517 research outputs found

    The relationship of affect and creativity

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    Thesis (B.S.) in Liberal Arts and Science -- University of Illinois at Urbana-Champaign, 1987.Bibliography: leaves 33-34.Microfiche of typescript. [Urbana, Ill.]: Photographic Services, University of Illinois, U of I Library, [1987]. 2 microfiches (78 frames): negative

    Attentional-shaping as a means to improve emotion perception deficits in schizophrenia

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    Inability to recognize emotional expressions of others (emotion perception) is one of the most common impairments observed among individuals with schizophrenia. Such deficits presumably contribute much to the social dysfunction characteristic of schizophrenia. This study examined the efficacy of a novel attentional-shaping intervention to improve emotion perception abilities. Sixty participants with schizophrenia were randomly assigned to one of three intervention conditions: 1) attentional-shaping, 2) contingent monetary reinforcement, or 3) repeated practice. Participants completed the Face Emotion Identification Test (FEIT) at pre-test, intervention, post-test, and one week follow-up. Participants also completed the Bell-Lysaker Emotion Recognition Test (BLERT) and the Social Behavior Scale at pre-test and follow-up to measure generalization

    Discovery and implementation of transcriptional biomarkers of synthetic LXR agonists in peripheral blood cells

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    <p>Abstract</p> <p>Background</p> <p>LXRs (Liver X Receptor α and β) are nuclear receptors that act as ligand-activated transcription factors. LXR activation causes upregulation of genes involved in reverse cholesterol transport (RCT), including ABCA1 and ABCG1 transporters, in macrophage and intestine. Anti-atherosclerotic effects of synthetic LXR agonists in murine models suggest clinical utility for such compounds.</p> <p>Objective</p> <p>Blood markers of LXR agonist exposure/activity were sought to support clinical development of novel synthetic LXR modulators.</p> <p>Methods</p> <p>Transcript levels of LXR target genes ABCA1 and ABCG1 were measured using quantitative reverse transcriptase/polymerase chain reaction assays (qRT-PCR) in peripheral blood from mice and rats (following a single oral dose) and monkeys (following 7 daily oral doses) of synthetic LXR agonists. LXRα, LXRβ, ABCA1, and ABCG1 mRNA were measured by qRT-PCR in human peripheral blood mononuclear cells (PBMC), monocytes, T- and B-cells treated <it>ex vivo </it>with WAY-252623 (LXR-623), and protein levels in human PBMC were measured by Western blotting. ABCA1/G1 transcript levels in whole-blood RNA were measured using analytically validated assays in human subjects participating in a Phase 1 SAD (Single Ascending Dose) clinical study of LXR-623.</p> <p>Results</p> <p>A single oral dose of LXR agonists induced ABCA1 and ABCG1 transcription in rodent peripheral blood in a dose- and time-dependent manner. Induction of gene expression in rat peripheral blood correlated with spleen expression, suggesting LXR gene regulation in blood has the potential to function as a marker of tissue gene regulation. Transcriptional response to LXR agonist was confirmed in primates, where peripheral blood ABCA1 and ABCG1 levels increased in a dose-dependent manner following oral treatment with LXR-623. Human PBMC, monocytes, T- and B cells all expressed both LXRα and LXRβ, and all cell types significantly increased ABCA1 and ABCG1 expression upon <it>ex vivo </it>LXR-623 treatment. Peripheral blood from a representative human subject receiving a single oral dose of LXR-623 showed significant time-dependent increases in ABCA1 and ABCG1 transcription.</p> <p>Conclusion</p> <p>Peripheral blood cells express LXRα and LXRβ, and respond to LXR agonist treatment by time- and dose-dependently inducing LXR target genes. Transcript levels of LXR target genes in peripheral blood are relevant and useful biological indicators for clinical development of synthetic LXR modulators.</p

    The lncRNA CASC15 regulates SOX4 expression in RUNX1-rearranged acute leukemia

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    Abstract Background Long non-coding RNAs (lncRNAs) play a variety of cellular roles, including regulation of transcription and translation, leading to alterations in gene expression. Some lncRNAs modulate the expression of chromosomally adjacent genes. Here, we assess the roles of the lncRNA CASC15 in regulation of a chromosomally nearby gene, SOX4, and its function in RUNX1/AML translocated leukemia. Results CASC15 is a conserved lncRNA that was upregulated in pediatric B-acute lymphoblastic leukemia (B-ALL) with t (12; 21) as well as pediatric acute myeloid leukemia (AML) with t (8; 21), both of which are associated with relatively better prognosis. Enforced expression of CASC15 led to a myeloid bias in development, and overall, decreased engraftment and colony formation. At the cellular level, CASC15 regulated cellular survival, proliferation, and the expression of its chromosomally adjacent gene, SOX4. Differentially regulated genes following CASC15 knockdown were enriched for predicted transcriptional targets of the Yin and Yang-1 (YY1) transcription factor. Interestingly, we found that CASC15 enhances YY1-mediated regulation of the SOX4 promoter. Conclusions Our findings represent the first characterization of this CASC15 in RUNX1-translocated leukemia, and point towards a mechanistic basis for its action

