Frontiers

User Collection Public
UNC logo

UNC-authored articles published by Frontiers

Works (775)

View results as:
List List Masonry Masonry Slideshow Slideshow
Sort the listing of items  

591. Influence of host iron status on Plasmodium falciparum infection

Title Tesim:
Influence of host iron status on Plasmodium falciparum infection
Creator:
Clark, Martha A., Cerami, Carla, and Goheen, Morgan M.
Date of publication:
2014
Abstract Tesim:
Iron deficiency affects one quarter of the world's population and causes significant morbidity, including detrimental effects on immune function and cognitive development. Accordingly, the World Health Organization (WHO) recommends routine iron supplementation in children and adults in areas with a high prevalence of iron deficiency. However, a large body of clinical and epidemiological evidence has accumulated which clearly demonstrates that host iron deficiency is protective against falciparum malaria and that host iron supplementation may increase the risk of malaria. Although many effective antimalarial treatments and preventive measures are available, malaria remains a significant public health problem, in part because the mechanisms of malaria pathogenesis remain obscured by the complexity of the relationships that exist between parasite virulence factors, host susceptibility traits, and the immune responses that modulate disease. Here we review (i) the clinical and epidemiological data that describes the relationship between host iron status and malaria infection and (ii) the current understanding of the biological basis for these clinical and epidemiological observations.
Resource type:
Article
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/qg1y-9t20
Identifier:
PMID: 24834053, PMCID: PMC4018558, Onescience id: 6ec21acdefbc2979a3006d6e4e25645beac7614c, and Publisher DOI: https://doi.org/10.3389/fphar.2014.00084
ISSN:
1663-9812
Journal Title:
Frontiers in Pharmacology
Journal Volume:
5
Keyword:
iron supplementation, Iron, plasmodium falciparu, iron deficiency anemia, and Malaria
Language Label:
English
Person:
Clark, Martha A., Cerami, Carla, and Goheen, Morgan M.
Rights Statement Label:
In Copyright
Source:
4t64gv56d

592. Exploring BSEP inhibition-mediated toxicity with a mechanistic model of drug-induced liver injury

Title Tesim:
Exploring BSEP inhibition-mediated toxicity with a mechanistic model of drug-induced liver injury
Creator:
Siler, Scott Q., Barton, Hugh A., Watkins, Paul B., Yang, Kyunghee, Brouwer, Kim L. R., Woodhead, Jeffrey L., and Howell, Brett A.
Date of publication:
2014
Abstract Tesim:
Inhibition of the bile salt export pump (BSEP) has been linked to incidence of drug-induced liver injury (DILI), presumably by the accumulation of toxic bile acids in the liver. We have previously constructed and validated a model of bile acid disposition within DILIsym®, a mechanistic model of DILI. In this paper, we use DILIsym® to simulate the DILI response of the hepatotoxic BSEP inhibitors bosentan and CP-724,714 and the non-hepatotoxic BSEP inhibitor telmisartan in humans in order to explore whether we can predict that hepatotoxic BSEP inhibitors can cause bile acid accumulation to reach toxic levels. We also simulate bosentan in rats in order to illuminate potential reasons behind the lack of toxicity in rats compared to the toxicity observed in humans. DILIsym® predicts that bosentan, but not telmisartan, will cause mild hepatocellular ATP decline and serum ALT elevation in a simulated population of humans. The difference in hepatotoxic potential between bosentan and telmisartan is consistent with clinical observations. However, DILIsym® underpredicts the incidence of bosentan toxicity. DILIsym® also predicts that bosentan will not cause toxicity in a simulated population of rats, and that the difference between the response to bosentan in rats and in humans is primarily due to the less toxic bile acid pool in rats. Our simulations also suggest a potential synergistic role for bile acid accumulation and mitochondrial electron transport chain (ETC) inhibition in producing the observed toxicity in CP-724,714, and suggest that CP-724,714 metabolites may also play a role in the observed toxicity. Our work also compares the impact of competitive and noncompetitive BSEP inhibition for CP-724,714 and demonstrates that noncompetitive inhibition leads to much greater bile acid accumulation and potential toxicity. Our research demonstrates the potential for mechanistic modeling to contribute to the understanding of how bile acid transport inhibitors cause DILI.
Resource type:
Article
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/919x-mc77
Identifier:
PMID: 25426072, PMCID: PMC4224072, Publisher DOI: https://doi.org/10.3389/fphar.2014.00240, and Onescience id: 22985988118a977f7f6fa6d6af3c43f9ed5db0b9
ISSN:
1663-9812
Journal Title:
Frontiers in Pharmacology
Journal Volume:
5
Keyword:
BSEP inhibition, CP-724, bosentan, population variability, mechanistic modeling, bile acids and salts, drug-induced liver injury, and 714
Language Label:
English
Person:
Siler, Scott Q., Barton, Hugh A., Watkins, Paul B., Yang, Kyunghee, Brouwer, Kim L. R., Woodhead, Jeffrey L., and Howell, Brett A.
Rights Statement Label:
In Copyright
Source:
xw42ng03d

