic reticulum associated degradation (ERAD pathway. Here, we investigate the role of EDEM1 in the processing of tyrosinase, a tumour antigen overexpressed in melanoma cells. First, we analyzed and modeled EDEM1 major domains. The homology model raised on the crystal structures of human and Saccharomyces cerevisiae ER class I α1,2-mannosidases reveals that the major mannosidase domain located between aminoacids 121-598 fits with high accuracy. We have further identified an N-terminal region located between aminoacids 40-119, predicted to be intrinsically disordered (ID and susceptible to adopt multiple conformations, hence facilitating protein-protein interactions. To investigate these two domains we have constructed an EDEM1 deletion mutant lacking the ID region and a triple mutant disrupting the glycan-binding domain and analyzed their association with tyrosinase. Tyrosinase is a glycoprotein partly degraded endogenously by ERAD and the ubiquitin proteasomal system. We found that the degradation of wild type and misfolded tyrosinase was enhanced when EDEM1 was overexpressed. Glycosylated and non-glycosylated mutants co-immunoprecipitated with EDEM1 even in the absence of its intact mannosidase-like domain, but not when the ID region was deleted. In contrast, calnexin and SEL 1L associated with the deletion mutant. Our data suggest that the ID region identified in the N-terminal end of EDEM1 is involved in the binding of glycosylated and non-glycosylated misfolded proteins. Accelerating tyrosinase degradation by EDEM1 overexpression may lead to an efficient antigen presentation and enhanced elimination of melanoma cells.

  17. Analysis of complete mitochondrial genomes from extinct and extant rhinoceroses reveals lack of phylogenetic resolution

    Science.gov (United States)

    Willerslev, Eske; Gilbert, M Thomas P; Binladen, Jonas; Ho, Simon YW; Campos, Paula F; Ratan, Aakrosh; Tomsho, Lynn P; da Fonseca, Rute R; Sher, Andrei; Kuznetsova, Tatanya V; Nowak-Kemp, Malgosia; Roth, Terri L; Miller, Webb; Schuster, Stephan C

    2009-01-01

    Background The scientific literature contains many examples where DNA sequence analyses have been used to provide definitive answers to phylogenetic problems that traditional (non-DNA based) approaches alone have failed to resolve. One notable example concerns the rhinoceroses, a group for which several contradictory phylogenies were proposed on the basis of morphology, then apparently resolved using mitochondrial DNA fragments. Results In this study we report the first complete mitochondrial genome sequences of the extinct ice-age woolly rhinoceros (Coelodonta antiquitatis), and the threatened Javan (Rhinoceros sondaicus), Sumatran (Dicerorhinus sumatrensis), and black (Diceros bicornis) rhinoceroses. In combination with the previously published mitochondrial genomes of the white (Ceratotherium simum) and Indian (Rhinoceros unicornis) rhinoceroses, this data set putatively enables reconstruction of the rhinoceros phylogeny. While the six species cluster into three strongly supported sister-pairings: (i) The black/white, (ii) the woolly/Sumatran, and (iii) the Javan/Indian, resolution of the higher-level relationships has no statistical support. The phylogenetic signal from individual genes is highly diffuse, with mixed topological support from different genes. Furthermore, the choice of outgroup (horse vs tapir) has considerable effect on reconstruction of the phylogeny. The lack of resolution is suggestive of a hard polytomy at the base of crown-group Rhinocerotidae, and this is supported by an investigation of the relative branch lengths. Conclusion Satisfactory resolution of the rhinoceros phylogeny may not be achievable without additional analyses of substantial amounts of nuclear DNA. This study provides a compelling demonstration that, in spite of substantial sequence length, there are significant limitations with single-locus phylogenetics. We expect further examples of this to appear as next-generation, large-scale sequencing of complete mitochondrial

  18. Analysis of complete mitochondrial genomes from extinct and extant rhinoceroses reveals lack of phylogenetic resolution

    Directory of Open Access Journals (Sweden)

    Nowak-Kemp Malgosia

    2009-05-01

    Full Text Available Abstract Background The scientific literature contains many examples where DNA sequence analyses have been used to provide definitive answers to phylogenetic problems that traditional (non-DNA based approaches alone have failed to resolve. One notable example concerns the rhinoceroses, a group for which several contradictory phylogenies were proposed on the basis of morphology, then apparently resolved using mitochondrial DNA fragments. Results In this study we report the first complete mitochondrial genome sequences of the extinct ice-age woolly rhinoceros (Coelodonta antiquitatis, and the threatened Javan (Rhinoceros sondaicus, Sumatran (Dicerorhinus sumatrensis, and black (Diceros bicornis rhinoceroses. In combination with the previously published mitochondrial genomes of the white (Ceratotherium simum and Indian (Rhinoceros unicornis rhinoceroses, this data set putatively enables reconstruction of the rhinoceros phylogeny. While the six species cluster into three strongly supported sister-pairings: (i The black/white, (ii the woolly/Sumatran, and (iii the Javan/Indian, resolution of the higher-level relationships has no statistical support. The phylogenetic signal from individual genes is highly diffuse, with mixed topological support from different genes. Furthermore, the choice of outgroup (horse vs tapir has considerable effect on reconstruction of the phylogeny. The lack of resolution is suggestive of a hard polytomy at the base of crown-group Rhinocerotidae, and this is supported by an investigation of the relative branch lengths. Conclusion Satisfactory resolution of the rhinoceros phylogeny may not be achievable without additional analyses of substantial amounts of nuclear DNA. This study provides a compelling demonstration that, in spite of substantial sequence length, there are significant limitations with single-locus phylogenetics. We expect further examples of this to appear as next-generation, large-scale sequencing of complete

  19. Increased brain damage after ischaemic stroke in mice lacking the chemokine receptor CCR5

    Science.gov (United States)

    Sorce, S; Bonnefont, J; Julien, S; Marq-Lin, N; Rodriguez, I; Dubois-Dauphin, M; Krause, KH

    2010-01-01

    Background and purpose: The chemokine receptor CCR5 is well known for its function in immune cells; however, it is also expressed in the brain, where its specific role remains to be elucidated. Because genetic factors may influence the risk of developing cerebral ischaemia or affect its clinical outcome, we have analysed the role of CCR5 in experimental stroke. Experimental approach: Permanent cerebral ischaemia was performed by occlusion of the middle cerebral artery in wild-type and CCR5-deficient mice. Locomotor behaviour, infarct size and histochemical alterations were analysed at different time points after occlusion. Key results: The cerebral vasculature was comparable in wild-type and CCR5-deficient mice. However, the size of the infarct and the motor deficits after occlusion were markedly increased in CCR5-deficient mice as compared with wild type. No differences between wild-type and CCR5-deficient mice were elicited by occlusion with respect to the morphology and abundance of astrocytes and microglia. Seven days after occlusion the majority of CCR5-deficient mice displayed neutrophil invasion in the infarct region, which was not observed in wild type. As compared with wild type, the infarct regions of CCR5-deficient mice were characterized by increased neuronal death. Conclusions and implications: Lack of CCR5 increased the severity of brain injury following occlusion of the middle cerebral artery. This is of particular interest with respect to the relatively frequent occurrence of CCR5 deficiency in the human population (1–2% of the Caucasian population) and the advent of CCR5 inhibitors as novel drugs. PMID:20423342

  20. Spdef null mice lack conjunctival goblet cells and provide a model of dry eye.

    Science.gov (United States)

    Marko, Christina K; Menon, Balaraj B; Chen, Gang; Whitsett, Jeffrey A; Clevers, Hans; Gipson, Ilene K

    2013-07-01

    Goblet cell numbers decrease within the conjunctival epithelium in drying and cicatrizing ocular surface diseases. Factors regulating goblet cell differentiation in conjunctival epithelium are unknown. Recent data indicate that the transcription factor SAM-pointed domain epithelial-specific transcription factor (Spdef) is essential for goblet cell differentiation in tracheobronchial and gastrointestinal epithelium of mice. Using Spdef(-/-) mice, we determined that Spdef is required for conjunctival goblet cell differentiation and that Spdef(-/-) mice, which lack conjunctival goblet cells, have significantly increased corneal surface fluorescein staining and tear volume, a phenotype consistent with dry eye. Microarray analysis of conjunctival epithelium in Spdef(-/-) mice revealed down-regulation of goblet cell-specific genes (Muc5ac, Tff1, Gcnt3). Up-regulated genes included epithelial cell differentiation/keratinization genes (Sprr2h, Tgm1) and proinflammatory genes (Il1-α, Il-1β, Tnf-α), all of which are up-regulated in dry eye. Interestingly, four Wnt pathway genes were down-regulated. SPDEF expression was significantly decreased in the conjunctival epithelium of Sjögren syndrome patients with dry eye and decreased goblet cell mucin expression. These data demonstrate that Spdef is required for conjunctival goblet cell differentiation and down-regulation of SPDEF may play a role in human dry eye with goblet cell loss. Spdef(-/-) mice have an ocular surface phenotype similar to that in moderate dry eye, providing a new, more convenient model for the disease. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  1. Development of a lack of appetite item bank for computer-adaptive testing (CAT)

    DEFF Research Database (Denmark)

    Thamsborg, Lise Laurberg Holst; Petersen, Morten Aa; Aaronson, Neil K

    2015-01-01

    to 12 lack of appetite items. CONCLUSIONS: Phases 1-3 resulted in 12 lack of appetite candidate items. Based on a field testing (phase 4), the psychometric characteristics of the items will be assessed and the final item bank will be generated. This CAT item bank is expected to provide precise...

  2. The Lack of Motivation to Pursue Postsecondary Education among Hmong Students: A Grounded Theory Study

    Science.gov (United States)

    Lee, Xang

    2015-01-01

    In rural areas, a lack of motivation to pursue a postsecondary degree continues to affect Hmong students at the postsecondary education level. The purpose of this qualitative grounded theory research was to create a model based on the exploration of the lack of motivation to pursue postsecondary education among Hmong high school students.…

  3. Lack of Neuronal IFN-β-IFNAR Causes Lewy Body- and Parkinson's Disease-like Dementia

    DEFF Research Database (Denmark)

    Ejlerskov, Patrick; Hultberg, Jeanette Göransdotter; Wang, JunYang

    2015-01-01

    -causing mutant proteins. Mice lacking Ifnb function exhibited motor and cognitive learning impairments with accompanying α-synuclein-containing Lewy bodies in the brain, as well as a reduction in dopaminergic neurons and defective dopamine signaling in the nigrostriatal region. Lack of IFN-β signaling caused...

  4. Human NKCC2 cation–Cl– co-transporter complements lack of Vhc1 transporter in yeast vacuolar membranes

    Czech Academy of Sciences Publication Activity Database

    Petrezsélyová, Silvia; Domínguez, A.; Herynková, Pavla; Macias, J. F.; Sychrová, Hana

    2013-01-01

    Roč. 30, č. 10 (2013), s. 395-402 ISSN 0749-503X R&D Projects: GA MŠk(CZ) LC531; GA AV ČR(CZ) IAA500110801 Grant - others:Rada Programu interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M200110901 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : heterologous expression * CCC family * alkali-metal-cation tolerance * Saccharomyces cerevisiae * ion homeostasis Subject RIV: EE - Microbiology, Virology Impact factor: 1.742, year: 2013

  5. The blind brain: how (lack of) vision shapes the morphological and functional architecture of the human brain.

    Science.gov (United States)

    Ricciardi, Emiliano; Handjaras, Giacomo; Pietrini, Pietro

    2014-11-01

    Since the early days, how we represent the world around us has been a matter of philosophical speculation. Over the last few decades, modern neuroscience, and specifically the development of methodologies for the structural and the functional exploration of the brain have made it possible to investigate old questions with an innovative approach. In this brief review, we discuss the main findings from a series of brain anatomical and functional studies conducted in sighted and congenitally blind individuals by our's and others' laboratories. Historically, research on the 'blind brain' has focused mainly on the cross-modal plastic changes that follow sensory deprivation. More recently, a novel line of research has been developed to determine to what extent visual experience is truly required to achieve a representation of the surrounding environment. Overall, the results of these studies indicate that most of the brain fine morphological and functional architecture is programmed to develop and function independently from any visual experience. Distinct cortical areas are able to process information in a supramodal fashion, that is, independently from the sensory modality that carries that information to the brain. These observations strongly support the hypothesis of a modality-independent, i.e. more abstract, cortical organization, and may contribute to explain how congenitally blind individuals may interact efficiently with an external world that they have never seen. © 2014 by the Society for Experimental Biology and Medicine.

  6. The Lack of Impact of Dissensus Inspired Analysis on Developments in the Field of Human Resource Management

    NARCIS (Netherlands)

    Keegan, A.; Boselie, P.

    2006-01-01

    Mainstream HRM journals have largely ignored critical perspectives on HRM. This is the main finding from our study examining trends in publishing on HRM through an analysis of published work in the period 1995 to 2000. Using the ‘dissensus-consensus’ dimension of a framework developed by Deetz

  7. Lack of effects of atomic bomb radiation on genetic instability of tandem-repetitive elements in human germ cells

    International Nuclear Information System (INIS)

    Kodaira, Mieko; Satoh, Chiyoko; Hiyama, Keiko

    1995-01-01

    In a pilot study to detect the potential effects of atomic bomb radiation on germ-line instability, we screened 64 children from 50 exposed families and 60 from 50 control families for mutations at six minisatellite loci by using Southern blot analysis with Pc-1, λTM-18, ChdTC-15, pλg3, λMS-1, and CEB-1 probes. In the exposed families, one or both parents received a radiation dose >0.01 Sv. Among the 64 children, only one child had parents who were both exposed. Thus, of a total of 128 gametes that produced the 64 children, 65 gametes were derived from exposed parents and 63 were from unexposed parents, the latter being included in a group of 183 unexposed gametes used for calculating mutation rates. The average parental gonadal dose for the 65 gametes was 1.9 Sv. We detected a total of 28 mutations at the pλg3, λMS-1, and CEB-1 loci, but no mutations at the Pc-1, λTM-18, and ChdTC-15 loci. We detected 6 mutations in 390 alleles of the 65 exposed gametes and 22 mutations in 1098 alleles of the 183 gametes from the unexposed parents. The mean mutation rate per locus per gamete in these six minisatellite loci was 1.5% in the exposed parents and 2.0% in the unexposed parents. We observed no significant difference in mutation rates in the children of the exposed and the unexposed parents (P = .37, Fisher's exact probability test). 38 refs., 1 fig., 5 tabs

  8. Q&A. Does lack of product management impact the users of open source?

    OpenAIRE

    Paul Young

    2008-01-01

    Most commercial software companies employ product managers to handle the planning and marketing of software products, whereas few open source projects have a product manager. Does lack of product management impact the users of open source?

  9. Q&A. Does lack of product management impact the users of open source?

    Directory of Open Access Journals (Sweden)

    Paul Young

    2008-05-01

    Full Text Available Most commercial software companies employ product managers to handle the planning and marketing of software products, whereas few open source projects have a product manager. Does lack of product management impact the users of open source?

  10. American Joint Helicopter Command: Addressing a Lack of Operational Control of Rotary Assets

    National Research Council Canada - National Science Library

    Marsowicz, Brandon

    2007-01-01

    ... to achieve unity of effort. Based on the tenets of operational command and control by Milan Vego, across all services, the United States helicopter forces fare lacking operational command and control...

  11. Enhancement of immune response induced by DNA vaccine cocktail expressing complete LACK and TSA genes against Leishmania major.

    Science.gov (United States)

    Ghaffarifar, Fatemeh; Jorjani, Ogholniaz; Sharifi, Zohreh; Dalimi, Abdolhossein; Hassan, Zuhair M; Tabatabaie, Fatemeh; Khoshzaban, Fariba; Hezarjaribi, Hajar Ziaei

    2013-04-01

    Leishmaniasis is an important disease in humans. Leishmania homologue of receptor for Activated C Kinase (LACK) and thiol specific antioxidant (TSA) as immuno-dominant antigens of Leishmania major are considered the most promising molecules for a DNA vaccine. We constructed a DNA cocktail, containing plasmids encoding LACK and TSA genes of Leishmania major and evaluated the immune response and survival rate in BALB/c mice. IgG and Interferon gamma values were noticeably increased in the immunized group with DNA cocktail vaccine, which were significantly higher than those in the single-gene vaccinated and control groups (p 0.05). The immunized mice with the cocktail DNA vaccine presented a considerable reduction in diameter of lesion compared to other groups and a significant difference was observed (p < 0.05) in this regard. The survival time of the immunized mice with the cocktail DNA vaccine was significantly higher than that in the other groups (p < 0.05) after their being challenged with Leishmania major. The findings of this study indicated that the cocktail DNA vaccine increased the cellular response and survival rate and induced protection against infection with Leishmania in the mice. © 2012 The Authors © 2012 APMIS.

  12. The Biology of Autoimmune Response in the Scurfy Mice that Lack the CD4+Foxp3+ Regulatory T-Cells.

    Science.gov (United States)

    Ju, Shyr-Te; Sharma, Rahul; Gaskin, Felicia; Kung, John T; Fu, Shu Man

    2012-04-04

    Due to a mutation in the Foxp3 transcription factor, Scurfy mice lack regulatory T-cells that maintain self-tolerance of the immune system. They develop multi-organ inflammation (MOI) and die around four weeks old. The affected organs are skin, tail, lungs and liver. In humans, endocrine and gastrointestinal inflammation are also observed, hence the disease is termed IPEX (Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked) syndrome. The three week period of fatal MOI offers a useful autoimmune model in which the controls by genetics, T-cell subsets, cytokines, and effector mechanisms could be efficiently investigated. In this report, we will review published work, summarize our recent studies of Scurfy double mutants lacking specific autoimmune-related genes, discuss the cellular and cytokine controls by these genes on MOI, the organ-specificities of the MOI controlled by environments, and the effector mechanisms regulated by specific Th cytokines, including several newly identified control mechanisms for organ-specific autoimmune response.

  13. Fentanyl-related designer drugs W-18 and W-15 lack appreciable opioid activity in vitro and in vivo.

    Science.gov (United States)

    Huang, Xi-Ping; Che, Tao; Mangano, Thomas J; Le Rouzic, Valerie; Pan, Ying-Xian; Majumdar, Susruta; Cameron, Michael D; Baumann, Michael H; Pasternak, Gavril W; Roth, Bryan L

    2017-11-16

    W-18 (4-chloro-N-[1-[2-(4-nitrophenyl)ethyl]-2-piperidinylidene]-benzenesulfonamide) and W-15 (4-chloro-N-[1-(2-phenylethyl)-2-piperidinylidene]-benzenesulfonamide) represent two emerging drugs of abuse chemically related to the potent opioid agonist fentanyl (N-(1-(2-phenylethyl)-4-piperidinyl)-N-phenylpropanamide). Here, we describe the comprehensive pharmacological profiles of W-18 and W-15, as examination of their structural features predicted that they might lack opioid activity. We found W-18 and W-15 to be without detectible activity at μ, δ, κ, and nociception opioid receptors in a variety of assays. We also tested W-18 and W-15 for activity as allosteric modulators at opioid receptors and found them devoid of significant positive or negative allosteric modulatory activity. Comprehensive profiling at essentially all the druggable GPCRs in the human genome using the PRESTO-Tango platform revealed no significant activity. Weak activity at the sigma receptors and the peripheral benzodiazepine receptor was found for W-18 (Ki = 271 nM). W-18 showed no activity in either the radiant heat tail-flick or the writhing assays and also did not induce classical opioid behaviors. W-18 is extensively metabolized, but its metabolites also lack opioid activity. Thus, although W-18 and W-15 have been suggested to be potent opioid agonists, our results reveal no significant activity at these or other known targets for psychoactive drugs.

  14. Minor abnormalities of testis development in mice lacking the gene encoding the MAPK signalling component, MAP3K1.

    Directory of Open Access Journals (Sweden)

    Nick Warr

    2011-05-01

    Full Text Available In mammals, the Y chromosome is a dominant male determinant, causing the bipotential gonad to develop as a testis. Recently, cases of familial and spontaneous 46,XY disorders of sex development (DSD have been attributed to mutations in the human gene encoding mitogen-activated protein kinase kinase kinase 1, MAP3K1, a component of the mitogen-activated protein kinase (MAPK signal transduction pathway. In individuals harbouring heterozygous mutations in MAP3K1, dysregulation of MAPK signalling was observed in lymphoblastoid cell lines, suggesting a causal role for these mutations in disrupting XY sexual development. Mice lacking the cognate gene, Map3k1, are viable and exhibit the eyes open at birth (EOB phenotype on a mixed genetic background, but on the C57BL/6J genetic background most mice die at around 14.5 dpc due to a failure of erythropoiesis in the fetal liver. However, no systematic examination of sexual development in Map3k1-deficient mice has been described, an omission that is especially relevant in the case of C57BL/6J, a genetic background that is sensitized to disruptions to testis determination. Here, we report that on a mixed genetic background mice lacking Map3k1 are fertile and exhibit no overt abnormalities of testis development. On C57BL/6J, significant non-viability is observed with very few animals surviving to adulthood. However, an examination of development in Map3k1-deficient XY embryos on this genetic background revealed no significant defects in testis determination, although minor abnormalities were observed, including an increase in gonadal length. Based on these observations, we conclude that MAP3K1 is not required for mouse testis determination. We discuss the significance of these data for the functional interpretation of sex-reversing MAP3K1 mutations in humans.

  15. Analysis of the lack of scientific and technological talents of high-level women in China

    Science.gov (United States)

    Lin, Wang

    2017-08-01

    The growth and development of high-level female scientific and technological talents has become a global problem, facing severe challenges. The lack of high-level women in science and technology has become a global problem. How to recruit and help female scientists and technological talents grow raises awareness from the industry. To find out the main reasons for the lack of high-level female scientific and technological talent. This paper analyses the impact of gender discrimination on the lack of high-level female scientific and technological talents, the impact of disciplinary differences on female roles. The main reasons are: women’s natural disadvantage of mathematical thinking; female birth, the traditional culture on the role of women and the impact of values.

  16. Competency to stand trial and defendants who lack insight into their mental illness.

    Science.gov (United States)

    Reisner, Andrew D; Piel, Jennifer; Makey, Miller

    2013-01-01

    Forensic evaluators often assess patients who lack insight into their mental illnesses. This lack of insight can have a significant impact on the defendant's ability to make legal strategy decisions that rely on their acceptance of their mental illness. In this article, the relationship between refusing an insanity plea and competency to stand trial will be explored in the context of defendants who lack insight into their mental illness. The authors argue that an adequate competency assessment should take into account the defendant's ability to consider his available pleas rationally. Such evaluations may have the effect of negating the necessity of a Frendak inquiry in those jurisdictions that can impose the insanity defense on defendants.

  17. Identifying and Prioritizing the Effective Parameters on Lack of Timeliness of Operations of Sugarcane Production using Analytical Hierarchy Process (AHP

    Directory of Open Access Journals (Sweden)

    N Monjezi

    2017-10-01

    and income criteria. Criterions and prioritizing of them was done by questionnaire and interview with sophisticated experts. This technique determined and ranked the importance of criteria affecting on lack of timeliness of operations based on attributing relative weights to factors with respect to comments provided in the questionnaires. By using of software (Expert choice Analytical Hierarchy Process was done and the inconsistency rate on expert judgments was investigated. Expert Choice software (Expert Choice 1999 was applied to examine the structure of the proposed model and achieve synthesis/ graphical results considering inconsistency ratios. Results and Discussion The Expert Choice software performed well in conjunction with the panel of experts for choosing the criteria and assigning weights under the AHP methodology. According to results, effective parameters on lack of timeliness of operations of sugarcane production consist of delays caused by management, delays caused by human, delays caused by machine and delays caused by procedure (the production process.Weight of criteria effective factors (yield, cost and income on lack of timeliness of operations obtained from paired comparison in the experts’ view which has been calculated with Expert choice software. The result of this survey by AHP techniques showed that cost criteria had the most and income criteria had the least importance for expert in sugarcane production. In this stage of research, alternatives paired comparison relative to criteria was separately formed and information of questionnaire which relates to paired comparison of criteria was obtained. Between effective parameters on lack of timeliness of operations, machine factors to 0.366 weighted average was the most effective factor and production process to 0.298 weighted average, management factors to 0.177 weighted average and human factors to 0.160 weighted average was later respectively (Inconsistence Rate =0.03. The results are examined

  18. Lack of stimulation of 24-hour growth hormone release by hypocaloric diet in obesity

    DEFF Research Database (Denmark)

    Rasmussen, M H; Juul, A; Kjems, L L

    1995-01-01

    . This suggests a reversible defect in GH release, rather than a persistent preexisting disorder. It is hypothesized that enhanced bioavailability of IGF-I, acting in concert with elevated proinsulin and insulin levels, may account for the lack of stimulation of 24-hr GH release by the hypocaloric diet in obese...... subjects. We conclude that the increase in 24-h spontaneous GH release and IGFBP-1 levels observed in normal subjects during the last 24 h of a 96-h VLCD is abolished in obese subjects. The lack of short term hypocaloric stimulation of spontaneous GH release may promote the retention of body fat...

  19. The Rolf and Gertrud Dahlgren Prize for 2017 Awarded to Hans Walter Lack

    DEFF Research Database (Denmark)

    Friis, Ib

    2018-01-01

    The reasons for awarding the Rolf and Gertrud Dahlgren Prize to Hans Walter Lack are summarised and the prize described. It is also mentioned that Rosén's Linnaeus Medal in Gold was awarded to Arne Strid at the same ceremony.......The reasons for awarding the Rolf and Gertrud Dahlgren Prize to Hans Walter Lack are summarised and the prize described. It is also mentioned that Rosén's Linnaeus Medal in Gold was awarded to Arne Strid at the same ceremony....

  20. Lack of diffuseness in wave propagation in lightweight joist-floors

    DEFF Research Database (Denmark)

    Brunskog, Jonas; Chung, Hyuck

    2007-01-01

    . The structures under consideration are rib-reinforced plate structures. These may be a lightweight floor/joist structure in a building or hull of a ship. The diffuseness or rather the lack of diffuseness, in such 'ribbed-plate' structures is examined. The amount of power transported at an angle is calculated...

  1. Quantitative trait loci for a neurocranium deformity, lack of operculum, in gilthead seabream (Sparus aurata L.).

    Science.gov (United States)

    Negrín-Báez, D; Navarro, A; Afonso, J M; Toro, M A; Zamorano, M J

    2016-04-01

    Lack of operculum, a neurocranial deformity, is the most common external abnormality to be found among industrially produced gilthead seabream (Sparus aurata L.), and this entails significant financial losses. This study conducts, for the first time in this species, a quantitative trait loci (QTL) analysis of the lack of operculum. A total of 142 individuals from a paternal half-sibling family (six full-sibling families) were selected for QTL mapping. They had previously shown a highly significant association with the prevalence of lack of operculum in a segregation analysis. All the fish were genotyped for 106 microsatellite markers using a set of multiplex PCRs (ReMsa1-ReMsa13). A linear regression methodology was used for the QTL analysis. Four QTL were detected for this deformity, two of which (QTLOP1 and QTLOP2) were significant. They were located at LG (linkage group) nine and LG10 respectively. Both QTL showed a large effect (about 27%), and furthermore, the association between lack of operculum and sire allelic segregation observed was statistically significant in the QTLOP1 analysis. These results represent a significant step towards including marker-assisted selection for this deformity in genetic breeding programmes to reduce the incidence of the deformity in the species. © 2016 Stichting International Foundation for Animal Genetics.

  2. Patient demands, lack of reciprocity, and burnout: a five-year longitudinal study about general practitioners.

    NARCIS (Netherlands)

    Bakker, A.B.; Schaufeli, W.B.; Sixma, H.J.; Bosveld, W.; Dierendonck, D. van

    2000-01-01

    This study among a sample of 207 general practitioners (GPs) uses a five-year longitudinal design to test a process model of burnout. On the basis of social exchange and equity theory, it is hypothesized and found that demanding patient contacts produce a lack of reciprocity in the GP-patient

  3. 25 CFR 170.811 - What happens if lack of funds results in inadequate maintenance?

    Science.gov (United States)

    2010-04-01

    ... maintenance? 170.811 Section 170.811 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN RESERVATION ROADS PROGRAM BIA Road Maintenance § 170.811 What happens if lack of funds results in inadequate maintenance? If BIA determines that an IRR transportation facility is not being...

  4. Who Lacks Support and Why? An Examination of Mothers' Personal Safety Nets

    Science.gov (United States)

    Harknett, Kristen S.; Hartnett, Caroline Sten

    2011-01-01

    We use data from the Fragile Families and Child Wellbeing Study (N = 12,140 person-waves) to identify characteristics associated with mothers' having or lacking "personal safety net" support from family and friends. We focus on characteristics that are likely to increase the importance of having support available but may also interfere with the…

  5. Deregulated MAPK activity prevents adipocyte differentiation of fibroblasts lacking the retinoblastoma protein

    DEFF Research Database (Denmark)

    Hansen, Jacob B; Petersen, Rasmus K; Jørgensen, Claus

    2002-01-01

    A functional retinoblastoma protein (pRB) is required for adipose conversion of preadipocyte cell lines and primary mouse embryo fibroblasts (MEFs) in response to treatment with standard adipogenic inducers. Interestingly, lack of functional pRB in MEFs was recently linked to elevated Ras activity...

  6. Five reasons for the lack of nursing students' motivation to learn public health.

    Science.gov (United States)

    Kudo, Yasushi; Hayashi, Sachiko; Yoshimura, Emiko; Tsunoda, Masashi; Tsutsumi, Akizumi; Shibuya, Akitaka; Aizawa, Yoshiharu

    2013-11-01

    Prevention is better than cure. Public health plays an important role in promoting prevent medicine. To obtain the abilities to provide appropriate nursing services, learning public health is necessary for students who want to become registered nurses. When teachers teach public health to nursing students, it is important to motivate them to learn it. Therefore, we investigated the reasons for the lack of motivation to learn public health by conducting a questionnaire survey. The subjects were female nursing students in 29 vocational schools in Kanagawa and Chiba prefectures of Japan that allow graduation after a 3-year study period. We asked the students whether or not they had completed the subject of public health and analyzed those students who answered affirmatively. We analyzed 1,553 respondents whose average age was 22.6 ± 5.2 years (range, 18 to 45). Using factor analysis, we discovered the 5 reasons that lead to the lack of nursing students' motivation to learn public health: "Difficulties acquiring knowledge of public health," "Inappropriate attitudes of public health teachers," "Thinking lightly about the national examination in the field of public health," "Lack of understanding the importance of learning public health," and "Future plans that do not specialize in public health." Using multiple linear regression analysis, these 5 reasons were significant predictors for the lack of students' motivation. Older students also had significantly less motivation to learn public health than did younger students. When teachers instruct their students, they should teach public health better with the present knowledge.

  7. [Psychosocial functioning in non-psychiatric acute and chronic inpatients: depression, alexithymia and lack of assertiveness].

    Science.gov (United States)

    Arancibia, Marcelo; Behar, Rosa; Marín, Sofía; Inzunza, Nicolás; Madrid, Eva

    2016-11-01

    Depression, alexithymia, and lack of assertiveness interfere with individual psychosocial functioning and may result in longer hospitalization stay and poorer therapeutic results. To analyze the psychosocial functioning in acute and chronic patients and its association with psychological, clinical and sociodemographic variables. We performed a cross-sectional study that included 80 inpatients of both sexes with organic pathology, aged between 18 to 70 years old, without any current psychiatric disorder. Clinical and sociodemographic data were collected from a semi-structured interview and hospital records. Beck Depression Inventory-IA, Toronto Alexithymia Scale-20 and Rathus Assertiveness Scale were administered. Fifty five percent of patients had some degree of depression, 33% alexithymia and 34% lack of assertiveness. The levels of depression, alexithymia and lack of assertiveness in chronic patients were significantly higher than those observed in acute patients. Women and participants older than 60 years exhibited the highest degrees of depression. Alexithymia and lack of assertiveness were associated with a lower educational level. A negative significant correlation between alexithymia and assertiveness scores was observed among acute patients. Participants with chronic diseases had a lower psychosocial functioning. Less educated patients showed more alexithymic and less assertive features. We emphasized the need of a better management of these aspects by the health team, since social functioning might interfere with the outcome of physical illnesses.

  8. Do semantic standards lack quality? A survey among 34 semantic standards

    NARCIS (Netherlands)

    Folmer, E.J.A.; Oude Luttighuis, P.H.W.M.; Hillegersberg, J. van

    2011-01-01

    The adoption of standards to improve interoperability in the automotive, aerospace, shipbuilding and other sectors could save billions. While interoperability standards have been created for a number of industries, problems persist, suggesting a lack of quality of the standards themselves. The issue

  9. Do semantic standards lack quality? A survey among 34 semantic standards.

    NARCIS (Netherlands)

    Folmer, Erwin Johan Albert; Oude Luttighuis, Paul; van Hillegersberg, Jos

    2011-01-01

    The adoption of standards to improve interoperability in the automotive, aerospace, shipbuilding and other sectors could save billions. While interoperability standards have been created for a number of industries, problems persist, suggesting a lack of quality of the standards themselves. The issue

  10. The lack of theoretical support for using person trade-offs in QALY-type models

    DEFF Research Database (Denmark)

    Østerdal, Lars Peter Raahave

    2009-01-01

    -adjusted life years (DALYs). This paper discusses the theoretical support for the use of person trade-offs in QALY-type measurement of (changes in) population health. It argues that measures of this type based on such quality-adjustment factors almost always violate the Pareto principle, and so lack normative...

  11. Rape as Spectator Sport and Creepshot Entertainment: Social Media and the Valorization of Lack of Consent

    Directory of Open Access Journals (Sweden)

    Kelly Oliver

    2016-10-01

    Full Text Available Lack of consent is valorized within popular culture to the point that sexual assault has become a spectator sport and creepshot entertainment on social media. Indeed, the valorization of nonconsensual sex has reached the extreme where sex with unconscious girls, especially accompanied by photographs as trophies, has become a goal of some boys and men.

  12. Mind Maps to Modify Lack of Attention among Saudi Kindergarten Children

    Science.gov (United States)

    Daghistan, Bulquees Ismail Abdul Majid

    2016-01-01

    This research study aims at investigating the impact of Mind Maps on modifying the lack of attention in Arabic language class among Saudi Kindergarten children. To achieve the goals of this study the researcher used an experimental design with a random sample from AlRae'd Kindergarten's children in Riyadh -Saudi Arabia for the academic year…

  13. Lack of credibility in food markets - driving medium quality food out of the market

    DEFF Research Database (Denmark)

    Christensen, Jan; Graversen, Jesper Tranbjerg

    Some food markets are dominated by high quality and standard quality segments, whereas me-dium quality products are almost absent. A modeling framework with asymmetric information regard-ing true quality of the products and the resulting lack of consumer confidence is presented. Uncer...

  14. Uncertainties associated with lacking data for predictions of solid-solution partitioning of metals in soil

    International Nuclear Information System (INIS)

    Le, T.T. Yen; Hendriks, A. Jan

    2014-01-01

    Soil properties, i.e., pH and contents of soil organic matter (SOM), dissolved organic carbon (DOC), clay, oxides, and reactive metals, are required inputs to both mechanistic and empirical modeling in assessing metal solid-solution partitioning. Several of these properties are rarely measured in site-specific risk assessment. We compared the uncertainties induced by lacking data on these soil properties in estimating metal soil solution concentrations. The predictions by the Orchestra framework were more sensitive to lacking soil property data than the predictions by the transfer functions. The deviations between soil solution concentrations of Cd, Ni, Zn, Ba, and Co estimated with measured SOM and those estimated with generic SOM by the Orchestra framework were about 10 times larger than the deviations in the predictions by the transfer functions. High uncertainties were induced by lacking data in assessing solid-solution partitioning of oxy-anions like As, Mo, Sb, Se, and V. Deviations associated with lacking data in predicting soil solution concentrations of these metals by the Orchestra framework reached three-to-six orders of magnitude. The solid-solution partitioning of metal cations was strongly influenced by pH and contents of organic matter, oxides, and reactive metals. Deviations of more than two orders of magnitude were frequently observed between the estimates of soil solution concentrations with the generic values of these properties and the estimates based on the measured data. Reliable information on these properties is preferred to be included in the assessment by either the Orchestra framework or transfer functions. - Highlights: • Estimates of metal solid-solution partitioning sensitive to soil property data. • Uncertainty mainly due to lacking reactive metal contents, pH, and organic matter. • Soil solution concentrations of oxy-anions highly influenced by oxide contents. • Clay contents had least effects on solid-solution partitioning

  15. Uncertainties associated with lacking data for predictions of solid-solution partitioning of metals in soil

    Energy Technology Data Exchange (ETDEWEB)

    Le, T.T. Yen, E-mail: YenLe@science.ru.nl; Hendriks, A. Jan

    2014-08-15

    Soil properties, i.e., pH and contents of soil organic matter (SOM), dissolved organic carbon (DOC), clay, oxides, and reactive metals, are required inputs to both mechanistic and empirical modeling in assessing metal solid-solution partitioning. Several of these properties are rarely measured in site-specific risk assessment. We compared the uncertainties induced by lacking data on these soil properties in estimating metal soil solution concentrations. The predictions by the Orchestra framework were more sensitive to lacking soil property data than the predictions by the transfer functions. The deviations between soil solution concentrations of Cd, Ni, Zn, Ba, and Co estimated with measured SOM and those estimated with generic SOM by the Orchestra framework were about 10 times larger than the deviations in the predictions by the transfer functions. High uncertainties were induced by lacking data in assessing solid-solution partitioning of oxy-anions like As, Mo, Sb, Se, and V. Deviations associated with lacking data in predicting soil solution concentrations of these metals by the Orchestra framework reached three-to-six orders of magnitude. The solid-solution partitioning of metal cations was strongly influenced by pH and contents of organic matter, oxides, and reactive metals. Deviations of more than two orders of magnitude were frequently observed between the estimates of soil solution concentrations with the generic values of these properties and the estimates based on the measured data. Reliable information on these properties is preferred to be included in the assessment by either the Orchestra framework or transfer functions. - Highlights: • Estimates of metal solid-solution partitioning sensitive to soil property data. • Uncertainty mainly due to lacking reactive metal contents, pH, and organic matter. • Soil solution concentrations of oxy-anions highly influenced by oxide contents. • Clay contents had least effects on solid-solution partitioning

  16. Waste - the human factor

    International Nuclear Information System (INIS)

    McLaren, D.J.

    1993-01-01

    Waste is a human concept, referring to things that have no use to human beings and arising entirely from human activities. It is the useless residue of any human process that affects the economy or environment. The changes brought about by the industrial revolution are enormous; fossil fuels, not just photosynthesis, now provide energy and wastes at rates far exceeding the capacity of the ecosystem to absorb or recycle. Three major problems face the Planet: accelerated population growth, accelerated use of resources for energy and industry, and the disproportionate use of resources and waste between the northern and southern parts of the Planet. Knowledge and science are in a position to provide both human creativity and the directed technology to take remedial action and rediscover harmony between nature and mankind. Only social and political will is lacking

  17. IARC use of oxidative stress as key mode of action characteristic for facilitating cancer classification: Glyphosate case example illustrating a lack of robustness in interpretative implementation.

    Science.gov (United States)

    Bus, James S

    2017-06-01

    The International Agency for Research on Cancer (IARC) has formulated 10 key characteristics of human carcinogens to incorporate mechanistic data into cancer hazard classifications. The analysis used glyphosate as a case example to examine the robustness of IARC's determination of oxidative stress as "strong" evidence supporting a plausible cancer mechanism in humans. The IARC analysis primarily relied on 14 human/mammalian studies; 19 non-mammalian studies were uninformative of human cancer given the broad spectrum of test species and extensive use of formulations and aquatic testing. The mammalian studies had substantial experimental limitations for informing cancer mechanism including use of: single doses and time points; cytotoxic/toxic test doses; tissues not identified as potential cancer targets; glyphosate formulations or mixtures; technically limited oxidative stress biomarkers. The doses were many orders of magnitude higher than human exposures determined in human biomonitoring studies. The glyphosate case example reveals that the IARC evaluation fell substantially short of "strong" supporting evidence of oxidative stress as a plausible human cancer mechanism, and suggests that other IARC monographs relying on the 10 key characteristics approach should be similarly examined for a lack of robust data integration fundamental to reasonable mode of action evaluations. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Early development of the human pelvic diaphragm

    NARCIS (Netherlands)

    Koch, Wijnandus Franciscus Robertus Maria

    2006-01-01

    The last decade an increasing interest in the pelvic floor can be observed in medical sciences. The lack of data on the development of the human pelvic floor is striking. The early development of the human pelvic diaphragm was studied. Materials and methodsUse was made of 38 human embryos and

  19. Lack of plasma albumin impairs intravascular lipolysis and explains the associated free fatty acids deficiency and hypertriglyceridemia

    Directory of Open Access Journals (Sweden)

    Oliveira Helena CF

    2010-12-01

    Full Text Available Abstract Background Abnormalities in lipid metabolism and transport are hallmarks in analbuminemic Nagase rats (NAR and humans. Triglyceridemia is nearly 3- to 5-fold higher in female NAR than in control Sprague-Dawley rats (SDR. Also, NAR present with a severe plasma free fatty acid (FFA deficit. There are conflicting results regarding the mechanisms underlying NAR hypertriglyceridemia. Objective We aimed at investigating whether liver lipogenesis and triglyceride secretion rates into the plasma contribute to the hypertriglyceridemia in NAR. We also studied whether heparin or albumin administration would release the hypothesized lipolysis inhibition in NAR. Methods The incorporation of tritiated water into lipids and the linear accumulation rate of plasma triglycerides after Triton WR1339 injection were the measures of liver lipogenesis and triglyceride secretion rates. Results Lipogenesis (596 ± 40 vs. 929 ± 124 μmol 3H2O/g/h and triglyceride (4.25 ± 1.00 vs. 7.04 ± 1.68 mg/dL/min secretion rates were slower (P ≤ 0.05 in fasted NAR than in control SDR. The injection of either heparin or albumin elicited an increase in NAR plasma FFA levels over time. FFA levels reached control levels 90 min after the albumin administration, increasing from 0.36 ± 0.05 to 1.34 ± 0.16 mEq/L (P ≤ 0.05. These results indicate that the lack of plasma albumin inhibits intravascular lipolysis and causes the FFA deficit observed in NAR. Conclusion NAR hepatic triglyceride synthesis and output do not contribute to NAR hypertriglyceridemia. We propose that the lack of albumin diminishes intravascular lipolysis which reduces the plasma triglyceride removal rate and explain both NAR hypertriglyceridemia and FFA deficiency.

  20. Full Length Research Paper Lack of correlation between H 2O 2 ...

    African Journals Online (AJOL)

    Lactobacilli are considered to play important roles in human health as they are known to secrete inhibitory substances to prevent infection by pathogenic organisms. Previously we have isolated 77 strains of Lactobacillus spp. from human vaginas. In this study, using the plate diffusion method, strains showing in vitro ...

  1. Negotiating the Lack of Intimacy in Assisted Living: Resident Desires, Barriers, and Strategies.

    Science.gov (United States)

    Bender, Alexis A; Burgess, Elisabeth O; Barmon, Christina

    2017-12-01

    Despite continuity in the desire for sex and partnership, many older adults experience a lack of intimacy in late life. The use of assisted living is a complicating factor for understanding issues of partnership, sex, and intimacy for older adults. Using in-depth interviews with 23 assisted living residents and grounded theory methods, we examined how residents negotiate a lack of intimacy in assisted living. The process of negotiation entailed three factors: desire, barriers, and strategies. Although some residents continued to desire intimacy, there was a marked absence of dating or intimacy in our study sites. Findings highlight unique barriers to acting on desire and the strategies residents used as aligning actions between desire and barriers. This research expands previous studies of sexuality and older adults by examining the complex ways in which they balanced desire and barriers through the use of strategies within the assisted living environment.

  2. Appetite and tuberculosis: is the lack of appetite an unidentified risk factor for tuberculosis?

    Science.gov (United States)

    Hernández-Garduño, Eduardo; Pérez-Guzmán, Carlos

    2007-01-01

    Different risk factors have been identified as associated with tuberculosis (TB), an important and common one is malnutrition, however, the causes of malnutrition have not been studied in detail, the lack of food and poverty are among the most frequent in developing countries but others are yet to be identified. We hypothesized that chronic lack of appetite can be one of the causes of malnutrition associated to TB and therefore be a potential independent risk factor for latent tuberculosis infection (LTBI) or TB disease. If this is true, contact subjects with LTBI who have poor appetite will be at higher risk for getting the disease and people with the disease will be at risk for poor treatment outcomes.

  3. The Effects of Lack of Joint Goal Planning on Divorce over 10 Years.

    Science.gov (United States)

    Gere, Judith; Almeida, David M; Martire, Lynn M

    Given the negative consequences of divorce on health and well-being, it is important to try to identify its predictors. In the current study we used data from the National Survey of Midlife Development (N = 2801) to examine the longitudinal effects of lack of joint goal planning with a romantic relationship partner on divorce over a 10-year period. Multilevel regression analyses showed that lack of joint planning with the relationship partner was associated with a 19% increase in the odds of divorce, even when controlling for various demographic (i.e., age, gender, relationship length, number of children in the household), individual (i.e., neuroticism, positive affect, negative affect, physical symptoms, planning), and relationship (i.e., marital empathy, partner strain, partner disagreement, marital satisfaction, commitment). These results demonstrate the importance of considering one's partner when making decisions and plans for the future, given that it has clear implications for relationship dissolution.

  4. Lacking Community Out-Reach of Chinese Mining Investors in the Arctic

    DEFF Research Database (Denmark)

    Zeuthen, Jesper Willaing

    Lacking Community Out-Reach of Chinese Mining Investors in the Arctic Despite China’s bad reputation as a mining investor, in a context of dramatically falling mineral prices, Chinese investments seem to be needed in order to realize most new mining projects across the globe. In Greenland...... and Arctic Canada, potential Chinese investors have been met with even more suspicion than elsewhere. National governments are worried about what state owned Chinese investors will mean for their control over national resources while local governments and the public fear what Chinese investors will mean...... for labour conditions and local environment. They fear a lack of social corporate responsibility (CSR) from Chinese investors. This paper assumes that the possible interest in Arctic mineral resources by the Chinese state combined with a strong demand from Greenland and Canada would make the Arctic a most...

  5. Coalitional Games, Excessive Competition and a Lack of Trust: an Experimental Aproach

    Directory of Open Access Journals (Sweden)

    Dawid Ners

    2017-06-01

    Full Text Available The article tackles the issues of the effectiveness and rationality of making choices in the conditions of competition and cooperation. It confronts the economic theory of rational choice with the empirical results from an experiment. The aim of the article is to show that excessive competition and a lack of trust cause limitation of rational choice in coalitional games. In the experiment conducted for this study purposes, a public good was used to construct a situation in which making a huge coalition is the winning strategy. Despite this fact, the research proves that under competition supported by uncertainty, which results from the lack of trust, the decision making entities behave far less rationally than the game theory would suggest. People competing with each other often take decisions irrationally.

  6. And now, Jose? The punctuation by the bias of the notions of lack and excess

    Directory of Open Access Journals (Sweden)

    Marilei Resmini Grantham

    2017-11-01

    Full Text Available This work has as its starting point the concepts developed and operationalized by Ernst (2009 in the text “Lack, excess and strangeness in the constitution / interpretation of the discursive corpus”. Of the three notions developed by Ernst in her work, I pay attention to those of lack and excess, and I propose to examine these concepts through the bias of punctuation. With this purpose, I choose as an analytical corpus the poem “José”, by Carlos Drummond de Andrade, and, particularly, the formulation “And now, José?”, present throughout the poem. My goal is to work on the notions developed by Ernst, evidencing the discursive functioning of punctuation and seeking to expand my own reflections.

  7. Deriving mechanisms responsible for the lack of correlation between hypoxia and acidity in solid tumors.

    Directory of Open Access Journals (Sweden)

    Hamid R Molavian

    Full Text Available Hypoxia and acidity are two main microenvironmental factors intimately associated with solid tumors and play critical roles in tumor growth and metastasis. The experimental results of Helmlinger and colleagues (Nature Medicine 3, 177, 1997 provide evidence of a lack of correlation between these factors on the micrometer scale in vivo and further show that the distribution of pH and pO(2 are heterogeneous. Here, using computational simulations, grounded in these experimental results, we show that the lack of correlation between pH and pO(2 and the heterogeneity in their shapes are related to the heterogeneous concentration of buffers and oxygen in the blood vessels, further amplified by the network of blood vessels and the cell metabolism. We also demonstrate that, although the judicious administration of anti-angiogenesis agents (normalization process in tumors may lead to recovery of the correlation between hypoxia and acidity, it may not normalize the pH throughout the whole tumor. However, an increase in the buffering capacity inside the blood vessels does appear to increase the extracellular pH throughout the whole tumor. Based on these results, we propose that the application of anti-angiogenic agents and at the same time increasing the buffering capacity of the tumor extracellular environment may be the most efficient way of normalizing the tumor microenvironment. As a by-product of our simulation we show that the recently observed lack of correlation between glucose consumption and hypoxia in cells which rely on respiration is related to the inhomogeneous consumption of glucose to oxygen concentration. We also demonstrate that this lack of correlation in cells which rely on glycolysis could be related to the heterogeneous concentration of oxygen inside the blood vessels.

  8. Defective tubulin organization and proplatelet formation in murine megakaryocytes lacking Rac1 and Cdc42

    DEFF Research Database (Denmark)

    Pleines, Irina; Dütting, Sebastian; Cherpokova, Deya

    2013-01-01

    Blood platelets are anuclear cell fragments that are essential for blood clotting. Platelets are produced by bone marrow megakaryocytes (MKs), which extend protrusions, or so-called proplatelets, into bone marrow sinusoids. Proplatelet formation requires a profound reorganization of the MK actin...... normally in vivo but displayed highly abnormal morphology and uncontrolled fragmentation. Consistently, a lack of Rac1/Cdc42 virtually abrogated proplatelet formation in vitro. Strikingly, this phenotype was associated with severely defective tubulin organization, whereas actin assembly and structure were...

  9. The Causes for Lack of Interest to Blood Donation in Eligible Individuals, Mashhad, Northeastern Iran

    OpenAIRE

    Shakeri, M T; Vafaee, A; Esmaeily, H; Shafiei, N; Bazargani, R; Khayamy, ME

    2012-01-01

    Background Donor recruitment and retention are significant problems in blood collection agencies around the world. The Aim of this study was to determine the causes of lack of interest to blood donation in eligible individu­als in Mashhad, Northeast of Iran. Methods This was a descriptive study. Cases were 1130 non-donor individuals. Participants were selected from eligible individuals in different regions of Mashhad. In this study, surveys included information about age groups, gender, resid...

