489 research outputs found

    AFRICAN AMERICAN MEN\u27S PROSTATE CANCER KNOWLEDGE AND SELF-EFFICACY FOR INFORMED DECISION-MAKING: A MIXED METHODS STUDY

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    A mixed methods study was conducted whereby, the quantitative portion has a randomized control design, in an urban Delaware community to examine the effectiveness of an educational intervention, which included the testimony of an African American (AA) prostate cancer survivor on AA men’s (n=98) prostate cancer knowledge and self-efficacy for informed decision making. Guided by Bandura’s Social Cognitive theory, participants’ prostate cancer knowledge measured by PROCASE and for self-efficacy measured by the Prostate Cancer Screening Self-efficacy scale, were evaluated before and following viewing of the American Cancer Society’s prostate cancer video. Participants randomized to the intervention completed evaluations after the intervention. A sample (n=10) from each group participated in their respective focus groups. A control focus group (those who neither watched video or heard speaker) was also evaluated. The MANCOVA, using Pillai’s trace, demonstrated a significant effect of the intervention on knowledge and self-efficacy posttest scores, (V= .28, F6,82 = 4.937, p= .000). Combining a prostate cancer survivor’s testimonial with an educational video increases knowledge and self-efficacy among AA men in this urban community

    Juxta-membrane S-acylation of plant receptor-like kinases is likely fortuitous and does not necessarily impact upon function

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    This work was funded by UK Biotechnology and Biological Sciences Research Council Grants BB/M024911/1 and BB/M010996/1 to P.A.H.S-acylation is a common post-translational modification of membrane protein cysteine residues with many regulatory roles. S-acylation adjacent to transmembrane domains has been described in the literature as affecting diverse protein properties including turnover, trafficking and microdomain partitioning. However, all of these data are derived from mammalian and yeast systems. Here we examine the role of S-acylation adjacent to the transmembrane domain of the plant pathogen perceiving receptor-like kinase FLS2. Surprisingly, S-acylation of FLS2 adjacent to the transmembrane domain is not required for either FLS2 trafficking or signalling function. Expanding this analysis to the wider plant receptor-like kinase family we find that S-acylation adjacent to receptor-like kinase domains is common, affecting ~25% of Arabidopsis receptor-like kinases, but poorly conserved between orthologues through evolution. This suggests that S-acylation of receptor-like kinases at this site is likely the result of chance mutation leading to cysteine occurrence. As transmembrane domains followed by cysteine residues are common motifs for S-acylation to occur, and many S-acyl transferases appear to have lax substrate specificity, we propose that many receptor-like kinases are fortuitously S-acylated once chance mutation has introduced a cysteine at this site. Interestingly some receptor-like kinases show conservation of S-acylation sites between orthologues suggesting that S-acylation has come to play a role and has been positively selected for during evolution. The most notable example of this is in the ERECTA-like family where S-acylation of ERECTA adjacent to the transmembrane domain occurs in all ERECTA orthologues but not in the parental ERECTA-like clade. This suggests that ERECTA S-acylation occurred when ERECTA emerged during the evolution of angiosperms and may have contributed to the neo-functionalisation of ERECTA from ERECTA-like proteins.Publisher PDFPeer reviewe

    Citizenship, Values, & Cultural Concerns: What Americans Want From Immigration Reform

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    In February 2013, Public Religion Research Institute (PRRI), in partnership with the Brookings Institution, conducted one of the largest surveys ever fielded on immigration policy, immigrants, and religious and cultural changes in the U.S. The survey of nearly 4,500 American adults explores the many divisions -- political, religious, ethnic, geographical, and generational -- within the nation over core values and their relationship to immigration. The new survey also tracks key questions from surveys conducted by PRRI in 2010-2011. This report presents the results of these surveys

    Structure of an archaeal PCNA1-PCNA2-FEN1 complex: elucidating PCNA subunit and client enzyme specificity.

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    The archaeal/eukaryotic proliferating cell nuclear antigen (PCNA) toroidal clamp interacts with a host of DNA modifying enzymes, providing a stable anchorage and enhancing their respective processivities. Given the broad range of enzymes with which PCNA has been shown to interact, relatively little is known about the mode of assembly of functionally meaningful combinations of enzymes on the PCNA clamp. We have determined the X-ray crystal structure of the Sulfolobus solfataricus PCNA1-PCNA2 heterodimer, bound to a single copy of the flap endonuclease FEN1 at 2.9 A resolution. We demonstrate the specificity of interaction of the PCNA subunits to form the PCNA1-PCNA2-PCNA3 heterotrimer, as well as providing a rationale for the specific interaction of the C-terminal PIP-box motif of FEN1 for the PCNA1 subunit. The structure explains the specificity of the individual archaeal PCNA subunits for selected repair enzyme 'clients', and provides insights into the co-ordinated assembly of sequential enzymatic steps in PCNA-scaffolded DNA repair cascades

    Predicting outcome in acute low back pain using different models of patient profiling

