HeyL regulates the number of TrkC neurons in dorsal root ganglia

AbstractThe basic-helix-loop-helix transcription factor HeyL is expressed at high levels by neural crest progenitor cells (NCPs) that give rise to neurons and glia in dorsal root ganglia (DRG). Since HeyL expression was observed in these NCPs during the period of neurogenesis, we generated HeyL null mutants to help examine the factor's role in ganglion neuronal specification. Homozygous null mutation of HeyL reduced the number of TrkC+ neurons in DRG at birth including the subpopulation that expresses the ETS transcription factor ER81. Conversely, null mutation of the Hey paralog, Hey1, increased the number of TrkC+ neurons. Null mutation of HeyL increased expression of the Hey paralogs Hey1 and Hey2, suggesting that HeyL normally inhibits their expression. Double null mutation of both Hey1 and HeyL rescued TrkC+ neuron numbers to control levels. Thus, the balance between HeyL and Hey1 expression regulates the differentiation of a subpopulation of TrkC+ neurons in the DRG

Using carbon isotope fractionation to constrain the extent of methane dissolution into the water column surrounding a natural hydrocarbon gas seep in the northern Gulf of Mexico

Author Posting. © American Geophysical Union, 2018. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Using carbon isotope fractionation to constrain the extent of methane dissolution into the water column surrounding a natural hydrocarbon gas seep in the northern gulf of Mexico. Geochemistry Geophysics Geosystems, 19(11), (2018); 4459-4475., doi:10.1029/2018GC007705.A gas bubble seep located in the northern Gulf of Mexico was investigated over several days to determine whether changes in the stable carbon isotopic ratio of methane can be used as a tracer for methane dissolution through the water column. Gas bubble and water samples were collected at the seafloor and throughout the water column for isotopic ratio analysis of methane. Our results show that changes in methane isotopic ratios are consistent with laboratory experiments that measured the isotopic fractionation from methane dissolution. A Rayleigh isotope model was applied to the isotope data to determine the fraction of methane dissolved at each depth. On average, the fraction of methane dissolved surpasses 90% past an altitude of 400 m above the seafloor. Methane dissolution was also investigated using a modified version of the Texas A&M Oil spill (Outfall) Calculator (TAMOC) where changes in methane isotopic ratios could be calculated. The TAMOC model results show that dissolution depends on depth and bubble size, explaining the spread in measured isotopic ratios during our investigations. Both the Rayleigh and TAMOC models show that methane bubbles quickly dissolve following emission from the seafloor. Together, these results show that it is possible to use measurements of natural methane isotopes to constrain the extent of methane dissolution following seafloor emission.This research was made possible by two grants from the Gulf of Mexico Research Initiative: Gulf Integrated Spill Response (GISR) Consortium (awarded to J. D. K. and S. A. S.) and Center for Integrated Modeling and Assessment of the Gulf Ecosystem (C‐IMAGE) II (awarded to S. A. S.). Additional support was provided by the U.S. Department of Energy (DE‐FE0028980; awarded to J. D. K.). Data are publicly available through the Gulf of Mexico Research Initiative Information & Data Cooperative (GRIIDC). Methane concentration and isotopic ratio data can be found at https://data.gulfresearchinitiative.org/data/R1.x137.000:0025, and TAMOC model scripts and results are found at https://data.gulfresearchinitiative.org/data/R1.x137.000:0026. The coversion of methane isotopic ratio data used in this manuscript can be found at https://data.gulfresearchinitiative.org/data/R1.x137.000:0028. We want to thank the captain and crew of the E/V Nautilus and the operators of ROV Hercules and Argus during the GISR G08 cruise and Nicole Raineault for their outstanding support at sea. Acoustically identifying the bubble flare was managed by Andone Lavery, and support for collecting gas and water samples was provided by John Bailey. We also want to thank Sean Sylva for analytical assistance on shore, Inok Jun for helping create the sampling schematics, and David Brink‐Roby for helping create the sample site map.2019-04-2

Recent trends in primary-care antidepressant prescribing to children and young people: an e-cohort study

