3,675 research outputs found

    Seizures and disturbed brain potassium dynamics in the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts

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    OBJECTIVE: Loss of function of the astrocyte-specific protein MLC1 leads to the childhood-onset leukodystrophy "megalencephalic leukoencephalopathy with subcortical cysts" (MLC). Studies on isolated cells show a role for MLC1 in astrocyte volume regulation and suggest that disturbed brain ion and water homeostasis is central to the disease. Excitability of neuronal networks is particularly sensitive to ion and water homeostasis. In line with this, reports of seizures and epilepsy in MLC patients exist. However, systematic assessment and mechanistic understanding of seizures in MLC are lacking. METHODS: We analyzed an MLC patient inventory to study occurrence of seizures in MLC. We used two distinct genetic mouse models of MLC to further study epileptiform activity and seizure threshold through wireless extracellular field potential recordings. Whole-cell patch-clamp recordings and K+-sensitive electrode recordings in mouse brain slices were used to explore the underlying mechanisms of epilepsy in MLC. RESULTS: An early onset of seizures is common in MLC. Similarly, in MLC mice, we uncovered spontaneous epileptiform brain activity and a lowered threshold for induced seizures. At the cellular level, we found that although passive and active properties of individual pyramidal neurons are unchanged, extracellular K+dynamics and neuronal network activity are abnormal in MLC mice. INTERPRETATION: Disturbed astrocyte regulation of ion and water homeostasis in MLC causes hyperexcitability of neuronal networks and seizures. These findings suggest a role for defective astrocyte volume regulation in epilepsy. Ann Neurol 2018;83:636-649

    Sequestration of Martian CO2 by mineral carbonation

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    Carbonation is the water-mediated replacement of silicate minerals, such as olivine, by carbonate, and is commonplace in the Earth’s crust. This reaction can remove significant quantities of CO2 from the atmosphere and store it over geological timescales. Here we present the first direct evidence for CO2 sequestration and storage on Mars by mineral carbonation. Electron beam imaging and analysis show that olivine and a plagioclase feldspar-rich mesostasis in the Lafayette meteorite have been replaced by carbonate. The susceptibility of olivine to replacement was enhanced by the presence of smectite veins along which CO2-rich fluids gained access to grain interiors. Lafayette was partially carbonated during the Amazonian, when liquid water was available intermittently and atmospheric CO2 concentrations were close to their present-day values. Earlier in Mars’ history, when the planet had a much thicker atmosphere and an active hydrosphere, carbonation is likely to have been an effective mechanism for sequestration of CO2

    Fitness benefits of prolonged post-reproductive lifespan in women

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    Most animals reproduce until they die, but in humans, females can survive long after ceasing reproduction. In theory, a prolonged post-reproductive lifespan will evolve when females can gain greater fitness by increasing the success of their offspring than by continuing to breed themselves. Although reproductive success is known to decline in old age, it is unknown whether women gain fitness by prolonging lifespan post-reproduction. Using complete multi-generational demographic records, we show that women with a prolonged post-reproductive lifespan have more grandchildren, and hence greater fitness, in pre-modern populations of both Finns and Canadians. This fitness benefit arises because post-reproductive mothers enhance the lifetime reproductive success of their offspring by allowing them to breed earlier, more frequently and more successfully. Finally, the fitness benefits of prolonged lifespan diminish as the reproductive output of offspring declines. This suggests that in female humans, selection for deferred ageing should wane when one's own offspring become post-reproductive and, correspondingly, we show that rates of female mortality accelerate as their offspring terminate reproduction

    ABJM Dibaryon Spectroscopy

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    We extend the proposal for a detailed map between wrapped D-branes in Anti-de Sitter space and baryon-like operators in the associated dual conformal field theory provided in hep-th/0202150 to the recently formulated AdS_4 \times CP^3/ABJM correspondence. In this example, the role of the dibaryon operator of the 3-dimensional CFT is played by a D4-brane wrapping a CP^2 \subset CP^3. This topologically stable D-brane in the AdS_4 \times CP^3 is nothing but one-half of the maximal giant graviton on CP^3.Comment: 26 page

    Comparative acute efficacy and tolerability of OROS and immediate release formulations of methylphenidate in the treatment of adults with attention-deficit/hyperactivity disorder

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    <p>Abstract</p> <p>Background</p> <p>The main aim of this study was to compare the safety and efficacy of IR MPH administered three times daily to those of once daily OROS-MPH.</p> <p>Methods</p> <p>Subjects were outpatient adults satisfying full diagnostic criteria for DSM-IV ADHD between 19 and 60 years of age. Data from two independently conducted 6-week placebo controlled, randomized clinical trials of IR-MPH (tid) and of OROS-MPH were pooled to create three study groups: Placebo (N = 116), IR-MPH (tid) (N = 102) and OROS-MPH (N = 67).</p> <p>Results</p> <p>Eight-five percent (N = 99) of placebo treated subjects, 77% (N = 79) of the IR-MPH (tid) treated subjects, and 82% (N = 55) of the OROS-MPH treated subjects completed the 6-week trial. Total daily doses at endpoint were 80.9 ± 31.9 mg, 74.8 ± 26.2 mg, and 95.4 ± 26.3 mg in the OROS-MPH, IR-MPH (tid), and placebo groups, respectively. At endpoint, 66% (N = 44) of subjects receiving OROS-MPH and 70% (N = 71) of subjects receiving IR-MPH (tid) were considered responders compared with 31% (N = 36) on placebo.</p> <p>Conclusion</p> <p>Comparison of data from two similarly designed, large, randomized, placebo-controlled, trials, showed that equipotent daily doses of once daily OROS-MPH had similar efficacy to that of TID administered IR MPH.</p> <p>Trial Registration</p> <p>The trial of OROS-MPH was registered at clinicaltrials.gov, number NCT00181571.</p

