Functional and genetic evidence that nucleoside transport is highly conserved in Leishmania species: Implications for pyrimidine-based chemotherapy

Leishmania pyrimidine salvage is replete with opportunities for therapeutic intervention with enzyme inhibitors or antimetabolites. Their uptake into cells depends upon specific transporters; therefore it is essential to establish whether various Leishmania species possess similar pyrimidine transporters capable of drug uptake. Here, we report a comprehensive characterization of pyrimidine transport in L. major and L. mexicana. In both species, two transporters for uridine/adenosine were detected, one of which also transported uracil and the antimetabolites 5-fluoruracil (5-FU) and 5F,2′deoxyuridine (5F,2′dUrd), and was designated uridine-uracil transporter 1 (UUT1); the other transporter mediated uptake of adenosine, uridine, 5F,2′dUrd and thymidine and was designated Nucleoside Transporter 1 (NT1). To verify the reported L. donovani model of two NT1-like genes encoding uridine/adenosine transporters, and an NT2 gene encoding an inosine transporter, we cloned the corresponding L. major and L. mexicana genes, expressing each in T. brucei. Consistent with the L. donovani reports, the NT1-like genes of either species mediated the adenosine-sensitive uptake of [3H]-uridine but not of [3H]-inosine. Conversely, the NT2-like genes mediated uptake of [3H]-inosine but not [3H]-uridine. Among pyrimidine antimetabolites tested, 5-FU and 5F,2′dUrd were the most effective antileishmanials; resistance to both analogs was induced in L. major and L. mexicana. In each case it was found that the resistant cells had lost the transport capacity for the inducing drug. Metabolomics analysis found that the mechanism of action of 5-FU and 5F-2′dUrd was similar in both Leishmania species, with major changes in deoxynucleotide metabolism. We conclude that the pyrimidine salvage system is highly conserved in Leishmania species - essential information for the development of pyrimidine-based chemotherapy

Empowering youth sport environments: Implications for daily moderate-to-vigorous physical activity and adiposity

AbstractBackgroundEvidence suggests involvement in youth sport does not guarantee daily guidelines for moderate-to-vigorous physical activity (MVPA) are met, and participation may not mitigate the risks associated with physical inactivity. The need to promote higher habitual MVPA engagement amongst children active in the youth sport context has therefore been underlined. Framed by self-determination theory, the aim of the present study was to examine the implications of the motivational climate created in youth sport, for children's daily engagement in MVPA and associated adiposity. Specifically, we sought to test a motivational sequence in which children's perceptions of an empowering coach-created motivational climate were related to autonomous and controlled motivation, which in turn predicted sport-related enjoyment. Finally, enjoyment is assumed to predict accelerometer assessed daily MVPA and, following this, adiposity.MethodsMale and female youth sport participants aged 9–16 years (n = 112) completed multi-section questionnaires assessing their perceptions of the motivational climate created in youth sport (i.e., autonomy supportive, task involving, socially supportive), autonomous and controlled motivation, and sport-related enjoyment. Daily MVPA engagement was determined via 7 days of accelerometry. Percent body fat (BF%) was estimated using bio-electrical impedance analysis.ResultsPath analysis revealed perceptions of an empowering motivational climate positively predicted players' autonomous motivation, and in turn, sport-related enjoyment. Enjoyment was also significantly negatively related to players' BF%, via a positive association with daily MVPA.ConclusionFostering more empowering youth sport environments may hold implications for the prevention of excess adiposity, through encouraging higher habitual MVPA engagement. Findings may inform the optimal design of youth sport settings for MVPA promotion, and contribute towards associated healthy weight maintenance amongst youth active in this context. Longitudinal and intervention studies are required to confirm these results

Equivalence of the Siegert-pseudostate and Lagrange-mesh R-matrix methods

Siegert pseudostates are purely outgoing states at some fixed point expanded over a finite basis. With discretized variables, they provide an accurate description of scattering in the s wave for short-range potentials with few basis states. The R-matrix method combined with a Lagrange basis, i.e. functions which vanish at all points of a mesh but one, leads to simple mesh-like equations which also allow an accurate description of scattering. These methods are shown to be exactly equivalent for any basis size, with or without discretization. The comparison of their assumptions shows how to accurately derive poles of the scattering matrix in the R-matrix formalism and suggests how to extend the Siegert-pseudostate method to higher partial waves. The different concepts are illustrated with the Bargmann potential and with the centrifugal potential. A simplification of the R-matrix treatment can usefully be extended to the Siegert-pseudostate method.Comment: 19 pages, 1 figur

Quantum fluctuations of classical skyrmions in quantum Hall Ferromagnets

In this article, we discuss the effect of the zero point quantum fluctuations to improve the results of the minimal field theory which has been applied to study %SMG the skyrmions in the quantum Hall systems. Our calculation which is based on the semiclassical treatment of the quantum fluctuations, shows that the one-loop quantum correction provides more accurate results for the minimal field theory.Comment: A few errors are corrected. Accepted for publication in Rapid Communication, Phys. Rev.