  10. Lack of focus on cardiovascular disease in sub-Saharan Africa

    OpenAIRE

    Mocumbi, Ana Olga

    2012-01-01

    Research into cardiovascular disease in Sub-Saharan Africa has been hampered by lack of funding and expertise. However, hospital- and community-based data reveal high economic and social costs of these diseases to the national health services and the communities, with the region facing a mixed burden of diseases related to poverty and infections, emergence of risk factors and diseases of affluence, as well as new cardiovascular problems caused by the HIV/AIDS epidemics. The availability of ec...

  11. Cross-cultural comparison of lack of regular physical activity among college students: Universal versus transversal.

    Science.gov (United States)

    Seo, Dong-Chul; Torabi, Mohammad R; Jiang, Nan; Fernandez-Rojas, Xinia; Park, Bock-Hee

    2009-01-01

    This study examined cultural influence on personal and behavioral correlates of lack of regular physical activity (PA) among college students in four countries, i.e., the United States, Costa Rica, India, and South Korea. Public universities were randomly chosen among the four countries. A total of 4,685 students participated in the study during the 2006-2007 academic year with a response rate of 90.1%. The vast majority of the questions on the instrument were adopted from the Youth Risk Behavior Survey and the Behavioral Risk Factor Surveillance System questionnaires. The instrument was translated into Spanish and Korean and then back-translated into English to check accuracy of the translation. Low fruit consumption was a culture-universal predictor of lack of regular PA. Gender, perceived body weight, vegetable consumption, and cigarette smoking were culture-specific predictors, indicating PA might be a transversal value. Body mass index, binge drinking, and TV/video watching were not associated with lack of regular PA in any of the four countries. While PA is valued across different segments of many cultures, given the several culture-specific predictors, PA appears to be more transversal than universal. Therefore, culturally sensitive interventions are necessary to promote PA among young adults.

  12. LEMONS - A Tool for the Identification of Splice Junctions in Transcriptomes of Organisms Lacking Reference Genomes.

    Directory of Open Access Journals (Sweden)

    Liron Levin

    Full Text Available RNA-seq is becoming a preferred tool for genomics studies of model and non-model organisms. However, DNA-based analysis of organisms lacking sequenced genomes cannot rely on RNA-seq data alone to isolate most genes of interest, as DNA codes both exons and introns. With this in mind, we designed a novel tool, LEMONS, that exploits the evolutionary conservation of both exon/intron boundary positions and splice junction recognition signals to produce high throughput splice-junction predictions in the absence of a reference genome. When tested on multiple annotated vertebrate mRNA data, LEMONS accurately identified 87% (average of the splice-junctions. LEMONS was then applied to our updated Mediterranean chameleon transcriptome, which lacks a reference genome, and predicted a total of 90,820 exon-exon junctions. We experimentally verified these splice-junction predictions by amplifying and sequencing twenty randomly selected genes from chameleon DNA templates. Exons and introns were detected in 19 of 20 of the positions predicted by LEMONS. To the best of our knowledge, LEMONS is currently the only experimentally verified tool that can accurately predict splice-junctions in organisms that lack a reference genome.

  13. Diurnal cortisol rhythm: Associated with anxiety and depression, or just an indication of lack of energy?

    Science.gov (United States)

    Harris, Anette; Endresen Reme, Silje; Tangen, Tone; Hansen, Åse Marie; Helene Garde, Anne; Eriksen, Hege Randi

    2015-08-15

    Dysregulation of hypothalamus-pituitary-adrenal-activity has been associated with low back pain (LBP). The underlying mechanisms are not fully explained, but psychological mechanisms are considered important. In this study we examine the association between psychiatric disorders/symptoms measured with different instruments, and cortisol in a population with LBP. Participants (n=305) sick-listed 2-10 months due to non-specific LBP were included in the study. The screening instruments were the MINI-interview, HADS and HSCL-25. Saliva cortisol were measured on 2 consecutive days; at awakening, 30min later, at 15:00h and 22:00h. Results showed no associations between any of the main diagnostic categories from the MINI-interview, or anxiety/depression measured with HADS or HSCL-25 and cortisol. However, significant associations were found between low cortisol awakening response, low cortisol slope during the day and the somatization scale from HSCL-25 (dizziness or lack of energy, lack of sexual interest, the feeling that everything requires substantial efforts, difficulties to fall asleep, headache). The results indicate that cortisol, may not be directly associated with psychopathology, such as anxiety and depression, but instead are associated with one dimension of the psychopathology, namely lack of energy. This could help explain the inconsistency in the literature, and it should be explored further. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Parental lack of care and overprotection. Longitudinal associations with DSM-III-R disorders.

    Science.gov (United States)

    Overbeek, Geertjan; ten Have, Margreet; Vollebergh, Wilma; de Graaf, Ron

    2007-02-01

    This study served to replicate and extend the findings from the National Comorbidity Survey [Enns MW, Cox BJ, Clara I (2002) Psychol Med 32:997-1008], in examining associations between recalled parental bonding and the prevalence and incidence of mental disorders in adulthood. Data were used from 4,796 adults aged 18-64, who had participated in three waves (i.e., 1996, 1997, and 1999) of a large-scale Dutch epidemiological study. Parental lack of care and overprotection were significantly associated with both prevalence and incidence of DSM-III-R disorders. However, the impact of parental bonding was modest, explaining only 1-5% of the variance in the occurrence and onset of psychopathology. Chi-square tests demonstrated there were no differences between the impact of paternal and maternal rearing behaviors on mental disorders, or between lack of care and overprotection in the prediction of mental disorders. Overall, individuals' recollections of parental lack of care and overprotection appear to be non-specifically, modestly related to the prevalence and incidence of DSM-III-R disorders in adults from the general population. Future research may examine indirect or mediated links between parental bonding and (clinical diagnoses of) mental health problems.

  15. Scaffold proteins LACK and TRACK as potential drug targets in kinetoplastid parasites: Development of inhibitors

    Directory of Open Access Journals (Sweden)

    Nir Qvit

    2016-04-01

    Full Text Available Parasitic diseases cause ∼500,000 deaths annually and remain a major challenge for therapeutic development. Using a rational design based approach, we developed peptide inhibitors with anti-parasitic activity that were derived from the sequences of parasite scaffold proteins LACK (Leishmania's receptor for activated C-kinase and TRACK (Trypanosoma receptor for activated C-kinase. We hypothesized that sequences in LACK and TRACK that are conserved in the parasites, but not in the mammalian ortholog, RACK (Receptor for activated C-kinase, may be interaction sites for signaling proteins that are critical for the parasites' viability. One of these peptides exhibited leishmanicidal and trypanocidal activity in culture. Moreover, in infected mice, this peptide was also effective in reducing parasitemia and increasing survival without toxic effects. The identified peptide is a promising new anti-parasitic drug lead, as its unique features may limit toxicity and drug-resistance, thus overcoming central limitations of most anti-parasitic drugs. Keywords: Chagas disease, Leishmaniasis, Peptide, LACK, TRACK, Scaffold protein

  16. Lack of genetic polymorphism among peregrine falcons Falco peregrinus of Fiji

    Science.gov (United States)

    Talbot, Sandra; Palmer, Angela G.; Sage, George K.; Sonsthagen, Sarah A.; Swem, Ted; Brimm, Daniel J.; White, Clayton M

    2014-01-01

    We compared levels of genetic diversity and isolation among peregrine falcons Falco peregrinus from two South Pacific island complexes (Fiji and Vanuatu: F. p. nesiotes), relative to other island and mainland populations. Fragment data from 12 microsatellite loci and sequence information from the control region of the mitochondrial DNA indicated levels of genetic variation in the South Pacific populations were lower than other island and mainland populations. Indeed, diversity varied from extremely low (Vanuatu) to completely absent (Fiji). We find little support for a hypothesis that populations on Fiji or Vanuatu were colonized via Australia. The complete lack of polymorphism in peregrine falcons of Fiji is remarkable, and to our knowledge has not been observed in a natural avian population. This lack of polymorphism, and the inability to test for decrease in polymorphism using museum samples, precludes testing whether the lack of genetic diversity in the population on Fiji is due to a recent bottleneck, or sustained isolation over evolutionary time. Increased fertility in eggs of Fiji peregrines upon outbreeding with males from other areas is consistent with inbreeding depression within a population typified by heterozygote deficiency.

  17. Ground state properties of a spin chain within Heisenberg model with a single lacking spin site

    International Nuclear Information System (INIS)

    Mebrouki, M.

    2011-01-01

    The ground state and first excited state energies of an antiferromagnetic spin-1/2 chain with and without a single lacking spin site are computed using exact diagonalization method, within the Heisenberg model. In order to keep both parts of a spin chain with a lacking site connected, next nearest neighbors interactions are then introduced. Also, the Density Matrix Renormalization Group (DMRG) method is used, to investigate ground state energies of large system sizes; which permits us to inquire about the effect of large system sizes on energies. Other quantum quantities such as fidelity and correlation functions are also studied and compared in both cases. - Research highlights: → In this paper we compute ground state and first excited state energies of a spin chain with and without a lacking spin site. The next nearest neighbors are introduced with the antiferromagnetic Heisenberg spin-half. → Exact diagonalization is used for small systems, where DMRG method is used to compute energies for large systems. Other quantities like quantum fidelity and correlation are also computed. → Results are presented in figures with comments. → E 0 /N is computed in a function of N for several values of J 2 and for both systems. First excited energies are also investigated.

  18. More Human than Human.

    Science.gov (United States)

    Lawrence, David

    2017-07-01

    Within the literature surrounding nonhuman animals on the one hand and cognitively disabled humans on the other, there is much discussion of where beings that do not satisfy the criteria for personhood fit in our moral deliberations. In the future, we may face a different but related problem: that we might create (or cause the creation of) beings that not only satisfy but exceed these criteria. The question becomes whether these are minimal criteria, or hierarchical, such that those who fulfill them to greater degree should be afforded greater consideration. This article questions the validity and necessity of drawing divisions among beings that satisfy the minimum requirements for personhood; considering how future beings-intelligent androids, synthezoids, even alternate-substrate sentiences-might fit alongside the "baseline" human. I ask whether these alternate beings ought to be considered different to us, and why this may or may not matter in terms of a notion of "human community." The film Blade Runner, concerned in large part with humanity and its key synthezoid antagonist Roy Batty, forms a framing touchstone for my discussion. Batty is stronger, faster, more resilient, and more intelligent than Homo sapiens. His exploits, far beyond the capability of normal humans, are contrasted with his frailty and transient lifespan, his aesthetic appreciation of the sights he has seen, and his burgeoning empathy. Not for nothing does his creator within the mythos term him "more human than human."

  19. Lack of association of CTLA-4 +49 A/G polymorphism with ...

    African Journals Online (AJOL)

    Azza M. Kamel

    2013-10-15

    Oct 15, 2013 ... The Egyptian Journal of Medical Human Genetics ... Twenty-two cases had a history of viral infection or exanthematous disease and four had associated ... mother with type 1 diabetes mellitus is 4–10 times while that.

  20. Lack of variation of ATTCT pentanucleotide repeats at ATXN10 gene ...

    Indian Academy of Sciences (India)

    ized incoordination of gait, speech and limb movements. (Tang et ... ataxia (SCA); ATXN10 gene; nucleotide repeat; mutation detection; capillary electrophoresis; human genetics. ... Southern blot analysis using EcoRI was performed to distin-.

  1. Lack of correlation between H2O2 production and in vitro anti ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-05-18

    May 18, 2009 ... the vaginal epithelium, the intestinal tract, and oral cavity of humans and ... possess that make them effective probiotic agents? Although the answer is not fully ... antagonistic effect against urinary and vaginal pathogens. The.

  2. p53-dependent control of cell death by nicastrin: lack of requirement for presenilin-dependent gamma-secretase complex.

    Science.gov (United States)

    Pardossi-Piquard, Raphaëlle; Dunys, Julie; Giaime, Emilie; Guillot-Sestier, Marie-Victoire; St George-Hyslop, Peter; Checler, Frédéric; Alves da Costa, Cristine

    2009-04-01

    Nicastrin (NCT) is a component of the presenilin (PS)-dependent gamma-secretase complexes that liberate amyloid beta-peptides from the beta-Amyloid Precursor Protein. Several lines of evidence indicate that the members of these complexes could also contribute to the control of cell death. Here we show that over-expression of NCT increases the viability of human embryonic kidney (HEK293) cells and decreases staurosporine (STS)- and thapsigargin (TPS)-induced caspase-3 activation in various cell lines from human and neuronal origins by Akt-dependent pathway. NCT lowers p53 expression, transcriptional activity and promoter transactivation and reduces p53 phosphorylation. NCT-associated protection against STS-stimulated cell death was completely abolished by p53 deficiency. Conversely, the depletion of NCT drastically enhances STS-induced caspase-3 activation and p53 pathway and favored p53 nuclear translocation. We examined whether NCT protective function depends on PS-dependent gamma-secretase activity. First, a 29-amino acid deletion known to reduce NCT-dependent amyloid beta-peptide production did not affect NCT-associated protective phenotype. Second, NCT still reduces STS-induced caspase-3 activation in fibroblasts lacking PS1 and PS2. Third, the gamma-secretase inhibitor DFK167 did not affect NCT-mediated reduction of p53 activity. Altogether, our study indicates that NCT controls cell death via phosphoinositide 3-kinase/Akt and p53-dependent pathways and that this function remains independent of the activity and molecular integrity of the gamma-secretase complexes.

  3. Lack of the nucleoside transporter ENT1 results in the Augustine-null blood type and ectopic mineralization.

    Science.gov (United States)

    Daniels, Geoff; Ballif, Bryan A; Helias, Virginie; Saison, Carole; Grimsley, Shane; Mannessier, Lucienne; Hustinx, Hein; Lee, Edmond; Cartron, Jean-Pierre; Peyrard, Thierry; Arnaud, Lionel

    2015-06-04

    The Augustine-negative alias At(a-) blood type, which seems to be restricted to people of African ancestry, was identified half a century ago but remains one of the last blood types with no known genetic basis. Here we report that a nonsynonymous single nucleotide polymorphism in SLC29A1 (rs45458701) is responsible for the At(a-) blood type. The resulting p.Glu391Lys variation in the last extracellular loop of the equilibrative nucleoside transporter 1 (ENT1; also called SLC29a1) is known not to alter its ability to transport nucleosides and nucleoside analog drugs. Furthermore, we identified 3 individuals of European ancestry who are homozygous for a null mutation in SLC29A1 (c.589+1G>C) and thus have the Augustine-null blood type. These individuals lacking ENT1 exhibit periarticular and ectopic mineralization, which confirms an important role for ENT1/SLC29A1 in human bone homeostasis as recently suggested by the skeletal phenotype of aging Slc29a1(-/-) mice. Our results establish Augustine as a new blood group system and place SLC29A1 as a new candidate gene for idiopathic disorders characterized with ectopic calcification/mineralization. © 2015 by The American Society of Hematology.

  4. Identification of a GTP-binding protein α subunit that lacks an apparent ADP-ribosylation site for pertussis toxin

    International Nuclear Information System (INIS)

    Fong, H.K.W.; Yoshimoto, K.K.; Eversole-Cire, P.; Simon, M.I.

    1988-01-01

    Recent molecular cloning of cDNA for the α subunit of bovine transducin (a guanine nucleotide-binding regulatory protein, or G protein) has revealed the presence of two retinal-specific transducins, called T/sub r/ and T/sub c/, which are expressed in rod or cone photoreceptor cells. In a further study of G-protein diversity and signal transduction in the retina, the authors have identified a G-protein α subunit, which they refer to as G/sub z/α, by isolating a human retinal cDNA clone that cross-hybridizes at reduced stringency with bovine T/sub r/ α-subunit cDNA. The deduced amino acid sequence of G/sub z/α is 41-67% identical with those of other known G-protein α subunits. However, the 355-residue G/sub z/α lacks a consensus site for ADP-ribosylation by pertussis toxin, and its amino acid sequence varies within a number of regions that are strongly conserved among all of the other G-protein α subunits. They suggest that G/sub z/α, which appears to be highly expressed in neural tissues, represents a member of a subfamily of G proteins that mediate signal transduction in pertussis toxin-insensitive systems

  5. Proteasome-mediated degradation of integral inner nuclear membrane protein emerin in fibroblasts lacking A-type lamins

    International Nuclear Information System (INIS)

    Muchir, Antoine; Massart, Catherine; Engelen, Baziel G. van; Lammens, Martin; Bonne, Gisele; Worman, Howard J.

    2006-01-01

    We previously identified and characterized a homozygous LMNA nonsense mutation leading to the absence of A-type lamins in a premature neonate who died at birth. We show here that the absence of A-type lamins is due to degradation of the aberrant mRNA transcript with a premature termination codon. In cultured fibroblasts from the subject with the homozygous LMNA nonsense mutation, there was a decreased steady-state expression of the integral inner nuclear membrane proteins emerin and nesprin-1α associated with their mislocalization to the bulk endoplasmic reticulum and a hyperphosphorylation of emerin. To determine if decreased emerin expression occurred post-translationally, we treated cells with a selective proteasome inhibitor and observed an increase in expression. Our results show that mislocalization of integral inner nuclear membrane proteins to the endoplasmic reticulum in human cells lacking A-type lamins leads to their degradation and provides the first evidence that their degradation is mediated by the proteasome

  6. Lack of effect on rat testicular organogenesis after in utero exposure to 3-monochloropropane-1,2-diol (3-MCPD).

    Science.gov (United States)

    El Ramy, Rosy; Ould Elhkim, Mostafa; Poul, Martine; Forest, Maguelone G; Leduque, Patrick; Le Magueresse-Battistoni, Brigitte

    2006-10-01

    3-Monochloropropane-1,2-diol (3-MCPD) is a food-born contaminant known to display toxic effects on male reproduction, producing infertility in rats and humans. Using the rat as a model, we investigated whether or not testicular organogenesis, which, in the rat species, occurs during the second half of gestation, was at particular risk regarding 3-MCPD toxicity. Pregnant rats were given daily doses of 5, 10 or 25 mg/kg BW of 3-MCPD from days 11.5-18.5 postcoitum (dpc). On 19.5 dpc, testes were removed from fetuses for histological examination and testosterone analysis. Eight genes were selected among the differentiation markers of testicular cell lineages, and their expression was studied by RT-PCR. The levels of 3-MCPD and its main metabolite, beta-chlorolactic acid, were assayed in fetal tissues and dam plasma. Our results show a statistically significant decrease in the mean body weight gain of pregnant rats treated with 10 and 25 mg/kg BW of 3-MCPD. Fetal testes exposed to 3-MCPD exhibited normal histology and produced testosterone at levels that were similar to controls. In addition, 3-MCPD did not alter gene expression in the fetal testes. This lack of effect occurred under conditions where 3-MCPD and beta-chlorolactic acid were found to readily cross the placental barrier and diffuse throughout the fetal tissues. Our findings indicate that 3-MCPD has minimal effect on rat testicular organogenesis.

  7. Lacking Ketohexokinase-A Exacerbates Renal Injury in Streptozotocin-induced Diabetic Mice.

    Science.gov (United States)

    Doke, Tomohito; Ishimoto, Takuji; Hayasaki, Takahiro; Ikeda, Satsuki; Hasebe, Masako; Hirayama, Akiyoshi; Soga, Tomoyoshi; Kato, Noritoshi; Kosugi, Tomoki; Tsuboi, Naotake; Lanaspa, Miguel A; Johnson, Richard J; Kadomatsu, Kenji; Maruyama, Shoichi

    2018-03-28

    Ketohexokinase (KHK), a primary enzyme in fructose metabolism, has two isoforms, namely, KHK-A and KHK-C. Previously, we reported that renal injury was reduced in streptozotocin-induced diabetic mice which lacked both isoforms. Although both isoforms express in kidney, it has not been elucidated whether each isoform plays distinct roles in the development of diabetic kidney disease (DKD). The aim of the study is to elucidate the role of KHK-A for DKD progression. Diabetes was induced by five consecutive daily intraperitoneal injections of streptozotocin (50 mg/kg) in C57BL/6 J wild-type mice, mice lacking KHK-A alone (KHK-A KO), and mice lacking both KHK-A and KHK-C (KHK-A/C KO). At 35 weeks, renal injury, inflammation, hypoxia, and oxidative stress were examined. Metabolomic analysis including polyol pathway, fructose metabolism, glycolysis, TCA (tricarboxylic acid) cycle, and NAD (nicotinamide adenine dinucleotide) metabolism in kidney and urine was done. Diabetic KHK-A KO mice developed severe renal injury compared to diabetic wild-type mice, and this was associated with further increases of intrarenal fructose, dihydroxyacetone phosphate (DHAP), TCA cycle intermediates levels, and severe inflammation. In contrast, renal injury was prevented in diabetic KHK-A/C KO mice compared to both wild-type and KHK-A KO diabetic mice. Further, diabetic KHK-A KO mice contained decreased renal NAD + level with the increase of renal hypoxia-inducible factor 1-alpha expression despite having increased renal nicotinamide (NAM) level. These results suggest that KHK-C might play a deleterious role in DKD progression through endogenous fructose metabolism, and that KHK-A plays a unique protective role against the development of DKD. Copyright © 2018. Published by Elsevier Inc.

  8. Lacking quality in research: Is behavioral neuroscience affected more than other areas of biomedical science?

    Science.gov (United States)

    Bespalov, Anton; Steckler, Thomas

    2018-04-15

    There are many reasons why novel therapeutics fail in clinical trials but these failures are often attributed to lacking quality of preclinical data. These problems are not limited to any specific therapeutic area, academic or industrial research and are due in large part to several generic factors influencing research quality (e.g., related to definition of pre-specified endpoints, principles of study design and analysis, biased reporting, and lack of proper training). Yet, neuroscience drug discovery is often said to be affected more than the other fields. Within neuroscience, behavioral studies are the most blamed for being poorly designed, underpowered and mis-reported and there are indeed several factors that may be rather unique for behavioral research, such as a multitude of environmental conditions that are difficult to control and that are often not reported, ethical concerns about in vivo research and the pressure to reduce animal numbers, contributing to under-powered studies, and the complexity of study design and analysis, creating too much room for post hoc data massaging and selective reporting. Also, the blood-brain barrier as a frequently neglected complicating factor has to be considered in CNS research. The importance of these factors is increasingly recognized and urgent efforts are needed to demonstrate that behavioral methods of preclinical neuroscience research deliver results that can be as robust as with the non-behavioral methods Until this goal is achieved, behavioral neuroscience and neuroscience in general may be losing young talent, CNS drug discovery may lack the needed investment and this field may indeed be amongst the most affected by the current preclinical data quality crisis. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Acute respiratory distress syndrome mimickers lacking common risk factors of the Berlin definition.

    Science.gov (United States)

    Gibelin, Aude; Parrot, Antoine; Maitre, Bernard; Brun-Buisson, Christian; Mekontso Dessap, Armand; Fartoukh, Muriel; de Prost, Nicolas

    2016-02-01

    Some patients presenting with acute respiratory failure and meeting the Berlin criteria for acute respiratory distress syndrome (ARDS) lack exposure to common risk factors (CRF). These so-called ARDS mimickers often lack histological diffuse alveolar damage. We aimed to describe such ARDS mimickers lacking CRF (ARDS CRF-) in comparison with others (ARDS CRF+). Retrospective study including all patients receiving invasive mechanical ventilation for ARDS admitted to the intensive care units (ICUs) of two tertiary care centers from January 2003 to December 2012. The prevalence of ARDS CRF- was 7.5 % (95 % CI [5.5-9.5]; n = 50/665). On the basis of medical history, bronchoalveolar lavage fluid cytology, and chest CT scan patterns, four etiological categories were identified: immune (n = 18; 36 %), drug-induced (n = 13; 26 %), malignant (n = 7; 14 %), and idiopathic (n = 12; 24 %). Although the ARDS CRF- patients had a lower logistic organ dysfunction score (4 [3-8] vs. 10 [6-13]; p logistic regression analysis (adjusted OR = 2.06; 95 % CI [1.02-4.18]; p = 0.044). Among ARDS CRF- patients, the presence of potentially reversible lung lesions with corticosteroids (aOR = 0.14; 95 % CI [0.03-0.62]) was associated with ICU survival. The absence of CRF among patients with ARDS is common and associated with a higher risk of mortality. For such atypical ARDS, a complete diagnostic workup, including bronchoalveolar lavage fluid cytology and chest CT scan patterns, should be performed to identify those patients who might benefit from specific therapies, including corticosteroids.

  10. Factors associated with lack of prenatal care in a large municipality

    Directory of Open Access Journals (Sweden)

    Cristiane Quadrado da Rosa

    2014-12-01

    Full Text Available OBJECTIVE To analyze the factors associated with a lack of prenatal care in a large municipality in southern Brazil. METHODS In this case-control age-matched study, 716 women were evaluated; of these, 179 did not receive prenatal care and 537 received prenatal care (controls. These women were identified using the Sistema Nacional de Informação sobre Nascidos Vivos (Live Birth Information System of Pelotas, RS, Southern Brazil, between 2009 and 2010. Multivariate analysis was performed using conditional logistic regression to estimate the odds ratios (OR. RESULTS In the final model, the variables associated with a lack of prenatal care were the level of education, particularly when it was lesser than four years [OR 4.46; 95% confidence interval (CI 1.92;10.36], being single (OR 3.61; 95%CI 1.85;7.04, and multiparity (OR 2.89; 95%CI 1.72;4.85. The prevalence of a lack of prenatal care among administrative regions varied between 0.7% and 3.9%. CONCLUSIONS The risk factors identified must be considered when planning actions for the inclusion of women in prenatal care by both the central management and healthcare teams. These indicated the municipal areas with greater deficits in prenatal care. The reorganization of the actions to identify women with risk factors in the community can be considered to be a starting point of this process. In addition, the integration of the activities of local programs that target the mother and child is essential to constantly identify pregnant women without prenatal care.

  11. THE LACK OF SCIENTIFIC ATTITUDE AS A PROBLEM IN THE DESIGNING OF A YACHT CLUB

    Directory of Open Access Journals (Sweden)

    Екатерина Анатольевна Пирогова

    2016-08-01

    Full Text Available The papers draws attention the fact that nowadays there is a lack of scientific basis for designinh of yacht clubs and ports. There is no legal framework and many terms are misinterpreted. This can be observed in the new decree issued by the Government of the Leningrad region. The author considers it is necessary to develop a uniform legal framework for the design of yacht clubs and ports. The framework should posess a single classification, which allows not only to project a modern yacht education, but to develop yachting infrastructure.

  12. Software Prototyping: A Strategy to Use When User Lacks Data Processing Experience

    OpenAIRE

    Peter M Ogedebe; Babatunde Peter Jacob

    2012-01-01

    A prototype is a working physical model of a system and it serves as a preliminary version of the system. One of the major challenges faced by developers is to know when to use prototype and when not to. This is so considering that there are many disagreements among developers on the proper use of prototyping. This study looked at the question “Is prototyping the best strategy to use when the user lacks data processing?” There is an accepted assumption about users by application developers; t...

  13. A Study of the Impact of the Lack of a Cost Accounting Standards Board.

    Science.gov (United States)

    1987-06-01

    California 00 ,: SE P 9 7 THESIS SE& A STUDY OF THE IMPACT OF THE LACK OF A COST ACCOUNTING STANDARDS BOARD by James F. Sumner, III June 1987 Thesis...O’ATON COSA1. CODES 16 SuB,*CT j’J.45 Comr~nue n- p.ono ol neeeterV ani denltiy by flO(k f1LrmbCr) E,) ROUP StA IRucost accounting , cost accounting ...thesis has two purposes. First, it attempts to determine whether the absence of the Cost Accounting Standards Board (CASB) has given rise to any areas

  14. Inhibition of cell division in hupA hupB mutant bacteria lacking HU protein.

    OpenAIRE

    Dri, A M; Rouviere-Yaniv, J; Moreau, P L

    1991-01-01

    Escherichia coli hupA hypB double mutants that lack HU protein have severe cellular defects in cell division, DNA folding, and DNA partitioning. Here we show that the sfiA11 mutation, which alters the SfiA cell division inhibitor, reduces filamentation and production of anucleate cells in AB1157 hupA hupB strains. However, lexA3(Ind-) and sfiB(ftsZ)114 mutations, which normally counteract the effect of the SfiA inhibitor, could not restore a normal morphology to hupA hupB mutant bacteria. The...

  15. Factors associated with lack of awareness and uncontrolled high blood pressure among Canadian adults with hypertension.

    Science.gov (United States)

    Gee, Marianne E; Bienek, Asako; McAlister, Finlay A; Robitaille, Cynthia; Joffres, Michel; Tremblay, Mark S; Johansen, Helen; Campbell, Norm R C

    2012-05-01

    Approximately 17% of Canadians with high blood pressure were unaware of their condition, and of Canadians aware of having the condition, approximately 1 in 5 have uncontrolled high blood pressure despite high rates of pharmacotherapy. The objectives of the current study are to estimate the prevalence of resistant hypertension and examine factors associated with (1) lack of awareness and (2) uncontrolled hypertension despite pharmacotherapy. Using the 2007-2009 Canadian Health Measures Survey (N = 3473, aged 20-79 years) and logistic regression, we quantified relationships between characteristics and (1) presence of hypertension, (2) lack of awareness (among those with hypertension), and (3) uncontrolled high blood pressure (among those treated for hypertension). Older age, lowest income, and less than high school education were associated with presence of hypertension. Men (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.2) and adults high blood pressure (OR, 2.4; 95% CI, 1.1-5.2) despite treatment. Elevated systolic blood pressure was the issue in over 90% of women and 80% of men with uncontrolled hypertension. Depending on the definition employed, 4.4% (95% CI, 2.4-6.4) to 7.8% (95% CI, 6.0-9.6) of the population with hypertension had resistant hypertension. Messaging or interventions encouraging screening may be helpful for all younger Canadian adults and men; programs encouraging blood pressure control may help older women. Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  16. Compensatory evolution of gene regulation in response to stress by Escherichia coli lacking RpoS.

    Directory of Open Access Journals (Sweden)

    Daniel M Stoebel

    2009-10-01

    Full Text Available The RpoS sigma factor protein of Escherichia coli RNA polymerase is the master transcriptional regulator of physiological responses to a variety of stresses. This stress response comes at the expense of scavenging for scarce resources, causing a trade-off between stress tolerance and nutrient acquisition. This trade-off favors non-functional rpoS alleles in nutrient-poor environments. We used experimental evolution to explore how natural selection modifies the regulatory network of strains lacking RpoS when they evolve in an osmotically stressful environment. We found that strains lacking RpoS adapt less variably, in terms of both fitness increase and changes in patterns of transcription, than strains with functional RpoS. This phenotypic uniformity was caused by the same adaptive mutation in every independent population: the insertion of IS10 into the promoter of the otsBA operon. OtsA and OtsB are required to synthesize the osmoprotectant trehalose, and transcription of otsBA requires RpoS in the wild-type genetic background. The evolved IS10 insertion rewires expression of otsBA from RpoS-dependent to RpoS-independent, allowing for partial restoration of wild-type response to osmotic stress. Our results show that the regulatory networks of bacteria can evolve new structures in ways that are both rapid and repeatable.

  17. Lack of support structures in prioritization decision making concerning patients and resources. Interviews with Swedish physicians.

    Science.gov (United States)

    Werntoft, Elisabet; Edberg, Anna-Karin

    2011-08-01

    To investigate physicians' experiences in relation to prioritization and financing in health care in order to gain a deeper understanding of the reasons behind their standpoints. Eighteen physicians, seven women and eleven men, aged 30 to 69 years were interviewed and the text was analyzed using an inductive approach, also described as conventional qualitative content analysis. Experience of setting healthcare priorities and difficult decision making differed widely among the physicians and seemed to be related to the number of years in professional practice. Their view of how resources should be allocated between disciplines/patients showed that they wanted politicians to make the decisions, with support from medical professions. The overwhelming impression of their reasoning showed that they lacked support structures for their decision making and could be understood under the following categories: prioritisation, easier in theory than in practice, and increasing costs threaten the Swedish welfare model. The findings of this study highlight the importance of practical national guidelines concerning vertical prioritization, also as an important measure to make prioritization more distinct and transparent. The physicians further had a need for tools to increase patients' awareness of their health. The findings of this study also showed that an awareness of the actual costs involved might increase the responsibility among both physicians and patients. The physicians' lack of support structures implies an urgent need for practical national guidelines, especially concerning vertical prioritization. This will also make prioritization appear clear and transparent for citizens.

  18. Lack of motivation: a new modifiable risk factor for peritonitis in patients undergoing peritoneal dialysis?

    Science.gov (United States)

    Paudel, Klara; Namagondlu, Girish; Samad, Nasreen; McKitty, Khadija; Fan, Stanley L

    2015-03-01

    Can we identify modifiable risk factors for peritonitis in patients undergoing peritoneal dialysis (PD)? We aimed to determine whether housing standard, PD exchange technique or patient motivation might be modifiable risks for peritonitis. We also explored the relationship between lack of motivation and depression. Nurse home visits assessed PD exchange technique, environment and patient motivation. Motivation scores were correlated separately with an Apathy Evaluation Score and a depression score using PHQ-9 questionnaires. Home hygiene, exchange technique and motivation were above average in 53%, 56% and 60%, respectively in 104 patients undergoing PD. After 15 months, 25.9% patients developed peritonitis but nurses' ratings of homes and exchange techniques were not predictive. Low patient motivation was predictive. Patients rated to have above or below median motivation had significantly different Apathy Scores (p = 0.0002). Unmotivated depressed patients were significantly more likely to develop peritonitis compared to motivated depressed patients. Lack of motivation predicted peritonitis particularly if associated with depression. Further studies are required focusing on specific motivation scoring schemes and the psychosocial support that might lead to better outcomes. © 2014 European Dialysis and Transplant Nurses Association/European Renal Care Association.

  19. Lack of the purinergic receptor P2X7 results in resistance to contact hypersensitivity

    Science.gov (United States)

    Weber, Felix C.; Esser, Philipp R.; Müller, Tobias; Ganesan, Jayanthi; Pellegatti, Patrizia; Simon, Markus M.; Zeiser, Robert; Idzko, Marco; Jakob, Thilo

    2010-01-01

    Sensitization to contact allergens requires activation of the innate immune system by endogenous danger signals. However, the mechanisms through which contact allergens activate innate signaling pathways are incompletely understood. In this study, we demonstrate that mice lacking the adenosine triphosphate (ATP) receptor P2X7 are resistant to contact hypersensitivity (CHS). P2X7-deficient dendritic cells fail to induce sensitization to contact allergens and do not release IL-1β in response to lipopolysaccharide (LPS) and ATP. These defects are restored by pretreatment with LPS and alum in an NLRP3- and ASC-dependent manner. Whereas pretreatment of wild-type mice with P2X7 antagonists, the ATP-degrading enzyme apyrase or IL-1 receptor antagonist, prevents CHS, IL-1β injection restores CHS in P2X7-deficient mice. Thus, P2X7 is a crucial receptor for extracellular ATP released in skin in response to contact allergens. The lack of P2X7 triggering prevents IL-1β release, which is an essential step in the sensitization process. Interference with P2X7 signaling may be a promising strategy for the prevention of allergic contact dermatitis. PMID:21059855

  20. Lack of color integration in visual short-term memory binding.

    Science.gov (United States)

    Parra, Mario A; Cubelli, Roberto; Della Sala, Sergio

    2011-10-01

    Bicolored objects are retained in visual short-term memory (VSTM) less efficiently than unicolored objects. This is unlike shape-color combinations, whose retention in VSTM does not differ from that observed for shapes only. It is debated whether this is due to a lack of color integration and whether this may reflect the function of separate memory mechanisms. Participants judged whether the colors of bicolored objects (each with an external and an internalcolor) were the same or different across two consecutive screens. Colors had to be remembered either individually or in combination. In Experiment 1, external colors in the combined colors condition were remembered better than the internal colors, and performance for both was worse than that in the individual colors condition. The lack of color integration observed in Experiment 1 was further supported by a reduced capacity of VSTM to retain color combinations, relative to individual colors (Experiment 2). An additional account was found in Experiment 3, which showed spared color-color binding in the presence of impaired shape-color binding in a brain-damaged patient, thus suggesting that these two memory mechanisms are different.

  1. Identification of sulfur volatiles in canned orange juices lacking orange flavor.

    Science.gov (United States)

    Perez-Cacho, Pilar Ruiz; Mahattanatawee, Kanjana; Smoot, John M; Rouseff, Russell

    2007-07-11

    The purpose of this study was to understand why some canned orange juices are not perceived as orange juice. Sensory flavor profile data indicated that the primary odor (orthonasal) attributes were tropical fruit/grapefruit, cooked/caramel, musty, and medicine. By comparison fresh-squeezed juice lacked these odor attributes. GC-O analysis found 43 odor-active components in canned juices. Eight of these aroma volatiles were sulfur based. Four of the 12 most intense aroma peaks were sulfur compounds that included methanethiol, 1-p-menth-1-ene-8-thiol, 2-methyl-3-furanthiol, and dimethyl trisulfide. The other most intense odorants included 7-methyl-3-methylene-1,6-octadiene (myrcene), octanal, 2-methoxyphenol (guaiacol), 2-ethyl-4-hydroxy-5-methyl-3(2H)-furanone (homofuraneol), (E)-non-2-enal, (E,E)-deca-2,4-dienal, 4-hydroxy-3-methoxybenzaldehyde (vanillin), and alpha-sinensal. Odorants probably responsible for the undesirable sensory attributes included grapefruit (1-p-menth-1-ene-8-thiol), cooked [2-ethyl-4-hydroxy-5-methyl-3(2H)-furanone, 4-hydroxy-2,5-dimethyl-3(2H)-furanone (Furaneol), and 3-(methylthio)propanal (methional)], musty [7-methyl-3-methylene-1,6-octadiene and (E)-non-2-enal], and medicine (2-methoxyphenol). The canned juices also lacked several aldehydes and esters normally found in fresh orange juice.

  2. Marines, medics, and machismo: lack of fit with masculine occupational stereotypes discourages men's participation.

    Science.gov (United States)

    Peters, Kim; Ryan, Michelle K; Haslam, S Alexander

    2015-11-01

    Women have made substantial inroads into some traditionally masculine occupations (e.g., accounting, journalism) but not into others (e.g., military, surgery). Evidence suggests the latter group of occupations is characterized by hyper-masculine 'macho' stereotypes that are especially disadvantageous to women. Here, we explore whether such macho occupational stereotypes may be especially tenacious, not just because of their impact on women, but also because of their impact on men. We examined whether macho stereotypes associated with marine commandos and surgeons discourage men who feel that they are 'not man enough'. Study 1 demonstrates that male new recruits' (N = 218) perceived lack of fit with masculine commandos was associated with reduced occupational identification and motivation. Study 2 demonstrates that male surgical trainees' (N = 117) perceived lack of fit with masculine surgeons was associated with reduced identification and increased psychological exit a year later. Together, this suggests that macho occupational stereotypes may discourage the very men who may challenge them. © 2014 The British Psychological Society.

  3. Cytoplasmic tethering of a RING protein RBCK1 by its splice variant lacking the RING domain

    International Nuclear Information System (INIS)

    Yoshimoto, Nobuo; Tatematsu, Kenji; Koyanagi, Tomoyoshi; Okajima, Toshihide; Tanizawa, Katsuyuki; Kuroda, Shun'ichi

    2005-01-01

    RBCC protein interacting with PKC 1 (RBCK1) is a transcription factor belonging to the RING-IBR protein family and has been shown to shuttle between the nucleus and cytoplasm, possessing both the nuclear export and localization signals within its amino acid sequence. RBCK2, lacking the C-terminal half of RBCK1 including the RING-IBR domain, has also been identified as an alternative splice variant of RBCK1. RBCK2 shows no transcriptional activity and instead it represses the transcriptional activity of RBCK1. Here, we show that RBCK2 is present usually in the cytoplasm containing two Leu-rich regions that presumably serve as a nuclear export signal (NES). Moreover, an NES-disrupted RBCK1 that is mostly localized within the nucleus is translocated to the cytoplasm when coexpressed with RBCK2, suggesting that RBCK2 serves as a cytoplasmic tethering protein for RBCK1. We propose a novel and general function of RING-lacking splice variants of RING proteins to control the intracellular localization and functions of the parental RING proteins by forming a hetero-oligomeric complex

  4. Characterisation of Mycobacterium tuberculosis isolates lacking IS6110 in Viet Nam.

    Science.gov (United States)

    Huyen, M N T; Tiemersma, E W; Kremer, K; de Haas, P; Lan, N T N; Buu, T N; Sola, C; Cobelens, F G J; van Soolingen, D

    2013-11-01

    The molecular diagnosis of tuberculosis (TB) in Viet Nam is often based on the detection of insertion sequence (IS) 6110 in Mycobacterium tuberculosis. However, 8-11% of M. tuberculosis strains in South-East Asia do not contain this target and this undermines the validity of these molecular tests. We quantified the frequency of M. tuberculosis strains lacking IS6110 in rural Viet Nam and studied their epidemiological and clinical characteristics. Consecutively diagnosed adult TB patients in rural Southern Viet Nam submitted two sputum samples for culture, IS6110 restriction fragment length polymorphism (RFLP) spoligotyping and 15-loci variable number tandem repeat typing. Polymerase chain reaction (PCR) was performed to confirm the absence of IS6110 elements in strains lacking IS6110 hybridisation in RFLP. Among 2664 TB patient isolates examined, 109 (4.1%) had no IS6110 element. Compared to other strains, these no-copy strains were less often resistant to anti-tuberculosis drugs, particularly to streptomycin (adjusted OR 0.2, 95%CI 0.1-0.5), and showed significant geographic variation. No associations with TB history or demographic factors were found. Strains without the IS6110 target pose a problem in Viet Nam as regards false-negative molecular TB diagnosis in PCR. Compared to other strains circulating in Viet Nam, no-copy strains are more susceptible to anti-tuberculosis drugs.

  5. Inhibition of cell division in hupA hupB mutant bacteria lacking HU protein.

    Science.gov (United States)

    Dri, A M; Rouviere-Yaniv, J; Moreau, P L

    1991-01-01

    Escherichia coli hupA hypB double mutants that lack HU protein have severe cellular defects in cell division, DNA folding, and DNA partitioning. Here we show that the sfiA11 mutation, which alters the SfiA cell division inhibitor, reduces filamentation and production of anucleate cells in AB1157 hupA hupB strains. However, lexA3(Ind-) and sfiB(ftsZ)114 mutations, which normally counteract the effect of the SfiA inhibitor, could not restore a normal morphology to hupA hupB mutant bacteria. The LexA repressor, which controls the expression of the sfiA gene, was present in hupA hupB mutant bacteria in concentrations half of those of the parent bacteria, but this decrease was independent of the specific cleavage of the LexA repressor by activated RecA protein. One possibility to account for the filamentous morphology of hupA hupB mutant bacteria is that the lack of HU protein alters the expression of specific genes, such as lexA and fts cell division genes. Images PMID:2019558

  6. Nicotine anxiogenic and rewarding effects are decreased in mice lacking beta-endorphin.

    Science.gov (United States)

    Trigo, José M; Zimmer, Andreas; Maldonado, Rafael

    2009-06-01

    The endogenous opioid system plays an important role in the behavioral effects of nicotine. Thus, micro-opioid receptor and the endogenous opioids derived from proenkephalin are involved in the central effects of nicotine. However, the role played by the different endogenous opioid peptides in the acute and chronic effects of nicotine remains to be fully established. Mice lacking beta-endorphin were acutely injected with nicotine at different doses to evaluate locomotor, anxiogenic and antinociceptive responses. The rewarding properties of nicotine were evaluated by using the conditioned place-preference paradigm. Mice chronically treated with nicotine were acutely injected with mecamylamine to study the behavioral expression of nicotine withdrawal. Mice lacking beta-endorphin exhibited a spontaneous hypoalgesia and hyperlocomotion and a reduction on the anxiogenic and rewarding effects induced by nicotine. Nicotine induced similar antinociception and hypolocomotion in both genotypes and no differences were found in the development of physical dependence. The dissociation between nicotine rewarding properties and physical dependence suggests a differential implication of beta-endorphin in these addictive related responses.

  7. Nicotine anxiogenic and rewarding effects are decreased in mice lacking β-endorphin

    Science.gov (United States)

    Trigo, José M.; Zimmer, Andreas; Maldonado, Rafael

    2009-01-01

    The endogenous opioid system plays an important role in the behavioral effects of nicotine. Thus, μ-opioid receptor and the endogenous opioids derived from proenkephalin are involved in the central effects of nicotine. However, the role played by the different endogenous opioid peptides in the acute and chronic effects of nicotine remains to be fully established. Mice lacking β-endorphin were acutely injected with nicotine at different doses to evaluate locomotor, anxiogenic and antinociceptive responses. The rewarding properties of nicotine were evaluated by using the conditioned place-preference paradigm. Mice chronically treated with nicotine were acutely injected with mecamylamine to study the behavioral expression of nicotine withdrawal. Mice lacking β-endorphin exhibited a spontaneous hypoalgesia and hyperlocomotion and a reduction on the anxiogenic and rewarding effects induced by nicotine. Nicotine induced similar antinociception and hypolocomotion in both genotypes and no differences were found in the development of physical dependence. The dissociation between nicotine rewarding properties and physical dependence suggests a differential implication of β-endorphin in these addictive related responses. PMID:19376143

  8. Lack of concordance in parapneumonic effusion management in children in central Europe.

    Science.gov (United States)

    Hafen, Gaudenz M; Grenzbach, Andrea-Claudia; Moeller, Alexander; Rochat, Mascha K

    2016-04-01

    Treatment of parapneumonic effusion in children remains controversial in the literature and in clinical practice. The aim of this study was to determine whether mutual consensus exists in the diagnosis and treatment of parapneumonic effusion in Central European countries. A questionnaire was sent to all directors of pediatric respiratory units in four adjacent Central European countries (Austria, France, Germany, Switzerland). The response rate was 61.8%. Responses reflected acceptable agreement regarding initial diagnostic procedures, as most centers performed chest X-ray and biological exams, followed by ultrasound, thoracocentesis, or computed tomography. However, antibiotic regimens were very heterogeneous, and the survey revealed complete lack of agreement on the indications and effusion volume threshold for invasive procedures, such as fibrinolytic instillation and thoracoscopy. In conclusion, apart from initial diagnostic procedures, this study showed a lack of mutual consensus among the four countries regarding the management of pediatric parapneumonic effusion. Multicenter prospective trials are clearly needed to acquire more evidence on the management of childhood parapneumonic effusion, enabling the development of evidence-based algorithms that could help to avoid unnecessary examinations with potential long-term side effects, such as radiation exposure at a young age. © 2015 Wiley Periodicals, Inc.

  9. Does lack of resources impair access to breast and cervical cancer screening in Japan?

    Science.gov (United States)

    Sano, Hiroshi; Goto, Rei; Hamashima, Chisato

    2017-01-01

    To assess the impact of the quantity of resources for breast and cervical cancer screening on the participation rates in screening in clinical settings in municipalities, as well as to clarify whether lack of resources impairs access to cancer screening in Japan. Of the 1,746 municipalities in 2010, 1,443 (82.6%) and 1,469 (84.1%) were included in the analyses for breast and cervical cancer screening, respectively. In order to estimate the effects of the number of mammography units and of gynecologists on the participation rates in breast and cervical cancer screening in clinical settings, multiple regression analyses were performed using the interaction term for urban municipalities. The average participation rate in screening in clinical settings was 6.01% for breast cancer, and was 8.93% for cervical cancer. The marginal effect of the number of mammography units per 1,000 women was significantly positive in urban municipalities (8.20 percent point). The marginal effect of the number of gynecologists per 1,000 women was significantly positive in all municipalities (2.54 percent point) and rural municipalities (3.68 percent point). Lack of mammography units in urban areas and of gynecologists particularly in rural areas impaired access to breast and cervical cancer screening. Strategies are required that quickly improve access for the residents and increase their participation rates in cancer screening.

  10. Lack of integration governance in ERP development: a case study on causes and effects

    Science.gov (United States)

    Kähkönen, Tommi; Smolander, Kari; Maglyas, Andrey

    2017-09-01

    The development of an enterprise resource planning (ERP) system starts actually after it has been implemented and taken into use. It is necessary to integrate ERP with other business information systems inside and outside the company. With the grounded theory, we aim to understand how integration challenges emerged in a large manufacturing enterprise when the long-term ERP system reached the beginning of its retirement. Structural changes, an information technology governance model, lack of organisational vision, having no architectural descriptions, lack of collaboration, cost cutting, and organisational culture made integration governance troublesome. As a consequence, the enterprise suffered from several undesired effects, such as complex integration scenarios between internal systems, and failing to provide its customers the needed information. The reduction of costs strengthened the organisational silos further and led to unrealised business process improvements. We provide practitioners with four recommendations. First, the organisational goals for integration should be exposed. Second, when evaluating the needs and impacts of integration, a documented architectural description about the system landscape needs to be utilised. Third, the role of IT should be emphasised in development decision-making, and fourth, collaboration is the core ingredient for successful integration governance.

  11. Wheat crown rot pathogens Fusarium graminearum and F. pseudograminearum lack specialization.

    Science.gov (United States)

    Chakraborty, Sukumar; Obanor, Friday; Westecott, Rhyannyn; Abeywickrama, Krishanthi

    2010-10-01

    This article reports a lack of pathogenic specialization among Australian Fusarium graminearum and F. pseudograminearum causing crown rot (CR) of wheat using analysis of variance (ANOVA), principal component and biplot analysis, Kendall's coefficient of concordance (W), and κ statistics. Overall, F. pseudograminearum was more aggressive than F. graminearum, supporting earlier delineation of the crown-infecting group as a new species. Although significant wheat line-pathogen isolate interaction in ANOVA suggested putative specialization when seedlings of 60 wheat lines were inoculated with 4 pathogen isolates or 26 wheat lines were inoculated with 10 isolates, significant W and κ showed agreement in rank order of wheat lines, indicating a lack of specialization. The first principal component representing nondifferential aggressiveness explained a large part (up to 65%) of the variation in CR severity. The differential components were small and more pronounced in seedlings than in adult plants. By maximizing variance on the first two principal components, biplots were useful for highlighting the association between isolates and wheat lines. A key finding of this work is that a range of analytical tools are needed to explore pathogenic specialization, and a statistically significant interaction in an ANOVA cannot be taken as conclusive evidence of specialization. With no highly resistant wheat cultivars, Fusarium isolates mostly differ in aggressiveness; however, specialization may appear as more resistant cultivars become widespread.