    Stressor- and Corticotropin releasing Factor-induced Reinstatement and Active Stress-related Behavioral Responses are Augmented Following Long-access Cocaine Self-administration by Rats

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    Rationale Stressful events during periods of drug abstinence likely contribute to relapse in cocaine-dependent individuals. Excessive cocaine use may increase susceptibility to stressor-induced relapse through alterations in brain corticotropin-releasing factor (CRF) responsiveness. Objectives This study examined stressor- and CRF-induced cocaine seeking and other stress-related behaviors in rats with different histories of cocaine self-administration (SA). Materials and methods Rats self-administered cocaine under short-access (ShA; 2 h daily) or long-access (LgA; 6 h daily) conditions for 14 days or were provided access to saline and were tested for reinstatement by a stressor (electric footshock), cocaine or an icv injection of CRF and for behavioral responsiveness on the elevated plus maze, in a novel environment and in the light–dark box after a 14- to 17-day extinction/withdrawal period. Results LgA rats showed escalating patterns of cocaine SA and were more susceptible to reinstatement by cocaine, EFS, or icv CRF than ShA rats. Overall, cocaine SA increased activity in the center field of a novel environment, on the open arms of the elevated plus maze, and in the light compartment of a light–dark box. In most cases, the effects of cocaine SA were dependent on the pattern/amount of cocaine intake with statistically significant differences from saline self-administering controls only observed in LgA rats. Conclusions When examined after several weeks of extinction/ withdrawal, cocaine SA promotes a more active pattern of behavior during times of stress that is associated with a heightened susceptibility to stressor-induced cocaine-seeking behavior and may be the consequence of augmented CRF regulation of addiction-related neurocircuitry

    Activation of superior colliculi in humans during visual exploration

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    <p>Abstract</p> <p>Background</p> <p>Visual, oculomotor, and – recently – cognitive functions of the superior colliculi (SC) have been documented in detail in non-human primates in the past. Evidence for corresponding functions of the SC in humans is still rare. We examined activity changes in the human tectum and the lateral geniculate nuclei (LGN) in a visual search task using functional magnetic resonance imaging (fMRI) and anatomically defined regions of interest (ROI). Healthy subjects conducted a free visual search task and two voluntary eye movement tasks with and without irrelevant visual distracters. Blood oxygen level dependent (BOLD) signals in the SC were compared to activity in the inferior colliculi (IC) and LGN.</p> <p>Results</p> <p>Neural activity increased during free exploration only in the SC in comparison to both control tasks. Saccade frequency did not exert a significant effect on BOLD signal changes. No corresponding differences between experimental tasks were found in the IC or the LGN. However, while the IC revealed no signal increase from the baseline, BOLD signal changes at the LGN were consistently positive in all experimental conditions.</p> <p>Conclusion</p> <p>Our data demonstrate the involvement of the SC in a visual search task. In contrast to the results of previous studies, signal changes could not be seen to be driven by either visual stimulation or oculomotor control on their own. Further, we can exclude the influence of any nearby neural structures (e.g. pulvinar, tegmentum) or of typical artefacts at the brainstem on the observed signal changes at the SC. Corresponding to findings in non-human primates, our data support a dependency of SC activity on functions beyond oculomotor control and visual processing.</p

    Absence of system xc⁻ on immune cells invading the central nervous system alleviates experimental autoimmune encephalitis

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    Background: Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS), leading to neurodegeneration and chronic disability. Accumulating evidence points to a key role for neuroinflammation, oxidative stress, and excitotoxicity in this degenerative process. System x(c)- or the cystine/glutamate antiporter could tie these pathological mechanisms together: its activity is enhanced by reactive oxygen species and inflammatory stimuli, and its enhancement might lead to the release of toxic amounts of glutamate, thereby triggering excitotoxicity and neurodegeneration. Methods: Semi-quantitative Western blotting served to study protein expression of xCT, the specific subunit of system x(c)-, as well as of regulators of xCT transcription, in the normal appearing white matter (NAWM) of MS patients and in the CNS and spleen of mice exposed to experimental autoimmune encephalomyelitis (EAE), an accepted mouse model of MS. We next compared the clinical course of the EAE disease, the extent of demyelination, the infiltration of immune cells and microglial activation in xCT-knockout (xCT(-/-)) mice and irradiated mice reconstituted in xCT(-/-) bone marrow (BM), to their proper wild type (xCT(+/+)) controls. Results: xCT protein expression levels were upregulated in the NAWM of MS patients and in the brain, spinal cord, and spleen of EAE mice. The pathways involved in this upregulation in NAWM of MS patients remain unresolved. Compared to xCT(+/+) mice, xCT(-/-) mice were equally susceptible to EAE, whereas mice transplanted with xCT(-/-) BM, and as such only exhibiting loss of xCT in their immune cells, were less susceptible to EAE. In none of the above-described conditions, demyelination, microglial activation, or infiltration of immune cells were affected. Conclusions: Our findings demonstrate enhancement of xCT protein expression in MS pathology and suggest that system x(c)- on immune cells invading the CNS participates to EAE. Since a total loss of system x(c)- had no net beneficial effects, these results have important implications for targeting system x(c)- for treatment of MS

