2,328 research outputs found

    Bats Use Magnetite to Detect the Earth's Magnetic Field

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    While the role of magnetic cues for compass orientation has been confirmed in numerous animals, the mechanism of detection is still debated. Two hypotheses have been proposed, one based on a light dependent mechanism, apparently used by birds and another based on a ā€œcompass organelleā€ containing the iron oxide particles magnetite (Fe3O4). Bats have recently been shown to use magnetic cues for compass orientation but the method by which they detect the Earth's magnetic field remains unknown. Here we use the classic ā€œKalmijn-Blakemoreā€ pulse re-magnetization experiment, whereby the polarity of cellular magnetite is reversed. The results demonstrate that the big brown bat Eptesicus fuscus uses single domain magnetite to detect the Earths magnetic field and the response indicates a polarity based receptor. Polarity detection is a prerequisite for the use of magnetite as a compass and suggests that big brown bats use magnetite to detect the magnetic field as a compass. Our results indicate the possibility that sensory cells in bats contain freely rotating magnetite particles, which appears not to be the case in birds. It is crucial that the ultrastructure of the magnetite containing magnetoreceptors is described for our understanding of magnetoreception in animals

    Thereā€™s no such thing as a free lunch:evidence of altruism and agency from household expenditure responses to child nutrition programs

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    Many countries provide transfers for particular client groups such as children and often such transfers are in-kind rather than cash. However, this may, at least partially, crowd out private expenditures on the goods in question because they reduce the incentive for other individuals, like parents, to make altruistic transfers. They are often made to one household member on behalf of another so there may also be agency concerns: the recipient may divert some of the transfer away from the intended beneficiary. This paper throws light on these issues using three nutrition programs for children in UK households: free lunch at school for children from poor households; free milk to poor households with pre-school children; and free milk at day-care for pre-school children in attendance regardless of parental income. We provide difference in difference estimates based on a welfare reform and on variation in the timing of school holidays. These estimates are broadly consistent with estimates of a structural model that is identified using the same welfare reform. This gives us confidence in the interpretation of our estimates that the structural model provides but the simple difference-in-difference cannot

    The latent stem cell population is retained in the hippocampus of transgenic Huntington's disease mice but not wild-type mice

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    The demonstration of the brain's ability to initiate repair in response to disease or injury has sparked considerable interest in therapeutic strategies to stimulate adult neurogenesis. In this study we examined the effect of a progressive neurodegenerative condition on neural precursor activity in the subventricular zone (SVZ) and hippocampus of the R6/1 transgenic mouse model of Huntington's disease (HD). Our results revealed an age-related decline in SVZ precursor numbers in both wild-type (WT) and HD mice. Interestingly, hippocampal precursor numbers declined with age in WT mice, although we observed maintenance in hippocampal precursor number in the HD animals in response to advancement of the disease. This maintenance was consistent with activation of a recently identified latent hippocampal precursor population. We found that the small latent stem cell population was also maintained in the HD hippocampus at 33 weeks, whereas it was not present in the WT. Our findings demonstrate that, despite a loss of neurogenesis in the HD hippocampus in vivo, there is a unique maintenance of the precursor and stem cells, which may potentially be activated to ameliorate disease symptoms

    Simultaneous localization of MLL, AF4 and ENL genes in interphase nuclei by 3D-FISH: MLL translocation revisited

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    BACKGROUND: Haematological cancer is characterised by chromosomal translocation (e.g. MLL translocation in acute leukaemia) and two models have been proposed to explain the origins of recurrent reciprocal translocation. The first, established from pairs of translocated genes (such as BCR and ABL), considers the spatial proximity of loci in interphase nuclei (static "contact first" model). The second model is based on the dynamics of double strand break ends during repair processes (dynamic "breakage first" model). Since the MLL gene involved in 11q23 translocation has more than 40 partners, the study of the relative positions of the MLL gene with both the most frequent partner gene (AF4) and a less frequent partner gene (ENL), should elucidate the MLL translocation mechanism. METHODS: Using triple labeling 3D FISH experiments, we have determined the relative positions of MLL, AF4 and ENL genes, in two lymphoblastic and two myeloid human cell lines. RESULTS: In all cell lines, the ENL gene is significantly closer to the MLL gene than the AF4 gene (with P value < 0.0001). According to the static "contact first" model of the translocation mechanism, a minimal distance between loci would indicate a greater probability of the occurrence of t(11;19)(q23;p13.3) compared to t(4;11)(q21;q23). However this is in contradiction to the epidemiology of 11q23 translocation. CONCLUSION: The simultaneous multi-probe hybridization in 3D-FISH is a new approach in addressing the correlation between spatial proximity and occurrence of translocation. Our observations are not consistent with the static "contact first" model of translocation. The recently proposed dynamic "breakage first" model offers an attractive alternative explanation

    Moral enhancement: do means matter morally?