  12. Human Rights in Indonesian Constitutional Amendments

    OpenAIRE

    Kharlie, Ahmad Tholabi

    2013-01-01

    Human Rights in Indonesian Constitutional Amendments. Indonesian constitutional amendments incorporated human rights principles into the Constitution of the Republic of Indonesia 1945 (UUD NRI), especially in the second amendment in 2000. Under that amendment, the UUD NRI currently stipulates human rights principles as provided for in the Universal Declaration of Human Rights (UDHR). However, there are some important notes, which at its core is a lack of emphasis on the vision and mission of ...

  13. Developing T lymphocytes are uniquely sensitive to a lack of topoisomerase III alpha

    DEFF Research Database (Denmark)

    Mönnich, Maren; Hess, Isabell; Wiest, Waltraud

    2010-01-01

    All organisms possess at least one type IA DNA topoisomerase. These topoisomerases function as part of a DNA structure-specific "dissolvasome," also known as the RTR complex, which has critical functions in faithful DNA replication, recombination, and chromosome segregation. In humans, the hetero......All organisms possess at least one type IA DNA topoisomerase. These topoisomerases function as part of a DNA structure-specific "dissolvasome," also known as the RTR complex, which has critical functions in faithful DNA replication, recombination, and chromosome segregation. In humans...

  14. Protein Crystal Recombinant Human Insulin

    Science.gov (United States)

    1994-01-01

    The comparison of protein crystal, Recombiant Human Insulin; space-grown (left) and earth-grown (right). On STS-60, Spacehab II indicated that space-grown crystals are larger and of greater optical clarity than their earth-grown counterparts. Recombiant Human Insulin facilitates the incorporation of glucose into cells. In diabetics, there is either a decrease in or complete lack of insulin, thereby leading to several harmful complications. Principal Investigator is Larry DeLucas.

  15. Lack of association between rs10491334 in the CAMK4 gene and ...

    Indian Academy of Sciences (India)

    human longevity in a Chinese population and found that the. SNP was negatively ... 10,000 inhabitants, 65 years of age or older, is in Hainan. (16.64), followed by .... ified analyses by sex and did not observe positive effect of rs10491334 in ...

  16. Lack of Direct Cytotoxicity of Extracellular ATP against Hepatocytes: Role in the Mechanism of Acetaminophen Hepatotoxicity

    NARCIS (Netherlands)

    Xie, Yuchao; Woolbright, Benjamin L.; Kos, Milan; McGill, Mitchell R.; Dorko, Kenneth; Kumer, Sean C.; Schmitt, Timothy M.; Jaeschke, Hartmut

    2015-01-01

    Acetaminophen (APAP) hepatotoxicity is a major cause of acute liver failure in many countries. Mechanistic studies in mice and humans have implicated formation of a reactive metabolite, mitochondrial dysfunction and oxidant stress as critical events in the pathophysiology of APAP-induced liver cell

  17. Lack of genotoxic potential of acetylated monoglyceride: An alternative plasticiser to phthalates

    DEFF Research Database (Denmark)

    Mortensen, Alicja; Wedebye, Eva Bay; Niemelä, Jay Russell

    2011-01-01

    Purpose: With a yearly polymer production of more than 400 million tons, phthalates based on non sustainable petrochemical materials are the most used group of plasticisers. Their low biodegradability and endocrine activity suspected to affect reproductive ability of animals and humans caused...

  18. Lack of direct effects of agrochemicals on zoonotic pathogens and fecal indicator bacteria.

    Science.gov (United States)

    Staley, Zachery R; Senkbeil, Jacob K; Rohr, Jason R; Harwood, Valerie J

    2012-11-01

    Agrochemicals, fecal indicator bacteria (FIB), and pathogens frequently contaminate water simultaneously. No significant direct effects of fertilizer, atrazine, malathion, and chlorothalonil on the survival of Escherichia coli, Enterococcus faecalis, Salmonella enterica, human polyomaviruses, and adenovirus were detected, supporting the assertion that previously observed effects of agrochemicals on FIB were indirect.

  19. Pandemic H1N1 2009 virus in Danish pigs: Diagnosis and lack of surveillance

    DEFF Research Database (Denmark)

    Larsen, Lars Erik; Nielsen, L. P.; Breum, Solvej Østergaard

    In March-April 2009, a novel pandemic H1N1 virus (H1N1v) of likely swine origin emerged in the human population globally. The first case in pigs was reported from Canada in May 2009 and presently almost all countries with pig production have reported cases. The emergence of a new influenza subtype...

  20. Lack of Ubiquitin Specific Protease 8 (USP8) Mutations in Canine Corticotroph Pituitary Adenomas

    NARCIS (Netherlands)

    Sbiera, Silviu; Tryfonidou, Marianna A; Weigand, Isabel; Grinwis, Guy C M; Broeckx, Bart; Herterich, Sabine; Allolio, Bruno; Deutschbein, Timo; Fassnacht, Martin; Meij, Björn P

    2016-01-01

    PURPOSE: Cushing's disease (CD), also known as pituitary-dependent hyperadrenocorticism, is caused by adrenocorticotropic hormone (ACTH)-secreting pituitary tumours. Affected humans and dogs have similar clinical manifestations, however, the incidence of the canine disease is thousand-fold higher.

  1. Mice lacking desmocollin 1 show epidermal fragility accompanied by barrier defects and abnormal differentiation

    DEFF Research Database (Denmark)

    Chidgey, M; Brakebusch, C; Gustafsson, E

    2001-01-01

    epidermis because environmental insults are more stringent and wound healing is less rapid than in neonatal mice. This dermatitis is accompanied by localized hair loss associated with formation of utriculi and dermal cysts, denoting hair follicle degeneration. Possible resemblance of the lesions to human...

  2. Lack of Precision of Burn Surface Area Calculation by UK Armed Forces Medical Personnel

    Science.gov (United States)

    2014-03-01

    computer screen or tablet , and therefore the variability in perception and representation inherent in having a human assess and draw the burn remains...Potential solutions to this source of error include 3D MRI and TeraHertz scanning technologies [40], but at the time of writing, these are not yet

  3. Maternofetal transplacental transport of recombinant IgG antibodies lacking effector functions

    DEFF Research Database (Denmark)

    Mathiesen, Line; Nielsen, Leif K; Andersen, Jan Terje

    2013-01-01

    alloimmunity, which may be lethal. A novel strategy to control pathogenic antibodies would be administration of a non-destructive IgG antibody blocking antigen binding while retaining binding to FcRn. We report on two human IgG3 antibodies with a hinge deletion and a C131S point mutation (IgG3ΔHinge...

  4. Normal hematopoiesis and lack of β-catenin activation in osteoblasts of patients and mice harboring Lrp5 gain of function mutations

    DEFF Research Database (Denmark)

    Galan-Diez, Marta; Isa, Adiba; Ponzetti, Marco

    2016-01-01

    of hematopoiesis and leukemogenic properties of β-catenin activation in osteoblasts, that lead to development of acute myeloid leukemia (AML). Using mice with gain-of-function (GOF) Lrp5 alleles (Lrp5(A214V)) that recapitulate the human high bone mass (HBM) phenotype, as well as patients with the T253I HBM Lrp5...... mutation, we show here that Lrp5 GOF mutations in both humans and mice do not activate β-catenin signaling in osteoblasts. Consistent with a lack of β-catenin activation in their osteoblasts, Lrp5(A214V) mice have normal trilinear hematopoiesis. In contrast to leukemic mice with constitutive activation...... of β-catenin in osteoblasts (Ctnnb1(CAosb)), accumulation of early myeloid progenitors, a characteristic of AML, myeloid-blasts in blood, and segmented neutrophils or dysplastic megakaryocytes in the bone marrow, are not observed in Lrp5(A214V) mice. Likewise, peripheral blood count analysis in HBM...

  5. Double gene deletion reveals the lack of cooperation between PPARα and PPARβ in skeletal muscle

    International Nuclear Information System (INIS)

    Bedu, E.; Desplanches, D.; Pequignot, J.; Bordier, B.; Desvergne, B.

    2007-01-01

    The peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of most of the pathways linked to lipid metabolism. PPARα and PPARβ isotypes are known to regulate muscle fatty acid oxidation and a reciprocal compensation of their function has been proposed. Herein, we investigated muscle contractile and metabolic phenotypes in PPARα-/-, PPARβ-/-, and double PPARα-/- β-/- mice. Heart and soleus muscle analyses show that the deletion of PPARα induces a decrease of the HAD activity (β-oxidation) while soleus contractile phenotype remains unchanged. A PPARβ deletion alone has no effect. However, these mild phenotypes are not due to a reciprocal compensation of PPARβ and PPARα functions since double gene deletion PPARα-PPARβ mostly reproduces the null PPARα-mediated reduced β-oxidation, in addition to a shift from fast to slow fibers. In conclusion, PPARβ is not required for maintaining skeletal muscle metabolic activity and does not compensate the lack of PPARα in PPARα null mice

  6. Lack of Parental Rules for Cell Phone Use among Low Income Mexican Descendent Adolescents

    Directory of Open Access Journals (Sweden)

    Christine Bracamonte Wiggs

    2013-12-01

    Full Text Available Youth have access to and utilize various types of technology at a growing rate. Cell phones are a portable way for adolescents to remain in constant contact with friends, parents, and others. While White youth are more likely to have a cell phone compared to Latino youth, the trends for cell phone use are similar among all teens with text messaging serving as the most popular means of communication. Despite their high volume of communication with others via cell phones, adolescents are likely to have little or no adult supervision while using technology. With a lack of parental supervision or awareness regarding youth technology use, adolescents may be especially vulnerable to cyberbullying and other negative health impacts. The current study investigates cell phone and texting use among a community sample of Latino adolescents and examines how parental rules regarding cell phone use influences adolescents’ cell phone and texting behaviors.

  7. Lack of anomalous diffusion in linear translationally-invariant systems determined by only one initial condition

    International Nuclear Information System (INIS)

    Khorrami, Mohammad; Shariati, Ahmad; Aghamohammadi, Amir; Fatollahi, Amir H.

    2012-01-01

    It is shown that as far as the linear diffusion equation meets both time- and space-translational invariance, the time dependence of a moment of degree α is a polynomial of degree at most equal to α, while all connected moments are at most linear functions of time. As a special case, the variance is an at most linear function of time. -- Highlights: ► The sufficient conditions for having the non-anomalous diffusion are given. ► Conditions are linearity, space-time translation invariance, solution uniqueness. ► Some versions of the fractional derivatives lack the translational invariance. ► It is shown the encoded inhomogeneity in derivatives causes anomalous behavior.

  8. Lack of anomalous diffusion in linear translationally-invariant systems determined by only one initial condition

    Energy Technology Data Exchange (ETDEWEB)

    Khorrami, Mohammad, E-mail: mamwad@mailaps.org [Department of Physics, Alzahra University, Tehran 19938-93973 (Iran, Islamic Republic of); Shariati, Ahmad, E-mail: shariati@mailaps.org [Department of Physics, Alzahra University, Tehran 19938-93973 (Iran, Islamic Republic of); Aghamohammadi, Amir, E-mail: mohamadi@alzahra.ac.ir [Department of Physics, Alzahra University, Tehran 19938-93973 (Iran, Islamic Republic of); Fatollahi, Amir H., E-mail: ahfatol@gmail.com [Department of Physics, Alzahra University, Tehran 19938-93973 (Iran, Islamic Republic of)

    2012-01-16

    It is shown that as far as the linear diffusion equation meets both time- and space-translational invariance, the time dependence of a moment of degree α is a polynomial of degree at most equal to α, while all connected moments are at most linear functions of time. As a special case, the variance is an at most linear function of time. -- Highlights: ► The sufficient conditions for having the non-anomalous diffusion are given. ► Conditions are linearity, space-time translation invariance, solution uniqueness. ► Some versions of the fractional derivatives lack the translational invariance. ► It is shown the encoded inhomogeneity in derivatives causes anomalous behavior.

  9. Lack of consensus in the diagnosis and treatment for ocular tuberculosis among uveitis specialists.

    Science.gov (United States)

    Lou, Susan M; Larkin, Kelly L; Winthrop, Kevin; Rosenbaum, James T

    2015-02-01

    To assess the approach of specialists to ocular tuberculosis (TB). The American Uveitis Society (AUS) Listserv was surveyed using two clinical cases and general questions. Of 196 members, 87 responded (44.4%), of whom 64 were affiliated with practices in North America, while 23 were outside of North America. The survey provided normative data on how physicians evaluate patients with uveitis as well as opinions about ocular TB. Responses varied widely on such issues as (1) the pretest probability that a patient with granulomatous panuveitis had TB uveitis (range 1-75%) or that a patient with a risk factor for TB had ocular TB (range 0-90%); (2) the optimal duration of anti-TB therapy; and (3) whether therapy should be discontinued after 2 months in nonresponders. Consensus is lacking among uveitis specialists for the diagnosis or management of ocular TB.

  10. Doing many things at a time: Lack of power decreases the ability to multitask.

    Science.gov (United States)

    Cai, Ran Alice; Guinote, Ana

    2017-09-01

    Three studies investigated the effects of power on the ability to pursue multiple, concomitant goals, also known as multitasking. It was predicted that powerless participants will show lower multitasking ability than control and powerful participants. Study 1 focused on self-reported ability to multitask in a sample of executives and subordinate employees. Studies 2 and 3 investigated the ability to dual-task and to switch between tasks, respectively, using dual-task and task-switching paradigms. Across the studies, powerless individuals were less able to effectively multitask compared with control and powerful participants, suggesting that the detrimental effects of lack of power extend beyond single-task environments, shown in past research, into multitasking environments. Underlying mechanisms are discussed. © 2017 The British Psychological Society.

  11. Domestic Labor and the Lack of Social Security Protection in Brazil: Questions for Analysis

    Directory of Open Access Journals (Sweden)

    Rita de Lourdes de Lima

    2010-01-01

    Full Text Available This article analyzes domestic labor in Brazil, considering gender, the sexual division of labor and social security, which are influenced by the social transformations of the late 20th century. To do so, a dialog was established with various theoreticians including: Boschetti, Hirata, Kergoat, Nogueira and Saffioti.A historical review of the sexual division of labor in capitalist society is conducted, utilizing the concept of gender and examining inequality between men and women in the work force. Then, looking at social security in Brazil, the  implications of counter reforms to the system for female labor and particularly for domestic work are analyzed, identifying the real lack of social protection suffered by the entire working class.

  12. Lack of Knowledge Sharing Amongst Institutions in Denmark Responsible for Vulnerable Groups

    DEFF Research Database (Denmark)

    Bojsen, Ann Kristina Mikkelsen

    they share their knowledge about risk and policy management. In order to protect vulnerable groups such as children, disabled, sick and elderly people, we need to learn more about the general risk understanding and sharing of such according to region, responsibility, common events and hazards....... This information is needed to protect against future unintentional and intentional hazards and compare those with the institutional responsibilities. Risk understanding and knowledge sharing among professionals with responsibility for vulnerable groups can be a crucial tool for handling everyday threats as well......Lack of Knowledge Sharing Amongst Institutions in Denmark Responsible for Vulnerable Groups Ann Bojsen, Senior Lecturer Emergency and Risk Management Department, Metropolitan University College, Copenhagen, Denmark Even though understanding risk and how it is enacted is regarded as a crucial step...

  13. A CLOSER LOOK AT (LACK OF OBVIATION PHENOMENA IN ROMANIAN SUBJUNCTIVE COMPLEMENTS

    Directory of Open Access Journals (Sweden)

    Maria Aurelia Cotfas

    2011-05-01

    Full Text Available The paper looks at Romanian subjunctive complements selected by volitional verbs and considers the interpretation of their null subjects and why – unlike the case of other Romance languages – these can co-refer with a main clause antecedent (what has been called “lack of obviation” in the literature. What we want to show (against claims made by Roussou 2001 and Landau 2004 is that null subject ca-subjunctives in Romanian do not trigger obviation (disjoint subjects and that obviation effects in such contexts can appear not because of ca, but in cases where the subject of the subjunctive complement is an overt 3rd person pronoun whose phi-features match those of the main clause subject. Supporting evidence for the different interpretation of null vs. overt pronouns comes from Reinhart’s (1999, 2000 variable binding vs. co-valuation (Rule I and Ariel’s (1991, 1994 Accessibility Theory.

  14. A closer look at (lack of obviation phenomena in Romanian subjunctive complements

    Directory of Open Access Journals (Sweden)

    Maria Aurelia Cotfas

    2011-01-01

    Full Text Available The paper looks at Romanian subjunctive complements selected by volitional verbs and considers the interpretation of their null subjects and why – unlike the case of other Romance languages – these can co-refer with a main clause antecedent (what has been called “lack of obviation” in the literature. What we want to show (against claims made by Roussou 2001 and Landau 2004 is that null subject ca-subjunctives in Romanian do not trigger obviation (disjoint subjects and that obviation effects in such contexts can appear not because of ca, but in cases where the subject of the subjunctive complement is an overt 3rd person pronoun whose phi-features match those of the main clause subject. Supporting evidence for the different interpretation of null vs. overt pronouns comes from Reinhart’s (1999, 2000 variable binding vs. co-valuation (Rule I and Ariel’s (1991, 1994 Accessibility Theory.

  15. Lack of circadian variation in the activity of the autonomic nervous system after major abdominal operations

    DEFF Research Database (Denmark)

    Gögenur, Ismail; Rosenberg-Adamsen, Susan; Lie, Claus

    2002-01-01

    OBJECTIVE: Most sudden postoperative deaths occur during the night and we conjectured that this was associated with circadian variations in the autonomic nervous tone, reflected in heart rate variability. DESIGN: Prospective clinical study. SETTINGS: University hospital, Denmark. SUBJECTS: 44...... OUTCOME MEASURES: Heart rate and heart rate variability. RESULTS: Circadian variation calculated from the SDNN (p = 0.43) the pNN50 (p = 0.11), the RMSSD (p = 0.47), and mean NN:SDNN ratio (p = 0.13) was absent postoperatively. Circadian variation in the heart rate was present but was set on a higher...... level compared with reference values. CONCLUSION: After major abdominal operations there was a lack of circadian variation in the autonomic nervous tone....

  16. An engineered split M.HhaI-zinc finger fusion lacks the intended methyltransferase specificity

    International Nuclear Information System (INIS)

    Meister, Glenna E.; Chandrasegaran, Srinivasan; Ostermeier, Marc

    2008-01-01

    The ability to site-specifically methylate DNA in vivo would have wide applicability to the study of basic biomedical problems as well as enable studies on the potential of site-specific DNA methylation as a therapeutic strategy for the treatment of diseases. Natural DNA methyltransferases lack the specificity required for these applications. Nomura and Barbas [W. Nomura, C.F. Barbas 3rd, In vivo site-specific DNA methylation with a designed sequence-enabled DNA methylase, J. Am. Chem. Soc. 129 (2007) 8676-8677] have reported that an engineered DNA methyltransferase comprised of fragments of M.HhaI methyltransferase and zinc finger proteins has very high specificity for the chosen target site. Our analysis of this engineered enzyme shows that the fusion protein methylates target and non-target sites with similar efficiency

  17. Lack of reliable alternatives means France faces challenges finding a replacement for nuclear

    Energy Technology Data Exchange (ETDEWEB)

    Dalton, David [NucNet, Brussels (Belgium)

    2017-03-15

    The lack of alternative low-carbon energy sources that are as reliable as nuclear means France's ''ambitious'' plans to reduce its share of nuclear from 78 % in 2015 to 50 % by 2025 might not be achievable, the International Energy Agency (IEA) said in its January 2017 report. The Paris-based agency said France - which has the world's highest share of nuclear in its electricity mix - must assess possible changes in energy demand and supply and to guarantee ''continuous security of electricity supply'' as it pushes ahead with its plans for an ''energy transition'' up to 2050. The Energy Transition for Green Growth Act (Loi relative a la transition energetique pour la croissance verte, LTECV) was the result of consultations that ran from January to July 2013.

  18. Leishmania promastigotes lack phosphatidylserine but bind annexin V upon permeabilization or miltefosine treatment.

    Directory of Open Access Journals (Sweden)

    Adrien Weingärtner

    Full Text Available The protozoan parasite Leishmania is an intracellular pathogen infecting and replicating inside vertebrate host macrophages. A recent model suggests that promastigote and amastigote forms of the parasite mimic mammalian apoptotic cells by exposing phosphatidylserine (PS at the cell surface to trigger their phagocytic uptake into host macrophages. PS presentation at the cell surface is typically analyzed using fluorescence-labeled annexin V. Here we show that Leishmania promastigotes can be stained by fluorescence-labeled annexin V upon permeabilization or miltefosine treatment. However, combined lipid analysis by thin-layer chromatography, mass spectrometry and (31P nuclear magnetic resonance (NMR spectroscopy revealed that Leishmania promastigotes lack any detectable amount of PS. Instead, we identified several other phospholipid classes such phosphatidic acid, phosphatidylethanolamine; phosphatidylglycerol and phosphatidylinositol as candidate lipids enabling annexin V staining.

  19. The causes for lack of interest to blood donation in eligible individuals, mashhad, northeastern iran.

    Science.gov (United States)

    Shakeri, M T; Vafaee, A; Esmaeily, H; Shafiei, N; Bazargani, R; Khayamy, Me

    2012-01-01

    Donor recruitment and retention are significant problems in blood collection agencies around the world. The Aim of this study was to determine the causes of lack of interest to blood donation in eligible individu-als in Mashhad, Northeast of Iran. This was a descriptive study. Cases were 1130 non-donor individuals. Participants were selected from eligible individuals in different regions of Mashhad. In this study, surveys included information about age groups, gender, residence area, marriage, education; living situation and job as background variables. Less than 30% of the cases had enough knowledge about blood donation. There was a significant rela-tionship between location, age, education, occupation and social status with knowledge of blood donation, but there was not a correlation between gender and marital status. There are some factors which affect the decision for blood donation. There is a need to change the negative attitude by increasing the knowledge considering the individual and the social status.

  20. Characterization of a bacteriophage T4 mutant lacking DNA-dependent ATPase

    International Nuclear Information System (INIS)

    Behme, M.T.; Ebisuzaki, K.

    1975-01-01

    A DNA-dependent ATPase has previously been purified from bacteriophage T4-infected Escherichia coli. A mutant phage strain lacking this enzyme has been isolated and characterized. Although the mutant strain produced no detectable DNA-dependent ATPase, growth properties were not affected. Burst sizes were similar for the mutant phage and T4D in polAl, recB, recC, uvrA, uvrB, uvrC, and various DNA-negative E. coli. UV sensitivity and genetic recombination were normal in a variety of E. coli hosts. Mapping data indicate that the genetic locus controlling the mutant occurs near gene 56. The nonessential nature of this gene is discussed

  1. Lack of Population Structure in Coriander Populations Based on SDS (Seed Storage Protein Page Analysis

    Directory of Open Access Journals (Sweden)

    Gülsüm Yaldiz

    2016-08-01

    Full Text Available Genetic variation is prerequisite for plant breeding. Nothing information existed in the literature for available diversity of Coriander accession in Turkey. Plant breeding activities are negligible in Turkey. So in order to start effective plant breeding program in Turkey, information on the available genetic diversity is viable. Therefore we planned to study the genetic variation and population structure of 29 Coriander accessions by seed storage protein (SDS. SDS analysis elaborated the lack of population structure and genetic bottleneck in the Coriander accessions in Turkey. Based on the results of this study, it was clear that sampling strategy was not appropriate and plant introduction should be made from different sources and diverse genotypes should be used as parents to initialize the effective Turkish Coriander breeding program.

  2. The diageotropica mutant of tomato lacks high specific activity auxin sites

    International Nuclear Information System (INIS)

    Hicks, G.R.; Lomax, T.L.; Rayle, D.L.

    1989-01-01

    Tomato (Lycopersicum esculentum, Mill) plants homozygous for the single gene diageotropica (dgt) mutation have reduced shoot growth, abnormal vascular tissue, altered leaf morphology, and lack of lateral root branching. These and other morphological and physiological abnormalities suggest that dgt plants are unable to respond to the plant growth hormone auxin (indole-3-acetic acid, IAA). The photoaffinity auxin analogue 3 H-5N 3 -IAA specifically labels a polypeptide doublet of 40 ad 42 kD in membrane preparations from stems of the parental variety VFN8, but not from stems of dgt. In elongation tests, excised dgt roots respond in the same manner to IAA an VFN8 roots. These data suggest that the two polypeptides are part of a physiologically important auxin receptor system which is altered in a tissue-specific manner in the mutant

  3. Lack of cyclophilin B in osteogenesis imperfecta with normal collagen folding.

    Science.gov (United States)

    Barnes, Aileen M; Carter, Erin M; Cabral, Wayne A; Weis, MaryAnn; Chang, Weizhong; Makareeva, Elena; Leikin, Sergey; Rotimi, Charles N; Eyre, David R; Raggio, Cathleen L; Marini, Joan C

    2010-02-11

    Osteogenesis imperfecta is a heritable disorder that causes bone fragility. Mutations in type I collagen result in autosomal dominant osteogenesis imperfecta, whereas mutations in either of two components of the collagen prolyl 3-hydroxylation complex (cartilage-associated protein [CRTAP] and prolyl 3-hydroxylase 1 [P3H1]) cause autosomal recessive osteogenesis imperfecta with rhizomelia (shortening of proximal segments of upper and lower limbs) and delayed collagen folding. We identified two siblings who had recessive osteogenesis imperfecta without rhizomelia. They had a homozygous start-codon mutation in the peptidyl-prolyl isomerase B gene (PPIB), which results in a lack of cyclophilin B (CyPB), the third component of the complex. The proband's collagen had normal collagen folding and normal prolyl 3-hydroxylation, suggesting that CyPB is not the exclusive peptidyl-prolyl cis-trans isomerase that catalyzes the rate-limiting step in collagen folding, as is currently thought. 2010 Massachusetts Medical Society

  4. Salt stress causes cell wall damage in yeast cells lacking mitochondrial DNA.

    Science.gov (United States)

    Gao, Qiuqiang; Liou, Liang-Chun; Ren, Qun; Bao, Xiaoming; Zhang, Zhaojie

    2014-03-03

    The yeast cell wall plays an important role in maintaining cell morphology, cell integrity and response to environmental stresses. Here, we report that salt stress causes cell wall damage in yeast cells lacking mitochondrial DNA (ρ 0 ). Upon salt treatment, the cell wall is thickened, broken and becomes more sensitive to the cell wall-perturbing agent sodium dodecyl sulfate (SDS). Also, SCW11 mRNA levels are elevated in ρ 0 cells. Deletion of SCW11 significantly decreases the sensitivity of ρ 0 cells to SDS after salt treatment, while overexpression of SCW11 results in higher sensitivity. In addition, salt stress in ρ 0 cells induces high levels of reactive oxygen species (ROS), which further damages the cell wall, causing cells to become more sensitive towards the cell wall-perturbing agent.

  5. A Spline-Based Lack-Of-Fit Test for Independent Variable Effect in Poisson Regression.

    Science.gov (United States)

    Li, Chin-Shang; Tu, Wanzhu

    2007-05-01

    In regression analysis of count data, independent variables are often modeled by their linear effects under the assumption of log-linearity. In reality, the validity of such an assumption is rarely tested, and its use is at times unjustifiable. A lack-of-fit test is proposed for the adequacy of a postulated functional form of an independent variable within the framework of semiparametric Poisson regression models based on penalized splines. It offers added flexibility in accommodating the potentially non-loglinear effect of the independent variable. A likelihood ratio test is constructed for the adequacy of the postulated parametric form, for example log-linearity, of the independent variable effect. Simulations indicate that the proposed model performs well, and misspecified parametric model has much reduced power. An example is given.

  6. Telemedicine: The legal framework (or the lack of it) in Europe.

    Science.gov (United States)

    Raposo, Vera Lúcia

    2016-01-01

    In the framework of European law telemedicine is, simultaneously, a health service and an information service, therefore, both regulations apply. In what concerns healthcare and the practice of medicine there are no uniform regulations at the European level. Concerning health services the most relevant achievement to regulate this domain is Directive 2011/24/EU. In what regards information and telecommunications we must have in consideration Directive 95/46/EU, Directive 2000/31/EC and Directive 2002/58/EC. However, many issues still lack uniform regulation, mainly the domain of medical liability and of medical leges artis. Probably such standardization will never take place, since the European Union does not have, until now, a common set of norms regarding tort and criminal liability, much less specific legal norms on medical liability. These gaps may jeopardize a truly European internal market in health services and hamper the development of telemedicine in the European zone.

  7. PROPOSED CARDIAC STEM CELLS DERIVED FROM “CARDIOSPHERES” LACK CARDIOMYOGENIC POTENTIAL

    DEFF Research Database (Denmark)

    Andersen, Ditte Caroline

       Recent studies have reported that clinical relevant numbers of cardiac stem cells (CSCs) with cardiomyogenic potential can be obtained from small heart tissue biopsies, by an intrinsic ability of CSCs to form beating cardiospheres (CSs) during ex vivo culture. Such data have provided optimism...... that injuried heart tissue may be repaired by stem cell therapy using autologous CS derived cells, and pre-clinical studies have already been described in literature.    Herein, we established CSs from neonatal rats, and by immunofluorescence, qRT-PCR, and microscopic examination we demonstrated...... to form CSs by themselves. Phenotypically, CS cells largely resembled fibroblasts, and they lacked cardiomyogenic as well as endothelial differentiation potential.    Our data imply that at least the murine cardiosphere model seems unsuitable for enrichment of cardiac stem cells with cardiomyogenic...

  8. Spin-charge conversion in disordered two-dimensional electron gases lacking inversion symmetry

    Science.gov (United States)

    Huang, Chunli; Milletarı, Mirco; Cazalilla, Miguel A.

    2017-11-01

    We study the spin-charge conversion mechanisms in a two-dimensional gas of electrons moving in a smooth disorder potential by accounting for both Rashba-type and Mott's skew scattering contributions. We find that the quantum interference effects between spin-flip and skew scattering give rise to anisotropic spin precession scattering (ASP), a direct spin-charge conversion mechanism that was discovered in an earlier study of graphene decorated with adatoms [Huang et al., Phys. Rev. B 94, 085414 (2016), 10.1103/PhysRevB.94.085414]. Our findings suggest that, together with other spin-charge conversion mechanisms such as the inverse galvanic effect, ASP is a fairly universal phenomenon that should be present in disordered two-dimensional systems lacking inversion symmetry.

  9. Mechanisms of collective cell movement lacking a leading or free front edge in vivo.

    Science.gov (United States)

    Uechi, Hiroyuki; Kuranaga, Erina

    2017-08-01

    Collective cell movement is one of the strategies for achieving the complex shapes of tissues and organs. In this process, multiple cells within a group held together by cell-cell adhesion acquire mobility and move together in the same direction. In some well-studied models of collective cell movement, the mobility depends strongly on traction generated at the leading edge by cells located at the front. However, recent advances in live-imaging techniques have led to the discovery of other types of collective cell movement lacking a leading edge or even a free edge at the front, in a diverse array of morphological events, including tubule elongation, epithelial sheet extension, and tissue rotation. We herein review some of the developmental events that are organized by collective cell movement and attempt to elucidate the underlying cellular and molecular mechanisms, which include membrane protrusions, guidance cues, cell intercalation, and planer cell polarity, or chirality pathways.

  10. Lack of efficacy during the switch from brand to generic allopurinol.

    Science.gov (United States)

    De Vuono, Antonio; Scicchitano, Francesca; Palleria, Caterina; Russo, Emilio; De Sarro, Giovambattista; Gallelli, Luca

    2013-07-01

    We report for the first time the lack of therapeutic effects after the switch from a brand formulation of allopurinol to a generic one. A 56-year-old man, with a 5 years history of well-treated gout arthropathy with allopurinol (Zyloric(®) 300 mg/die), developed acute gout arthropathy after the switch from the brand formulation of allopurinol to a generic one. Clinical evaluation and laboratory findings confirmed the diagnosis of acute gout arthropathy. Generic formulation of the drug was dismissed and Zyloric(®) was administered with an improvement of both clinical symptoms and laboratory findings. In conclusion, even if generic formulations are considered to have the same effects in comparison to the brand one, more data are necessaries in order to well define their effectiveness and rationale use. Copyright © 2013 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  11. Lack of individualized perspective: a qualitative study of diabetes care for immigrants in Sweden.

    Science.gov (United States)

    Brämberg, Elisabeth Björk; Dahlborg-Lyckhage, Elisabeth; Määttä, Sylvia

    2012-06-01

    This study describes the care provided by a diabetes nurse specialist, and the care needs expressed by people with type 2 diabetes mellitus and an immigrant background. Clinical encounters between a diabetes nurse specialist and 10 people diagnosed with type 2 diabetes mellitus were observed and analyzed by means of qualitative content analysis. One theme, "the diabetes nurse specialist as the conductor of the visit", and four categories emerged from the findings, illustrating the power imbalance between the patients and the diabetes nurse specialist, as well as the lack of an individual perspective. Shifting from a medical perspective to one of openness towards the people's experiences provides a possibility for caregivers to empower patients suffering from type 2 diabetes mellitus. The medical perspective seemed to steer the visit towards curative activities. Thus, technique-centered care should be developed by including individualized care. © 2012 Blackwell Publishing Asia Pty Ltd.

  12. Human Estimation of Slope, Distance, and Height of Terrain in Simulated Lunar Conditions

    National Research Council Canada - National Science Library

    Oravetz, Christopher

    2009-01-01

    .... These unique lunar conditions are expected to affect human perception: the lack of an atmosphere, the non-Lambertian regolith reflectance properties, the lack of familiar objects, and the physiological effects of reduced gravity...

  13. The lack of autophagy triggers precocious activation of Notch signaling during Drosophila oogenesis

    Directory of Open Access Journals (Sweden)

    Barth Julia MI

    2012-12-01

    Full Text Available Abstract Background The proper balance of autophagy, a lysosome-mediated degradation process, is indispensable for oogenesis in Drosophila. We recently demonstrated that egg development depends on autophagy in the somatic follicle cells (FC, but not in the germline cells (GCs. However, the lack of autophagy only affects oogenesis when FCs are autophagy-deficient but GCs are wild type, indicating that a dysfunctional signaling between soma and germline may be responsible for the oogenesis defects. Thus, autophagy could play an essential role in modulating signal transduction pathways during egg development. Results Here, we provide further evidence for the necessity of autophagy during oogenesis and demonstrate that autophagy is especially required in subsets of FCs. Generation of autophagy-deficient FCs leads to a wide range of phenotypes that are similar to mutants with defects in the classical cell-cell signaling pathways in the ovary. Interestingly, we observe that loss of autophagy leads to a precocious activation of the Notch pathway in the FCs as monitored by the expression of Cut and Hindsight, two downstream effectors of Notch signaling. Conclusion Our findings point to an unexpected function for autophagy in the modulation of the Notch signaling pathway during Drosophila oogenesis and suggest a function for autophagy in proper receptor activation. Egg development is affected by an imbalance of autophagy between signal sending (germline and signal receiving cell (FC, thus the lack of autophagy in the germline is likely to decrease the amount of active ligand and accordingly compensates for increased signaling in autophagy-defective follicle cells.

  14. Myocardial mitochondrial and contractile function are preserved in mice lacking adiponectin.

    Directory of Open Access Journals (Sweden)

    Martin Braun

    Full Text Available Adiponectin deficiency leads to increased myocardial infarct size following ischemia reperfusion and to exaggerated cardiac hypertrophy following pressure overload, entities that are causally linked to mitochondrial dysfunction. In skeletal muscle, lack of adiponectin results in impaired mitochondrial function. Thus, it was our objective to investigate whether adiponectin deficiency impairs mitochondrial energetics in the heart. At 8 weeks of age, heart weight-to-body weight ratios were not different between adiponectin knockout (ADQ-/- mice and wildtypes (WT. In isolated working hearts, cardiac output, aortic developed pressure and cardiac power were preserved in ADQ-/- mice. Rates of fatty acid oxidation, glucose oxidation and glycolysis were unchanged between groups. While myocardial oxygen consumption was slightly reduced (-24% in ADQ-/- mice in isolated working hearts, rates of maximal ADP-stimulated mitochondrial oxygen consumption and ATP synthesis in saponin-permeabilized cardiac fibers were preserved in ADQ-/- mice with glutamate, pyruvate or palmitoyl-carnitine as a substrate. In addition, enzymatic activity of respiratory complexes I and II was unchanged between groups. Phosphorylation of AMP-activated protein kinase and SIRT1 activity were not decreased, expression and acetylation of PGC-1α were unchanged, and mitochondrial content of OXPHOS subunits was not decreased in ADQ-/- mice. Finally, increasing energy demands due to prolonged subcutaneous infusion of isoproterenol did not differentially affect cardiac contractility or mitochondrial function in ADQ-/- mice compared to WT. Thus, mitochondrial and contractile function are preserved in hearts of mice lacking adiponectin, suggesting that adiponectin may be expendable in the regulation of mitochondrial energetics and contractile function in the heart under non-pathological conditions.

  15. Increased consumption of ethanol and sugar water in mice lacking the dopamine D2 long receptor.

    Science.gov (United States)

    Bulwa, Zachary B; Sharlin, Jordan A; Clark, Peter J; Bhattacharya, Tushar K; Kilby, Chessa N; Wang, Yanyan; Rhodes, Justin S

    2011-11-01

    Individual differences in dopamine D2 receptor (D2R) expression in the brain are thought to influence motivation and reinforcement for ethanol and other rewards. D2R exists in two isoforms, D2 long (D2LR) and D2 short (D2SR), produced by alternative splicing of the same gene. The relative contributions of D2LR versus D2SR to ethanol and sugar water drinking are not known. Genetic engineering was used to produce a line of knockout (KO) mice that lack D2LR and consequently have increased expression of D2SR. KO and wild-type (WT) mice of both sexes were tested for intake of 20% ethanol, 10% sugar water and plain tap water using established drinking-in-the-dark procedures. Mice were also tested for effects of the D2 antagonist eticlopride on intake of ethanol to determine whether KO responses were caused by lack of D2LR or overrepresentation of D2SR. Locomotor activity on running wheels and in cages without wheels was also measured for comparison. D2L KO mice drank significantly more ethanol than WT in both sexes. KO mice drank more sugar water than WT in females but not in males. Eticlopride dose dependently decreased ethanol intake in all groups except male KO. KO mice were less physically active than WT in cages with or without running wheels. Results suggest that overrepresentation of D2SR contributes to increased intake of ethanol in the KO mice. Decreasing wheel running and general levels of physical activity in the KO mice rules out the possibility that higher intake results from higher motor activity. Results extend the literature implicating altered expression of D2R in risk for addiction by delineating the contribution of individual D2R isoforms. These findings suggest that D2LR and D2SR play differential roles in consumption of alcohol and sugar rewards. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Lack of recruitment in Lavandula stoechas subsp. pedunculata: a case of safe-site limitation

    Science.gov (United States)

    Sánchez, Ana M.; Peco, Begoña

    2007-01-01

    Lavandula stoechas subsp. pedunculata regeneration depends exclusively on the establishment of new individuals. Seed availability and seedling emergence and survival are therefore critical life stages and processes for species regeneration. In this study, seedling emergence and survival was monitored for two years in the scrub, both in clearings and adjacent to adult plants, and the surrounding perennial grassland, at 1, 3 and 5 m from the scrub. Soil seed bank spatial distribution was also studied for one year in the same two habitats, using the same sampling design. Soil seed availability in the scrub is high regardless of the distance from the adult individuals. On the contrary, the adjacent grassland shows a drastic fall in seed density, and almost no seedlings were observed there. In the scrub, seedling density was negatively related to distance from the three nearest adult plants in the clearings, and positively related to adult plant size beneath the adult Lavandula plants. There was also a negative relationship between seedling density and the percentage of bare soil. Only one seedling survived the first drought period, with no detection of effects of either position with respect to adult individuals or seedling density. We hypothesized that the study populations suffer a lack of appropriate safe sites within the scrubland while in the adjacent perennial grassland, observed low seed availability was added to safe-site limitation. That results in a lack of successful seedling establishments and a poor expansion potential of Lavandula scrublands, whose edges remain static in the short and medium term. As found in other Mediterranean scrubland, recruitment may only occur in years with particularly favourable weather, under disturbance regimes that increase seedling survival probability or when external dispersal agents increased seed availability in adequate places for Lavandula establishment.

  17. [Quality management in emergency departments: Lack of uniform standards for fact-based controlling].

    Science.gov (United States)

    Ries, M; Christ, M

    2015-11-01

    The general high occupancy of emergency departments during the winter months of 2014/2015 outlined deficits in health politics. Whether on the regional, province, or federal level, verifiable and accepted figures to enable in depth analysis and fact-based controlling of emergency care systems are lacking. As the first step, reasons for the current situation are outlined in order to developed concrete recommendations for individual hospitals. This work is based on a selective literature search with focus on quality management, ratio driven management, and process management within emergency departments as well as personal experience with implementation of a key ratio system in a German maximum care hospital. The insufficient integration of emergencies into the DRG systematic, the role as gatekeeper between inpatient and outpatient care sector, the decentralized organization of emergency departments in many hospitals, and the inconsistent representation within the medical societies can be mentioned as reasons for the lack of key ratio systems. In addition to the important role within treatment procedures, emergency departments also have an immense economic importance. Consequently, the management of individual hospitals should promote implementation of key ratio systems to enable controlling of emergency care processes. Thereby the perspectives finance, employees, processes as well as partners and patients should be equally considered. Within the process perspective, milestones could be used to enable detailed controlling of treatment procedures. An implementation of key ratio systems without IT support is not feasible; thus, existing digital data should be used and future data analysis should already be considered during implementation of new IT systems.

  18. Regulation of ENaC in mice lacking renal insulin receptors in the collecting duct

    Science.gov (United States)

    Pavlov, Tengis S.; Ilatovskaya, Daria V.; Levchenko, Vladislav; Li, Lijun; Ecelbarger, Carolyn M.; Staruschenko, Alexander

    2013-01-01

    The epithelial sodium channel (ENaC) is one of the central effectors involved in regulation of salt and water homeostasis in the kidney. To study mechanisms of ENaC regulation, we generated knockout mice lacking the insulin receptor (InsR KO) specifically in the collecting duct principal cells. Single-channel analysis in freshly isolated split-open tubules demonstrated that the InsR-KO mice have significantly lower ENaC activity compared to their wild-type (C57BL/6J) littermates when animals were fed either normal or sodium-deficient diets. Immunohistochemical and Western blot assays demonstrated no significant changes in expression of ENaC subunits in InsR-KO mice compared to wild-type littermates. Insulin treatment caused greater ENaC activity in split-open tubules isolated from wild-type mice but did not have this effect in the InsR-KO mice. Thus, these results suggest that insulin increases ENaC activity via its own receptor affecting the channel open probability. To further determine the mechanism of the action of insulin on ENaC, we used mouse mpkCCDc14 principal cells. Insulin significantly augmented amiloride-sensitive transepithelial flux in these cells. Pretreatment of the mpkCCDc14 cells with phosphatidylinositol 3-kinase (LY294002; 10 μM) or mTOR (PP242; 100 nM) inhibitors precluded this effect. This study provides new information about the importance of insulin receptors expressed in collecting duct principal cells for ENaC activity.—Pavlov, T. S., Ilatovskaya, D. V., Levchenko, V., Li, L., Ecelbarger, C. M., Staruschenko, A. Regulation of ENaC in mice lacking renal insulin receptors in the collecting duct. PMID:23558339

  19. A Survey of Women's Awareness of and Reasons for Lack of Postfracture Osteoporotic Care.

    Science.gov (United States)

    Boudreau, Denise M; Yu, Onchee; Balasubramanian, Akhila; Wirtz, Heidi; Grauer, Andreas; Crittenden, Daria B; Scholes, Delia

    2017-08-01

    To identify women's beliefs and other factors associated with lack of osteoporosis (OP) pharmacotherapy (OP-RX) during the 6 months after a fragility fracture, including the woman's perspective on fracture risk, OP, and treatment. Cross-sectional. Group Health Cooperative, a mixed-model delivery system. Female Group Health Cooperative enrollees aged 55 and older with an OP-related fracture according to diagnostic and procedure codes from January 1, 2013, to March 30, 2014 (N = 985). OP-RX and participant characteristics were ascertained from electronic health records including medications dispensed. A mailed survey was used to obtain data on health behaviors; OP-related history; concern about, knowledge of, and perceived risk of future fracture; beliefs about OP-RX; sources of information on OP; postfracture discussions with providers; and provider recommendations. The response rate was 73%. Of 634 eligible respondents, 84% did not undergo OP-RX during the 6 months after fracture. Fewer than 20% of women thought that OP caused their fracture, 52% did not think they were at risk of future fracture, and 75% did not think or know whether OP-RX reduces risk of fracture. Knowledge about OP and the benefits of treatment was higher in the 16% of women who underwent OP-RX after their fracture. Women reported low levels of engagement with their healthcare providers regarding OP and fracture risk management. These findings suggest low awareness about OP and its contribution to fracture risk, lack of understanding about the benefits of pharmacotherapy, and limited discussion about OP with primary care physicians. Information about individual's beliefs and knowledge gaps can help design targeted patient and provider education to improve treatment rates. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

  20. Lack of liver glycogen causes hepatic insulin resistance and steatosis in mice.

    Science.gov (United States)

    Irimia, Jose M; Meyer, Catalina M; Segvich, Dyann M; Surendran, Sneha; DePaoli-Roach, Anna A; Morral, Nuria; Roach, Peter J

    2017-06-23

    Disruption of the Gys2 gene encoding the liver isoform of glycogen synthase generates a mouse strain (LGSKO) that almost completely lacks hepatic glycogen, has impaired glucose disposal, and is pre-disposed to entering the fasted state. This study investigated how the lack of liver glycogen increases fat accumulation and the development of liver insulin resistance. Insulin signaling in LGSKO mice was reduced in liver, but not muscle, suggesting an organ-specific defect. Phosphorylation of components of the hepatic insulin-signaling pathway, namely IRS1, Akt, and GSK3, was decreased in LGSKO mice. Moreover, insulin stimulation of their phosphorylation was significantly suppressed, both temporally and in an insulin dose response. Phosphorylation of the insulin-regulated transcription factor FoxO1 was somewhat reduced and insulin treatment did not elicit normal translocation of FoxO1 out of the nucleus. Fat overaccumulated in LGSKO livers, showing an aberrant distribution in the acinus, an increase not explained by a reduction in hepatic triglyceride export. Rather, when administered orally to fasted mice, glucose was directed toward hepatic lipogenesis as judged by the activity, protein levels, and expression of several fatty acid synthesis genes, namely, acetyl-CoA carboxylase, fatty acid synthase, SREBP1c, chREBP, glucokinase, and pyruvate kinase. Furthermore, using cultured primary hepatocytes, we found that lipogenesis was increased by 40% in LGSKO cells compared with controls. Of note, the hepatic insulin resistance was not associated with increased levels of pro-inflammatory markers. Our results suggest that loss of liver glycogen synthesis diverts glucose toward fat synthesis, correlating with impaired hepatic insulin signaling and glucose disposal. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Generation of a non-transmissive Borna disease virus vector lacking both matrix and glycoprotein genes.

    Science.gov (United States)

    Fujino, Kan; Yamamoto, Yusuke; Daito, Takuji; Makino, Akiko; Honda, Tomoyuki; Tomonaga, Keizo

    2017-09-01

    Borna disease virus (BoDV), a prototype of mammalian bornavirus, is a non-segmented, negative strand RNA virus that often causes severe neurological disorders in infected animals, including horses and sheep. Unique among animal RNA viruses, BoDV transcribes and replicates non-cytopathically in the cell nucleus, leading to establishment of long-lasting persistent infection. This striking feature of BoDV indicates its potential as an RNA virus vector system. It has previously been demonstrated by our team that recombinant BoDV (rBoDV) lacking an envelope glycoprotein (G) gene develops persistent infections in transduced cells without loss of the viral genome. In this study, a novel non-transmissive rBoDV, rBoDV ΔMG, which lacks both matrix (M) and G genes in the genome, is reported. rBoDV-ΔMG expressing green fluorescence protein (GFP), rBoDV ΔMG-GFP, was efficiently generated in Vero/MG cells stably expressing both BoDV M and G proteins. Infection with rBoDV ΔMG-GFP was persistently maintained in the parent Vero cells without propagation within cell culture. The optimal ratio of M and G for efficient viral particle production by transient transfection of M and G expression plasmids into cells persistently infected with rBoDV ΔMG-GFP was also demonstrated. These findings indicate that the rBoDV ΔMG-based BoDV vector may provide an extremely safe virus vector system and could be a novel strategy for investigating the function of M and G proteins and the host range of bornaviruses. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

  2. Lithium carbonate in amyotrophic lateral sclerosis: lack of efficacy in a dose-finding trial.

    Science.gov (United States)

    Chiò, A; Borghero, G; Calvo, A; Capasso, M; Caponnetto, C; Corbo, M; Giannini, F; Logroscino, G; Mandrioli, J; Marcello, N; Mazzini, L; Moglia, C; Monsurrò, M R; Mora, G; Patti, F; Perini, M; Pietrini, V; Pisano, F; Pupillo, E; Sabatelli, M; Salvi, F; Silani, V; Simone, I L; Sorarù, G; Tola, M R; Volanti, P; Beghi, E

    2010-08-17

    A neuroprotective effect of lithium in amyotrophic lateral sclerosis (ALS) has been recently reported. We performed a multicenter trial with lithium carbonate to assess its tolerability, safety, and efficacy in patients with ALS, comparing 2 different target blood levels (0.4-0.8 mEq/L, therapeutic group [TG], vs 0.2-0.4 mEq/L, subtherapeutic group [STG]). The study was a multicenter, single-blind, randomized, dose-finding trial, conducted from May 2008 to November 2009 in 21 Italian ALS centers. The trial was registered with the public database of the Italian Agency for Drugs (http://oss-sper-clin.agenziafarmaco.it/) (EudraCT number 2008-001094-15). As of October 2009, a total of 171 patients had been enrolled, 87 randomized to the TG and 84 to the STG. The interim data analysis, performed per protocol, showed that 117 patients (68.4%) discontinued the study because of death/tracheotomy/severe disability, adverse events (AEs)/serious AEs (SAEs), or lack of efficacy. The Data Monitoring Committee recommended stopping the trial on November 2, 2009. Lithium was not well-tolerated in this cohort of patients with ALS, even at subtherapeutic doses. The 2 doses were equivalent in terms of survival/severe disability and functional data. The relatively high frequency of AEs/SAEs and the reduced tolerability of lithium raised serious doubts about its safety in ALS. The study provides Class II evidence that therapeutic (0.4-0.8 mEq/L) vs subtherapeutic (0.2-0.4 mEq/L) lithium carbonate did not differ in the primary outcome of efficacy (survival/loss of autonomy) in ALS. Both target levels led to dropouts in more than 30% of participants due to patient-perceived lack of efficacy and AEs.

