979 research outputs found
Education, Attitudes, and Language of Higher Education: Francophone Students in Northern Ontario
Data from 1586 Francophone students in Northeastern Ontario concerning their attitudes towards French and English show seven independent factors affect linguistic beliefs. Three factors -believing French unimportant, believing English practically dominant, and believing their French inadequate - lead students to continue their post-secondary education solely in English. Believing French more pleasurable is positively, and believing English superior is negatively, related to continuing post-secondary education solely in French. Educational level is negatively related to believing English superior and to believing French unimportant but positively related to believing English dominant, French pleasurable, and their French inadequate. Policy should therefore focus on countering the belief in English dominance and the belief in the inadequacy of their ability in French.Les données recueillies par Laflamme et Dennie (1990) auprès de 1586 étudiants francophones du Nord-Est de l'Ontario, données portant notamment sur les attitudes envers le français et l'anglais, révèlent sept facteurs déterminants des croyances linguistiques. Trois facteurs - croire que le français n'est pas important, que l'anglais est en réalité dominant et que le français qu'on parle est inadéquat - incitent les étudiants à poursuivre leurs études en anglais seulement. Croire que le français constitue, plus que l'anglais, une langue de plaisir est positivement relié au fait de poursuivre des études postsecondaires en français seulement, alors que tenir l'anglais pour une langue supérieure est négativement relié au fait de poursuivre des études en français seulement. Le niveau d'éducation est négativement relié à la croyance en la supériorité de l'anglais et à celle en la non-importance du français, mais il est relié positivement au fait de croire en la domination de l'anglais, au français comme langue de plaisir et au manque de compétence à s'exprimer dans sa langue. Par conséquent, les décisions politiques devraient veiller à contrecarrer la croyance en la domination de l'anglais et celle en l'incompétence de la personne dans sa langue
Should Australia allow mitochondrial donation?
Is there any ethical reason why legislation should prevent the use of donor mitochondria in cases where children are likely to inherit mitochondrial disease from their mothers
Proteases and Programmed Cell Death in Fungi
Programmed cell death in animals, plants and protists is in part regulated by a variety of proteases, including cysteine aspartyl proteases, (caspases, paracaspases and metacaspases), cathepsins, subtilisin-like serine proteases, vacuolar processing enzymes and the proteasome. The role of different proteases in the cell death responses of the fungi is however largely unknown. A greater understanding of the fungal cell death machinery may provide new insights into the mechanisms and evolution of PCD and potentially reveal novel targets for a new generation of antifungal drugs.
The role of a metacaspase encoding gene, MCA1, in the cell death response of the human pathogen Candida albicans pathogen has been investigated by functional analysis. MCA1 deletion not only alters the sensitivity of cells to a number of cell death stimuli, it also enhances virulence in an insect model. C. albicans shows altered cell and colony morphology on Lee’s medium. Evidence is presented to suggest that these functions appear to be dependent upon active mitochondria.
In this study it has also been shown that key caspase substrates may be conserved between humans and the yeasts Saccharomyces cerevisiae and Candida albicans. Many substrates, particularly those which are essential, have retained their caspase cleavage motifs. 14 protease mutants displayed altered activity against caspase 1, 3, 6 or 8 substrates during acetic acid-induced PCD and caspase 1-like activity appeared to be particularly associated with PCD.
Using a novel bioinformatic analysis of experimental LC-MS/MS data, changes in the degradation patterns of the proteome (destructome) following acetic acid-induced cell death have been investigated in wild-type yeast. In addition, potential native substrates of the yeast Mca1 have also been identified.
