2,266 research outputs found

    Functional Characterisation of Spc29p, a Component of the Saccharomyces cerevisiae Spindle Pole Body

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    In the budding yeast Saccharomyces cerevisiae, microtubule organising functions are carried out by the spindle pole body (SPB). The SPB is a disk-like, multilayered structure that is embedded in the nuclear membrane throughout the cell cycle. The major substructures of the SPB are the outer, central and inner plaques and the half-bridge. The central plaque is embedded in the nuclear membrane. The outer and inner plaques are positioned on the cytoplasmic and nuclear side of the central plaque where they organise the cytoplasmic and nuclear microtubules respectively. The half-bridge extends from the central plaque along the nuclear envelope and is involved in SPB duplication and organises cytoplasmic microtubules during G1 of the cell cycle and during mating. Described within is the identification and characterisation of a novel SPB component, Spc29p. Spc29p was found as a component of a salt stable SPB subcomplex composed of central and inner plaque SPB components. This complex contained Spc29p, the central plaque component Spc42p, the ?-tubulin-complex-binding protein Spe110p and calmodulin. Spc29p acts as a linker between Spc42p and the globular C-terminus of Spc110p at the central plaque. Evidence is provided that the calmodulin-binding site of Spc110p influences the binding of Spc29p to Spc110p. In addition, co-overexpression of Spc29p, Spc42p and Spc110p resulted in a three fold increase in the diameter of the SPB, indicating that expression levels of SPB components may be involved in the size control of the SPB. Construction and analysis of spc29 temperature sensitive mutants uncovered another important function of Spc29p. Using immunofluorescence, FACS analysis and electron microscopy the spc29(ts) mutants were found to have an SPB duplication defect. A role for Spc29p in SPB duplication was supported by the genetic and biochemical interactions between Spc29p and other SPB components involved in SPB duplication, namely the half-bridge components Cdc3 1p and Karlp. Evidence is also provided for an interaction between Spc29p at the periphery of the central plaque, with the Bbplp/Mps2p complex, which is involved in embedding the SPB in the nuclear envelope. Spc29p was also found to be phosphorylated in a cell cycle dependent manner

    Health taxes on tobacco, alcohol, food and drinks in low- and middle-income countries: a scoping review of policy content, actors, process and context

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    Background: Taxation of tobacco, food, alcohol and other beverages has gained renewed attention in responding to non-communicable diseases (NCDs). While largely built on evidence from high-income countries (HICs), the projected economic and health benefits of these measures have increased calls for their use in price-sensitive low- and middle-income countries (LMICs). However, uptake has been sporadic and there remains little research on why and how LMICs utilise fiscal measures in response to NCDs. Methods: This scoping review analyses factors influencing the design and implementation of health-related fiscal measures in LMICs. Utilising Arksey and O'Malley's scoping review methodology and Walt and Gilson’s policy triangle, we considered the contextual, procedural, content and stakeholder-related factors that influenced measures. Results: We identified 75 papers focussing on health-related fiscal measures, with 47 (63%) focused on tobacco, 5 on alcohol, 6 on soft drink and 4 studies on food-related fiscal regulation. Thirteen papers analysed multiple measures and most papers (n = 66, 88%) were less than a decade old. Key factors enabling the design and implementation of measures included localised health and economic evidence, policy championing, inter-ministerial support, and global or regional momentum. Impeding factors encompassed negative framing and retaliation by industry, vested interests and governmental policy disjuncture. Aligning with theoretic insights from the policy triangle, findings consistently demonstrated that the interplay between factors – rather than the presence or absence of particular factors – has the most profound impact on policy implementation. Conclusion: Given the growing urgency to address NCDs in LMICs, this review highlights the need for recognition and rigorous exploration of political economy factors influencing the design and implementation of fiscal measures. Broader LMIC-specific empirical research is needed to overcome an implication noted in much of the literature: that mechanisms used to enact tobacco taxation are universally applicable to measures targeting foods, alcohol and other beverages

    Spatial and seasonal relationships between Pacific harbor seals (Phoca vitulina richardii) and their prey, at multiple scales

