242 research outputs found

    The Influence of Aid and Income on Persistence at a Small Private College

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    In the 1990s, many private institutions gave up the practice of making need-blind admission decisions and stopped aiding students to the full extent of their need

    Effects of Music on Physiological Response

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    For this study the heart rates of twenty-two members of a college-level music appreciation class were recorded while students listened to the first movement of Beethoven's fifth symphony. The measurements were taken at three different times over a six-week period before, during, and after experimental treatment. Experimental treatment consisted of either audiotutorial tapes or repetitive listening sessions devised for specific musical-ability groups. The same test music was used throughout the entire study to determine the effects of learning and repetitive exposure on heart rate response. A control group had no further exposure to the test music during the study. Stable segments of the test music provoked tachycardia (elevated heart rate) in the subjects, while alternating segments produced bradycardia (lowered heart rate). Heart rate response to music was found to be linked with the presence or absence of learning.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

    HX600, a synthetic agonist for RXR-Nurr1 heterodimer complex, prevents ischemia-induced neuronal damage

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    Ischemic stroke is amongst the leading causes of death and disabilities. The available treatments are suitable for only a fraction of patients and thus novel therapies are urgently needed. Blockage of one of the cerebral arteries leads to massive and persisting inflammatory reaction contributing to the nearby neuronal damage. Targeting the detrimental pathways of neuroinflammation has been suggested to be beneficial in conditions of ischemic stroke. Nuclear receptor 4A-family (NR4A) member Nurr1 has been shown to be a potent modulator of harmful inflammatory reactions, yet the role of Nurr1 in cerebral stroke remains unknown. Here we show for the first time that an agonist for the dimeric transcription factor Nurr1/retinoid X receptor (RXR), HX600, reduces microglia expressed proinflammatory mediators and prevents inflammation induced neuronal death in in vitro co-culture model of neurons and microglia. Importantly, HX600 was protective in a mouse model of permanent middle cerebral artery occlusion and alleviated the stroke induced motor deficits. Along with the anti-inflammatory capacity of HX600 in vitro, treatment of ischemic mice with HX600 reduced ischemia induced Iba-1, p38 and TREM2 immunoreactivities, protected endogenous microglia from ischemia induced death and prevented leukocyte infiltration. These anti-inflammatory functions were associated with reduced levels of brain lysophosphatidylcholines (lysoPCs) and acylcarnitines, metabolites related to proinflammatory events. These data demonstrate that HX600 driven Nurr1 activation is beneficial in ischemic stroke and propose that targeting Nurr1 is a novel candidate for conditions involving neuroinflammatory component.Peer reviewe

    CNS-Native Myeloid Cells Drive Immune Suppression in the Brain Metastatic Niche through Cxcl10

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    Brain metastasis (br-met) develops in an immunologically unique br-met niche. Central nervous system-native myeloid cells (CNS-myeloids) and bone-marrow-derived myeloid cells (BMDMs) cooperatively regulate brain immunity. The phenotypic heterogeneity and specific roles of these myeloid subsets in shaping the br-met niche to regulate br-met outgrowth have not been fully revealed. Applying multimodal single-cell analyses, we elucidated a heterogeneous but spatially defined CNS-myeloid response during br-met outgrowth. We found Ccr2+ BMDMs minimally influenced br-met while CNS-myeloid promoted br-met outgrowth. Additionally, br-met-associated CNS-myeloid exhibited downregulation of Cx3cr1. Cx3cr1 knockout in CNS-myeloid increased br-met incidence, leading to an enriched interferon response signature and Cxcl10 upregulation. Significantly, neutralization of Cxcl10 reduced br-met, while rCxcl10 increased br-met and recruited VISTAHi PD-L1+ CNS-myeloid to br-met lesions. Inhibiting VISTA- and PD-L1-signaling relieved immune suppression and reduced br-met burden. Our results demonstrate that loss of Cx3cr1 in CNS-myeloid triggers a Cxcl10-mediated vicious cycle, cultivating a br-met-promoting, immune-suppressive niche

    Air pollution exposure during critical time periods in gestation and alterations in cord blood lymphocyte distribution: a cohort of livebirths

