Browsing by Subject "Blood"

Now showing 1 - 10 of 17
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    Assessing Unequal Airborne Exposure to Lead Associated With Race in the USA
    (Wiley, 2023-07-24) Laidlaw, Mark A. S.; Mielke, Howard W.; Filippelli, Gabriel M.; Earth and Environmental Sciences, School of Science
    Recent research applied the United States Environmental Protection Agency's Chemical Speciation Network and Interagency Monitoring of Protected Visual Environments monitoring stations and observed that mean concentrations of atmospheric lead (Pb) in highly segregated counties are a factor of 5 higher than in well‐integrated counties and argument is made that regulation of existing airborne Pb emissions will reduce children's Pb exposure. We argue that one of the main sources of children's current Pb exposure is from resuspension of legacy Pb in soil dust and that the racial disparity of Pb exposure is associated with Pb‐contaminated community soils.
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    Association of Host and Microbial Species Diversity across Spatial Scales in Desert Rodent Communities
    (PLOS (Public Library of Science), 2014-10-24) Gavish, Yoni; Kedem, Hadar; Messika, Irit; Cohen, Carmit; Toh, Evelyn; Munro, Daniel; Dong, Qunfeng; Fuqua, Clay; Clay, Keith; Hawlena, Hadas; Department of Microbiology & Immunology, School of Medicine
    Relationships between host and microbial diversity have important ecological and applied implications. Theory predicts that these relationships will depend on the spatio-temporal scale of the analysis and the niche breadth of the organisms in question, but representative data on host-microbial community assemblage in nature is lacking. We employed a natural gradient of rodent species richness and quantified bacterial communities in rodent blood at several hierarchical spatial scales to test the hypothesis that associations between host and microbial species diversity will be positive in communities dominated by organisms with broad niches sampled at large scales. Following pyrosequencing of rodent blood samples, bacterial communities were found to be comprised primarily of broad niche lineages. These communities exhibited positive correlations between host diversity, microbial diversity and the likelihood for rare pathogens at the regional scale but not at finer scales. These findings demonstrate how microbial diversity is affected by host diversity at different spatial scales and suggest that the relationships between host diversity and overall disease risk are not always negative, as the dilution hypothesis predicts.
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    Bleeding the laboratory mouse: Not all methods are equal
    (Elsevier, 2016-02) Hoggatt, Jonathan; Hoggatt, Amber F.; Tate, Tiffany A.; Fortman, Jeffrey; Pelus, Louis M.; Microbiology and Immunology, School of Medicine
    The laboratory mouse is the model most frequently used in hematologic studies and assessment of blood parameters across a broad range of disciplines. Often, analysis of blood occurs in a nonterminal manner. However, the small body size of the mouse limits collection based on volume, frequency, and accessible sites. Commonly used sites in the mouse include the retro-orbital sinus, facial vein, tail vein, saphenous vein, and heart. The method of blood acquisition varies considerably across laboratories and is often not reported in detail. In this study, we report significant alterations in blood parameters, particularly of total white blood cells, specific populations of dendritic cells and myeloid-derived suppressor cells, and hematopoietic progenitor cells, as a result of site and manner of sampling. Intriguingly, warming of mice prior to tail bleeding was found to significantly alter blood values. Our findings suggest that the same method should be used across an entire study, that mice should be warmed prior to tail bleeds to make levels uniform, and that accurate description of bleeding methods in publications should be provided to allow for interpretation of comparative reports and inter- and intralaboratory experimental variability.
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    Blood-based biomarkers for Alzheimer's disease
    (EMBO Press, 2022) Leuzy, Antoine; Mattsson-Carlgren, Niklas; Palmqvist, Sebastian; Janelidze, Shorena; Dage, Jeffrey L.; Hansson, Oskar; Neurology, School of Medicine
    Neurodegenerative disorders such as Alzheimer's disease (AD) represent a mounting public health challenge. As these diseases are difficult to diagnose clinically, biomarkers of underlying pathophysiology are playing an ever‐increasing role in research, clinical trials, and in the clinical work‐up of patients. Though cerebrospinal fluid (CSF) and positron emission tomography (PET)‐based measures are available, their use is not widespread due to limitations, including high costs and perceived invasiveness. As a result of rapid advances in the development of ultra‐sensitive assays, the levels of pathological brain‐ and AD‐related proteins can now be measured in blood, with recent work showing promising results. Plasma P‐tau appears to be the best candidate marker during symptomatic AD (i.e., prodromal AD and AD dementia) and preclinical AD when combined with Aβ42/Aβ40. Though not AD‐specific, blood NfL appears promising for the detection of neurodegeneration and could potentially be used to detect the effects of disease‐modifying therapies. This review provides an overview of the progress achieved thus far using AD blood‐based biomarkers, highlighting key areas of application and unmet challenges.
