2,672 research outputs found

    Acute Ethanol Administration Rapidly Increases Phosphorylation of Conventional Protein Kinase C in Specific Mammalian Brain Regions in Vivo

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    Background Protein kinase C (PKC) is a family of isoenzymes that regulate a variety of functions in the central nervous system including neurotransmitter release, ion channel activity, and cell differentiation. Growing evidence suggests that specific isoforms of PKC influence a variety of behavioral, biochemical, and physiological effects of ethanol in mammals. The purpose of this study was to determine whether acute ethanol exposure alters phosphorylation of conventional PKC isoforms at a threonine 674 (p-cPKC) site in the hydrophobic domain of the kinase, which is required for its catalytic activity. Methods Male rats were administered a dose range of ethanol (0, 0.5, 1, or 2 g/kg, intragastric) and brain tissue was removed 10 minutes later for evaluation of changes in p-cPKC expression using immunohistochemistry and Western blot methods. Results Immunohistochemical data show that the highest dose of ethanol (2 g/kg) rapidly increases p-cPKC immunoreactivity specifically in the nucleus accumbens (core and shell), lateral septum, and hippocampus (CA3 and dentate gyrus). Western blot analysis further showed that ethanol (2 g/kg) increased p-cPKC expression in the P2 membrane fraction of tissue from the nucleus accumbens and hippocampus. Although p-cPKC was expressed in numerous other brain regions, including the caudate nucleus, amygdala, and cortex, no changes were observed in response to acute ethanol. Total PKC? immunoreactivity was surveyed throughout the brain and showed no change following acute ethanol injection

    Effects of Supersymmetric Threshold Corrections on High-Scale Flavor Textures

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    Integration of superpartners out of the spectrum induces potentially large contributions to Yukawa couplings. These corrections, the supersymmetric threshold corrections, therefore influence the CKM matrix prediction in a non-trivial way. We study effects of threshold corrections on high-scale flavor structures specified at the gauge coupling unification scale in supersymmetry. In our analysis, we first consider high-scale Yukawa textures which qualify phenomenologically viable at tree level, and find that they get completely disqualified after incorporating the threshold corrections. Next, we consider Yukawa couplings, such as those with five texture zeroes, which are incapable of explaining flavor-changing proceses. Incorporation of threshold corrections, however, makes them phenomenologically viable textures. Therefore, supersymmetric threshold corrections are found to leave observable impact on Yukawa couplings of quarks, and any confrontation of high-scale textures with experiments at the weak scale must take into account such corrections.Comment: 25 pages, submitted to JHE

    The astrophysics of nanohertz gravitational waves

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    Pulsar timing array (PTA) collaborations in North America, Australia, and Europe, have been exploiting the exquisite timing precision of millisecond pulsars over decades of observations to search for correlated timing deviations induced by gravitational waves (GWs). PTAs are sensitive to the frequency band ranging just below 1 nanohertz to a few tens of microhertz. The discovery space of this band is potentially rich with populations of inspiraling supermassive black hole binaries, decaying cosmic string networks, relic post-inflation GWs, and even non-GW imprints of axionic dark matter. This article aims to provide an understanding of the exciting open science questions in cosmology, galaxy evolution, and fundamental physics that will be addressed by the detection and study of GWs through PTAs. The focus of the article is on providing an understanding of the mechanisms by which PTAs can address specific questions in these fields, and to outline some of the subtleties and difficulties in each case. The material included is weighted most heavily toward the questions which we expect will be answered in the near-term with PTAs; however, we have made efforts to include most currently anticipated applications of nanohertz GWs

    Cue-Reactors: Individual Differences in Cue-Induced Craving after Food or Smoking Abstinence

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    Background: Pavlovian conditioning plays a critical role in both drug addiction and binge eating. Recent animal research suggests that certain individuals are highly sensitive to conditioned cues, whether they signal food or drugs. Are certain humans also more reactive to both food and drug cues? Methods: We examined cue-induced craving for both cigarettes and food, in the same individuals (n = 15 adult smokers). Subjects viewed smoking-related or food-related images after abstaining from either smoking or eating. Results: Certain individuals reported strong cue-induced craving after both smoking and food cues. That is, subjects who reported strong cue-induced craving for cigarettes also rated stronger cue-induced food craving. Conclusions: In humans, like in nonhumans, there may be a ‘‘cue-reactive’ ’ phenotype, consisting of individuals who are highly sensitive to conditioned stimuli. This finding extends recent reports from nonhuman studies. Further understanding this subgroup of smokers may allow clinicians to individually tailor therapies for smoking cessation

