Life Sciences Commons^™

Disease-Related Microglia Heterogeneity In The Hippocampus Of Alzheimer's Disease, Dementia With Lewy Bodies, And Hippocampal Sclerosis Of Aging, Adam D. Bachstetter, Linda J. Van Eldik, Frederick A. Schmitt, Janna H. Neltner, Eseosa T. Ighodaro, Scott J. Webster, Ela Patel, Erin L. Abner, Richard J. Kryscio, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Introduction: Neuropathological, genetic, and biochemical studies have provided support for the hypothesis that microglia participate in Alzheimer's disease (AD) pathogenesis. Despite the extensive characterization of AD microglia, there are still many unanswered questions, and little is known about microglial morphology in other common forms of age-related dementia: particularly, dementia with Lewy bodies (DLB) and hippocampal sclerosis of aging (HS-Aging). In addition, no prior studies have attempted to compare and contrast the microglia morphology in the hippocampus of various neurodegenerative conditions.

Results: Here we studied cases with pathologically-confirmed AD (n = 7), HS-Aging (n = 7), AD + HS-aging …

The Effects Of 12 Weeks Of Instructor-Led Yoga Classes On Balance In Older Adults, Patricia C. Hart

Evidence-Based Practice Project Reports

Participation in a regular exercise program is an effective way to reduce and/or prevent a number of functional declines associated with aging (Chodzko-Zajo et al., 2009). Older adults are advised to participate in regular aerobic activity and practice muscle strengthening activities and exercise that maintains or improves balance (U.S. Department of Health and Human Service, [USDHHS], 2012). Less than one third of older adults engage in 30 minutes of low to moderate intense physical activity at least five days a week as recommended in current guidelines (USDHHS, 2012), and these guidelines fail to address losses in strength and flexibility seen …

Zhx2 Enhances The Cytotoxicity Of Chemotherapeutic Drugs In Liver Tumor Cells By Repressing Mdr1 Via Interfering With Nf-Ya, Hongxin Ma, Xuetian Yue, Lifen Gao, Xiaohong Liang, Wenjiang Yan, Zhenyu Zhang, Haixia Shan, Hualin Zhang, Brett T. Spear, Chunhong Ma

Microbiology, Immunology, and Molecular Genetics Faculty Publications

We previously reported the tumor suppressor function of Zinc-fingers and homeoboxes 2 (ZHX2) in hepatocellular carcinoma (HCC). Other studies indicate the association of increased ZHX2 expression with improved response to high dose chemotherapy in multiple myeloma. Here, we aim to test whether increased ZHX2 levels in HCC cells repress multidrug resistance 1(MDR1) expression resulting in increased sensitivity to chemotherapeutic drugs. We showed evidence that increased ZHX2 levels correlated with reduced MDR1 expression and enhanced the cytotoxicity of CDDP and ADM in different HCC cell lines. Consistently, elevated ZHX2 significantly reduced ADM efflux in HepG2 cells and greatly increased the CDDP-mediated …

Systems Level Analysis Of Systemic Sclerosis Shows A Network Of Immune And Profibrotic Pathways Connected With Genetic Polymorphisms, J. Matthew Mahoney, Jaclyn Taroni, Viktor Martyanov, Tammara A. A. Wood, Casey S. Greene, Patricia A. Pioli, Monique E. Hinchcliff, Michael L. Whitfield

Dartmouth Scholarship

Systemic sclerosis (SSc) is a rare systemic autoimmune disease characterized by skin and organ fibrosis. The pathogenesis of SSc and its progression are poorly understood. The SSc intrinsic gene expression subsets (inflammatory, fibroproliferative, normal-like, and limited) are observed in multiple clinical cohorts of patients with SSc. Analysis of longitudinal skin biopsies suggests that a patient's subset assignment is stable over 6-12 months. Genetically, SSc is multi-factorial with many genetic risk loci for SSc generally and for specific clinical manifestations. Here we identify the genes consistently associated with the intrinsic subsets across three independent cohorts, show the relationship between these genes …