593. Flavonol-rich dark cocoa significantly decreases plasma endothelin-1 and improves cognition in urban children

Title Tesim:
Flavonol-rich dark cocoa significantly decreases plasma endothelin-1 and improves cognition in urban children
Creator:
Zhu, Hongtu, Solorio, Edelmira, Medina-Cortina, Humberto, Chao, Chih-kai, Mora-Tiscareño, Antonieta, Cross, Janet V., D'Angiulli, Amedeo, Engle, Randall, Gómez-Garza, Gilberto, Mukherjee, Partha S., Torres-Jardón, Ricardo, Ferreira-Azevedo, Lara, Jewells, Valerie, Franco-Lira, Maricela, Calderón-Garcidueñas, Lilian, and Aragón-Flores, Mariana
Date of publication:
2013
Abstract Tesim:
Air pollution exposures are linked to systemic inflammation, cardiovascular and respiratory morbidity and mortality, neuroinflammation and neuropathology in young urbanites. In particular, most Mexico City Metropolitan Area (MCMA) children exhibit subtle cognitive deficits, and neuropathology studies show 40% of them exhibiting frontal tau hyperphosphorylation and 51% amyloid-β diffuse plaques (compared to 0% in low pollution control children). We assessed whether a short cocoa intervention can be effective in decreasing plasma endothelin 1 (ET-1) and/or inflammatory mediators in MCMA children. Thirty gram of dark cocoa with 680 mg of total flavonols were given daily for 10.11 ± 3.4 days (range 9–24 days) to 18 children (10.55 years, SD = 1.45; 11F/7M). Key metabolite ratios in frontal white matter and in hippocampus pre and during cocoa intervention were quantified by magnetic resonance spectroscopy. ET-1 significantly decreased after cocoa treatment (p = 0.0002). Fifteen children (83%) showed a marginally significant individual improvement in one or both of the applied simple short memory tasks. Endothelial dysfunction is a key feature of exposure to particulate matter (PM) and decreased endothelin-1 bioavailability is likely useful for brain function in the context of air pollution. Our findings suggest that cocoa interventions may be critical for early implementation of neuroprotection of highly exposed urban children. Multi-domain nutraceutical interventions could limit the risk for endothelial dysfunction, cerebral hypoperfusion, neuroinflammation, cognitive deficits, structural volumetric detrimental brain effects, and the early development of the neuropathological hallmarks of Alzheimer's and Parkinson's diseases.
Resource type:
Article
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/hz8k-zf86
Identifier:
PMID: 23986703, PMCID: PMC3749371, Publisher DOI: https://doi.org/10.3389/fphar.2013.00104, and Onescience id: d96ee0a3c153c92823dba208e3d52afe7e3d54b0
ISSN:
1663-9812
Journal Title:
Frontiers in Pharmacology
Journal Volume:
4
Keyword:
Amyloid, Cities, Air, Morbidity, Alzheimer’s and Parkinson’s disease risk, Endothelin-1, Brain, Cognition, Risk, Theobroma cacao, Fine Particulate Matter, Air Pollution, Children, Parkinson Disease, Inflammation, Biological Availability, Particulate Matter, Magnetic Resonance Spectroscopy, Therapeutics, Cocoa, Hippocampus, Flavonols, Plasma, Mortality, White Matter, and Homo sapiens
Language Label:
English
Person:
Zhu, Hongtu, Solorio, Edelmira, Medina-Cortina, Humberto, Chao, Chih-kai, Mora-Tiscareño, Antonieta, Cross, Janet V., D'Angiulli, Amedeo, Engle, Randall, Gómez-Garza, Gilberto, Mukherjee, Partha S., Torres-Jardón, Ricardo, Ferreira-Azevedo, Lara, Jewells, Valerie, Franco-Lira, Maricela, Calderón-Garcidueñas, Lilian, and Aragón-Flores, Mariana
Rights Statement Label:
In Copyright
Source:
3t945z13z