Exercise Training Reduces Liver Fat and Increases Rates of VLDL Clearance, but not VLDL Production in NAFLD

Context Randomised controlled trials in non-alcoholic fatty liver disease (NAFLD) have shown that regular exercise, even without calorie restriction, reduces liver steatosis. A previous study has shown that 16 weeks supervised exercise training in NAFLD did not affect total VLDL kinetics. Objective To determine the effect of exercise training on intrahepatocellular fat (IHCL) and the kinetics of large triglyceride-(TG)-rich VLDL1 and smaller denser VLDL2 which has a lower TG content. Design A 16 week randomised controlled trial. Patients 27 sedentary patients with NAFLD. Intervention Supervised exercise with moderate-intensity aerobic exercise or conventional lifestyle advice (control). Main outcome Very low density lipoprotein1 (VLDL1) and VLDL2-TG and apolipoproteinB (apoB) kinetics investigated using stable isotopes before and after the intervention. Results In the exercise group VO2max increased by 31±6% (mean±SEM) and IHCL decreased from 19.6% (14.8, 30.0) to 8.9% (5.4, 17.3) (median (IQR)) with no significant change in VO2max or IHCL in the control group (change between groups p<0.001 and p=0.02, respectively). Exercise training increased VLDL1-TG and apoB fractional catabolic rates, a measure of clearance, (change between groups p=0.02 and p=0.01, respectively), and VLDL1-apoB production rate (change between groups p=0.006), with no change in VLDL1 -TG production rate. Plasma TG did not change in either group. Conclusion An increased clearance of VLDL1 may contribute to the significant decrease in liver fat following 16 weeks of exercise in NAFLD. A longer duration or higher intensity exercise interventions may be needed to lower plasma TG and VLDL production rate

Clastic Polygonal Networks Around Lyot Crater, Mars: Possible Formation Mechanisms From Morphometric Analysis

Polygonal networks of patterned ground are a common feature in cold-climate environments. They can form through the thermal contraction of ice-cemented sediment (i.e. formed from fractures), or the freezing and thawing of ground ice (i.e. formed by patterns of clasts, or ground deformation). The characteristics of these landforms provide information about environmental conditions. Analogous polygonal forms have been observed on Mars leading to inferences about environmental conditions. We have identified clastic polygonal features located around Lyot crater, Mars (50°N, 30°E). These polygons are unusually large (> 100 m diameter) compared to terrestrial clastic polygons, and contain very large clasts, some of which are up to 15 metres in diameter. The polygons are distributed in a wide arc around the eastern side of Lyot crater, at a consistent distance from the crater rim. Using high-resolution imaging data, we digitised these features to extract morphological information. These data are compared to existing terrestrial and Martian polygon data to look for similarities and differences and to inform hypotheses concerning possible formation mechanisms. Our results show the clastic polygons do not have any morphometric features that indicate they are similar to terrestrial sorted, clastic polygons formed by freeze-thaw processes. They are too large, do not show the expected variation in form with slope, and have clasts that do not scale in size with polygon diameter. However, the clastic networks are similar in network morphology to thermal contraction cracks, and there is a potential direct Martian analogue in a sub-type of thermal contraction polygons located in Utopia Planitia. Based upon our observations, we reject the hypothesis that polygons located around Lyot formed as freeze-thaw polygons and instead an alternative mechanism is put forward: they result from the infilling of earlier thermal contraction cracks by wind-blown material, which then became compressed and/or cemented resulting in a resistant fill. Erosion then leads to preservation of these polygons in positive relief, while later weathering results in the fracturing of the fill material to form angular clasts. These results suggest that there was an extensive area of ice-rich terrain, the extent of which is linked to ejecta from Lyot crater