Clinical Significance Of A Point Mutation In Dna Polymerase Beta (Polb) Gene In Gastric Cancer., Xiaohui Tan, Hongyi Wang, Guangbin Luo, Shuyang Ren, Wenmei Li, Jiantao Cui, Harindarpal S. Gill, Sidney W. Fu, Youyong Lu

Medicine Faculty Publications

Gastric cancer (GC) is a major cause of global cancer mortality. Genetic variations in DNA repair genes can modulate DNA repair capability and, consequently, have been associated with risk of developing cancer. We have previously identified a T to C point mutation at nucleotide 889 (T889C) in DNA polymerase beta (POLB) gene, a key enzyme involved in base excision repair in primary GCs. The purpose of this study was to evaluate the mutation and expression of POLB in a larger cohort and to identify possible prognostic roles of the POLB alterations in GC. Primary GC specimens and their matched normal …

Lean Body Mass Associated With Upper Body Strength In Healthy Older Adults While Higher Body Fat Limits Lower Extremity Performance And Endurance, Karen Charlton, Marijka Batterham, Kelly Langford, Jenna Lateo, Erin Brock, Karen Walton, Philipa Lyons-Wall, Katie Eisenhauer, Nick Green, Cameron Mclean

Research outputs 2014 to 2021

Impaired strength adversely influences an older person’s ability to perform activities of daily living. A cross-sectional study of 117 independently living men and women (age = 73.4 ± 9.4 year; body mass index (BMI) = 27.6 ± 4.8 kg/m2) aimed to assess the association between body composition and: (1) upper body strength (handgrip strength, HGS); (2) lower extremity performance (timed up and go (TUG) and sit to stand test (STS)); and (3) endurance (6-minute walk (SMWT). Body composition (% fat; lean body mass (LBM)) was assessed using bioelectrical impedance. Habitual physical activity was measured using the Minnesota Leisure Time Physical …

Evaluation Of A Mobile Phone Image-Based Dietary Assessment Method In Adults With Type 2 Diabetes, Megan E. Rollo, Susan Ash, Philipa Lyons-Wall, Anthony W. Russell

Research outputs 2014 to 2021

Image-based dietary records have limited evidence evaluating their performance and use among adults with a chronic disease. This study evaluated the performance of a 3-day mobile phone image-based dietary record, the Nutricam Dietary Assessment Method (NuDAM), in adults with type 2 diabetes mellitus (T2DM). Criterion validity was determined by comparing energy intake (EI) with total energy expenditure (TEE) measured by the doubly-labelled water technique. Relative validity was established by comparison to a weighed food record (WFR). Inter-rater reliability was assessed by comparing estimates of intake from three dietitians. Ten adults (6 males, age: 61.2 ± 6.9 years old, BMI: 31.0 …

Assessing Climate Variability Effects On Dengue Incidence In San Juan, Puerto Rico, Pablo Méndez-Lázaro, Frank E. Muller-Karger, Daniel Otis, Matthew J Mccarthy, Marisol Peña-Orellana

Marine Science Faculty Publications

We test the hypothesis that climate and environmental conditions are becoming favorable for dengue transmission in San Juan, Puerto Rico. Sea Level Pressure (SLP), Mean Sea Level (MSL), Wind, Sea Surface Temperature (SST), Air Surface Temperature (AST), Rainfall, and confirmed dengue cases were analyzed. We evaluated the dengue incidence and environmental data with Principal Component Analysis, Pearson correlation coefficient, Mann-Kendall trend test and logistic regressions. Results indicated that dry days are increasing and wet days are decreasing. MSL is increasing, posing higher risk of dengue as the perimeter of the San Juan Bay estuary expands and shorelines move inland. Warming …

An Intronic Picalm Polymorphism, Rs588076, Is Associated With Allelic Expression Of A Picalm Isoform, Ishita Parikh, Christopher Medway, Steven Younkin, David Fardo, Steven Estus

Physiology Faculty Publications

BACKGROUND: Although genome wide studies have associated single nucleotide polymorphisms (SNP)s near PICALM with Alzheimer's disease (AD), the mechanism underlying this association is unclear. PICALM is involved in clathrin-mediated endocytosis and modulates Aß clearance in vitro. Comparing allelic expression provides the means to detect cis-acting regulatory polymorphisms. Thus, we evaluated whether PICALM showed allele expression imbalance (AEI) and whether this imbalance was associated with the AD-associated polymorphism, rs3851179.

