23,342 research outputs found
Iron metabolism in trypanosomatids, and its crucial role in infection.
Iron is almost ubiquitous in living organisms due to the utility of its redox chemistry. It is also dangerous as it can catalyse the formation of reactive free radicals - a classical double-edged sword. In this review, we examine the uptake and usage of iron by trypanosomatids and discuss how modulation of host iron metabolism plays an important role in the protective response. Trypanosomatids require iron for crucial processes including DNA replication, antioxidant defence, mitochondrial respiration, synthesis of the modified base J and, in African trypanosomes, the alternative oxidase. The source of iron varies between species. Bloodstream-form African trypanosomes acquire iron from their host by uptake of transferrin, and Leishmania amazonensis expresses a ZIP family cation transporter in the plasma membrane. In other trypanosomatids, iron uptake has been poorly characterized. Iron-withholding responses by the host can be a major determinant of disease outcome. Their role in trypanosomatid infections is becoming apparent. For example, the cytosolic sequestration properties of NRAMP1, confer resistance against leishmaniasis. Conversely, cytoplasmic sequestration of iron may be favourable rather than detrimental to Trypanosoma cruzi. The central role of iron in both parasite metabolism and the host response is attracting interest as a possible point of therapeutic intervention
Collaborative learning: a connected community approach
Collaborative Learning in group settings currently occurs across a substantial portion of the UK Higher Education curriculum. This style of learning has many roots including: Enterprise in Higher Education, Action Learning and Action Research, Problem Based Learning, and Practice Based Learning. As such our focus on Collaborative Learning development can be viewed as an evolutionary. This collaborative and active group learning provides the foundation for what can be collectively called connectivist ‘Learning Communities’. In this setting a primary feature of a ‘Learning Community’ is one that carries a responsibility to promote one another’s learning.
This paper will outline a developmental collaborative learning approach and describe a supporting software environment, known as the Salford Personal Development Environment (SPDE), that has been developed and implemented to assist in delivering collaborative learning for post graduate and other provision. This is done against a background of much research evidence that group based activity can enhance learning. These findings cover many approaches to group based learning and over a significant period of time.
This paper reports on work-in-progress and the features of the environment that are designed to help promote individual and group or community learning that have been influenced by the broad base of research findings in this area
Stimulation of microglial metabotropic glutamate receptor mGlu2 triggers tumor necrosis factor alpha-induced neurotoxicity in concert with microglial-derived fas ligand
Activated microglia may be detrimental to neuronal survival in a number of neurodegenerative diseases. Thus, strategies that reduce microglial neurotoxicity may have therapeutic benefit. Stimulation of group II metabotropic glutamate (mGlu) receptors on rat primary microglia with the specific group II agonist 2S, 2 ' R, 3 ' R- 2-(2 ', 3 '-dicarboxy-cyclopropyl) glycine for 24 h induced microglial activation and resulted in a neurotoxic microglial phenotype. These effects were attributable to preferential mGlu2 stimulation, because N-acetyl-L-aspartyl-L-glutamate, a specific mGlu3 agonist, did not induce microglial activation or neurotoxicity. Stimulation of microglial mGlu2 but not mGlu3 induced caspase-3 activation in cerebellar granule neurons in culture, using microglial-conditioned media as well as cocultures. Stimulation of microglial mGlu2 induced tumor necrosis factor-alpha(TNF alpha) release, which contributed to microglial neurotoxicity mediated via neuronal TNF receptor 1 and caspase-3 activation. Stimulation of microglial group I or III mGlu receptors did not induce TNF alpha release. TNF alpha was only neurotoxic in the presence of microglia or microglial-conditioned medium. The toxicity of TNF alpha could be prevented by coexposure of neurons to conditioned medium from microglia stimulated by the specific group III agonist L-2-amino-4-phosphono-butyric acid. The neurotoxicity of TNF alpha derived from mGlu2-stimulated microglia was potentiated by microglial-derived Fas ligand (FasL), the death receptor ligand. FasL was constitutively expressed in microglia and shed after mGlu2 stimulation. Our data suggest that selective and inverse modulation of microglial mGlu2 and mGlu3 may prove a therapeutic target in neuroinflammatory diseases such as Alzheimer's disease and multiple sclerosis
Distribution and conservation status of the Mt Mangana stag beetle, Lissotes menalcas (Coleoptera: Lucanidae)
Lissotes menalcas (the Mt Mangana Stag Beetle) is an obligate log dwelling beetle and is presently classified as vulnerable under the Tasmanian Threatened Species Protection Act 1995. The distribution, habitat and conservation status of this species were investigated through a combination of collation of known locations and searches for the in decaying logs across likely areas of occurrence.
