2,294 research outputs found

    Gaussian Process Modelling for Improved Resolution in Faraday Depth Reconstruction

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    The incomplete sampling of data in complex polarization measurements from radio telescopes negatively affects both the rotation measure (RM) transfer function and the Faraday depth spectra derived from these data. Such gaps in polarization data are mostly caused by flagging of radio frequency interference and their effects worsen as the percentage of missing data increases. In this paper we present a novel method for inferring missing polarization data based on Gaussian processes (GPs). Gaussian processes are stochastic processes that enable us to encode prior knowledge in our models. They also provide a comprehensive way of incorporating and quantifying uncertainties in regression modelling. In addition to providing non-parametric model estimates for missing values, we also demonstrate that Gaussian process modelling can be used for recovering rotation measure values directly from complex polarization data, and that inferring missing polarization data using this probabilistic method improves the resolution of reconstructed Faraday depth spectra.Comment: 16 pages, 10 figures, submitted to MNRA

    The Impact of Volunteering on Seniors’ Health and Quality of Life: An Assessment of the Retired and Senior Volunteer Program

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    Past research suggests that senior citizens often face challenges related to deteriorating physical and men- tal health, and the quality of their lives may suffer as a result. Past research also suggests that volunteering can improve the health and quality of life for seniors. In the present study, 451 volunteers enrolled in the Retired and Senior Volunteer Program (RSVP) completed surveys including questions regarding their volunteer experiences and how these experiences have affected their health and quality of life. The results suggest that volunteering through RSVP is associated with improvements in health and quality of life across a variety of dimensions. Furthermore, these improvements may be particularly greater for women, current volunteers, and older seniors. These findings may help guide interventions designed to enhance the health and well-being of senior citizens in a variety of settings

    Bradyzoite pseudokinase 1 is crucial for efficient oral infectivity of the Toxoplasma gondii tissue cyst.

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    The tissue cyst formed by the bradyzoite stage of Toxoplasma gondii is essential for persistent infection of the host and oral transmission. Bradyzoite pseudokinase 1 (BPK1) is a component of the cyst wall, but nothing has previously been known about its function. Here, we show that immunoprecipitation of BPK1 from in vitro bradyzoite cultures, 4 days postinfection, identifies at least four associating proteins: MAG1, MCP4, GRA8, and GRA9. To determine the role of BPK1, a strain of Toxoplasma was generated with the bpk1 locus deleted. This BPK1 knockout strain (Δbpk1) was investigated in vitro and in vivo. No defect was found in terms of in vitro cyst formation and no difference in pathogenesis or cyst burden 4 weeks postinfection (wpi) was detected after intraperitoneal (i.p.) infection with Δbpk1 tachyzoites, although the Δbpk1 cysts were significantly smaller than parental or BPK1-complemented strains at 8 wpi. Pepsin-acid treatment of 4 wpi in vivo cysts revealed that Δbpk1 parasites are significantly more sensitive to this treatment than the parental and complemented strains. Consistent with this, 4 wpi Δbpk1 cysts showed reduced ability to cause oral infection compared to the parental and complemented strains. Together, these data reveal that BPK1 plays a crucial role in the in vivo development and infectivity of Toxoplasma cysts

    <i>Schizosaccharomyces pombe</i> Pol II transcription elongation factor ELL functions as part of a rudimentary super elongation complex

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    ELL family transcription factors activate the overall rate of RNA polymerase II (Pol II) transcription elongation by binding directly to Pol II and suppressing its tendency to pause. In metazoa, ELL regulates Pol II transcription elongation as part of a large multisubunit complex referred to as the Super Elongation Complex (SEC), which includes P-TEFb and EAF, AF9 or ENL, and an AFF family protein. Although orthologs of ELL and EAF have been identified in lower eukaryotes including Schizosaccharomyces pombe, it has been unclear whether SEClike complexes function in lower eukaryotes. In this report, we describe isolation from S. pombe of an ELL-containing complex with features of a rudimentary SEC. This complex includes S. pombe Ell1, Eaf1, and a previously uncharacterized protein we designate Ell1 binding protein 1 (Ebp1), which is distantly related to metazoan AFF family members. Like the metazoan SEC, this S. pombe ELL complex appears to function broadly in Pol II transcription. Interestingly, it appears to have a particularly important role in regulating genes involved in cell separation

    Modeling peptide fragmentation with dynamic Bayesian networks for peptide identification

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    Motivation: Tandem mass spectrometry (MS/MS) is an indispensable technology for identification of proteins from complex mixtures. Proteins are digested to peptides that are then identified by their fragmentation patterns in the mass spectrometer. Thus, at its core, MS/MS protein identification relies on the relative predictability of peptide fragmentation. Unfortunately, peptide fragmentation is complex and not fully understood, and what is understood is not always exploited by peptide identification algorithms

    Current challenges in software solutions for mass spectrometry-based quantitative proteomics

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    This work was in part supported by the PRIME-XS project, grant agreement number 262067, funded by the European Union seventh Framework Programme; The Netherlands Proteomics Centre, embedded in The Netherlands Genomics Initiative; The Netherlands Bioinformatics Centre; and the Centre for Biomedical Genetics (to S.C., B.B. and A.J.R.H); by NIH grants NCRR RR001614 and RR019934 (to the UCSF Mass Spectrometry Facility, director: A.L. Burlingame, P.B.); and by grants from the MRC, CR-UK, BBSRC and Barts and the London Charity (to P.C.

