5,792 research outputs found
Neuronal Circuitry Mechanisms Regulating Adult Mammalian Neurogenesis
The adult mammalian brain is a dynamic structure, capable of remodeling in response to various physiological and pathological stimuli. One dramatic example of brain plasticity is the birth and subsequent integration of newborn neurons into the existing circuitry. This process, termed adult neurogenesis, recapitulates neural developmental events in two specialized adult brain regions: the lateral ventricles of the forebrain. Recent studies have begun to delineate how the existing neuronal circuits influence the dynamic process of adult neurogenesis, from activation of quiescent neural stem cells (NSCs) to the integration and survival of newborn neurons. Here, we review recent progress toward understanding the circuit-based regulation of adult neurogenesis in the hippocampus and olfactory bulb
Reliability and validity of neurobehavioral function on the Psychology Experimental Building Language test battery in young adults
Background. The Psychology Experiment Building Language (PEBL) software consists of over one-hundred computerized tests based on classic and novel cognitive neuropsychology and behavioral neurology measures. Although the PEBL tests are becoming more widely utilized, there is currently very limited information about the psychometric properties of these measures.
Methods. Study I examined inter-relationships among nine PEBL tests including indices of motor-function (Pursuit Rotor and Dexterity), attention (Test of Attentional Vigilance and Time-Wall), working memory (Digit Span Forward), and executive-function (PEBL Trail Making Test, Berg/Wisconsin Card Sorting Test, Iowa Gambling Test, and Mental Rotation) in a normative sample (N = 189, ages 18â22). Study II evaluated testâretest reliability with a two-week interest interval between administrations in a separate sample (N = 79, ages 18â22).
Results. Moderate intra-test, but low inter-test, correlations were observed and ceiling/floor effects were uncommon. Sex differences were identified on the Pursuit Rotor (Cohenâs d = 0.89) and Mental Rotation (d = 0.31) tests. The correlation between the test and retest was high for tests of motor learning (Pursuit Rotor time on target r = .86) and attention (Test of Attentional Vigilance response time r = .79), intermediate for memory (digit span r = .63) but lower for the executive function indices (Wisconsin/Berg Card Sorting Test perseverative errors = .45, Tower of London moves = .15). Significant practice effects were identified on several indices of executive function.
Conclusions. These results are broadly supportive of the reliability and validity of individual PEBL tests in this sample. These findings indicate that the freely downloadable, open-source PEBL battery (http://pebl.sourceforge.net) is a versatile research tool to study individual differences in neurocognitive performance
Elucidation of The Behavioral Program and Neuronal Network Encoded by Dorsal Raphe Serotonergic Neurons
Elucidating how the brain's serotonergic network mediates diverse behavioral actions over both relatively short (minutesâhours) and long period of time (daysâweeks) remains a major challenge for neuroscience. Our relative ignorance is largely due to the lack of technologies with robustness, reversibility, and spatio-temporal control. Recently, we have demonstrated that our chemogenetic approach (eg, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)) provides a reliable and robust tool for controlling genetically defined neural populations. Here we show how short- and long-term activation of dorsal raphe nucleus (DRN) serotonergic neurons induces robust behavioral responses. We found that both short- and long-term activation of DRN serotonergic neurons induce antidepressant-like behavioral responses. However, only short-term activation induces anxiogenic-like behaviors. In parallel, these behavioral phenotypes were associated with a metabolic map of whole brain network activity via a recently developed non-invasive imaging technology DREAMM (DREADD Associated Metabolic Mapping). Our findings reveal a previously unappreciated brain network elicited by selective activation of DRN serotonin neurons and illuminate potential therapeutic and adverse effects of drugs targeting DRN neurons
Molecular mechanism of biased signaling at the kappa opioid receptor
The Îş-opioid receptor (KOR) has emerged as an attractive drug target for pain management without addiction, and biased signaling through particular pathways of KOR may be key to maintaining this benefit while minimizing side-effect liabilities. As for most G protein-coupled receptors (GPCRs), however, the molecular mechanisms of ligand-specific signaling at KOR have remained unclear. To better understand the molecular determinants of KOR signaling bias, we apply structure determination, atomic-level molecular dynamics (MD) simulations, and functional assays. We determine a crystal structure of KOR bound to the G protein-biased agonist nalfurafine, the first approved KOR-targeting drug. We also identify an arrestin-biased KOR agonist, WMS-X600. Using MD simulations of KOR bound to nalfurafine, WMS-X600, and a balanced agonist U50,488, we identify three active-state receptor conformations, including one that appears to favor arrestin signaling over G protein signaling and another that appears to favor G protein signaling over arrestin signaling. These results, combined with mutagenesis validation, provide a molecular explanation of how agonists achieve biased signaling at KOR