L. menalcas was found to have a wide distribution in south eastern Tasmania and is now recorded from 34 localities. The species was found in a variety of wet forest habitats from old-growth mixed forest through to 23-year-old wet eucalypt silvicultural regrowth. About 12% of wet eucalypt forest within the predicted range of L. menalcas is formally reserved, and another 14% on Crown land is unlikely to be subject to logging. L. menalcas appears to tolerate both wildfire and clear felling with regeneration burning. Because the species depends on an ongoing supply of rotting logs for its long-term survival, plantation development will probably lead to the elimination of the species from such areas. Analysis of the likely impact of plantation establishment within its range over the next ten years indicates that it will not reach levels that would lead it to be considered as vulnerable. Thus, it is recommended that the status of the species be changed from vulnerable to rare. However, there is a need to determine the ecological sustainability of present forest management practices in relation to the decaying-log habitat and to continue to monitor the extent of clearing and modification of the species' habitat
Spectral analysis of the biharmonic operator subject to Neumann boundary conditions on dumbbell domains
We consider the biharmonic operator subject to homogeneous boundary
conditions of Neumann type on a planar dumbbell domain which consists of two
disjoint domains connected by a thin channel. We analyse the spectral behaviour
of the operator, characterizing the limit of the eigenvalues and of the
eigenprojections as the thickness of the channel goes to zero. In applications
to linear elasticity, the fourth order operator under consideration is related
to the deformation of a free elastic plate, a part of which shrinks to a
segment. In contrast to what happens with the classical second order case, it
turns out that the limiting equation is here distorted by a strange factor
depending on a parameter which plays the role of the Poisson coefficient of the
represented plate.Comment: To appear in "Integral Equations and Operator Theory
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Distributions of brominated organic compounds in the troposphere and lower stratosphere
A comprehensive suite of brominated organic compounds was measured from whole air samples collected during the 1996 NASA Stratospheric Tracers of Atmospheric Transport aircraft campaign and the 1996 NASA Global Tropospheric Experiment Pacific Exploratory Mission-Tropics aircraft campaign. Measurements of individual species and total organic bromine were utilized to describe latitudinal and vertical distributions in the troposphere and lower stratosphere, fractional contributions to total organic bromine by individual species, fractional dissociation of the long-lived species relative to CFC-11, and the Ozone Depletion Potential of the halons and CH3Br. Spatial differences in the various organic brominated compounds were related to their respective sources and chemical lifetimes. The difference between tropospheric mixing ratios in the Northern and Southern Hemispheres for halons was approximately equivalent to their annual tropospheric growth rates, while the interhemispheric ratio of CH3Br was 1.18. The shorter-lived brominated organic species showed larger tropospheric mixing ratios in the tropics relative to midlatitudes, which may reflect marine biogenic sources. Significant vertical gradients in the troposphere were observed for the short-lived species with upper troposphere values 40-70% of the lower troposphere values. Much smaller vertical gradients (3-14%) were observed for CH3Br, and no significant vertical gradients were observed for the halons. Above the tropopause, the decrease in organic bromine compounds was found to have some seasonal and latitudinal differences. The combined losses of the individual compounds resulted in a loss of total organic bromine between the tropopause and 20 km of 38-40% in the tropics and 75-85% in midlatitudes. The fractional dissociation of the halons and CH3Br relative to CFC-11 showed latitudinal differences, with larger values in the tropics. Copyright 1999 by the American Geophysical Union
Coupling molecular spin states by photon-assisted tunneling
Artificial molecules containing just one or two electrons provide a powerful
platform for studies of orbital and spin quantum dynamics in nanoscale devices.
