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The Effects Of Bacterial Endotoxin Lps On Synaptic Transmission At The Neuromuscular Junction, Robin L. Cooper, Micaiah Mcnabb, Jeremy Nadolski Mar 2019

The Effects Of Bacterial Endotoxin Lps On Synaptic Transmission At The Neuromuscular Junction, Robin L. Cooper, Micaiah Mcnabb, Jeremy Nadolski

Biology Faculty Publications

The direct action of bacterial lipopolysaccharides (LPS) endotoxin was shown to enhance synaptic transmission and hyperpolarize the membrane potential at low doses, but block glutamatergic receptors and decrease observable spontaneous events at a high dosage. The dosage effects are LPS type specific. The hyperpolarization is not due to voltage-gated potassium channels or to activation of nitric oxide synthase (NOS). The effects are induced directly by LPS, independent of an immune response.


Proteomic Alterations Of Hdl In Youth With Type 1 Diabetes And Their Associations With Glycemic Control: A Case-Control Study, Evgenia Gourgari, Junfeng Ma, Martin P. Playford, Nehal N. Mehta, Radoslav Goldman, Alan T. Remaley, Scott M. Gordon Mar 2019

Proteomic Alterations Of Hdl In Youth With Type 1 Diabetes And Their Associations With Glycemic Control: A Case-Control Study, Evgenia Gourgari, Junfeng Ma, Martin P. Playford, Nehal N. Mehta, Radoslav Goldman, Alan T. Remaley, Scott M. Gordon

Saha Cardiovascular Research Center Faculty Publications

Background: Patients with type 1 diabetes (T1DM) typically have normal or even elevated plasma high density lipoprotein (HDL) cholesterol concentrations; however, HDL protein composition can be altered without a change in cholesterol content. Alteration of the HDL proteome can result in dysfunctional HDL particles with reduced ability to protect against cardiovascular disease (CVD). The objective of this study was to compare the HDL proteomes of youth with T1DM and healthy controls (HC) and to evaluate the influence of glycemic control on HDL protein composition.

Methods: This was a cross-sectional case–control study. Blood samples were obtained from patients with T1DM and …


Kinase Suppressor Of Ras 1 And Exo70 Promote Fatty Acid-Stimulated Neurotensin Secretion Through Erk1/2 Signaling, Stephanie Rock, Xian Li, Jun Song, Courtney M. Townsend, Heidi L. Weiss, Piotr G. Rychahou, Tianyan Gao, Jing Li, B. Mark Evers Mar 2019

Kinase Suppressor Of Ras 1 And Exo70 Promote Fatty Acid-Stimulated Neurotensin Secretion Through Erk1/2 Signaling, Stephanie Rock, Xian Li, Jun Song, Courtney M. Townsend, Heidi L. Weiss, Piotr G. Rychahou, Tianyan Gao, Jing Li, B. Mark Evers

Markey Cancer Center Faculty Publications

Neurotensin is a peptide hormone released from enteroendocrine cells in the small intestine in response to fat ingestion. Although the mechanisms regulating neurotensin secretion are still incompletely understood, our recent findings implicate a role for extracellular signal–regulated kinase 1 and 2 as positive regulators of free fatty acid-stimulated neurotensin secretion. Previous studies have shown that kinase suppressor of Ras 1 acts as a molecular scaffold of the Raf/MEK/extracellular signal–regulated kinase 1 and 2 kinase cascade and regulates intensity and duration of extracellular signal–regulated kinase 1 and 2 signaling. Here, we demonstrate that inhibition of kinase suppressor of Ras 1 attenuates …


Temporary Fracture Stabilization Device, Steven J. Lawrence Mar 2019

Temporary Fracture Stabilization Device, Steven J. Lawrence

Orthopaedic Surgery and Sports Medicine Faculty Patents

A temporary fracture stabilization device includes a first intramedullary fixation rod, a second intramedullary fixation rod, a first extramedullary connector, a second extramedullary connector and a fastener. A field kit for temporary fracture stabilization is also disclosed.


