396 research outputs found

    Inhibiting histone deacetylase 1 suppresses both inflammation and bone loss in arthritis

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    Objective. Histone deacetylase 1 (HDAC1) is highly expressed in the synovium of RA patients. Thus we aimed to investigate a novel HDAC inhibitor (HDACi), NW-21, designed to target HDAC1. The effect of NW-21 on osteoclast formation and activity, cytokine and chemokine expression in vitro and arthritis in mice was assessed

    Bed bug deterrence

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    A recent study in BMC Biology has determined that the immature stage of the bed bug (the nymph) signals its reproductive status to adult males using pheromones and thus avoids the trauma associated with copulation in this species. The success of this nymphal strategy of deterrence is instructive. Against the background of increasing problems with bed bugs, this research raises the question whether pheromones might be used to control them

    Hypothalamic ERK Mediates the Anorectic and Thermogenic Sympathetic Effects of Leptin

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    OBJECTIVE—Leptin is an adipocyte hormone that plays a major role in energy balance. Leptin receptors in the hypothalamus are known to signal via distinct mechanisms, including signal transducer and activator of transcription-3 (STAT3) and phosphoinositol-3 kinase (PI 3-kinase). Here, we tested the hypothesis that extracellular signal–regulated kinase (ERK) is mediating leptin action in the hypothalamus

    Vaccination with DNA plasmids expressing Gn coupled to C3d or alphavirus replicons expressing Gn protects mice against rift valley fever virus

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    Background: Rift Valley fever (RVF) is an arthropod-borne viral zoonosis. Rift Valley fever virus (RVFV) is an important biological threat with the potential to spread to new susceptible areas. In addition, it is a potential biowarfare agent. Methodology/Principal Findings: We developed two potential vaccines, DNA plasmids and alphavirus replicons, expressing the Gn glycoprotein of RVFV alone or fused to three copies of complement protein, C3d. Each vaccine was administered to mice in an all DNA, all replicon, or a DNA prime/replicon boost strategy and both the humoral and cellular responses were assessed. DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited high titer neutralizing antibodies that were similar to titers elicited by the live-attenuated MP12 virus. Mice vaccinated with an inactivated form of MP12 did elicit high titer antibodies, but these antibodies were unable to neutralize RVFV infection. However, only vaccine strategies incorporating alphavirus replicons elicited cellular responses to Gn. Both vaccines strategies completely prevented weight loss and morbidity and protected against lethal RVFV challenge. Passive transfer of antisera from vaccinated mice into naïve mice showed that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited antibodies that protected mice as well as sera from mice immunized with MP12. Conclusion/Significance: These results show that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn administered alone or in a DNA prime/replicon boost strategy are effective RVFV vaccines. These vaccine strategies provide safer alternatives to using live-attenuated RVFV vaccines for human use. © 2010 Bhardwaj et al

    Measuring the mass of the central black hole in the bulgeless galaxy ngc 4395 from gas dynamical modeling

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    NGC 4395 is a bulgeless spiral galaxy, harboring one of the nearest known type 1 Seyfert nuclei. Although there is no consensus on the mass of its central engine, several estimates suggest it is one of the lightest massive black holes (MBHs) known. We present the first direct dynamical measurement of the mass of this MBH from a combination of two-dimensional gas kinematic data, obtained with the adaptive optics assisted near-infrared integral field spectrograph Gemini/NIFS and high-resolution multiband photometric data from Hubble Space Telescope's Wide Field Camera 3. We use the photometric data to model the shape and stellar mass-to-light ratio of the nuclear star cluster (NSC). From the Gemini/NIFS observations, we derive the kinematics of warm molecular hydrogen gas as traced by emission through the H2 1–0 S(1) transition. These kinematics show a clear rotational signal, with a position angle orthogonal to NGC 4395's radio jet. Our best-fitting tilted ring models of the kinematics of the molecular hydrogen gas contain a black hole with mass M={4}-3+8× {10}5 M⊙ (3σ uncertainties) embedded in an NSC of mass M=2× {10}6 M⊙. Our black hole mass measurement is in excellent agreement with the reverberation mapping mass estimate of Peterson et al. but shows some tension with other mass measurement methods based on accretion signals