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    <p>Abstract</p> <p>Background</p> <p>Toxic exposures have been shown to influence maturation of the immune system during gestation. This study investigates the association between cord blood lymphocyte proportions and maternal exposure to air pollution during each gestational month.</p> <p>Methods</p> <p>Cord blood was analyzed using a FACSort flow cytometer to determine proportions of T lymphocytes (CD3<sup>+ </sup>cells and their subsets, CD4<sup>+ </sup>and CD8<sup>+</sup>), B lymphocytes (CD19<sup>+</sup>) and natural killer (NK) cells. Ambient air concentrations of 12 polycyclic aromatic hydrocarbons (PAH) and particulate matter < 2.5 micrometer in diameter (PM<sub>2.5</sub>) were measured using fixed site monitors. Arithmetic means of these pollutants, calculated for each gestational month, were used as exposure metrics. Data on covariates were obtained from medical records and questionnaires. Multivariable linear regression models were fitted to estimate associations between monthly PAH or PM<sub>2.5 </sub>and cord blood lymphocytes, adjusting for year of birth and district of residence and, in further models, gestational season and number of prior live births.</p> <p>Results</p> <p>The adjusted models show significant associations between PAHs or PM<sub>2.5 </sub>during early gestation and increases in CD3<sup>+ </sup>and CD4<sup>+ </sup>lymphocytes percentages and decreases in CD19<sup>+ </sup>and NK cell percentages in cord blood. In contrast, exposures during late gestation were associated with decreases in CD3<sup>+ </sup>and CD4<sup>+ </sup>fractions and increases in CD19<sup>+ </sup>and NK cell fractions. There was no significant association between alterations in lymphocyte distribution and air pollution exposure during the mid gestation.</p> <p>Conclusions</p> <p>PAHs and PM<sub>2.5 </sub>in ambient air may influence fetal immune development via shifts in cord blood lymphocytes distributions. Associations appear to differ by exposure in early versus late gestation.</p

    Non-Steroidal Anti-Inflammatory Drugs and Cognitive Function: Are Prostaglandins at the Heart of Cognitive Impairment in Dementia and Delirium ?

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    Studies of non-steroidal anti-inflammatory drugs (NSAIDs) in rheumatoid arthritis imply that inflammation is important in the development of Alzheimer’s disease (AD). However, these drugs have not alleviated the symptoms of AD in those who have already developed dementia. This suggests that the primary mediator targeted by these drugs, PGE2, is not actively suppressing memory function in AD. Amyloid-β oligomers appear to be important for the mild cognitive changes seen in AD transgenic mice, yet amyloid immunotherapy has also proven unsuccessful in clinical trials. Collectively, these findings indicate that NSAIDs may target a prodromal process in mice that has already passed in those diagnosed with AD, and that synaptic and neuronal loss are key determinants of cognitive dysfunction in AD. While the role of inflammation has not yet become clear, inflammatory processes definitely have a negative impact on cognitive function during episodes of delirium during dementia. Delirium is an acute and profound impairment of cognitive function frequently occurring in aged and demented patients exposed to systemic inflammatory insults, which is now recognised to contribute to long-term cognitive decline. Recent work in animal models is beginning to shed light on the interactions between systemic inflammation and CNS pathology in these acute exacerbations of dementia. This review will assess the role of prostaglandin synthesis in the memory impairments observed in dementia and delirium and will examine the relative contribution of amyloid, synaptic and neuronal loss. We will also discuss how understanding the role of inflammatory mediators in delirious episodes will have major implications for ameliorating the rate of decline in the demented population

    The peroxisome: still a mysterious organelle

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    More than half a century of research on peroxisomes has revealed unique features of this ubiquitous subcellular organelle, which have often been in disagreement with existing dogmas in cell biology. About 50 peroxisomal enzymes have so far been identified, which contribute to several crucial metabolic processes such as β-oxidation of fatty acids, biosynthesis of ether phospholipids and metabolism of reactive oxygen species, and render peroxisomes indispensable for human health and development. It became obvious that peroxisomes are highly dynamic organelles that rapidly assemble, multiply and degrade in response to metabolic needs. However, many aspects of peroxisome biology are still mysterious. This review addresses recent exciting discoveries on the biogenesis, formation and degradation of peroxisomes, on peroxisomal dynamics and division, as well as on the interaction and cross talk of peroxisomes with other subcellular compartments. Furthermore, recent advances on the role of peroxisomes in medicine and in the identification of novel peroxisomal proteins are discussed

    From Wald to Savage: homo economicus becomes a Bayesian statistician

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    Bayesian rationality is the paradigm of rational behavior in neoclassical economics. A rational agent in an economic model is one who maximizes her subjective expected utility and consistently revises her beliefs according to Bayes’s rule. The paper raises the question of how, when and why this characterization of rationality came to be endorsed by mainstream economists. Though no definitive answer is provided, it is argued that the question is far from trivial and of great historiographic importance. The story begins with Abraham Wald’s behaviorist approach to statistics and culminates with Leonard J. Savage’s elaboration of subjective expected utility theory in his 1954 classic The Foundations of Statistics. It is the latter’s acknowledged fiasco to achieve its planned goal, the reinterpretation of traditional inferential techniques along subjectivist and behaviorist lines, which raises the puzzle of how a failed project in statistics could turn into such a tremendous hit in economics. A couple of tentative answers are also offered, involving the role of the consistency requirement in neoclassical analysis and the impact of the postwar transformation of US business schools
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