Digital Commons Network^™

Could A Common Mechanism Of Protein Degradation Impairment Underlie Many Neurodegenerative Diseases?, David M. Smith

Faculty & Staff Scholarship

At the cellular level, many neurodegenerative diseases (NDs), often considered proteinopathies, are characterized by the accumulation of misfolded and damaged proteins into large insoluble aggregates. Prominent species that accumulate early and play fundamental roles in disease pathogenesis are amyloid β (Aβ) and tau in Alzheimer disease, α-synuclein (α-syn) in Parkinson disease, and polyQ-expanded huntingtin (Htt) in Huntington disease. Although significant efforts have focused on how the cell deals with these protein aggregates, why is it that these misfolded proteins are not degraded normally in the first place? A vast body of literature supports the notion that the cell’s protein degradation …

Quantum Confined Peptide Assemblies With Tunable Visible To Near-Infrared Spectral Range, Kai Tao, Zhen Fan, Leming Sun, Pandeeswar Makam, Zhen Tian, Mark Ruegsegger, Shira Shaham-Niv, Derek Hansford, Ruth Aizen, Zui Pan, Scott Galster, Jianjie Ma, Fan Yuan, Mingsu Si, Songnan Qu, Mingjun Zhang, Ehud Gazit, Junbai Li

Faculty & Staff Scholarship

Quantum confined materials have been extensively studied for photoluminescent applica- tions. Due to intrinsic limitations of low biocompatibility and challenging modulation, the utilization of conventional inorganic quantum confined photoluminescent materials in bio- imaging and bio-machine interface faces critical restrictions. Here, we present aromatic cyclo-dipeptides that dimerize into quantum dots, which serve as building blocks to further self-assemble into quantum confined supramolecular structures with diverse morphologies and photoluminescence properties. Especially, the emission can be tuned from the visible region to the near-infrared region (420 nm to 820 nm) by modulating the self-assembly process. Moreover, no obvious cytotoxic effect is observed for …

Integrated Analysis Of Lncrna And Mrna Expression In Rainbow Trout Families Showing Variation In Muscle Growth And Fillet Quality Traits, Ali Ali, Rafet Al-Tobasei, Brett Kenney, Timothy D. Leeds, Mohamed Salem

Faculty & Staff Scholarship

Muscle yield and quality traits are important for the aquaculture industry and consumers. Genetic selection for these traits is difficult because they are polygenic and result from multifactorial interactions. To study the genetic architecture of these traits, phenotypic characterization of whole body weight (WBW), muscle yield, fat content, shear force and whiteness were measured in ~500 fish representing 98 families from a growth-selected line. RNA-Seq was used to sequence the muscle transcriptome of different families exhibiting divergent phenotypes for each trait. We have identified 240 and 1,280 differentially expressed (DE) protein-coding genes and long noncoding RNAs (lncRNAs), respectively, in fish …

Experimental Intravascular Hemolysis Induces Hemodynamic And Pathological Pulmonary Hypertension: Association With Accelerated Purine Metabolism, Victor P. Bilan, Frank Schneider, Enrico M. Novelli, Eric E. Kelley, Sruti Shiva, Mark T. Gladwin, Edwin K. Jackson, Stevan P. Tofovic

Faculty & Staff Scholarship

Pulmonary hypertension (PH) is emerging as a serious complication associated with hemolytic disorders, and plexiform lesions (PXL) have been reported in patients with sickle cell disease (SCD). We hypothesized that repetitive hemolysis per se induces PH and angioproliferative vasculopathy and evaluated a new mechanism for hemolysis-associated PH (HA-PH) that involves the release of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) from erythrocytes. In healthy rats, repetitive admin- istration of hemolyzed autologous blood (HAB) for 10 days produced reversible pulmonary parenchymal injury and vascular remodeling and PH. Moreover, the combination of a single dose of Sugen-5416 (SU, 200mg/kg) and 10-day …