594. Chronic Administration of a Leupeptin-Derived Calpain Inhibitor Fails to Ameliorate Severe Muscle Pathology in a Canine Model of Duchenne Muscular Dystrophy

Title Tesim:
Chronic Administration of a Leupeptin-Derived Calpain Inhibitor Fails to Ameliorate Severe Muscle Pathology in a Canine Model of Duchenne Muscular Dystrophy
Creator:
Grange, Robert W., Greiner, Hansel, Bogan, Daniel J., Kornegay, Joe N., Childers, Martin K., Bogan, Janet R., and Holder, Melanie
Date of publication:
2012
Abstract Tesim:
Calpains likely play a role in the pathogenesis of Duchenne muscular dystrophy (DMD). Accordingly, calpain inhibition may provide therapeutic benefit to DMD patients. In the present study, we sought to measure benefit from administration of a novel calpain inhibitor, C101, in a canine muscular dystrophy model. Specifically, we tested the hypothesis that treatment with C101 mitigates progressive weakness and severe muscle pathology observed in young dogs with golden retriever muscular dystrophy (GRMD). Young (6-week-old) GRMD dogs were treated daily with either C101 (17 mg/kg twice daily oral dose, n = 9) or placebo (vehicle only, n = 7) for 8 weeks. A battery of functional tests, including tibiotarsal joint angle, muscle/fat composition, and pelvic limb muscle strength were performed at baseline and every 2 weeks during the 8-week study. Results indicate that C101-treated GRMD dogs maintained strength in their cranial pelvic limb muscles (tibiotarsal flexors) while placebo-treated dogs progressively lost strength. However, concomitant improvement was not observed in posterior pelvic limb muscles (tibiotarsal extensors). C101 treatment did not mitigate force drop following repeated eccentric contractions and no improvement was seen in the development of joint contractures, lean muscle mass, or muscle histopathology. Taken together, these data do not support the hypothesis that treatment with C101 mitigates progressive weakness or ameliorates severe muscle pathology observed in young dogs with GRMD.
Resource type:
Article
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/4qg7-ha07
Identifier:
PMID: 22291646, Onescience id: c443361cbe68f0933155825fa550f78dc3d6fba8, Publisher DOI: https://doi.org/10.3389/fphar.2011.00089, and PMCID: PMC3253583
ISSN:
1663-9812
Journal Title:
Frontiers in Pharmacology
Journal Volume:
2
Keyword:
calpain, skeletal muscle, muscular dystrophy, canine, protease, and animal
Language Label:
English
Person:
Grange, Robert W., Greiner, Hansel, Bogan, Daniel J., Kornegay, Joe N., Childers, Martin K., Bogan, Janet R., and Holder, Melanie
Rights Statement Label:
In Copyright
Source:
dn39x795x

595. Reducing Auditory Hypersensitivities in Autistic Spectrum Disorder: Preliminary Findings Evaluating the Listening Project Protocol