    NK- and T-cell granzyme B and K expression correlates with age, CMV infection and influenza vaccine-induced antibody titres in older adults

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    Granzymes are a family of serine-proteases that act as critical mediators in the cytolytic and immunomodulatory activities of immune cells such as CD8+ T-cells and natural killer (NK) cells. Previous work indicates that both granzyme B (GZB) and K (GZK) are increased with age in CD8+ T-cells, and in the case of GZB, contribute to dysfunctional immune processes observed in older adults. Here, we sought to determine how GZB and GZK expression in NK-cells, and CD4+, CD8+, and gamma-delta T-cells, quantified in terms of positive cell frequency and mean fluorescence intensity (MFI), differed with age, age-related health-traits and the antibody response to high-dose influenza vaccine. We found that the frequency and MFI of GZB-expressing NK-cells, and CD8+ and Vδ1+ T-cells, and GZK-expressing CD8+ T-cells was significantly higher in older (66–97 years old; n = 75) vs. younger (24–37 years old; n = 10) adults by up to 5-fold. There were no significant associations of GZB/GZK expression with sex, frailty or plasma levels of TNF or IL-6 in older adults, but those who were seropositive for cytomegalovirus (CMV) exhibited significantly higher frequencies of GZB+ NK-cells, and CD4+, CD8+ and Vδ1+ T-cells, and GZK+ CD8+ T-cells (Cohen’s d = .5–1.5). Pre-vaccination frequencies of GZB+ NK-cells were positively correlated with vaccine antibody responses against A/H3N2 (d = .17), while the frequencies of GZK+ NK and CD8+ T-cells were inversely associated with A/H1N1 (d = −0.18 to −0.20). Interestingly, GZK+ NK-cell frequency was inversely correlated with pre-vaccination A/H1N1 antibody titres, as well as those measured over the previous 4 years, further supporting a role for this subset in influencing vaccine antibody-responses. These findings further our understanding of how granzyme expression in different lymphoid cell-types may change with age, while suggesting that they influence vaccine responsiveness in older adults

    Drug information resources used by nurse practitioners and collaborating physicians at the point of care in Nova Scotia, Canada: a survey and review of the literature

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    BACKGROUND: Keeping current with drug therapy information is challenging for health care practitioners. Technologies are often implemented to facilitate access to current and credible drug information sources. In the Canadian province of Nova Scotia, legislation was passed in 2002 to allow nurse practitioners (NPs) to practice collaboratively with physician partners. The purpose of this study was to determine the current utilization patterns of information technologies by these groups of practitioners. METHODS: Nurse practitioners and their collaborating physician partners in Nova Scotia were sent a survey in February 2005 to determine the frequency of use, usefulness, accessibility, credibility, and current/timeliness of personal digital assistant (PDA), computer, and print drug information resources. Two surveys were developed (one for PDA users and one for computer users) and revised based on a literature search, stakeholder consultation, and pilot-testing results. A second distribution to nonresponders occurred two weeks following the first. Data were entered and analysed with SPSS. RESULTS: Twenty-seven (14 NPs and 13 physicians) of 36 (75%) recipients responded. 22% (6) returned personal digital assistant (PDA) surveys. Respondents reported print, health professionals, and online/electronic resources as the most to least preferred means to access drug information, respectively. 37% and 35% of respondents reported using "both print and electronic but print more than electronic" and "print only", respectively, to search monograph-related drug information queries whereas 4% reported using "PDA only". Analysis of respondent ratings for all resources in the categories print, health professionals and other, and online/electronic resources, indicated that the Compendium of Pharmaceuticals and Specialties and pharmacists ranked highly for frequency of use, usefulness, accessibility, credibility, and current/timeliness by both groups of practitioners. Respondents' preferences and resource ratings were consistent with self-reported methods for conducting drug information queries. Few differences existed between NP and physician rankings of resources. CONCLUSION: The use of computers and PDAs remains limited, which is also consistent with preferred and frequent use of print resources. Education for these practitioners regarding available electronic drug information resources may facilitate future computer and PDA use. Further research is needed to determine methods to increase computer and PDA use and whether these technologies affect prescribing and patient outcomes
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