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    Combined reflectance spectroscopy and stochastic modeling approach for noninvasive hemoglobin determination via palpebral conjunctiva
    (Wiley, 2014-01-08) Kim, Oleg; McMurdy, John; Jay, Gregory; Lines, Collin; Crawford, Gregory; Alber, Mark; Medicine, School of Medicine
    A combination of stochastic photon propagation model in a multilayered human eyelid tissue and reflectance spectroscopy was used to study palpebral conjunctiva spectral reflectance for hemoglobin (Hgb) determination. The developed model is the first biologically relevant model of eyelid tissue, which was shown to provide very good approximation to the measured spectra. Tissue optical parameters were defined using previous histological and microscopy studies of a human eyelid. After calibration of the model parameters the responses of reflectance spectra to Hgb level and blood oxygenation variations were calculated. The stimulated reflectance spectra in adults with normal and low Hgb levels agreed well with experimental data for Hgb concentrations from 8.1 to 16.7 g/dL. The extracted Hgb levels were compared with in vitro Hgb measurements. The root mean square error of cross-validation was 1.64 g/dL. The method was shown to provide 86% sensitivity estimates for clinically diagnosed anemia cases. A combination of the model with spectroscopy measurements provides a new tool for noninvasive study of human conjunctiva to aid in diagnosing blood disorders such as anemia.
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    Constructal law of vascular trees for facilitation of flow
    (PLoS, 2014-12-31) Razavi, Mohammad S.; Shirani, Ebrahim; Salimpour, Mohammad Reza; Kassab, Ghassan S.; Department of Biomedical Engineering, School of Engineering and Technology
    Diverse tree structures such as blood vessels, branches of a tree and river basins exist in nature. The constructal law states that the evolution of flow structures in nature has a tendency to facilitate flow. This study suggests a theoretical basis for evaluation of flow facilitation within vascular structure from the perspective of evolution. A novel evolution parameter (Ev) is proposed to quantify the flow capacity of vascular structures. Ev is defined as the ratio of the flow conductance of an evolving structure (configuration with imperfection) to the flow conductance of structure with least imperfection. Attaining higher Ev enables the structure to expedite flow circulation with less energy dissipation. For both Newtonian and non-Newtonian fluids, the evolution parameter was developed as a function of geometrical shape factors in laminar and turbulent fully developed flows. It was found that the non-Newtonian or Newtonian behavior of fluid as well as flow behavior such as laminar or turbulent behavior affects the evolution parameter. Using measured vascular morphometric data of various organs and species, the evolution parameter was calculated. The evolution parameter of the tree structures in biological systems was found to be in the range of 0.95 to 1. The conclusion is that various organs in various species have high capacity to facilitate flow within their respective vascular structures.
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    Discovery and validation of blood biomarkers for suicidality
    (Springer Nature, 2013) Le-Niculescu, H.; Levey, D. F.; Ayalew, M.; Palmer, L.; Gavrin, L. M.; Jain, N.; Winiger, E.; Bhosrekar, S.; Shankar, G.; Radel, M.; Bellanger, E.; Duckworth, H.; Olesek, K.; Vergo, J.; Schweitzer, R.; Yard, M.; Ballew, A.; Shekhar, A.; Sandusky, G. E.; Schork, N. J.; Kurian, S. M.; Salomon, D. R.; Niculescu, A. B., III; Psychiatry, School of Medicine
    Suicides are a leading cause of death in psychiatric patients, and in society at large. Developing more quantitative and objective ways (biomarkers) for predicting and tracking suicidal states would have immediate practical applications and positive societal implications. We undertook such an endeavor. First, building on our previous blood biomarker work in mood disorders and psychosis, we decided to identify blood gene expression biomarkers for suicidality, looking at differential expression of genes in the blood of subjects with a major mood disorder (bipolar disorder), a high-risk population prone to suicidality. We compared no suicidal ideation (SI) states and high SI states using a powerful intrasubject design, as well as an intersubject case-case design, to generate a list of differentially expressed genes. Second, we used a comprehensive Convergent Functional Genomics (CFG) approach to identify and prioritize from the list of differentially expressed gene biomarkers of relevance to suicidality. CFG integrates multiple independent lines of evidence-genetic and functional genomic data-as a Bayesian strategy for identifying and prioritizing findings, reducing the false-positives and false-negatives inherent in each individual approach. Third, we examined whether expression levels of the blood biomarkers identified by us in the live bipolar subject cohort are actually altered in the blood in an age-matched cohort of suicide completers collected from the coroner's office, and report that 13 out of the 41 top CFG scoring biomarkers (32%) show step-wise significant change from no SI to high SI states, and then to the suicide completers group. Six out of them (15%) remained significant after strict Bonferroni correction for multiple comparisons. Fourth, we show that the blood levels of SAT1 (spermidine/spermine N1-acetyltransferase 1), the top biomarker identified by us, at the time of testing for this study, differentiated future as well as past hospitalizations with suicidality, in a live cohort of bipolar disorder subjects, and exhibited a similar but weaker pattern in a live cohort of psychosis (schizophrenia/schizoaffective disorder) subjects. Three other (phosphatase and tensin homolog (PTEN), myristoylated alanine-rich protein kinase C substrate (MARCKS), and mitogen-activated protein kinase kinase kinase 3 (MAP3K3)) of the six biomarkers that survived Bonferroni correction showed similar but weaker effects. Taken together, the prospective and retrospective hospitalization data suggests SAT1, PTEN, MARCKS and MAP3K3 might be not only state biomarkers but trait biomarkers as well. Fifth, we show how a multi-dimensional approach using SAT1 blood expression levels and two simple visual-analog scales for anxiety and mood enhances predictions of future hospitalizations for suicidality in the bipolar cohort (receiver-operating characteristic curve with area under the curve of 0.813). Of note, this simple approach does not directly ask about SI, which some individuals may deny or choose not to share with clinicians. Lastly, we conducted bioinformatic analyses to identify biological pathways, mechanisms and medication targets. Overall, suicidality may be underlined, at least in part, by biological mechanisms related to stress, inflammation and apoptosis.
