277 research outputs found

    Accuracies and inaccuracies in autobiographical memories

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    Records of everyday autobiographical events were gathered from a small group of adults during a 4-month period. This was followed by five memory tests extending over 21/2 years. Recognition memory, temporal ordering, and dating accuracy declined as the events tested became more remote. Recognition accuracy on original items was high over the entire study; whereas the false recognition of nonevent, foil items increased after a 1- to 3-month delay. Confidence ratings of recognition accuracy remained consistently high over all tests, even though recognition accuracy deteriorated. Additional analyses of foil items indicated that false recognitions of nonevents as one's own memories were related positively to the semantic similarity between foils and the original records from which they were constructed. Taken together, the data support the hypothesis that the same autobiographical schemata account for the correct recognition of actual events, the false recognition of certain nonevents as one's own memories, the correct rejection of other nonevents, and an overconfidence in the "facts" of one's life.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26271/1/0000356.pd

    A tale of two capitalisms: preliminary spatial and historical comparisons of homicide rates in Western Europe and the USA

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    This article examines comparative homicide rates in the United States and Western Europe in an era of increasingly globalized neoliberal economics. The main finding of this preliminary analysis is that historical and spatial correlations between distinct forms of political economy and homicide rates are consistent enough to suggest that social democratic regimes are more successful at fostering the socio-cultural conditions necessary for reduced homicide rates. Thus Western Europe and all continents and nations should approach the importation of American neo-liberal economic policies with extreme caution. The article concludes by suggesting that the indirect but crucial causal connection between political economy and homicide rates, prematurely pushed into the background of criminological thought during the ‘cultural turn’, should be returned to the foreground

    Issues in Research on the Young Chronically III Child

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    A major goal of research on chronic illness in children is to determine how the illness interacts with developmental processes. The child must be studied within the context of the family, the school, and the health care system. Problems in research include the use of appropriate control groups and matching on control variables. The generic, or cross-categorical, approach has led to the identification of factors affecting children regardless of particular illness. Adjustment to school depends on coordination of the family and health professionals with personnel within the school.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68724/2/10.1177_027112148600500406.pd

    Thermoregulation by captive and free-ranging Egyptian rousette bats (Rousettus aegyptiacus) in South Africa

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    Many bats, including some small-bodied tropical and sub-tropical Pteropodidae, use torpor to offset energetic constraints. We tested the hypothesis that medium sized (110-160 g) cave-roosting Egyptian rousette bats (Rousettus aegyptiacus) at the southern extent of their range are able to employ torpor. We measured daytime body temperatures (Tb) of nine wild individuals using implanted temperature-sensitive radio-transmitters. The bats roosted in a cave on Table Mountain, Cape Town, South Africa (a typically cool and wet area). Daily mean cave temperature (Tc) ranged between 7 and 12 °C (mean 9.3 °C). All wild individuals exhibited a circadian cycle in Tb, with an average of 37.7 °C upon return from foraging, decreasing to 35.5 °C by mid-day. Before emergence for feeding, Tb increased to about 37 °C. No individual allowed Tb to drop below 34 °C indicating (assuming a threshold temperature of 30 °C) that individuals in this population do not use torpor. Bats were active throughout the day within the roost and metabolic heat production may have contributed to the maintenance of rest phase Tb. Ten individuals implanted with temperature sensitive passive integrated transponder tags were held in captivity at temperatures of 25-30 °C and subjected to food deprivation for 2-3 days. The lowest Tb recorded for any captive individual was 33.4 °C despite losing an average of 10% of their initial body mass. Despite exposure to cool Ta in the cave, and often cold, wet and windy conditions whilst foraging, or substantial food restriction in captive bats, R. aegyptiacus did not resort to using torpor.Grants to DSJ from the University of Cape Town and the South African Research Chair Initiative of the Department of Science and Technology, administered by the NRF (GUN 64798), NSERC Discovery grants to RMRM and RMB, and an NRF grant to AEM, WM and JP (GUN98339).http://jmammal.oxfordjournals.org2018-02-28hb2017Mammal Research InstituteMedical VirologyZoology and Entomolog

    Pharmacokinetic/pharmacodynamic modelling approaches in paediatric infectious diseases and immunology.

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    Pharmacokinetic/pharmacodynamic (PKPD) modelling is used to describe and quantify dose-concentration-effect relationships. Within paediatric studies in infectious diseases and immunology these methods are often applied to developing guidance on appropriate dosing. In this paper, an introduction to the field of PKPD modelling is given, followed by a review of the PKPD studies that have been undertaken in paediatric infectious diseases and immunology. The main focus is on identifying the methodological approaches used to define the PKPD relationship in these studies. The major findings were that most studies of infectious diseases have developed a PK model and then used simulations to define a dose recommendation based on a pre-defined PD target, which may have been defined in adults or in vitro. For immunological studies much of the modelling has focused on either PK or PD, and since multiple drugs are usually used, delineating the relative contributions of each is challenging. The use of dynamical modelling of in vitro antibacterial studies, and paediatric HIV mechanistic PD models linked with the PK of all drugs, are emerging methods that should enhance PKPD-based recommendations in the future

    Structure-Function Study of Mammalian Munc18-1 and C. elegans UNC-18 Implicates Domain 3b in the Regulation of Exocytosis