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    Knowing where pinnipeds forage is vital to managing and protecting their populations, and for assessing potential interactions with fisheries. We assessed the spatial relationship between the seasonal distribution of Pacific harbor seals (Phoca vitulina richardii) outfitted with satellite transmitters and the seasonal distributions of potential harbor seal prey species in San Francisco Bay, California. Pearson’s correlation coefficients were calculated between the number of harbor seal locations in an area of the San Francisco Bay and the abundance of specific prey species in the same area. The influence of scale on the analyses was assessed by varying the scale of analysis from 1 to 10 km. There was consistency in the prey species targeted by harbor seals year-round, although there were seasonal differences between the most important prey species. The highest correlations between harbor seals and their prey were found for seasonally abundant benthic species, located within about 10 km of the primary haul-out site. Probable foraging habitat for harbor seals was identified, based on areas with high abundances of prey species that were strongly correlated with harbor seal distribution. With comparable local data inputs, this approach has potential application to pinniped management in other areas, and to decisions about the location of marine reserves designed to protect these species

    Response normalization and blur adaptation:data and multi-scale model

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    Adapting to blurred or sharpened images alters perceived blur of a focused image (M. A. Webster, M. A. Georgeson, & S. M. Webster, 2002). We asked whether blur adaptation results in (a) renormalization of perceived focus or (b) a repulsion aftereffect. Images were checkerboards or 2-D Gaussian noise, whose amplitude spectra had (log-log) slopes from -2 (strongly blurred) to 0 (strongly sharpened). Observers adjusted the spectral slope of a comparison image to match different test slopes after adaptation to blurred or sharpened images. Results did not show repulsion effects but were consistent with some renormalization. Test blur levels at and near a blurred or sharpened adaptation level were matched by more focused slopes (closer to 1/f) but with little or no change in appearance after adaptation to focused (1/f) images. A model of contrast adaptation and blur coding by multiple-scale spatial filters predicts these blur aftereffects and those of Webster et al. (2002). A key proposal is that observers are pre-adapted to natural spectra, and blurred or sharpened spectra induce changes in the state of adaptation. The model illustrates how norms might be encoded and recalibrated in the visual system even when they are represented only implicitly by the distribution of responses across multiple channels

    Structural determinants for EB1-mediated recruitment of APC and spectraplakins to the microtubule plus end

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    EB1 is a member of a conserved protein family that localizes to growing microtubule plus ends. EB1 proteins also recruit cell polarity and signaling molecules to microtubule tips. However, the mechanism by which EB1 recognizes cargo is unknown. Here, we have defined a repeat sequence in adenomatous polyposis coli (APC) that binds to EB1's COOH-terminal domain and identified a similar sequence in members of the microtubule actin cross-linking factor (MACF) family of spectraplakins. We show that MACFs directly bind EB1 and exhibit EB1-dependent plus end tracking in vivo. To understand how EB1 recognizes APC and MACFs, we solved the crystal structure of the EB1 COOH-terminal domain. The structure reveals a novel homodimeric fold comprised of a coiled coil and four-helix bundle motif. Mutational analysis reveals that the cargo binding site for MACFs maps to a cluster of conserved residues at the junction between the coiled coil and four-helix bundle. These results provide a structural understanding of how EB1 binds two regulators of microtubule-based cell polarity

    Koinonia

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    In This IssuePeople are Hungry to Talk About Deep Things (Reprint from The Embarrassed Believer: Reviving Christian Witness in an Age of Unbelief), Hugh Hewitt The Legacy of Ernest L. Boyer, Sr.: The Boyer Center at Messiah College, Debra L. Elliott Filling the Voids in Christian Leadership Training Today: Connecting Student Development, Stewardship & Nonprofit Education with Emerging Leaders, An Interview with Scott Preissler, The Christian Stewardship Association Reply to an Idealistic Job-Searcher, Dana Alexander In The FieldBeyond the Horizon: Student Affairs Practice in the 21st Century, Dennis A. Sheridan Around CampusAnd God Created . . . Sex, Theresa Hannerman and Sarah Marcum Regular FeaturesPresident\u27s Corner Editor\u27s Disk Annual Conference News from the Regions: Spotlight on the Southeast Book Reviews: The Embarrassed Believer: When Hope and Fear Collide Perspective: The Ultimate Student Service: Prayer?https://pillars.taylor.edu/acsd_koinonia/1017/thumbnail.jp