The Flavonoid Metabolite 2,4,6-Trihydroxybenzoic Acid Is A Cdk Inhibitor And An Anti-Proliferative Agent: A Potential Role In Cancer Prevention, Ranjini Sankaranarayanan, Chaitanya K. Valiveti, Ramesh Kumar Dhandapani, Severine Van Slambrouck, Siddharth S. Kesharwani, Teresa Seefeldt, Joy Scaria, Hemachand Tummala, G. Jayarama Bhat Mar 2019

The Flavonoid Metabolite 2,4,6-Trihydroxybenzoic Acid Is A Cdk Inhibitor And An Anti-Proliferative Agent: A Potential Role In Cancer Prevention, Ranjini Sankaranarayanan, Chaitanya K. Valiveti, Ramesh Kumar Dhandapani, Severine Van Slambrouck, Siddharth S. Kesharwani, Teresa Seefeldt, Joy Scaria, Hemachand Tummala, G. Jayarama Bhat

Entomology Faculty Publications

Flavonoids have emerged as promising compounds capable of preventing colorectal cancer (CRC) due to their anti-oxidant and anti-inflammatory properties. It is hypothesized that the metabolites of flavonoids are primarily responsible for the observed anti-cancer effects owing to the unstable nature of the parent compounds and their degradation by colonic microflora. In this study, we investigated the ability of one metabolite, 2,4,6-trihydroxybenzoic acid (2,4,6-THBA) to inhibit Cyclin Dependent Kinase (CDK) activity and cancer cell proliferation. Using in vitro kinase assays, we demonstrated that 2,4,6-THBA dose-dependently inhibited CDKs 1, 2 and 4 and in silico studies identified key amino acids involved in …


Session 3a: Drinking Water, Kentucky Water Resources Research Institute, University Of Kentucky Mar 2019

Session 3a: Drinking Water, Kentucky Water Resources Research Institute, University Of Kentucky

Kentucky Water Resources Annual Symposium

  • Evaluating Potential Health Threats from Untreated Karst Springs as Community Drinking Water Sources, Monroe County, Kentucky
  • Benefits of Energy Savings Performance Contracting for Water and Wastewater Treatment Facilities
  • Self-Cleaning Nanocomposite Membranes with Phosphorene-Based Pore Fillers for Water Treatment


Poster Session 2, Kentucky Water Resources Research Institute, University Of Kentucky Mar 2019

Poster Session 2, Kentucky Water Resources Research Institute, University Of Kentucky

Kentucky Water Resources Annual Symposium

  • 2.1 Climate Change Impacts on Sediment Transport in a Lowland Watershed System: Controlling Processes and Projection
  • 2.2 Assessment of MRSA Presence in Suburban WWTPs Effluent and Receiving Streams in Lexington, Kentucky
  • 2.3 Heavy Metal Capture and Detection Using Colored Synthetic Dithiol
  • 2.4 Quantifying Nutrient Fate and Transport in Karst Agroecosystems of Central Kentucky: Application of High-Resolution Sensors, Numerical Modeling, and Isotope Tracers
  • 2.5 Magnetic Nanocomposite Materials for the Detection and Removal of Halogenated Organic Pollutants in Contaminated Water Sources
  • 2.6 Measuring and Modeling Morphologic Processes in Karst to Sustain Water Resources in the Future
  • 2.7 Impedance Spectroscopy Based Evaluation of …


Poster Session 1, Kentucky Water Resources Research Institute, University Of Kentucky Mar 2019

Poster Session 1, Kentucky Water Resources Research Institute, University Of Kentucky