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    This is a non-final version of an article published in final form in Spine, 34(18), 1970 - 1975, 2009. Copyright © 2009 Lippincott Williams & Wilkins, Inc.Study Design. Prospective observational study of prognostic indicators, using data from a randomized, controlled trial of physiotherapy care of acute low back pain (ALBP) with follow-up at 6 weeks, 3 months, and 6 months. Objective. To evaluate which patient profile offers the most useful guide to long-term outcome in ALBP. Summary of Background Data. The evidence used to inform prognostic decision-making is derived largely from studies where baseline data are used to predict future status. Clinicians often see patients on multiple occasions so may profile patients in a variety of ways. It is worth considering if better prognostic decisions can be made from alternative profiles. Methods. Clinical, psychological, and demographic data were collected from a sample of 54 ALBP patients. Three clinical profiles were developed from information collected at baseline, information collected at 6 weeks, and the change in status between these 2 time points. A series of regression models were used to determine the independent and relative contributions of these profiles to the prediction of chronic pain and disability. Results. The baseline profile predicted long-term pain only. The 6-week profile predicted both long-term pain and disability. The change profile only predicted long-term disability (P 0.05). A similar result was obtained when the order of entry was reversed. When predicting long-term disability, after the 6-week profile was entered at the first step, the change profile was not significant when forced in at the second step. However, when the change profile was entered at the first step and the 6-week clinical profile was forced in at the second step, a significant contribution of the 6-week profile was found. Conclusion. The profile derived from information collected at 6 weeks provided the best guide to long-term pain and disability. The baseline profile and change in status offered less predictive value

    Measuring nociception in knee osteoarthritis using physiological and movement responses: a proof-of-concept study

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    Background: Current tools to measure pain are broadly subjective impressions of the impact of the nociceptive impulse felt by the patient. A direct measure of nociception may offer a more objective indicator. Specifically, movement-induced physiological responses to nociception may offer a useful way to monitor knee OA. In this proof-of-concept study, we evaluated whether integrated biomechanical and physiological sensor datasets could display linked and quantifiable information to a nociceptive stimulus. Method: Following ethical approval, we applied a quantified thermal pain stimulus to a volunteer during stationary standing in a gait lab setting. An inertial measurement unit (IMU) and an electromyography (EMG) lower body marker set were tested and integrated with ground reaction force (GRF) data collection. Galvanic skin response electrodes and skin thermal sensors were manually timestamp linked to the integrated system. Results: The integrated EMG, GRF and IMU data show fluctuations within 0.5 seconds of each other when a thermal pain trigger is applied at several time points during a stationary standing test. Manually timestamped physiology measures displayed increased values during testing for skin conductivity (up to 5 µSiemens, 37% compared to baseline) and skin temperature (up to 0.3˚C, 1% compared to baseline). Discussion: This proof-of-concept study suggests that physiological data mimics biomechanical data in response to a known pain stimuli. While this protocol requires further evaluation as to the measurement parameters, the association of the physiological output to the known pain stimulus suggests the potential development of wearable nociceptive sensors that can measure disease progression and treatment effectiveness

    S-acylation stabilizes ligand-induced receptor kinase complex formation during plant pattern-triggered immune signaling

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    Plant receptor kinases are key transducers of extracellular stimuli, such as the presence of beneficial or pathogenic microbes or secreted signaling molecules. Receptor kinases are regulated by numerous post-translational modifications.1,2,3 Here, using the immune receptor kinases FLS24 and EFR,5 we show that S-acylation at a cysteine conserved in all plant receptor kinases is crucial for function. S-acylation involves the addition of long-chain fatty acids to cysteine residues within proteins, altering their biochemical properties and behavior within the membrane environment.6 We observe S-acylation of FLS2 at C-terminal kinase domain cysteine residues within minutes following the perception of its ligand, flg22, in a BAK1 co-receptor and PUB12/13 ubiquitin ligase-dependent manner. We demonstrate that S-acylation is essential for FLS2-mediated immune signaling and resistance to bacterial infection. Similarly, mutating the corresponding conserved cysteine residue in EFR suppressed elf18-triggered signaling. Analysis of unstimulated and activated FLS2-containing complexes using microscopy, detergents, and native membrane DIBMA nanodiscs indicates that S-acylation stabilizes, and promotes retention of, activated receptor kinase complexes at the plasma membrane to increase signaling efficiency

    S-acylation stabilizes ligand-induced receptor kinase complex formation during plant pattern-triggered immune signalling

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    SummaryPlant receptor kinases are key transducers of extracellular stimuli, such as the presence of beneficial or pathogenic microbes or secreted signalling molecules. Receptor kinases are regulated by numerous post-translational modifications. Here, using the immune receptor kinases FLS2 and EFR, we show that S-acylation at a cysteine conserved in all plant receptor kinases is crucial for function. S-acylation involves the addition of long-chain fatty acids to cysteine residues within proteins, altering their biophysical properties and behaviour within the membrane environment. We observe S-acylation of FLS2 at C-terminal kinase domain cysteine residues within minutes following perception of its ligand flg22, in a BAK1 co-receptor dependent manner. We demonstrate that S-acylation is essential for FLS2-mediated immune signalling and resistance to bacterial infection. Similarly, mutating the corresponding conserved cysteine residue in EFR supressed elf18 triggered signalling. Analysis of unstimulated and activated FLS2-containing complexes using microscopy, detergents and native membrane DIBMA nanodiscs indicates that S-acylation stabilises and promotes retention of activated receptor kinase complexes at the plasma membrane to increase signalling efficiency
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