“My Tummy Tells Me” Cognitions, Barriers And Supports Of Parents And School-Age Children For Appropriate Portion Sizes, Kaitlyn M. Eck, Colleen L. Delaney, Mirian P. Leary, Oluremi A. Famodou, Melissa D. Olfert, Karla P. Shelnutt, Carol Bryd-Bredbenner

Faculty & Staff Scholarship

Larger portion sizes have increased in tandem with the rise in obesity. Elucidation of the cognitions of children and parents related to portion size is needed to inform the development of effective obesity prevention programs. This study examined cognitions of parents (n = 36) and their school-age children (6 to 11 years; n = 35) related to portion sizes via focus group discussions. Parents and children believed controlling portion sizes promoted health and weight control. Some parents felt controlling portions was unnecessary, particularly if kids were a healthy weight because kids can self-regulate intake. Barriers to serving appropriate portions identified …

Relationship Between Diet And Mental Health In A Young Adult Appalachian College Population, Rachel A. Wattick, Rebecca L. Hagedorn, Melissa D. Olfert

Faculty & Staff Scholarship

Young adults in Appalachia may face poor nutritional status due to low access to healthy food and high mental health symptoms attributed to high stress and the college environment. A cross-sectional design was used to investigate the relationship between diet intake and mental health status of this population via surveys. Participant responses (n = 1956) showed students’ mean number of depressed days over the past 30 days was 9.67 ± 8.80, and of anxious days, 14.1 ± 10.03. The mean fruit and vegetable intake was 1.80 ± 1.27 times per day and the mean added sugars intake was 1.79 ± …

Repeated Translocation Of A Gene Cassette Drives Sex-Chromosome Turnover In Strawberries, Jacob A. Tennessen, Na Wei, Shannon C.K. Straub, Rajanikanth Govindarajulu, Aaron Liston, Tia-Lynn Ashman

Faculty & Staff Scholarship

Turnovers of sex-determining systems represent important diversifying forces across eukary- otes. Shifts in sex chromosomes—but conservation of the master sex-determining genes— characterize distantly related animal lineages. Yet in plants, in which separate sexes have evolved repeatedly and sex chromosomes are typically homomorphic, we do not know whether such translocations drive sex-chromosome turnovers within closely related taxo- nomic groups. This phenomenon can only be demonstrated by identifying sex-associated nucleotide sequences, still largely unknown in plants. The wild North American octoploid strawberries (Fragaria) exhibit separate sexes (dioecy) with homomorphic, female heteroga- metic (ZW) inheritance, yet sex maps to three different chromosomes in …

Inhibition Of Phosphodiesterase-4 Reverses Aβ-Induced Memory Impairment By Regulation Of Hpa Axis Related Camp Signaling, Ying Xu, Naping Zhu, Wen Xu, Han Ye, Kaiping Liu, Feiyan Wu, Meixi Zhang, Yun Ding, Chong Zhang, Hanting Zhang, James O'Donnell, Jiangchun Pan

Faculty & Staff Scholarship

Beta amyloid peptides (Aβ) are found to be associated with dysfunction of hypothalamic-pituitary-adrenal axis (HPA axis) that leads to memory and cognitive deficits in patients with Alzheimer’s disease (AD). Phosphodiesterase 4 (PDE4) inhibitors increase the intracellular cAMP activities, which may ameliorate cognitive deficits associated with AD. However, it remains unclear whether PDE4-mediated reversal of cognitive impairment in mouse model of AD is related to HPA axis and downstream cAMP-dependent pathway. The present study investigated the effects of PDE4 inhibitor rolipram on Aβ1-42-induced cognitive dysfunction and its underlying mechanisms. The step-down passive avoidance (PA) and Morris water-maze (MWM) tests were conducted …

Fasudil In Combination With Bone Marrow Stromal Cells (Bmscs) Attenuates Alzheimer’S Disease-Related Changes Through The Regulation Of The Peripheral Immune System, Jiezhong Yu, Yuqing Yan, Qingfang Gu, Gajendra Kumar, Hongqiang Yu, Yijin Zhao, Chunyun Liu, Ye Gao, Zhi Chai, Jasleen Chumber, Bao-Guo Xiao, Guang-Xian Zhang, Han-Ting Zhang, Yuqiang Jiang, Cun-Gen Ma