Title Tesim:
Reducing Auditory Hypersensitivities in Autistic Spectrum Disorder: Preliminary Findings Evaluating the Listening Project Protocol
Creator:
Cook, Edwin H., Porges, Stephen W., Lewis, Gregory F., Bazhenova, Olga V., Sorokin, Yevgeniya, Carlson, Nancy, Heilman, Keri J., and Bal, Elgiz
Date of publication:
2014
Abstract Tesim:
Auditory hypersensitivities are a common feature of autism spectrum disorder (ASD). In the present study, the effectiveness of a novel intervention, the listening project protocol (LPP), was evaluated in two trials conducted with children diagnosed with ASD. LPP was developed to reduce auditory hypersensitivities. LPP is based on a theoretical “neural exercise” model that uses computer altered acoustic stimulation to recruit the neural regulation of middle ear muscles. Features of the intervention stimuli were informed by basic research in speech and hearing sciences that has identified the specific acoustic frequencies necessary to understand speech, which must pass through middle ear structures before being processed by other components of the auditory system. LPP was hypothesized to reduce auditory hypersensitivities by increasing the neural tone to the middle ear muscles to functionally dampen competing sounds in frequencies lower than human speech. The trials demonstrated that LPP, when contrasted to control conditions, selectively reduced auditory hypersensitivities. These findings are consistent with the polyvagal theory, which emphasizes the role of the middle ear muscles in social communication.
Resource type:
Article
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/f21k-v162
Identifier:
PMID: 25136545, PMCID: PMC4117928, Publisher DOI: https://doi.org/10.3389/fped.2014.00080, and Onescience id: 99fe75c178dae2758404616ad285fb909d427526
ISSN:
2296-2360
Journal Title:
Frontiers in Pediatrics
Journal Volume:
2
Keyword:
auditory hypersensitivities, polyvagal theory, autism, listening, and social engagement behaviors
Language Label:
English
Person:
Cook, Edwin H., Porges, Stephen W., Lewis, Gregory F., Bazhenova, Olga V., Sorokin, Yevgeniya, Carlson, Nancy, Heilman, Keri J., and Bal, Elgiz
Rights Statement Label:
In Copyright
Source:
n870zz44m

596. Robust estimation of group-wise cortical correspondence with an application to macaque and human neuroimaging studies

Title Tesim:
Robust estimation of group-wise cortical correspondence with an application to macaque and human neuroimaging studies
Creator:
Yoo, Sang W., Shi, Yundi, Kim, Sun H., Niethammer, Marc, Styner, Martin A., Seong, Joon-Kyung, Evans, Alan, Sanchez, Mar, and Lyu, Ilwoo
Date of publication:
2015
Abstract Tesim:
We present a novel group-wise registration method for cortical correspondence for local cortical thickness analysis in human and non-human primate neuroimaging studies. The proposed method is based on our earlier template based registration that estimates a continuous, smooth deformation field via sulcal curve-constrained registration employing spherical harmonic decomposition of the deformation field. This pairwise registration though results in a well-known template selection bias, which we aim to overcome here via a group-wise approach. We propose the use of an unbiased ensemble entropy minimization following the use of the pairwise registration as an initialization. An individual deformation field is then iteratively updated onto the unbiased average. For the optimization, we use metrics specific for cortical correspondence though all of these are straightforwardly extendable to the generic setting: The first focused on optimizing the correspondence of automatically extracted sulcal landmarks and the second on that of sulcal depth property maps. We further propose a robust entropy metric and a hierarchical optimization by employing spherical harmonic basis orthogonality. We also provide the detailed methodological description of both our earlier work and the proposed method with a set of experiments on a population of human and non-human primate subjects. In the experiment, we have shown that our method achieves superior results on consistency through quantitative and visual comparisons as compared to the existing methods.
Resource type:
Article
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/6sg1-xv43
Identifier:
Publisher DOI: https://doi.org/10.3389/fnins.2015.00210, PMCID: PMC4462677, Onescience id: 4f574bff5c5bffd43cbe6f395c6100eecf7f5ec2, and PMID: 26113807
ISSN:
1662-453X and 1662-4548
Journal Title:
Frontiers in Neuroscience
Journal Volume:
9
Keyword:
sulcal curve, spherical harmonics, Group-wise registration, Entropy minimization, Surface Registration, and cortical surface
Language Label:
English
Person:
Yoo, Sang W., Shi, Yundi, Kim, Sun H., Niethammer, Marc, Styner, Martin A., Seong, Joon-Kyung, Evans, Alan, Sanchez, Mar, and Lyu, Ilwoo
Rights Statement Label:
In Copyright
Source:
00000604b