The future challenge is to characterise the destructome of different proteases under a range of cell death conditions. In this way it may be possible to identify key components of the cell death machinery and their substrates and so reveal the most promising targets for future therapeutics.Biotechnology and Biological Sciences Research Counci
Ethical and Policy Issues Raised by Uterus Transplants
Introduction: In 2014, Brännström and colleagues reported the first human live birth following uterine transplantation (UTx). Research into this treatment for absolute uterine factor infertility has since grown with clinical trials currently taking place across centers in at least thirteen countries worldwide. Sources of data: This review summarizes and critiques the academic literature on ethical and policy issues raised by UTx. Areas of agreement: There is general agreement on the importance of risk reduction and, in principle, to the sharing and maintenance of patient data on an international registry. Areas of controversy: There are numerous areas of controversy ranging from whether it is ethically justified to carry out uterus transplants at all (considering the associated health risks) to how deceased donor organs for transplant should be allocated. This review focuses on three key issues: the choice between deceased and living donors, ensuring valid consent to the procedure and access to treatment. Growing points; UTx is presently a novel and rare procedure but is likely to become more commonplace in the foreseeable future, given the large number of surgical teams working on it worldwide. Areas timely for developing research: Uterus transplantation requires us to re-examine fundamental questions about the ethical and social value of gestation. If eventually extended to transgender women or even to men, it may also require us to reconceptualize what it is to be a ‘father’ or to be a ‘mother’, and the definition of these terms in law
Global changes in gene expression associated with phenotypic switching of wild yeast
BACKGROUND: Saccharomyces cerevisiae strains isolated from natural settings form structured biofilm colonies that are equipped with intricate protective mechanisms. These wild strains are able to reprogram themselves with a certain frequency during cultivation in plentiful laboratory conditions. The resulting domesticated strains switch off certain protective mechanisms and form smooth colonies that resemble those of common laboratory strains. RESULTS: Here, we show that domestication can be reversed when a domesticated strain is challenged by various adverse conditions; the resulting feral strain restores its ability to form structured biofilm colonies. Phenotypic, microscopic and transcriptomic analyses show that phenotypic transition is a complex process that affects various aspects of feral strain physiology; it leads to a phenotype that resembles the original wild strain in some aspects and the domesticated derivative in others. We specify the genetic determinants that are likely involved in the formation of a structured biofilm colonies. In addition to FLO11, these determinants include genes that affect the cell wall and membrane composition. We also identify changes occurring during phenotypic transitions that affect other properties of phenotypic strain-variants, such as resistance to the impact of environmental stress. Here we document the regulatory role of the histone deacetylase Hda1p in developing such a resistance. CONCLUSIONS: We provide detailed analysis of transcriptomic and phenotypic modulations of three related S. cerevisiae strains that arose by phenotypic switching under diverse environmental conditions. We identify changes specifically related to a strain’s ability to create complex structured colonies; we also show that other changes, such as genome rearrangement(s), are unrelated to this ability. Finally, we identify the importance of histone deacetylase Hda1p in strain resistance to stresses
The crystal structure of superoxide dismutase from Plasmodium falciparum
Background: Superoxide dismutases (SODs) are important enzymes in defence against oxidative stress. In Plasmodium falciparum, they may be expected to have special significance since part of the parasite life cycle is spent in red blood cells where the formation of reactive oxygen species is likely to be promoted by the products of haemoglobin breakdown. Thus, inhibitors of P. falciparum SODs have potential as anti-malarial compounds. As a step towards their development we have determined the crystal structure of the parasite's cytosolic iron superoxide dismutase. Results: The cytosolic iron superoxide dismutase from P. falciparum (PfFeSOD) has been overexpressed in E. coli in a catalytically active form. Its crystal structure has been solved by molecular replacement and refined against data extending to 2.5 angstrom resolution. The structure reveals a two-domain organisation and an iron centre in which the metal is coordinated by three histidines, an aspartate and a solvent molecule. Consistent with ultracentrifugation analysis the enzyme is a dimer in which a hydrogen bonding lattice links the two active centres. Conclusion: The tertiary structure of PfFeSOD is very similar to those of a number of other iron-and manganese-dependent superoxide dismutases, moreover the active site residues are conserved suggesting a common mechanism of action. Comparison of the dimer interfaces of PfFeSOD with the human manganese-dependent superoxide dismutase reveals a number of differences, which may underpin the design of parasite-selective superoxide dismutase inhibitors