Faculty & Staff Scholarship

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease. Its mechanism is still not clear. Majority of research focused on the central nervous system (CNS) changes, while few studies emphasize on peripheral immune system modulation. Our study aimed to investigate the regulation of the peripheral immune system and its relationship to the severity of the disease after treatment in an AD model of APPswe/PSEN1dE9 transgenic (APP/PS1 Tg) mice. APP/PS1 Tg mice (8 months old) were treated with the ROCK-II inhibitor 1-(5-isoquinolinesulfonyl)- homo-piperazine (Fasudil) (intraperitoneal (i.p.) injections, 25 mg/kg/day), bone marrow stromal cells (BMSCs; caudal vein injections, 1 × 106 BMSCs …

In Utero Gene Expression In The Slc39a8(Neo/Neo) Knockdown Mouse, Jing Chen, Marina Galvez-Peralta, Xiang Zhang, Jingyuan Deng, Zijuan Liu, Daniel W. Nebert

Faculty & Staff Scholarship

Slc39a8 encodes ZIP8, a divalent cation/bicarbonate symporter expressed in pluripotent mouse embryonic stem cells, and therefore ubiquitous in adult tissues; ZIP8 influxes Zn2+, Mn2+ and Fe2+. Slc39a8(neo/neo) knockdown mice exhibit 10–15% of wild-type ZIP8 mRNA and protein levels, and show pleiotropic phenotype of stunted growth, neonatal lethality, multi-organ dysmorphogenesis, and dysregulated hematopoiesis manifested as severe anemia. Herein we performed RNA-seq analysis of gestational day (GD)13.5 yolk sac and placenta, and GD16.5 liver, kidney, lung, heart and cerebellum,comparing Slc39a8(neo/neo) with Slc39a8(+/+) wild-type. Meta-data analysis of differentially- expressed genes revealed 29 unique genes from all tissues — having enriched GO categories associated …

Neck Circumference Positively Relates To Cardiovascular Risk Factors In College Students, Oluremi A. Famodu, Makenzie L. Barr, Sarah E. Colby, Wenjun Zhou, Ida Holaskova, Miriam P. Leary, Carol Bryd-Bredbenner, Anne E. Matthews, Melissa D. Olfert

Faculty & Staff Scholarship

The objective of this study was to determine the relationship between neck circumference (NC) and other anthropometric measures and examine cut-off points for males and females according to existing waist circumference cut-off levels in this age group. Across 8 universities, 1562 students underwent a physical assessment. Spearman rho correlations (ρ) were calculated to determine associations between NC and other continuous variables of health. Receiving operating characteristic curves were constructed to assess the optimal cut-off levels of NC of males and females with central obesity. Participants were predominantly Caucasian (67%), female (70%), and outside of Appalachia 2 (82%). Forty-one percent of …

Tuberculosis-Like Respiratory Infection In 245-Million-Year-Old Marine Reptile Suggested By Bone Pathologies, Dawid Surmik, Tomasz Szczygielski, Katarzyna Janiszewska, Bruce M. Rothschild

Faculty & Staff Scholarship

An absence of ancient archaeological and palaeontological evidence of pneumonia contrasts with its recognition in the more recent archaeological record. We document an apparent infection-mediated periosteal reaction affecting the dorsal ribs in a Middle Triassic eosauropterygian historically referred to as ‘Proneusticosaurus’ silesiacus. High- resolution X-ray microtomography and histological studies of the pathologically altered ribs revealed the presence of a continuous solid periosteal reaction with multiple superficial blebs (protrusions) on the visceral surfaces of several ribs. Increased vascularization and uneven lines of arrested growth document that the pathology was the result of a multi- seasonal disease. While visceral surface localization of …

The Impact Of Conjunctival Flap Method And Drainage Cannula Diameter On Bleb Survival In The Rabbit Model, Cooper D. Rodgers, Alissa M. Meyer, Nicole C. Rosenberg, Zachary L. Lukowski, Jamie L. Schaefer, Gina M. Martorana, Monica A. Levine, Craig A. Meyers, Mark B. Sherwood

Faculty & Staff Scholarship

Purpose

To examine the effect of cannula diameter and conjunctival flap method on bleb survival in rabbits undergoing cannula-based glaucoma filtration surgery (GFS).