597. Targeting central melanocortin receptors: a promising novel approach for treating alcohol abuse disorders

Title Tesim:
Targeting central melanocortin receptors: a promising novel approach for treating alcohol abuse disorders
Creator:
Navarro, Montserrat, Thiele, Todd E., and Olney, Jeffrey J.
Date of publication:
2014
Abstract Tesim:
The melanocortin (MC) peptides are produced centrally by propiomelanocortin (POMC) neurons within the arcuate nucleus of the hypothalamus and act through five seven-transmembrane G-protein coupled melanocortin receptor (MCR) subtypes. The MC3R and MC4R subtypes, the most abundant central MCRs, are widely expressed in brain regions known to modulate neurobiological responses to ethanol, including regions of the hypothalamus and extended amygdala. Agouti-related protein (AgRP), also produced in the arcuate nucleus, is secreted in terminals expressing MCRs and functions as an endogenous MCR antagonist. This review highlights recent genetic and pharmacological findings that have implicated roles for the MC and AgRP systems in modulating ethanol consumption. Ethanol consumption is associated with significant alterations in the expression levels of various MC peptides/protein, which suggests that ethanol-induced perturbations of MC/AgRP signaling may modulate excessive ethanol intake. Consistently, MCR agonists decrease, and AgRP increases, ethanol consumption in mice. MCR agonists fail to blunt ethanol intake in mutant mice lacking the MC4R, suggesting that the protective effects of MCR agonists are modulated by the MC4R. Interestingly, recent evidence reveals that MCR agonists are more effective at blunting binge-like ethanol intake in mutant mice lacking the MC3R, suggesting that the MC3R has opposing effects on the MC4R. Finally, mutant mice lacking AgRP exhibit blunted voluntary and binge-like ethanol drinking, consistent with pharmacological studies. Collectively, these preclinical observations provide compelling evidence that compounds that target the MC system may provide therapeutic value for treating alcohol abuse disorders and that the utilization of currently available MC-targeting compounds- such as those being used to treat eating disorders- may be used as effective treatments to this end.
Resource type:
Article
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/smy7-j586
Identifier:
Onescience id: d8b910ee1fa050821c3a9217894b07158dd67724, Publisher DOI: https://doi.org/10.3389/fnins.2014.00128, PMID: 24917782, and PMCID: PMC4042890
ISSN:
1662-453X and 1662-4548
Journal Title:
Frontiers in Neuroscience
Journal Volume:
8
Keyword:
Brain, Arcuate Nucleus of Hypothalamus, Mus musculus, Neurons, Mc4r, Drinking, Agouti-Related Protein, Eating Disorders, AGRP, Proteins, AgRP, Therapeutics, Receptors, G-Protein-Coupled, MC4R, Mc3r, Ethanol, Agrp, melanocortin, Pomc, α-MSH, MC3R, Amygdala, Hypothalamus, Melanocortins, POMC, Receptors, Melanocortin, Peptides, and Alcoholism
Language Label:
English
Person:
Navarro, Montserrat, Thiele, Todd E., and Olney, Jeffrey J.
Rights Statement Label:
In Copyright
Source:
zc77sx60d