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    Dysregulated expression levels of APH1B in peripheral blood are associated with brain atrophy and amyloid-β deposition in Alzheimer's disease
    (BMC, 2021-11-03) Park, Young Ho; Pyun, Jung‑Min; Hodges, Angela; Jang, Jae‑Won; Bice, Paula J.; Kim, SangYun; Saykin, Andrew J.; Nho, Kwangsik; Radiology and Imaging Sciences, School of Medicine
    Background: The interaction between the brain and periphery might play a crucial role in the development of Alzheimer's disease (AD). Methods: Using blood transcriptomic profile data from two independent AD cohorts, we performed expression quantitative trait locus (cis-eQTL) analysis of 29 significant genetic loci from a recent large-scale genome-wide association study to investigate the effects of the AD genetic variants on gene expression levels and identify their potential target genes. We then performed differential gene expression analysis of identified AD target genes and linear regression analysis to evaluate the association of differentially expressed genes with neuroimaging biomarkers. Results: A cis-eQTL analysis identified and replicated significant associations in seven genes (APH1B, BIN1, FCER1G, GATS, MS4A6A, RABEP1, TRIM4). APH1B expression levels in the blood increased in AD and were associated with entorhinal cortical thickness and global cortical amyloid-β deposition. Conclusion: An integrative analysis of genetics, blood-based transcriptomic profiles, and imaging biomarkers suggests that APH1B expression levels in the blood might play a role in the pathogenesis of AD.
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    Generation of mice carrying a knockout-first and conditional-ready allele of transforming growth factor beta2 gene
    (Wiley, 2014-09) Ahmed, A. S. Ishtiaq; Bose, Gracelyn C.; Huang, Li; Azhar, Mohamad; Department of Pediatrics, Indiana University School of Medicine
    Transforming growth factor beta2 (TGFβ2) is a multifunctional protein which is expressed in several embryonic and adult organs. TGFB2 mutations can cause Loeys Dietz syndrome, and its dysregulation is involved in cardiovascular, skeletal, ocular, and neuromuscular diseases, osteoarthritis, tissue fibrosis, and various forms of cancer. TGFβ2 is involved in cell growth, apoptosis, cell migration, cell differentiation, cell-matrix remodeling, epithelial-mesenchymal transition, and wound healing in a highly context-dependent and tissue-specific manner. Tgfb2(-/-) mice die perinatally from congenital heart disease, precluding functional studies in adults. Here, we have generated mice harboring Tgfb2(βgeo) (knockout-first lacZ-tagged insertion) gene-trap allele and Tgfb2(flox) conditional allele. Tgfb2(βgeo/βgeo) or Tgfb2(βgeo/-) mice died at perinatal stage from the same congenital heart defects as Tgfb2(-/-) mice. β-galactosidase staining successfully detected Tgfb2 expression in the heterozygous Tgfb2(βgeo) fetal tissue sections. Tgfb2(flox) mice were produced by crossing the Tgfb2(+/βgeo) mice with the FLPeR mice. Tgfb2(flox/-) mice were viable. Tgfb2 conditional knockout (Tgfb2(cko/-) ) fetuses were generated by crossing of Tgfb2(flox/-) mice with Tgfb2(+/-) ; EIIaCre mice. Systemic Tgfb2(cko/-) embryos developed cardiac defects which resembled the Tgfb2(βgeo/βgeo) , Tgfb2(βgeo/-) , and Tgfb2(-/-) fetuses. In conclusion, Tgfb2(βgeo) and Tgfb2(flox) mice are novel mouse strains which will be useful for investigating the tissue specific expression and function of TGFβ2 in embryonic development, adult organs, and disease pathogenesis and cancer. genesis