Kentucky Water Resources Annual Symposium

  • 1.1 Evaluating Soil Characteristics in Rural and Urban Areas
  • 1.2 Use of eDNA in Detection of Multiple Salamander Species in Eastern Kentucky Streams
  • 1.3 Evaluation of biomass and filtration method on eDNA detection of fantail darters (Etheostoma flabellare)
  • 1.4 The Impact of Agricultural Development on Nutrient Contamination Hotspots Within a Small, Intermittent Watershed at EKU’s Meadowbrook Farm, Madison County, Kentucky
  • 1.5 How Does Drought Length Impact the Runoff and Nutrient Storm Response in an Agricultural, Intermittent Catchment in Central Kentucky?
  • 1.6 Analyzing Sanitary Sewer Overflow Sensitivity to Storm Characteristics
  • 1.7 Evaluating Soil Properties in No-Till and Conventional Tillage Systems
  • 1.8 …


Proceedings Of 2019 Kentucky Water Resources Annual Symposium, Kentucky Water Resources Research Institute, University Of Kentucky Mar 2019

Proceedings Of 2019 Kentucky Water Resources Annual Symposium, Kentucky Water Resources Research Institute, University Of Kentucky

Kentucky Water Resources Annual Symposium

This symposium was planned and conducted as a part of the state water resources research institute annual program that is supported by Grant/Cooperative Agreement Number G16AP00055 from the United States Geological Survey. The contents of this proceedings document and the views and conclusions presented at the symposium are solely the responsibility of the individual authors and presenters and do not necessarily represent the official views of the USGS or of the symposium organizers and sponsors. This publication is produced with the understanding that the United States Government is authorized to reproduce and distribute reprints for government purposes. Mention of trade …


Dirt, Saliva And Leprosy: Anti-Inflammatory And Anti-Infectious Effects, Helieh S. Oz Mar 2019

Dirt, Saliva And Leprosy: Anti-Inflammatory And Anti-Infectious Effects, Helieh S. Oz

Internal Medicine Faculty Publications

Ancient Egyptians smeared a mixture of dark soil on their eyelids and believed it protected eyes from unknown forces (illness). Recent studies have proven that the dark soil across the Nile River is rich in natural compounds including lead sulfide, which in low levels, promotes the production of nitric oxide (240-fold) by keratinocytes, with strong immune stimulatory and antimicrobial properties. Current investigations reveal anti-inflammatory and anti-infectious activities—including cytokines and chemokines—in saliva, as well as its friendly microbiota, which lines the surface of the oral cavity, its protection against inflammatory and infectious organisms in the stoma and other organs, such as …


Photocatalytic Degradation Of Profenofos And Triazophos Residues In The Chinese Cabbage, Brassica Chinensis, Using Ce-Doped Tio2, Xiangying Liu, You Zhan, Zhongqin Zhang, Lang Pan, Lifeng Hui, Kailin Liu, Xuguo Zhou, Lianyang Bai Mar 2019

Photocatalytic Degradation Of Profenofos And Triazophos Residues In The Chinese Cabbage, Brassica Chinensis, Using Ce-Doped Tio2, Xiangying Liu, You Zhan, Zhongqin Zhang, Lang Pan, Lifeng Hui, Kailin Liu, Xuguo Zhou, Lianyang Bai

Entomology Faculty Publications

Pesticides have revolutionized the modern day of agriculture and substantially reduced crop losses. Synthetic pesticides pose a potential risk to the ecosystem and to the non-target organisms due to their persistency and bioaccumulation in the environment. In recent years, a light-mediated advanced oxidation processes (AOPs) has been adopted to resolve pesticide residue issues in the field. Among the current available semiconductors, titanium dioxide (TiO2) is one of the most promising photocatalysts. In this study, we investigated the photocatalytic degradation of profenofos and triazophos residues in Chinese cabbage, Brassica chinensis, using a Cerium-doped nano semiconductor TiO2 (TiO …


Unusual Substrate And Halide Versatility Of Phenolic Halogenase Pltm, Shogo Mori, Allan H. Pang, Nishad Thamban Chandrika, Sylvie Garneau-Tsodikova, Oleg V. Tsodikov Mar 2019

Unusual Substrate And Halide Versatility Of Phenolic Halogenase Pltm, Shogo Mori, Allan H. Pang, Nishad Thamban Chandrika, Sylvie Garneau-Tsodikova, Oleg V. Tsodikov

Pharmaceutical Sciences Faculty Publications

Controlled halogenation of chemically versatile substrates is difficult to achieve. Here we describe a unique flavin-dependent halogenase, PltM, which is capable of utilizing a wide range of halides for installation on a diverse array of phenolic compounds, including FDA-approved drugs and natural products, such as terbutaline, fenoterol, resveratrol, and catechin. Crystal structures of PltM in complex with phloroglucinol and FAD in different states yield insight into substrate recognition and the FAD recycling mechanism of this halogenase.