598. Individual differences in social information gathering revealed through Bayesian hierarchical models

Title Tesim:
Individual differences in social information gathering revealed through Bayesian hierarchical models
Creator:
Watson, Karli K., Ebitz, R. Becket, Platt, Michael L., Klein, Jeffrey T., and Pearson, John M.
Date of publication:
2013
Abstract Tesim:
As studies of the neural circuits underlying choice expand to include more complicated behaviors, analysis of behaviors elicited in laboratory paradigms has grown increasingly difficult. Social behaviors present a particular challenge, since inter- and intra-individual variation are expected to play key roles. However, due to limitations on data collection, studies must often choose between pooling data across all subjects or using individual subjects' data in isolation. Hierarchical models mediate between these two extremes by modeling individual subjects as drawn from a population distribution, allowing the population at large to serve as prior information about individuals' behavior. Here, we apply this method to data collected across multiple experimental sessions from a set of rhesus macaques performing a social information valuation task. We show that, while the values of social images vary markedly between individuals and between experimental sessions for the same individual, individuals also differentially value particular categories of social images. Furthermore, we demonstrate covariance between values for image categories within individuals and find evidence suggesting that magnitudes of stimulus values tend to diminish over time.
Resource type:
Article
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/6c93-5w33
Identifier:
Onescience id: b7412be4542eec1f9005f4441250f0f09e4ea448, PMCID: PMC3771214, Publisher DOI: https://doi.org/10.3389/fnins.2013.00165, and PMID: 24062635
ISSN:
1662-4548 and 1662-453X
Journal Title:
Frontiers in Neuroscience
Journal Volume:
7
Keyword:
foraging, pay-per-view, information foraging, Bayesian Models, and social neuroscience
Language Label:
English
Person:
Watson, Karli K., Ebitz, R. Becket, Platt, Michael L., Klein, Jeffrey T., and Pearson, John M.
Rights Statement Label:
In Copyright
Source:
s7526k777

599. Brain immune interactions and air pollution: macrophage inhibitory factor (MIF), prion cellular protein (PrPC), Interleukin-6 (IL-6), interleukin 1 receptor antagonist (IL-1Ra), and interleukin-2 (IL-2) in cerebrospinal fluid and MIF in serum differentiate urban children exposed to severe vs. low air pollution

Title Tesim:
Brain immune interactions and air pollution: macrophage inhibitory factor (MIF), prion cellular protein (PrPC), Interleukin-6 (IL-6), interleukin 1 receptor antagonist (IL-1Ra), and interleukin-2 (IL-2) in cerebrospinal fluid and MIF in serum differentiate urban children exposed to severe vs. low air pollution
Creator:
Chang, Jing, Zhu, Hongtu, Torres-Jardón, Ricardo, Aragón-Flores, Mariana, Thompson, Charles, Chao, Chih-kai, D'Angiulli, Amedeo, Franco-Lira, Maricela, Calderón-Garcidueñas, Lilian, Kavanaugh, Michael, and Cross, Janet V.
Date of publication:
2013
Abstract Tesim:
Mexico City Metropolitan Area children chronically exposed to high concentrations of air pollutants exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, innate and adaptive immune responses along with accumulation of misfolded proteins observed in the early stages of Alzheimer and Parkinson's diseases. A complex modulation of serum cytokines and chemokines influences children's brain structural and gray/white matter volumetric responses to air pollution. The search for biomarkers associating systemic and CNS inflammation to brain growth and cognitive deficits in the short term and neurodegeneration in the long-term is our principal aim. We explored and compared a profile of cytokines, chemokines (Multiplexing LASER Bead Technology) and Cellular prion protein (PrPC) in normal cerebro-spinal-fluid (CSF) of urban children with high vs. low air pollution exposures. PrPC and macrophage inhibitory factor (MIF) were also measured in serum. Samples from 139 children ages 11.91 ± 4.2 years were measured. Highly exposed children exhibited significant increases in CSF MIF (p = 0.002), IL6 (p = 0.006), IL1ra (p = 0.014), IL-2 (p = 0.04), and PrPC (p = 0.039) vs. controls. MIF serum concentrations were higher in exposed children (p = 0.009). Our results suggest CSF as a MIF, IL6, IL1Ra, IL-2, and PrPC compartment that can possibly differentiate air pollution exposures in children. MIF, a key neuro-immune mediator, is a potential biomarker bridge to identify children with CNS inflammation. Fine tuning of immune-to-brain communication is crucial to neural networks appropriate functioning, thus the short and long term effects of systemic inflammation and dysregulated neural immune responses are of deep concern for millions of exposed children. Defining the linkage and the health consequences of the brain / immune system interactions in the developing brain chronically exposed to air pollutants ought to be of pressing importance for public health.
Resource type:
Article
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/yf7g-xc18
Identifier:
PMCID: PMC3794301, Publisher DOI: https://doi.org/10.3389/fnins.2013.00183, PMID: 24133408, and Onescience id: bd61be773f3d2cc47e4fc1155a9f798c61d050e8
ISSN:
1662-453X and 1662-4548
Journal Title:
Frontiers in Neuroscience
Journal Volume:
7
Keyword:
Serum, Parkinson Disease, Receptors, Interleukin-1, Brain, Chemokines, Biological Markers, IL2, Immune System, Interleukin-6, Prions, Proteins, IL1RN, Cytokines, Growth, Interleukin-2, IL6, PRNP, Protein C, Cerebrospinal Fluid, Adaptive Immunity, Air Pollutants, Genes, White Matter, Interleukin 1 Receptor Antagonist Protein, Cities, Macrophages, and Inflammation
Language Label:
English
Person:
Chang, Jing, Zhu, Hongtu, Torres-Jardón, Ricardo, Aragón-Flores, Mariana, Thompson, Charles, Chao, Chih-kai, D'Angiulli, Amedeo, Franco-Lira, Maricela, Calderón-Garcidueñas, Lilian, Kavanaugh, Michael, and Cross, Janet V.
Rights Statement Label:
In Copyright
Source:
47429g81z

