Output from VIP cells of the mammalian central clock regulates daily physiological rhythms

The suprachiasmatic nucleus (SCN) circadian clock is critical for optimising daily cycles in mammalian physiology and behaviour. The roles of the various SCN cell types in communicating timing information to downstream physiological systems remain incompletely understood, however. In particular, while vasoactive intestinal polypeptide (VIP) signalling is essential for SCN function and whole animal circadian rhythmicity, the specific contributions of VIP cell output to physiological control remains uncertain. Here we reveal a key role for SCN VIP cells in central clock output. Using multielectrode recording and optogenetic manipulations, we show that VIP neurons provide coordinated daily waves of GABAergic input to target cells across the paraventricular hypothalamus and ventral thalamus, supressing their activity during the mid to late day. Using chemogenetic manipulation, we further demonstrate specific roles for this circuitry in the daily control of heart rate and corticosterone secretion, collectively establishing SCN VIP cells as influential regulators of physiological timing

Topology by Design in Magnetic nano-Materials: Artificial Spin Ice

Artificial Spin Ices are two dimensional arrays of magnetic, interacting nano-structures whose geometry can be chosen at will, and whose elementary degrees of freedom can be characterized directly. They were introduced at first to study frustration in a controllable setting, to mimic the behavior of spin ice rare earth pyrochlores, but at more useful temperature and field ranges and with direct characterization, and to provide practical implementation to celebrated, exactly solvable models of statistical mechanics previously devised to gain an understanding of degenerate ensembles with residual entropy. With the evolution of nano--fabrication and of experimental protocols it is now possible to characterize the material in real-time, real-space, and to realize virtually any geometry, for direct control over the collective dynamics. This has recently opened a path toward the deliberate design of novel, exotic states, not found in natural materials, and often characterized by topological properties. Without any pretense of exhaustiveness, we will provide an introduction to the material, the early works, and then, by reporting on more recent results, we will proceed to describe the new direction, which includes the design of desired topological states and their implications to kinetics.Comment: 29 pages, 13 figures, 116 references, Book Chapte

Evidence for the return of subducted continental crust

Author Posting. © Nature Publishing Group, 2007. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 448 (2007): 684-687, doi:10.1038/nature06048.Substantial quantities of terrigenous sediments are known to enter the mantle at subduction zones, but little is known about their fate in the mantle. Subducted sediment may be entrained in buoyantly upwelling plumes and returned to the earth’s surface at hotspots, but the proportion of recycled sediment in the mantle is small and clear examples of recycled sediment in hotspot lavas are rare. We report here remarkably enriched 87Sr/86Sr and 143Nd/144Nd isotope signatures (up to 0.720830 and 0.512285, respectively) in Samoan lavas from three dredge locations on the underwater flanks of Savai’i island, Western Samoa. The submarine Savai’i lavas represent the most extreme 87Sr/86Sr isotope compositions reported for ocean island basalts (OIBs) to date. The data are consistent with the presence of a recycled sediment component (with a composition similar to upper continental crust, or UCC) in the Samoan mantle. Trace element data show similar affinities with UCC—including exceptionally low Ce/Pb and Nb/U ratios—that complement the enriched 87Sr/86Sr and 143Nd/144Nd isotope signatures. The geochemical evidence from the new Samoan lavas radically redefines the composition of the EM2 (enriched mantle 2) mantle endmember, and points to the presence of an ancient recycled UCC component in the Samoan plume

Feasibility study of computed tomography colonography using limited bowel preparation at normal and low-dose levels study

The purpose was to evaluate low-dose CT colonography without cathartic cleansing in terms of image quality, polyp visualization and patient acceptance. Sixty-one patients scheduled for colonoscopy started a low-fiber diet, lactulose and amidotrizoic-acid for fecal tagging 2 days prior to the CT scan (standard dose, 5.8–8.2 mSv). The original raw data of 51 patients were modified and reconstructed at simulated 2.3 and 0.7 mSv levels. Two observers evaluated the standard dose scan regarding image quality and polyps. A third evaluated the presence of polyps at all three mSv levels in a blinded prospective way. All observers were blinded to the reference standard: colonoscopy. At three times patients were given questionnaires relating to their experiences and preference. Image quality was sufficient in all patients, but significantly lower in the cecum, sigmoid and rectum. The two observers correctly identified respectively 10/15 (67%) and 9/15 (60%) polyps ≥10 mm, with 5 and 8 false-positive lesions (standard dose scan). Dose reduction down to 0.7 mSv was not associated with significant changes in diagnostic value (polyps ≥10 mm). Eighty percent of patients preferred CT colonography and 13% preferred colonoscopy (P<0.001). CT colonography without cleansing is preferred to colonoscopy and shows sufficient image quality and moderate sensitivity, without impaired diagnostic value at dose-levels as low as 0.7 mSv

Involvement of Skeletal Muscle Gene Regulatory Network in Susceptibility to Wound Infection Following Trauma

Despite recent advances in our understanding the pathophysiology of trauma, the basis of the predisposition of trauma patients to infection remains unclear. A Drosophila melanogaster/Pseudomonas aeruginosa injury and infection model was used to identify host genetic components that contribute to the hyper-susceptibility to infection that follows severe trauma. We show that P. aeruginosa compromises skeletal muscle gene (SMG) expression at the injury site to promote infection. We demonstrate that activation of SMG structural components is under the control of cJun-N-terminal Kinase (JNK) Kinase, Hemipterous (Hep), and activation of this pathway promotes local resistance to P. aeruginosa in flies and mice. Our study links SMG expression and function to increased susceptibility to infection, and suggests that P. aeruginosa affects SMG homeostasis locally by restricting SMG expression in injured skeletal muscle tissue. Local potentiation of these host responses, and/or inhibition of their suppression by virulent P. aeruginosa cells, could lead to novel therapies that prevent or treat deleterious and potentially fatal infections in severely injured individuals