Feature Selection For Longitudinal Data By Using Sign Averages To Summarize Gene Expression Values Over Time, Suyan Tian, Chi Wang Mar 2019

Feature Selection For Longitudinal Data By Using Sign Averages To Summarize Gene Expression Values Over Time, Suyan Tian, Chi Wang

Biostatistics Faculty Publications

With the rapid evolution of high-throughput technologies, time series/longitudinal high-throughput experiments have become possible and affordable. However, the development of statistical methods dealing with gene expression profiles across time points has not kept up with the explosion of such data. The feature selection process is of critical importance for longitudinal microarray data. In this study, we proposed aggregating a gene’s expression values across time into a single value using the sign average method, thereby degrading a longitudinal feature selection process into a classic one. Regularized logistic regression models with pseudogenes (i.e., the sign average of genes across time as predictors) …


Examining Medline Search Query Reproducibility And Resulting Variation In Search Results, C. Sean Burns, Robert M. Shapiro Ii, Tyler Nix, Jeffrey T. Huber Mar 2019

Examining Medline Search Query Reproducibility And Resulting Variation In Search Results, C. Sean Burns, Robert M. Shapiro Ii, Tyler Nix, Jeffrey T. Huber

Information Science Faculty Publications

The MEDLINE database is publicly available through the National Library of Medicine’s PubMed but the data file itself is also licensed to a number of vendors, who may offer their versions to institutional and other parties as part of a database platform. These vendors provide their own interface to the MEDLINE file and offer other technologies that attempt to make their version useful to subscribers. However, little is known about how vendor platforms ingest and interact with MEDLINE data files, nor how these changes influence the construction of search queries and the results they produce. This poster presents a longitudinal …


Impact Of Row Spacing, Sowing Density And Nitrogen Fertilization On Yield And Quality Traits Of Chia (Salvia Hispanica L.) Cultivated In Southwestern Germany, Samantha J. Grimes, Timothy D. Phillips, Filippo Capezzone, Simone Graeff-Hönninger Mar 2019

Impact Of Row Spacing, Sowing Density And Nitrogen Fertilization On Yield And Quality Traits Of Chia (Salvia Hispanica L.) Cultivated In Southwestern Germany, Samantha J. Grimes, Timothy D. Phillips, Filippo Capezzone, Simone Graeff-Hönninger

Plant and Soil Sciences Faculty Publications

To obtain high chia seed yields and seed qualities, a suitable crop management system needs to be developed for the given growing conditions in southwestern Germany. Field experiments were conducted at the experimental station Ihinger Hof in two consecutive years (2016, 2017). The study aimed to evaluate yield and quality traits of chia depending on different (i) row spacing (35, 50 and 75 cm), (ii) sowing densities (1, 1.5 and 2 kg ha−1) and, (iii) N-fertilization rates (0, 20 and 40 kg N ha−1). It consisted of three independent, completely randomized field experiments with three replications. …


Efficacy Of Leukemia Inhibitory Factor As A Therapeutic For Permanent Large Vessel Stroke Differs Among Aged Male And Female Rats, Stephanie M. Davis, Lisa A. Collier, Sarah J. Goodwin, Douglas E. Lukins, David K. Powell, Keith R. Pennypacker Mar 2019

Efficacy Of Leukemia Inhibitory Factor As A Therapeutic For Permanent Large Vessel Stroke Differs Among Aged Male And Female Rats, Stephanie M. Davis, Lisa A. Collier, Sarah J. Goodwin, Douglas E. Lukins, David K. Powell, Keith R. Pennypacker