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    Munc18-1 is an essential synaptic protein functioning during multiple stages of the exocytotic process including vesicle recruitment, docking and fusion. These functions require a number of distinct syntaxin-dependent interactions; however, Munc18-1 also regulates vesicle fusion via syntaxin-independent interactions with other exocytotic proteins. Although the structural regions of the Munc18-1 protein involved in closed-conformation syntaxin binding have been thoroughly examined, regions of the protein involved in other interactions are poorly characterised. To investigate this we performed a random transposon mutagenesis, identifying domain 3b of Munc18-1 as a functionally important region of the protein. Transposon insertion in an exposed loop within this domain specifically disrupted Mint1 binding despite leaving affinity for closed conformation syntaxin and binding to the SNARE complex unaffected. The insertion mutation significantly reduced total amounts of exocytosis as measured by carbon fiber amperometry in chromaffin cells. Introduction of the equivalent mutation in UNC-18 in Caenorhabditis elegans also reduced neurotransmitter release as assessed by aldicarb sensitivity. Correlation between the two experimental methods for recording changes in the number of exocytotic events was verified using a previously identified gain of function Munc18-1 mutation E466K (increased exocytosis in chromaffin cells and aldicarb hypersensitivity of C. elegans). These data implicate a novel role for an exposed loop in domain 3b of Munc18-1 in transducing regulation of vesicle fusion independent of closed-conformation syntaxin binding

    Torpor on Demand: Heterothermy in the Non-Lemur Primate Galago moholi

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    Hibernation and daily torpor are energy- and water-saving adaptations employed to survive unfavourable periods mostly in temperate and arctic environments, but also in tropical and arid climates. Heterothermy has been found in a number of mammalian orders, but within the primates so far it seems to be restricted to one family of Malagasy lemurs. As currently there is no evidence of heterothermy of a primate outside of Madagascar, the aim of our study was to investigate whether small primates from mainland Africa are indeed always homeothermic despite pronounced seasonal changes in weather and food availability., which inhabits a highly seasonal habitat with a hot wet-season and a cold dry-season with lower food abundance, was investigated to determine whether it is capable of heterothermy. We measured skin temperature of free-ranging individuals throughout the cool dry season using temperature-sensitive collars as well as metabolic rate in captured individuals. Torpor was employed by 15% of 20 animals. Only one of these animals displayed heterothermy in response to natural availability of food and water, whereas the other animals became torpid without access to food and water. are physiologically capable of employing torpor. However they do not use it as a routine behaviour, but only under adverse conditions. This reluctance is presumably a result of conflicting selective pressures for energy savings versus other ecological and evolutionary forces, such as reproduction or territory defence. Our results support the view that heterothermy in primates evolved before the division of African and Malagasy Strepsirhini, with the possible implication that more primate species than previously thought might still have the potential to call upon this possibility, if the situation necessitates it

    Morphological docking of secretory vesicles

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    Calcium-dependent secretion of neurotransmitters and hormones is essential for brain function and neuroendocrine-signaling. Prior to exocytosis, neurotransmitter-containing vesicles dock to the target membrane. In electron micrographs of neurons and neuroendocrine cells, like chromaffin cells many synaptic vesicles (SVs) and large dense-core vesicles (LDCVs) are docked. For many years the molecular identity of the morphologically docked state was unknown. Recently, we resolved the minimal docking machinery in adrenal medullary chromaffin cells using embryonic mouse model systems together with electron-microscopic analyses and also found that docking is controlled by the sub-membrane filamentous (F-)actin. Currently it is unclear if the same docking machinery operates in synapses. Here, I will review our docking assay that led to the identification of the LDCV docking machinery in chromaffin cells and also discuss whether identical docking proteins are required for SV docking in synapses

    The role of the myosin ATPase activity in adaptive thermogenesis by skeletal muscle

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    Resting skeletal muscle is a major contributor to adaptive thermogenesis, i.e., the thermogenesis that changes in response to exposure to cold or to overfeeding. The identification of the “furnace” that is responsible for increased heat generation in resting muscle has been the subject of a number of investigations. A new state of myosin, the super relaxed state (SRX), with a very slow ATP turnover rate has recently been observed in skeletal muscle (Stewart et al. in Proc Natl Acad Sci USA 107:430–435, 2010). Inhibition of the myosin ATPase activity in the SRX was suggested to be caused by binding of the myosin head to the core of the thick filament in a structural motif identified earlier by electron microscopy. To be compatible with the basal metabolic rate observed in vivo for resting muscle, most myosin heads would have to be in the SRX. Modulation of the population of this state, relative to the normal relaxed state, was proposed to be a major contributor to adaptive thermogenesis in resting muscle. Transfer of only 20% of myosin heads from the SRX into the normal relaxed state would cause muscle thermogenesis to double. Phosphorylation of the myosin regulatory light chain was shown to transfer myosin heads from the SRX into the relaxed state, which would increase thermogenesis. In particular, thermogenesis by myosin has been proposed to play a role in the dissipation of calories during overfeeding. Up-regulation of muscle thermogenesis by pharmaceuticals that target the SRX would provide new approaches to the treatment of obesity or high blood sugar levels
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