RESULTS: We measured PICALM allelic expression in 42 human brain samples by using next-generation sequencing. Overall, PICALM demonstrated equal allelic expression with no detectable influence by rs3851179. A single sample demonstrated …

Self-Reported Head Injury And Risk Of Late-Life Impairment And Ad Pathology In An Ad Center Cohort, Erin L. Abner, Peter T. Nelson, Frederick A. Schmitt, Steven R. Browning, David W. Fardo, Lijie Wan, Gregory A. Jicha, Gregory E. Cooper, Charles D. Smith, Allison M. Caban-Holt, Linda J. Van Eldik, Richard J. Kryscio

Sanders-Brown Center on Aging Faculty Publications

Aims: To evaluate the relationship between self-reported head injury and cognitive impairment, dementia, mortality, and Alzheimer's disease (AD)-type pathological changes. Methods: Clinical and neuropathological data from participants enrolled in a longitudinal study of aging and cognition (n = 649) were analyzed to assess the chronic effects of self-reported head injury. Results: The effect of self-reported head injury on the clinical state depended on the age at assessment: for a 1-year increase in age, the OR for the transition to clinical mild cognitive impairment (MCI) at the next visit for participants with a history of head injury was 1.21 and 1.34 …

The Effectiveness Of Telemedicine For Weight Management In The Move! Program, April D. Ahrendt, Kendra K. Kattelmann, Thomas S. Rector, David A Maddox

Health and Nutritional Sciences Faculty Publications

PURPOSE: To examine the effectiveness of videoconferencing technology for delivering comprehensive weight management treatment.
METHODS: This retrospective cohort study was conducted by extraction of data from medical records for the years 2008-2010. The treatment included a series of 12 weekly MOVE!® classes delivered using videoconferencing. Data were extracted from the time of baseline weight to 1 year after baseline weight for the MOVE! participants (n = 60) and from a concurrent control group (n = 60) that did not participate in MOVE! treatment.
FINDINGS: Results indicated that the MOVE! group lost weight while the control group gained weight, resulting in …

Myo/Nog Cells: Targets For Preventing The Accumulation Of Skeletal Muscle-Like Cells In The Human Lens, Jacquelyn Gerhart, M. Greenbaum, V. Scheinfeld, P. Fitzgerald, M. Crawford, Arturo Bravo Nuevo, M. Pitts, Mindy George-Weinstein

PCOM Scholarly Works

Posterior capsule opacification (PCO) is a vision impairing condition that arises in some patients following cataract surgery. The fibrotic form of PCO is caused by myofibroblasts that may emerge in the lens years after surgery. In the chick embryo lens, myofibroblasts are derived from Myo/Nog cells that are identified by their expression of the skeletal muscle specific transcription factor MyoD, the bone morphogenetic protein inhibitor Noggin, and the epitope recognized by the G8 monoclonal antibody. The goal of this study was to test the hypothesis that depletion of Myo/Nog cells will prevent the accumulation of myofibroblasts in human lens tissue. …

A Population-Based Case–Control Study Of Urinary Arsenic Species And Squamous Cell Carcinoma In New Hampshire, Usa, Diane Gilbert-Diamond, Zhigang Li, Ann E. Perry, Steven K. Spencer, A Jay Gandolfi, Margaret R. Karagas

Dartmouth Scholarship

Background: Chronic high arsenic exposure is associated with squamous cell carcinoma (SCC) of the skin, and inorganic arsenic (iAs) metabolites may play an important role in this association. However, little is known about the carcinogenicity of arsenic at levels commonly observed in the United States.

Objective: We estimated associations between total urinary arsenic and arsenic species and SCC in a U.S. population.