Assessment of Neglect Dyslexia with Functional Materials

Spatial neglect is a neurocognitive disorder, affecting perception, representation, and/or motor planning. Neglect dyslexia in spatial neglect after right hemisphere damage (RHD) may co-occur with, or be dissociated from, other spatial neglect signs (Arduino, Daini, & Silveri, 2005; Lee et al., 2009; Vallar, Burani, & Arduino, 2010). Previous neglect dyslexia research focused on word-level stimuli and reading errors, primarily identifying letter omissions and substitutions to the left of the word midpoint (Ellis, Flude, & Young, 1987). However, functional materials may be more challenging to read (greater spatial extent of sentences and paragraphs, versus words). Although experimental studies that focus on reading at the single-word level may ask interesting theoretical questions regarding the sources of errors in the reading stages and systems, it is not often in the real-world that people read single words in isolation. We hypothesized that assessment materials with ecological validity such as reading a menu and reading an article would be more reflective of the degree to which reading errors and neglect dyslexia was detected in individuals with RHD than assessments that contained only single words or short phrases, which are rarely read in isolation in everyday life

Composable security of delegated quantum computation

Delegating difficult computations to remote large computation facilities, with appropriate security guarantees, is a possible solution for the ever-growing needs of personal computing power. For delegated computation protocols to be usable in a larger context---or simply to securely run two protocols in parallel---the security definitions need to be composable. Here, we define composable security for delegated quantum computation. We distinguish between protocols which provide only blindness---the computation is hidden from the server---and those that are also verifiable---the client can check that it has received the correct result. We show that the composable security definition capturing both these notions can be reduced to a combination of several distinct "trace-distance-type" criteria---which are, individually, non-composable security definitions. Additionally, we study the security of some known delegated quantum computation protocols, including Broadbent, Fitzsimons and Kashefi's Universal Blind Quantum Computation protocol. Even though these protocols were originally proposed with insufficient security criteria, they turn out to still be secure given the stronger composable definitions.Comment: 37+9 pages, 13 figures. v3: minor changes, new references. v2: extended the reduction between composable and local security to include entangled inputs, substantially rewritten the introduction to the Abstract Cryptography (AC) framewor

A new classification of Cyperaceae (Poales) supported by phylogenomic data

Cyperaceae (sedges) are the third largest monocot family and are of considerable economic and ecological importance. Sedges represent an ideal model family to study evolutionary biology due to their species richness, global distribution, large discrepancies in lineage diversity, broad range of ecological preferences, and adaptations including multiple origins of C4 photosynthesis and holocentric chromosomes. Goetghebeur′s seminal work on Cyperaceae published in 1998 provided the most recent complete classification at tribal and generic level, based on a morphological study of Cyperaceae inflorescence, spikelet, flower, and embryo characters, plus anatomical and other information. Since then, several family-level molecular phylogenetic studies using Sanger sequence data have been published. Here, more than 20 years after the last comprehensive classification of the family, we present the first family-wide phylogenomic study of Cyperaceae based on targeted sequencing using the Angiosperms353 probe kit sampling 311 accessions. In addition, 62 accessions available from GenBank were mined for overlapping reads and included in the phylogenomic analyses. Informed by this backbone phylogeny, a new classification for the family at the tribal, subtribal, and generic levels is proposed. The majority of previously recognized suprageneric groups are supported, and for the first time, we establish support for tribe Cryptangieae as a clade including the genus Koyamaea. We provide a taxonomic treatment including identification keys and diagnoses for the 2 subfamilies, 24 tribes, and 10 subtribes, and basic information on the 95 genera. The classification includes five new subtribes in tribe Schoeneae: Anthelepidinae, Caustiinae, Gymnoschoeninae, Lepidospermatinae, and Oreobolinae

Anisotropic Transport of Quantum Hall Meron-Pair Excitations

Double-layer quantum Hall systems at total filling factor $\nu_T=1$ can exhibit a commensurate-incommensurate phase transition driven by a magnetic field $B_{\parallel}$ oriented parallel to the layers. Within the commensurate phase, the lowest charge excitations are believed to be linearly-confined Meron pairs, which are energetically favored to align with $B_{\parallel}$. In order to investigate this interesting object, we propose a gated double-layer Hall bar experiment in which $B_{\parallel}$ can be rotated with respect to the direction of a constriction. We demonstrate the strong angle-dependent transport due to the anisotropic nature of linearly-confined Meron pairs and discuss how it would be manifested in experiment.Comment: 4 pages, RevTex, 3 postscript figure