A Machine Learning Compatible Method For ordinal Propensity Score Stratification and Matching
Although machine learning techniques that estimate propensity scores for observational studies with multivalued treatments have advanced rapidly in recent years, the development of propensity score adjustment techniques has not kept pace. While machine learning propensity models provide numerous benefits, they do not produce a single variable balancing score that can be used for propensity score stratification and matching. This issue motivates the development of a flexible ordinal propensity scoring methodology that does not require parametric assumptions for the propensity model. The proposed method fits a one-parameter power function to the cumulative distribution function (CDF) of the generalized propensity score (GPS) vector resulting from any machine learning propensity model, and is henceforth called the GPS-CDF method. The estimated parameter from the GPS-CDF method
Kinetics of Mycobacterium tuberculosis-specific IFN-γ responses and sputum bacillary clearance in HIV-infected adults during treatment of pulmonary tuberculosis
This work was supported by funding from the Wellcome Trust (UK) through Fellowships 092773/Z/10/Z (to D.T.M), 086757/Z/08/Z (to D.J.S) and 088696/Z/09/Z (to H.C.M). Core funding from the Wellcome Trust supports the laboratory and office facilities at the Malawi-Liverpool-Wellcome Trust Clinical Research Programme.In HIV-uninfected adults with pulmonary tuberculosis (TB), anti-TB treatment is associated with changes in Mycobacterium tuberculosis (Mtb)-specific immune responses, which correlate with sputum bacillary load. It is unclear if this occurs in HIV-infected TB patients. We investigated changes in Mtb-specific immune responses and sputum bacillary clearance during anti-TB treatment in HIV-infected and HIV-uninfected adults with pulmonary TB. Sputum bacillary load was assessed by smear microscopy and culture. Mtb-specific IFN-γ secreting peripheral blood mononuclear cells were enumerated using an ELISPOT assay following stimulation with PPD, ESAT-6 and CFP-10. The baseline frequency of Mtb-specific IFN-γ secreting cells was lower in HIV-infected than HIV-uninfected patients (median PPD 32 vs. 104 Spot Forming Units (SFU), p = 0.05; CFP-10 19 vs. 74 SFU, p = 0.01). ESAT-6-specific IFN-γ secreting cells and sputum bacillary load declined progressively during treatment in both HIV-infected and HIV-uninfected patients. HIV infection did not influence the 2-month sputum culture conversion rate (Odds Ratio 0.89, p = 0.95). These findings suggest that changes in ESAT-6-specific immune responses during anti-TB treatment correspond with changes in sputum bacillary load irrespective of host HIV infection status. The utility of Mtb-specific IFN-γ responses as a proxy measure of treatment response in HIV-infected TB patients warrants further evaluation in other settings.Publisher PDFPeer reviewe
A prospective cohort study investigating the effects of the combined scarf and akin osteotomy, with or without 2/3 digital correction, on pain and quality of life 6 months post-surgery
Derek Santos - ORCID: 0000-0001-9936-715X
https://orcid.org/0000-0001-9936-715XBackground: Hallux valgus is a common deformity of the forefoot that affects the first ray and may lead to pain. The mainstay of treatment is operative correction and this commonly involves a combination of scarf and Akin osteotomies. The aim of the study was to investigate the effects of the combined scarf and Akin osteotomy for Hallux valgus deformity (with or without 2/3 digital correction) on pain levels and health related quality of life 6 months postoperative.Methods: A prospective cohort study was carried out. Thirty adult participants with a clinical and radiographic diagnosis of hallux valgus were recruited, one was lost to follow-up. A combined scarf and Akin osteotomy with or without
2/3 digital correction was carried out. Participants were asked to complete the outcomes of VAS for foot pain and the
health Manchester-Oxford Foot Questionnaire (MOXFQ) for quality of life before and six months post-surgery.Results: Mean age was 59 (SD10) years with 14% males and 86% females. Median VAS pain score reduced from 6 to 0
(p<0.0001). The health MOXFQ domains for foot pain decreased from 60 to 5 (p<0.0001), walking/standing from 50 to
0 (p<0.0001) and social interaction from 50 to 0 (p<0.0001).Conclusion: This study has international impact and contributes to current evidence that the combined scarf and Akin
osteotomy with or without 2/3 digital correction is effective in the operative management of symptomatic hallux valgus foot deformity with improvements in pain and health related quality of life by 6 months post-surgery.https://sciencevolks.com/neurology/pdf/SVOA-NE-02-017.pdf2pubpub
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