Methods: We conducted a population-based case–control SCC study (470 cases, 447 controls) in a U.S. region with moderate arsenic exposure through private well water and diet. We measured urinary iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA), and …

Excitatory Amino Acids Display Compartmental Disparity Between Plasma And Synovial Fluid In Clinical Arthropathies, Terry A. Mcnearney, Karin N. Westlund

Physiology Faculty Publications

BACKGROUND: Previous studies have demonstrated elevated levels of excitatory amino acids (EAA) glutamate (Glu) and aspartate (Asp) in the synovial fluid (SF) of patients with active arthritis. The source of SF EAA concentrations are thought in large part to be secondary to passive diffusion from the plasma across synovial membranes and less so, reflective of local synovial pathology.

OBJECTIVE: This descriptive report assesses the hypothesis that the SF EAA levels reflect inflammatory processes of the joint and are not dependent on plasma levels.

METHODS: Simultaneously drawn plasma and SF samples were obtained from 14 recently deceased cadavers and 10 patients …

Adenosine Deaminase Enhances The Immunogenicity Of Human Dendritic Cells From Healthy And Hiv-Infected Individuals, Víctor Casanova, Isaac Isaac Naval-Macabuhay, Marta Massanella, Marta Rodríguez-García

Dartmouth Scholarship

ADA is an enzyme implicated in purine metabolism, and is critical to ensure normal immune function. Its congenital deficit leads to severe combined immunodeficiency (SCID). ADA binding to adenosine receptors on dendritic cell surface enables T-cell costimulation through CD26 crosslinking, which enhances T-cell activation and proliferation. Despite a large body of work on the actions of the ecto-enzyme ADA on T-cell activation, questions arise on whether ADA can also modulate dendritic cell maturation. To this end we investigated the effects of ADA on human monocyte derived dendritic cell biology. Our results show that both the enzymatic and non-enzymatic activities of …

G9a Interacts With Snail And Is Critical For Snail-Mediated E-Cadherin Repression In Human Breast Cancer, Chenfang Dong, Yadi Wu, Jun Yao, Yifan Wang, Yinhua Yu, Piotr G. Rychahou, B. Mark Evers, Binhua P. Zhou

Molecular and Cellular Biochemistry Faculty Publications

Breast cancers are highly heterogeneous but can be grouped into subtypes based on several criteria, including level of expression of certain markers. Claudin-low breast cancer (CLBC) is associated with early metastasis and resistance to chemotherapy, while gene profiling indicates it is characterized by the expression of markers of epithelial-mesenchymal transition (EMT) - a phenotypic conversion linked with metastasis. Although the epigenetic program controlling the phenotypic and cellular plasticity of EMT remains unclear, one contributor may be methylation of the E-cadherin promoter, resulting in decreased E-cadherin expression, a hallmark of EMT. Indeed, reduced E-cadherin often occurs in CLBC and may contribute …

Rna Oxidation Adducts 8-Ohg And 8-Oha Change With Aβ42 Levels In Late-Stage Alzheimer's Disease, Adam M. Weidner, Melissa A. Bradley, Tina L. Beckett, Dana M. Niedowicz, Amy L.S. Dowling, Sergey V. Matveev, Harry Levine, Mark A. Lovell, M. Paul Murphy

Sanders-Brown Center on Aging Faculty Publications

While research supports amyloid-β (Aβ) as the etiologic agent of Alzheimer's disease (AD), the mechanism of action remains unclear. Evidence indicates that adducts of RNA caused by oxidation also represent an early phenomenon in AD. It is currently unknown what type of influence these two observations have on each other, if any. We quantified five RNA adducts by gas chromatography/mass spectroscopy across five brain regions from AD cases and age-matched controls. We then used a reductive directed analysis to compare the RNA adducts to common indices of AD neuropathology and various pools of Aβ. Using data from four disease-affected brain …

Aging Is Associated With Positive Responding To Neutral Information But Reduced Recovery From Negative Information, Carien M. Van Reekum, Stacey M. Schaefer, Regina C. Lapate, Catherine J. Norris, Lawrence L. Greischar, Richard J. Davidson