Neurology Faculty Publications

Preclinical studies using rodent models of stroke have had difficulty in translating their results to human patients. One possible factor behind this inability is the lack of studies utilizing aged rodents of both sexes. Previously, this lab showed that leukemia inhibitory factor (LIF) promoted recovery after stroke through antioxidant enzyme upregulation. This study examined whether LIF promotes neuroprotection in aged rats of both sexes. LIF did not reduce tissue damage in aged animals, but LIF-treated female rats showed partial motor skill recovery. The LIF receptor (LIFR) showed membrane localization in young male and aged rats of both sexes after stroke. …


Induction Of Ampk Activation By N,N'-Diarylurea Fnd-4b Decreases Growth And Increases Apoptosis In Triple Negative And Estrogen-Receptor Positive Breast Cancers, Jeremy Johnson, Piotr G. Rychahou, Vitaliy M. Sviripa, Heidi L. Weiss, Chunming Liu, David S. Watt, B. Mark Evers Mar 2019

Induction Of Ampk Activation By N,N'-Diarylurea Fnd-4b Decreases Growth And Increases Apoptosis In Triple Negative And Estrogen-Receptor Positive Breast Cancers, Jeremy Johnson, Piotr G. Rychahou, Vitaliy M. Sviripa, Heidi L. Weiss, Chunming Liu, David S. Watt, B. Mark Evers

Markey Cancer Center Faculty Publications

Purpose

Triple negative breast cancer (TNBC) is the most lethal and aggressive subtype of breast cancer. AMP-activated protein kinase (AMPK) is a major energy regulator that suppresses tumor growth, and 1-(3-chloro-4-((trifluoromethyl)thio)phenyl)-3-(4-(trifluoromethoxy)phenyl)urea (FND-4b) is a novel AMPK activator that inhibits growth and induces apoptosis in colon cancer. The purpose of this project was to test the effects of FND-4b on AMPK activation, proliferation, and apoptosis in breast cancer with a particular emphasis on TNBC.

Materials and methods

(i) Estrogen-receptor positive breast cancer (ER+BC; MCF-7, and T-47D), TNBC (MDA-MB-231 and HCC-1806), and breast cancer stem cells were treated with FND-4b for 24h. …


Nitrogen Fertilizer Suppresses Mineralization Of Soil Organic Matter In Maize Agroecosystems, Navreet K. Mahal, William R. Osterholz, Fernando E. Miguez, Hanna J. Poffenbarger, John E. Sawyer, Daniel C. Olk, Sotirios V. Archontoulis, Michael J. Castellano Mar 2019

Nitrogen Fertilizer Suppresses Mineralization Of Soil Organic Matter In Maize Agroecosystems, Navreet K. Mahal, William R. Osterholz, Fernando E. Miguez, Hanna J. Poffenbarger, John E. Sawyer, Daniel C. Olk, Sotirios V. Archontoulis, Michael J. Castellano

Plant and Soil Sciences Faculty Publications

The possibility that N fertilizer increases soil organic matter (SOM) mineralization and, as a result, reduces SOM stocks has led to a great debate about the long-term sustainability of maize-based agroecosystems as well as the best method to estimate fertilizer N use efficiency (FNUE). Much of this debate is because synthetic N fertilizer can positively or negatively affect SOM mineralization via several direct and indirect pathways. Here, we test a series of hypotheses to determine the direction, magnitude, and mechanism of N fertilizer effect on SOM mineralization and discuss the implications for methods to estimate FNUE. We measured the effect …


Favorable Outcomes With Ventricular Assist Device Exchange, Megan Carroll, Meghan Tooman, Markian Bochan, Christopher Salerno, Ashwin Ravichandran Mar 2019

Favorable Outcomes With Ventricular Assist Device Exchange, Megan Carroll, Meghan Tooman, Markian Bochan, Christopher Salerno, Ashwin Ravichandran