A well-known example of these dynamics is tunneling of electrons between two
coupled quantum dots triggered by microwave irradiation. So far, these
tunneling processes have been treated as electric dipole-allowed
spin-conserving events. Here we report that microwaves can also excite
tunneling transitions between states with different spin. In this work, the
dominant mechanism responsible for violation of spin conservation is the
spin-orbit interaction. These transitions make it possible to perform detailed
microwave spectroscopy of the molecular spin states of an artificial hydrogen
molecule and open up the possibility of realizing full quantum control of a two
spin system via microwave excitation.Comment: 13 pages, 9 figure
Stability-based multivariate mapping using SCoRS
Recently we proposed a feature selection method based on stability theory (SCoRS - Survival Count on Random Subspaces) and showed that the proposed approach was able to improve classification accuracy using different datasets. In the present work we propose: (i) an extension of SCoRS using reproducibility instead of model accuracy as the parameter optimization criterion and (ii) a procedure to estimate the rate of false positive selection associated with the set of features obtained. Our results using the proposed framework showed that, as expected, the optimal parameter was more stable across the cross-validation folds, the spatial map displaying the features selected was less noisy and there was no decrease in classification accuracy. In addition, our results suggest that the estimated false positive rate for the features selected by SCoRS is under 0.05 for both optimization approaches, nevertheless lower when optimizing reproducibility in comparison with the standard optimization approach
Validating the Philadelphia Mindfulness Scale [PMS] for Those with Fibromyalgia
Objectives: Dispositional mindfulness [DM] has become an important construct in understanding and treating fibromyalgia. However, few DM measures exist that have been validated in those with fibromyalgia. The Philadelphia Mindfulness Scale [PMS] is a self-report of DM. In the current study, we validate the PMS within a sample of individuals with fibromyalgia. Design: This was a cross-sectional online study. This enabled the recruitment of a larger sample of individuals with experiences of fibromyalgia than may have been achieved through face-to-face assessment. A cross-sectional approach was adopted to minimise resource demands. Method: The PMS alongside measures of fibromyalgia severity [The Revised Fibromyalgia Impact Questionnaire], affect [Positive and Negative Affect Scale] and decentring [Experiences Questionnaire] were completed online by a sample of N=936 individuals with fibromyalgia. Results: Confirmatory factor analysis supported a revised three-factor structure for the PMS. This factor structure excluded items which could overlap with hypervigilance within fibromyalgia. The three supported factors were Awareness, Non-judging/Control and Non-suppression/reactivity. Concurrent validity of the subscales was partially supported via correlations with positive affect [PA] and negative affect [NA] and decentring. Conclusions: The results support the use of the PMS in individuals with fibromyalgia, and in particular the use of this measure to compare those with and without experience of meditation. The PMS may be a useful tool in evaluating mindfulness-based interventions [MBIs] within this population. Limitations: The online design prevented more in-depth assessment of fibromyalgia. As the study was cross-sectional, test re-test reliability could not be assessed
A new feature selection method based on stability theory - Exploring parameters space to evaluate classification accuracy in neuroimaging data
Recently we proposed a feature selection method based on stability theory. In the present work we present an evaluation of its performance in different contexts through a grid search performed in a subset of its parameters space. The main contributions of this work are: we show that the method can improve the classification accuracy in relation to the wholebrain in different functional datasets; we evaluate the parameters influence in the results, getting some insight in reasonable ranges of values; and we show that combinations of parameters that yield the best accuracies are stable (i.e., they have low rates of false positive selections)
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