Dartmouth Scholarship

Studies on aging and emotion suggest an increase in reported positive affect, a processing bias of positive over negative information, as well as increasingly adaptive regulation in response to negative events with advancing age. These findings imply that older individuals evaluate information differently, resulting in lowered reactivity to, and/or faster recovery from, negative information, while maintaining more positive responding to positive information. We examined this hypothesis in an ongoing study on Midlife in the US (MIDUS II) where emotional reactivity and recovery were assessed in a large number of respondents (N = 159) from a wide age range (36–84 …

Alterations In Multiple Measures Of White Matter Integrity In Normal Women At High Risk For Alzheimer's Disease, Brian T. Gold, David K. Powell, Anders H. Andersen, Charles D. Smith

Neuroscience Faculty Publications

There is evidence that disruption of white matter (WM) microstructure is an early event in the course of Alzheimer's disease (AD). However, the neurobiological bases of WM microstructural declines in presymptomatic AD are unknown. In the present study we address this issue using a multimodal imaging approach to the study of presymptomatic AD. Participants were 37 high-risk (both family history of dementia and one or more APOE4 alleles) women and 20 low-risk (neither family history nor APOE4) women. Groups were matched for age, education, neuropsychological performance, and vascular factors that could affect white matter. Whole-brain analyses of diffusion tensor imaging …

Genetic Population Structure Analysis In New Hampshire Reveals Eastern European Ancestry, Chantel D. Sloan, Angeline D. Andrew, Eric J. Duell, Scott M. Williams, Margaret R. Karagas, Jason H. Moore

Dartmouth Scholarship

Genetic structure due to ancestry has been well documented among many divergent human populations. However, the ability to associate ancestry with genetic substructure without using supervised clustering has not been explored in more presumably homogeneous and admixed US populations. The goal of this study was to determine if genetic structure could be detected in a United States population from a single state where the individuals have mixed European ancestry. Using Bayesian clustering with a set of 960 single nucleotide polymorphisms (SNPs) we found evidence of population stratification in 864 individuals from New Hampshire that can be used to differentiate the …

Human Cerebral Neuropathology Of Type 2 Diabetes Mellitus, Peter T. Nelson, Charles D. Smith, Erin L. Abner, Frederick A. Schmitt, Stephen W. Scheff, Gregory J. Davis, Jeffrey N. Keller, Gregory A. Jicha, Daron Davis, Wang-Xia Wang, Adria Hartman, Douglas G. Katz, William R. Markesbery

Pathology and Laboratory Medicine Faculty Publications

The cerebral neuropathology of Type 2 diabetes (CNDM2) has not been positively defined. This review includes a description of CNDM2 research from before the ‘Pubmed Era’. Recent neuroimaging studies have focused on cerebrovascular and white matter pathology. These and prior studies about cerebrovascular histopathology in diabetes are reviewed. Evidence is also described for and against the link between CNDM2 and Alzheimer's disease pathogenesis. To study this matter directly, we evaluated data from University of Kentucky Alzheimer's Disease Center (UK ADC) patients recruited while non-demented and followed longitudinally. Of patients who had come to autopsy (N = 234), 139 met …

Long-Term Survival After Multidisciplinary Management Of Resected Pancreatic Adenocarcinoma, Matthew H G Katz, Huamin Wang, Jason B Fleming, Charlotte C Sun, Rosa F Hwang, Robert A Wolff, Gauri Varadhachary, James L Abbruzzese, Christopher H Crane, Sunil Krishnan, Jean-Nicolas Vauthey, Eddie K Abdalla, Jeffrey E Lee, Peter W T Pisters, Douglas B Evans

Faculty, Staff and Student Publications

INTRODUCTION: Actual 5-year survival rates of 10-18% have been reported for patients with resected pancreatic adenocarcinoma (PC), but the use of multimodality therapy was uncommon in these series. We evaluated long-term survival and patterns of recurrence in patients treated for PC with contemporary staging and multimodality therapy.