  3. The Impact of Racism and Midwifery's Lack of Racial Diversity: A Literature Review.

    Science.gov (United States)

    Wren Serbin, Jyesha; Donnelly, Elizabeth

    2016-11-01

    The United States is increasingly racially diverse. Racial disparities in maternal-child health persist. Despite national calls for workforce diversification, more than 90% of certified nurse-midwives are white. This systematic review examines how racism and midwifery's lack of racial diversity impact both midwives and their patients. Databases were searched in January 2016 for studies that explored 1) racially concordant or racially discordant maternity care provided, at least in part, by midwives; 2) women of color's experience of race and discrimination in maternity care provided, at least in part, by midwives; and 3) midwives of color's experience of race and discrimination in clinical, educational, and/or professional settings. Studies were excluded if they were conducted outside the United States, focused on recent immigrant populations, or didn't have an English-language abstract. Selected studies were each reviewed by 2 independent reviewers, and data from the studies were entered into literature tables and synthesized for discussion. A total of 7 studies was retained for review-3 on the experience of patients and 4 on the experience of providers. The studies show racism is common in midwifery education, professional organizations, and clinical practices. Racism and midwifery's lack of racial diversity act as a barrier to people of color completing midwifery education programs and fully participating in midwifery professional organizations. Both patients and midwives of color identified midwives of color as uniquely positioned to provide high-quality care for communities of color. The midwifery profession and its patients stand to substantially benefit from diversification of the field, which requires addressing racism within the profession. Structural competency is a new theory that offers an effective framework to guide these efforts. © 2016 by the American College of Nurse-Midwives.

  4. Lack of metformin effect on mouse embryo AMPK activity: implications for metformin treatment during pregnancy.

    Science.gov (United States)

    Lee, Hyung-Yul; Wei, Dan; Loeken, Mary R

    2014-01-01

    Adenosine monophosphate-activated protein kinase (AMPK) is stimulated in embryos during diabetic pregnancy by maternal hyperglycaemia-induced embryo oxidative stress. Stimulation of AMPK disrupts embryo gene expression and causes neural tube defects. Metformin, which may be taken during early pregnancy, has been reported to stimulate AMPK activity. Thus, the benefits of improved glycaemic control could be offset by stimulated embryo AMPK activity. Here, we investigated whether metformin can stimulate AMPK activity in mouse embryos and can adversely affect embryo gene expression and neural tube defects. Pregnant nondiabetic mice were administered metformin beginning on the first day of pregnancy. Activation of maternal and embryo AMPK [phospho-AMPK α (Thr172) relative to total AMPK], expression of Pax3, a gene required for neural tube closure, and neural tube defects were studied. Mouse embryonic stem cells were used as a cell culture model of embryonic neuroepithelium to study metformin effects on AMPK and Pax3 expression. Metformin had no effect on AMPK in embryos or maternal skeletal muscle but increased activated AMPK in maternal liver. Metformin did not inhibit Pax3 expression or increase neural tube defects. However, metformin increased activated AMPK and inhibited Pax3 expression by mouse embryonic stem cells. Mate1/Slc47a1 and Oct3/Slc22a, which encode metformin transporters, were expressed at barely detectable levels by embryos. Although metformin can have effects associated with diabetic embryopathy in vitro, the lack of effects on mouse embryos in vivo may be due to lack of metformin transporters and indicates that the benefits of metformin on glycaemic control are not counteracted by stimulation of embryo AMPK activity and consequent embryopathy. Copyright © 2013 John Wiley & Sons, Ltd.

  5. Managing human performance

    International Nuclear Information System (INIS)

    Strucic, M.; Kavsek, D.

    2004-01-01

    Human performance remains a significant factor for management attention not only from a reactor safety perspective, but also from a financial one. Recent significant events analysis shows that human errors are still dominant causes and contributors to them. An analysis of significant events in nuclear industry occurred through 15-years period revealed that three of four significant events were triggered by human error, although the number of events have dropped by more than a factor of four. A number of human performance breakdowns occurred in the application of errorprevention techniques. These included a lack of pre-job briefs, inadequate turnover of tasks, ineffective use of peer checking, inadequate procedure adherence, and failure to apply a questioning attitude when unexpected changes were encountered in the task. Attempts by the industry to improve human performance have traditionally focused at the worker level. However, human error occurs within the context of the organization, which can either foster or resist human error. The greatest room for improvement lies not only in the continued improvement of front-line worker performance but more so in the identification and elimination of weaknesses in the organizational and managerial domains that contributes to worker performance at the job site. Based on mentioned analysis, other industrial sources and own operating experience, NPP Krsko is paying more attention to improve human performance among own as well as contractor workers. Through series of programs and activities, such as Reactivity Management Program, Safety Culture Program, Self-assessment Program, Corrective Action Program, Plant Performance Monitoring Program, developed in last few years, and through new procedures, written guides and publications, training and management efforts, number of human errors is going to be reduced. Involvement of higher levels of NPP Krsko organization in promotion and use of Human Performance techniques is

  6. Infection and transmission of Rift Valley fever viruses lacking the NSs and/or NSm genes in mosquitoes: potential role for NSm in mosquito infection.

    Science.gov (United States)

    Crabtree, Mary B; Kent Crockett, Rebekah J; Bird, Brian H; Nichol, Stuart T; Erickson, Bobbie Rae; Biggerstaff, Brad J; Horiuchi, Kalanthe; Miller, Barry R

    2012-01-01

    Rift Valley fever virus is an arthropod-borne human and animal pathogen responsible for large outbreaks of acute and febrile illness throughout Africa and the Arabian Peninsula. Reverse genetics technology has been used to develop deletion mutants of the virus that lack the NSs and/or NSm virulence genes and have been shown to be stable, immunogenic and protective against Rift Valley fever virus infection in animals. We assessed the potential for these deletion mutant viruses to infect and be transmitted by Aedes mosquitoes, which are the principal vectors for maintenance of the virus in nature and emergence of virus initiating disease outbreaks, and by Culex mosquitoes which are important amplification vectors. Aedes aegypti and Culex quinquefasciatus mosquitoes were fed bloodmeals containing the deletion mutant viruses. Two weeks post-exposure mosquitoes were assayed for infection, dissemination, and transmission. In Ae. aegypti, infection and transmission rates of the NSs deletion virus were similar to wild type virus while dissemination rates were significantly reduced. Infection and dissemination rates for the NSm deletion virus were lower compared to wild type. Virus lacking both NSs and NSm failed to infect Ae. aegypti. In Cx. quinquefasciatus, infection rates for viruses lacking NSm or both NSs and NSm were lower than for wild type virus. In both species, deletion of NSm or both NSs and NSm reduced the infection and transmission potential of the virus. Deletion of both NSs and NSm resulted in the highest level of attenuation of virus replication. Deletion of NSm alone was sufficient to nearly abolish infection in Aedes aegypti mosquitoes, indicating an important role for this protein. The double deleted viruses represent an ideal vaccine profile in terms of environmental containment due to lack of ability to efficiently infect and be transmitted by mosquitoes.

  7. Infection and transmission of Rift Valley fever viruses lacking the NSs and/or NSm genes in mosquitoes: potential role for NSm in mosquito infection.

    Directory of Open Access Journals (Sweden)

    Mary B Crabtree

    Full Text Available BACKGROUND: Rift Valley fever virus is an arthropod-borne human and animal pathogen responsible for large outbreaks of acute and febrile illness throughout Africa and the Arabian Peninsula. Reverse genetics technology has been used to develop deletion mutants of the virus that lack the NSs and/or NSm virulence genes and have been shown to be stable, immunogenic and protective against Rift Valley fever virus infection in animals. We assessed the potential for these deletion mutant viruses to infect and be transmitted by Aedes mosquitoes, which are the principal vectors for maintenance of the virus in nature and emergence of virus initiating disease outbreaks, and by Culex mosquitoes which are important amplification vectors. METHODOLOGY AND PRINCIPAL FINDINGS: Aedes aegypti and Culex quinquefasciatus mosquitoes were fed bloodmeals containing the deletion mutant viruses. Two weeks post-exposure mosquitoes were assayed for infection, dissemination, and transmission. In Ae. aegypti, infection and transmission rates of the NSs deletion virus were similar to wild type virus while dissemination rates were significantly reduced. Infection and dissemination rates for the NSm deletion virus were lower compared to wild type. Virus lacking both NSs and NSm failed to infect Ae. aegypti. In Cx. quinquefasciatus, infection rates for viruses lacking NSm or both NSs and NSm were lower than for wild type virus. CONCLUSIONS/SIGNIFICANCE: In both species, deletion of NSm or both NSs and NSm reduced the infection and transmission potential of the virus. Deletion of both NSs and NSm resulted in the highest level of attenuation of virus replication. Deletion of NSm alone was sufficient to nearly abolish infection in Aedes aegypti mosquitoes, indicating an important role for this protein. The double deleted viruses represent an ideal vaccine profile in terms of environmental containment due to lack of ability to efficiently infect and be transmitted by mosquitoes.

  8. Lack of mitochondrial MutS homolog 1 in Toxoplasma gondii disrupts maintenance and fidelity of mitochondrial DNA and reveals metabolic plasticity.

    Directory of Open Access Journals (Sweden)

    Tamila Garbuz

    Full Text Available The importance of maintaining the fidelity of the mitochondrial genome is underscored by the presence of various repair pathways within this organelle. Presumably, the repair of mitochondrial DNA would be of particular importance in organisms that possess only a single mitochondrion, like the human pathogens Plasmodium falciparum and Toxoplasma gondii. Understanding the machinery that maintains mitochondrial DNA in these parasites is of particular relevance, as mitochondrial function is a validated and effective target for anti-parasitic drugs. We previously determined that the Toxoplasma MutS homolog TgMSH1 localizes to the mitochondrion. MutS homologs are key components of the nuclear mismatch repair system in mammalian cells, and both yeast and plants possess MutS homologs that localize to the mitochondria where they regulate DNA stability. Here we show that the lack of TgMSH1 results in accumulation of single nucleotide variations in mitochondrial DNA and a reduction in mitochondrial DNA content. Additionally, parasites lacking TgMSH1 function can survive treatment with the cytochrome b inhibitor atovaquone. While the Tgmsh1 knockout strain has several missense mutations in cytochrome b, none affect amino acids known to be determinants of atovaquone sensitivity and atovaquone is still able to inhibit electron transport in the Tgmsh1 mutants. Furthermore, culture of Tgmsh1 mutant in the presence atovaquone leads to parasites with enhanced atovaquone resistance and complete shutdown of respiration. Thus, parasites lacking TgMSH1 overcome the disruption of mitochondrial DNA by adapting their physiology allowing them to forgo the need for oxidative phosphorylation. Consistent with this idea, the Tgmsh1 mutant is resistant to mitochondrial inhibitors with diverse targets and exhibits reduced ability to grow in the absence of glucose. This work shows TgMSH1 as critical for the maintenance and fidelity of the mitochondrial DNA in Toxoplasma

  9. Lack of radioimmunodetection and complications associated with monoclonal anticarcinoembryonic antigen antibody cross-reactivity with an antigen on circulating cells

    International Nuclear Information System (INIS)

    Dillman, R.O.; Beauregard, J.C.; Sobol, R.E.; Royston, I.; Bartholomew, R.M.; Hagan, P.S.; Halpern, S.E.

    1984-01-01

    Characterization of several high-affinity murine monoclonal anticarcinoembryonic antigen (CEA) antibodies suggested good specificity except for cross-reactivity with an antigen on granulocytes and erythrocytes which was different from the previously described normal cross-reacting antigen of granulocytes. In vivo studies in athymic mice using an indium conjugate of an anti-CEA monoclonal antibody (MoAb) revealed excellent specific uptake in colorectal carcinoma xenografts. Studies were conducted in humans to determine the limitations produced by the cross-reactivity with granulocytes and erythrocytes. Patients with metastatic colorectal cancer received 3 to 6 mg of anti-CEA MoAb over 10 min or 2 hr. In five of six trials, the MoAb infusion was associated with a 40 to 90% decrease in circulating granulocytes and systemic toxicity including fever, rigors, and emesis. One patient had no change in cell count and had no toxicity. Radionuclide scans with 111 In-anti-CEA MoAb showed marked uptake in the spleen when cells were eliminated, and in the liver, especially when pretreatment CEA levels were high. Metastatic tumor sites failed to concentrate the isotope. This study emphasizes the potential limitations for radioimmunodetection and/or radioimmunotherapy imposed by reactivity with circulating cells, and suggests that certain toxic reactions associated with MoAb infusions are related to destruction of circulating cells rather than allergic reactions to mouse protein. It also emphasizes how variables such as dose and binding affinity of antibody, radioisotope used, and assessment at different observation points can obscure lack of antibody specificity

  10. Lack of radioimmunodetection and complications associated with monoclonal anticarcinoembryonic antigen antibody cross-reactivity with an antigen on circulating cells

    Energy Technology Data Exchange (ETDEWEB)

    Dillman, R.O.; Beauregard, J.C.; Sobol, R.E.; Royston, I.; Bartholomew, R.M.; Hagan, P.S.; Halpern, S.E.

    1984-05-01

    Characterization of several high-affinity murine monoclonal anticarcinoembryonic antigen (CEA) antibodies suggested good specificity except for cross-reactivity with an antigen on granulocytes and erythrocytes which was different from the previously described normal cross-reacting antigen of granulocytes. In vivo studies in athymic mice using an indium conjugate of an anti-CEA monoclonal antibody (MoAb) revealed excellent specific uptake in colorectal carcinoma xenografts. Studies were conducted in humans to determine the limitations produced by the cross-reactivity with granulocytes and erythrocytes. Patients with metastatic colorectal cancer received 3 to 6 mg of anti-CEA MoAb over 10 min or 2 hr. In five of six trials, the MoAb infusion was associated with a 40 to 90% decrease in circulating granulocytes and systemic toxicity including fever, rigors, and emesis. One patient had no change in cell count and had no toxicity. Radionuclide scans with /sup 111/In-anti-CEA MoAb showed marked uptake in the spleen when cells were eliminated, and in the liver, especially when pretreatment CEA levels were high. Metastatic tumor sites failed to concentrate the isotope. This study emphasizes the potential limitations for radioimmunodetection and/or radioimmunotherapy imposed by reactivity with circulating cells, and suggests that certain toxic reactions associated with MoAb infusions are related to destruction of circulating cells rather than allergic reactions to mouse protein. It also emphasizes how variables such as dose and binding affinity of antibody, radioisotope used, and assessment at different observation points can obscure lack of antibody specificity.

  11. Epithelial cell stretching and luminal acidification lead to a retarded development of stria vascularis and deafness in mice lacking pendrin.

    Directory of Open Access Journals (Sweden)

    Hyoung-Mi Kim

    2011-03-01

    Full Text Available Loss-of-function mutations of SLC26A4/pendrin are among the most prevalent causes of deafness. Deafness and vestibular dysfunction in the corresponding mouse model, Slc26a4(-/-, are associated with an enlargement and acidification of the membranous labyrinth. Here we relate the onset of expression of the HCO(3 (- transporter pendrin to the luminal pH and to enlargement-associated epithelial cell stretching. We determined expression with immunocytochemistry, cell stretching by digital morphometry and pH with double-barreled ion-selective electrodes. Pendrin was first expressed in the endolymphatic sac at embryonic day (E 11.5, in the cochlear hook-region at E13.5, in the utricle and saccule at E14.5, in ampullae at E16.5, and in the upper turn of the cochlea at E17.5. Epithelial cell stretching in Slc26a4(-/- mice began at E14.5. pH changes occurred first in the cochlea at E15.5 and in the endolymphatic sac at E17.5. At postnatal day 2, stria vascularis, outer sulcus and Reissner's membrane epithelial cells, and utricular and saccular transitional cells were stretched, whereas sensory cells in the cochlea, utricle and saccule did not differ between Slc26a4(+/- and Slc26a4(-/- mice. Structural development of stria vascularis, including vascularization, was retarded in Slc26a4(-/- mice. In conclusion, the data demonstrate that the enlargement and stretching of non-sensory epithelial cells precedes luminal acidification in the cochlea and the endolymphatic sac. Stretching and luminal acidification may alter cell-to-cell communication and lead to the observed retarded development of stria vascularis, which may be an important step on the path to deafness in Slc26a4(-/- mice, and possibly in humans, lacking functional pendrin expression.

  12. Lack of diurnal rhythm of low molecular weight insulin-like growth factor binding protein in patients with Cushing's disease

    International Nuclear Information System (INIS)

    Degerblad, M.; Povoa, G.; Thoren, M.; Wivall, I.-L.; Hall, K.

    1989-01-01

    A specific radioimmunoassay with antibodies raised against the 25 kD insulin-like growth factor binding protein (25 kD IGFBP) in amniotic fluid was used to measure levels of cross-reacting protein in human serum and plasma. Plasma samples collected continually at 20-min intervals during 24-h in 6 healthy adults revealed a distinct diurnal rhythm in the concentration of 25 kD IGFBP. The lowest levels (9-13 μg/l) were found between 13.00 and 24.00 h with a rise after midnight to maximum levels (23-71 μg/l) between 03.00 and 09.00 h. There was no relation between the patterns of GH and 25 kD IGFBP. In 3 patients with active Cushing's disease, the levels of 25 kD IGFBP in plasma samples collected during 12 h. 19.00-07.00 h, were generally low and without nocturnal variations. One of the patients studied after extirpation of a pituitary adenoma displayed a nocturnal rhythm with maximum levels of 25 kD IGFBP between 03.00 and 07.00 h. Eight patients treated with stereotactic pituitary irradiation owing to Cushing's disease also showed a distinct nocturnal increase of 25 kD IGFBP. The results indicate the existence of a diurnal rhythm of 25 kD IGFBP in adults. Further, low levels and lack of diurnal rhythm of 25 kD IGFBP are demonstrated in Cushing's disease. (author)

  13. HIV seroprevalence among hospital workers in Kinshasa, Zaire: lack of association with occupational exposure

    International Nuclear Information System (INIS)

    Mann, J.M.; Francis, H.; Quinn, T.C.

    1986-01-01

    A study of seroprevalence of the human immunodeficiency virus involving 2384 (96%) of Mama Yemo Hospital's (Kinshasa, Zaire) 2492 personnel found 152 (6.4%) to be seropositive. Prevalence was higher among women than among men (8.1% vs 5.2%); in women peak seroprevalence (13.9%) occurred in 20 to 29-year-olds. Workers most likely to be seropositive were those who were relatively young, those who were unmarried, those reporting a blood transfusion or hospitalization during the previous ten years, and those receiving medical injections during the previous three years. Medical, administrative, and manual workers had similar seroprevalence (6.5%, 6.4%, and 6.0%, respectively), and seropositivity was not associated with any measure of patient, blood, or needle contact. These findings are consistent with other hospital-based studies indicating low risks for occupational transmission of human immunodeficiency virus

  14. Autosomal dominant epidermodysplasia verruciformis lacking a known EVER1 or EVER2 mutation

    OpenAIRE

    McDermott, David H.; Gammon, Bryan; Snijders, Peter J.; Mbata, Ihunanya; Phifer, Beth; Hartley, A. Howland; Lee, Chyi-Chia Richard; Murphy, Philip M.; Hwang, Sam T.

    2009-01-01

    Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by abnormal susceptibility to infection with specific human papillomavirus (HPV) serotypes. EV is a genetically heterogeneous disease, and autosomal recessive and X-linked inheritance patterns have been reported. Nonsense mutations in the genes EVER1 and EVER2 have been identified in over 75% of cases. We present EV in a father and son with typical histologic and clinical findings that occur in the absence of mutation...

  15. Ancient DNA reveals lack of continuity between neolithic hunter-gatherers and contemporary Scandinavians

    DEFF Research Database (Denmark)

    Malmström, Helena; Gilbert, M Thomas P; Thomas, Mark G

    2009-01-01

    of the two cultures in Scandinavia has been cited as an argument against population replacement between the Mesolithic and the present [7, 8]. Through analysis of DNA extracted from ancient Scandinavian human remains, we show that people of the Pitted Ware culture were not the direct ancestors of modern......]. Furthermore, our data are consistent with the view that the eastern Baltic represents a genetic refugia for some of the European hunter-gatherer populations....

  16. Signal peptide of eosinophil cationic protein is toxic to cells lacking signal peptide peptidase

    International Nuclear Information System (INIS)

    Wu, C.-M.; Chang, Margaret Dah-Tsyr

    2004-01-01

    Eosinophil cationic protein (ECP) is a toxin secreted by activated human eosinophils. The properties of mature ECP have been well studied but those of the signal peptide of ECP (ECPsp) are not clear. In this study, several chimeric proteins containing N-terminal fusion of ECPsp were generated, and introduced into Escherichia coli, Pichia pastoris, and human epidermoid carcinoma cell line A431 to study the function of ECPsp. We found that expression of ECPsp chimeric proteins inhibited the growth of E. coli and P. pastoris but not A431 cells. Primary sequence analysis and in vitro transcription/translation of ECPsp have revealed that it is a potential substrate for human signal peptide peptidase (hSPP), an intramembrane protease located in endoplasmic reticulum. In addition, knockdown of the hSPP mRNA expression in ECPsp-eGFP/A431 cells caused the growth inhibitory effect, whereas complementally expression of hSPP in P. pastoris system rescued the cell growth. Taken together, we have demonstrated that ECPsp is a toxic signal peptide, and expression of hSPP protects the cells from growth inhibition

  17. 10 CFR 503.31 - Lack of alternate fuel supply for the first 10 years of useful life.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Lack of alternate fuel supply for the first 10 years of useful life. 503.31 Section 503.31 Energy DEPARTMENT OF ENERGY (CONTINUED) ALTERNATE FUELS NEW FACILITIES Permanent Exemptions for New Facilities § 503.31 Lack of alternate fuel supply for the first 10 years of...

  18. Human engineering

    International Nuclear Information System (INIS)

    Yang, Seong Hwan; Park, Bum; Gang, Yeong Sik; Gal, Won Mo; Baek, Seung Ryeol; Choe, Jeong Hwa; Kim, Dae Sung

    2006-07-01

    This book mentions human engineering, which deals with introduction of human engineering, Man-Machine system like system design, and analysis and evaluation of Man-Machine system, data processing and data input, display, system control of man, human mistake and reliability, human measurement and design of working place, human working, hand tool and manual material handling, condition of working circumstance, working management, working analysis, motion analysis working measurement, and working improvement and design in human engineering.

  19. Lack of direct evidence for natural selection at the candidate thrifty gene locus, PPARGC1A.

    Science.gov (United States)

    Cadzow, Murray; Merriman, Tony R; Boocock, James; Dalbeth, Nicola; Stamp, Lisa K; Black, Michael A; Visscher, Peter M; Wilcox, Phillip L

    2016-11-15

    The gene PPARGC1A, in particular the Gly482Ser variant (rs8192678), had been proposed to be subject to natural selection, particularly in recent progenitors of extant Polynesian populations. Reasons include high levels of population differentiation and increased frequencies of the derived type 2 diabetes (T2D) risk 482Ser allele, and association with body mass index (BMI) in a small Tongan population. However, no direct statistical tests for selection have been applied. Using a range of Polynesian populations (Tongan, Māori, Samoan) we re-examined evidence for association between Gly482Ser with T2D and BMI as well as gout. Using also Asian, European, and African 1000 Genome Project samples a range of statistical tests for selection (F ST , integrated haplotype score (iHS), cross population extended haplotype homozygosity (XP-EHH), Tajima's D and Fay and Wu's H) were conducted on the PPARGC1A locus. No statistically significant evidence for association between Gly482Ser and any of BMI, T2D or gout was found. Population differentiation (F ST ) was smallest between Asian and Pacific populations (New Zealand Māori ≤ 0.35, Samoan ≤ 0.20). When compared to European (New Zealand Māori ≤ 0.40, Samoan ≤ 0.25) or African populations (New Zealand Māori ≤ 0.80, Samoan ≤ 0.66) this differentiation was larger. We did not find any strong evidence for departure from neutral evolution at this locus when applying any of the other statistical tests for selection. However, using the same analytical methods, we found evidence for selection in specific populations at previously identified loci, indicating that lack of selection was the most likely explanation for the lack of evidence of selection in PPARGC1A. We conclude that there is no compelling evidence for selection at this locus, and that this gene should not be considered a candidate thrifty gene locus in Pacific populations. High levels of population differentiation at this locus and the

  20. Lack of effectiveness of primary conservative management for infants with brachial plexus birth palsy.

    Science.gov (United States)

    Bialocerkowski, Andrea Emmi; Vladusic, Sharon; Moore, Rosemary Patricia

    Brachial plexus birth palsy (BPBP) is the most common peripheral nerve injury in children (prevalence microsurgical repair of the brachial plexus, surgical management of secondary deformities or received other treatments traditionally delivered by surgeons, such as Botulinum toxin injections. The eligibility of each study identified from the database searches was evaluated against the inclusion criteria by two independent reviewers. These studies were then critically appraised for level of evidence using the National Health and Medical Research Council of Australia Hierarchy of Evidence and methodological quality using the Critical Review Form - Quantitative Studies. Data pertaining to the demographic characteristics of study participants, treatments received, main results and outcome measures used were also extracted. Where any disagreement between reviewers occurred, consensus was reached by discussion. Data from the recently published studies were narratively synthesised and then combined with the data gained from our previous systematic review to create a body of evidence on primary conservative management for BPBP infants. Four publications, representing three studies (one comparative study, two case series), were sourced. Methodological quality scores of these studies ranged from 6 to 12 (maximum =16). The current body of evidence (publications from 1992 to 2008) therefore comprises 11 studies, four using a comparative design and seven using a case series design. Six of the 11 studies were classified as being of "poor" methodological quality (score <8). Conservative management mainly consisted of exercise therapy, although splinting, massage and dynamic traction were also used. All studies lacked a clear definition of conservative management sufficient to allow replication of the treatment in a clinical setting. A variety of outcome measures were used, limiting comparability of the studies. Data from the three case studies suggests that conservative

  1. Lack of recording of systemic lupus erythematosus in the death certificates of lupus patients.

    Science.gov (United States)

    Calvo-Alén, J; Alarcón, G S; Campbell, R; Fernández, M; Reveille, J D; Cooper, G S

    2005-09-01

    To determine to what extent the diagnosis of systemic lupus erythematosus (SLE) in deceased lupus patients is under-reported in death certificates, and the patient characteristics associated with such an occurrence. The death certificates of 76 of the 81 deceased SLE patients from two US lupus cohorts (LUMINA for Lupus in Minorities: Nature vs Nurture and CLU for Carolina Lupus Study), including 570 and 265 patients, respectively, were obtained from the Offices of Vital Statistics of the states where the patients died (Alabama, Georgia, North Carolina, South Carolina, Tennessee and Texas). Both cohorts included patients with SLE as per the American College of Rheumatology criteria, aged > or =16 yr, and disease duration at enrolment of < or =5 yr. The median duration of follow-up in each cohort at the time of these analyses ranged from 38.1 to 53.0 months. Standard univariable analyses were performed comparing patients with SLE recorded anywhere in the death certificate and those without it. A multivariable logistic regression model was performed to identify the variables independently associated with not recording SLE in death certificates. In 30 (40%) death certificates, SLE was not recorded anywhere in the death certificate. In univariable analyses, older age was associated with lack of recording of SLE in death certificates [mean age (standard deviation) 50.9 (15.6) years and 39.1 (18.6) yr among those for whom SLE was omitted and included on the death certificates, respectively, P = 0.005]. Patients without health insurance, those dying of a cardiovascular event and those of Caucasian ethnicity were also more likely to be in the non-recorded group. In the multivariable analysis, variables independently associated with not recording SLE as cause of death were older age [odds ratio = (95% confidence interval) 1.043 (1.005-1.083 per yr increase); P = 0.023] and lack of health insurance [4.649 (1.152-18.768); P = 0.031]. A high proportion of SLE diagnoses are not

  2. Impaired Glucose Metabolism in Mice Lacking the Tas1r3 Taste Receptor Gene.

    Science.gov (United States)

    Murovets, Vladimir O; Bachmanov, Alexander A; Zolotarev, Vasiliy A

    2015-01-01

    The G-protein-coupled sweet taste receptor dimer T1R2/T1R3 is expressed in taste bud cells in the oral cavity. In recent years, its involvement in membrane glucose sensing was discovered in endocrine cells regulating glucose homeostasis. We investigated importance of extraorally expressed T1R3 taste receptor protein in age-dependent control of blood glucose homeostasis in vivo, using nonfasted mice with a targeted mutation of the Tas1r3 gene that encodes the T1R3 protein. Glucose and insulin tolerance tests, as well as behavioral tests measuring taste responses to sucrose solutions, were performed with C57BL/6ByJ (Tas1r3+/+) inbred mice bearing the wild-type allele and C57BL/6J-Tas1r3tm1Rfm mice lacking the entire Tas1r3 coding region and devoid of the T1R3 protein (Tas1r3-/-). Compared with Tas1r3+/+ mice, Tas1r3-/- mice lacked attraction to sucrose in brief-access licking tests, had diminished taste preferences for sucrose solutions in the two-bottle tests, and had reduced insulin sensitivity and tolerance to glucose administered intraperitoneally or intragastrically, which suggests that these effects are due to absence of T1R3. Impairment of glucose clearance in Tas1r3-/- mice was exacerbated with age after intraperitoneal but not intragastric administration of glucose, pointing to a compensatory role of extraoral T1R3-dependent mechanisms in offsetting age-dependent decline in regulation of glucose homeostasis. Incretin effects were similar in Tas1r3+/+ and Tas1r3-/- mice, which suggests that control of blood glucose clearance is associated with effects of extraoral T1R3 in tissues other than the gastrointestinal tract. Collectively, the obtained data demonstrate that the T1R3 receptor protein plays an important role in control of glucose homeostasis not only by regulating sugar intake but also via its extraoral function, probably in the pancreas and brain.

  3. Impaired Glucose Metabolism in Mice Lacking the Tas1r3 Taste Receptor Gene.

    Directory of Open Access Journals (Sweden)

    Vladimir O Murovets

    Full Text Available The G-protein-coupled sweet taste receptor dimer T1R2/T1R3 is expressed in taste bud cells in the oral cavity. In recent years, its involvement in membrane glucose sensing was discovered in endocrine cells regulating glucose homeostasis. We investigated importance of extraorally expressed T1R3 taste receptor protein in age-dependent control of blood glucose homeostasis in vivo, using nonfasted mice with a targeted mutation of the Tas1r3 gene that encodes the T1R3 protein. Glucose and insulin tolerance tests, as well as behavioral tests measuring taste responses to sucrose solutions, were performed with C57BL/6ByJ (Tas1r3+/+ inbred mice bearing the wild-type allele and C57BL/6J-Tas1r3tm1Rfm mice lacking the entire Tas1r3 coding region and devoid of the T1R3 protein (Tas1r3-/-. Compared with Tas1r3+/+ mice, Tas1r3-/- mice lacked attraction to sucrose in brief-access licking tests, had diminished taste preferences for sucrose solutions in the two-bottle tests, and had reduced insulin sensitivity and tolerance to glucose administered intraperitoneally or intragastrically, which suggests that these effects are due to absence of T1R3. Impairment of glucose clearance in Tas1r3-/- mice was exacerbated with age after intraperitoneal but not intragastric administration of glucose, pointing to a compensatory role of extraoral T1R3-dependent mechanisms in offsetting age-dependent decline in regulation of glucose homeostasis. Incretin effects were similar in Tas1r3+/+ and Tas1r3-/- mice, which suggests that control of blood glucose clearance is associated with effects of extraoral T1R3 in tissues other than the gastrointestinal tract. Collectively, the obtained data demonstrate that the T1R3 receptor protein plays an important role in control of glucose homeostasis not only by regulating sugar intake but also via its extraoral function, probably in the pancreas and brain.

  4. Cytokines in human milk.

    Science.gov (United States)

    Garofalo, Roberto

    2010-02-01

    Epidemiologic studies conducted in the past 30 years to investigate the protective functions of human milk strongly support the notion that breastfeeding prevents infantile infections, particularly those affecting the gastrointestinal and respiratory tracts. However, more recent clinical and experimental observations also suggest that human milk not only provides passive protection, but also can directly modulate the immunological development of the recipient infant. The study of this remarkable defense system in human milk has been difficult because of its biochemical complexity, the small concentration of certain bioactive components, the compartmentalization of some of these agents, the dynamic quantitative and qualitative changes of milk during lactation, and the lack of specific reagents to quantify these agents. However, a host of bioactive substances, including hormones, growth factors, and immunological factors such as cytokines, have been identified in human milk. Cytokines are pluripotent polypeptides that act in autocrine/paracrine fashions by binding to specific cellular receptors. They operate in networks and orchestrate the development and functions of immune system. Several different cytokines and chemokines have been discovered in human milk in the past years, and the list is growing very rapidly. This article will review the current knowledge about the increasingly complex network of chemoattractants, activators, and anti-inflammatory cytokines present in human milk and their potential role in compensating for the developmental delay of the neonate immune system. Copyright 2010. Published by Mosby, Inc.

  5. Systematic Assessment Reveals Lack of Understandability for Prostate Biopsy Online Patient Education Materials.

    Science.gov (United States)

    Maciolek, Kimberly A; Jarrard, David F; Abel, E Jason; Best, Sara L

    2017-11-01

    To evaluate the accuracy, readability, understandability, and actionability of Internet patient education materials (PEM) about transrectal ultrasound-guided prostate biopsy. A comprehensive Internet search was performed to find PEM with pre- or postbiopsy instructions. PEM that were duplicates, government affiliated, international, or video based were excluded. Biopsy instructions were evaluated for accuracy and presence of essential topics. Readability was assessed via word count and Flesch-Kincaid Grade Level. Understandability and actionability were measured using the Patient Education Materials Assessment Tool (PEMAT). Effects of authorship and geographical variation were determined using Fischer exact and Kruskal-Wallis tests. We identified 148 unique PEM. Only 31 (21%) sites adhered to the recommended reading level. Most PEM did not contain recommended graphics (14%), checklists (2%), or summaries (6%). The PEMAT understandability score for academic PEM was higher than private (P = .02) and unaffiliated PEM (P = .01). No websites had inaccurate content. Only 2 PEM sites (1%) included all essential content (stop anticoagulants, antibiotics, need for urinalysis, biopsy pain, when to resume activity, and bleeding complications). Few significant differences based on geographic region were observed for word count, readability, PEMAT scores, or content. Transrectal ultrasound-guided prostate biopsy PEM adhere poorly to guidelines for easy-to-understand materials. Most PEM lack vital information and are written at a reading level that is too complex for patient comprehension. The urology community can construct better websites by consulting PEM advisory materials and providing nontechnical language, figures, and specific instructions. Published by Elsevier Inc.

  6. Lack of behavioural evidence for kin avoidance in mate choice in a hymenopteran parasitoid (Hymenoptera: Braconidae).

    Science.gov (United States)

    Bourdais, D; Hance, T

    2009-05-01

    Mechanisms for inbreeding avoidance should be prevalent in insects that reproduce by arrhenotokous haplodiploidy because of the higher potential production of unviable diploid males in inbred matings. Few studies have focused on mating strategies in insect parasitoids and even less on kinship relationships during mate choice. In this study we tested avoidance of kin as mate in the parasitic wasp Aphidius matricariae (Hymenoptera: Braconidae) using an ethological approach. Key mating parameters, such as male wing fanning, latent period before genitalia contact and duration of copulation were measured. No evidence for kin avoidance in mate choice in both A. matricariae males and females was observed in our behaviour (no choice or choice tests) tests. This lack of ethological sib mating avoidance could be due to different factors such as sex determination rule different than the single locus complementary sex determination, making lower the proportion of diploid males in case of sib matings and thus its negative consequence. The existence of other inbreeding avoidance strategies and mechanisms that reduce the probability of 2 receptive relatives meeting in nature may be common, for example, inbred mating may be rare through differential dispersal, delayed maturation, or protandry.

  7. Lack of specific (3H) prazosin binding sites in dog and rabbit cerebral arteries

    International Nuclear Information System (INIS)

    Ferron, P.M.; Banner, W. Jr.; Duckles, S.P.

    1984-01-01

    In order to explore the characteristics of alpha adrenergic receptors on cerebrovascular smooth muscle, specific binding sites for the alpha 1 adrenergic ligand, ( 3 H) prazosin, were studied in blood vessel homogenates. No specific ( 3 H) prazosin binding was found in either rabbit or dog cerebral arteries, but specific binding was demonstrated in the rabbit saphenous and ear arteries. In the ear artery 3 H-prazosin binding was saturable with a K/sub d/ of 0.51 +/- 0.20 nM and a Bmax of 89 +/- 29 fmoles/mg protein. To confirm the adequacy of our membrane preparation, homogenates of both dog and rabbit cerebral arteries showed saturable specific binding with two different ligands: one for muscarinic receptors, [ 3 H](-) quinuclidinyl benzilate (QNB) and one for alpha 2 adrenergic receptors, ( 3 H) yohimbine. The results of these studies demonstrate a lack of alpha 1 adrenergic receptors on cerebral blood vessels, confirming functional studies showing only a weak contractile response to norepinephrine. 29 references, 3 figures, 2 tables

  8. A systematic literature search on psychological first aid: lack of evidence to develop guidelines.

    Science.gov (United States)

    Dieltjens, Tessa; Moonens, Inge; Van Praet, Koen; De Buck, Emmy; Vandekerckhove, Philippe

    2014-01-01

    Providing psychological first aid (PFA) is generally considered to be an important element in preliminary care of disaster victims. Using the best available scientific basis for courses and educational materials, the Belgian Red Cross-Flanders wants to ensure that its volunteers are trained in the best way possible. To identify effective PFA practices, by systematically reviewing the evidence in existing guidelines, systematic reviews and individual studies. Systematic literature searches in five bibliographic databases (MEDLINE, PsycINFO, The Cochrane Library, PILOTS and G-I-N) were conducted from inception to July 2013. Five practice guidelines were included which were found to vary in the development process (AGREE II score 20-53%) and evidence base used. None of them provides solid evidence concerning the effectiveness of PFA practices. Additionally, two systematic reviews of PFA were found, both noting a lack of studies on PFA. A complementary search for individual studies, using a more sensitive search strategy, identified 11 237 references of which 102 were included for further full-text examination, none of which ultimately provides solid evidence concerning the effectiveness of PFA practices. The scientific literature on psychological first aid available to date, does not provide any evidence about the effectiveness of PFA interventions. Currently it is impossible to make evidence-based guidelines about which practices in psychosocial support are most effective to help disaster and trauma victims.

  9. A systematic literature search on psychological first aid: lack of evidence to develop guidelines.

    Directory of Open Access Journals (Sweden)

    Tessa Dieltjens

    Full Text Available Providing psychological first aid (PFA is generally considered to be an important element in preliminary care of disaster victims. Using the best available scientific basis for courses and educational materials, the Belgian Red Cross-Flanders wants to ensure that its volunteers are trained in the best way possible.To identify effective PFA practices, by systematically reviewing the evidence in existing guidelines, systematic reviews and individual studies.Systematic literature searches in five bibliographic databases (MEDLINE, PsycINFO, The Cochrane Library, PILOTS and G-I-N were conducted from inception to July 2013.Five practice guidelines were included which were found to vary in the development process (AGREE II score 20-53% and evidence base used. None of them provides solid evidence concerning the effectiveness of PFA practices. Additionally, two systematic reviews of PFA were found, both noting a lack of studies on PFA. A complementary search for individual studies, using a more sensitive search strategy, identified 11 237 references of which 102 were included for further full-text examination, none of which ultimately provides solid evidence concerning the effectiveness of PFA practices.The scientific literature on psychological first aid available to date, does not provide any evidence about the effectiveness of PFA interventions. Currently it is impossible to make evidence-based guidelines about which practices in psychosocial support are most effective to help disaster and trauma victims.

  10. Hematopoietic Kit Deficiency, rather than Lack of Mast Cells, Protects Mice from Obesity and Insulin Resistance.

    Science.gov (United States)

    Gutierrez, Dario A; Muralidhar, Sathya; Feyerabend, Thorsten B; Herzig, Stephan; Rodewald, Hans-Reimer

    2015-05-05

    Obesity, insulin resistance, and related pathologies are associated with immune-mediated chronic inflammation. Kit mutant mice are protected from diet-induced obesity and associated co-morbidities, and this phenotype has previously been attributed to their lack of mast cells. We performed a comprehensive metabolic analysis of Kit-dependent Kit(W/Wv) and Kit-independent Cpa3(Cre/+) mast-cell-deficient mouse strains, employing diet-induced or genetic (Lep(Ob/Ob) background) models of obesity. Our results show that mast cell deficiency, in the absence of Kit mutations, plays no role in the regulation of weight gain or insulin resistance. Moreover, we provide evidence that the metabolic phenotype observed in Kit mutant mice, while independent of mast cells, is immune regulated. Our data underscore the value of definitive mast cell deficiency models to conclusively test the involvement of this enigmatic cell in immune-mediated pathologies and identify Kit as a key hematopoietic factor in the pathogenesis of metabolic syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Differential gene expression in the murine gastric fundus lacking interstitial cells of Cajal

    Directory of Open Access Journals (Sweden)

    Ward Sean M

    2003-06-01

    Full Text Available Abstract Background The muscle layers of murine gastric fundus have no interstitial cells of Cajal at the level of the myenteric plexus and only possess intramuscular interstitial cells and this tissue does not generate electric slow waves. The absence of intramuscular interstitial cells in W/WV mutants provides a unique opportunity to study the molecular changes that are associated with the loss of these intercalating cells. Method The gene expression profile of the gastric fundus of wild type and W/WV mice was assayed by murine microarray analysis displaying a total of 8734 elements. Queried genes from the microarray analysis were confirmed by semi-quantitative reverse transcription-polymerase chain reaction. Results Twenty-one genes were differentially expressed in wild type and W/WV mice. Eleven transcripts had 2.0–2.5 fold higher mRNA expression in W/WV gastric fundus when compared to wild type tissues. Ten transcripts had 2.1–3.9 fold lower expression in W/WV mutants in comparison with wild type animals. None of these genes have ever been implicated in any bowel motility function. Conclusions These data provides evidence that several important genes have significantly changed in the murine fundus of W/WV mutants that lack intramuscular interstitial cells of Cajal and have reduced enteric motor neurotransmission.

  12. Rats distinguish between absence of events and lack of evidence in contingency learning.

    Science.gov (United States)

    Waldmann, Michael R; Schmid, Martina; Wong, Jared; Blaisdell, Aaron P

    2012-09-01

    The goal of three experiments was to study whether rats are aware of the difference between absence of events and lack of evidence. We used a Pavlovian extinction paradigm in which lights consistently signaling sucrose were suddenly paired with the absence of sucrose. The crucial manipulation involved the absent outcomes in the extinction phase. Whereas in the Cover conditions, access to the drinking receptacle was blocked by a metal plate, in the No Cover conditions, the drinking receptacle was accessible. The Test phase showed that in the Cover conditions, the measured expectancies of sucrose were clearly at a higher level than in the No Cover conditions. We compare two competing theories potentially explaining the findings. A cognitive theory interprets the observed effect as evidence that the rats were able to understand that the cover blocked informational access to the outcome information, and therefore the changed learning input did not necessarily signify a change of the underlying contingency in the world. An alternative associationist account, renewal theory, might instead explain the relative sparing of extinction in the Cover condition as a consequence of context change. We discuss the merits of both theories as accounts of our data and conclude that the cognitive explanation is in this case preferred.

  13. Novel dehydrins lacking complete K-segments in Pinaceae. The exception rather than the rule

    Directory of Open Access Journals (Sweden)

    Pedro ePerdiguero

    2014-12-01

    Full Text Available Dehydrins are thought to play an essential role in the plant response, acclimation and tolerance to different abiotic stresses, such as cold and drought. These proteins contain conserved and repeated segments in their amino acid sequence, used for their classification. Thus, dehydrins from angiosperms present different repetitions of the segments Y, S and K, while gymnosperm dehydrins show A, E, S and K segments. The only fragment present in all the dehydrins described to date is the K-segment. Different works suggest the K-segment is involved in key protective functions during dehydration stress, mainly stabilizing membranes. In this work, we describe for the first time two Pinus pinaster proteins with truncated K-segments and a third one completely lacking K-segments, but whose sequence homology leads us to consider them still as dehydrins. qRT-PCR expression analysis show a significant induction of these dehydrins during a severe and prolonged drought stress. By in silico analysis we confirmed the presence of these dehydrins in other Pinaceae species, breaking the convention regarding the compulsory presence of K-segments in these proteins. The way of action of these unusual dehydrins remains unrevealed.

  14. Architecture and permeability of post-cytokinesis plasmodesmata lacking cytoplasmic sleeves.

    Science.gov (United States)

    Nicolas, William J; Grison, Magali S; Trépout, Sylvain; Gaston, Amélia; Fouché, Mathieu; Cordelières, Fabrice P; Oparka, Karl; Tilsner, Jens; Brocard, Lysiane; Bayer, Emmanuelle M

    2017-06-12

    Plasmodesmata are remarkable cellular machines responsible for the controlled exchange of proteins, small RNAs and signalling molecules between cells. They are lined by the plasma membrane (PM), contain a strand of tubular endoplasmic reticulum (ER), and the space between these two membranes is thought to control plasmodesmata permeability. Here, we have reconstructed plasmodesmata three-dimensional (3D) ultrastructure with an unprecedented level of 3D information using electron tomography. We show that within plasmodesmata, ER-PM contact sites undergo substantial remodelling events during cell differentiation. Instead of being open pores, post-cytokinesis plasmodesmata present such intimate ER-PM contact along the entire length of the pores that no intermembrane gap is visible. Later on, during cell expansion, the plasmodesmata pore widens and the two membranes separate, leaving a cytosolic sleeve spanned by tethers whose presence correlates with the appearance of the intermembrane gap. Surprisingly, the post-cytokinesis plasmodesmata allow diffusion of macromolecules despite the apparent lack of an open cytoplasmic sleeve, forcing the reassessment of the mechanisms that control plant cell-cell communication.

  15. Lack of the Lysosomal Membrane Protein, GLMP, in Mice Results in Metabolic Dysregulation in Liver.

    Directory of Open Access Journals (Sweden)

    Xiang Yi Kong

    Full Text Available Ablation of glycosylated lysosomal membrane protein (GLMP, formerly known as NCU-G1 has been shown to cause chronic liver injury which progresses into liver fibrosis in mice. Both lysosomal dysfunction and chronic liver injury can cause metabolic dysregulation. Glmp gt/gt mice (formerly known as Ncu-g1gt/gt mice were studied between 3 weeks and 9 months of age. Body weight gain and feed efficiency of Glmp gt/gt mice were comparable to wild type siblings, only at the age of 9 months the Glmp gt/gt siblings had significantly reduced body weight. Reduced size of epididymal fat pads was accompanied by hepatosplenomegaly in Glmp gt/gt mice. Blood analysis revealed reduced levels of blood glucose, circulating triacylglycerol and non-esterified fatty acids in Glmp gt/gt mice. Increased flux of glucose, increased de novo lipogenesis and lipid accumulation were detected in Glmp gt/gt primary hepatocytes, as well as elevated triacylglycerol levels in Glmp gt/gt liver homogenates, compared to hepatocytes and liver from wild type mice. Gene expression analysis showed an increased expression of genes involved in fatty acid uptake and lipogenesis in Glmp gt/gt liver compared to wild type. Our findings are in agreement with the metabolic alterations observed in other mouse models lacking lysosomal proteins, and with alterations characteristic for advanced chronic liver injury.

  16. Conflicts of Interest in Clinical Guidelines: Lack of Authors and Disclosures in the AAOMS White Papers.

    Science.gov (United States)

    Ji, Yisi D; Lahey, Edward T

    2018-03-02

    The purpose of this study was to evaluate current state of authorship, financial disclosures, and conflicts of interest in position papers published by the American Association of Oral and Maxillofacial Surgeons (AAOMS). This is a cross-sectional review of the position papers published by the AAOMS from 2013 to 2017. Primary outcome variables include position papers published by the AAOMS. Secondary outcome variables include declaration of authorship, financial disclosures, and financial payments. The Open Payments Database for financial disclosures was reviewed for the year the position paper was published and the immediate preceding year. Ten position papers were published by the AAOMS from 2013 to 2017. Of the 10 papers, authorship was listed in 3, and none explicitly addressed the presence or absence of financial disclosures or conflicts of interest. Contributors to 3 of the 3 authored papers were found at review of the Open Payments Database to have received industry funding in the year the position paper was published and the immediate preceding year. The remuneration ranged from less than $1,000 to $554,006.02. Position papers published by the AAOMS lack standardization for authorship and statements on potential financial disclosure. The authors suggest full disclosures of authorship and authors' conflicts of interest should be stated on all position papers to provide transparency to the process. Copyright © 2018 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  17. Lack of a Functioning P2X7 Receptor Leads to Increased Susceptibility to Toxoplasmic Ileitis.

    Directory of Open Access Journals (Sweden)

    Catherine M Miller

    Full Text Available Oral infection of C57BL/6J mice with the protozoan parasite Toxoplasma gondii leads to a lethal inflammatory ileitis.Mice lacking the purinergic receptor P2X7R are acutely susceptible to toxoplasmic ileitis, losing significantly more weight than C57BL/6J mice and exhibiting much greater intestinal inflammatory pathology in response to infection with only 10 cysts of T. gondii. This susceptibility is not dependent on the ability of P2X7R-deficient mice to control the parasite, which they accomplish just as efficiently as C57BL/6J mice. Rather, susceptibility is associated with elevated ileal concentrations of pro-inflammatory cytokines, reactive nitrogen intermediates and altered regulation of elements of NFκB activation in P2X7R-deficient mice.Our data support the thesis that P2X7R, a well-documented activator of pro-inflammatory cytokine production, also plays an important role in the regulation of intestinal inflammation.