Concerns relating to increased use of psychotropic medication contrast with those of under-treatment and under-recognition of common mental disorders in children and young people (CYP) across developed countries. Little is known about the indications recorded for antidepressant prescribing in primary care in CYP.This was an electronic cohort study of routinely collected primary-care data from a population of 1.9 million, Wales, UK. Poisson regression was undertaken to model adjusted counts of recorded depression symptoms, diagnoses and antidepressant prescriptions. Associated indications were explored.3 58 383 registered patients aged 6-18 years between 1 January 2003 and 31 December 2013 provided a total of 19 20 338 person-years of follow-up. The adjusted incidence of antidepressant prescribing increased significantly [incidence rate ratio (IRR) for 2013 = 1.28], mainly in older adolescents. The majority of new antidepressant prescriptions were for citalopram. Recorded depression diagnoses showed a steady decline (IRR = 0.72) while depression symptoms (IRR = 2.41) increased. Just over half of new antidepressant prescriptions were associated with depression (diagnosis or symptoms). Other antidepressant prescribing, largely unlicensed, was associated with diagnoses such as anxiety and pain.Antidepressant prescribing is increasing in CYP while recorded depression diagnoses decline. Unlicensed citalopram prescribing occurs outside current guidelines, despite its known toxicity in overdose. Unlicensed antidepressant prescribing is associated with a wide range of diagnoses, and while accepted practice, is often not supported by safety and efficacy studies. New strategies to implement current guidance for the management of depression in CYP are required

Inhibition of BMP signaling in P-Cadherin positive hair progenitor cells leads to trichofolliculoma-like hair follicle neoplasias

<p>Abstract</p> <p>Background</p> <p>Skin stem cells contribute to all three major lineages of epidermal appendages, i.e., the epidermis, the hair follicle, and the sebaceous gland. In hair follicles, highly proliferative committed progenitor cells, called matrix cells, are located at the base of the follicle in the hair bulb. The differentiation of these early progenitor cells leads to specification of a central hair shaft surrounded by an inner root sheath (IRS) and a companion layer. Multiple signaling molecules, including bone morphogenetic proteins (BMPs), have been implicated in this process.</p> <p>Methods</p> <p>To further probe the contribution of BMP signaling to hair follicle development and maintenance we employed a transgenic mouse that expresses the BMP inhibitor, Noggin, to disrupt BMP signaling specifically in subset of hair follicle progenitors under the control of neuron specific enolase (Nse) promoter. We then studied the skin tumor phenotypes of the transgenic mice through histology, immunohistochemistry and Western Blotting to delineate the underlying mechanisms. Double transgenic mice expressing BMP as well as noggin under control of the Nse promoter were used to rescue the skin tumor phenotypes.</p> <p>Results</p> <p>We found that the transgene is expressed specifically in a subpopulation of P-cadherin positive progenitor cells in Nse-Noggin mice. Blocking BMP signaling in this cell population led to benign hair follicle-derived neoplasias resembling human trichofolliculomas, associated with down-regulation of E-cadherin expression and dynamic regulation of CD44.</p> <p>Conclusions</p> <p>These observations further define a critical role for BMP signaling in maintaining the homeostasis of hair follicles, and suggest that dysregulation of BMP signaling in hair follicle progenitors may contribute to human trichofolliculoma.</p

BMP Signaling Mediates Effects of Exercise on Hippocampal Neurogenesis and Cognition in Mice

Exposure to exercise or to environmental enrichment increases the generation of new neurons in the adult hippocampus and promotes certain kinds of learning and memory. While the precise role of neurogenesis in cognition has been debated intensely, comparatively few studies have addressed the mechanisms linking environmental exposures to cellular and behavioral outcomes. Here we show that bone morphogenetic protein (BMP) signaling mediates the effects of exercise on neurogenesis and cognition in the adult hippocampus. Elective exercise reduces levels of hippocampal BMP signaling before and during its promotion of neurogenesis and learning. Transgenic mice with decreased BMP signaling or wild type mice infused with a BMP inhibitor both exhibit remarkable gains in hippocampal cognitive performance and neurogenesis, mirroring the effects of exercise. Conversely, transgenic mice with increased BMP signaling have diminished hippocampal neurogenesis and impaired cognition. Exercise exposure does not rescue these deficits, suggesting that reduced BMP signaling is required for environmental effects on neurogenesis and learning. Together, these observations show that BMP signaling is a fundamental mechanism linking environmental exposure with changes in cognitive function and cellular properties in the hippocampus

Testing Models of Intrinsic Brightness Variations in Type Ia Supernovae, and their Impact on Measuring Cosmological Parameters