METHODS: We analyzed 329 consecutive patients with PC evaluated between 1990 and 2002 who underwent resection. Each received a multidisciplinary evaluation and a standard operative approach. Pre- or postoperative chemotherapy and/or chemoradiation were routine. Surgical specimens of 5-year survivors were re-reviewed. A multivariate model of factors associated with long-term survival was constructed.

RESULTS: …

Aging And Endothelial Progenitor Cell Telomere Length In Healthy Men, Erich J Kushner, Gary Van Guilder, Owen J Maceneaney, Jennifer N Cech, Brian L Stauffer, Christopher A Desouza

Health and Nutritional Sciences Faculty Publications

BACKGROUND: Telomere length declines with age in mature endothelial cells and is thought to contribute to endothelial dysfunction and atherogenesis. Bone marrow-derived circulating endothelial progenitor cells (EPCs) are critical to vascular health as they contribute to both reendothelialization and neovascularization. We tested the hypothesis that EPC telomere length decreases with age in healthy adult humans.
METHODS: Peripheral blood samples were collected from 40 healthy, non-obese, sedentary men: 12 young (age 21-34 years), 12 middle-aged (43-55 years) and 16 older (57-68 years). Putative EPCs were isolated from peripheral blood mononuclear cells and telomere length was determined using genomic DNA preparation and …

Reduced Neutrophil Count In People Of African Descent Is Due To A Regulatory Variant In The Duffy Antigen Receptor For Chemokines Gene, David Reich, Michael A. Nalls, W H Linda Kao, Ermeg L. Akylbekova, Arti Tandon, Nick Patterson, James Mullikin, Wen-Chi Hsueh, Ching-Yu Cheng, Josef Coresh, Eric Boerwinkle, Man Li, Alicja Waliszewska, Julie Neubauer, Rongling Li, Tennille S. Leak, Lynette Ekunwe, Joe C. Files, Cheryl L. Hardy, Joseph M. Zmuda, Herman A. Taylor, Elad Ziv, Tamara B. Harris, James G. Wilson

Faculty, Staff and Student Publications

Persistently low white blood cell count (WBC) and neutrophil count is a well-described phenomenon in persons of African ancestry, whose etiology remains unknown. We recently used admixture mapping to identify an approximately 1-megabase region on chromosome 1, where ancestry status (African or European) almost entirely accounted for the difference in WBC between African Americans and European Americans. to identify the specific genetic change responsible for this association, we analyzed genotype and phenotype data from 6,005 African Americans from the Jackson Heart Study (JHS), the Health, Aging and Body Composition (Health ABC) Study, and the Atherosclerosis Risk in Communities (ARIC) Study. …

Drinking-Water Arsenic Exposure Modulates Gene Expression In Human Lymphocytes From A U.S. Population, Angeline S. Andrew, David A. Jewell, Rebecca A. Mason, Michael L. Whitfield, Jason H. Moore, Margaret R. Karagas

Dartmouth Scholarship

Background:

Arsenic exposure impairs development and can lead to cancer, cardiovascular disease, and diabetes. The mechanism underlying these effects remains unknown. Primarily because of geologic sources of contamination, drinking-water arsenic levels are above the current recommended maximum contaminant level of 10 μg/L in the northeastern, western, and north central regions of the United States.

Objectives:

We investigated the effects of arsenic exposure, defined by internal biomarkers at levels relevant to the United States and similarly exposed populations, on gene expression.

Methods:

We conducted separate Affymetrix microarray-based genomewide analyses of expression patterns. Peripheral blood lymphocyte samples from 21 controls interviewed (1999–2002) …

Focal White Matter Changes In Spasmodic Dysphonia: A Combined Diffusion Tensor Imaging And Neuropathological Study, Kristina Simonyan, Fernanda Tovar-Moll, John Ostuni, Mark Hallett, Victor F Kalasinsky, Michael R Lewin-Smith, Elisabeth J Rushing, Alexander O Vortmeyer, Christy L Ludlow