  18. Chronic Diseases, Lack of Medications, and Depression Among Syrian Refugees in Jordan, 2013–2014

    Science.gov (United States)

    Al-Smadi, Ahmed Mohammad; Tawalbeh, Loai Issa; Khoury, Laurice Sami

    2015-01-01

    Introduction Studying mental and physical health problems in refugees facilitates providing suitable health care, thus improving their quality of life. We studied depression tendency in Syrian refugees in Jordan in the light of chronic diseases and medication availability. Also, depression prevalence and depression comorbidity with chronic diseases were identified. Methods In this multicenter cross-sectional survey, data from Syrian refugees attending Caritas centers in 6 Jordanian cities from November 2013 through June 2014 were analyzed. Participants’ demographics, depression, previously diagnosed chronic diseases, and newly diagnosed chronic diseases and the availability of medications were studied. Logistic regression was used to examine predictors for depression. Results Of 765 refugees who participated, about one-third demonstrated significant depression as measured by the Beck Depression Inventory. Descriptive analyses showed that depression was comorbid in 35% of participants with previously diagnosed chronic diseases and in 40% of participants with newly diagnosed chronic diseases. Newly diagnosed chronic diseases and lack of medications significantly contributed to depression, but the regression model as a whole explained less than 5% of the variance. Conclusion Because the regression model showed low effect size, we concluded that newly diagnosed chronic diseases and medication shortages could not predict depression in Syrian refugees residing in Jordan. Therefore, further studies of additional factors are recommended. Prompt measures have to be taken to prevent the spread of chronic diseases and improve mental health in this fragile population. PMID:25633485

  19. Chronic diseases, lack of medications, and depression among Syrian refugees in Jordan, 2013-2014.

    Science.gov (United States)

    Gammouh, Omar Salem; Al-Smadi, Ahmed Mohammad; Tawalbeh, Loai Issa; Khoury, Laurice Sami

    2015-01-29

    Studying mental and physical health problems in refugees facilitates providing suitable health care, thus improving their quality of life. We studied depression tendency in Syrian refugees in Jordan in the light of chronic diseases and medication availability. Also, depression prevalence and depression comorbidity with chronic diseases were identified. In this multicenter cross-sectional survey, data from Syrian refugees attending Caritas centers in 6 Jordanian cities from November 2013 through June 2014 were analyzed. Participants' demographics, depression, previously diagnosed chronic diseases, and newly diagnosed chronic diseases and the availability of medications were studied. Logistic regression was used to examine predictors for depression. Of 765 refugees who participated, about one-third demonstrated significant depression as measured by the Beck Depression Inventory. Descriptive analyses showed that depression was comorbid in 35% of participants with previously diagnosed chronic diseases and in 40% of participants with newly diagnosed chronic diseases. Newly diagnosed chronic diseases and lack of medications significantly contributed to depression, but the regression model as a whole explained less than 5% of the variance. Because the regression model showed low effect size, we concluded that newly diagnosed chronic diseases and medication shortages could not predict depression in Syrian refugees residing in Jordan. Therefore, further studies of additional factors are recommended. Prompt measures have to be taken to prevent the spread of chronic diseases and improve mental health in this fragile population.

  20. Innate immune restriction and antagonism of viral RNA lacking 2'-O methylation

    Energy Technology Data Exchange (ETDEWEB)

    Hyde, Jennifer L. [Departments of Medicine, Washington University School of Medicine, St Louis., MO 63110 (United States); Diamond, Michael S., E-mail: diamond@borcim.wustl.edu [Departments of Medicine, Washington University School of Medicine, St Louis., MO 63110 (United States); Molecular Microbiology, Washington University School of Medicine, St Louis., MO 63110 (United States); Pathology & Immunology, Washington University School of Medicine, St Louis., MO 63110 (United States); The Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis., MO 63110 (United States)

    2015-05-15

    N-7 and 2′-O methylation of host cell mRNA occurs in the nucleus and results in the generation of cap structures (cap 0, m{sup 7}GpppN; cap 1, m{sup 7}GpppNm) that control gene expression by modulating nuclear export, splicing, turnover, and protein synthesis. Remarkably, RNA cap modification also contributes to mammalian cell host defense as viral RNA lacking 2′-O methylation is sensed and inhibited by IFIT1, an interferon (IFN) stimulated gene (ISG). Accordingly, pathogenic viruses that replicate in the cytoplasm have evolved mechanisms to circumvent IFIT1 restriction and facilitate infection of mammalian cells. These include: (a) generating cap 1 structures on their RNA through cap-snatching or virally-encoded 2′-O methyltransferases, (b) using cap-independent means of translation, or (c) using RNA secondary structural motifs to antagonize IFIT1 binding. This review will discuss new insights as to how specific modifications at the 5′-end of viral RNA modulate host pathogen recognition responses to promote infection and disease.

  1. Lack of resistance development in Bemisia tabaci to Isaria fumosorosea after multiple generations of selection

    Science.gov (United States)

    Gao, Tianni; Wang, Zhaolei; Huang, Yü; Keyhani, Nemat O.; Huang, Zhen

    2017-02-01

    The emergence of insecticide resistant insect pests is of significant concern worldwide. The whitefly, Bemisia tabaci, is an important agricultural pest and has shown incredible resilience developing resistance to a number of chemical pesticides. Entomopathogenic fungi such as Isaria fumosorosea offer an attractive alternative to chemical pesticides for insect control, and this fungus has been shown to be an effective pathogen of B. tabaci. Little is known concerning the potential for the development of resistance to I. fumosorosea by B. tabaci. Five generations of successive survivors of B. tabaci infected by I. fumosorosea were assayed with I. fumosorosea. No significant differences in susceptibility to I. fumosorosea, number of ovarioles, or ovipostioning were seen between any of the generations tested. Effects of I. fumosorosea and cell-free ethyl acetate fractions derived from the fungus on the B. tabaci fat body, ovary, and vitellogenin were also investigated. These data revealed significant deformation and degradation of ovary tissues and associated vitellogenin by the fungal mycelium as well as by cell-free ethyl acetate fungal extracts. These data indicate the lack of the emergence of resistance to I. fumosorosea under the conditions tested and demonstrate invasion of the insect reproductive tissues during fungal infection.

  2. Defective chemokine signal integration in leukocytes lacking activator of G protein signaling 3 (AGS3).

    Science.gov (United States)

    Branham-O'Connor, Melissa; Robichaux, William G; Zhang, Xian-Kui; Cho, Hyeseon; Kehrl, John H; Lanier, Stephen M; Blumer, Joe B

    2014-04-11

    Activator of G-protein signaling 3 (AGS3, gene name G-protein signaling modulator-1, Gpsm1), an accessory protein for G-protein signaling, has functional roles in the kidney and CNS. Here we show that AGS3 is expressed in spleen, thymus, and bone marrow-derived dendritic cells, and is up-regulated upon leukocyte activation. We explored the role of AGS3 in immune cell function by characterizing chemokine receptor signaling in leukocytes from mice lacking AGS3. No obvious differences in lymphocyte subsets were observed. Interestingly, however, AGS3-null B and T lymphocytes and bone marrow-derived dendritic cells exhibited significant chemotactic defects as well as reductions in chemokine-stimulated calcium mobilization and altered ERK and Akt activation. These studies indicate a role for AGS3 in the regulation of G-protein signaling in the immune system, providing unexpected venues for the potential development of therapeutic agents that modulate immune function by targeting these regulatory mechanisms.

  3. The effects of the lack, excess and strangeness in the discourses about the Portuguese language

    Directory of Open Access Journals (Sweden)

    Rosely Diniz da Silva Machado

    2017-11-01

    Full Text Available In this research based on the studies of the Discourse Analysis, we propose to analyze how students from a Language and Literature Course of Universidade Federal do Rio Grande (FURG move their discourses over the Portuguese language. The corpus has been collected for nine years, always on the first day of class, when they were invited to write about why they chose to study Language and Literature in the University. Through this theme, the ideological issue, the power relations, and the senses effect present therein are observed by triggering three key concepts studied by Ernst (2011: the lack, the excess and the strangeness. Therefore, from the marks left in the discourses of those university students as well as from their identifications with certain discourse formations, gestures of interpretation are mobilized. Such will allow us to analyze the ways of saying and not-saying about/in the language and, ultimately, how the sense effects in those specific discourses are produced.

  4. Excess, lack and strangeness in the self-regulation discourse by CONAR

    Directory of Open Access Journals (Sweden)

    Renata Silveira da Silva

    2017-11-01

    Full Text Available The Advertising Self-Regulation Council (Conselho de Autorregulamentação Publicitária - CONAR released, in 2014, an advertising campaign which drew criticism. Amid the materiality that expressed this discontentment there was a letter addressed to CONAR, which was signed by the Consumer Protection Institute (Instituto de Defesa do Consumidor - IDEC and thirty more organizations. This letter requested the campaign discontinuation in which CONAR had allegedly assigned itself an excessive power in evaluating ethics in Brazilian advertisement. Moreover, according to the letter, CONAR had also mocked social groups’ struggles.  Based on this event, this research proposes, based on Michel Pêcheux’s Discourse Analysis theories, a reflection on how the advertising self-regulation works. The discursive corpus is composed by scenes from two audiovisual advertisements called “Clown” and “Bean Stew”, and by excerpts of the aforementioned letter. This paper uses, as a theoretical and methodological approach, the concepts of saturated and gap memory (COURTINE, 1999 and connects them to the analytical procedures proposed by Ernst (2009, concerning excess, lack and strangeness.

  5. Novel dehydrins lacking complete K-segments in Pinaceae. The exception rather than the rule

    Science.gov (United States)

    Perdiguero, Pedro; Collada, Carmen; Soto, Álvaro

    2014-01-01

    Dehydrins are thought to play an essential role in the plant response, acclimation and tolerance to different abiotic stresses, such as cold and drought. These proteins contain conserved and repeated segments in their amino acid sequence, used for their classification. Thus, dehydrins from angiosperms present different repetitions of the segments Y, S, and K, while gymnosperm dehydrins show A, E, S, and K segments. The only fragment present in all the dehydrins described to date is the K-segment. Different works suggest the K-segment is involved in key protective functions during dehydration stress, mainly stabilizing membranes. In this work, we describe for the first time two Pinus pinaster proteins with truncated K-segments and a third one completely lacking K-segments, but whose sequence homology leads us to consider them still as dehydrins. qRT-PCR expression analysis show a significant induction of these dehydrins during a severe and prolonged drought stress. By in silico analysis we confirmed the presence of these dehydrins in other Pinaceae species, breaking the convention regarding the compulsory presence of K-segments in these proteins. The way of action of these unusual dehydrins remains unrevealed. PMID:25520734

  6. Is lack of sexual assertiveness among adolescent and young adult women a cause for concern?

    Science.gov (United States)

    Rickert, Vaughn I; Sanghvi, Rupal; Wiemann, Constance M

    2002-01-01

    Understanding young women's sexual assertiveness is critical to developing effective interventions to promote sexual health and reduce sexual risk-taking and violence. Young women's perception of their sexual rights may vary according to demographic characteristics, sexual health behaviors and victimization history. Data were collected from 904 sexually active 14-26-year-old clients of two family planning clinics in Texas, reflecting their perceptions of their right to communicate expectations about or control aspects of their sexual encounters. Logistic regression analysis was used to assess which characteristics were independently associated with believing that one never has each specified sexual right. Almost 2096 of women believed that they never have the right to make their own decisions about contraception, regardless of their partner's wishes; to tell their partner that they do not want to have intercourse without birth control, that they want to make love differently or that their partner is being too rough; and to stop foreplay at any time, including at the point of intercourse. Poor grades in school, sexual inexperience, inconsistent contraceptive use and minority ethnicity were independently associated with lacking sexual assertiveness. Many sexually active young women perceive that they do not have the right to communicate about or control aspects of their sexual behavior. Interventions to prevent sexually transmitted diseases, unwanted pregnancy and coercive sexual behaviors should include strategies to evaluate and address these perceptions.

  7. Plants lacking the main light-harvesting complex retain photosystem II macro-organization.

    Science.gov (United States)

    Ruban, A V; Wentworth, M; Yakushevska, A E; Andersson, J; Lee, P J; Keegstra, W; Dekker, J P; Boekema, E J; Jansson, S; Horton, P

    2003-02-06

    Photosystem II (PSII) is a key component of photosynthesis, the process of converting sunlight into the chemical energy of life. In plant cells, it forms a unique oligomeric macrostructure in membranes of the chloroplasts. Several light-harvesting antenna complexes are organized precisely in the PSII macrostructure-the major trimeric complexes (LHCII) that bind 70% of PSII chlorophyll and three minor monomeric complexes-which together form PSII supercomplexes. The antenna complexes are essential for collecting sunlight and regulating photosynthesis, but the relationship between these functions and their molecular architecture is unresolved. Here we report that antisense Arabidopsis plants lacking the proteins that form LHCII trimers have PSII supercomplexes with almost identical abundance and structure to those found in wild-type plants. The place of LHCII is taken by a normally minor and monomeric complex, CP26, which is synthesized in large amounts and organized into trimers. Trimerization is clearly not a specific attribute of LHCII. Our results highlight the importance of the PSII macrostructure: in the absence of one of its main components, another protein is recruited to allow it to assemble and function.

  8. Lack of collagen VI promotes neurodegeneration by impairing autophagy and inducing apoptosis during aging.

    Science.gov (United States)

    Cescon, Matilde; Chen, Peiwen; Castagnaro, Silvia; Gregorio, Ilaria; Bonaldo, Paolo

    2016-05-01

    Collagen VI is an extracellular matrix (ECM) protein with a broad distribution in different tissues and mostly deposited at the close periphery of the cell surface. Previous studies revealed that collagen VI protects neurons from the toxicity of amyloid-βpeptides and from UV-induced damage. However, the physiological role of this protein in the central nervous system (CNS) remains unknown. Here, we established primary neural cultures from murine cortex and hippocampus, and carried out in vitro and in vivo studies in wild-type and collagen VI null (Col6a1-/-) mice. Col6a1-/- neural cultures displayed an increased incidence of spontaneous apoptosis and higher vulnerability to oxidative stress, accompanied by altered regulation of autophagy with increased p62 protein levels and decreased LC3 lipidation. Analysis of brain sections confirmed increased apoptosis and abnormal regulation of autophagy in the CNS of collagen VI-deficient animals. To investigate the in vivo physiological consequences of these CNS defects, we carried out functional studies and found that motor and memory task performances were impaired in aged Col6a1-/-mice. These findings indicate that lack of collagen VI leads to spontaneous apoptosis and defective autophagy in neural cells, and point at a protective role for this ECM protein in the CNS during physiological aging.

  9. [Lack of association between LDL-cholesterol and carotid intima-media thickness in elderly women].

    Science.gov (United States)

    Mazza, Elisa; Salvati, Maria Antonietta; Ferro, Yvelise; De Bonis, Daniele; Gorgone, Gaetano

    2017-11-01

    It is known that the association between LDL-cholesterol (LDL-C) and cardiovascular morbidity and mortality in the elderly is controversial. The aim of this study was to investigate this issue using carotid intima-media thickness as a marker of cardiovascular disease. Women aged 35-79 years were consecutively enrolled in the study. They underwent a questionnaire to assess cardiovascular disease, a clinical examination to assess blood pressure and anthropometric variables, a biochemical evaluation of lipid profile and glucose, and an ultrasound evaluation of carotid arteries. The study population was divided into two age groups (≤65 years and >65 years), and each group was then divided into two subgroups according to LDL-C level (normal and high). A Student's t-test was used to compare mean values between groups, and a chi square test was used to compare the prevalence of carotid atherosclerosis. A lack of association between LDL-C and carotid intima-media thickness was observed in subjects aged >65 years, with the intima-media thickness average being similar between those with and without high LDL-C. Conversely, a significant difference in carotid intima-media thickness was observed among adults with and without high LDL-C level. Our findings, similar to those obtained in other epidemiological studies, provide the rationale for revising the use of statins in elderly women without cardiovascular disease.

  10. A Lack of Systemic Absorption Following the Repeated Application of Topical Quetiapine in Healthy Adults.

    Science.gov (United States)

    Kayhart, Bryce; Lapid, Maria I; Nelson, Sarah; Cunningham, Julie L; Thompson, Virginia H; Leung, Jonathan G

    2018-01-01

    In the absence of suitable oral or intravenous access for medication administration and when the intramuscular medications are undesirable, alternative routes for drug delivery may be considered. Antipsychotics administered via an inhaled, intranasal, rectal, or topical route have been described in the literature. Topically administered antipsychotics have been previously reported to produce negligible systemic absorption despite being used in clinical practice for nausea and behavioral symptoms associated with dementia. Additionally, the American Academy of Hospice and Palliative Medicine recommends against the use of topical medications that lack supporting literature. Three studies have assessed the systemic absorption of different antipsychotics after administration of only a single, topically applied dose. To evaluate whether the repeated administration of a topically applied antipsychotic may result in detectable serum levels in an accumulating fashion, a pharmacokinetic study was conducted. Five healthy, adult participants consented to receive extemporaneously prepared topical quetiapine in Lipoderm every 4 hours for a total of 5 doses. Blood samples were drawn at baseline and hours 2, 4, 8, 12, 16, and 24, and serum quetiapine concentrations were measured using high-performance liquid chromatography. Quetiapine was undetectable in every sample from 3 participants. Two participants had minimally detectable serum quetiapine levels no sooner than hour 12 of the study period. Extemporaneously prepared quetiapine in Lipoderm resulted in nonexistent or minimal serum level following repeated topical administration. The use of topically applied quetiapine should still be questioned.

  11. Lack of strategy holding: a new pattern of learning deficit in cortical dementias.

    Science.gov (United States)

    Benedet, María J; Lauro-Grotto, Rosapia; Giotti, Chiara

    2009-09-01

    The aim of this study was to demonstrate, by means of systematic research and qualitative data analysis, the presence, among a group of patients with fronto-temporal lobar degeneration of a subgroup that, at variance with the standard pattern, is able to devise and implement learning strategies, but appear impaired at carrying them on from a trial to the next. In order to provide evidence of the existence of a group of patients showing this type of learning disability, that we refer to as lack of strategy holding, we performed a stepwise hierarchical cluster analysis of a set of variables whose scores were selected from the subject's performance at the Test de Aprendizaje Verbal España-Complutense. Results substantiate the segregation of three groups of subjects characterized by the following patterns of performance: normal elderly individuals, who show a quite preserved ability to discover a semantic strategy along the learning trials and to carry it from a trial to the next, patients presenting with a deficit in implementing semantic learning strategies and possibly use of serial and/or phonological strategies to perform the task, and to patients who, although able to generate and implement appropriate learning strategies, appear unable to carry them over the learning trials. The presence of this new pattern raises a few questions that seem worth trying to address.

  12. Mice lacking cyclin-dependent kinase-like 5 manifest autistic and ADHD-like behaviors.

    Science.gov (United States)

    Jhang, Cian-Ling; Huang, Tzyy-Nan; Hsueh, Yi-Ping; Liao, Wenlin

    2017-10-15

    Neurodevelopmental disorders frequently share common clinical features and appear high rate of comorbidity, such as those present in patients with attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). While characterizing behavioral phenotypes in the mouse model of cyclin-dependent kinase-like 5 (CDKL5) disorder, a neurodevelopmental disorder caused by mutations in the X-linked gene encoding CDKL5, we found that these mice manifested behavioral phenotypes mimicking multiple key features of ASD, such as impaired social interaction and communication, as well as increased stereotypic digging behaviors. These mice also displayed hyper-locomotion, increased aggressiveness and impulsivity, plus deficits in motor and associative learning, resembling primary symptoms of ADHD. Through brain region-specific biochemical analysis, we uncovered that loss of CDKL5 disrupts dopamine synthesis and the expression of social communication-related key genes, such as forkhead-box P2 and mu-opioid receptor, in the corticostriatal circuit. Together, our findings support that CDKL5 plays a role in the comorbid features of autism and ADHD, and mice lacking CDKL5 may serve as an animal model to study the molecular and circuit mechanisms underlying autism-ADHD comorbidity. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Evidence for dynamic network regulation of Drosophila photoreceptor function from mutants lacking the neurotransmitter histamine

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    An eDau

    2016-03-01

    Full Text Available Synaptic feedback from interneurons to photoreceptors can help to optimize visual information flow by balancing its allocation on retinal pathways under changing light conditions. But little is known about how this critical network operation is regulated dynamically. Here, we investigate this question by comparing signaling properties and performance of wild-type Drosophila R1-R6 photoreceptors to those of the hdcJK910 mutant, which lacks the neurotransmitter histamine and therefore cannot transmit information to interneurons. Recordings show that hdcJK910 photoreceptors sample similar amounts of information from naturalistic stimulation to wild-type photoreceptors, but this information is packaged in smaller responses, especially under bright illumination. Analyses reveal how these altered dynamics primarily resulted from network overload that affected hdcJK910 photoreceptors in two ways. First, the missing inhibitory histamine input to interneurons almost certainly depolarized them irrevocably, which in turn increased their excitatory feedback to hdcJK910 R1-R6s. This tonic excitation depolarized the photoreceptors to artificially high potentials, reducing their operational range. Second, rescuing histamine input to interneurons in hdcJK910 mutant also restored their normal phasic feedback modulation to R1-R6s, causing photoreceptor output to accentuate dynamic intensity differences at bright illumination, similar to the wild-type. These results provide mechanistic explanations of how synaptic feedback connections optimize information packaging in photoreceptor output and novel insight into the operation and design of dynamic network regulation of sensory neurons.

  14. Lack of LTP-like plasticity in primary motor cortex in Parkinson's disease.

    Science.gov (United States)

    Suppa, A; Marsili, L; Belvisi, D; Conte, A; Iezzi, E; Modugno, N; Fabbrini, G; Berardelli, A

    2011-02-01

    In this study in patients with Parkinson's disease (PD), off and on dopaminergic therapy, with and without L-dopa-induced dyskinesias (LIDs), we tested intermittent theta-burst stimulation (iTBS), a technique currently used for non-invasively inducing long-term potentiation (LTP)-like plasticity in primary motor cortex (M1). The study group comprised 20 PD patients on and off dopaminergic therapy (11 patients without and 9 patients with LIDs), and 14 age-matched healthy subjects. Patients had mild-to-moderate PD, and no additional neuropsychiatric disorders. We clinically evaluated patients using the Unified Parkinson's Disease Rating Scale (UPDRS) and the Unified Dyskinesia Rating Scale (UDysRS). The left M1 was conditioned with iTBS at 80% active motor threshold intensity. Twenty motor evoked potentials (MEPs) were recorded from right first interosseous muscle before and at 5, 15 and 30 min after iTBS. Between-group analysis of variance (ANOVA) testing healthy subjects versus patients with and without LIDs, on and off therapy showed a significant interaction between factors "Group" and "Time". After iTBS, MEP amplitudes in healthy subjects increased significantly at 5, 15 and 30 min (piTBS fails to increase MEP responses. This finding suggests lack of iTBS-induced LTP-like plasticity in M1 in PD regardless of patients' clinical features. Copyright © 2010 Elsevier Inc. All rights reserved.

  15. Early signs of pathological cognitive aging in mice lacking high-affinity nicotinic receptors.

    Directory of Open Access Journals (Sweden)

    Eleni eKonsolaki

    2016-04-01

    Full Text Available In order to address pathological cognitive decline effectively, it is critical to adopt early preventive measures in individuals considered at risk. It is therefore essential to develop approaches that identify such individuals before the onset of irreversible dementia. Α deficient cholinergic system has been consistently implicated as one of the main factors associated with a heightened vulnerability to the aging process. In the present study we used mice lacking high affinity nicotinic receptors (β2-/-, which have been proposed as an animal model of accelerated/premature cognitive aging. Our aim was to identify behavioural signs that could serve as indicators or predictors of impending cognitive decline. We used test batteries in order to assess cognitive functions and additional tasks to investigate spontaneous behaviours, such as species-specific activities and exploration/locomotion in a novel environment. Our data confirm and extend the hypothesis that β2-/- animals exhibit age-related cognitive impairments, manifested in both spatial learning and recognition memory tasks. In addition, we reveal deficits in spontaneous behaviour and habituation processes earlier in life. To our knowledge, this is the first study to perform an extensive behavioural examination of an animal model of premature cognitive aging, and our results suggest that β2-nAChR dependent cognitive deterioration progressively evolves from initial subtle behavioural changes to global dementia due to the combined effect of the neuropathology and aging.

  16. Lack of gender effects on gray matter volumes in adolescent generalized anxiety disorder.

    Science.gov (United States)

    Liao, Mei; Yang, Fan; Zhang, Yan; He, Zhong; Su, Linyan; Li, Lingjiang

    2014-02-01

    Previous epidemiological and clinical studies have reported gender differences in prevalence and clinical features of generalized anxiety disorder (GAD). Such gender differences in clinical phenomenology suggest that the underlying neural circuitry of GAD could also be different in males and females. This study aimed to explore the possible gender effect on gray matter volumes in adolescents with GAD. Twenty-six adolescent GAD patients and 25 healthy controls participated and underwent high-resolution structural magnetic resonance scans. Voxel-based morphometry (VBM) was used to investigate gray matter alterations. Our study revealed a significant diagnosis main effect in the right putamen, with larger gray matter volumes in GAD patients compared to healthy controls, and a significant gender main effect in the left precuneus/posterior cingulate cortex, with larger gray matter volumes in males compared to females. No gender-by-diagnosis interaction effect was found in this study. The relatively small sample size in this study might result in a lack of power to demonstrate gender effects on brain structure in GAD. The results suggested that there are differences in gray matter volumes between males and females, but gray matter volumes in GAD are not influenced by gender. © 2013 Published by Elsevier B.V.

  17. Regional Development and Decentralization – two Options to Overcome Lack of Funding

    Directory of Open Access Journals (Sweden)

    Dubravka JURLINA ALIBEGOVIC

    2014-11-01

    Full Text Available Decentralization can be generally described as a process in which selected functions are assigned to sub-national units. The literature identifies a number of positive consequences of decentralization which all lead to a better satisfaction of citizens’ needs for public services. Although the decentralization process in Croatia started more than ten years ago, it has not yet been completed. While leading to a new allocation of authorities and responsibilities to local government units, the level of fiscal decentralization remained lower than in the EU countries.In this paper we analyze the fiscal capacity of local government units to provide an insight into the main problems of decentralization in Croatia. We show that most local government units have very low fiscal capacity, which is insufficient for financing basic public functions with their own resources. The paper presents the results of a survey relating to the decentralization process conducted among local councilors at the regional level in Croatia. We explore how local councilors at the regional level evaluate different goals of decentralization. With the lack of fiscal capacity in mind, we identify two possible solutions for an optimal provision of public functions. The first one is the level of political will for a joint provision of public functions by different local units, and the second one is a change in the territorial organization of the country. We measure the difference in the attitudes toward these questions across counties.

  18. Cells bearing chromosome aberrations lacking one telomere are selectively blocked at the G2/M checkpoint

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez, Pilar [Unitat de Biologia Cel.lular, Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Bellaterra (Spain); Barquinero, Joan Francesc [Unitat d' Antropologia Biologica, Departament de Biologia Animal, Biologia Vegetal i Ecologia, Universitat Autonoma de Barcelona, 08193 Bellaterra (Spain); Duran, Assumpta [Unitat de Biologia Cel.lular, Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Bellaterra (Spain); Caballin, Maria Rosa [Unitat d' Antropologia Biologica, Departament de Biologia Animal, Biologia Vegetal i Ecologia, Universitat Autonoma de Barcelona, 08193 Bellaterra (Spain); Ribas, Montserrat [Servei de Radiofisica i Radioproteccio de l' Hospital de la Santa Creu i Sant Pau, 08025 Barcelona (Spain); Barrios, Leonardo, E-mail: Lleonard.Barrios@uab.cat [Unitat de Biologia Cel.lular, Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Bellaterra (Spain)

    2009-11-02

    Cell cycle checkpoints are part of the cellular mechanisms to maintain genomic integrity. After ionizing radiation exposure, the cells can show delay or arrest in their progression through the cell cycle, as well as an activation of the DNA repair machinery in order to reduce the damage. The G2/M checkpoint prevents G2 cells entering mitosis until the DNA damage has been reduced. The present study evaluates which G0 radiation-induced chromosome aberrations are negatively selected in the G2/M checkpoint. For this purpose, peripheral blood samples were irradiated at 1 and 3 Gy of {gamma}-rays, and lymphocytes were cultured for 48 h. Calyculin-A and Colcemid were used to analyze, in the same slide, cells in G2 and M. Chromosome spreads were consecutively analyzed by solid stain, pancentromeric and pantelomeric FISH and mFISH. The results show that the frequency of incomplete chromosome elements, those lacking a telomeric signal at one end, decreases abruptly from G2 to M. This indicates that cells with incomplete chromosome elements can progress from G0 to G2, but at the G2/M checkpoint suffer a strong negative selection.

  19. Cells bearing chromosome aberrations lacking one telomere are selectively blocked at the G2/M checkpoint

    International Nuclear Information System (INIS)

    Rodriguez, Pilar; Barquinero, Joan Francesc; Duran, Assumpta; Caballin, Maria Rosa; Ribas, Montserrat; Barrios, Leonardo

    2009-01-01

    Cell cycle checkpoints are part of the cellular mechanisms to maintain genomic integrity. After ionizing radiation exposure, the cells can show delay or arrest in their progression through the cell cycle, as well as an activation of the DNA repair machinery in order to reduce the damage. The G2/M checkpoint prevents G2 cells entering mitosis until the DNA damage has been reduced. The present study evaluates which G0 radiation-induced chromosome aberrations are negatively selected in the G2/M checkpoint. For this purpose, peripheral blood samples were irradiated at 1 and 3 Gy of γ-rays, and lymphocytes were cultured for 48 h. Calyculin-A and Colcemid were used to analyze, in the same slide, cells in G2 and M. Chromosome spreads were consecutively analyzed by solid stain, pancentromeric and pantelomeric FISH and mFISH. The results show that the frequency of incomplete chromosome elements, those lacking a telomeric signal at one end, decreases abruptly from G2 to M. This indicates that cells with incomplete chromosome elements can progress from G0 to G2, but at the G2/M checkpoint suffer a strong negative selection.

  20. Public opinion towards castration without anaesthesia and lack of access to pasture in beef cattle production.

    Science.gov (United States)

    Lemos Teixeira, Dayane; Larraín, Rafael; Melo, Oscar; Hötzel, María José

    2018-01-01

    Recent publications have shown that citizens in developing nations are gaining interest in farm animal welfare. The aims of this study were to assess the opinion of Chilean citizens about surgical castration without anaesthesia and lack of access to pasture in beef cattle production, to investigate how involvement in livestock production influences opinions, and to evaluate if different types of information would affect their opinion towards these management practices. The study was carried out in the Metropolitan Region of Santiago, Chile, and consisted of two surveys with 400 participants in each study. The first one used an online, self-administered questionnaire and the second one used a face to face questionnaire. The second questionnaire had four information treatments assigned randomly to survey participants (no information; negative information; negative and positive information; positive information). Most participants were aware that the two management practices are common in beef production systems and were opposed to them. Involvement in animal production was associated with greater acceptance of both management practices and participants that had visited a beef production farm before the study were more likely to support castration without anaesthesia in Survey 1. Belonging to any socioeconomic group and providing negative or positive information had no impact on participants' opinion. The results show a disconnection between the views of participants recruited for this study and beef production systems that do not provide pain control for male cattle surgical castration or provide little or no access to pasture.

  1. The brain functional connectome is robustly altered by lack of sleep.

    Science.gov (United States)

    Kaufmann, Tobias; Elvsåshagen, Torbjørn; Alnæs, Dag; Zak, Nathalia; Pedersen, Per Ø; Norbom, Linn B; Quraishi, Sophia H; Tagliazucchi, Enzo; Laufs, Helmut; Bjørnerud, Atle; Malt, Ulrik F; Andreassen, Ole A; Roussos, Evangelos; Duff, Eugene P; Smith, Stephen M; Groote, Inge R; Westlye, Lars T

    2016-02-15

    Sleep is a universal phenomenon necessary for maintaining homeostasis and function across a range of organs. Lack of sleep has severe health-related consequences affecting whole-body functioning, yet no other organ is as severely affected as the brain. The neurophysiological mechanisms underlying these deficits are poorly understood. Here, we characterize the dynamic changes in brain connectivity profiles inflicted by sleep deprivation and how they deviate from regular daily variability. To this end, we obtained functional magnetic resonance imaging data from 60 young, adult male participants, scanned in the morning and evening of the same day and again the following morning. 41 participants underwent total sleep deprivation before the third scan, whereas the remainder had another night of regular sleep. Sleep deprivation strongly altered the connectivity of several resting-state networks, including dorsal attention, default mode, and hippocampal networks. Multivariate classification based on connectivity profiles predicted deprivation state with high accuracy, corroborating the robustness of the findings on an individual level. Finally, correlation analysis suggested that morning-to-evening connectivity changes were reverted by sleep (control group)-a pattern which did not occur after deprivation. We conclude that both, a day of waking and a night of sleep deprivation dynamically alter the brain functional connectome. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. [Replantation of fingertip amputation in lack of availability of intravenous anastomosis].

    Science.gov (United States)

    Wei, Jian-Min; Sun, Jun-Suo; Jiao, Xiao-Hu; Jing, Dou-Xing; He, Wei; Jin, Wen-Kuo; Chen, Shi-Gao

    2012-08-01

    To discuss the replantation of fingertip amputation in lack of availability of intravenous anastomosis. From November 2009 to November 2010, 86 patients (104 fingers) with fingertip amputation were treated with replantatioin, including 64 males and 22 females, with an average age of 26 years ranging from 2 to 64 years. The time from injury to therapy was from 30 min to 12 h, time of broken finger ischemia was from 2.5 to 12 h. Preoperative examination showed no obvious abnormalities. Four different replantation methods were selectively applied to these 104 amputated fingertips of 86 cases: (1) replantation with anastomosis of single or bilateral proper digital artery in 37 fingers; (2) replantation with arteriovenous bypass in 27 fingers; (3) replantation with exclusive anastomosis of digital artery in 24 fingers; (4) replantation with removing the palmar pocket method in 16 fingers. One hundred and two of 104 amputated fingertips were survived. Among these survived fingers,75 cases (92 fingers) were followed-up for 6 to 24 months. According to the assessment standard of Chinese Medical Association of Hand Surgery, the results were excellent in 52 cases, good in 19, poor in 4. It benefits to expand the indications and improve the survival rate of replantation of fingertip amputation with the correct choice of different replantation methods according to the injury situation of the broken fingertip artery after debridement under the microscope.

  3. Lack of diurnal effects on periodic exercise during prolonged cold water immersion.

    Science.gov (United States)

    Doubt, T J; Smith, D J

    1990-03-01

    Diurnal effects on periodic exercise were examined in 8 male divers wearing passive thermal protection during whole body immersions in 5 degrees C water for periods of up to 6 h. Studies were done during the course of 5-day air saturation dives at a depth of 1.61 ATA, with immersions beginning at 1000 h (AM) and 2200 h (PM). During each hour of immersion, leg exercise was done for 3 min each at workloads of 50, 70, and 90 W. Heart rate (HR) at each workload increased uniformly with immersion time, without a change in slope of HR vs. workload. No AM or PM differences occurred. AM resting VO2 increased linearly, and to the same extent as PM, with exposure time. VO2 at 50 W also increased at the same rate as resting values. VO2 at 70 and 90 W were similar for AM and PM and did not vary significantly during the 6-h immersions. Temporal increases in exercise HR may reflect cardiac compensation of diminished plasma volume. Workloads greater than or equal to 70 W generate enough metabolic heat in this specific condition to meet the thermogenic requirement. Lack of diurnal effects on exercise variables may be due to environmental conditions suppressing circadian rhythms.

  4. Remodeling of the Cervix and Parturition in Mice Lacking the Progesterone Receptor B Isoform1

    Science.gov (United States)

    Yellon, Steven M.; Oshiro, Bryan T.; Chhaya, Tejas Y.; Lechuga, Thomas J.; Dias, Rejane M.; Burns, Alexandra E.; Force, Lindsey; Apostolakis, Ede M.

    2011-01-01

    Withdrawal of progestational support for pregnancy is part of the final common pathways for parturition, but the role of nuclear progesterone receptor (PGR) isoforms in this process is not known. To determine if the PGR-B isoform participates in cervical remodeling at term, cervices were obtained from mice lacking PGR-B (PGR-BKO) and from wild-type (WT) controls before or after birth. PGR-BKO mice gave birth to viable pups at the same time as WT controls during the early morning of Day 19 postbreeding. Morphological analyses indicated that by the day before birth, cervices from PGR-BKO and WT mice had increased in size, with fewer cell nuclei/area as well as diminished collagen content and structure, as evidenced by optical density of picrosirius red-stained sections, compared to cervices from nonpregnant mice. Moreover, increased numbers of resident macrophages, but not neutrophils, were found in the prepartum cervix of PGR-BKO compared to nonpregnant mice, parallel to findings in WT mice. These results suggest that PGR-B does not contribute to the growth or degradation of the extracellular matrix or proinflammatory processes associated with recruitment of macrophages in the cervix leading up to birth. Rather, other receptors may contribute to the progesterone-dependent mechanism that promotes remodeling of the cervix during pregnancy and in the proinflammatory process associated with ripening before parturition. PMID:21613631

  5. Lack of protein-tyrosine sulfation disrupts photoreceptor outer segment morphogenesis, retinal function and retinal anatomy.

    Science.gov (United States)

    Sherry, David M; Murray, Anne R; Kanan, Yogita; Arbogast, Kelsey L; Hamilton, Robert A; Fliesler, Steven J; Burns, Marie E; Moore, Kevin L; Al-Ubaidi, Muayyad R

    2010-11-01

    To investigate the role(s) of protein-tyrosine sulfation in the retina, we examined retinal function and structure in mice lacking tyrosylprotein sulfotransferases (TPST) 1 and 2. Tpst double knockout (DKO; Tpst1(-/-) /Tpst2 (-/-) ) retinas had drastically reduced electroretinographic responses, although their photoreceptors exhibited normal responses in single cell recordings. These retinas appeared normal histologically; however, the rod photoreceptors had ultrastructurally abnormal outer segments, with membrane evulsions into the extracellular space, irregular disc membrane spacing and expanded intradiscal space. Photoreceptor synaptic terminals were disorganized in Tpst DKO retinas, but established ultrastructurally normal synapses, as did bipolar and amacrine cells; however, the morphology and organization of neuronal processes in the inner retina were abnormal. These results indicate that protein-tyrosine sulfation is essential for proper outer segment morphogenesis and synaptic function, but is not critical for overall retinal structure or synapse formation, and may serve broader functions in neuronal development and maintenance. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  6. Lack of Melanopsin Is Associated with Extreme Weight Loss in Mice upon Dietary Challenge.

    Directory of Open Access Journals (Sweden)

    Didem Göz Aytürk

    Full Text Available Metabolic disorders have been established as major risk factors for ocular complications and poor vision. However, little is known about the inverse possibility that ocular disease may cause metabolic dysfunction. To test this hypothesis, we assessed the metabolic consequences of a robust dietary challenge in several mouse models suffering from retinal mutations. To this end, mice null for melanopsin (Opn4-/-, the photopigment of intrinsically photosensitive retinal ganglion cells (ipRGCs, were subjected to five weeks of a ketogenic diet. These mice lost significantly more weight than wild-type controls or mice lacking rod and cone photoreceptors (Pde6brd1/rd1. Although ipRGCs are critical for proper circadian entrainment, and circadian misalignment has been implicated in metabolic pathology, we observed no differences in entrainment between Opn4-/- and control mice. Additionally, we observed no differences in any tested metabolic parameter between these mouse strains. Further studies are required to establish the mechanism giving rise to this dramatic phenotype observed in melanopsin-null mice. We conclude that the causality between ocular disease and metabolic disorders merits further investigation due to the popularity of diets that rely on the induction of a ketogenic state. Our study is a first step toward understanding retinal pathology as a potential cause of metabolic dysfunction.

  7. Factors that hinder organ donation: religio-cultural or lack of information and trust.

    Science.gov (United States)

    Tumin, Makmor; Noh, Abdillah; Jajri, Idris; Chong, Chin-Sieng; Manikam, Rishya; Abdullah, Nawi

    2013-06-01

    This paper examines factors that influence Malaysian persons with a tertiary level of education on their willingness to donate organs. A survey was done in the Klang Valley (Kuala Lumpur and its suburbs) at several designated locations. A total of 1420 people were approached, and we focused the sample of 688 respondents with a tertiary level of education. Respondents were given 2 sets of answers: (1) a religio-cultural category and (2) a structural category. They were allowed to choose more than 1 reason. Our findings revealed that only 47.5 percent of respondents declined becoming organ donors. The highest frequency recorded was "I am not convinced that my body part will be used beneficially " (30.1%), followed by "I do not have enough access to information " (29.2%), "I want my body to remain intact after death " (16.9%), and "It is against my religion " (9.9%). Our study revealed that religio-cultural factors are not a prime explanation for the lack of organ donation in the Malaysian case. This study suggests that better procurement methods used by dedicated agencies, as well as better education, could reduce the shortage between organ supply and demand.

  8. Polymorphisms in the selenoprotein S gene: lack of association with autoimmune inflammatory diseases

    Directory of Open Access Journals (Sweden)

    Díaz-Rubio Manuel

    2008-07-01

    Full Text Available Abstract Background Selenoprotein S (SelS protects the functional integrity of the endoplasmic reticulum against the deleterious effects of metabolic stress. SEPS1/SelS polymorphisms have been involved in the increased release of pro-inflammatory cytokines interleukin (IL-1β, tumor necrosis factor (TNF-α and IL-6 in macrophages. We aimed at investigating the role of the SEPS1 variants previously associated with higher plasma levels of these cytokines and of the SEPS1 haplotypes in the susceptibility to develop immune-mediated diseases characterized by an inflammatory component. Results Six polymorphisms distributed through the SEPS1 gene (rs11327127, rs28665122, rs4965814, rs12917258, rs4965373 and rs2101171 were genotyped in more than two thousand patients suffering from type 1 diabetes, rheumatoid arthritis or inflammatory bowel diseases and 550 healthy controls included in the case-control study. Conclusion Lack of association of SEPS1 polymorphisms or haplotypes precludes a major role of this gene increasing predisposition to these inflammatory diseases.

  9. Lack of protection against gentamicin ototoxicity by auditory conditioning with noise

    Directory of Open Access Journals (Sweden)

    Alex Strose

    2014-10-01

    Full Text Available INTRODUCTION: Auditory conditioning consists of the pre-exposure to low levels of a potential harmful agent to protect against a subsequent harmful presentation. OBJECTIVE: To confirm if conditioning with an agent different from the used to cause the trauma can also be effective. METHOD: Experimental study with 17 guinea pigs divided as follows: group Som: exposed to 85 dB broadband noise centered at 4 kHz, 30 minutes a day for 10 consecutive days; group Cont: intramuscular administration of gentamicin 160 mg/kg a day for 10 consecutive days; group Expt: conditioned with noise similarly to group Som and, after each noise presentation, received gentamicin similarly to group Cont. The animals were evaluated by distortion product otoacoustic emissions (DPOAEs, brainstem auditory evoked potentials (BAEPs and scanning electron microscopy. RESULTS: The animals that were conditioned with noise did not show any protective effect compared to the ones that received only the ototoxic gentamicin administration. This lack of protection was observed functionally and morphologically. CONCLUSION: Conditioning with 85 dB broadband noise, 30 min a day for 10 consecutive days does not protect against an ototoxic gentamicin administration of 160 mg/kg a day for 10 consecutive days in the guinea pig.

  10. Adult hematopoietic stem cells lacking Hif-1α self-renew normally

    Science.gov (United States)

    Vukovic, Milica; Sepulveda, Catarina; Subramani, Chithra; Guitart, Amélie V.; Mohr, Jasmine; Allen, Lewis; Panagopoulou, Theano I.; Paris, Jasmin; Lawson, Hannah; Villacreces, Arnaud; Armesilla-Diaz, Alejandro; Gezer, Deniz; Holyoake, Tessa L.; Ratcliffe, Peter J.

    2016-01-01

    The hematopoietic stem cell (HSC) pool is maintained under hypoxic conditions within the bone marrow microenvironment. Cellular responses to hypoxia are largely mediated by the hypoxia-inducible factors, Hif-1 and Hif-2. The oxygen-regulated α subunits of Hif-1 and Hif-2 (namely, Hif-1α and Hif-2α) form dimers with their stably expressed β subunits and control the transcription of downstream hypoxia-responsive genes to facilitate adaptation to low oxygen tension. An initial study concluded that Hif-1α is essential for HSC maintenance, whereby Hif-1α–deficient HSCs lost their ability to self-renew in serial transplantation assays. In another study, we demonstrated that Hif-2α is dispensable for cell-autonomous HSC maintenance, both under steady-state conditions and following transplantation. Given these unexpected findings, we set out to revisit the role of Hif-1α in cell-autonomous HSC functions. Here we demonstrate that inducible acute deletion of Hif-1α has no impact on HSC survival. Notably, unstressed HSCs lacking Hif-1α efficiently self-renew and sustain long-term multilineage hematopoiesis upon serial transplantation. Finally, Hif-1α–deficient HSCs recover normally after hematopoietic injury induced by serial administration of 5-fluorouracil. We therefore conclude that despite the hypoxic nature of the bone marrow microenvironment, Hif-1α is dispensable for cell-autonomous HSC maintenance. PMID:27060169

  11. Lack of the PGA exopolysaccharide in Salmonella as an adaptive trait for survival in the host.

    Directory of Open Access Journals (Sweden)

    Maite Echeverz

    2017-05-01

    Full Text Available Many bacteria build biofilm matrices using a conserved exopolysaccharide named PGA or PNAG (poly-β-1,6-N-acetyl-D-glucosamine. Interestingly, while E. coli and other members of the family Enterobacteriaceae encode the pgaABCD operon responsible for PGA synthesis, Salmonella lacks it. The evolutionary force driving this difference remains to be determined. Here, we report that Salmonella lost the pgaABCD operon after the divergence of Salmonella and Citrobacter clades, and previous to the diversification of the currently sequenced Salmonella strains. Reconstitution of the PGA machinery endows Salmonella with the capacity to produce PGA in a cyclic dimeric GMP (c-di-GMP dependent manner. Outside the host, the PGA polysaccharide does not seem to provide any significant benefit to Salmonella: resistance against chlorine treatment, ultraviolet light irradiation, heavy metal stress and phage infection remained the same as in a strain producing cellulose, the main biofilm exopolysaccharide naturally produced by Salmonella. In contrast, PGA production proved to be deleterious to Salmonella survival inside the host, since it increased susceptibility to bile salts and oxidative stress, and hindered the capacity of S. Enteritidis to survive inside macrophages and to colonize extraintestinal organs, including the gallbladder. Altogether, our observations indicate that PGA is an antivirulence factor whose loss may have been a necessary event during Salmonella speciation to permit survival inside the host.

  12. Mice lacking glutamate carboxypeptidase II develop normally, but are less susceptible to traumatic brain injury.

    Science.gov (United States)

    Gao, Yang; Xu, Siyi; Cui, Zhenwen; Zhang, Mingkun; Lin, Yingying; Cai, Lei; Wang, Zhugang; Luo, Xingguang; Zheng, Yan; Wang, Yong; Luo, Qizhong; Jiang, Jiyao; Neale, Joseph H; Zhong, Chunlong

    2015-07-01

    Glutamate carboxypeptidase II (GCPII) is a transmembrane zinc metallopeptidase found mainly in the nervous system, prostate and small intestine. In the nervous system, glia-bound GCPII mediates the hydrolysis of the neurotransmitter N-acetylaspartylglutamate (NAAG) into glutamate and N-acetylaspartate. Inhibition of GCPII has been shown to attenuate excitotoxicity associated with enhanced glutamate transmission under pathological conditions. However, different strains of mice lacking the GCPII gene are reported to exhibit striking phenotypic differences. In this study, a GCPII gene knockout (KO) strategy involved removing exons 3-5 of GCPII. This generated a new GCPII KO mice line with no overt differences in standard neurological behavior compared to their wild-type (WT) littermates. However, GCPII KO mice were significantly less susceptible to moderate traumatic brain injury (TBI). GCPII gene KO significantly lessened neuronal degeneration and astrocyte damage in the CA2 and CA3 regions of the hippocampus 24 h after moderate TBI. In addition, GCPII gene KO reduced TBI-induced deficits in long-term spatial learning/memory tested in the Morris water maze and motor balance tested via beam walking. Knockout of the GCPII gene is not embryonic lethal and affords histopathological protection with improved long-term behavioral outcomes after TBI, a result that further validates GCPII as a target for drug development consistent with results from studies using GCPII peptidase inhibitors. © 2015 International Society for Neurochemistry.

  13. Lack of functional specialization of neurons in the mouse primary visual cortex that have expressed calretinin

    Directory of Open Access Journals (Sweden)

    Daniela eCamillo

    2014-09-01

    Full Text Available Calretinin is a calcium-binding protein often used as a marker for a subset of inhibitory interneurons in the mammalian neocortex. We studied the labeled cells in offspring from a cross of a Cre-dependent reporter line with the CR-ires-Cre mice, which express Cre-recombinase in the same pattern as calretinin. We found that in the mature visual cortex, only a minority of the cells that have expressed calretinin and Cre-recombinase during their lifetime is GABAergic and only about 20% are immunoreactive for calretinin. The reason behind this is that calretinin is transiently expressed in many cortical pyramidal neurons during development. To determine whether neurons that express or have expressed calretinin share any distinct functional characteristics, we recorded their visual response properties using GCaMP6s calcium imaging. The average orientation selectivity, size tuning, and temporal and spatial frequency tuning of this group of cells, however, match the response profile of the general neuronal population, revealing the lack of functional specialization for the features studied.