Plasma Magnetohydrodynamics and Energy Conversion
Contains research objectives and reports on four research projects.U.S. Air Force (Aeronautical Systems Division) under Contract AF33(616)-7624 with the Aeronautical Accessories Laboratory, Wright-Patterson Air Force Base, OhioNational Science Foundation under Grant G-24073National Institutes of Health (Grant HTS-5550
On the Nature of Stars with Planets
We consider the metallicities and kinematics of nearby stars known to have
planetary-mass companions in the general context of the overall properties of
the local Galactic Disk. We have used Stromgren photometry to determine
abundances for both the extrasolar-planet host stars and for a volume-limited
sample of 486 F, G and K stars selected from the Hipparcos catalogue. The
latter data show that the Sun lies near the modal abundance of the disk, with
over 45% of local stars having super-solar metallicities. Twenty of the latter
stars (4.1%) are known to have planetary-mass companions. Using that ratio to
scale data for the complete sample of planetary host stars, we find that the
fraction of stars with extrasolar planets rises sharply with increasing
abundance, confirming previous results. However, the frequency remains at the
3-4% level for stars within 0.15 dex of solar abundance, and falls to ~1% only
for stars with abundances less than half solar. Given the present observational
constraints, both in velocity precision and in the available time baseline,
these numbers represent a lower limit to the frequency of extrasolar planetary
systems. A comparison between the kinematics of the planetary host stars and a
representative sample of disk stars suggests that the former have an average
age which is ~60% of the latter.Comment: 46 pages, 13 figures; accepted for PAS
A primary care, multi-disciplinary disease management program for opioid-treated patients with chronic non-cancer pain and a high burden of psychiatric comorbidity
BACKGROUND: Chronic non-cancer pain is a common problem that is often accompanied by psychiatric comorbidity and disability. The effectiveness of a multi-disciplinary pain management program was tested in a 3 month before and after trial. METHODS: Providers in an academic general medicine clinic referred patients with chronic non-cancer pain for participation in a program that combined the skills of internists, clinical pharmacists, and a psychiatrist. Patients were either receiving opioids or being considered for opioid therapy. The intervention consisted of structured clinical assessments, monthly follow-up, pain contracts, medication titration, and psychiatric consultation. Pain, mood, and function were assessed at baseline and 3 months using the Brief Pain Inventory (BPI), the Center for Epidemiological Studies-Depression Scale scale (CESD) and the Pain Disability Index (PDI). Patients were monitored for substance misuse. RESULTS: Eighty-five patients were enrolled. Mean age was 51 years, 60% were male, 78% were Caucasian, and 93% were receiving opioids. Baseline average pain was 6.5 on an 11 point scale. The average CESD score was 24.0, and the mean PDI score was 47.0. Sixty-three patients (73%) completed 3 month follow-up. Fifteen withdrew from the program after identification of substance misuse. Among those completing 3 month follow-up, the average pain score improved to 5.5 (p = 0.003). The mean PDI score improved to 39.3 (p < 0.001). Mean CESD score was reduced to 18.0 (p < 0.001), and the proportion of depressed patients fell from 79% to 54% (p = 0.003). Substance misuse was identified in 27 patients (32%). CONCLUSIONS: A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up
Space Radiation Alters GenotypeâPhenotype Correlations in Fear Learning and Memory Tests
Behavioral and cognitive traits have a genetic component even though contributions from individual genes and genomic loci are in many cases modest. Changes in the environment can alter genotypeâphenotype relationships. Space travel, which includes exposure to ionizing radiation, constitutes environmental challenges and is expected to induce not only dramatic behavioral and cognitive changes but also has the potential to induce physical DNA damage. In this study, we utilized a genetically heterogeneous mouse model, dense genotype data, and shifting environmental challenges, including ionizing radiation exposure, to explore and quantify the size and stability of the genetic component of fear learning and memory-related measures. Exposure to ionizing radiation and other external stressors altered the genotypeâphenotype correlations, although different behavioral and cognitive measures were affected to different extents. Utilizing an integrative genomic approach, we identified pathways and functional ontology categories associated with these behavioral and cognitive measures
Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV
A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay
channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7
TeV is presented. The data were collected at the LHC, with the CMS detector,
and correspond to an integrated luminosity of 4.6 inverse femtobarns. No
significant excess is observed above the background expectation, and upper
limits are set on the Higgs boson production cross section. The presence of the
standard model Higgs boson with a mass in the 270-440 GeV range is excluded at
95% confidence level.Comment: Submitted to JHE
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