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    One of the reasons why moral enhancement may be controversial, is because the advantages of moral enhancement may fall upon society rather than on those who are enhanced. If directed at individuals with certain counter-moral traits it may have direct societal benefits by lowering immoral behavior and increasing public safety, but it is not directly clear if this also benefits the individual in question. In this paper, we will discuss what we consider to be moral enhancement, how different means may be used to achieve it and whether the means we employ to reach moral enhancement matter morally. Are certain means to achieve moral enhancement wrong in themselves? Are certain means to achieve moral enhancement better than others, and if so, why? More specifically, we will investigate whether the difference between direct and indirect moral enhancement matters morally. Is it the case that indirect means are morally preferable to direct means of moral enhancement and can we indeed pinpoint relevant intrinsic, moral differences between both? We argue that the distinction between direct and indirect means is indeed morally relevant, but only insofar as it tracks an underlying distinction between active and passive interventions. Although passive interventions can be ethical provided specific safeguards are put in place, these interventions exhibit a greater potential to compromise autonomy and disrupt identity

    Mycobacterium tuberculosis osteomyelitis in a patient with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): a case report

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    The incidence of tuberculosis is increasing in the United States. Extra-pulmonary involvement is more common in patients with HIV/AIDS. The diagnosis of Tuberculosis osteomyelitis requires a high degree of suspicion for accurate and timely diagnosis

    Improving statistical inference on pathogen densities estimated by quantitative molecular methods: malaria gametocytaemia as a case study

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    BACKGROUND: Quantitative molecular methods (QMMs) such as quantitative real-time polymerase chain reaction (q-PCR), reverse-transcriptase PCR (qRT-PCR) and quantitative nucleic acid sequence-based amplification (QT-NASBA) are increasingly used to estimate pathogen density in a variety of clinical and epidemiological contexts. These methods are often classified as semi-quantitative, yet estimates of reliability or sensitivity are seldom reported. Here, a statistical framework is developed for assessing the reliability (uncertainty) of pathogen densities estimated using QMMs and the associated diagnostic sensitivity. The method is illustrated with quantification of Plasmodium falciparum gametocytaemia by QT-NASBA. RESULTS: The reliability of pathogen (e.g. gametocyte) densities, and the accompanying diagnostic sensitivity, estimated by two contrasting statistical calibration techniques, are compared; a traditional method and a mixed model Bayesian approach. The latter accounts for statistical dependence of QMM assays run under identical laboratory protocols and permits structural modelling of experimental measurements, allowing precision to vary with pathogen density. Traditional calibration cannot account for inter-assay variability arising from imperfect QMMs and generates estimates of pathogen density that have poor reliability, are variable among assays and inaccurately reflect diagnostic sensitivity. The Bayesian mixed model approach assimilates information from replica QMM assays, improving reliability and inter-assay homogeneity, providing an accurate appraisal of quantitative and diagnostic performance. CONCLUSIONS: Bayesian mixed model statistical calibration supersedes traditional techniques in the context of QMM-derived estimates of pathogen density, offering the potential to improve substantially the depth and quality of clinical and epidemiological inference for a wide variety of pathogens

    Potentially inappropriate medication in older participants of the Berlin Aging Study II (BASE-II) - Sex differences and associations with morbidity and medication use

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    INTRODUCTION: Multimorbidity in advanced age and the need for drug treatment may lead to polypharmacy, while pharmacokinetic and pharmacodynamic changes may increase the risk of adverse drug events (ADEs). OBJECTIVE: The aim of this study was to determine the proportion of subjects using potentially inappropriate medication (PIM) in a cohort of older and predominantly healthy adults in relation to polypharmacy and morbidity. METHODS: Cross-sectional data were available from 1,382 study participants (median age 69 years, IQR 67-71, 51.3% females) of the Berlin Aging Study II (BASE-II). PIM was classified according to the EU(7)-PIM and German PRISCUS (representing a subset of the former) list. Polypharmacy was defined as the concomitant use of at least five drugs. A morbidity index (MI) largely based on the Charlson Index was applied to evaluate the morbidity burden. RESULTS: Overall, 24.1% of the participants were affected by polypharmacy. On average, men used 2 (IQR 1-4) and women 3 drugs (IQR 1-5). According to PRISCUS and EU(7)-PIM, 5.9% and 22.6% of participants received at least one PIM, while use was significantly more prevalent in females (25.5%) compared to males (19.6%) considering EU(7)-PIM (p = 0.01). In addition, morbidity in males receiving PIM according to EU(7)-PIM was higher (median MI 1, IQR 1-3) compared to males without PIM use (median MI 1, IQR 0-2, p<0.001). CONCLUSION: PIM use occurred more frequently in women than in men, while it was associated with higher morbidity in males. As expected, EU(7)-PIM identifies more subjects as PIM users than the PRISCUS list but further studies are needed to investigate the differential impact of both lists on ADEs and outcome. KEY POINTS: We found PIM use to be associated with a higher number of regular medications and with increased morbidity. Additionally, we detected a higher prevalence of PIM use in females compared to males, suggesting that women and people needing intensive drug treatment are patient groups, who are particularly affected by PIM use

    Telomeric expression sites are highly conserved in trypanosoma brucei

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    Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology

    Cognitive engagement in the problem-based learning classroom

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    The objective of the present study was to examine to what extent autonomy in problem-based learning (PBL) results in cognitive engagement with the topic at hand. To that end, a short self-report instrument was devised and validated. Moreover, it was examined how cognitive engagement develops as a function of the learning process and the extent to which cognitive engagement determines subsequent levels of cognitive engagement during a one-day PBL event. Data were analyzed by means of confirmatory factor analysis, repeated measures ANOVA, and path analysis. The results showed that the new measure of situational cognitive engagement is valid and reliable. Furthermore, the results revealed that studentsā€™ cognitive engagement significantly increased as a function of the learning event. Implications of these findings for PBL are discussed
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