  14. Is that me or my twin? Lack of self-face recognition advantage in identical twins.

    Directory of Open Access Journals (Sweden)

    Matteo Martini

    Full Text Available Despite the increasing interest in twin studies and the stunning amount of research on face recognition, the ability of adult identical twins to discriminate their own faces from those of their co-twins has been scarcely investigated. One's own face is the most distinctive feature of the bodily self, and people typically show a clear advantage in recognizing their own face even more than other very familiar identities. Given the very high level of resemblance of their faces, monozygotic twins represent a unique model for exploring self-face processing. Herein we examined the ability of monozygotic twins to distinguish their own face from the face of their co-twin and of a highly familiar individual. Results show that twins equally recognize their own face and their twin's face. This lack of self-face advantage was negatively predicted by how much they felt physically similar to their co-twin and by their anxious or avoidant attachment style. We speculate that in monozygotic twins, the visual representation of the self-face overlaps with that of the co-twin. Thus, to distinguish the self from the co-twin, monozygotic twins have to rely much more than control participants on the multisensory integration processes upon which the sense of bodily self is based. Moreover, in keeping with the notion that attachment style influences perception of self and significant others, we propose that the observed self/co-twin confusion may depend upon insecure attachment.

  15. An investigation of culturally competent terminology in healthcare policy finds ambiguity and lack of definition.

    Science.gov (United States)

    Grant, Julian; Parry, Yvonne; Guerin, Pauline

    2013-06-01

    This research explored how the concept of cultural competence was represented and expressed through health policies that were intended to improve the quality and efficacy of healthcare provided to families from culturally marginalised communities, particularly women and children with refugee backgrounds. A critical document analysis was conducted of policies that inform healthcare for families from culturally marginalised communities in two local government areas in South Australia. The analysis identified two major themes: lack of, or inconsistent, definitions of 'culture' and 'cultural competency' and related terms; and the paradoxical use of language to determine care. Cultural competence within health services has been identified as an important factor that can improve the health outcomes for families from marginalised communities. However, inconsistency in definitions, understanding and implementation of cultural competence in health practice makes it difficult to implement care using these frameworks. Clearly defined pathways are necessary from health policy to inform culturally competent service delivery. The capacity for policy directives to effectively circumvent the potential deleterious outcomes of culturally incompetent services is only possible when that policy provides clear definitions and instructions. Consultation and partnership are necessary to develop effective definitions and processes relating to cultural competence. © 2013 The Authors. ANZJPH © 2013 Public Health Association of Australia.

  16. Lack of genotoxicity in vivo for food color additive Tartrazine.

    Science.gov (United States)

    Bastaki, Maria; Farrell, Thomas; Bhusari, Sachin; Pant, Kamala; Kulkarni, Rohan

    2017-07-01

    Tartrazine is approved as a food color additive internationally with INS number 102, in the United States as food color subject to batch certification "Food, Drug, and Cosmetic" (FD&C) Yellow No. 5, and in Europe as food color additive with E number 102. In their evaluation of the color (2013), the European Food Safety Authority (EFSA) expressed concerns of potential genotoxicity, based primarily on one genotoxicity study that was not conducted according to Guidelines. The present in vivo genotoxicity study was conducted according to OECD Guidelines in response to EFSA's request for additional data. The animal species and strain, and the tissues examined were selected specifically to address the previously reported findings. The results of this study show clear absence of genotoxic activity for Tartrazine, in the bone marrow micronucleus assay and the Comet assay in the liver, stomach, and colon. These data addressed EFSA's concerns for genotoxicity. The Joint WHO/FAO Committee on Food Additives (JECFA) (2016) also reviewed these data and concluded that there is no genotoxicity concern for Tartrazine. Negative findings in parallel genotoxicity studies on Allura Red AC and Ponceau 4R (published separately) are consistent with lack of genotoxicity for azo dyes used as food colors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Clinical practice guidelines for the diagnosis and management of melanoma: melanomas that lack classical clinical features.

    Science.gov (United States)

    Mar, Victoria J; Chamberlain, Alex J; Kelly, John W; Murray, William K; Thompson, John F

    2017-10-16

    A Cancer Council Australia multidisciplinary working group is currently revising and updating the 2008 evidence-based clinical practice guidelines for the management of cutaneous melanoma. While there have been many recent improvements in treatment options for metastatic melanoma, early diagnosis remains critical to reducing mortality from the disease. Improved awareness of the atypical presentations of this common malignancy is required to achieve this. A chapter of the new guidelines was therefore developed to aid recognition of atypical melanomas. Main recommendations: Because thick, life-threatening melanomas may lack the more classical ABCD (asymmetry, border irregularity, colour variegation, diameter > 6 mm) features of melanoma, a thorough history of the lesion with regard to change in morphology and growth over time is essential. Any lesion that is changing in morphology or growing over a period of more than one month should be excised or referred for prompt expert opinion. Changes in management as a result of the guidelines: These guidelines provide greater emphasis on improved recognition of the atypical presentations of melanoma, in particular nodular, desmoplastic and acral lentiginous subtypes, with particular awareness of hypomelanotic and amelanotic lesions.

  18. Evaluating mice lacking serum carboxylesterase as a behavioral model for nerve agent intoxication.

    Science.gov (United States)

    Dunn, Emily N; Ferrara-Bowens, Teresa M; Chachich, Mark E; Honnold, Cary L; Rothwell, Cristin C; Hoard-Fruchey, Heidi M; Lesyna, Catherine A; Johnson, Erik A; Cerasoli, Douglas M; McDonough, John H; Cadieux, C Linn

    2018-06-07

    Mice and other rodents are typically utilized for chemical warfare nerve agent research. Rodents have large amounts of carboxylesterase in their blood, while humans do not. Carboxylesterase nonspecifically binds to and detoxifies nerve agent. The presence of this natural bioscavenger makes mice and other rodents poor models for studies identifying therapeutics to treat humans exposed to nerve agents. To obviate this problem, a serum carboxylesterase knockout (Es1 KO) mouse was created. In this study, Es1 KO and wild type (WT) mice were assessed for differences in gene expression, nerve agent (soman; GD) median lethal dose (MLD) values, and behavior prior to and following nerve agent exposure. No expression differences were detected between Es1 KO and WT mice in more than 34 000 mouse genes tested. There was a significant difference between Es1 KO and WT mice in MLD values, as the MLD for GD-exposed WT mice was significantly higher than the MLD for GD-exposed Es1 KO mice. Behavioral assessments of Es1 KO and WT mice included an open field test, a zero maze, a Barnes maze, and a sucrose preference test (SPT). While sex differences were observed in various measures of these tests, overall, Es1 KO mice behaved similarly to WT mice. The two genotypes also showed virtually identical neuropathological changes following GD exposure. Es1 KO mice appear to have an enhanced susceptibility to GD toxicity while retaining all other behavioral and physiological responses to this nerve agent, making the Es1 KO mouse a more human-like model for nerve agent research.

  19. Lack of evidence for low-dimensional chaos in heart rate variability

    DEFF Research Database (Denmark)

    Kanters, J K; Holstein-Rathlou, N H; Agner, E

    1994-01-01

    INTRODUCTION: The term chaos is used to describe erratic or apparently random time-dependent behavior in deterministic systems. It has been suggested that the variability observed in the normal heart rate may be due to chaos, but this question has not been settled. METHODS AND RESULTS: Heart rate...... in the experimental data, but the prediction error as a function of the prediction length increased at a slower rate than characteristic of a low-dimensional chaotic system. CONCLUSION: There is no evidence for low-dimensional chaos in the time series of RR intervals from healthy human subjects. However, nonlinear...

  20. Lack of detectable DNA uptake by transmission of selected recipients in mono-associated rats

    DEFF Research Database (Denmark)

    Wilcks, Andrea; Jacobsen, Bodil B. L.

    2010-01-01

    for the construction of GM plants end up in pathogenic bacteria, eventually leading to untreatable disease. Three different bacterial species (Escherichia coli, Bacillus subtilis, Streptococcus gordonii), all natural inhabitants of the food and intestinal tract environment were used as recipients for uptake of DNA...... than the consumption of GM food harbouring antibiotic resistance genes.......An important concern revealed in the public discussion of the use of genetically modified (GM) plants for human consumption, is the potential transfer of DNA from these plants to bacteria present in the gastrointestinal tract. Especially, there is a concern that antibiotic resistance genes used...

  1. Human rights

    NARCIS (Netherlands)

    Gaay Fortman, B. de

    2006-01-01

    Human rights reflect a determined effort to protect the dignity of each and every human being against abuse of power. This endeavour is as old as human history. What is relatively new is the international venture for the protection of human dignity through internationally accepted legal standards

  2. A lack of appetite for information and computation. Simple heuristics in food choice.

    Science.gov (United States)

    Schulte-Mecklenbeck, Michael; Sohn, Matthias; de Bellis, Emanuel; Martin, Nathalie; Hertwig, Ralph

    2013-12-01

    The predominant, but largely untested, assumption in research on food choice is that people obey the classic commandments of rational behavior: they carefully look up every piece of relevant information, weight each piece according to subjective importance, and then combine them into a judgment or choice. In real world situations, however, the available time, motivation, and computational resources may simply not suffice to keep these commandments. Indeed, there is a large body of research suggesting that human choice is often better accommodated by heuristics-simple rules that enable decision making on the basis of a few, but important, pieces of information. We investigated the prevalence of such heuristics in a computerized experiment that engaged participants in a series of choices between two lunch dishes. Employing MouselabWeb, a process-tracing technique, we found that simple heuristics described an overwhelmingly large proportion of choices, whereas strategies traditionally deemed rational were barely apparent in our data. Replicating previous findings, we also observed that visual stimulus segments received a much larger proportion of attention than any nutritional values did. Our results suggest that, consistent with human behavior in other domains, people make their food choices on the basis of simple and informationally frugal heuristics. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Aberrant Bone Density in Aging Mice Lacking the Adenosine Transporter ENT1

    Science.gov (United States)

    Hinton, David J.; McGee-Lawrence, Meghan E.; Lee, Moonnoh R.; Kwong, Hoi K.; Westendorf, Jennifer J.; Choi, Doo-Sup

    2014-01-01

    Adenosine is known to regulate bone production and resorption in humans and mice. Type 1 equilibrative nucleoside transporter (ENT1) is responsible for the majority of adenosine transport across the plasma membrane and is ubiquitously expressed in both humans and mice. However, the contribution of ENT1-mediated adenosine levels has not been studied in bone remodeling. With the recent identification of the importance of adenosine signaling in bone homeostasis, it is essential to understand the role of ENT1 to develop novel therapeutic compounds for bone disorders. Here we examined the effect of ENT1 deletion on bone density using X-ray, dual energy X-ray absorptiometry and micro-computerized tomography analysis. Our results show that bone density and bone mineral density is reduced in the lower thoracic and lumbar spine as well as the femur of old ENT1 null mice (>7 months) compared to wild-type littermates. Furthermore, we found increased mRNA expression of tartrate-resistant acid phosphatase (TRAP), an osteoclast marker, in isolated long bones from 10 month old ENT1 null mice compared to wild-type mice. In addition, aged ENT1 null mice displayed severe deficit in motor coordination and locomotor activity, which might be attributed to dysregulated bone density. Overall, our study suggests that ENT1-regulated adenosine signaling plays an essential role in lumbar spine and femur bone density. PMID:24586402

  4. Aberrant bone density in aging mice lacking the adenosine transporter ENT1.

    Directory of Open Access Journals (Sweden)

    David J Hinton

    Full Text Available Adenosine is known to regulate bone production and resorption in humans and mice. Type 1 equilibrative nucleoside transporter (ENT1 is responsible for the majority of adenosine transport across the plasma membrane and is ubiquitously expressed in both humans and mice. However, the contribution of ENT1-mediated adenosine levels has not been studied in bone remodeling. With the recent identification of the importance of adenosine signaling in bone homeostasis, it is essential to understand the role of ENT1 to develop novel therapeutic compounds for bone disorders. Here we examined the effect of ENT1 deletion on bone density using X-ray, dual energy X-ray absorptiometry and micro-computerized tomography analysis. Our results show that bone density and bone mineral density is reduced in the lower thoracic and lumbar spine as well as the femur of old ENT1 null mice (>7 months compared to wild-type littermates. Furthermore, we found increased mRNA expression of tartrate-resistant acid phosphatase (TRAP, an osteoclast marker, in isolated long bones from 10 month old ENT1 null mice compared to wild-type mice. In addition, aged ENT1 null mice displayed severe deficit in motor coordination and locomotor activity, which might be attributed to dysregulated bone density. Overall, our study suggests that ENT1-regulated adenosine signaling plays an essential role in lumbar spine and femur bone density.

  5. Lack of Association of CD55 Receptor Genetic Variants and Severe Malaria in Ghanaian Children

    Directory of Open Access Journals (Sweden)

    Kathrin Schuldt

    2017-03-01

    Full Text Available In a recent report, the cellular receptor CD55 was identified as a molecule essential for the invasion of human erythrocytes by Plasmodium falciparum, the causal agent of the most severe form of malaria. As this invasion process represents a critical step during infection with the parasite, it was hypothesized that genetic variants in the gene could affect severe malaria (SM susceptibility. We performed high-resolution variant discovery of rare and common genetic variants in the human CD55 gene. Association testing of these variants in over 1700 SM cases and unaffected control individuals from the malaria-endemic Ashanti Region in Ghana, West Africa, were performed on the basis of single variants, combined rare variant analyses, and reconstructed haplotypes. A total of 26 genetic variants were detected in coding and regulatory regions of CD55. Five variants were previously unknown. None of the single variants, rare variants, or haplotypes showed evidence for association with SM or P. falciparum density. Here, we present the first comprehensive analysis of variation in the CD55 gene in the context of SM and show that genetic variants present in a Ghanaian study group appear not to influence susceptibility to the disease.

  6. Both bias and lack of knowledge influence organizational focus on first case of the day starts.

    Science.gov (United States)

    Dexter, Elisabeth U; Dexter, Franklin; Masursky, Danielle; Garver, Michael P; Nussmeier, Nancy A

    2009-04-01

    The economic costs of reducing first case delays are often high, because efforts need to be applied to multiple operating rooms (ORs) simultaneously. Nevertheless, delays in starting first cases of the day are a common topic in OR committee meetings. We added three scientific questions to a 24 question online, anonymous survey performed before the implementation of a new OR information system. The 57 respondents cared sufficiently about OR management at the United States teaching hospital to complete all questions. The survey revealed reasons why personnel may focus on the small reductions in nonoperative time achievable by reducing tardiness in first cases of the day. (A) Respondents lacked knowledge about principles in reducing over-utilized OR time to increase OR efficiency, based on their answering the relevant question correctly at a rate no different from guessing at random. Those results differed from prior findings of responses at a rate worse than random, resulting from a bias on the day of surgery of making decisions that increase clinical work per unit time. (B) Most respondents falsely believed that a 10 min delay at the start of the day causes subsequent cases to start at least 10 min late (P less time than scheduled (P = 0.008 versus chance). No one who demonstrated knowledge (C) about cases sometimes taking less time than scheduled applied that information to their response to (B) regarding cases starting late (P = 0.0002). Knowledge of OR efficiency was low among the respondents working in ORs. Nevertheless, the apparent absence of bias shows that education may influence behavior. In contrast, presence of bias on matters of tardiness of start times shows that education may be of no benefit. As the latter results match findings of previous studies of scheduling decisions, interventions to reduce patient and surgeon waiting from start times may depend principally on the application of automation to guide decision-making.

  7. Lack of pollinators limits fruit production in commercial blueberry (Vaccinium corymbosum).

    Science.gov (United States)

    Benjamin, Faye E; Winfree, Rachael

    2014-12-01

    Modern agriculture relies on domesticated pollinators such as the honey bee (Apis mellifera L.), and to a lesser extent on native pollinators, for the production of animal-pollinated crops. There is growing concern that pollinator availability may not keep pace with increasing agricultural production. However, whether crop production is in fact pollen-limited at the field scale has rarely been studied. Here, we ask whether commercial highbush blueberry (Vaccinium corymbosum L.) production in New Jersey is limited by a lack of pollination even when growers provide honey bees at recommended densities. We studied two varieties of blueberry over 3 yr to determine whether blueberry crop production is pollen-limited and to measure the relative contributions of honey bees and native bees to blueberry pollination. We found two lines of evidence for pollen limitation. First, berries receiving supplemental hand-pollination were generally heavier than berries receiving ambient pollination. Second, mean berry mass increased significantly and nonasymptotically with honey bee flower visitation rate. While honey bees provided 86% of pollination and thus drove the findings reported above, native bees still contributed 14% of total pollination even in our conventionally managed, high-input agricultural system. Honey bees and native bees were also similarly efficient as pollinators on a per-visit basis. Overall, our study shows that pollination can be a limiting factor in commercial fruit production. Yields might increase with increased honey bee stocking rates and improved dispersal of hives within crop fields, and with habitat restoration to increase pollination provided by native bees.

  8. On the lack of host-cell reactivation of UV-irradiated phage T5

    International Nuclear Information System (INIS)

    Chiang, T.; Harm, W.

    1976-01-01

    Previously reported experiments have shown that host-cell reactivation (HCR) of UV-irradiated phage T1 in excision-repair proficient Escherichia coli cells is inhibited by superinfection with phage T5. Theoretical considerations have led to predictions concerning the dependence of repair inhibition on the multiplicity of superinfecting T5 phage and on the UV fluence to which they were exposed. These predictions have been supported by experimental results described in this paper. The fluence dependence permitted calculation of the relative UV sensitivity of the gene function responsible for repair inhibition; it was found to be about 2.3% that of the plaque-forming ability of phage T5. The T5-inhibitable step in excision repair occurs early in the infective cycle of T1. Furthermore, experiments involving the presence of 400 μg/ml chloramphenicol showed that HCR inhibition of T1 is caused by a protein produced after the FST segment of T5 (i.e. the first 8% of the T5 genome) has entered the host cell. A previously described minor T1 recovery process, occuring in both excision-repair-proficient and -deficient host-cells, is inhibited by T5 infection due to a different substance, which is most likely associated with the 'second-step-transfer' region of T5 DNA (involving the remainder of the genome). Superinfection with T4v 1 phage resulted in HCR inhibition of T1, resembling that observed after T5 superinfection. The discussion of these results suggests that inhibition of the bacterial excision repair system by T5 or T4 infection occurs at the level of UV-endonucleolytic incision, and that lack of HCR both in T-even phages and in T5 can be explained in the same manner

  9. Evidence for abscisic acid biosynthesis in Cuscuta reflexa, a parasitic plant lacking neoxanthin.

    Science.gov (United States)

    Qin, Xiaoqiong; Yang, Seung Hwan; Kepsel, Andrea C; Schwartz, Steven H; Zeevaart, Jan A D

    2008-06-01

    Abscisic acid (ABA) is a plant hormone found in all higher plants; it plays an important role in seed dormancy, embryo development, and adaptation to environmental stresses, most notably drought. The regulatory step in ABA synthesis is the cleavage reaction of a 9-cis-epoxy-carotenoid catalyzed by the 9-cis-epoxy-carotenoid dioxygenases (NCEDs). The parasitic angiosperm Cuscuta reflexa lacks neoxanthin, one of the common precursors of ABA in all higher plants. Thus, is C. reflexa capable of synthesizing ABA, or does it acquire ABA from its host plants? Stem tips of C. reflexa were cultured in vitro and found to accumulate ABA in the absence of host plants. This demonstrates that this parasitic plant is capable of synthesizing ABA. Dehydration of detached stem tips caused a big rise in ABA content. During dehydration, 18O was incorporated into ABA from 18O2, indicating that ABA was synthesized de novo in C. reflexa. Two NCED genes, CrNCED1 and CrNCED2, were cloned from C. reflexa. Expression of CrNCEDs was up-regulated significantly by dehydration. In vitro enzyme assays with recombinant CrNCED1 protein showed that the protein is able to cleave both 9-cis-violaxanthin and 9'-cis-neoxanthin to give xanthoxin. Thus, despite the absence of neoxanthin in C. reflexa, the biochemical activity of CrNCED1 is similar to that of NCEDs from other higher plants. These results provide evidence for conservation of the ABA biosynthesis pathway among members of the plant kingdom.

  10. Lactose metabolism in Streptococcus lactis: studies with a mutant lacking glucokinase and mannose-phosphotransferase activities

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, J.; Chassy, B.M.; Egan, W.

    1985-04-01

    A mutant of Streptococcus lactis 133 has been isolated that lacks both glucokinase and phosphoenolpyruvate-dependent mannose- phosphotransferase (mannose-PTS) activities. The double mutant S. lactis 133 mannose-PTSd GK- is unable to utilize either exogenously supplied or intracellularly generated glucose for growth. Fluorographic analyses of metabolites formed during the metabolism of (/sup 14/C)lactose labeled specifically in the glucose or galactosyl moiety established that the cells were unable to phosphorylate intracellular glucose. However, cells of S. lactis 133 mannose-PTSd GK- readily metabolized intracellular glucose 6-phosphate, and the growth rates and cell yield of the mutant and parental strains on sucrose were the same. During growth on lactose, S. lactis 133 mannose-PTSd GK- fermented only the galactose moiety of the disaccharide, and 1 mol of glucose was generated per mol of lactose consumed. For an equivalent concentration of lactose, the cell yield of the mutant was 50% that of the wild type. The specific rate of lactose utilization by growing cells of S. lactis 133 mannose-PTSd GK- was ca. 50% greater than that of the wild type, but the cell doubling times were 70 and 47 min, respectively. High-resolution /sup 31/P nuclear magnetic resonance studies of lactose transport by starved cells of S. lactis 133 and S. lactis 133 mannose-PTSd GK- showed that the latter cells contained elevated lactose-PTS activity. Throughout exponential growth on lactose, the mutant maintained an intracellular steady-state glucose concentration of 100 mM.

  11. Lack of bcr and abr promotes hypoxia-induced pulmonary hypertension in mice.

    Directory of Open Access Journals (Sweden)

    Min Yu

    Full Text Available Bcr and Abr are GTPase activating proteins that specifically downregulate activity of the small GTPase Rac in restricted cell types in vivo. Rac1 is expressed in smooth muscle cells, a critical cell type involved in the pathogenesis of pulmonary hypertension. The molecular mechanisms that underlie hypoxia-associated pulmonary hypertension are not well-defined.Bcr and abr null mutant mice were compared to wild type controls for the development of pulmonary hypertension after exposure to hypoxia. Also, pulmonary arterial smooth muscle cells from those mice were cultured in hypoxia and examined for proliferation, p38 activation and IL-6 production. Mice lacking Bcr or Abr exposed to hypoxia developed increased right ventricular pressure, hypertrophy and pulmonary vascular remodeling. Perivascular leukocyte infiltration in the lungs was increased, and under hypoxia bcr-/- and abr-/- macrophages generated more reactive oxygen species. Consistent with a contribution of inflammation and oxidative stress in pulmonary hypertension-associated vascular damage, Bcr and Abr-deficient animals showed elevated endothelial leakage after hypoxia exposure. Hypoxia-treated pulmonary arterial smooth muscle cells from Bcr- or Abr-deficient mice also proliferated faster than those of wild type mice. Moreover, activated Rac1, phosphorylated p38 and interleukin 6 were increased in these cells in the absence of Bcr or Abr. Inhibition of Rac1 activation with Z62954982, a novel Rac inhibitor, decreased proliferation, p38 phosphorylation and IL-6 levels in pulmonary arterial smooth muscle cells exposed to hypoxia.Bcr and Abr play a critical role in down-regulating hypoxia-induced pulmonary hypertension by deactivating Rac1 and, through this, reducing both oxidative stress generated by leukocytes as well as p38 phosphorylation, IL-6 production and proliferation of pulmonary arterial smooth muscle cells.

  12. Lack of Population Genetic Structuring in Ocelots (Leopardus pardalis in a Fragmented Landscape

    Directory of Open Access Journals (Sweden)

    Marina G. Figueiredo

    2015-07-01

    Full Text Available Habitat fragmentation can promote patches of small and isolated populations, gene flow disruption between those populations, and reduction of local and total genetic variation. As a consequence, these small populations may go extinct in the long-term. The ocelot (Leopardus pardalis, originally distributed from Texas to southern Brazil and northern Argentina, has been impacted by habitat fragmentation throughout much of its range. To test whether habitat fragmentation has already induced genetic differentiation in an area where this process has been documented for a larger felid (jaguars, we analyzed molecular variation in ocelots inhabiting two Atlantic Forest fragments, Morro do Diabo (MD and Iguaçu Region (IR. Analyses using nine microsatellites revealed mean observed and expected heterozygosity of 0.68 and 0.70, respectively. The MD sampled population showed evidence of a genetic bottleneck under two mutational models (TPM = 0.03711 and SMM = 0.04883. Estimates of genetic structure (FST = 0.027; best fit of k = 1 with STRUCTURE revealed no meaningful differentiation between these populations. Thus, our results indicate that the ocelot populations sampled in these fragments are still not significantly different genetically, a pattern that strongly contrasts with that previously observed in jaguars for the same comparisons. This observation is likely due to a combination of two factors: (i larger effective population size of ocelots (relative to jaguars in each fragment, implying a slower effect of drift-induced differentiation; and (ii potentially some remaining permeability of the anthropogenic matrix for ocelots, as opposed to the observed lack of permeability for jaguars. The persistence of ocelot gene flow between these areas must be prioritized in long-term conservation planning on behalf of these felids.

  13. Lack of phenotypic and evolutionary cross-resistance against parasitoids and pathogens in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Alex R Kraaijeveld

    Full Text Available When organisms are attacked by multiple natural enemies, the evolution of a resistance mechanism to one natural enemy will be influenced by the degree of cross-resistance to another natural enemy. Cross-resistance can be positive, when a resistance mechanism against one natural enemy also offers resistance to another; or negative, in the form of a trade-off, when an increase in resistance against one natural enemy results in a decrease in resistance against another. Using Drosophila melanogaster, an important model system for the evolution of invertebrate immunity, we test for the existence of cross-resistance against parasites and pathogens, at both a phenotypic and evolutionary level.We used a field strain of D. melanogaster to test whether surviving parasitism by the parasitoid Asobara tabida has an effect on the resistance against Beauveria bassiana, an entomopathogenic fungus; and whether infection with the microsporidian Tubulinosema kingi has an effect on the resistance against A. tabida. We used lines selected for increased resistance to A. tabida to test whether increased parasitoid resistance has an effect on resistance against B. bassiana and T. kingi. We used lines selected for increased tolerance against B. bassiana to test whether increased fungal resistance has an effect on resistance against A. tabida.We found no positive cross-resistance or trade-offs in the resistance to parasites and pathogens. This is an important finding, given the use of D. melanogaster as a model system for the evolution of invertebrate immunity. The lack of any cross-resistance to parasites and pathogens, at both the phenotypic and the evolutionary level, suggests that evolution of resistance against one class of natural enemies is largely independent of evolution of resistance against the other.

  14. Male-like sexual behavior of female mouse lacking fucose mutarotase

    Directory of Open Access Journals (Sweden)

    Lim Dae-sik

    2010-07-01

    Full Text Available Abstract Background Mutarotases are recently characterized family of enzymes that are involved in the anomeric conversions of monosaccharides. The mammalian fucose mutarotase (FucM was reported in cultured cells to facilitate fucose utilization and incorporation into protein by glycosylation. However, the role of this enzyme in animal has not been elucidated. Results We generated a mutant mouse specifically lacking the fucose mutarotase (FucM gene. The FucM knockout mice displayed an abnormal sexual receptivity with a drastic reduction in lordosis score, although the animals were fertile due to a rare and forced intromission by a typical male. We examined the anteroventral periventricular nucleus (AVPv of the preoptic region in brain and found that the mutant females showed a reduction in tyrosine hydoxylase positive neurons compared to that of a normal female. Furthermore, the mutant females exhibited a masculine behavior, such as mounting to a normal female partner as well as showing a preference to female urine. We found a reduction of fucosylated serum alpha-fetoprotein (AFP in a mutant embryo relative to that of a wild-type embryo. Conclusions The observation that FucM-/- female mouse exhibits a phenotypic similarity to a wild-type male in terms of its sexual behavior appears to be due to the neurodevelopmental changes in preoptic area of mutant brain resembling a wild-type male. Since the previous studies indicate that AFP plays a role in titrating estradiol that are required to consolidate sexual preference of female mice, we speculate that the reduced level of AFP in FucM-/- mouse, presumably resulting from the reduced fucosylation, is responsible for the male-like sexual behavior observed in the FucM knock-out mouse.

  15. Fetal growth retardation and lack of hypotaurine in ezrin knockout mice.

    Directory of Open Access Journals (Sweden)

    Tomohiro Nishimura

    Full Text Available Ezrin is a membrane-associated cytoplasmic protein that serves to link cell-membrane proteins with the actin-based cytoskeleton, and also plays a role in regulation of the functional activities of some transmembrane proteins. It is expressed in placental trophoblasts. We hypothesized that placental ezrin is involved in the supply of nutrients from mother to fetus, thereby influencing fetal growth. The aim of this study was firstly to clarify the effect of ezrin on fetal growth and secondly to determine whether knockout of ezrin is associated with decreased concentrations of serum and placental nutrients. Ezrin knockout mice (Ez(-/- were confirmed to exhibit fetal growth retardation. Metabolome analysis of fetal serum and placental extract of ezrin knockout mice by means of capillary electrophoresis-time-of-flight mass spectrometry revealed a markedly decreased concentration of hypotaurine, a precursor of taurine. However, placental levels of cysteine and cysteine sulfinic acid (precursors of hypotaurine and taurine were not affected. Lack of hypotaurine in Ez(-/- mice was confirmed by liquid chromatography with tandem mass spectrometry. Administration of hypotaurine to heterogenous dams significantly decreased the placenta-to-maternal plasma ratio of hypotaurine in wild-type fetuses but only slightly decreased it in ezrin knockout fetuses, indicating that the uptake of hypotaurine from mother to placenta is saturable and that disruption of ezrin impairs the uptake of hypotaurine by placental trophoblasts. These results indicate that ezrin is required for uptake of hypotaurine from maternal serum by placental trophoblasts, and plays an important role in fetal growth.

  16. Entrainment and phase-shifting by centrifugation abolished in mice lacking functional vestibular input

    Science.gov (United States)

    Fuller, Charles; Ringgold, Kristyn

    The circadian pacemaker can be phase shifted and entrained by appropriately timed locomotor activity, however the mechanism(s) involved remain poorly understood. Recent work in our lab has suggested the involvement of the vestibular otolith organs in activity-induced changes within the circadian timing system (CTS). For example, we have shown that changes in circa-dian period and phase in response to locomotion (wheel running) require functional macular gravity receptors. We believe the neurovestibular system is responsible for the transduction of gravitoinertial input associated with the types of locomotor activity that are known to af-fect the pacemaker. This study investigated the hypothesis that daily, timed gravitoinertial stimuli, as applied by centrifugation. would induce entrainment of circadian rhythms in only those animals with functional afferent vestibular input. To test this hypothesis, , chemically labyrinthectomized (Labx) mice, mice lacking macular vestibular input (head tilt or hets) and wildtype (WT) littermates were implanted i.p. with biotelemetry and individually housed in a 4-meter diameter centrifuge in constant darkness (DD). After 2 weeks in DD, the mice were exposed daily to 2G via centrifugation from 1000-1200 for 9 weeks. Only WT mice showed entrainment to the daily 2G pulse. The 2G pulse was then re-set to occur at 1200-1400 for 4 weeks. Only WT mice demonstrated a phase shift in response to the re-setting of the 2G pulse and subsequent re-entrainment to the new centrifugation schedule. These results provide further evidence that gravitoinertial stimuli require a functional vestibular system to both en-train and phase shift the CTS. Entrainment among only WT mice supports the role of macular gravity receptive cells in modulation of the CTS while also providing a functional mechanism by which gravitoinertial stimuli, including locomotor activity, may affect the pacemaker.

  17. Lack of grading agreement among international hemostasis external quality assessment programs.

    Science.gov (United States)

    Olson, John D; Jennings, Ian; Meijer, Piet; Bon, Chantal; Bonar, Roslyn; Favaloro, Emmanuel J; Higgins, Russell A; Keeney, Michael; Mammen, Joy; Marlar, Richard A; Meley, Roland; Nair, Sukesh C; Nichols, William L; Raby, Anne; Reverter, Joan C; Srivastava, Alok; Walker, Isobel

    2018-01-01

    : Laboratory quality programs rely on internal quality control and external quality assessment (EQA). EQA programs provide unknown specimens for the laboratory to test. The laboratory's result is compared with other (peer) laboratories performing the same test. EQA programs assign target values using a variety of methods statistical tools and performance assessment of 'pass' or 'fail' is made. EQA provider members of the international organization, external quality assurance in thrombosis and hemostasis, took part in a study to compare outcome of performance analysis using the same data set of laboratory results. Eleven EQA organizations using eight different analytical approaches participated. Data for a normal and prolonged activated partial thromboplastin time (aPTT) and a normal and reduced factor VIII (FVIII) from 218 laboratories were sent to the EQA providers who analyzed the data set using their method of evaluation for aPTT and FVIII, determining the performance for each laboratory record in the data set. Providers also summarized their statistical approach to assignment of target values and laboratory performance. Each laboratory record in the data set was graded pass/fail by all EQA providers for each of the four analytes. There was a lack of agreement of pass/fail grading among EQA programs. Discordance in the grading was 17.9 and 11% of normal and prolonged aPTT results, respectively, and 20.2 and 17.4% of normal and reduced FVIII results, respectively. All EQA programs in this study employed statistical methods compliant with the International Standardization Organization (ISO), ISO 13528, yet the evaluation of laboratory results for all four analytes showed remarkable grading discordance.

  18. A high-fat diet induces bone loss in mice lacking the Alox5 gene.

    Science.gov (United States)

    Le, Phuong; Kawai, Masanobu; Bornstein, Sheila; DeMambro, Victoria E; Horowitz, Mark C; Rosen, Clifford J

    2012-01-01

    5-Lipoxygenase catalyzes leukotriene generation from arachidonic acid. The gene that encodes 5-lipoxygenase, Alox5, has been identified in genome-wide association and mouse Quantitative Trait Locus studies as a candidate gene for obesity and low bone mass. Thus, we tested the hypothesis that Alox5(-/-) mice would exhibit metabolic and skeletal changes when challenged by a high-fat diet (HFD). On a regular diet, Alox5(-/-) mice did not differ in total body weight, percent fat mass, or bone mineral density compared with wild-type (WT) controls (P < 0.05). However, when placed on a HFD, Alox5(-/-) gained more fat mass and lost greater areal bone mass vs. WT (P < 0.05). Microarchitectural analyses revealed that on a HFD, WT showed increases in cortical area (P < 0.01) and trabecular thickness (P < 0.01), whereas Alox5(-/-) showed no change in cortical parameters but a decrease in trabecular number (P < 0.05) and bone volume fraction compared with WT controls (P < 0.05). By histomorphometry, a HFD did not change bone formation rates of either strain but produced an increase in osteoclast number per bone perimeter in Alox5(-/-) mice (P < 0.03). In vitro, osteoclastogenesis of marrow stromal cells was enhanced in mutant but not WT mice fed a HFD. Gene expression for Rankl, Pparg, and Cox-2 was greater in the femur of Alox5(-/-) than WT mice on a HFD (P < 0.01), but these increases were suppressed in the Alox5(-/-) mice after 8 wk of treatment with celecoxib, a cyclooxygenase-2 inhibitor. In sum, there is a strong gene by environmental interaction for bone mass when mice lacking the Alox5 gene are fed a HFD.

  19. Lack of grading agreement among international hemostasis external quality assessment programs

    Science.gov (United States)

    Olson, John D.; Jennings, Ian; Meijer, Piet; Bon, Chantal; Bonar, Roslyn; Favaloro, Emmanuel J.; Higgins, Russell A.; Keeney, Michael; Mammen, Joy; Marlar, Richard A.; Meley, Roland; Nair, Sukesh C.; Nichols, William L.; Raby, Anne; Reverter, Joan C.; Srivastava, Alok; Walker, Isobel

    2018-01-01

    Laboratory quality programs rely on internal quality control and external quality assessment (EQA). EQA programs provide unknown specimens for the laboratory to test. The laboratory's result is compared with other (peer) laboratories performing the same test. EQA programs assign target values using a variety of methods statistical tools and performance assessment of ‘pass’ or ‘fail’ is made. EQA provider members of the international organization, external quality assurance in thrombosis and hemostasis, took part in a study to compare outcome of performance analysis using the same data set of laboratory results. Eleven EQA organizations using eight different analytical approaches participated. Data for a normal and prolonged activated partial thromboplastin time (aPTT) and a normal and reduced factor VIII (FVIII) from 218 laboratories were sent to the EQA providers who analyzed the data set using their method of evaluation for aPTT and FVIII, determining the performance for each laboratory record in the data set. Providers also summarized their statistical approach to assignment of target values and laboratory performance. Each laboratory record in the data set was graded pass/fail by all EQA providers for each of the four analytes. There was a lack of agreement of pass/fail grading among EQA programs. Discordance in the grading was 17.9 and 11% of normal and prolonged aPTT results, respectively, and 20.2 and 17.4% of normal and reduced FVIII results, respectively. All EQA programs in this study employed statistical methods compliant with the International Standardization Organization (ISO), ISO 13528, yet the evaluation of laboratory results for all four analytes showed remarkable grading discordance. PMID:29232255

  20. [Factors related to lack of autonomous mobility during out-of-hospital emergency care].

    Science.gov (United States)

    Montero García, Antonio; Morales Asencio, José Miguel; Trujillo Illescas, Juan Alfonso; Martí, Celia

    2016-10-01

    To explore the frequency of lack of autonomous mobility and factors related to it in patients requiring prehospital emergency services. Cross-sectional, observational, retrospective analysis. We identified a stratified random sample of patients attended by the public health emergency service of Andalusia in 2011. The sample included 280 patients with a mean age of 56 years; 63.9% were men. The majority were attended in homes and streets or other public spaces. Most were transported to a hospital in a mobile intensive care unit. The reasons for calling the service were most often related to chest pain or injuries. Loss of autonomous mobility was seen more often in men, when care was required in a public area, when there were injuries or altered vital signs, and when the patient required transport in a mobile intensive care unit. Dependence on others was significantly associated with the presence of a prior condition before the patient required transport (odds ratio [OR], 3.27; 95% CI, 1.60-6.33), the use of immobilization strategies (OR, 7.71; 95% CI, 1.7-34.96], and the use of ambulance transport (OR, 4.35; 95% CI, 1.63-11.60]. The following 2 variables were at the limit of significance: pain during the care process (OR, 1.13; 95% CI, 0.99-1.29) and age (OR, 0.46; 95% CI, 0.97-1.01). The profile we identified for patients and situations in which patients cannot move autonomously during prehospital emergency care can be used to plan preventive strategies to ensure patient safety.

  1. Comparative Sex Chromosome Genomics in Snakes: Differentiation, Evolutionary Strata, and Lack of Global Dosage Compensation

    Science.gov (United States)

    Zektser, Yulia; Mahajan, Shivani; Bachtrog, Doris

    2013-01-01

    Snakes exhibit genetic sex determination, with female heterogametic sex chromosomes (ZZ males, ZW females). Extensive cytogenetic work has suggested that the level of sex chromosome heteromorphism varies among species, with Boidae having entirely homomorphic sex chromosomes, Viperidae having completely heteromorphic sex chromosomes, and Colubridae showing partial differentiation. Here, we take a genomic approach to compare sex chromosome differentiation in these three snake families. We identify homomorphic sex chromosomes in boas (Boidae), but completely heteromorphic sex chromosomes in both garter snakes (Colubridae) and pygmy rattlesnake (Viperidae). Detection of W-linked gametologs enables us to establish the presence of evolutionary strata on garter and pygmy rattlesnake sex chromosomes where recombination was abolished at different time points. Sequence analysis shows that all strata are shared between pygmy rattlesnake and garter snake, i.e., recombination was abolished between the sex chromosomes before the two lineages diverged. The sex-biased transmission of the Z and its hemizygosity in females can impact patterns of molecular evolution, and we show that rates of evolution for Z-linked genes are increased relative to their pseudoautosomal homologs, both at synonymous and amino acid sites (even after controlling for mutational biases). This demonstrates that mutation rates are male-biased in snakes (male-driven evolution), but also supports faster-Z evolution due to differential selective effects on the Z. Finally, we perform a transcriptome analysis in boa and pygmy rattlesnake to establish baseline levels of sex-biased expression in homomorphic sex chromosomes, and show that heteromorphic ZW chromosomes in rattlesnakes lack chromosome-wide dosage compensation. Our study provides the first full scale overview of the evolution of snake sex chromosomes at the genomic level, thus greatly expanding our knowledge of reptilian and vertebrate sex chromosomes

  2. Mice lacking hippocampal left-right asymmetry show non-spatial learning deficits.

    Science.gov (United States)

    Shimbo, Akihiro; Kosaki, Yutaka; Ito, Isao; Watanabe, Shigeru

    2018-01-15

    Left-right asymmetry is known to exist at several anatomical levels in the brain and recent studies have provided further evidence to show that it also exists at a molecular level in the hippocampal CA3-CA1 circuit. The distribution of N-methyl-d-aspartate (NMDA) receptor NR2B subunits in the apical and basal synapses of CA1 pyramidal neurons is asymmetrical if the input arrives from the left or right CA3 pyramidal neurons. In the present study, we examined the role of hippocampal asymmetry in cognitive function using β2-microglobulin knock-out (β2m KO) mice, which lack hippocampal asymmetry. We tested β2m KO mice in a series of spatial and non-spatial learning tasks and compared the performances of β2m KO and C57BL6/J wild-type (WT) mice. The β2m KO mice appeared normal in both spatial reference memory and spatial working memory tasks but they took more time than WT mice in learning the two non-spatial learning tasks (i.e., a differential reinforcement of lower rates of behavior (DRL) task and a straight runway task). The β2m KO mice also showed less precision in their response timing in the DRL task and showed weaker spontaneous recovery during extinction in the straight runway task. These results indicate that hippocampal asymmetry is important for certain characteristics of non-spatial learning. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Global survey of Klebsiella pneumoniae major porins from ertapenem non-susceptible isolates lacking carbapenemases.

    Science.gov (United States)

    Wise, Mark G; Horvath, Elizabeth; Young, Katherine; Sahm, Daniel F; Kazmierczak, Krystyna M

    2018-03-01

    To understand the diversity of porin disruption in Klebsiella pneumoniae, the major outer membrane protein (OMP) porins, OmpK35 and OmpK36, were examined in a set of isolates that did not harbour traditional carbapenem-hydrolysing enzymes, but nevertheless tested non-susceptible to ertapenem. A world-wide collection of Klebsiella pneumoniae isolates that were part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance project over the years 2008-2014 were characterised with regard to their β-lactamase gene carriage and potential permeability defects. Four hundred and eighty-seven isolates that did not carry carbapenemase genes, but were non-susceptible to ertapenem, were investigated by sequence analysis of the genes encoding OmpK35 and OmpK36. Isolates without obvious genetic lesions in either major porin gene were further examined by outer membrane protein SDS-PAGE. The majority of isolates, 83.0 % (404/487), exhibited clear genetic disruption in either or both of the ompK35 and ompK36 genes. Among the proportion of the collection with the highest ertapenem MIC value (>4 mg l -1 ), 60.5 % (115/190) showed mutation in both porin genes. Isolates without obvious genetic mutations were examined by SDS-PAGE, and 90.4 % (75/83) were found to lack or show altered expression of at least one of the major OMPs when compared to an ertapenem sensitive control strain. This study illustrates that porin deficiency in Klebsiella pneumoniae is a widespread phenomenon, and in combination with ESBLs and/or AmpC enzymes, likely accounts for the elevated ertapenem MICs observed in this study.

  4. Cadmium toxicity to Microcystis aeruginosa PCC 7806 and its microcystin-lacking mutant.

    Directory of Open Access Journals (Sweden)

    Bin Huang

    Full Text Available The adverse effects of microcystin (MC produced by cyanobacteria have drawn considerable attention from the public. Yet it remains unclear whether MC confers any benefits to the cyanobacteria themselves. One suggested function of MC is complexation, which may influence the bioaccumulation and toxicity of trace metals. To test this hypothesis, we examined Cd toxicity to wild-type Microcystis aeruginosa PCC 7806 (WT and its MC-lacking mutant (MT under nutrient-enriched (+NP, phosphorus-limited (-P, and nitrogen-limited (-N conditions. The accumulation of Cd and the biochemical parameters associated with its detoxification [total phosphorus (TP, inorganic polyphosphate (Poly-P, and glutathione (GSH in the cells as well as intra- and extra-cellular carbohydrates] were quantified. Although the -P cyanobacteria accumulated less Cd than their +NP and -N counterparts, the different nutrient-conditioned cyanobacteria were similarly inhibited by similar free ion concentration of Cd in the medium ([Cd2+]F. Such good toxicity predictability of [Cd2+]F was ascribed to the synchronous decrease in the intracellular concentrations of Cd and TP. Nevertheless, Cd toxicity was still determined by the intracellular Cd to phosphorus ratio (Cd/P, in accordance with what has been reported in the literature. On the other hand, the concentrations of TP, Poly-P, and carbohydrates went up, but GSH concentration dropped down with the enhancement of [Cd2+]F, indicating their association with Cd detoxification. Although the inactivation of MC peptide synthetase gene had some nutrient and Cd concentration dependent effects on the parameters above, both cyanobacterial strains showed the same Cd accumulation ability and displayed similar Cd sensitivity. These results suggest that MC cannot affect metal toxicity either by regulating metal accumulation or by altering the detoxification ability of the cyanobacteria. Other possible functions of MC need to be further investigated.

  5. Lactose metabolism in Streptococcus lactis: studies with a mutant lacking glucokinase and mannose-phosphotransferase activities

    International Nuclear Information System (INIS)

    Thompson, J.; Chassy, B.M.; Egan, W.

    1985-01-01

    A mutant of Streptococcus lactis 133 has been isolated that lacks both glucokinase and phosphoenolpyruvate-dependent mannose- phosphotransferase (mannose-PTS) activities. The double mutant S. lactis 133 mannose-PTSd GK- is unable to utilize either exogenously supplied or intracellularly generated glucose for growth. Fluorographic analyses of metabolites formed during the metabolism of [ 14 C]lactose labeled specifically in the glucose or galactosyl moiety established that the cells were unable to phosphorylate intracellular glucose. However, cells of S. lactis 133 mannose-PTSd GK- readily metabolized intracellular glucose 6-phosphate, and the growth rates and cell yield of the mutant and parental strains on sucrose were the same. During growth on lactose, S. lactis 133 mannose-PTSd GK- fermented only the galactose moiety of the disaccharide, and 1 mol of glucose was generated per mol of lactose consumed. For an equivalent concentration of lactose, the cell yield of the mutant was 50% that of the wild type. The specific rate of lactose utilization by growing cells of S. lactis 133 mannose-PTSd GK- was ca. 50% greater than that of the wild type, but the cell doubling times were 70 and 47 min, respectively. High-resolution 31 P nuclear magnetic resonance studies of lactose transport by starved cells of S. lactis 133 and S. lactis 133 mannose-PTSd GK- showed that the latter cells contained elevated lactose-PTS activity. Throughout exponential growth on lactose, the mutant maintained an intracellular steady-state glucose concentration of 100 mM

  6. Estimating open population site occupancy from presence-absence data lacking the robust design.

    Science.gov (United States)

    Dail, D; Madsen, L

    2013-03-01

    Many animal monitoring studies seek to estimate the proportion of a study area occupied by a target population. The study area is divided into spatially distinct sites where the detected presence or absence of the population is recorded, and this is repeated in time for multiple seasons. However, when occupied sites are detected with probability p Ecology 84, 2200-2207) developed a multiseason model for estimating seasonal site occupancy (ψt ) while accounting for unknown p. Their model performs well when observations are collected according to the robust design, where multiple sampling occasions occur during each season; the repeated sampling aids in the estimation p. However, their model does not perform as well when the robust design is lacking. In this paper, we propose an alternative likelihood model that yields improved seasonal estimates of p and Ψt in the absence of the robust design. We construct the marginal likelihood of the observed data by conditioning on, and summing out, the latent number of occupied sites during each season. A simulation study shows that in cases without the robust design, the proposed model estimates p with less bias than the MacKenzie et al. model and hence improves the estimates of Ψt . We apply both models to a data set consisting of repeated presence-absence observations of American robins (Turdus migratorius) with yearly survey periods. The two models are compared to a third estimator available when the repeated counts (from the same study) are considered, with the proposed model yielding estimates of Ψt closest to estimates from the point count model. Copyright © 2013, The International Biometric Society.

  7. Biomedical journals lack a consistent method to detect outcome reporting bias: a cross-sectional analysis.

    Science.gov (United States)

    Huan, L N; Tejani, A M; Egan, G

    2014-10-01

    An increasing amount of recently published literature has implicated outcome reporting bias (ORB) as a major contributor to skewing data in both randomized controlled trials and systematic reviews; however, little is known about the current methods in place to detect ORB. This study aims to gain insight into the detection and management of ORB by biomedical journals. This was a cross-sectional analysis involving standardized questions via email or telephone with the top 30 biomedical journals (2012) ranked by impact factor. The Cochrane Database of Systematic Reviews was excluded leaving 29 journals in the sample. Of 29 journals, 24 (83%) responded to our initial inquiry of which 14 (58%) answered our questions and 10 (42%) declined participation. Five (36%) of the responding journals indicated they had a specific method to detect ORB, whereas 9 (64%) did not have a specific method in place. The prevalence of ORB in the review process seemed to differ with 4 (29%) journals indicating ORB was found commonly, whereas 7 (50%) indicated ORB was uncommon or never detected by their journal previously. The majority (n = 10/14, 72%) of journals were unwilling to report or make discrepancies found in manuscripts available to the public. Although the minority, there were some journals (n = 4/14, 29%) which described thorough methods to detect ORB. Many journals seemed to lack a method with which to detect ORB and its estimated prevalence was much lower than that reported in literature suggesting inadequate detection. There exists a potential for overestimation of treatment effects of interventions and unclear risks. Fortunately, there are journals within this sample which appear to utilize comprehensive methods for detection of ORB, but overall, the data suggest improvements at the biomedical journal level for detecting and minimizing the effect of this bias are needed. © 2014 John Wiley & Sons Ltd.

  8. Progressive supranuclear palsy presenting as primary lateral sclerosis but lacking parkinsonism, gaze palsy, aphasia, or dementia.