Faculty, Staff and Student Publications

Spasmodic dysphonia is a neurological disorder characterized by involuntary spasms in the laryngeal muscles during speech production. Although the clinical symptoms are well characterized, the pathophysiology of this voice disorder is unknown. We describe here, for the first time to our knowledge, disorder-specific brain abnormalities in these patients as determined by a combined approach of diffusion tensor imaging (DTI) and postmortem histopathology. We used DTI to identify brain changes and to target those brain regions for neuropathological examination. DTI showed right-sided decrease of fractional anisotropy in the genu of the internal capsule and bilateral increase of overall water diffusivity in …

The Expression Of Microrna Mir-107 Decreases Early In Alzheimer's Disease And May Accelerate Disease Progression Through Regulation Of Β-Site Amyloid Precursor Protein-Cleaving Enzyme 1, Wang-Xia Wang, Bernard W. Rajeev, Arnold J. Stromberg, Na Ren, Guiliang Tang, Qingwei Huang, Isidore Rigoutsos, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are small regulatory RNAs that participate in posttranscriptional gene regulation in a sequence-specific manner. However, little is understood about the role(s) of miRNAs in Alzheimer's disease (AD). We used miRNA expression microarrays on RNA extracted from human brain tissue from the University of Kentucky Alzheimer's Disease Center Brain Bank with near-optimal clinicopathological correlation. Cases were separated into four groups: elderly nondemented with negligible AD-type pathology, nondemented with incipient AD pathology, mild cognitive impairment (MCI) with moderate AD pathology, and AD. Among the AD-related miRNA expression changes, miR-107 was exceptional because miR-107 levels decreased significantly even in patients with …

Effects, Uptake, And Fate Of 2,4,6-Trinitrotoluene Aged In Soil In Plants And Worms, Elly Ph Best, Henry E. Tatem, Kaaren N. Geter, Melissa L. Wells, Brian K. Lane

United States Army Corps of Engineers, Omaha District

The present study was aimed at providing data to be used at predicting exposure-based effects of 2,4,6-trinitrotoluene (TNT) aged in soil on endpoint organisms representing two trophic levels. These data can be used to define criteria or reference values for environmental management and conducting specific risk assessment. Long-term exposure tests were conducted to evaluate sublethal toxicity and uptake of aged soil-based explosives, with TNT as the main contaminant. In these tests, plants were exposed for 55 d, and biomass and explosives residues were determined. Worms were exposed for 28 and 42 d, and biomass, number, and tissue residues were determined. …

Expansion Of The Calcium Hypothesis Of Brain Aging And Alzheimer's Disease: Minding The Store, Olivier Thibault, John C. Gant, Philip W. Landfield

Pharmacology and Nutritional Sciences Faculty Publications

Evidence accumulated over more than two decades has implicated Ca2+ dysregulation in brain aging and Alzheimer's disease (AD), giving rise to the Ca2+ hypothesis of brain aging and dementia. Electrophysiological, imaging, and behavioral studies in hippocampal or cortical neurons of rodents and rabbits have revealed aging-related increases in the slow afterhyperpolarization, Ca2+ spikes and currents, Ca2+transients, and L-type voltage-gated Ca2+ channel (L-VGCC) activity. Several of these changes have been associated with age-related deficits in learning or memory. Consequently, one version of the Ca2+ hypothesis has been that increased L-VGCC activity drives many of the other Ca2+-related biomarkers of hippocampal aging. …

Genetic Polymorphisms Of The Interleukin-1 Gene And Early Marginal Bone Loss Around Endosseous Dental Implants, Hitomi Shimpuku, Yasuhiro Nosaka, Tatsuya Kawamura, Yoichi Tachi, Mitsuko Shinohara, Kiyoshi Ohura

Faculty, Staff and Student Publications

Dental implant surgery commonly proceeds in two stages. It is generally accepted that bone loss around implants does not occur at stage-II surgery because implants do not receive mechanical loading. However, early marginal bone loss around implants occasionally does occur during the healing period. Genetic polymorphisms in the interleukin-1 (IL-1) gene have been reported to be important for bone homeostasis and susceptibility to bone disease. We therefore investigated whether the idiopathic early marginal bone loss around implants is related to polymorphisms in the IL-1 gene. We performed a case-control study. Patients demonstrating marginal bone loss around implants at stage-II surgery …