The VAD Journal

Left ventricular assist device (LVAD) therapy remains a vital therapeutic option for patients with end-stage heart failure. Unfortunately, adverse events can occur and progress to require consideration for device exchange once the failure of medical management becomes evident, especially when heart transplantation is not possible in a timely manner. The aim of this analysis is to describe the incidence and outcomes of LVAD exchanges at our institution. Between April 2008 and May 2017, 397 patients underwent LVAD implantation, with 32 of those patients subsequently receiving exchange upon the recommendation of our multidisciplinary team due to refractory infection (n=12), device malfunction …


A Mentor-Led Text-Messaging Intervention Increases Intake Of Fruits And Vegetables And Goal Setting For Healthier Dietary Consumption Among Rural Adolescents In Kentucky And North Carolina, 2017, Alison A. Gustafson, Stephanie B. Jilcott Pitts, Kristen Mcquerry, Oyinlola Babtunde, Janet Mullins Mar 2019

A Mentor-Led Text-Messaging Intervention Increases Intake Of Fruits And Vegetables And Goal Setting For Healthier Dietary Consumption Among Rural Adolescents In Kentucky And North Carolina, 2017, Alison A. Gustafson, Stephanie B. Jilcott Pitts, Kristen Mcquerry, Oyinlola Babtunde, Janet Mullins

Dietetics and Human Nutrition Faculty Publications

Introduction—Text-messaging interventions hold promise for successful weight loss interventions. However, there is limited research on text-messaging interventions to improve dietary intake among rural adolescents, who are at greater risk for obesity and related risk factors. The goal of this study was to test an eight-week, mentor-led text-messaging intervention among 14–16-year-old rural adolescents: the “Go Big and Bring It Home” Project to improve fruit and vegetable and healthy beverage intake. Methods and Materials—Eight rural high schools in eastern Kentucky and eastern North Carolina participated (n = 4 were randomized as intervention schools and n = 4 were randomized as control …


H727 Cells Are Inherently Resistant To The Proteasome Inhibitor Carfilzomib, Yet Require Proteasome Activity For Cell Survival And Growth, Min Jae Lee, Zachary Miller, Ji Eun Park, Deepak Bhattarai, Wooin Lee, Kyung Bo Kim Mar 2019

H727 Cells Are Inherently Resistant To The Proteasome Inhibitor Carfilzomib, Yet Require Proteasome Activity For Cell Survival And Growth, Min Jae Lee, Zachary Miller, Ji Eun Park, Deepak Bhattarai, Wooin Lee, Kyung Bo Kim

Pharmaceutical Sciences Faculty Publications

The second-in-class proteasome inhibitor (PI) carfilzomib (Kyprolis, Cfz) has contributed to a substantial advancement in multiple myeloma treatment by improving patient survival and quality of life. A considerable portion of patients however display intrinsic resistance to Cfz. Our mechanistic understanding of intrinsic Cfz resistance is limited due to a lack of suitable cell-based models. We report that H727 human bronchial carcinoid cells are inherently resistant to Cfz, yet susceptible to other PIs and inhibitors targeting upstream components of the ubiquitin-proteasome system (UPS). These results indicate that H727 cells remain dependent on the UPS for cell survival and growth despite harboring …


Successful Extracorporeal Membrane Oxygenation In The Management Of Acute Respiratory Distress Syndrome And Cardiopulmonary Collapse Secondary To Amniotic Fluid Embolism, Sumon Roy, Nishit A. Biniwale, Venkata S. Pendela, Patricia Oates, Katrina Wojciechowski, Scott C. Feitell Mar 2019

Successful Extracorporeal Membrane Oxygenation In The Management Of Acute Respiratory Distress Syndrome And Cardiopulmonary Collapse Secondary To Amniotic Fluid Embolism, Sumon Roy, Nishit A. Biniwale, Venkata S. Pendela, Patricia Oates, Katrina Wojciechowski, Scott C. Feitell