    Science.gov (United States)

    Nagao, Shigeto; Yokota, Osamu; Nanba, Reiko; Takata, Hiroshi; Haraguchi, Takashi; Ishizu, Hideki; Ikeda, Chikako; Takeda, Naoya; Oshima, Etsuko; Sakane, Katsuaki; Terada, Seishi; Ihara, Yuetsu; Uchitomi, Yosuke

    2012-12-15

    We report an autopsy case of progressive supranuclear palsy (PSP) that clinically showed only slowly progressive and symmetric upper motor neuron syndrome over a disease course of 12 years. A female patient initially exhibited dysarthria at the age of 65, followed by gait disturbance and dysphagia. Neurological examination at age 67 disclosed pseudobulbar palsy, spastic gait, hyperreflexia, and presence of bilateral Hoffmann and Babinski signs. However, muscle atrophy, weakness, evidence of denervation on electromyography, vertical gaze palsy, parkinsonism, gait freezing, aphasia, speech apraxia, or dementia was not noted throughout the course. She was clinically diagnosed as having motor neuron disease consistent with so-called primary lateral sclerosis. Pathological examination disclosed histopathological features of PSP, including argyrophilic and tau-positive tufted astrocytes, neurofibrillary tangles, coiled bodies, and thread-like processes in the motor cortex and superior frontal gyrus, and to a lesser degree, in the basal ganglia and brain stem nuclei. In addition, severe fibrillary gliosis was noted in the precentral gyrus and corticospinal tract, being consistent with upper motor neuron syndrome observed in this case. No TAR-DNA binding protein 43-positive lesion, FUS pathology, Bunina body, or Lewy body-like hyaline inclusion was noted in the motor cortex or lower motor neurons. These findings suggest that when tau pathology is prominent in the motor cortex but is minimal in the basal ganglia and brain stem nuclei, a PSP case can lack all classic clinical features of PSP and show only slowly progressive upper motor syndrome, consistent with clinical picture of primary lateral sclerosis. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Selective reward deficit in mice lacking beta-endorphin and enkephalin.

    Science.gov (United States)

    Hayward, Michael D; Pintar, John E; Low, Malcolm J

    2002-09-15

    It has been impossible to unequivocally identify which endogenous opioids modulate the incentive value of rewarding stimuli because these peptides are not highly selective for any single opioid receptor subtype. Here, we present evidence based on the measurement of instrumental behavior of beta-endorphin and enkephalin knock-out mice that both opioid peptides play a positive role. A progressive ratio schedule was used to measure how hard an animal would work for food reinforcers. The loss of either opioid reduced responding under this schedule, regardless of the palatability of the three different formulas of reinforcers used. The phenotype of mice lacking both endogenous opioids was nearly identical to the phenotype of mice mutant for either individual opioid. Responses were tested in nondeprived and deprived feeding states but were reduced in beta-endorphin- and enkephalin-deficient mice only when they were maintained under nondeprived conditions. Other operant manipulations ruled out variables that might contribute nonspecifically to this result such as differences in acquisition, early satiation, motor performance deficit, and reduced resistance to extinction. In contrast to the effects on instrumental performance, the loss of either or both endogenous opioids did not influence preference for water flavored with sucrose or saccharin in a two-bottle free-choice drinking paradigm. We conclude that both beta-endorphin and enkephalin positively contribute to the incentive-motivation to acquire food reinforcers. Because the attenuation of operant responding was observed only during a nondeprived motivational state, the hedonics of feeding are likely altered rather than energy homeostasis.

  10. Guidelines warfare over interventional techniques: is there a lack of discourse or straw man?

    Science.gov (United States)

    Manchikanti, Laxmaiah; Benyamin, Ramsin M; Falco, Frank J E; Caraway, David L; Datta, Sukdeb; Hirsch, Joshua A

    2012-01-01

    Guideline development seems to have lost some of its grounding as a medical science. At their best, guidelines should be a constructive response to assist practicing physicians in applying the exponentially expanding body of medical knowledge. In fact, guideline development seems to be evolving into a cottage industry with multiple, frequently discordant guidance on the same subject. Evidence Based Medicine does not always provide for conclusive opinions. With competing interests of payers, practitioners, health policy makers, and third parties benefiting from development of the guidelines as cost saving measures, guideline preparation has been described as based on pre-possession, vagary, rationalization, or congeniality of conclusion. Beyond legitimate differences in opinions regarding the evidence that could yield different guidelines there are potentials for conflicts of interest and various other issues play a major role in guideline development. As is always the case, conflicts of interest in guideline preparation must be evaluated and considered. Following the development of American Pain Society (APS) guidelines there has been an uproar in interventional pain management communities on various issues related to not only the evidence synthesis, but conflicts of interest. A recent manuscript published by Chou et al, in addition to previous publications, appears to have limited clinician involvement in the development of APS guidelines, and demonstrates some of these challenges clearly. This manuscript illustrates the deficiencies of Chou et al's criticisms, and demonstrates their significant conflicts of interest, and use a lack of appropriate evaluations in interventional pain management as a straw man to support their argument. Further, this review will attempt to demonstrate that excessive focus on this straw man has inhibited critique of what we believe to be flaws in the approach.  

  11. Vinclozolin--the lack of a transgenerational effect after oral maternal exposure during organogenesis.

    Science.gov (United States)

    Schneider, Steffen; Kaufmann, Wolfgang; Buesen, Roland; van Ravenzwaay, Bennard

    2008-04-01

    The purpose of the study was to investigate a possible transgenerational effect of the fungicide vinclozolin on the male reproductive system following oral exposure since this effect was reported by Anway et al. [Anway MD, Cupp AS, Uzumcu M, Skinner MK. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 2005;308(5727 (June 3)):1466-9] after intraperitoneal administration. Pregnant Wistar rats were dosed by oral gavage with vinclozolin 0, 4 or 100mg/(kg bw day) on days 6-15 post coitum (p.c.). F1 male offspring was mated with untreated females to produce F2, which were then similarly mated to produce F3 offspring. F0 maternal treatment had no effect on mating and fertility indices or male offspring sexual development, mean sperm parameters, or histopathology of the sexual organs in F1, F2 or F3 males (at age 127-134 days). Apoptotic germ cell counts were statistically significantly lower in F1, F2 and F3 generations, however, control values showed a pronounced variance over time. Also, as anti-androgenic compounds are more likely to induce the opposite effect (increased apoptosis), this observation is not considered to be treatment related. Consequently, spermatogenesis was not affected by vinclozolin exposure in utero. As vinclozolin has been shown to induce clear anti-androgenic effects in offspring following treatment with 100mg/(kg bw day) during entire gestation, the lack of effects in this study indicates that the window of sensitivity for anti-androgenic effects is from days 16-20 p.c. No transgenerational effect on the male reproductive system was found. The NOAEL was >100mg/(kg bw day) for fertility and reproductive performance, for systemic parental and developmental toxicity in F1, F2 and F3 males.

  12. Ethanol-related behaviors in mice lacking the sigma-1 receptor.

    Science.gov (United States)

    Valenza, Marta; DiLeo, Alyssa; Steardo, Luca; Cottone, Pietro; Sabino, Valentina

    2016-01-15

    The Sigma-1 receptor (Sig-1R) is a chaperone protein that has been implicated in drug abuse and addiction. Multiple studies have characterized the role the Sig-1R plays in psychostimulant addiction; however, fewer studies have specifically investigated its role in alcohol addiction. We have previously shown that antagonism of the Sig-1R reduces excessive drinking and motivation to drink, whereas agonism induces binge-like drinking in rodents. The objectives of these studies were to investigate the impact of Sig-1R gene deletion in C57Bl/6J mice on ethanol drinking and other ethanol-related behaviors. We used an extensive panel of behavioral tests to examine ethanol actions in male, adult mice lacking Oprs1, the gene encoding the Sig-1R. To compare ethanol drinking behavior, Sig-1 knockout (KO) and wild type (WT) mice were subject to a two-bottle choice, continuous access paradigm with different concentrations of ethanol (3-20% v/v) vs. water. Consumption of sweet and bitter solutions was also assessed in Sig-1R KO and WT mice. Finally, motor stimulant sensitivity, taste aversion and ataxic effects of ethanol were assessed. Sig-1R KO mice displayed higher ethanol intake compared to WT mice; the two genotypes did not differ in their sweet or bitter taste perception. Sig-1R KO mice showed lower sensitivity to ethanol stimulant effects, but greater sensitivity to its taste aversive effects. Ethanol-induced sedation was instead unaltered in the mutants. Our results prove that the deletion of the Sig-1R increases ethanol consumption, likely by decreasing its rewarding effects, and therefore indicating that the Sig-1R is involved in modulation of the reinforcing effects of alcohol. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Test Your Memory is sensitive to cognitive change but lacks prospective validity.

    Science.gov (United States)

    Ferrero-Arias, J; Turrión-Rojo, M Á

    2016-03-01

    To determine the prospective validity of Test Your Memory (TYM) and its sensitivity to change in cognitive state. This longitudinal prospective study followed 71 patients with subjective cognitive symptoms and 48 with mild cognitive impairment for a mean time period of 35.2 ± 15 months. Subjects did not have dementia or depression at the beginning of follow-up and each participant was given the TYM at least two times. A psychometric threshold was established to determine presence of a cognitive deficit (z-score ≤ 1.5 on at least one cognitive domain) and the Disability Assessment for Dementia scale was used to ensure full functional ability. The criterion for deterioration was a change in the stage on the Global Deterioration Scale. Sixty-one patients remained cognitively stable and 58 worsened. There were no differences between them with respect to sex, educational attainment, the initial stage on the GDS, or the score on the first TYM. Subjects who worsened were older than those who did not. The TYM increased an average of 0.04 points per month in patients who remained stable or improved (95% CI, -0.01 to 0.08) and decreased an average of 0.14 points per month in those whose condition worsened (95% CI, -0.19 to -0.09). Subjects with mild cognitive impairment who worsened displayed a sharper loss of TYM points than did subjects with subjective cognitive symptoms. While the TYM lacks prospective validity, it is sensitive to changes in cognitive state. Copyright © 2015 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  14. Analgesic tone conferred by constitutively active mu opioid receptors in mice lacking β-arrestin 2

    Directory of Open Access Journals (Sweden)

    Hales Tim G

    2011-04-01

    Full Text Available Abstract Hedonic reward, dependence and addiction are unwanted effects of opioid analgesics, linked to the phasic cycle of μ opioid receptor activation, tolerance and withdrawal. In vitro studies of recombinant G protein coupled receptors (GPCRs over expressed in cell lines reveal an alternative tonic signaling mechanism that is independent of agonist. Such studies demonstrate that constitutive GPCR signaling can be inhibited by inverse agonists but not by neutral antagonists. However, ligand-independent activity has been difficult to examine in vivo, at the systems level, due to relatively low levels of constitutive activity of most GPCRs including μ receptors, often necessitating mutagenesis or pharmacological manipulation to enhance basal signaling. We previously demonstrated that the absence of β-arrestin 2 (β-arr2 augments the constitutive coupling of μ receptors to voltage-activated Ca2+ channels in primary afferent dorsal root ganglion neurons from β-arr2-/- mice. We used this in vitro approach to characterize neutral competitive antagonists and inverse agonists of the constitutively active wild type μ receptors in neurons. We administered these agents to β-arr2-/- mice to explore the role of constitutive μ receptor activity in nociception and hedonic tone. This study demonstrates that the induction of constitutive μ receptor activity in vivo in β-arr2-/- mice prolongs tail withdrawal from noxious heat, a phenomenon that was reversed by inverse agonists, but not by antagonists that lack negative efficacy. By contrast, the aversive effects of inverse agonists were similar in β-arr2-/- and β-arr2+/+ mice, suggesting that hedonic tone was unaffected.

  15. Systems biological approach to investigate the lack of familial link between Down's Syndrome & Neural Tube Disorders.

    Science.gov (United States)

    Ragunath, Pk; Abhinand, Pa

    2013-01-01

    Systems Biology involves the study of the interactions of biological systems and ultimately their functions. Down's syndrome (DS) is one of the most common genetic disorders which are caused by complete, or occasionally partial, triplication of chromosome 21, characterized by cognitive and language dysfunction coupled with sensory and neuromotor deficits. Neural Tube Disorders (NTDs) are a group of congenital malformations of the central nervous system and neighboring structures related to defective neural tube closure during the first trimester of pregnancy usually occurring between days 18-29 of gestation. Several studies in the past have provided considerable evidence that abnormal folate and methyl metabolism are associated with onset of DS & NTDs. There is a possible common etiological pathway for both NTDs and Down's syndrome. But, various research studies over the years have indicated very little evidence for familial link between the two disorders. Our research aimed at the gene expression profiling of microarray datasets pertaining to the two disorders to identify genes whose expression levels are significantly altered in these conditions. The genes which were 1.5 fold unregulated and having a p-value disorders were recognized and over representation analysis was carried out for each of the constituent genes. The comprehensive manual analysis of these genes yields a hypothetical understanding of the lack of familial link between DS and NTDs. There were no genes involved with folic acid present in the dense cliques. Only - CBL, EGFR genes were commonly present, which makes the allelic variants of these genes - good candidates for future studies regarding the familial link between DS and NTDs. NTD - Neural Tube Disorders, DS - Down's Syndrome, MTHFR - Methylenetetrahydrofolate reductase, MTRR- 5 - methyltetrahydrofolate-homocysteine methyltransferase reductase.

  16. Lack of acculturation is a risk factor for diabetes in arab immigrants in the US.

    Science.gov (United States)

    Jaber, Linda A; Brown, Morton B; Hammad, Adnan; Zhu, Qian; Herman, William H

    2003-07-01

    To examine the relationship between dysglycemia (impaired fasting glucose, impaired glucose tolerance, and diabetes) and acculturation, physical activity, and perceived stress in Arab immigrants in the U.S. In a cross-sectional population-based study, we examined 520 Arab Americans, aged 20-75 years, who were born in the Middle East and immigrated to southeastern Michigan. Dysglycemia was assessed by history and with a 2-h 75-g oral glucose tolerance test. Acculturation, physical activity, and perceived stress were measured with standardized questionnaires. Associations were found between dysglycemia in men and older age at immigration, unemployment, speaking Arabic with friends, being less active in Arabic organizations, more frequent consumption of Arabic food, and less integration into American society. Dysglycemia in women was associated with being raised in rural areas of the Middle East, older age at immigration, longer length of stay in the U.S., not being employed outside the home, less than high school education, not attending Arabic or American schools, and not being able to read Arabic. Among men, older age at immigration, shorter length of stay in the U.S., less activity in Arab organizations, and eating Arabic food were associated with dysglycemia independent of age and BMI. Among women, acculturation was very low and was confounded with age and BMI as powerful risk factors for dysglycemia. No association was found between physical activity, perceived stress, and the risk of dysglycemia in either sex. Lack of acculturation is an important risk factor for dysglycemia in immigrant Arab Americans. Intervention programs aimed at diabetes prevention should consider the acculturation process.

  17. Lack of Plasma Protein Hemopexin Results in Increased Duodenal Iron Uptake.

    Science.gov (United States)

    Fiorito, Veronica; Geninatti Crich, Simonetta; Silengo, Lorenzo; Aime, Silvio; Altruda, Fiorella; Tolosano, Emanuela

    2013-01-01

    The body concentration of iron is regulated by a fine equilibrium between absorption and losses of iron. Iron can be absorbed from diet as inorganic iron or as heme. Hemopexin is an acute phase protein that limits iron access to microorganisms. Moreover, it is the plasma protein with the highest binding affinity for heme and thus it mediates heme-iron recycling. Considering its involvement in iron homeostasis, it was postulated that hemopexin may play a role in the physiological absorption of inorganic iron. Hemopexin-null mice showed elevated iron deposits in enterocytes, associated with higher duodenal H-Ferritin levels and a significant increase in duodenal expression and activity of heme oxygenase. The expression of heme-iron and inorganic iron transporters was normal. The rate of iron absorption was assessed by measuring the amount of (57)Fe retained in tissues from hemopexin-null and wild-type animals after administration of an oral dose of (57)FeSO4 or of (57)Fe-labelled heme. Higher iron retention in the duodenum of hemopexin-null mice was observed as compared with normal mice. Conversely, iron transfer from enterocytes to liver and bone marrow was unaffected in hemopexin-null mice. The increased iron level in hemopexin-null duodenum can be accounted for by an increased iron uptake by enterocytes and storage in ferritins. These data indicate that the lack of hemopexin under physiological conditions leads to an enhanced duodenal iron uptake thus providing new insights to our understanding of body iron homeostasis.

  18. Lack of beat isochrony disrupts motor performance in a child drummer prodigy

    Directory of Open Access Journals (Sweden)

    Farrugia Nicolas

    2011-12-01

    Full Text Available Several studies have focused on coupling between perception and action (e.g., via finger tapping, and more generally on entrainment, in average musicians and non-musicians. Yet, little is known about the effects of entrainment on timing and movement kinematics in individuals exhibiting outstanding rhythmical abilities. In this study we examined the effect of beat isochrony on the performance of IF, a 7-year-old child drummer prodigy. IF displayed very early (at 3-4 years of age outstanding musical abilities, and exceptional sensorimotor synchronization. To assess whether temporal regularity of the underlying beat (i.e., isochrony during music playing affects IF’s performance we tested IF and a “control” group (i.e., children from music schools with 1-to1.5 years of percussion training in a motion capture study. Participants imitated a short 6-note isochronous metrical pattern (Strong-weak-weak-Strong-weak-weak on a percussion pad under four conditions. In the first condition the pattern was imitated repeatedly along with a metronome. In the second condition, the pattern was repeated but with a break in between repetitions, together with a metronome. In the third condition, similar breaks were introduced, but disrupting beat isochrony (i.e., with an irregular, though predictable, metronome. Finally, in the fourth condition break durations were random. IF exhibited higher temporal accuracy than controls with an isochronous metronome. However, his performance was much less accurate with disrupted beat isochrony. This was accompanied by overall differences between IF and controls in movement kinematics in terms of movement amplitude, and anticipation times. Enhanced performance in the presence of an isochronous beat, as opposed to lack of isochrony, suggests that motor entrainment may act as a marker of musical expertise early during development.

  19. Human reliability

    International Nuclear Information System (INIS)

    Embrey, D.E.

    1987-01-01

    Concepts and techniques of human reliability have been developed and are used mostly in probabilistic risk assessment. For this, the major application of human reliability assessment has been to identify the human errors which have a significant effect on the overall safety of the system and to quantify the probability of their occurrence. Some of the major issues within human reliability studies are reviewed and it is shown how these are applied to the assessment of human failures in systems. This is done under the following headings; models of human performance used in human reliability assessment, the nature of human error, classification of errors in man-machine systems, practical aspects, human reliability modelling in complex situations, quantification and examination of human reliability, judgement based approaches, holistic techniques and decision analytic approaches. (UK)

  20. Human Rights, Human Needs, Human Development, Human Security

    OpenAIRE

    Gasper, Des

    2009-01-01

    Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and politics; each has emerged within the United Nations world; each relies implicitly on a conceptualisation of human need; each has specific strengths. Yet mutual communication, understanding and co-operation are deficient, espec...

  1. Generation of mice lacking DUF1220 protein domains: effects on fecundity and hyperactivity

    Science.gov (United States)

    Keeney, JG; O’Bleness, MS; Anderson, N; Davis, JM; Arevalo, N; Busquet, N; Chick, W; Rozman, J; Hölter, SM; Garrett, L; Horsch, M; Beckers, J; Wurst, W; Klingenspor, M; Restrepo, D

    2014-01-01

    Sequences encoding DUF1220 protein domains show the most extreme human lineage-specific copy number increase of any coding region in the genome and have been linked to human brain evolution. In addition, DUF1220 copy number (dosage) has been implicated in influencing brain size within the human species, both in normal populations and in individuals associated with brain size pathologies (1q21-associated microcephaly and macrocephaly). More recently, increasing dosage of a subtype of DUF1220 has been linked with increasing severity of the primary symptoms of autism. Despite these intriguing associations, a function for these domains has not been described. As a first step in addressing this question we have developed the first transgenic model of DUF1220 function by removing the single DUF1220 domain (the ancestral form) encoded in the mouse genome. In a hypothesis generating exercise, these mice were evaluated by 197 different phenotype measurements. While resulting DUF1220-minus (KO) mice show no obvious anatomical peculiarities, they exhibit a significantly reduced fecundity (χ2= 19.1, df = 2, p = 7.0 × 10−5). Further extensive phenotypic analyses suggest hyperactivity (p < 0.05) of DUF1220 mice and changes in gene expression levels of brain associated with distinct neurological functions and disease. Other changes that met statistical significance include an increase in plasma glucose concentration (as measured by Area Under the Curve, AUC 0-30 and AUC 30-120) in male mutants, fasting glucose levels, reduce sodium levels in male mutants, increased levels of the liver functional indicator ALAT/GPT in males, levels of alkaline phosphatase (also an indicator of liver function), mean R and SR amplitude by electrocardiography, elevated IgG3 levels, a reduced ratio of CD4:CD8 cells, and a reduced frequency of T cells; though it should be noted that many of these differences are quite small and require further examination. The linking of DUF1220 loss to a

  2. Generation of mice lacking DUF1220 protein domains: effects on fecundity and hyperactivity.

    Science.gov (United States)

    Keeney, J G; O'Bleness, M S; Anderson, N; Davis, J M; Arevalo, N; Busquet, N; Chick, W; Rozman, J; Hölter, S M; Garrett, L; Horsch, M; Beckers, J; Wurst, W; Klingenspor, M; Restrepo, D; de Angelis, M Hrabě; Sikela, J M

    2015-02-01

    Sequences encoding DUF1220 protein domains show the most extreme human lineage-specific copy number increase of any coding region in the genome and have been linked to human brain evolution. In addition, DUF1220 copy number (dosage) has been implicated in influencing brain size within the human species, both in normal populations and in individuals associated with brain size pathologies (1q21-associated microcephaly and macrocephaly). More recently, increasing dosage of a subtype of DUF1220 has been linked with increasing severity of the primary symptoms of autism. Despite these intriguing associations, a function for these domains has not been described. As a first step in addressing this question, we have developed the first transgenic model of DUF1220 function by removing the single DUF1220 domain (the ancestral form) encoded in the mouse genome. In a hypothesis generating exercise, these mice were evaluated by 197 different phenotype measurements. While resulting DUF1220-minus (KO) mice show no obvious anatomical peculiarities, they exhibit a significantly reduced fecundity (χ(2) = 19.1, df = 2, p = 7.0 × 10(-5)). Further extensive phenotypic analyses suggest hyperactivity (p < 0.05) of DUF1220 mice and changes in gene expression levels of brain associated with distinct neurological functions and disease. Other changes that met statistical significance include an increase in plasma glucose concentration (as measured by area under the curve, AUC 0-30 and AUC 30-120) in male mutants, fasting glucose levels, reduce sodium levels in male mutants, increased levels of the liver functional indicator ALAT/GPT in males, levels of alkaline phosphatase (also an indicator of liver function), mean R and SR amplitude by electrocardiography, elevated IgG3 levels, a reduced ratio of CD4:CD8 cells, and a reduced frequency of T cells; though it should be noted that many of these differences are quite small and require further examination. The linking of DUF1220 loss to a

  3. Human cloning and human dignity

    Directory of Open Access Journals (Sweden)

    Hasan Eslami

    2006-12-01

    Full Text Available Catholic Church and most of Muslims believe that human cloning is in contrast with human rights. They argue that applying Somatic Nuclear Transfer Technique or so-called cloning to humans is against human dignity. Their main reason is that the cloned person would be a copy or shadow of another person and lack his or her identity and uniqueness. They also argue that in the process of cloning human beings would be treated as laboratory mice. This article tries to evaluate this kind of argumentation and shows that the "human dignity" expression in the relevant writings is vague and has been used inappropriately. مسیحیان و برخی از مسلمانان استدلال می‌کنند که کاربست تکنیک شبیه‌سازی ناقض کرامت انسانی است. این دلیل خود به صورت‌های مختلفی بیان می‌شود، مانند آنکه انسان موضوع آزمایش‌های علمی قرار می‌گیرد و با او مانند حیوانات رفتار می‌شود. گاه نیز تغییر نحوة تولید مثل، مایة نقض کرامت انسانی قلمداد می‌گردد و گاه به مسئلة از بین رفتن هویت فردی اشاره می‌شود. نگارنده در دو قسمت، دیدگاه مسیحیان و مسلمانان را در این باره نقل و تحلیل کرده است و کوشیده است نشان دهد که استناد به مفهوم کرامت انسانی در این جا مبهم و ناگویاست و مخالفان کوشش دقیقی در جهت تبیین دلیل خود به عمل نیاورده‌اند.

  4. Cells Lacking mtDNA Display Increased dNTP Pools upon DNA Damage

    DEFF Research Database (Denmark)

    Skovgaard, Tine; Rasmussen, Lene Juel; Munch-Petersen, Birgitte

    Imbalanced dNTP pools are highly mutagenic due to a deleterious effect on DNA polymerase fidelity. Mitochondrial DNA defects, including mutations and deletions, are commonly found in a wide variety of different cancer types. In order to further study the interconnection between dNTP pools...... and mitochondrial function we have examined the effect of DNA damage on dNTP pools in cells deficient of mtDNA. We show that DNA damage induced by UV irradiation, in a dose corresponding to LD50, induces an S phase delay in different human osteosarcoma cell lines. The UV pulse also has a destabilizing effect...... shows that normal mitochondrial function is prerequisite for retaining stable dNTP pools upon DNA damage. Therefore it is likely that mitochondrial deficiency defects may cause an increase in DNA mutations by disrupting dNTP pool balance....

  5. Lack of skilled personnel as threat to HR security of industrial enterprises

    Directory of Open Access Journals (Sweden)

    Ozernikova Tatiana

    2017-01-01

    Full Text Available The article assesses the needs of Russian industrial enterprises for skilled labor. The authors consider deficiency in qualified personnel as a threat to the human resources security of industrial enterprises, and analyze its causes. The study includes the criteria to distinguish highly skilled employees in the labor force (education level, occupation, correspondence of performed work to education, and analysis of the dynamics of their number. It identifies the internal and external factors that have a significant influence on the number of qualified personnel. The external factors include the size of the salary, population growth due to migration, the regional level of the socio-economic development. The applied methods of analysis are single-factor analysis of variance (F-test, multiple regression and descriptive statistics. The analysis is based on the materials of the Russian Federal State Statistics Service, as well as on the Russian Longitudinal Monitoring Survey - Higher School of Economics.

  6. Characterization of yeast mutants lacking alkaline ceramidases YPC1 and YDC1

    DEFF Research Database (Denmark)

    Voynova, Natalia S; Mallela, Shamroop K; Vazquez, Hector M

    2014-01-01

    Humans and yeast possess alkaline ceramidases located in the early secretory pathway. Single deletions of the highly homologous yeast alkaline ceramidases YPC1 and YDC1 have very little genetic interactions or phenotypes. Here, we performed chemical-genetic screens to find deletions...... reduces chronological life span. A novel finding is that, when working backwards as a ceramide synthase in vivo, Ypc1p prefers C24 and C26 fatty acids as substrates, whereas it prefers C16:0, when solubilized in detergent and working in vitro. Therefore, its physiological activity may not only concern...... the minor ceramides containing C14 and C16. Intriguingly, so far the sole discernable benefit of conserving YPC1 for yeast resides with its ability to convey relative resistance toward H2 O2 ....

  7. Lack of MRSP detection in healthy dogs attending a Danish referral hospital

    DEFF Research Database (Denmark)

    Paul, Narayan Chandra

    low in the Copenhagen area. This finding may explain why MRSP is rarely isolated from canine clinical at our diagnostic laboratory. Differently from S. aureus in humans, the perineum and the mouth are the body sites most frequently colonized with S. pseudintermedius in dogs. This information is highly......Introduction: Methicillin-resistant S. pseudintermedius (MRSP) is an emerging threat to pet animals due to its characteristic multidrug resistance profile. The current knowledge of the frequency of MRSP in the dog population is limited to few countries. Prior to this study, no information...... was available about the frequency of MRSP healthy dog carriers in Denmark. Objectives: The objectives of this study were i) to estimate the prevalence of MRSP and methicillin-susceptible S. pseudintermedius (MSSP) among healthy dogs in the area of Copenhagen, and ii) to compare the carriage rates at different...

  8. Mice lacking the kf-1 gene exhibit increased anxiety- but not despair-like behavior

    Directory of Open Access Journals (Sweden)

    Atsushi Tsujimura

    2008-09-01

    Full Text Available KF-1 was originally identified as a protein encoded by human gene with increased expression in the cerebral cortex of a patient with Alzheimer’s disease. In mouse brain, kf-1 mRNA is detected predominantly in the hippocampus and cerebellum, and kf-1 gene expression is elevated also in the frontal cortex of rats after chronic antidepressant treatments. KF-1 mediates E2-dependent ubiquitination and may modulate cellular protein levels as an E3 ubiquitin ligase, though its target proteins are not yet identified. To elucidate the role of kf-1 in the central nervous system, we generated kf-1 knockout mice by gene targeting, using Cre-lox recombination. The resulting kf-1−/− mice were normal and healthy in appearance. Behavioral analyses revealed that kf-1−/− mice showed significantly increased anxiety-like behavior compared with kf-1+/+ littermates in the light/dark transition and elevated plus maze tests; however, no significant differences were observed in exploratory locomotion using the open field test or in behavioral despair using the forced swim and tail suspension tests. These observations suggest that KF-1 suppresses selectively anxiety under physiological conditions probably through modulating protein levels of its unknown target(s. Interestingly, kf-1−/− mice exhibited significantly increased prepulse inhibition, which is usually reduced in human schizophrenic patients. Thus, the kf-1−/− mice provide a novel animal model for elucidating molecular mechanisms of psychiatric diseases such as anxiety/depression, and may be useful for screening novel anxiolytic/antidepressant compounds.

  9. Lack of experience is a significant factor in the missed diagnosis of perilunate fracture dislocation or isolated dislocation

    Directory of Open Access Journals (Sweden)

    Ilker Çolak

    2018-01-01

    Conclusion: The results of this study indicated that lack of experience was the most important factor in the misdiagnosis of perilunate fracture dislocation or isolated dislocation. Level of Evidence: Level IV, diagnostic study.

  10. Lack of seasonality in phytoplankton standing stock (chlorophyll a) and production in the western Bay of Bengal

    Digital Repository Service at National Institute of Oceanography (India)

    Madhu, N.V.; Jyothibabu, R.; Maheswaran, P.A.; Gerson, V.J.; Gopalakrishnan, T.C.; Nair, K.K.C.

    The investigations in the western Bay of Bengal (BoB) during summer, winter and spring intermonsoon periods evidenced lack of pronounced seasonal variation in phytoplankton standing stock (chlorophyll a) and primary production. The supply...

  11. [Lack of interest in general practice during the National Ranking Examination in 2005].

    Science.gov (United States)

    Lanson, Yves

    2006-03-01

    The second national ranking test took place in 2005 in the same conditions as the year before. Analysis of the results permits us to assess whether the objectives of this reform have been met so far. Data crossing of the results provided by the national testing center allowed us to rank: 1) the appeal of specializations for each geographic subdivision, 2) the candidates by medical school, and 3) the appeal of each subdivision by candidate rank. 66% of the students were classified high enough to be able to choose any specialization. Trends observed from the first examination, in 2004, were confirmed, with the clear desirability of medical specializations and a certain lack of interest in occupational medicine and public health. All the surgery posts were filled, even though the number of posts had increased enormously since the first examination. After adjustment for the number of posts available, the specializations in decreasing order of popularity were: medical, surgical, pediatrics, anesthesiology, gynecology-obstetrics, general medicine, psychiatry, and biology. Approximately 1000 posts in general medicine were not filled. The medical schools whose students ranked highest were Paris Pitié, Paris V, Paris West, Lyon North, Grenoble, and Aix-Marseille. Some medical schools did less well than previously: Marseille very slightly and Angers substantially. Strasbourg, Nancy Amiens and Bobigny were at the bottom of the list. The cities most desired for internships were Paris, Toulouse, Lyon, and Aix-Marseille, while Brest, Nancy, Limoges and the West Indies were ranked lowest, although each was chosen by highly ranked candidate. Two thirds of the students were ranked high enough to allow them a free choice of specializations. All the specializations except public health and occupational medicine had very highly ranked students. Medical specializations are the most desired, but surgery remains highly demanded, despite a substantial increase in the number of posts. All

  12. AFLP analysis reveals a lack of phylogenetic structure within Solanum section Petota

    Directory of Open Access Journals (Sweden)

    Vleeshouwers Vivianne GAA

    2008-05-01

    supported subdivisions, while a large part of the species cannot be structured at all. We believe that the lack of structure is not due to any methodological problem but represents the real biological situation within section Petota.

  13. A phase plane graph based model of the ovulatory cycle lacking the "positive feedback" phenomenon

    Directory of Open Access Journals (Sweden)

    Kurbel Sven

    2012-08-01

    sensitivity to estrogen is diminished due to lack of local ERs, hypothalamus switches back to the low GnRH secretion rate, leading to low secretion of gonadotropins and to lutheolysis. During low GnRH secretion rates, previously downregulated pituitary GnRH receptors recover to normal levels and thus allow the next cycle. Possible implications of the presented model on several topics related to reproductive physiology are shortly discussed with some evolutionary aspects including the emergence of menopause.

  14. Lack of adequate sun protection for children with oculocutaneous albinism in South Africa

    Science.gov (United States)

    Lund, Patricia M; Taylor, Julie S

    2008-01-01

    Background Childhood is a high risk time for ultraviolet induced skin damage as this age group has more time and opportunity to be outdoors in the sun. Children in Africa with the inherited condition oculocutaneous albinism (OCA) are especially vulnerable due to their lack of protective melanin. They are highly susceptible to developing skin lesions that have both cosmetic and health complications, with a high risk of developing skin cancers. The study aimed to explore the adequacy of sun protection strategies of children with albinism in order to inform future provision. Methods Community based participatory research methods were employed to investigate sun protection strategies in 90 pupils with OCA (40 female and 50 male) boarding at a special school educating pupils with visual impairment in a rural area of northern South Africa. Hats worn and sunscreen preparations used were examined during semi-structured face to face interviews conducted in small peer groups. The resident nurse interpreted if necessary and provided additional information on monitoring and treatment of skin lesions. Results Participants with albinism in this study were exposed to high levels of ultraviolet radiation throughout the year and showed skin damage despite wearing protective head gear. All except one pupil possessed at least one hat, with a mean brim width of 5.4 cm. Gender differences in sun avoidance behaviour were documented, with females seeking shade during recreational periods and males playing soccer outside. Although 38% of pupils were using a sunscreen with a sun protection factor (SPF) rating, only 12% had government sponsored tubes of SPF15 cream. Government sponsored sunscreen preparations were only provided if actively sought, involving time consuming trips to regional hospitals, with inadequate availability and insufficient supply. Conclusion Children with albinism living away from home in rural areas appear to have inadequate sun protection strategies. Changes in

  15. Circadian rhythms in the pineal organ persist in zebrafish larvae that lack ventral brain

    Directory of Open Access Journals (Sweden)

    Goldstein-Kral Lauren

    2011-01-01

    Full Text Available Abstract Background The mammalian suprachiasmatic nucleus (SCN, located in the ventral hypothalamus, is a major regulator of circadian rhythms in mammals and birds. However, the role of the SCN in lower vertebrates remains poorly understood. Zebrafish cyclops (cyc mutants lack ventral brain, including the region that gives rise to the SCN. We have used cyc embryos to define the function of the zebrafish SCN in regulating circadian rhythms in the developing pineal organ. The pineal organ is the major source of the circadian hormone melatonin, which regulates rhythms such as daily rest/activity cycles. Mammalian pineal rhythms are controlled almost exclusively by the SCN. In zebrafish and many other lower vertebrates, the pineal has an endogenous clock that is responsible in part for cyclic melatonin biosynthesis and gene expression. Results We find that pineal rhythms are present in cyc mutants despite the absence of an SCN. The arginine vasopressin-like protein (Avpl, formerly called Vasotocin is a peptide hormone expressed in and around the SCN. We find avpl mRNA is absent in cyc mutants, supporting previous work suggesting the SCN is missing. In contrast, expression of the putative circadian clock genes, cryptochrome 1b (cry1b and cryptochrome 3 (cry3, in the brain of the developing fish is unaltered. Expression of two pineal rhythmic genes, exo-rhodopsin (exorh and serotonin-N-acetyltransferase (aanat2, involved in photoreception and melatonin synthesis, respectively, is also similar between cyc embryos and their wildtype (WT siblings. The timing of the peaks and troughs of expression are the same, although the amplitude of expression is slightly decreased in the mutants. Cyclic gene expression persists for two days in cyc embryos transferred to constant light or constant dark, suggesting a circadian clock is driving the rhythms. However, the amplitude of rhythms in cyc mutants kept in constant conditions decreased more quickly than in their

  16. Traditional birth attendants lack basic information on HIV and safe delivery practices in rural Mysore, India.

    Science.gov (United States)

    Madhivanan, Purnima; Kumar, Bhavana N; Adamson, Paul; Krupp, Karl

    2010-09-22

    There is little research on HIV awareness and practices of traditional birth attendants (TBA) in India. This study investigated knowledge and attitudes among rural TBA in Karnataka as part of a project examining how traditional birth attendants could be integrated into prevention-of-mother-to-child transmission of HIV (PMTCT) programs in India. A cross-sectional survey was conducted between March 2008 and January 2009 among TBA in 144 villages in Mysore Taluk, Karnataka. Following informed consent, TBA underwent an interviewer-administered questionnaire in the local language of Kannada on practices and knowledge around birthing and HIV/PMTCT. Of the 417 TBA surveyed, the median age was 52 years and 96% were Hindus. A majority (324, 77.7%) had no formal schooling, 88 (21.1%) had up to 7 years and 5 (1%) had more than 7 yrs of education. Only 51 of the 417 TBA (12%) reported hearing about HIV/AIDS. Of those who had heard about HIV/AIDS, only 36 (72%) correctly reported that the virus could be spread from mother to child; 37 (74%) identified unprotected sex as a mode of transmission; and 26 (51%) correctly said healthy looking people could spread HIV. Just 22 (44%) knew that infected mothers could lower the risk of transmitting the virus to their infants. An overwhelming majority of TBA (401, 96.2%) did not provide antenatal care to their clients. Over half (254, 61%) said they would refer the woman to a hospital if she bled before delivery, and only 53 (13%) felt referral was necessary if excessive bleeding occurred after birth. Traditional birth attendants will continue to play an important role in maternal child health in India for the foreseeable future. This study demonstrates that a majority of TBA lack basic information about HIV/AIDS and safe delivery practices. Given the ongoing shortage of skilled birth attendance in rural areas, more studies are needed to examine whether TBA should be trained and integrated into PMTCT and maternal child health programs in

  17. Lack of adequate sun protection for children with oculocutaneous albinism in South Africa

    Directory of Open Access Journals (Sweden)

    Taylor Julie S

    2008-06-01

    Full Text Available Abstract Background Childhood is a high risk time for ultraviolet induced skin damage as this age group has more time and opportunity to be outdoors in the sun. Children in Africa with the inherited condition oculocutaneous albinism (OCA are especially vulnerable due to their lack of protective melanin. They are highly susceptible to developing skin lesions that have both cosmetic and health complications, with a high risk of developing skin cancers. The study aimed to explore the adequacy of sun protection strategies of children with albinism in order to inform future provision. Methods Community based participatory research methods were employed to investigate sun protection strategies in 90 pupils with OCA (40 female and 50 male boarding at a special school educating pupils with visual impairment in a rural area of northern South Africa. Hats worn and sunscreen preparations used were examined during semi-structured face to face interviews conducted in small peer groups. The resident nurse interpreted if necessary and provided additional information on monitoring and treatment of skin lesions. Results Participants with albinism in this study were exposed to high levels of ultraviolet radiation throughout the year and showed skin damage despite wearing protective head gear. All except one pupil possessed at least one hat, with a mean brim width of 5.4 cm. Gender differences in sun avoidance behaviour were documented, with females seeking shade during recreational periods and males playing soccer outside. Although 38% of pupils were using a sunscreen with a sun protection factor (SPF rating, only 12% had government sponsored tubes of SPF15 cream. Government sponsored sunscreen preparations were only provided if actively sought, involving time consuming trips to regional hospitals, with inadequate availability and insufficient supply. Conclusion Children with albinism living away from home in rural areas appear to have inadequate sun protection

  18. The More, the Better?! Multiple vs. Single Jobholders’ Job Satisfaction as a Matter of Lacked Information

    Science.gov (United States)

    Kottwitz, Maria U.; Hünefeld, Lena; Frank, Benjamin P.; Otto, Kathleen

    2017-01-01

    In recent decades, the working world has changed dramatically and rising demands on flexibility make the coordination of personal and professional life more difficult. Therefore, it is important that the incumbents are in possession of all necessary information concerning their job. This might be a key issue to remain satisfied. Simultaneously, atypical forms of employment have substantially increased in the labor market; one such form is holding more than one job. While the motives might differ from needing an additional income to broadening job opportunities, practicing several jobs requires coordination and thus, being informed. Building on research regarding organizational constraints and role ambiguity, we hypothesize that the paucity of information is negatively related to (dimensions of) job satisfaction. This effect should be stronger for multiple as compared to single jobbers; specifically when considering the job satisfaction with the social climate, given that being informed by others is an important factor in the coordination of several jobs. Data taken from the BiBB/BAuA-Employment-Survey provide a sample of 17,782 German employees (54% women), including 1,084 multiple jobbers (59% women). Job satisfaction was measured as employees global satisfaction and their satisfaction with facets dimensions: the social climate, structural working conditions, personal growth opportunities, and material incentives they receive for their work. Paucity of information was measured by the frequency of lacked information. Our study indicated that paucity of information was negatively related to both, global and all facets dimensions of job satisfaction. Multiple regression analyses further revealed interaction effects of paucity of information and form of employment. Specifically, the negative correlation of paucity of information with global as well as satisfaction with the social climate was stronger for employees’ holding more than one job. These results were

  19. The More, the Better?! Multiple vs. Single Jobholders’ Job Satisfaction as a Matter of Lacked Information

    Directory of Open Access Journals (Sweden)

    Maria U. Kottwitz

    2017-07-01

    Full Text Available In recent decades, the working world has changed dramatically and rising demands on flexibility make the coordination of personal and professional life more difficult. Therefore, it is important that the incumbents are in possession of all necessary information concerning their job. This might be a key issue to remain satisfied. Simultaneously, atypical forms of employment have substantially increased in the labor market; one such form is holding more than one job. While the motives might differ from needing an additional income to broadening job opportunities, practicing several jobs requires coordination and thus, being informed. Building on research regarding organizational constraints and role ambiguity, we hypothesize that the paucity of information is negatively related to (dimensions of job satisfaction. This effect should be stronger for multiple as compared to single jobbers; specifically when considering the job satisfaction with the social climate, given that being informed by others is an important factor in the coordination of several jobs. Data taken from the BiBB/BAuA-Employment-Survey provide a sample of 17,782 German employees (54% women, including 1,084 multiple jobbers (59% women. Job satisfaction was measured as employees global satisfaction and their satisfaction with facets dimensions: the social climate, structural working conditions, personal growth opportunities, and material incentives they receive for their work. Paucity of information was measured by the frequency of lacked information. Our study indicated that paucity of information was negatively related to both, global and all facets dimensions of job satisfaction. Multiple regression analyses further revealed interaction effects of paucity of information and form of employment. Specifically, the negative correlation of paucity of information with global as well as satisfaction with the social climate was stronger for employees’ holding more than one job. These

  20. The More, the Better?! Multiple vs. Single Jobholders' Job Satisfaction as a Matter of Lacked Information.

    Science.gov (United States)

    Kottwitz, Maria U; Hünefeld, Lena; Frank, Benjamin P; Otto, Kathleen

    2017-01-01

    In recent decades, the working world has changed dramatically and rising demands on flexibility make the coordination of personal and professional life more difficult. Therefore, it is important that the incumbents are in possession of all necessary information concerning their job. This might be a key issue to remain satisfied. Simultaneously, atypical forms of employment have substantially increased in the labor market; one such form is holding more than one job. While the motives might differ from needing an additional income to broadening job opportunities, practicing several jobs requires coordination and thus, being informed. Building on research regarding organizational constraints and role ambiguity, we hypothesize that the paucity of information is negatively related to (dimensions of) job satisfaction. This effect should be stronger for multiple as compared to single jobbers; specifically when considering the job satisfaction with the social climate, given that being informed by others is an important factor in the coordination of several jobs. Data taken from the BiBB/BAuA-Employment-Survey provide a sample of 17,782 German employees (54% women), including 1,084 multiple jobbers (59% women). Job satisfaction was measured as employees global satisfaction and their satisfaction with facets dimensions: the social climate, structural working conditions, personal growth opportunities, and material incentives they receive for their work. Paucity of information was measured by the frequency of lacked information. Our study indicated that paucity of information was negatively related to both, global and all facets dimensions of job satisfaction. Multiple regression analyses further revealed interaction effects of paucity of information and form of employment. Specifically, the negative correlation of paucity of information with global as well as satisfaction with the social climate was stronger for employees' holding more than one job. These results were

  1. Human niche, human behaviour, human nature.

    Science.gov (United States)

    Fuentes, Agustin

    2017-10-06

    The concept of a 'human nature' or 'human natures' retains a central role in theorizing about the human experience. In Homo sapiens it is clear that we have a suite of capacities generated via our evolutionary past, and present, and a flexible capacity to create and sustain particular kinds of cultures and to be shaped by them. Regardless of whether we label these capacities 'human natures' or not, humans occupy a distinctive niche and an evolutionary approach to examining it is critical. At present we are faced with a few different narratives as to exactly what such an evolutionary approach entails. There is a need for a robust and dynamic theoretical toolkit in order to develop a richer, and more nuanced, understanding of the cognitively sophisticated genus Homo and the diverse sorts of niches humans constructed and occupied across the Pleistocene, Holocene, and into the Anthropocene. Here I review current evolutionary approaches to 'human nature', arguing that we benefit from re-framing our investigations via the concept of the human niche and in the context of the extended evolutionary synthesis (EES). While not a replacement of standard evolutionary approaches, this is an expansion and enhancement of our toolkit. I offer brief examples from human evolution in support of these assertions.

  2. Lack of basic and luxury goods and health-related dysfunction in older persons; Findings from the longitudinal SMILE study

    Directory of Open Access Journals (Sweden)

    Kempen Gertrudis IJM

    2008-07-01

    Full Text Available Abstract Background More so than the traditional socioeconomic indicators, such as education and income, wealth reflects the accumulation of resources and makes socioeconomic ranking manifest and explicitly visible to the outside world. While the lack of basic goods, such as a refrigerator, may affect health directly, via biological pathways, the lack of luxury goods, such as an LCD television, may affect health indirectly through psychosocial mechanisms. We set out to examine, firstly, the relevance of both basic and luxury goods in explaining health-related dysfunction in older persons, and, secondly, the extent to which these associations are independent of traditional socioeconomic indicators. Methods Cross-sectional and longitudinal data from 2067 men and women aged 55 years and older who participated in the Study on Medical Information and Lifestyles Eindhoven (SMILE were gathered. Logistic regression analyses were used to study the relation between a lack of basic and luxury goods and health-related function, assessed with two sub-domains of the SF-36. Results The lack of basic goods was closely related to incident physical (OR = 2.32 and mental (OR = 2.12 dysfunction, even when the traditional measures of socioeconomic status, i.e. education or income, were taken into account. Cross-sectional analyses, in which basic and luxury goods were compared, showed that the lack of basic goods was strongly associated with mental dysfunction. Lack of luxury goods was, however, not related to dysfunction. Conclusion Even in a relatively wealthy country like the Netherlands, the lack of certain basic goods is not uncommon. More importantly, lack of basic goods, as an indicator of wealth, was strongly related to health-related dysfunction also when traditional measures of socioeconomic status were taken into account. In contrast, no effects of luxury goods on physical or mental dysfunction were found. Future longitudinal research is necessary to

  3. Lack of basic and luxury goods and health-related dysfunction in older persons; findings from the longitudinal SMILE study.

    Science.gov (United States)

    Groffen, Daniëlle A I; Bosma, Hans; van den Akker, Marjan; Kempen, Gertrudis I J M; van Eijk, Jacques T M

    2008-07-17

    More so than the traditional socioeconomic indicators, such as education and income, wealth reflects the accumulation of resources and makes socioeconomic ranking manifest and explicitly visible to the outside world. While the lack of basic goods, such as a refrigerator, may affect health directly, via biological pathways, the lack of luxury goods, such as an LCD television, may affect health indirectly through psychosocial mechanisms. We set out to examine, firstly, the relevance of both basic and luxury goods in explaining health-related dysfunction in older persons, and, secondly, the extent to which these associations are independent of traditional socioeconomic indicators. Cross-sectional and longitudinal data from 2067 men and women aged 55 years and older who participated in the Study on Medical Information and Lifestyles Eindhoven (SMILE) were gathered. Logistic regression analyses were used to study the relation between a lack of basic and luxury goods and health-related function, assessed with two sub-domains of the SF-36. The lack of basic goods was closely related to incident physical (OR = 2.32) and mental (OR = 2.12) dysfunction, even when the traditional measures of socioeconomic status, i.e. education or income, were taken into account. Cross-sectional analyses, in which basic and luxury goods were compared, showed that the lack of basic goods was strongly associated with mental dysfunction. Lack of luxury goods was, however, not related to dysfunction. Even in a relatively wealthy country like the Netherlands, the lack of certain basic goods is not uncommon. More importantly, lack of basic goods, as an indicator of wealth, was strongly related to health-related dysfunction also when traditional measures of socioeconomic status were taken into account. In contrast, no effects of luxury goods on physical or mental dysfunction were found. Future longitudinal research is necessary to clarify the precise mechanisms underlying these effects.

  4. Lack of basic and luxury goods and health-related dysfunction in older persons; Findings from the longitudinal SMILE study

    OpenAIRE

    Groffen, Daniëlle AI; Bosma, Hans; van den Akker, Marjan; Kempen, Gertrudis IJM; van Eijk, Jacques TM

    2008-01-01

    Abstract Background More so than the traditional socioeconomic indicators, such as education and income, wealth reflects the accumulation of resources and makes socioeconomic ranking manifest and explicitly visible to the outside world. While the lack of basic goods, such as a refrigerator, may affect health directly, via biological pathways, the lack of luxury goods, such as an LCD television, may affect health indirectly through psychosocial mechanisms. We set out to examine, firstly, the r...

  5. How career counseling, management coaching, and mentoring can assist in reducing today’s lack of ethics in business

    OpenAIRE

    Ronald Jean Degen

    2013-01-01

    This paper discusses how career counseling, management coaching, and mentoring can assist in reducing today’s lack of ethics in business by orienting future corporate leaders not only to identifying their skills, making better career choices, and becoming more productive and satisfied in their work, but also by explaining how to behave and decide properly when confronted with the myriad ethical dilemmas of the corporate world. Thus it is essential that they understand today’s lack of business...