600. A multi-site resting state fMRI study on the amplitude of low frequency fluctuations in schizophrenia

Title Tesim:
A multi-site resting state fMRI study on the amplitude of low frequency fluctuations in schizophrenia
Creator:
Turner, Jessica A
Date of publication:
2013
Abstract Tesim:
Background: This multi-site study compares resting state fMRI amplitude of low frequency fluctuations (ALFF) and fractional ALFF (fALFF) between patients with schizophrenia (SZ) and healthy controls (HC).Methods: Eyes-closed resting fMRI scans (5:38 min; n = 306, 146 SZ) were collected from 6 Siemens 3T scanners and one GE 3T scanner. Imaging data were pre-processed using an SPM pipeline. Power in the low frequency band (0.01–0.08 Hz) was calculated both for the original pre-processed data as well as for the pre-processed data after regressing out the six rigid-body motion parameters, mean white matter (WM) and cerebral spinal fluid (CSF) signals. Both original and regressed ALFF and fALFF measures were modeled with site, diagnosis, age, and diagnosis × age interactions.Results: Regressing out motion and non-gray matter signals significantly decreased fALFF throughout the brain as well as ALFF in the cortical edge, but significantly increased ALFF in subcortical regions. Regression had little effect on site, age, and diagnosis effects on ALFF, other than to reduce diagnosis effects in subcortical regions. There were significant effects of site across the brain in all the analyses, largely due to vendor differences. HC showed greater ALFF in the occipital, posterior parietal, and superior temporal lobe, while SZ showed smaller clusters of greater ALFF in the frontal and temporal/insular regions as well as in the caudate, putamen, and hippocampus. HC showed greater fALFF compared with SZ in all regions, though subcortical differences were only significant for original fALFF.Conclusions: SZ show greater eyes-closed resting state low frequency power in frontal cortex, and less power in posterior lobes than do HC; fALFF, however, is lower in SZ than HC throughout the cortex. These effects are robust to multi-site variability. Regressing out physiological noise signals significantly affects both total and fALFF measures, but does not affect the pattern of case/control differences.
Resource type:
Article
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/qnng-w562
Identifier:
PMID: 23964193, PMCID: PMC3737471, Onescience id: ce2ee538d9cc61e2c9919b8c3a7c54ea0fd2b990, and Publisher DOI: https://doi.org/10.3389/fnins.2013.00137
ISSN:
1662-453X and 1662-4548
Journal Title:
Frontiers in Neuroscience
Journal Volume:
7
Keyword:
multi-site study, LFO, Schizophrenia, ALFF, resting state fMRI, and effect size
Language Label:
English
Person:
Turner, Jessica A
Rights Statement Label:
In Copyright
Source:
3n2044934