13,612 research outputs found

    Recent advances in malaria genomics and epigenomics

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    Malaria continues to impose a significant disease burden on low- and middle-income countries in the tropics. However, revolutionary progress over the last 3 years in nucleic acid sequencing, reverse genetics, and post-genome analyses has generated step changes in our understanding of malaria parasite (Plasmodium spp.) biology and its interactions with its host and vector. Driven by the availability of vast amounts of genome sequence data from Plasmodium species strains, relevant human populations of different ethnicities, and mosquito vectors, researchers can consider any biological component of the malarial process in isolation or in the interactive setting that is infection. In particular, considerable progress has been made in the area of population genomics, with Plasmodium falciparum serving as a highly relevant model. Such studies have demonstrated that genome evolution under strong selective pressure can be detected. These data, combined with reverse genetics, have enabled the identification of the region of the P. falciparum genome that is under selective pressure and the confirmation of the functionality of the mutations in the kelch13 gene that accompany resistance to the major frontline antimalarial, artemisinin. Furthermore, the central role of epigenetic regulation of gene expression and antigenic variation and developmental fate in P. falciparum is becoming ever clearer. This review summarizes recent exciting discoveries that genome technologies have enabled in malaria research and highlights some of their applications to healthcare. The knowledge gained will help to develop surveillance approaches for the emergence or spread of drug resistance and to identify new targets for the development of antimalarial drugs and perhaps vaccines

    Microscopic Theory of Spontaneous Decay in a Dielectric

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    The local field correction to the spontanous dacay rate of an impurity source atom imbedded in a disordered dielectric is calculated to second order in the dielectric density. The result is found to differ from predictions associated with both "virtual" and "real" cavity models of this decay process. However, if the contributions from two dielectric atoms at the same position are included, the virtual cavity result is reproduced.Comment: 12 Page

    The SKA as a Doorway to Angular Momentum

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    Angular momentum is one of the most fundamental physical quantities governing galactic evolution. Differences in the colours, morphologies, star formation rates and gas fractions amongst galaxies of equal stellar/baryon mass M are potentially widely explained by variations in their specific stellar/baryon angular momentum j. The enormous potential of angular momentum science is only just being realised, thanks to the emergence of the first simulations of galaxies with converged spins, paralleled by a dramatic increase in kinematic observations. Such observations are still challenged by the fact that most of the stellar/baryon angular momentum resides at large radii. In fact, the radius that maximally contributes to the angular momentum of an exponential disk (3Re-4Re) is twice as large as the radius that maximally contributes to the disk mass; thus converged measurements of angular momentum require either extremely deep IFS data or, alternatively, kinematic measurements of neutral atomic hydrogen (HI), which naturally resides at the large disk radii that dominate the angular momentum. The SKA has a unique opportunity to become the world-leading facility for angular momentum studies due to its ability to measure the resolved and/or global HI kinematics in very large and well-characterised galaxy samples. These measurements will allow, for example, (1) a very robust determination of the two-dimensional distribution of galaxies in the (M,j)-plane, (2) the largest, systematic measurement of the relationship between M, j, and tertiary galaxy properties, and (3) the most accurate measurement of the large-scale distribution and environmental dependence of angular momentum vectors, both in terms of norm and orientation. All these measurements will represent exquisite tools to build a next generation of galaxy evolution models.Comment: 13 pages, 5 figures, 3 table

    Brazilian WHOQOL-OLD module version: a Rasch analysis of a new instrument

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    OBJECTIVE: To evaluate the Brazilian version of WHOQOL-OLD Module and to test potential changes to the instrument to increase its psychometric adequacy. METHODS: A total of 424 older adults living in a city in Southern Brazil completed the WHOQOL-OLD instrument, in 2005. Rasch analysis was used to explore the psychometric performance of the scale, as implemented by the RUMM2020 software. Item-trait interaction, threshold disorders, presence of differential item functioning and item fit, were analyzed. RESULTS: Two ("death and dying" and "sensory abilities") out of six domains showed inadequate item-trait interactions. Rescoring the response scale and deleting the most misperforming items led to scale improvement. The evaluation of domains and items individually showed that the "intimacy" domain does perform well in contrast to the findings using the classical approach. In addition, the "sensory abilities" domain does not derive an interval measure in its current format. CONCLUSIONS: Unidimensionality and local independence were seen in all domains. Changes in the response scale and deletion of problematic items improved the scale's performance

    Nuclear calcium signaling evoked by cholinergic stimulation in hippocampal CA1 pyramidal neurons

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    The cholinergic system is thought to play an important role in hippocampal-dependent learning and memory. However, the mechanism of action of the cholinergic system in these actions in not well understood. Here we examined the effect of muscarinic receptor stimulation in hippocampal CA1 pyramidal neurons using whole-cell recordings in acute brain slices coupled with high-speed imaging of intracellular calcium. Activation of muscarinic acetylcholine receptors by synaptic stimulation of cholinergic afferents or application of muscarinic agonist in CA1 pyramidal neurons evoked a focal rise in free calcium in the apical dendrite that propagated as a wave into the soma and invaded the nucleus. The calcium rise to a single action potential was reduced during muscarinic stimulation. Conversely, the calcium rise during trains of action potentials was enhanced during muscarinic stimulation. The enhancement of free intracellular calcium was most pronounced in the soma and nuclear regions. In many cases, the calcium rise was distinguished by a clear inflection in the rising phase of the calcium transient, indicative of a regenerative response. Both calcium waves and the amplification of action potential-induced calcium transients were blocked the emptying of intracellular calcium stores or by antagonism of inositol 1,4,5-trisphosphate receptors with heparin or caffeine. Ryanodine receptors were not essential for the calcium waves or enhancement of calcium responses. Because rises in nuclear calcium are known to initiate the transcription of novel genes, we suggest that these actions of cholinergic stimulation may underlie its effects on learning and memory

    Guiding of Rydberg atoms in a high-gradient magnetic guide

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    We study the guiding of 87^{87}Rb 59D5/2_{5/2} Rydberg atoms in a linear, high-gradient, two-wire magnetic guide. Time delayed microwave ionization and ion detection are used to probe the Rydberg atom motion. We observe guiding of Rydberg atoms over a period of 5 ms following excitation. The decay time of the guided atom signal is about five times that of the initial state. We attribute the lifetime increase to an initial phase of ll-changing collisions and thermally induced Rydberg-Rydberg transitions. Detailed simulations of Rydberg atom guiding reproduce most experimental observations and offer insight into the internal-state evolution
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