    Validation of self-reported help-seeking, and measurement of the patient interval, for cancer symptoms:an observational study to inform methodological challenges in symptomatic presentation research

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    BackgroundTo improve earlier presentation with potential symptoms of cancer, accurate data are needed on how people respond to these symptoms. It is currently unclear how self-reported medical help-seeking for symptoms associated with cancer by people from the community correspond to what is recorded in their general practice records, or how well the patient interval (time from symptom onset to first presentation to a health-professional) can be estimated from patient records.MethodData from two studies that reviewed general practice electronic records of residents in Scotland, (i) the ‘Useful Study’: respondents to a general population survey who reported experiencing symptoms potentially associated with one of four common cancers (breast, colorectal, lung and upper gastro-intestinal) and (ii) the ‘Detect Cancer Early’ programme: cancer patients with one of the same four cancers. Survey respondents’ self-reported help-seeking (yes/no) was corroborated; Cohen’s Kappa assessed level of agreement. Combined data on the patient interval were evaluated using descriptive analysis.Results‘Useful Study’ respondents’ self-report of help-seeking showed exact correspondence with general practice electronic records in 72% of cases (n = 136, kappa 0.453, moderate agreement). Between both studies, 1269 patient records from 35 general practices were reviewed. The patient interval could not be determined in 44% (n = 809) of symptoms presented by these individuals.ConclusionsPatient self-report of help-seeking for symptoms potentially associated with cancer offer a reasonably accurate method to research responses to these symptoms. Incomplete patient interval data suggest routine general practice records are unreliable for measuring this important part of the patient’s symptom journey

    Kinetochore alignment within the metaphase plate is regulated by centromere stiffness and microtubule depolymerases

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    During mitosis in most eukaryotic cells, chromosomes align and form a metaphase plate halfway between the spindle poles, about which they exhibit oscillatory movement. These movements are accompanied by changes in the distance between sister kinetochores, commonly referred to as breathing. We developed a live cell imaging assay combined with computational image analysis to quantify the properties and dynamics of sister kinetochores in three dimensions. We show that baseline oscillation and breathing speeds in late prometaphase and metaphase are set by microtubule depolymerases, whereas oscillation and breathing periods depend on the stiffness of the mechanical linkage between sisters. Metaphase plates become thinner as cells progress toward anaphase as a result of reduced oscillation speed at a relatively constant oscillation period. The progressive slowdown of oscillation speed and its coupling to plate thickness depend nonlinearly on the stiffness of the mechanical linkage between sisters. We propose that metaphase plate formation and thinning require tight control of the state of the mechanical linkage between sisters mediated by centromeric chromatin and cohesion

    Serum relaxin levels are reduced in pregnant women with a history of recurrent miscarriage, and correlate with maternal uterine artery Doppler indices in first trimester

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    Objectives: Defective implantation is a mechanism for recurrent pregnancy loss (RPL). We sought to determine whether the serum expression of human relaxin-2 (RLX) is impaired in women with a history of RPL. Study design: Employing a prospective case-controlled design we studied 20 pregnant women with a history of RPL and 20 age-matched women with no history of RPL (NRPL). We measured serum relaxin-2 levels by ELISA at 6-8. 10-12, 20, and 34 weeks gestation and in cord blood, and maternal uterine artery Doppler resistance index (RI) at >= 10 weeks gestation. Results: Relaxin rose to a peak at 12 weeks, and gradually declined towards term. At all gestations, women with a history of RPL had lower RLX levels than women without. At 10-12 weeks gestation, uterine artery RI correlated with serum RLX for both RPL and NRPL. In the NRPL group at 10-12 weeks the presence of a notched waveform was associated with higher RLX levels than the absence of a notch (mean 2.1 ng/ml vs. 1.3 ng/ml, P < 0.05) and also at 20 weeks (2.1 ng/ml vs. 0.95 ng/ml, P < 0.05) but no such difference was seen in the RPL group. Umbilical venous RLX was 4-fold higher in the RPL group than the NRPL group. Conclusion: Women with a history of RPL demonstrate attenuated levels of serum RLX across all pregnancy trimesters. How dysregulated RLX metabolism may contribute to adverse pregnancy outcome in RPL requires further investigation. Crown Copyright (C) 2009 Published by Elsevier Ireland Ltd. All rights reserved
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