    Southeast Asia and the Politics of Vulnerability

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    The economic and political crises that have recently engulfed the countries of Southeast Asia provide a stark reminder of just how difficult the challenge of sustained regional development remains. In retrospect, the hyperbole that surrounded the 'East Asian miracle' looks overblown, and testimony to the manner in which rhetoric can outstrip reality, especially in the minds of international investors. Certainly, some observers had questioned the depth and resilience of capitalist development in Southeast Asia, but in the years immediately prior to 1997 such analyses tended to be in the minority. Now, of course, it is painfully obvious that much of Southeast Asia's economic and political development was extremely fragile. When seen in historical context, this outcome should not have been surprising since the countries of modern Southeast Asia, both as independent nations and as colonies of various imperial powers, have been highly vulnerable to the actions of powerful external political and economic forces. This paper will examine the economic bases and the political consequences of this vulnerablity, both domestically and at a regional level. I argue that the recent crisis has served as an unwelcome reminder of just how constrained, dependent and vulnerable the Southeast Asia region's development prospects remain, a situation that is exacerbated by, and which contributes to, domestic political crises

    Proteomic analysis of the Plasmodium male gamete reveals the key role for glycolysis in flagellar motility.

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    BACKGROUND: Gametogenesis and fertilization play crucial roles in malaria transmission. While male gametes are thought to be amongst the simplest eukaryotic cells and are proven targets of transmission blocking immunity, little is known about their molecular organization. For example, the pathway of energy metabolism that power motility, a feature that facilitates gamete encounter and fertilization, is unknown. METHODS: Plasmodium berghei microgametes were purified and analysed by whole-cell proteomic analysis for the first time. Data are available via ProteomeXchange with identifier PXD001163. RESULTS: 615 proteins were recovered, they included all male gamete proteins described thus far. Amongst them were the 11 enzymes of the glycolytic pathway. The hexose transporter was localized to the gamete plasma membrane and it was shown that microgamete motility can be suppressed effectively by inhibitors of this transporter and of the glycolytic pathway. CONCLUSIONS: This study describes the first whole-cell proteomic analysis of the malaria male gamete. It identifies glycolysis as the likely exclusive source of energy for flagellar beat, and provides new insights in original features of Plasmodium flagellar organization

    Activation of the steroid and xenobiotic receptor, SXR, induces apoptosis in breast cancer cells

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    <p>Abstract</p> <p>Background</p> <p>The steroid and xenobiotic receptor, SXR, is an orphan nuclear receptor that regulates metabolism of diverse dietary, endobiotic, and xenobiotic compounds. SXR is expressed at high levels in the liver and intestine, and at lower levels in breast and other tissues where its function was unknown. Since many breast cancer preventive and therapeutic compounds are SXR activators, we hypothesized that some beneficial effects of these compounds are mediated through SXR.</p> <p>Methods</p> <p>To test this hypothesis, we measured proliferation of breast cancer cells in response to SXR activators and evaluated consequent changes in the expression of genes critical for proliferation and cell-cycle control using quantitative RT-PCR and western blotting. Results were confirmed using siRNA-mediated gene knockdown. Statistical analysis was by t-test or ANOVA and a P value ≤ 0.05 was considered to be significant.</p> <p>Results</p> <p>Many structurally and functionally distinct SXR activators inhibited the proliferation of MCF-7 and ZR-75-1 breast cancer cells by inducing cell cycle arrest at the G1/S phase followed by apoptosis. Decreased growth in response to SXR activation was associated with stabilization of p53 and up-regulation of cell cycle regulatory and pro-apoptotic genes such as p21, PUMA and BAX. These gene expression changes were preceded by an increase in inducible nitric oxide synthase and nitric oxide in these cells. Inhibition of iNOS blocked the induction of p53. p53 knockdown inhibited up-regulation of p21 and BAX. We infer that NO is required for p53 induction and that p53 is required for up-regulation of cell cycle regulatory and apoptotic genes in this system. SXR activator-induced increases in iNOS levels were inhibited by siRNA-mediated knockdown of SXR, indicating that SXR activation is necessary for subsequent regulation of iNOS expression.</p> <p>Conclusion</p> <p>We conclude that activation of SXR is anti-proliferative in p53 wild type breast cancer cells and that this effect is mechanistically dependent upon the local production of NO and NO-dependent up-regulation of p53. These findings reveal a novel biological function for SXR and suggest that a subset of SXR activators may function as effective therapeutic and chemo-preventative agents for certain types of breast cancers.</p