Caffeine Ingestion Reverses the Circadian Rhythm Effects on Neuromuscular Performance in Highly Resistance-Trained Men

Purpose: To investigate whether caffeine ingestion counteracts the morning reduction in neuromuscular performance associated with the circadian rhythm pattern. Methods: Twelve highly resistance-trained men underwent a battery of neuromuscular tests under three different conditions; i) morning (10:00 a.m.) with caffeine ingestion (i.e., 3 mg kg 21; AMCAFF trial); ii) morning (10:00 a.m.) with placebo ingestion (AMPLAC trial); and iii) afternoon (18:00 p.m.) with placebo ingestion (PMPLAC trial). A randomized, doubleblind, crossover, placebo controlled experimental design was used, with all subjects serving as their own controls. The neuromuscular test battery consisted in the measurement of bar displacement velocity during free-weight full-squat (SQ) and bench press (BP) exercises against loads that elicit maximum strength (75 % 1RM load) and muscle power adaptations (1 m s 21 load). Isometric maximum voluntary contraction (MVCLEG) and isometric electrically evoked strength of the right knee (EVOK LEG) were measured to identify caffeine’s action mechanisms. Steroid hormone levels (serum testosterone, cortisol and growth hormone) were evaluated at the beginning of each trial (PRE). In addition, plasma norepinephrine (NE) and epinephrine were measured PRE and at the end of each trial following a standardized intense (85 % 1RM) 6 repetitions bout of SQ (POST). Results: In the PM PLAC trial, dynamic muscle strength and power output were significantly enhanced compared with AM PLA

Replicative Age Induces Mitotic Recombination in the Ribosomal RNA Gene Cluster of Saccharomyces cerevisiae

Somatic mutations contribute to the development of age-associated disease. In earlier work, we found that, at high frequency, aging Saccharomyces cerevisiae diploid cells produce daughters without mitochondrial DNA, leading to loss of respiration competence and increased loss of heterozygosity (LOH) in the nuclear genome. Here we used the recently developed Mother Enrichment Program to ask whether aging cells that maintain the ability to produce respiration-competent daughters also experience increased genomic instability. We discovered that this population exhibits a distinct genomic instability phenotype that primarily affects the repeated ribosomal RNA gene array (rDNA array). As diploid cells passed their median replicative life span, recombination rates between rDNA arrays on homologous chromosomes progressively increased, resulting in mutational events that generated LOH at >300 contiguous open reading frames on the right arm of chromosome XII. We show that, while these recombination events were dependent on the replication fork block protein Fob1, the aging process that underlies this phenotype is Fob1-independent. Furthermore, we provide evidence that this aging process is not driven by mechanisms that modulate rDNA recombination in young cells, including loss of cohesion within the rDNA array or loss of Sir2 function. Instead, we suggest that the age-associated increase in rDNA recombination is a response to increasing DNA replication stress generated in aging cells

Complications and pitfalls of lumbar interlaminar and transforaminal epidural injections

Lumbar interlaminar and transforaminal epidural injections are used in the treatment of lumbar radicular pain and other lumbar spinal pain syndromes. Complications from these procedures arise from needle placement and the administration of medication. Potential risks include infection, hematoma, intravascular injection of medication, direct nerve trauma, subdural injection of medication, air embolism, disc entry, urinary retention, radiation exposure, and hypersensitivity reactions. The objective of this article is to review the complications of lumbar interlaminar and transforaminal epidural injections and discuss the potential pitfalls related to these procedures. We performed a comprehensive literature review through a Medline search for relevant case reports, clinical trials, and review articles. Complications from lumbar epidural injections are extremely rare. Most if not all complications can be avoided by careful technique with accurate needle placement, sterile precautions, and a thorough understanding of the relevant anatomy and contrast patterns on fluoroscopic imaging

Deconstructing Insight: EEG Correlates of Insightful Problem Solving

Background: Cognitive insight phenomenon lies at the core of numerous discoveries. Behavioral research indicates four salient features of insightful problem solving: (i) mental impasse, followed by (ii) restructuring of the problem representation, which leads to (iii) a deeper understanding of the problem, and finally culminates in (iv) an “Aha!” feeling of suddenness and obviousness of the solution. However, until now no efforts have been made to investigate the neural mechanisms of these constituent features of insight in a unified framework. Methodology/Principal Findings: In an electroencephalographic study using verbal remote associate problems, we identified neural correlates of these four features of insightful problem solving. Hints were provided for unsolved problems or after mental impasse. Subjective ratings of the restructuring process and the feeling of suddenness were obtained on trial-by-trial basis. A negative correlation was found between these two ratings indicating that sudden insightful solutions, where restructuring is a key feature, involve automatic, subconscious recombination of information. Electroencephalogram signals were analyzed in the space×time×frequency domain with a nonparametric cluster randomization test. First, we found strong gamma band responses at parieto-occipital regions which we interpreted as (i) an adjustment of selective attention (leading to a mental impasse or to a correct solution depending on the gamma band power level) and (ii) encoding and retrieval processes for the emergence of spontaneous new solutions. Secondly, we observed an increased upper alpha band response in right temporal regions (suggesting active suppression of weakly activated solution relevant information) for initially unsuccessful trials that after hint presentation led to a correct solution. Finally, for trials with high restructuring, decreased alpha power (suggesting greater cortical excitation) was observed in right prefrontal area. Conclusions/Significance: Our results provide a first account of cognitive insight by dissociating its constituent components and potential neural correlates