Methods

Twelve New Zealand White rabbits underwent GFS in both eyes. The twenty-four eyes were divided into four groups. Two of the four groups (N = 12) received limbus-based con- junctival flaps (LBCF), and the other two (N = 12) received fornix-based conjunctival flaps (FBCF). Six FBCF rabbit eyes were implanted with 22-gauge drainage tubes, and the other six were implanted with 26-gauge tubes. Likewise, six LBCF rabbits received 22-gauge drainage tubes and six received 26-gauge tubes. …

A Small Molecule P53 Activator Attenuates Fanconi Anemia Leukemic Stem Cell Proliferation, Wei Du, Xiaoli Li, Andrew F. Wilson, Qishen Pang

Faculty & Staff Scholarship

Although p53 mutations are common in solid tumors, such mutations are found at a lower frequency in hematologic malignancies. In the genetic disorder Fanconi anemia (FA), p53 has been proposed as an important pathophysiological factor for two important hematologic hallmarks of the disease: bone marrow failure and leukemogenesis. Here we show that low levels of the p53 protein enhance the capacity of leukemic stem cells from FA patients to repopulate immunodeficient mice. Furthermore, boosting p53 protein levels with the use of the small molecule Nutlin-3 reduced leukemia burden in recipient mice. These results demonstrate that the level of p53 protein …

Longitudinal Analysis Of Raccoon Rabies In West Virginia, 2000–2015: A Preliminary Investigation, K. Bert Plants, Sijin Wen, Jeffery Wimsatt, Sarah Knox

Faculty & Staff Scholarship

Animal borne rabies virus is a source of infection in humans, and raccoons (Procyon lotor) are the primary terrestrial reservoir in West Virginia (WV). To assess the behavior and status of raccoon variant rabies virus (RRV) cases in WV, a longitudinal analysis for the period 2000–2015 was performed, using data provided by the state Bureau of Public Health. The analytic approach used was negative binomial regression, with exclusion of those counties that had not experienced RRV cases in the study period, and with further examination of those counties where oral rabies vaccine (ORV) baits had been distributed as compared with …

Short Term Evaluation Of Respiratory Effort By Premature Infants Supported With Bubble Nasal Continuous Airway Pressure Using Seattle-Pap And A Standard Bubble Device, Stephen E. Welty, Craig G. Rusin, Larissa I. Stanberry, George T. Mandy, Alfred L. Gest, Jeremy M. Ford, Carl H. Backes Jr, C. Peter Richardson, Christopher R. Howard, Thomas N. Hansen, Charles V. Smith

Faculty & Staff Scholarship

Background

Almost one million prematurely born infants die annually from respiratory insufficiency, pre- dominantly in countries with limited access to respiratory support for neonates. The primary hypothesis tested in the present study was that a modified device for bubble nasal continu- ous positive airway pressure (Bn-CPAP) would provide lower work of spontaneous breath- ing, estimated by esophageal pressure-rate products.

Methods

Infants born

Results

All 40 infants enrolled completed the study and follow-up through 36 wks post menstrual age or hospital discharge, whichever came first. No infants were on supplemental oxygen at completion of follow-up. No infants developed pneumothoraces or nasal …

Possible Bite-Induced Abscess And Osteomyelitis In Lufengosaurus (Dinosauria: Sauropodomorph) From The Lower Jurassic Of The Yimen Basin, China, Lida Xing, Bruce M. Rothschild, Patrick S. Randolph-Quinney, Yi Wang, Alexander H. Parkinson, Hao Ran