The VAD Journal

Amniotic fluid embolism (AFE) is one of the most devastating complications of pregnancy that typically manifests as acute cardiopulmonary collapse during delivery or in the postpartum period. The potential role of extracorporeal membrane oxygenation (ECMO) as a management technique in severe cases of AFE remains largely unknown given the limited literature available. In this report, we present the first case, to our knowledge, of successful implementation of ECMO as a life-saving measure in a case of hemorrhagic shock due to postpartum bleeding complicated by severe AFE leading to acute respiratory distress syndrome (ARDS) ultimately requiring tracheostomy. Hemodynamic decompensation is often …


The Effects Of Huntingtin-Lowering: What Do We Know So Far?, William F. Kaemmerer, Richard C. Grondin Mar 2019

The Effects Of Huntingtin-Lowering: What Do We Know So Far?, William F. Kaemmerer, Richard C. Grondin

Neuroscience Faculty Publications

Therapies targeting mutant huntingtin DNA, mRNA, and protein have a chance at becoming the first disease-modifying treatments for Huntington’s disease, a fatal inherited neurodegenerative disorder for which only symptom management treatments are available today. This review focuses on evidence addressing several key questions pertinent to huntingtin-lowering, ranging from the functions of wild-type huntingtin (wtHTT) that may be disrupted by huntingtin-lowering treatments through the various ways huntingtin can be lowered, the tolerability of wtHTT-lowering in mice and primates, what has been found in the Ionis Pharmaceutical safety trial of a huntingtin-lowering therapy, and to the question of how much mutant huntingtin …


Mutational Effects Of Human Dopamine Transporter At Tyrosine88, Lysine92, And Histidine547 On Basal And Hiv-1 Tat-Inhibited Dopamine Transport, Wei-Lun Sun, Pamela M. Quizon, Yaxia Yuan, Matthew J. Strauss, Richard Mccain Jr., Chang-Guo Zhan, Jun Zhu Mar 2019

Mutational Effects Of Human Dopamine Transporter At Tyrosine88, Lysine92, And Histidine547 On Basal And Hiv-1 Tat-Inhibited Dopamine Transport, Wei-Lun Sun, Pamela M. Quizon, Yaxia Yuan, Matthew J. Strauss, Richard Mccain Jr., Chang-Guo Zhan, Jun Zhu

Molecular Modeling and Biopharmaceutical Center Faculty Publications

Dysregulation of dopaminergic system induced by HIV-1 Tat protein-mediated direct inhibition of the dopamine transporter (DAT) has been implicated as a mediating factor of HIV-1 associated neurocognitive disorders. We have reported that single point mutations on human DAT (hDAT) at tyrosine88 (Y88F), lysine92 (K92M), and histidine547 (H547A) differentially regulate basal dopamine uptake but diminish Tat-induced inhibition of dopamine uptake by changing dopamine transport process. This study evaluated the effects of double (Y88F/H547A) and triple (Y88F/K92M/H547A) mutations on basal dopamine uptake, Tat-induced inhibition of DAT function, and dynamic transport process. Compared to wild-type hDAT, the Vmax values of [3 …


Dennd5b Regulates Intestinal Triglyceride Absorption And Body Mass, Scott M. Gordon, Edward B. Neufeld, Zhihong Yang, Milton Pryor, Lita A. Freeman, Xiao Fan, Iftikhar J. Kullo, Leslie G. Biesecker, Alan T. Remaley Mar 2019

Dennd5b Regulates Intestinal Triglyceride Absorption And Body Mass, Scott M. Gordon, Edward B. Neufeld, Zhihong Yang, Milton Pryor, Lita A. Freeman, Xiao Fan, Iftikhar J. Kullo, Leslie G. Biesecker, Alan T. Remaley

Saha Cardiovascular Research Center Faculty Publications

Regulation of lipid absorption by enterocytes can influence metabolic status in humans and contribute to obesity and related complications. The intracellular steps of chylomicron biogenesis and transport from the Endoplasmic Reticulum (ER) to the Golgi complex have been described, but the mechanisms for post-Golgi transport and secretion of chylomicrons have not been identified. Using a newly generated Dennd5b−/− mouse, we demonstrate an essential role for this gene in Golgi to plasma membrane transport of chylomicron secretory vesicles. In mice, loss of Dennd5b results in resistance to western diet induced obesity, changes in plasma lipids, and reduced aortic atherosclerosis. In …