For spectroscopically confirmed Type Ia supernovae we evaluate models of intrinsic brightness variations with detailed data/Monte Carlo comparisons of the dispersion in the following quantities: Hubble-diagram scatter, color difference (B-V-c) between the true B-V color and the fitted color (c) from the SALT-II light curve model, and photometric redshift residual. The data sample includes 251 ugriz light curves from the 3-season Sloan Digital Sky Survey-II, and 191 griz light curves from the Supernova Legacy Survey 3-year data release. We find that the simplest model of a wavelength-independent (coherent) scatter is not adequate, and that to describe the data the intrinsic scatter model must have wavelength-dependent variations. We use Monte Carlo simulations to examine the standard approach of adding a coherent scatter term in quadrature to the distance-modulus uncertainty in order to bring the reduced chi2 to unity when fitting a Hubble diagram. If the light curve fits include model uncertainties with the correct wavelength dependence of the scatter, we find that the bias on the dark energy equation of state parameter $w$ is negligible. However, incorrect model uncertainties can lead to a significant bias on the distance moduli, with up to ~0.05 mag redshift-dependent variation. For the recent SNLS3 cosmology results we estimate that this effect introduces an additional systematic uncertainty on $w$ of ~0.02, well below the total uncertainty. However, this uncertainty depends on the samples used, and thus this small $w$-uncertainty is not guaranteed in future cosmology results.Comment: accepted by Ap

Statement of Fred W. Garmone

This is a transcript of statements by Attorney, Fred W. Garmone (Counsel for Sam Sheppard) regarding a short in-chambers conference pre-trial with the Honorable Judge Blythin. Mr. Garmone stated to Judge Blythin, because of the fact that his son (Ed Blythin) at the time of trial was a member of the Homicide Unit, and was actively engaged in the investigation of this death of Marilyn Sheppard, that it was his feeling that he should withdraw or disqualify himself as the Judge to hear the case. Along with Mr. Garmone\u27s statement is a brief question/answer exchange between members of the Prosecution and the Sheppard Counsel present; conversation exchange inquires of pre-trial defense attorney dissension or discord and whether there was a formal affidavit of prejudice against Judge Blythin for his personal connection to the criminal investigation. These inquiries prompted negative responses from Mr. Garmone

Problem gambling and suicidality in England: secondary analysis of a representative cross-sectional survey

Objectives: Problem gamblers in treatment are known to be at high risk for suicidality, but few studies have examined if this is evident in community samples. Evidence is mixed on the extent to which an association between problem gambling and suicidality may be explained by psychiatric comorbidity. We tested whether they are associated after adjustment for co-occurring mental disorders and other factors. Study design: Secondary analysis of the Adult Psychiatric Morbidity Survey 2007, a cross-sectional na- tional probability sample survey of 7403 adults living in households in England. Methods: Rates of suicidality in problem gamblers and the rest of the population were compared. A series of logistic regression models assessed the impact of adjustment on the relationship between problem gambling and suicidality. Results: Past year suicidality was reported in 19.2% of problem gamblers, compared with 4.4% in the rest of the population. Their unadjusted odds ratios (OR) of suicidality were 5.3 times higher. Odds attenuated but remained significant when depression and anxiety disorders, substance dependences, attention- deficit/hyperactivity disorder, and other factors were accounted for (adjusted OR 1⁄4 2.9, 95% confi- dence interval 1⁄4 1. 1, 8.1 P 1⁄4 0.023). Conclusions: Problem gamblers are a high-risk group for suicidality. This should be recognised in indi- vidual suicide prevention plans and local and national suicide prevention strategies. While some of this relationship is explained by other factors, a significant and substantial association between problem gambling and suicidality remains

Long range transport of ultra cold atoms in a far-detuned 1D optical lattice

We present a novel method to transport ultra cold atoms in a focused optical lattice over macroscopic distances of many Rayleigh ranges. With this method ultra cold atoms were transported over 5 cm in 250 ms without significant atom loss or heating. By translating the interference pattern together with the beam geometry the trap parameters are maintained over the full transport range. Thus, the presented method is well suited for tightly focused optical lattices that have sufficient trap depth only close to the focus. Tight focusing is usually required for far-detuned optical traps or traps that require high laser intensity for other reasons. The transport time is short and thus compatible with the operation of an optical lattice clock in which atoms are probed in a well designed environment spatially separated from the preparation and detection region.Comment: 14 pages, 6 figure

Tunable Pinning of Burst-Waves in Extended Systems with Discrete Sources

We study the dynamics of waves in a system of diffusively coupled discrete nonlinear sources. We show that the system exhibits burst waves which are periodic in a traveling-wave reference frame. We demonstrate that the burst waves are pinned if the diffusive coupling is below a critical value. When the coupling crosses the critical value the system undergoes a depinning instability via a saddle-node bifurcation, and the wave begins to move. We obtain the universal scaling for the mean wave velocity just above threshold.Comment: 4 pages, 5 figures, revte