  6. Serum-free microcarrier based production of replication deficient Influenza vaccine candidate virus lacking NS1 using Vero cells

    Directory of Open Access Journals (Sweden)

    Yan Mylene L

    2011-08-01

    Full Text Available Abstract Background Influenza virus is a major health concern that has huge impacts on the human society, and vaccination remains as one of the most effective ways to mitigate this disease. Comparing the two types of commercially available Influenza vaccine, the live attenuated virus vaccine is more cross-reactive and easier to administer than the traditional inactivated vaccines. One promising live attenuated Influenza vaccine that has completed Phase I clinical trial is deltaFLU, a deletion mutant lacking the viral Nonstructural Protein 1 (NS1 gene. As a consequence of this gene deletion, this mutant virus can only propagate effectively in cells with a deficient interferon-mediated antiviral response. To demonstrate the manufacturability of this vaccine candidate, a batch bioreactor production process using adherent Vero cells on microcarriers in commercially available animal-component free, serum-free media is described. Results Five commercially available animal-component free, serum-free media (SFM were evaluated for growth of Vero cells in agitated Cytodex 1 spinner flask microcarrier cultures. EX-CELL Vero SFM achieved the highest cell concentration of 2.6 × 10^6 cells/ml, whereas other SFM achieved about 1.2 × 10^6 cells/ml. Time points for infection between the late exponential and stationary phases of cell growth had no significant effect in the final virus titres. A virus yield of 7.6 Log10 TCID50/ml was achieved using trypsin concentration of 10 μg/ml and MOI of 0.001. The Influenza vaccine production process was scaled up to a 3 liter controlled stirred tank bioreactor to achieve a cell density of 2.7 × 10^6 cells/ml and virus titre of 8.3 Log10 TCID50/ml. Finally, the bioreactor system was tested for the production of the corresponding wild type H1N1 Influenza virus, which is conventionally used in the production of inactivated vaccine. High virus titres of up to 10 Log10 TCID50/ml were achieved. Conclusions We describe for the

  7. Susceptibility and lack of evidence for a viremic state of rabies in the night owl monkey, Aotus nancymaae

    Directory of Open Access Journals (Sweden)

    Reaves Erik J

    2012-05-01

    Full Text Available Abstract Background Rabies causes an acute fatal encephalomyelitis in most mammals following infection with rhabdovirus of the genus Lyssavirus. Little is known about rabies virus infection in species of New World non-human Primates (NHP. To investigate the suitability of the owl monkey Aotus nancymaae asissue sections examined were unremarkable for inflammation or other histologic signs of rabies a viable animal model for rabies virus candidate vaccine testing, we used clinical presentation, serology, viral isolation, and PCR to evaluate the incubation period, immunity, and pathogenesis of infected animals. We tested the hypothesis that no viremic state exists for rabies virus. Methods Eight monkeys divided into two equal groups were inoculated intramuscularly either in the neck or footpad with 105 pfu of rabies virus (Pasteur/V-13R and observed for >130 days. Oral and blood samples were collected and analyzed. Results Two monkeys inoculated in the neck displayed classic paralytic rabies. The mean incubation period was 11.5 days. The average maximum IgG response (antibody titer >0.200 O.D. was achieved at day 10.0 and 62.3 in the clinical rabies and non-clinical rabies cases, respectively (p = 0.0429. No difference in IgM or IgG time to seroconversion or average maximum IgM level was observed between neck versus footpad inoculation groups. No viremia or viral shedding was detected by PCR or viral isolation during the observation period, including within the two symptomatic animals three days after disease onset. Tissue sections examined were unremarkable for inflammation or other histologic signs of rabies within the asymptomatic animal. Similarly none of the brain sections exhibited immunoreactivity for rabies virus antibody. Discussion This study demonstrates there is no difference in time to immune response between inoculation sites and distance to the brain; however, immune response tends to be more rapid in cases of clinically

  8. Conditioned place preference and locomotor activity in response to methylphenidate, amphetamine and cocaine in mice lacking dopamine D4 receptors

    Energy Technology Data Exchange (ETDEWEB)

    Thanos, P.K.; Thanos, P.K.; Bermeo, C.; Rubinstein, M.; Suchland, K.L.; Wang, G.-J.; Grandy, D.K.; Volkow, N.D.

    2010-05-01

    Methylphenidate (MP) and amphetamine (AMPH) are the most frequently prescribed medications for the treatment of attention-deficit/hyperactivity disorder (ADHD). Both drugs are believed to derive their therapeutic benefit by virtue of their dopamine (DA)-enhancing effects, yet an explanation for the observation that some patients with ADHD respond well to one medication but not to the other remains elusive. The dopaminergic effects of MP and AMPH are also thought to underlie their reinforcing properties and ultimately their abuse. Polymorphisms in the human gene that codes for the DA D4 receptor (D4R) have been repeatedly associated with ADHD and may correlate with the therapeutic as well as the reinforcing effects of responses to these psychostimulant medications. Conditioned place preference (CPP) for MP, AMPH and cocaine were evaluated in wild-type (WT) mice and their genetically engineered littermates, congenic on the C57Bl/6J background, that completely lack D4Rs (knockout or KO). In addition, the locomotor activity in these mice during the conditioning phase of CPP was tested in the CPP chambers. D4 receptor KO and WT mice showed CPP and increased locomotor activity in response to each of the three psychostimulants tested. D4R differentially modulates the CPP responses to MP, AMPH and cocaine. While the D4R genotype affected CPP responses to MP (high dose only) and AMPH (low dose only) it had no effects on cocaine. Inasmuch as CPP is considered an indicator of sensitivity to reinforcing responses to drugs these data suggest a significant but limited role of D4Rs in modulating conditioning responses to MP and AMPH. In the locomotor test, D4 receptor KO mice displayed attenuated increases in AMPH-induced locomotor activity whereas responses to cocaine and MP did not differ. These results suggest distinct mechanisms for D4 receptor modulation of the reinforcing (perhaps via attenuating dopaminergic signalling) and locomotor properties of these stimulant drugs

  9. [Autism spectrum disorders and bisphenol A: Is serotonin the lacking link in the chain?

    Science.gov (United States)

    Sarrouilhe, D; Dejean, C

    2017-08-01

    The etiology of autism spectrum disorders (ASD) is believed to be multifactorial and to involve genetic and environmental components. Environmental chemical exposures are increasingly understood to be important in causing neurotoxicity in fetuses and newborns. Recent data from the Centers for Disease Control and Prevention in the United States suggest a substantial increase in ASD prevalence, only partly explicable by factors such as diagnostic substitution. Bisphenol A (BPA) is an ubiquitous xenoestrogen widely employed in a variety of consumer products including plastic and metal food and beverage containers, dental sealants and fillings, medical equipment and thermal receipts. Therefore, most people are exposed almost continuously to BPA in industrialized countries. Sources of BPA exposure are predominantly diet, but also through inhalation or dermal absorption. BPA can be measured in many human fluids and tissues including saliva, serum, urine, amniotic fluid, follicular fluid, placental tissue and breast milk. There is concern that BPA exposure may influence human brain development and may contribute to the increasing prevalence of neurodevelopmental and behavioural problems. Epigenetic mechanisms are suggested by a mouse study that demonstrated that BPA exposure during gestation had long lasting, transgenerational effects on social recognition. Previous epidemiological studies suggested a relationship between maternal BPA exposure and ASD. A recent study of 46 children with ASD and 52 controls found for the first time a direct association between children with ASD and BPA exposure and demonstrated that BPA is not metabolized well in children with ASD. The metabolomic analyses showed a correlation between ASD and essential amino acid metabolism pathways. Essential amino acids are precursors of neurotransmitters, for example tryptophan for serotonin. Fetal and prenatal BPA exposure was suggested to perturb the serotonergic system in rat and mice models. On

  10. Response to Bile Salts in Clinical Strains of Acinetobacter baumannii Lacking the AdeABC Efflux Pump: Virulence Associated with Quorum Sensing

    Directory of Open Access Journals (Sweden)

    Maria López

    2017-05-01

    Full Text Available Introduction:Acinetobacter baumannii is an opportunistic nosocomial pathogen associated with multiple infections. This pathogen usually colonizes (first stage of microbial infection host tissues that are in contact with the external environment. As one of the sites of entry in human hosts is the gastrointestinal tract, the pathogen must be capable of tolerating bile salts. However, studies analyzing the molecular characteristics involved in the response to bile salts in clinical strains of A. baumannii are scarce.Material and Methods: Microbiological and transcriptional studies (arrays and RT-PCR in the response to bile salts were carried out in isogenic (A. baumanni ΔadeB ATCC 17978 and A. baumannii ΔadeL ATCC 17978 and clinical strains from clone ST79/PFGE-HUI-1 which is characterized by lacking the AdeABC efflux pump and by overexpression the AdeFGH efflux pump.Results and Discussion: In presence of bile salts, in addition to the glutamate/aspartate transporter were found overexpressed in A. baumannii ΔadeB ATCC 17978, the virulence factors (surface motility, biofilm, and Type VI Secretion System which are associated with activation of the Quorum Sensing system. Overexpression of these factors was confirmed in clinical strains of clone ST79/PFGE-HUI-1.Conclusions: This the first study about the adaptive response to bile salts investigating the molecular and microbiological characteristics in response to bile salts of an isogenic model of A. baumannii ATCC 17978 and clinical isolates of A. baumannii (clinical strains of ST79/PFGE-HUI-1 lacking the main RND efflux pump (AdeABC. Clinical isolates of A. baumannii lacking the AdeABC efflux pump (clone ST79/PFGE-HUI-1 displayed a new clinical profile (increased invasiveness possibly associated with the response to stress conditions (such as the presence of bile salts.

  11. Response to Bile Salts in Clinical Strains of Acinetobacter baumannii Lacking the AdeABC Efflux Pump: Virulence Associated with Quorum Sensing.

    Science.gov (United States)

    López, Maria; Blasco, Lucia; Gato, Eva; Perez, Astrid; Fernández-Garcia, Laura; Martínez-Martinez, Luis; Fernández-Cuenca, Felipe; Rodríguez-Baño, Jesús; Pascual, Alvaro; Bou, German; Tomás, Maria

    2017-01-01

    Introduction: Acinetobacter baumannii is an opportunistic nosocomial pathogen associated with multiple infections. This pathogen usually colonizes (first stage of microbial infection) host tissues that are in contact with the external environment. As one of the sites of entry in human hosts is the gastrointestinal tract, the pathogen must be capable of tolerating bile salts. However, studies analyzing the molecular characteristics involved in the response to bile salts in clinical strains of A. baumannii are scarce. Material and Methods: Microbiological and transcriptional studies (arrays and RT-PCR) in the response to bile salts were carried out in isogenic ( A. baumanni Δ adeB ATCC 17978 and A. baumannii Δ adeL ATCC 17978) and clinical strains from clone ST79/PFGE-HUI-1 which is characterized by lacking the AdeABC efflux pump and by overexpression the AdeFGH efflux pump. Results and Discussion: In presence of bile salts, in addition to the glutamate/aspartate transporter were found overexpressed in A. baumannii Δ adeB ATCC 17978, the virulence factors (surface motility, biofilm, and Type VI Secretion System) which are associated with activation of the Quorum Sensing system. Overexpression of these factors was confirmed in clinical strains of clone ST79/PFGE-HUI-1. Conclusions: This the first study about the adaptive response to bile salts investigating the molecular and microbiological characteristics in response to bile salts of an isogenic model of A. baumannii ATCC 17978 and clinical isolates of A. baumannii (clinical strains of ST79/PFGE-HUI-1) lacking the main RND efflux pump (AdeABC). Clinical isolates of A. baumannii lacking the AdeABC efflux pump (clone ST79/PFGE-HUI-1) displayed a new clinical profile (increased invasiveness) possibly associated with the response to stress conditions (such as the presence of bile salts).

  12. A mesenchymal-like phenotype and expression of CD44 predict lack of apoptotic response to sorafenib in liver tumor cells.

    Science.gov (United States)

    Fernando, Joan; Malfettone, Andrea; Cepeda, Edgar B; Vilarrasa-Blasi, Roser; Bertran, Esther; Raimondi, Giulia; Fabra, Àngels; Alvarez-Barrientos, Alberto; Fernández-Salguero, Pedro; Fernández-Rodríguez, Conrado M; Giannelli, Gianluigi; Sancho, Patricia; Fabregat, Isabel

    2015-02-15

    The multikinase inhibitor sorafenib is the only effective drug in advanced cases of hepatocellular carcinoma (HCC). However, response differs among patients and effectiveness only implies a delay. We have recently described that sorafenib sensitizes HCC cells to apoptosis. In this work, we have explored the response to this drug of six different liver tumor cell lines to define a phenotypic signature that may predict lack of response in HCC patients. Results have indicated that liver tumor cells that show a mesenchymal-like phenotype, resistance to the suppressor effects of transforming growth factor beta (TGF-β) and high expression of the stem cell marker CD44 were refractory to sorafenib-induced cell death in in vitro studies, which correlated with lack of response to sorafenib in nude mice xenograft models of human HCC. In contrast, epithelial-like cells expressing the stem-related proteins EpCAM or CD133 were sensitive to sorafenib-induced apoptosis both in vitro and in vivo. A cross-talk between the TGF-β pathway and the acquisition of a mesenchymal-like phenotype with up-regulation of CD44 expression was found in the HCC cell lines. Targeted CD44 knock-down in the mesenchymal-like cells indicated that CD44 plays an active role in protecting HCC cells from sorafenib-induced apoptosis. However, CD44 effect requires a TGF-β-induced mesenchymal background, since the only overexpression of CD44 in epithelial-like HCC cells is not sufficient to impair sorafenib-induced cell death. In conclusion, a mesenchymal profile and expression of CD44, linked to activation of the TGF-β pathway, may predict lack of response to sorafenib in HCC patients. © 2014 UICC.

  13. Management and human performance

    International Nuclear Information System (INIS)

    Russell, W.T.

    1988-01-01

    Past human performance and management problems have been well documented. The accidents at Three Mile Island and Chernobyl have significant root causes in human factors and in plant management. The failure of plant personnel to recognize the safety significance of their actions, procedures which were knowingly violated, a lack of awareness of plant conditions and status, and operators being misled by incorrect data and information were root causes of these accidents. Safety culture starts with personal dedication and accountability beginning at the top with senior corporate management. It is formed by policies and administrative controls which when implemented ensure that correct practices are followed. Senior management fosters an attitude and safety consciousness in all personnel with responsibility for supervision, operation and maintenance of the nuclear power plant

  14. Lack of acute cardioprotective effect from preischaemic erythropoietin administration in a porcine coronary occlusion model

    DEFF Research Database (Denmark)

    Kristensen, Jens; Mæng, Michael; Rehling, Michael

    2005-01-01

    preconditioning may be involved. Before clinical testing such possible cardioprotective effects needs assessment in an experimental large animal model with closer similarity to human ischaemic pathophysiology. METHODS: A control group and two rhEPO groups were studied. EPO1 pigs were given EPO corresponding...... by myocardial perfusion imaging (MPI) and postmortem by a histochemical procedure (at 150 min of reperfusion). RESULTS: IS/AAR did not differ significantly between control (C), EPO1 and EPO2 groups, neither measured by MPI (mean+/-SD for C: 0.87+/-0.13; EPO1: 0.92+/-0.08; EPO2: 0.87+/-0.11), nor histochemically...... (mean+/-SD for C: 0.64+/-0.20; EPO1: 0.75+/-0.17; EPO2: 0.80+/-0.07). In the EPO2 group mean arterial pulmonary pressure and dP/dtmax were increased compared with control group. CONCLUSION: Despite promising results from studies in rodents, rhEPO did not reduce infarct size measured after 2.5 h...

  15. Lack of efflux mediated quinolone resistance in Salmonella enterica serovars Typhi and Paratyphi A

    Directory of Open Access Journals (Sweden)

    Sylvie eBaucheron

    2014-01-01

    Full Text Available Salmonella enterica serovars Typhi and Paratyphi A isolates from human patients in France displaying different levels of resistance to quinolones or fluoroquinolones were studied for resistance mechanisms to these antimicrobial agents. All resistant isolates carried either single or multiple target gene mutations (i.e. in gyrA, gyrB, or parC correlating with the resistance levels observed. Active efflux, through upregulation of multipartite efflux systems, has also been previously reported as contributing mechanism for other serovars. Therefore, we investigated also the occurrence of non-target gene mutations in regulatory regions affecting efflux pump expression. However, no mutation was detected in these regions in both Typhi and Paratyphi isolates of this study. Besides, no overexpression of the major efflux systems was observed for these isolates. Nevertheless, a large deletion of 2334 bp was identified in the acrS-acrE region of all S. Typhi strains but which did not affect the resistance phenotype. As being specific to S. Typhi, this deletion could be used for specific molecular detection purposes. In conclusion, the different levels of quinolone or FQ resistance in both S. Typhi and S. Paratyphi A seem to rely only on target modifications.

  16. Lack of evidence for an association of Epstein–Barr virus infection with breast carcinoma

    International Nuclear Information System (INIS)

    Herrmann, Kathrin; Niedobitek, Gerald

    2003-01-01

    Epstein–Barr virus (EBV) is a ubiquitous human γ-herpes virus infecting more than 90% of the population worldwide. EBV is associated with certain malignancies (e.g. Burkitt lymphoma, Hodgkin lymphoma and nasopharyngeal carcinoma). Recent studies have raised the possibility that EBV may also be involved in the pathogenesis of breast carcinoma, the most common carcinoma of females. If substantiated, this finding would have major implications regarding prevention and therapy of the disease. The studies published so far have employed diverse methods, however, and the results have been controversial. Using the EBV DNA PCR, EBV DNA in situ hybridisation and in situ hybridisation for the detection of the EBV-encoded RNAs, and using immunohistochemistry for the demonstration of the EBV-encoded nuclear antigen 1, we have studied a series of 59 invasive breast carcinomas for evidence of EBV infection. EBV-encoded RNA-specific in situ hybridisation and EBV-encoded nuclear antigen 1 immunohistochemistry were negative in all cases. Using the PCR, EBV DNA was detected in four out of 59 cases. These cases were further studied by EBV DNA in situ hybridisation, showing an absence of viral DNA from the tumour cells. These results indicate that breast carcinoma is not an EBV-associated tumour

  17. CAG Expansions Are Genetically Stable and Form Nontoxic Aggregates in Cells Lacking Endogenous Polyglutamine Proteins

    Directory of Open Access Journals (Sweden)

    Ashley A. Zurawel

    2016-09-01

    Full Text Available Proteins containing polyglutamine (polyQ regions are found in almost all eukaryotes, albeit with various frequencies. In humans, proteins such as huntingtin (Htt with abnormally expanded polyQ regions cause neurodegenerative diseases such as Huntington’s disease (HD. To study how the presence of endogenous polyQ aggregation modulates polyQ aggregation and toxicity, we expressed polyQ expanded Htt fragments (polyQ Htt in Schizosaccharomyces pombe. In stark contrast to other unicellular fungi, such as Saccharomyces cerevisiae, S. pombe is uniquely devoid of proteins with more than 10 Q repeats. We found that polyQ Htt forms aggregates within S. pombe cells only with exceedingly long polyQ expansions. Surprisingly, despite the presence of polyQ Htt aggregates in both the cytoplasm and nucleus, no significant growth defect was observed in S. pombe cells. Further, PCR analysis showed that the repetitive polyQ-encoding DNA region remained constant following transformation and after multiple divisions in S. pombe, in contrast to the genetic instability of polyQ DNA sequences in other organisms. These results demonstrate that cells with a low content of polyQ or other aggregation-prone proteins can show a striking resilience with respect to polyQ toxicity and that genetic instability of repetitive DNA sequences may have played an important role in the evolutionary emergence and exclusion of polyQ expansion proteins in different organisms.

  18. Neocortical Transplants in the Mammalian Brain Lack a Blood-Brain Barrier to Macromolecules

    Science.gov (United States)

    Rosenstein, Jeffrey M.

    1987-02-01

    In order to determine whether the blood-brain barrier was present in transplants of central nervous tissue, fetal neocortex, which already possesses blood-brain and blood-cerebrospinal fluid barriers to protein, was grafted into the undamaged fourth ventricle or directly into the neocortex of recipient rats. Horseradish peroxidase or a conjugated human immunoglobulin G-peroxidase molecule was systemically administered into the host. These proteins were detected within the cortical transplants within 2 minutes regardless of the age of the donor or postoperative time. At later times these compounds, which normally do not cross the blood-brain barrier, inundated the grafts and adjacent host brain and also entered the cerebrospinal fluid. Endogenous serum albumin detected immunocytochemically in untreated hosts had a comparable although less extensive distribution. Thus, transplants of fetal central nervous tissue have permanent barrier dysfunction, probably due to microvascular changes, and are not integrated physiologically within the host. Blood-borne compounds, either systemically administered or naturally occurring, which should never contact normal brain tissue, have direct access to these transplants and might affect neuronal function.

  19. Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects

    International Nuclear Information System (INIS)

    Huang, Shang-Lang; Chao, Chuck C.-K.

    2015-01-01

    A previous genome-wide screening analysis identified a panel of genes that sensitize the human non-small-cell lung carcinoma cell line NCI-H1155 to taxol. However, whether the identified genes sensitize other cancer cells to taxol has not been examined. Here, we silenced the taxol-sensitizer genes identified (acrbp, atp6v0d2, fgd4, hs6st2, psma6, and tubgcp2) in nine other cancer cell types (including lung, cervical, ovarian, and hepatocellular carcinoma cell lines) that showed reduced cell viability in the presence of a sub-lethal concentration of taxol. Surprisingly, none of the genes studied increased sensitivity to taxol in the tested panel of cell lines. As observed in H1155 cells, SKOV3 cells displayed induction of five of the six genes studied in response to a cell killing dose of taxol. The other cell types were much less responsive to taxol. Notably, four of the five inducible taxol-sensitizer genes tested (acrbp, atp6v0d2, psma6, and tubgcp2) were upregulated in a taxol-resistant ovarian cancer cell line. These results indicate that the previously identified taxol-sensitizer loci are not conserved genetic targets involved in inhibiting cell proliferation in response to taxol. Our findings also suggest that regulation of taxol-sensitizer genes by taxol may be critical for acquired cell resistance to the drug

  20. Malnourished Children in Refugee Camps and Lack of Connection with Services After US Resettlement

    Science.gov (United States)

    Cookson, Susan T.; Talley, Leisel; Rochat, Roger

    2016-01-01

    Identifying and addressing malnutrition among US-bound refugee children is an important human rights issue. Failure to address childhood malnutrition can impair cognitive development and productivity. The target population was children aged 6–59 months, originating from eight countries representing 51 % of US-resettled refugees for 2005–2011, living in 22 camps prior to potential US-resettlement. The corresponding camp-level nutritional survey data were evaluated. State Refugee Health Coordinators were surveyed on nutritional assessment, reporting and referrals for their US-refugee medical screenings. From 2004 to 2010, half of the camps (63 total surveys) had global acute malnutrition prevalence over 15 % at least once (surveys not done annually) and anemia prevalence greater than 40 %. The majority of US-refugee medical screenings included height and weight measurements but few used national or WHO standards to evaluate presence or level of malnutrition. Improve overseas camp monitoring and link these nutritional data to US-resettling refugee children to inform potential nutritional interventions. Domestically, use WHO or US growth standards for anthropometrics to determine presence of malnutrition and need for corrective action. PMID:23430464

  1. Dwarfism and early death in mice lacking C-type natriuretic peptide

    Science.gov (United States)

    Chusho, Hideki; Tamura, Naohisa; Ogawa, Yoshihiro; Yasoda, Akihiro; Suda, Michio; Miyazawa, Takashi; Nakamura, Kenji; Nakao, Kazuki; Kurihara, Tatsuya; Komatsu, Yasato; Itoh, Hiroshi; Tanaka, Kiyoshi; Saito, Yoshihiko; Katsuki, Motoya; Nakao, Kazuwa

    2001-01-01

    Longitudinal bone growth is determined by endochondral ossification that occurs as chondrocytes in the cartilaginous growth plate undergo proliferation, hypertrophy, cell death, and osteoblastic replacement. The natriuretic peptide family consists of three structurally related endogenous ligands, atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP), and is thought to be involved in a variety of homeostatic processes. To investigate the physiological significance of CNP in vivo, we generated mice with targeted disruption of CNP (Nppc−/− mice). The Nppc−/− mice show severe dwarfism as a result of impaired endochondral ossification. They are all viable perinatally, but less than half can survive during postnatal development. The skeletal phenotypes are histologically similar to those seen in patients with achondroplasia, the most common genetic form of human dwarfism. Targeted expression of CNP in the growth plate chondrocytes can rescue the skeletal defect of Nppc−/− mice and allow their prolonged survival. This study demonstrates that CNP acts locally as a positive regulator of endochondral ossification in vivo and suggests its pathophysiological and therapeutic implication in some forms of skeletal dysplasia. PMID:11259675

  2. Hepatic stellate cells lack AP-1 responsiveness to electrophiles and phorbol 12-myristate-13-acetate

    International Nuclear Information System (INIS)

    Reichard, John F.; Petersen, Dennis R.

    2004-01-01

    Stellate cell profibrotic gene induction and transdifferentiation are central events in liver fibrosis. Oxidative stress has been implicated as an activator of the transcription factors Nrf2 and AP-1 through shared kinase signaling pathways that also purportedly contribute to stellate cell activation. The present study examined the role of oxidative stress in ARE- and TRE-regulated gene induction in isolated hepatic stellate cells. Using a portion of the human Nqo1 promoter consisting of an ARE imbedded TRE, it was demonstrated that while the ARE was responsible for mediating inducible gene expression in response to the electrophiles 4-HNE and tBHQ, the TRE was refractory to induction by either electrophiles or PMA. It was demonstrated that stellate cells possess nuclear TRE-binding proteins that were identified as JunB, JunD, Fra1, and Fra2, which were unaffected by either electrophiles or PMA treatment. This report demonstrates that, in contrast to the ARE, the TRE and its binding cognate AP-1 did not mediate independent gene induction in hepatic stellate cells. This observation is significant given the presumed importance attributed to AP-1 in mediating profibrogenic gene expression

  3. Lack of mutational hot spots during decitabine-mediated HIV-1 mutagenesis.

    Science.gov (United States)

    Rawson, Jonathan M O; Landman, Sean R; Reilly, Cavan S; Bonnac, Laurent; Patterson, Steven E; Mansky, Louis M

    2015-11-01

    Decitabine has previously been shown to induce lethal mutagenesis of human immunodeficiency virus type 1 (HIV-1). However, the factors that determine the susceptibilities of individual sequence positions in HIV-1 to decitabine have not yet been defined. To investigate this, we performed Illumina high-throughput sequencing of multiple amplicons prepared from proviral DNA that was recovered from decitabine-treated cells infected with HIV-1. We found that decitabine induced an ≈4.1-fold increase in the total mutation frequency of HIV-1, primarily due to a striking ≈155-fold increase in the G-to-C transversion frequency. Intriguingly, decitabine also led to an ≈29-fold increase in the C-to-G transversion frequency. G-to-C frequencies varied substantially (up to ≈80-fold) depending upon sequence position, but surprisingly, mutational hot spots (defined as upper outliers within the mutation frequency distribution) were not observed. We further found that every single guanine position examined was significantly susceptible to the mutagenic effects of decitabine. Taken together, these observations demonstrate for the first time that decitabine-mediated HIV-1 mutagenesis is promiscuous and occurs in the absence of a clear bias for mutational hot spots. These data imply that decitabine-mediated G-to-C mutagenesis is a highly effective antiviral mechanism for extinguishing HIV-1 infectivity. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  4. Inherent Immunogenicity or Lack Thereof of Pluripotent Stem Cells: Implications for Cell Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Arvind Chhabra

    2017-08-01

    Full Text Available Donor-specific induced pluripotent stem cells (iPSCs offer opportunities for personalized cell replacement therapeutic approaches due to their unlimited self-renewal potential and ability to differentiate into different somatic cells. A significant progress has been made toward generating iPSC lines that are free of integrating viral vectors, development of xeno-free culture conditions, and differentiation of pluripotent stem cells (PSCs into functional somatic cell lineages. Since donor-specific iPSC lines are genetically identical to the individual, they are expected to be immunologically matched and these iPSC lines and their cellular derivatives are not expected to be immunologically rejected. However, studies in mouse models, utilizing rejection of teratomas as a model, have claimed that syngenic iPSC lines, especially the iPSC lines derived with integrating viral vectors, could be inherently immunogenic. This manuscript reviews current understanding of inherent immunogenicity of PSC lines, especially that of the human iPSC lines and their cellular derivatives, and strategies to overcome it.

  5. Lack of prion transmission by sexual or parental routes in experimentally infected hamsters.

    Science.gov (United States)

    Morales, Rodrigo; Pritzkow, Sandra; Hu, Ping Ping; Duran-Aniotz, Claudia; Soto, Claudio

    2013-01-01

    Prion diseases are a group of neurodegenerative disorders affecting humans as well as captive and wild animals. The mechanisms and routes governing the natural spread of prions are not completely understood and several hypotheses have been proposed. In this study, we analyzed the effect of gender in prion incubation period, as well as the possibility of prion transmission by sexual and parental contact using 263K infected hamsters as a model. Our results show that males have significantly longer incubation periods compared with females when exposed to the same quantity of infectious material. Importantly, no evidence of sexual or parental prion transmission was found, even 500 d after sexual contact or birth, respectively. Western blotting and PMCA were unable to detect sub-clinical levels of PrP(Sc) in experimental subjects, suggesting a complete absence of prion transmission by these routes. Our results show that sexual and parental transmission of prions does not occur in this model. It remains to be studied whether this conclusion is valid also for other prion strains and species.

  6. Lack of genetic association of neutral endopeptidase (NEP) with complex regional pain syndrome (CRPS).

    Science.gov (United States)

    Huehne, Kathrin; Schaal, Ute; Leis, Stefan; Uebe, Steffen; Gosso, M Florencia; van den Maagdenberg, Arn M J M; Maihöfner, Christian; Birklein, Frank; Rautenstrauss, Bernd; Winterpacht, Andreas

    2010-03-12

    Complex regional pain syndrome (CRPS) is a condition that is characterized by severe pain and exaggerated neurogenic inflammation, which may develop after injury or surgery. Neurogenic inflammation is mediated by neuropeptides, such as calcitonin gene-related peptide (CGRP) and substance P (SP) that are released from nociceptors. Genetic factors may play a role in CRPS as was suggested by the occurrence of familial cases and several genetic association studies investigating mainly the human leukocyte antigen (HLA) system. Here we investigated the role of neutral endopeptidase (NEP), a key enzyme in neuropeptide catabolism. NEP dysfunction resulting in reduced inactivation of neuropeptides may be a possible pathomechanism in CRPS. To this end, we tested a GT-repeat polymorphism in the NEP promoter region as well as 18 tag-SNPs in six linkage disequilibrium (LD) blocks in the NEP gene region in 320 CRPS patients and 376 controls. No significant genetic association was observed. Thus, we conclude that the NEP gene does not seem to be a major risk factor for CRPS. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  7. Malnourished children in refugee camps and lack of connection with services after US resettlement.

    Science.gov (United States)

    Lutfy, Caitlyn; Cookson, Susan T; Talley, Leisel; Rochat, Roger

    2014-10-01

    Identifying and addressing malnutrition among US-bound refugee children is an important human rights issue. Failure to address childhood malnutrition can impair cognitive development and productivity. The target population was children aged 6-59 months, originating from eight countries representing 51 % of US-resettled refugees for 2005-2011, living in 22 camps prior to potential US-resettlement. The corresponding camp-level nutritional survey data were evaluated. State Refugee Health Coordinators were surveyed on nutritional assessment, reporting and referrals for their US-refugee medical screenings. From 2004 to 2010, half of the camps (63 total surveys) had global acute malnutrition prevalence over 15 % at least once (surveys not done annually) and anemia prevalence greater than 40 %. The majority of US-refugee medical screenings included height and weight measurements but few used national or WHO standards to evaluate presence or level of malnutrition. Improve overseas camp monitoring and link these nutritional data to US-resettling refugee children to inform potential nutritional interventions. Domestically, use WHO or US growth standards for anthropometrics to determine presence of malnutrition and need for corrective action.

  8. Lack of Durable Cross-Neutralizing Antibodies Against Zika Virus from Dengue Virus Infection.

    Science.gov (United States)

    Collins, Matthew H; McGowan, Eileen; Jadi, Ramesh; Young, Ellen; Lopez, Cesar A; Baric, Ralph S; Lazear, Helen M; de Silva, Aravinda M

    2017-05-01

    Cross-reactive antibodies elicited by dengue virus (DENV) infection might affect Zika virus infection and confound serologic tests. Recent data demonstrate neutralization of Zika virus by monoclonal antibodies or human serum collected early after DENV infection. Whether this finding is true in late DENV convalescence (>6 months after infection) is unknown. We studied late convalescent serum samples from persons with prior DENV or Zika virus exposure. Despite extensive cross-reactivity in IgG binding, Zika virus neutralization was not observed among primary DENV infections. We observed low-frequency (23%) Zika virus cross-neutralization in repeat DENV infections. DENV-immune persons who had Zika virus as a secondary infection had distinct populations of antibodies that neutralized DENVs and Zika virus, as shown by DENV-reactive antibody depletion experiments. These data suggest that most DENV infections do not induce durable, high-level Zika virus cross-neutralizing antibodies. Zika virus-specific antibody populations develop after Zika virus infection irrespective of prior DENV immunity.

  9. KIR-HLA genotypes in HIV-infected patients lacking immunological recovery despite effective antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Alessandro Soria

    Full Text Available BACKGROUND: In HIV-infected individuals, mechanisms underlying unsatisfactory immune recovery during effective combination antiretroviral therapy (cART have yet to be fully understood. We investigated whether polymorphism of genes encoding immune-regulating molecules, such as killer immunoglobulin-like receptors (KIR and their ligands class I human leukocyte antigen (HLA, could influence immunological response to cART. METHODS: KIR and HLA frequencies were analyzed in 154 HIV-infected and cART-treated patients with undetectable viral load divided into two groups: 'immunological non responders' (INR, N = 50, CD4(+ T-cell count 350/mm(3. Molecular KIR were typed using polymerase chain reaction-based genotyping. Comparisons were adjusted for baseline patient characteristics. RESULTS: The frequency of KIR2DL3 allele was significantly higher in FR than in INR (83.7% vs. 62%, P = 0.005. The functional compound genotype HLA-C1(+/KIR2DL3(+, even at multivariable analysis, when adjusted for nadir CD4(+ T-cell count, was associated with reduced risk of INR status: odds ratio (95% Confidence Intervals 0.34 (0.13-0.88, P = 0.03. CONCLUSIONS: Reduced presence of the inhibitory KIR2DL3 genotype detected in INR might provoke an imbalance in NK function, possibly leading to increased immune activation, impaired killing of latently infected cells, and higher proviral burden. These factors would hinder full immune recovery during therapy.

  10. Driven to distraction: A lack of change gives rise to mind wandering.

    Science.gov (United States)

    Faber, Myrthe; Radvansky, Gabriel A; D'Mello, Sidney K

    2018-04-01

    How does the dynamic structure of the external world direct attention? We examined the relationship between event structure and attention to test the hypothesis that narrative shifts (both theoretical and perceived) negatively predict attentional lapses. Self-caught instances of mind wandering were collected while 108 participants watched a 32.5 min film called The Red Balloon. We used theoretical codings of situational change and human perceptions of event boundaries to predict mind wandering in 5-s intervals. Our findings suggest a temporal alignment between the structural dynamics of the film and mind wandering reports. Specifically, the number of situational changes and likelihood of perceiving event boundaries in the prior 0-15 s interval negatively predicted mind wandering net of low-level audiovisual features. Thus, mind wandering is less likely to occur when there is more event change, suggesting that narrative shifts keep attention from drifting inwards. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Lack of association of ghrelin precursor gene variants and percentage body fat or serum lipid profiles.

    Science.gov (United States)

    Martin, Glynn R; Loredo, J C; Sun, Guang

    2008-04-01

    Ghrelin has been recognized for its involvement in food intake, control of energy homeostasis, and lipid metabolism. However, the roles of genetic variations in the ghrelin precursor gene (GHRL) on body compositions and serum lipids are not clear in humans. Our study investigated five single-nucleotide polymorphisms (SNPs) within GHRL to determine their relationship with body fat percentage (BF), trunk fat percentage (TF), lower body (legs) fat percentage (LF), and serum lipids in 1,464 subjects, which were recruited from the genetically homogeneous population of Newfoundland and Labrador (NL), Canada. Serum glucose, insulin, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglycerides were determined. Five SNPs are rs35684 (A/G: a transition substitution in exon 1), rs4684677 (A/T: a missense mutation), rs2075356 (C/T: intron), rs26802 (G/T: intron), and rs26311 (A/G: near the 3' untranslated region) of GHRL were genotyped using TaqMan validated or functionally tested SNP genotyping assays. Our study found no significant evidence of an allele or genotype association between any of the variant sites and body compositions or serum lipids. Furthermore, haplotype frequencies were not found to be significantly different between lean and obese subjects. In summary, the results of our study do not support a significant role for genetic variations in GHRL in the differences of body fat and serum lipid profiles in the NL population.

  12. Lack of association of TNFalpha gene polymorphisms and recurrent pregnancy loss in Caucasian women.

    Science.gov (United States)

    Pietrowski, Detlef; Bettendorf, Herta; Keck, Christoph; Bürkle, Bernd; Unfried, Gertrud; Riener, Eva-Katrin; Hefler, Lukas A; Tempfer, Clemens

    2004-02-01

    The tumor necrosis factor alpha (TNFalpha) gene plays an important role in immunology and inflammation. Variant alleles of TNFalpha are associated with altered RNA and serum protein levels in humans. Conflicting results have been obtained regarding the role of TNFalpha during pregnancy and recurrent pregnancy loss (RPL). This study investigated the relationship between RPL and two polymorphisms in the promoter of the TNFalpha gene (TNFalpha -308 and -863). Genotyping was performed in 168 RPL women and 212 ethnically matched healthy individuals. In addition, we performed analysis of TNFalpha serum protein levels. We demonstrate that neither the polymorphism -308 nor the polymorphism -863 of the TNFalpha gene is associated with RPL in Caucasian women. In addition, we did not find any association between TNFalpha serum levels and the occurrence of RPL in a subset of 36 RPL women and 36 healthy individuals. We conclude that TNFalpha polymorphisms and resting blood TNFalpha levels do not correlate with the propensity to recurrent pregnancy loss in Caucasian women.

  13. Lack of Any Relationship of Stomach Cancer Incidence and Mortality with Development in Asia.

    Science.gov (United States)

    RaFiei, Elahe; Mohammadian-Hafshejani, Abdollah; Towhidi, Farhad; Makhsosi, Behnam Reza; Salehiniya, Hamid

    2016-01-01

    The aim of this study was to evaluate the incidence and mortality of stomach cancer, and its relationship with the Human Development Index (HDI) and its components in Asia in 2012. This ecological study was conducted based on GLOBOCAN project of WHO for Asian countries. We assessed the correlations between standardized incidence rates (SIR) and standardized mortality rates (SMR) of stomach cancer with HDI and its components using SPSS18. A total of 696,231 cases (68.7% in males and 31.3% in females, ratio of 2.19:1) and 524,465 deaths (67.1% in men and 33.0% in women, ratio 2.03:1) were included in 2012. Five countries with the highest SIR of stomach cancer were Republic Korea, Mongolia, Japan, China and Tajikistan. Five countries with the highest SMR of stomach cancer were Mongolia, Tajikistan, Kyrgyzstan, Kazakhstan and China. Correlation between HDI and SIR was 0.241 (p = 0.106), in men 0.236 (p = 0.114) and in women -0.250 (p = 0.094). Also between HDI and SMR -0.250 (p = 0.871) in men -0.018 (p = 0.903) and in women -0.014 (p = 0.927). No significant correlation was observed between the SIR of stomach cancer, and the HDI and its dimensions, such as life expectancy at birth, mean years of schooling, and income level of the population.

  14. Hyperactivity and lack of social discrimination in the adolescent Fmr1 knockout mouse.

    Science.gov (United States)

    Sørensen, Emilie M; Bertelsen, Freja; Weikop, Pia; Skovborg, Maria M; Banke, Tue; Drasbek, Kim R; Scheel-Krüger, Jørgen

    2015-12-01

    The aims of this study were to investigate behaviour relevant to human autism spectrum disorder (ASD) and the fragile X syndrome in adolescent Fmr1 knockout (KO) mice and to evaluate the tissue levels of striatal monoamines. Fmr1 KO mice were evaluated in the open field, marble burying and three-chamber test for the presence of hyperactivity, anxiety, repetitive behaviour, sociability and observation of social novelty compared with wild-type (WT) mice. The Fmr1 KO mice expressed anxiety and hyperactivity in the open field compared with WT mice. This increased level of hyperactivity was confirmed in the three-chamber test. Fmr1 KO mice spent more time with stranger mice compared with the WT. However, after a correction for hyperactivity, their apparent increase in sociability became identical to that of the WT. Furthermore, the Fmr1 KO mice could not differentiate between a familiar or a novel mouse. Monoamines were measured by HPLC: Fmr1 KO mice showed an increase in the striatal dopamine level. We conclude that the fragile X syndrome model seems to be useful for understanding certain aspects of ASD and may have translational interest for studies of social behaviour when hyperactivity coexists in ASD patients.

  15. Lack of detection of XMRV in seminal plasma from HIV-1 infected men in The Netherlands.

    Directory of Open Access Journals (Sweden)

    Marion Cornelissen

    Full Text Available BACKGROUND: Xenotropic murine leukaemia virus-related virus (XMRV is a recently discovered human gammaretrovirus with yet unknown prevalence and transmission route(s. Its presence in prostate stromal fibroblasts and prostatic secretions suggests that XMRV might be sexually transmitted. We chose to study a compartment closely connected to the prostate, a location where XMRV was detected in independent studies. Seminal plasma samples from HIV-1 infected men were examined as they have an increased probability of acquiring sexually transmitted pathogens. METHODOLOGY/PRINCIPAL FINDINGS: We studied the prevalence of XMRV in 93 seminal plasma samples of 54 HIV-1 infected men living in The Netherlands with a nested PCR amplification specifically targeting the XMRV gag gene. As a control for the presence and integrity of retrovirus particles, HIV-1 was amplified from the same samples with a PCR amplification targeting the env gene of the virus, or HIV-1 was quantified with a real-time PCR amplifying part of the pol gene. CONCLUSIONS/SIGNIFICANCE: Although HIV-1 was amplified from 25% of the seminal plasma samples, no XMRV was detected, suggesting that either the prevalence of XMRV is very low in The Netherlands, or that XMRV is not naturally present in the seminal plasma.

  16. Bee declines driven by combined stress from parasites, pesticides, and lack of flowers.

    Science.gov (United States)

    Goulson, Dave; Nicholls, Elizabeth; Botías, Cristina; Rotheray, Ellen L

    2015-03-27

    Bees are subject to numerous pressures in the modern world. The abundance and diversity of flowers has declined; bees are chronically exposed to cocktails of agrochemicals, and they are simultaneously exposed to novel parasites accidentally spread by humans. Climate change is likely to exacerbate these problems in the future. Stressors do not act in isolation; for example, pesticide exposure can impair both detoxification mechanisms and immune responses, rendering bees more susceptible to parasites. It seems certain that chronic exposure to multiple interacting stressors is driving honey bee colony losses and declines of wild pollinators, but such interactions are not addressed by current regulatory procedures, and studying these interactions experimentally poses a major challenge. In the meantime, taking steps to reduce stress on bees would seem prudent; incorporating flower-rich habitat into farmland, reducing pesticide use through adopting more sustainable farming methods, and enforcing effective quarantine measures on bee movements are all practical measures that should be adopted. Effective monitoring of wild pollinator populations is urgently needed to inform management strategies into the future. Copyright © 2015, American Association for the Advancement of Science.

  17. c-KIT positive schistosomal urinary bladder carcinoma are frequent but lack KIT gene mutations.

    Science.gov (United States)

    Shams, Tahany M; Metawea, Mokhtar; Salim, Elsayed I

    2013-01-01

    Urinary bladder squamous cell carcinoma (SCC), one of the most common neoplasms in Egypt, is attributed to chronic urinary infection with Schistosoma haematobium (Schistosomiasis). The proto-oncogene c-KIT, encoding a tyrosine kinase receptor and implicated in the development of a number of human malignancies, has not been studied so far in schistosomal urinary bladder SCCs. We therefore determined immunohistochemical (IHC) expression of c-KIT in paraffin sections from 120 radical cystectomies of SCCs originally obtained from the Pathology Department of Suez Canal University (Ismailia, Egypt). Each slide was evaluated for staining intensity where the staining extent of >10% of cells was considered positive. c-KIT overexpression was detected in 78.3% (94/120) of the patients, the staining extents in the tumor cells were 11-50% and >50% in 40 (42.6%) and 54 (57.4%) respectively. The positive cases had 14.9%, 63.8%, 21.3% as weak, moderate and strong intensity respectively. Patients with positive bilharzial ova had significantly higher c-KIT expression than patients without (95.2% vs. 38.9%, P=0.000). Mutation analysis of exons 9-13 was negative in thirty KIT positive cases. The high rate of positivity in SBSCC was one of the striking findings; However, CD117 may be a potential target for site specific immunotherapy to improve the outcome of this tumor.

  18. Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Shang-Lang [Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Chao, Chuck C.-K., E-mail: cckchao@mail.cgu.edu.tw [Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Department of Medical Research and Development, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan (China)

    2015-06-16

    A previous genome-wide screening analysis identified a panel of genes that sensitize the human non-small-cell lung carcinoma cell line NCI-H1155 to taxol. However, whether the identified genes sensitize other cancer cells to taxol has not been examined. Here, we silenced the taxol-sensitizer genes identified (acrbp, atp6v0d2, fgd4, hs6st2, psma6, and tubgcp2) in nine other cancer cell types (including lung, cervical, ovarian, and hepatocellular carcinoma cell lines) that showed reduced cell viability in the presence of a sub-lethal concentration of taxol. Surprisingly, none of the genes studied increased sensitivity to taxol in the tested panel of cell lines. As observed in H1155 cells, SKOV3 cells displayed induction of five of the six genes studied in response to a cell killing dose of taxol. The other cell types were much less responsive to taxol. Notably, four of the five inducible taxol-sensitizer genes tested (acrbp, atp6v0d2, psma6, and tubgcp2) were upregulated in a taxol-resistant ovarian cancer cell line. These results indicate that the previously identified taxol-sensitizer loci are not conserved genetic targets involved in inhibiting cell proliferation in response to taxol. Our findings also suggest that regulation of taxol-sensitizer genes by taxol may be critical for acquired cell resistance to the drug.

  19. Plant-Associated Symbiotic Burkholderia Species Lack Hallmark Strategies Required in Mammalian Pathogenesis

    Science.gov (United States)

    Fong, Stephanie; Yerrapragada, Shailaja; Estrada-de los Santos, Paulina; Yang, Paul; Song, Nannie; Kano, Stephanie; de Faria, Sergio M.; Dakora, Felix D.; Weinstock, George; Hirsch, Ann M.

    2014-01-01

    Burkholderia is a diverse and dynamic genus, containing pathogenic species as well as species that form complex interactions with plants. Pathogenic strains, such as B. pseudomallei and B. mallei, can cause serious disease in mammals, while other Burkholderia strains are opportunistic pathogens, infecting humans or animals with a compromised immune system. Although some of the opportunistic Burkholderia pathogens are known to promote plant growth and even fix nitrogen, the risk of infection to infants, the elderly, and people who are immunocompromised has not only resulted in a restriction on their use, but has also limited the application of non-pathogenic, symbiotic species, several of which nodulate legume roots or have positive effects on plant growth. However, recent phylogenetic analyses have demonstrated that Burkholderia species separate into distinct lineages, suggesting the possibility for safe use of certain symbiotic species in agricultural contexts. A number of environmental strains that promote plant growth or degrade xenobiotics are also included in the symbiotic lineage. Many of these species have the potential to enhance agriculture in areas where fertilizers are not readily available and may serve in the future as inocula for crops growing in soils impacted by climate change. Here we address the pathogenic potential of several of the symbiotic Burkholderia strains using bioinformatics and functional tests. A series of infection experiments using Caenorhabditis elegans and HeLa cells, as well as genomic characterization of pathogenic loci, show that the risk of opportunistic infection by symbiotic strains such as B. tuberum is extremely low. PMID:24416172

  20. Interleukin-17A and vascular remodelling in severe asthma; lack of evidence for a direct role.

    Science.gov (United States)

    Panariti, A; Baglole, C J; Sanchez, V; Eidelman, D H; Hussain, S; Olivenstein, R; Martin, J G; Hamid, Q

    2018-04-01

    Bronchial vascular remodelling may contribute to the severity of airway narrowing through mucosal congestion. Interleukin (IL)-17A is associated with the most severe asthmatic phenotype but whether it might contribute to vascular remodelling is uncertain. To assess vascular remodelling in severe asthma and whether IL-17A directly or indirectly may cause endothelial cell activation and angiogenesis. Bronchial vascularization was quantified in asthmatic subjects, COPD and healthy subjects together with the number of IL-17A + cells as well as the concentration of angiogenic factors in the sputum. The effect of IL-17A on in vitro angiogenesis, cell migration and endothelial permeability was assessed directly on primary human lung microvascular endothelial cells (HMVEC-L) or indirectly with conditioned medium derived from normal bronchial epithelial cells (NHBEC), fibroblasts (NHBF) and airway smooth muscle cells (ASMC) after IL-17A stimulation. Severe asthmatics have increased vascularity compared to the other groups, which correlates positively with the concentrations of angiogenic factors in sputum. Interestingly, we demonstrated that increased bronchial vascularity correlates positively with the number of subepithelial IL-17A + cells. However IL-17A had no direct effect on HMVEC-L function but it enhanced endothelial tube formation and cell migration through the production of angiogenic factors by NHBE and ASMC. Our results shed light on the role of IL-17A in vascular remodelling, most likely through stimulating the synthesis of other angiogenic factors. Knowledge of these pathways may aid in the identification of new therapeutic targets. © 2018 John Wiley & Sons Ltd.