Practice Makes Imperfect: Restorative Effects of Sleep on Motor Learning

Emerging evidence suggests that sleep plays a key role in procedural learning, particularly in the continued development of motor skill learning following initial acquisition. We argue that a detailed examination of the time course of performance across sleep on the finger-tapping task, established as the paradigm for studying the effect of sleep on motor learning, will help distinguish a restorative role of sleep in motor skill learning from a proactive one. Healthy subjects rehearsed for 12 trials and, following a night of sleep, were tested. Early training rapidly improved speed as well as accuracy on pre-sleep training. Additional rehearsal caused a marked slow-down in further improvement or partial reversal in performance to observed levels below theoretical upper limits derived on the basis of early pre-sleep rehearsal. This decrement in learning efficacy does not occur always, but if and only if it does, overnight sleep has an effect in fully or partly restoring the efficacy and actual performance to the optimal theoretically achieveable level. Our findings re-interpret the sleep-dependent memory enhancement in motor learning reported in the literature as a restoration of fatigued circuitry specialized for the skill. In providing restitution to the fatigued brain, sleep eliminates the rehearsal-induced synaptic fatigue of the circuitry specialized for the task and restores the benefit of early pre-sleep rehearsal. The present findings lend support to the notion that latent sleep-dependent enhancement of performance is a behavioral expression of the brain's restitution in sleep

A breath-hold R2 mapping pulse sequence detects a decrease in myocardial ferritin iron after one-week of iron chelation

Oral Abstract Session XI – New CMR Methods Applied to Human Imaging: O69Intracellular ferritin iron is evidently in equilibrium with the cytosolic iron pool that can change rapidly with iron chelation. This study demonstrates the feasibility of quantitatively detecting short-term changes in myocardial iron produced by iron-chelating therapy using RR2 measurement.postprintThe 13th Annual Scientific Sessions of the Society for Cardiovascular Magnetic Resonance (SCMR), Phoenix, AZ., 21-24 January 2010. In Final Program of the 13th Annual Scientific Sessions of SCMR, 2010, p. 29, abstract no. O6

Novel insights into host-fungal pathogen interactions derived from live-cell imaging

Acknowledgments The authors acknowledge funding from the Wellcome Trust (080088, 086827, 075470 and 099215) including a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377 and FP7-2007–2013 grant agreement HEALTH-F2-2010-260338–ALLFUN to NARG.Peer reviewedPublisher PD

Global and regional brain metabolic scaling and its functional consequences

Background: Information processing in the brain requires large amounts of metabolic energy, the spatial distribution of which is highly heterogeneous reflecting complex activity patterns in the mammalian brain. Results: Here, it is found based on empirical data that, despite this heterogeneity, the volume-specific cerebral glucose metabolic rate of many different brain structures scales with brain volume with almost the same exponent around -0.15. The exception is white matter, the metabolism of which seems to scale with a standard specific exponent -1/4. The scaling exponents for the total oxygen and glucose consumptions in the brain in relation to its volume are identical and equal to $0.86\pm 0.03$, which is significantly larger than the exponents 3/4 and 2/3 suggested for whole body basal metabolism on body mass. Conclusions: These findings show explicitly that in mammals (i) volume-specific scaling exponents of the cerebral energy expenditure in different brain parts are approximately constant (except brain stem structures), and (ii) the total cerebral metabolic exponent against brain volume is greater than the much-cited Kleiber's 3/4 exponent. The neurophysiological factors that might account for the regional uniformity of the exponents and for the excessive scaling of the total brain metabolism are discussed, along with the relationship between brain metabolic scaling and computation.Comment: Brain metabolism scales with its mass well above 3/4 exponen

Intestinal Epithelial Cell-Specific Deletion of PLD2 Alleviates DSS-Induced Colitis by Regulating Occludin

Ulcerative colitis is a multi-factorial disease involving a dysregulated immune response. Disruptions to the intestinal epithelial barrier and translocation of bacteria, resulting in inflammation, are common in colitis. The mechanisms underlying epithelial barrier dysfunction or regulation of tight junction proteins during disease progression of colitis have not been clearly elucidated. Increase in phospholipase D (PLD) activity is associated with disease severity in colitis animal models. However, the role of PLD2 in the maintenance of intestinal barrier integrity remains elusive. We have generated intestinal specific Pld2 knockout mice (Pld2 IEC-KO) to investigate the mechanism of intestinal epithelial PLD2 in colitis. We show that the knockout of Pld2 confers protection against dextran sodium sulphate (DSS)-induced colitis in mice. Treatment with DSS induced the expression of PLD2 and downregulated occludin in colon epithelial cells. PLD2 was shown to mediate phosphorylation of occludin and induce its proteasomal degradation in a c-Src kinase-dependent pathway. Additionally, we have shown that treatment with an inhibitor of PLD2 can rescue mice from DSS-induced colitis. To our knowledge, this is the first report showing that PLD2 is pivotal in the regulation of the integrity of epithelial tight junctions and occludin turn over, thereby implicating it in the pathogenesis of colitis

Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c

Cortico-basal ganglia circuits are critical for speech and language and are implicated in autism spectrum disorder, in which language function can be severely affected. We demonstrate that in the mouse striatum, the gene Foxp2 negatively interacts with the synapse suppressor gene Mef2c. We present causal evidence that Mef2c inhibition by Foxp2 in neonatal mouse striatum controls synaptogenesis of corticostriatal inputs and vocalization in neonates. Mef2c suppresses corticostriatal synapse formation and striatal spinogenesis, but can itself be repressed by Foxp2 through direct DNA binding. Foxp2 deletion de-represses Mef2c, and both intrastriatal and global decrease of Mef2c rescue vocalization and striatal spinogenesis defects of Foxp2-deletion mutants. These findings suggest that Foxp2-Mef2C signaling is critical to corticostriatal circuit formation. If found in humans, such signaling defects could contribute to a range of neurologic and neuropsychiatric disorders.National Institutes of Health (U.S.) (Grant R37 HD028341)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (Award R37 HD028341

Fractal Dimensions and Scaling Laws in the Interstellar Medium and Galaxy Distributions: a new Field Theory Approach

We develop a field theoretical approach to the cold interstellar medium (ISM) and large structure of the universe. We show that a non-relativistic self- gravitating gas in thermal equilibrium with variable number of atoms or fragments is exactly equivalent to a field theory of a scalar field phi(x) with exponential self-interaction. We analyze this field theory perturbatively and non-perturbatively through the renormalization group(RG).We show scaling behaviour (critical) for a continuous range of the physical parameters as the temperature. We derive in this framework the scaling relation M(R) \sim R^{d_H} for the mass on a region of size R, and Delta v \sim R^\frac12(d_H -1) for the velocity dispersion. For the density-density correlations we find a power-law behaviour for large distances \sim |r_1 - r_2|^{2D - 6}.The fractal dimension D turns to be related with the critical exponent \nu by D = 1/ \nu. Mean field theory yields \nu = 1/2, D = 2. Both the Ising and the mean field values are compatible with the present ISM observational data:1.4\leq D \leq 2. We develop a field theoretical approach to the galaxy distribution considering a gas of self-gravitating masses on the FRW background, in quasi-thermal equi- librium. We show that it exhibits scaling behaviour by RG methods. The galaxy correlations are computed without assuming homogeneity. We find \sim r^{D-3} $. The theory allows to compute the three and higher density correlators without any assumption.We find that the connected N-points density scales as r_1^{N(D-3)}, when$ r_1 >> r_i

Measurement and initial characterization of leukocyte telomere length in 474,074 participants in UK Biobank

Leukocyte telomere length (LTL) is a proposed marker of biological age. Here we report the measurement and initial characterization of LTL in 474,074 participants in UK Biobank. We confirm that older age and male sex associate with shorter LTL, with women on average ~7 years younger in 'biological age' than men. Compared to white Europeans, LTL is markedly longer in African and Chinese ancestries. Older paternal age at birth is associated with longer individual LTL. Higher white cell count is associated with shorter LTL, but proportions of white cell subtypes show weaker associations. Age, ethnicity, sex and white cell count explain ~5.5% of LTL variance. Using paired samples from 1,351 participants taken ~5 years apart, we estimate the within-individual variability in LTL and provide a correction factor for this. This resource provides opportunities to investigate determinants and biomedical consequences of variation in LTL

Polygenic basis and biomedical consequences of telomere length variation

Telomeres, the end fragments of chromosomes, play key roles in cellular proliferation and senescence. Here we characterize the genetic architecture of naturally occurring variation in leukocyte telomere length (LTL) and identify causal links between LTL and biomedical phenotypes in 472,174 well-characterized UK Biobank participants. We identified 197 independent sentinel variants associated with LTL at 138 genomic loci (108 new). Genetically determined differences in LTL were associated with multiple biological traits, ranging from height to bone marrow function, as well as several diseases spanning neoplastic, vascular and inflammatory pathologies. Finally, we estimated that, at the age of 40 years, people with an LTL >1 s.d. shorter than the population mean had a 2.5-year-lower life expectancy compared with the group with ≥1 s.d. longer LDL. Overall, we furnish new insights into the genetic regulation of LTL, reveal wide-ranging influences of LTL on physiological traits, diseases and longevity, and provide a powerful resource available to the global research community

Cold streams in early massive hot haloes as the main mode of galaxy formation

The massive galaxies in the young universe, ten billion years ago, formed stars at surprising intensities. Although this is commonly attributed to violent mergers, the properties of many of these galaxies are incompatible with such events, showing gas-rich, clumpy, extended rotating disks not dominated by spheroids (Genzel et al. 2006, 2008). Cosmological simulations and clustering theory are used to explore how these galaxies acquired their gas. Here we report that they are stream-fed galaxies, formed from steady, narrow, cold gas streams that penetrate the shock-heated media of massive dark matter haloes (Dekel & Birnboim 2006; Keres et al. 2005). A comparison with the observed abundance of star-forming galaxies implies that most of the input gas must rapidly convert to stars. One-third of the stream mass is in gas clumps leading to mergers of mass ratio greater than 1:10, and the rest is in smoother flows. With a merger duy cycle of 0.1, three-quarters of the galaxies forming stars at a given rate are fed by smooth streams. The rarer, submillimetre galaxies that form stars even more intensely are largely merger-induced starbursts. Unlike destructive mergers, the streams are likely to keep the rotating disk configuration intact, although turbulent and broken into giant star-forming clumps that merge into a central spheroid (Noguchi 1999; Genzel et al. 2008, Elmegreen, Bournaud & Elmegreen 2008, Dekel, Sari & Ceverino 2009). This stream-driven scenario for the formation of disks and spheroids is an alternative to the merger picture.Comment: Improved version, 25 pages, 13 figures, Letter to Nature with Supplementary Informatio