    Intraspecfic variation in cold-temperature metabolic phenotypes of Arabidopsis lyrata ssp petraea

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    Atmospheric temperature is a key factor in determining the distribution of a plant species. Alongside this, plant populations growing at the margin of their range may exhibit traits that indicate genetic differentiation and adaptation to their local abiotic environment. We investigated whether geographically separated marginal populations of Arabidopsis lyrata ssp. petraea have distinct metabolic phenotypes associated with exposure to cold temperatures. Seeds of A. petraea were obtained from populations along a latitudinal gradient, namely Wales, Sweden and Iceland and grown in a controlled cabinet environment. Mannose, glucose, fructose, sucrose and raffinose concentrations were different between cold treatments and populations, especially in the Welsh population, but polyhydric alcohol concentrations were not. The free amino acid compositions were population specific, with fold differences in most amino acids, especially in the Icelandic populations, with gross changes in amino acids, particularly those associated with glutamine metabolism. Metabolic fingerprints and profiles were obtained. Principal component analysis (PCA) of metabolite fingerprints revealed metabolic characteristic phenotypes for each population and temperature. It is suggested that amino acids and carbohydrates were responsible for discriminating populations within the PCA. Metabolite fingerprinting and profiling has proved to be sufficiently sensitive to identify metabolic differences between plant populations at different atmospheric temperatures. These findings show that there is significant natural variation in cold metabolism among populations of A. l. petraea which may signify plant adaptation to local climates

    Non-singlet Baryons in Less Supersymmetric Backgrounds

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    We analyze the holographic description of non-singlet baryons in various backgrounds with reduced supersymmetries and/or confinement. We show that they exist in all AdS_5xY_5 backgrounds with Y_5 an Einstein manifold bearing five form flux, for a number of quarks 5N/8< k< N, independently on the supersymmetries preserved. This result still holds for gamma_i deformations. In the confining Maldacena-Nunez background non-singlet baryons also exist, although in this case the interval for the number of quarks is reduced as compared to the conformal case. We generalize these configurations to include a non-vanishing magnetic flux such that a complementary microscopical description can be given in terms of lower dimensional branes expanding into fuzzy baryons. This description is a first step towards exploring the finite 't Hooft coupling region.Comment: 36 Pages, 1 figure, Latex, v2: few minor changes, JHEP versio

    Helpful Female Subordinate Cichlids Are More Likely to Reproduce

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    BACKGROUND: In many cooperatively breeding vertebrates, subordinates assist a dominant pair to raise the dominants' offspring. Previously, it has been suggested that subordinates may help in payment for continued residency on the territory (the 'pay-to-stay hypothesis'), but payment might also be reciprocated or might allow subordinates access to reproductive opportunities. METHODOLOGY/PRINCIPAL FINDINGS: We measured dominant and subordinate female alloparental brood care and reproductive success in four separate experiments and show that unrelated female dominant and subordinate cichlid fish care for each other's broods (alloparental brood care), but that there is no evidence for reciprocal 'altruism' (no correlation between alloparental care received and given). Instead, subordinate females appear to pay with alloparental care for own direct reproduction. CONCLUSIONS/SIGNIFICANCE: Our results suggest subordinate females pay with alloparental care to ensure access to the breeding substrate and thereby increase their opportunities to lay their own clutches. Subordinates' eggs are laid, on average, five days after the dominant female has produced her first brood. We suggest that immediate reproductive benefits need to be considered in tests of the pay-to-stay hypothesis

    Phage inducible islands in the gram-positive cocci

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    The SaPIs are a cohesive subfamily of extremely common phage-inducible chromosomal islands (PICIs) that reside quiescently at specific att sites in the staphylococcal chromosome and are induced by helper phages to excise and replicate. They are usually packaged in small capsids composed of phage virion proteins, giving rise to very high transfer frequencies, which they enhance by interfering with helper phage reproduction. As the SaPIs represent a highly successful biological strategy, with many natural Staphylococcus aureus strains containing two or more, we assumed that similar elements would be widespread in the Gram-positive cocci. On the basis of resemblance to the paradigmatic SaPI genome, we have readily identified large cohesive families of similar elements in the lactococci and pneumococci/streptococci plus a few such elements in Enterococcus faecalis. Based on extensive ortholog analyses, we found that the PICI elements in the four different genera all represent distinct but parallel lineages, suggesting that they represent convergent evolution towards a highly successful lifestyle. We have characterized in depth the enterococcal element, EfCIV583, and have shown that it very closely resembles the SaPIs in functionality as well as in genome organization, setting the stage for expansion of the study of elements of this type. In summary, our findings greatly broaden the PICI family to include elements from at least three genera of cocci
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