    Standardized research protocols enable transdisciplinary research of climate variation impacts in corn production systems

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    The important questions about agriculture, climate, and sustainability have become increasingly complex and require a coordinated, multifaceted approach for developing new knowledge and understanding. A multistate, transdisciplinary project was begun in 2011 to study the potential for both mitigation and adaptation of corn-based cropping systems to climate variations. The team is measuring the baseline as well as change of the system\u27s carbon (C), nitrogen (N), and water footprints, crop productivity, and pest pressure in response to existing and novel production practices. Nine states and 11 institutions are participating in the project, necessitating a well thought out approach to coordinating field data collection procedures at 35 research sites. In addition, the collected data must be brought together in a way that can be stored and used by persons not originally involved in the data collection, necessitating robust procedures for linking metadata with the data and clearly delineated rules for use and publication of data from the overall project. In order to improve the ability to compare data across sites and begin to make inferences about soil and cropping system responses to climate across the region, detailed research protocols were developed to standardize the types of measurements taken and the specific details such as depth, time, method, numbers of samples, and minimum data set required from each site. This process required significant time, debate, and commitment of all the investigators involved with field data collection and was also informed by the data needed to run the simulation models and life cycle analyses. Although individual research teams are collecting additional measurements beyond those stated in the standardized protocols, the written protocols are used by the team for the base measurements to be compared across the region. A centralized database was constructed to meet the needs of current researchers on this project as well as for future use for data synthesis and modeling for agricultural, ecosystem, and climate sciences

    Developmental Shift of Cyclophilin D Contribution to Hypoxic-Ischemic Brain Injury

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    Cyclophilin D (CypD), a regulator of the mitochondrial membrane permeability transition pore (PTP), enhances Ca(2+)-induced mitochondrial permeabilization and cell death in the brain. However, the role of CypD in hypoxic-ischemic (HI) brain injury at different developmental ages is unknown. At postnatal day (P) 9 or P60, littermates of CypD-deficient [knock-out (KO)], wild-type (WT), and heterozygous mice were subjected to HI, and brain injury was evaluated 7 d after HI. CypD deficiency resulted in a significant reduction of HI brain injury at P60 but worsened injury at P9. After HI, caspase-dependent and -independent cell death pathways were more induced in P9 CypD KO mice than in WT controls, and apoptotic activation was minimal at P60. The PTP had a considerably higher induction threshold and lower sensitivity to cyclosporin A in neonatal versus adult mice. On the contrary, Bax inhibition markedly reduced caspase activation and brain injury in immature mice but was ineffective in the adult brain. Our findings suggest that CypD/PTP is critical for the development of brain injury in the adult, whereas Bax-dependent mechanisms prevail in the immature brain. The role of CypD in HI shifts from a predominantly prosurvival protein in the immature to a cell death mediator in the adult brain

    XIPE: the X-ray Imaging Polarimetry Explorer

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    X-ray polarimetry, sometimes alone, and sometimes coupled to spectral and temporal variability measurements and to imaging, allows a wealth of physical phenomena in astrophysics to be studied. X-ray polarimetry investigates the acceleration process, for example, including those typical of magnetic reconnection in solar flares, but also emission in the strong magnetic fields of neutron stars and white dwarfs. It detects scattering in asymmetric structures such as accretion disks and columns, and in the so-called molecular torus and ionization cones. In addition, it allows fundamental physics in regimes of gravity and of magnetic field intensity not accessible to experiments on the Earth to be probed. Finally, models that describe fundamental interactions (e.g. quantum gravity and the extension of the Standard Model) can be tested. We describe in this paper the X-ray Imaging Polarimetry Explorer (XIPE), proposed in June 2012 to the first ESA call for a small mission with a launch in 2017 but not selected. XIPE is composed of two out of the three existing JET-X telescopes with two Gas Pixel Detectors (GPD) filled with a He-DME mixture at their focus and two additional GPDs filled with pressurized Ar-DME facing the sun. The Minimum Detectable Polarization is 14 % at 1 mCrab in 10E5 s (2-10 keV) and 0.6 % for an X10 class flare. The Half Energy Width, measured at PANTER X-ray test facility (MPE, Germany) with JET-X optics is 24 arcsec. XIPE takes advantage of a low-earth equatorial orbit with Malindi as down-link station and of a Mission Operation Center (MOC) at INPE (Brazil).Comment: 49 pages, 14 figures, 6 tables. Paper published in Experimental Astronomy http://link.springer.com/journal/1068
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