Faculty & Staff Scholarship

We report an osseous abnormality on a specimen of the sauropod dinosaur Lufengosaurus huenei from the Fengjiahe Formation in Yuxi Basin, China. A gross pathological defect occurs on the right third rib, which was subjected to micro-computed tomographic imaging as an aid in diagnosis. The analysis of pathological characteristics and the shape of the abnormality is incompatible with impact or healed trauma, such as a common rib fracture, and instead suggests focal penetration of the rib, possibly due to a failed predator attack. The identification of characteristics based on gross morphology and internal micro-morphology presented by the specimen, suggests an …

Osseointegrated Transcutaneous Device For Amputees: A Pilot Large Animal Model, Brian T. Grisez, Andrew E. Hanselman, Karim W. Boukhemis, Trapper A.J. Lalli, Brock A. Lindsey

Faculty & Staff Scholarship

Traditional above-the-knee amputation prosthetics utilize a stump-socket interface that is well-known for skin/socket problems, sitting difficulty, disuse osteopenia, and increased work of ambulation. As a result, we evaluated a novel osseointegrated transcutaneous implant in a large animal. The implant was designed to promote osseointegration at the bone-implant interface and minimize complications. As proof of concept, four Dorset sheep underwent a two-stage surgery for forelimb placement of an osseointegrated transcutaneous implant utilizing Compress�� technology (Biomet, Inc., Warsaw, IN). Two sheep received a long anchor plug (90 mm long x 9 mm in diameter) and two received a short anchor plug (46 …

Navigating The “No Man's Land” Of Tki-Failed Egfr-Mutated Non– Small Cell Lung Cancer (Nsclc): A Review, Bryan Oronsky, Patrick Ma, Tony R. Reid, Pedro Cabrales, Michelle Lybeck, Arnold Oronsky, Neil Oronsky, Corey A. Carter

Faculty & Staff Scholarship

As the leading cause of cancer-related mortality, lung cancer is a worldwide health issue that is overwhelmingly caused by smoking. However, a substantial minority (~25%) of patients with non–small cell lung cancer (NSCLC) has never smoked. In these patients, activating mutations of the epidermal growth factor receptor (EGFR) are more likely, which render their tumors susceptible for a finite period to treatment with EGFR tyrosine kinase inhibitors (TKIs) and confer a better prognosis than EGFR wild-type NSCLC. On progression, due to the inevitable insurgence of resistance, TKIs are generally followed by second- or third-line salvage chemotherapy until treatment failure, after …

2018 Symposium Brochure

Programs

No abstract provided.

Validation Of A Dietary Screening Tool In A Middle-Aged Appalachian Population, Melissa Ventura Marra, Sowmyanarayanan V. Thuppal, Elizabeth J. Johnson, Regan L. Bailey

Faculty & Staff Scholarship

Proactive nutrition screening is an effective public health strategy for identifying and targeting individuals who could benefit from making dietary improvements for primary and secondary prevention of disease. The Dietary Screening Tool (DST) was developed and validated to assess nutritional risk among rural older adults. The purpose of this study was to evaluate the utility and validity of the DST to identify nutritional risk in middle-aged adults. This cross-sectional study in middle-aged adults (45–64 year olds, n = 87) who reside in Appalachia, examined nutritional status using an online health survey, biochemical measures, anthropometry, and three representative 24-h dietary recalls. …

The Antioxidant Xanthorrhizol Prevents Amyloid-Β-Induced Oxidative Modification And Inactivation Of Neprilysin, Chol Seung Lim, Jung-Soo Han

Faculty & Staff Scholarship

Activity of neprilysin (NEP), the major protease which cleaves amyloid-β peptide (Aβ), is reportedly reduced in the brains of patients with Alzheimer’s disease (AD). Accumulation of Aβ generates reactive oxygen species (ROS) such as 4-hydroxynonenal (HNE), and then reduces activities of Aβ-degrading enzymes including NEP. Xanthorrhizol (Xan), a natural sesquiterpenoid, has been reported to possess antioxidant and anti-inflammatory proper- ties. The present study examined the effects of Xan on HNE- or oligomeric Aβ42-induced ox- idative modification of NEP protein. Xan was added to the HNE- or oligomeric Aβ42-treated SK-N-SH human neuroblastoma cells and then levels, oxidative modification and enzymatic activities …