    Parameter identification problems in the modelling of cell motility

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    We present a novel parameter identification algorithm for the estimation of parameters in models of cell motility using imaging data of migrating cells. Two alternative formulations of the objective functional that measures the difference between the computed and observed data are proposed and the parameter identification problem is formulated as a minimisation problem of nonlinear least squares type. A Levenberg–Marquardt based optimisation method is applied to the solution of the minimisation problem and the details of the implementation are discussed. A number of numerical experiments are presented which illustrate the robustness of the algorithm to parameter identification in the presence of large deformations and noisy data and parameter identification in three dimensional models of cell motility. An application to experimental data is also presented in which we seek to identify parameters in a model for the monopolar growth of fission yeast cells using experimental imaging data. Our numerical tests allow us to compare the method with the two different formulations of the objective functional and we conclude that the results with both objective functionals seem to agree

    Computational analysis suggests that virulence of Chromobacterium violaceum might be linked to biofilm formation and poly-NAG biosynthesis

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    Groups of genes that produce exopolysaccharide with a N-acetyl-D-glucosamine monomer are in the genome of several pathogenic bacteria. Chromobacterium violaceum, an opportunistic pathogen, has the operon hmsHFR-CV2940, whose proteins can synthesize such polysaccharide. In this work, multiple alignments among proteins from bacteria that synthesize such polysaccharide were used to verify the existence of amino acids that might be critical for pathogen activity. Three-dimensional models were generated for spatial visualization of these amino acid residues. The analysis carried out showed that the protein HmsR preserves the amino acids D135, D228, Q264 and R267, considered critical for the formation of biofilms and, furthermore, that these amino acids are close to each other. The protein HmsF of C. violaceum preserves the residues D86, D87, H156 and W115. It was also shown that these residues are also close to each other in their spatial arrangement. For the proteins HmsH and CV2940 there is evidence of conservation of the residues R104 and W94, respectively. Conservation and favorable spatial location of those critical amino acids that constitute the proteins of the operon indicates that they preserve the same enzymatic function in biofilm synthesis. This is an indicator that the operon hmsHFR-CV2940 is a possible target in C. violaceum pathogenicity

    Discovery of a black smoker vent field and vent fauna at the Arctic Mid-Ocean Ridge

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    The Arctic Mid-Ocean Ridge (AMOR) represents one of the most slow-spreading ridge systems on Earth. Previous attempts to locate hydrothermal vent fields and unravel the nature of venting, as well as the provenance of vent fauna at this northern and insular termination of the global ridge system, have been unsuccessful. Here, we report the first discovery of a black smoker vent field at the AMOR. The field is located on the crest of an axial volcanic ridge (AVR) and is associated with an unusually large hydrothermal deposit, which documents that extensive venting and long-lived hydrothermal systems exist at ultraslow-spreading ridges, despite their strongly reduced volcanic activity. The vent field hosts a distinct vent fauna that differs from the fauna to the south along the Mid-Atlantic Ridge. The novel vent fauna seems to have developed by local specialization and by migration of fauna from cold seeps and the Pacific

    Autoregulation of the Drosophila Noncoding roX1 RNA Gene

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    Most genes along the male single X chromosome in Drosophila are hypertranscribed about two-fold relative to each of the two female X chromosomes. This is accomplished by the MSL (male-specific lethal) complex that acetylates histone H4 at lysine 16. The MSL complex contains two large noncoding RNAs, roX1 (RNA on X) and roX2, that help target chromatin modifying enzymes to the X. The roX RNAs are functionally redundant but differ in size, sequence, and transcriptional control. We wanted to find out how roX1 production is regulated. Ectopic DC can be induced in wild-type (roX1+ roX2+) females if we provide a heterologous source of MSL2. However, in the absence of roX2, we found that roX1 expression failed to come on reliably. Using an in situ hybridization probe that is specific only to endogenous roX1, we found that expression was restored if we introduced either roX2 or a truncated but functional version of roX1. This shows that pre-existing roX RNA is required to positively autoregulate roX1 expression. We also observed massive cis spreading of the MSL complex from the site of roX1 transcription at its endogenous location on the X chromosome. We propose that retention of newly assembled MSL complex around the roX gene is needed to drive sustained transcription and that spreading into flanking chromatin contributes to the X chromosome targeting specificity. Finally, we found that the gene encoding the key male-limited protein subunit, msl2, is transcribed predominantly during DNA replication. This suggests that new MSL complex is made as the chromatin template doubles. We offer a model describing how the production of roX1 and msl2, two key components of the MSL complex, are coordinated to meet the dosage compensation demands of the male cell
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