Study On The Relationship Between Expression Patterns Of Cocaine-And Amphetamine Regulated Transcript And Hormones Secretion In Porcine Ovarian Follicles, Pengfei Li, Jinzhu Meng, Jiongjie Jing, Qingling Hao, Zhiwei Zhu, Jianbo Yao, Lihua Lyu

Faculty & Staff Scholarship

Background: Cocaine-and amphetamine regulated transcript (CART) is an endogenous neuropeptide, which is widespread in animals, plays a key role in regulation of follicular atresia in cattle and sheep. Among animal ovaries, CART mRNA was firstly found in the cattle ovaries. CART was localized in the antral follicles oocytes, granulosa and cumulus cells by immunohistochemistry and in situ hybridization. Further research found that secretion of E2 was inhibited in granulosa cells with a certain dose of CART, the effect depends on the stage of cell differentiation, sug- gesting that CART could play a crucial role in regulating follicle atresia. The objective …

Hyperspectral Imaging And K-Means Classification For Histologic Evaluation Of Ductal Carcinoma In Situ, Yasser Khouj, Jeremy Dawson, James Coad, Linda Vona-Davis

Faculty & Staff Scholarship

Hyperspectral imaging (HSI) is a non-invasive optical imaging modality that shows the potential to aid pathologists in breast cancer diagnoses cases. In this study, breast cancer tissues from different patients were imaged by a hyperspectral system to detect spectral differences between normal and breast cancer tissues. Tissue samples mounted on slides were identified from 10 different patients. Samples from each patient included both normal and ductal carcinoma tissue, both stained with hematoxylin and eosin stain and unstained. Slides were imaged using a snapshot HSI system, and the spec- tral reflectance differences were evaluated. Analysis of the spectral reflectance values indicated …

Three-Dimensional Imaging Of Kndy Neurons In The Mammalian Brain Using Optical Tissue Clearing And Multiple-Label Immunocytochemistry, Aleisha M. Moore, Kathryn A. Lucas, Robert L. Goodman, Lique M. Coolen, Michael N. Lehman

Faculty & Staff Scholarship

Kisspeptin/Neurokinin B/Dynorphin (KNDy) neurons of the arcuate nucleus (ARC) play a key role in the regulation of fertility. The ability to detect features of KNDy neurons that are essential for fertility may require three-dimensional (3D) imaging of the complete population. Recently developed protocols for optical tissue clearing permits 3D imaging of neuronal populations in un-sectioned brains. However, these techniques have largely been described in the mouse brain. We report 3D imaging of the KNDy cell population in the whole rat brain and sheep hypothalamus using immunolabelling and modification of a solvent-based clearing protocol, iDISCO. This study expands the use of …

Transcriptional Profiling Of Saccharomyces Cerevisiae Reveals The Impact Of Variation Of A Single Transcription Factor On Differential Gene Expression In 4nqo, Fermentable, And Nonfermentable Carbon Sources, Xiaoqing Rong-Mullins, Michael C. Ayers, Mahmoud Summers, Jennifer E.G. Gallagher

Faculty & Staff Scholarship

Cellular metabolism can change the potency of a chemical’s tumorigenicity. 4-nitroquinoline-1-oxide (4NQO) is a tumorigenic drug widely used on animal models for cancer research. Polymorphisms of the transcription factor Yrr1 confer different levels of resistance to 4NQO in Saccharomyces cerevisiae. To study how different Yrr1 alleles regulate gene expression leading to resistance, transcriptomes of three isogenic S. cerevisiae strains carrying different Yrr1 alleles were profiled via RNA sequencing (RNA-Seq) and chromatin immunoprecipitation coupled with sequencing (ChIP-Seq) in the presence and absence of 4NQO. In response to 4NQO, all alleles of Yrr1 drove the expression of SNQ2 (a multidrug transporter), which …

Maternal Engineered Nanomaterial Inhalation During Gestation Alters The Fetal Transcriptome, P.A. Stapleton, Q.A. Hathaway, C.E. Nichols, A.B. Abukabda, M.V. Pinti, D.L. Shepherd, C.R. Mcbride, J. Yi, V.C. Castranova, J.M Hollander, Timothy Robert Nurkiewicz

Faculty & Staff Scholarship

Background: The integration of engineered nanomaterials (ENM) is well-established and widespread in clinical, commercial, and domestic applications. Cardiovascular dysfunctions have been reported in adult populations after exposure to a variety of ENM. As the diversity of these exposures continues to increase, the fetal ramifications of maternal exposures have yet to be determined. We, and others, have explored the consequences of ENM inhalation during gestation and identified many cardiovascular and metabolic outcomes in the F1 generation. The purpose of these studies was to identify genetic alterations in the F1 generation of Sprague-Dawley rats that result from maternal ENM inhalation during gestation. …

Macrophage Sensing Of Single- Walled Carbon Nanotubes Via Toll- Like Receptors, Sourav P. Mukherjee, Olesja Bondarenko, Pekka Kohonen, Fernando T. Andon, Tana Brzicova, Isabel Gessner, Sanjay Mathur, Massimo Bottini, Paolo Calligari, Lorenzo Stella, Elena Kisin, Anna Shvedova, Reija Autio, Heli Salminen-Mankonen, Ritta Lahesmaa, Bengt Fadeel

Faculty & Staff Scholarship

Carbon-based nanomaterials including carbon nanotubes (CNTs) have been shown to trigger

inflammation. However, how these materials are ‘sensed’ by immune cells is not known. Here we compared the effects of two carbon-based nanomaterials, single-walled CNTs (SWCNTs) and graphene oxide (GO), on primary human monocyte-derived macrophages. Genome-wide transcriptomics assessment was performed at sub-cytotoxic doses. Pathway analysis of the microarray data revealed pronounced effects on chemokine-encoding genes in macrophages exposed to SWCNTs, but not in response to GO, and these results were validated by multiplex array-based cytokine and chemokine profiling. Conditioned medium from SWCNT-exposed cells acted as a chemoattractant for dendritic cells. …

Absolute Lymphocyte And Neutrophil Counts In Neonatal Ischemic Brain Injury, Jessica M. Povroznik, Elizabeth B. Engler-Chiurazzi, Tania Nanavati, Paola Pergami

Faculty & Staff Scholarship

Objectives: This study aimed to identify differences in absolute neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio between neonates with two forms of ischemic brain injury, hypoxic-ischemic encephalopathy, and acute ischemic stroke, compared to controls. We also aimed to determine whether this neutrophil/lymphocyte response pattern is associated with disease severity or is a consequence of the effects of total-body cooling, an approved treatment for moderate-to-severe hypoxic-ischemic encephalopathy. Methods: A retrospective chart review of 101 neonates with hypoxic-ischemic encephalopathy + total-body cooling (n = 26), hypoxic-ischemic encephalopathy (n=12), acute ischemic stroke (n=15), and transient tachypnea of the newborn (n=48) was conducted; transient tachypnea of …

Hcn2 Channels In The Ventral Tegmental Area Regulate Behavioral Responses To Chronic Stress, Peng Zhong, Casey R. Vickstrom, Xiaojie Liu, Ying Hu, Laikang Yu, Han-Gang Yu, Qing-Song Liu

Faculty & Staff Scholarship

Dopamine neurons in the ventral tegmental area (VTA) are powerful regulators of depression-related behavior. Dopamine neuron activity is altered in chronic stress-based models of depression, but the underlying mechanisms remain incompletely understood. Here, we show that mice subject to chronic mild unpredictable stress (CMS) exhibit anxiety- and depressive-like behavior, which was associated with decreased VTA dopamine neuron firing in vivo and ex vivo. Dopamine neuron firing is governed by voltage-gated ion channels, in particular hyperpolarization- activated cyclic nucleotide-gated (HCN) channels. Following CMS, HCN-mediated currents were decreased in nucleus accumbens-projecting VTA dopamine neurons. Furthermore, shRNA-mediated HCN2 knockdown in the VTA was …