Genetic Interaction Analysis Among Oncogenesis-Related Genes Revealed Novel Genes And Networks In Lung Cancer Development, Yafang Li, Xiangjun Xiao, Yohan Bossé, Olga Gorlova, Ivan Gorlov, Younghun Han, Jinyoung Byun, Natasha Leighl, Jakob S. Johansen, Matt Barnett, Chu Chen, Gary Goodman, Angela Cox, Fiona Taylor, Penella Woll, H. Erich Wichmann, Judith Manz, Thomas Muley, Angela Risch, Albert Rosenberger, Jiali Han, Katherine Siminovitch, Susanne M. Arnold, Eric B. Haura, Ciprian Bolca, Ivana Holcatova, Vladimir Janout, Milica Kontic, Jolanta Lissowska, Anush Mukeria Mar 2019

Genetic Interaction Analysis Among Oncogenesis-Related Genes Revealed Novel Genes And Networks In Lung Cancer Development, Yafang Li, Xiangjun Xiao, Yohan Bossé, Olga Gorlova, Ivan Gorlov, Younghun Han, Jinyoung Byun, Natasha Leighl, Jakob S. Johansen, Matt Barnett, Chu Chen, Gary Goodman, Angela Cox, Fiona Taylor, Penella Woll, H. Erich Wichmann, Judith Manz, Thomas Muley, Angela Risch, Albert Rosenberger, Jiali Han, Katherine Siminovitch, Susanne M. Arnold, Eric B. Haura, Ciprian Bolca, Ivana Holcatova, Vladimir Janout, Milica Kontic, Jolanta Lissowska, Anush Mukeria

Markey Cancer Center Faculty Publications

The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterationsand tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study. Using a two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis, we identified …


Preventive Benefits Of U.S. Childcare Subsidies In Supervisory Child Neglect, Kathryn Maguire-Jack, Kelly M. Purtell, Kathryn Showalter, Sheila Barnhart, Mi-Youn Yang Mar 2019

Preventive Benefits Of U.S. Childcare Subsidies In Supervisory Child Neglect, Kathryn Maguire-Jack, Kelly M. Purtell, Kathryn Showalter, Sheila Barnhart, Mi-Youn Yang

Social Work Faculty Publications

Using data from age 3 of the Fragile Families and Child Wellbeing Study, the current study explores the complex relationships between U.S. child care subsidies and neglect. Specifically, the study examines two research questions: (1) Are U.S. child care subsidies associated with selfreported neglect among low-income mothers? (2) What individual types of self-reported neglect are significantly reduced by receipt of child care subsidy? Using negative binomial regression examining the relationships among mothers who were income-eligible for child care subsidy, we found that child care subsidy was associated with lower levels of supervisory neglect, indicating an important role of subsidy in …


Latent Sensitization In A Mouse Model Of Ocular Neuropathic Pain, Jooyoung Cho, Nicholas Bell, Gregory Botzet, Paras Vora, Benjamin J. Fowler, Renee R. Donahue, Heather M. Bush, Bradley K. Taylor, Romulo J. C. Albuquerque Mar 2019

Latent Sensitization In A Mouse Model Of Ocular Neuropathic Pain, Jooyoung Cho, Nicholas Bell, Gregory Botzet, Paras Vora, Benjamin J. Fowler, Renee R. Donahue, Heather M. Bush, Bradley K. Taylor, Romulo J. C. Albuquerque

Ophthalmology and Visual Science Faculty Publications

Purpose: Chronic ocular pain is poorly understood and difficult to manage. We developed a murine model of corneal surface injury (CSI)–induced chronic ocular neuropathic pain. The study focuses on changes in corneal nerve morphology and associated short- and long-term pain-like behavior after CSI.

Methods: CSI was induced in mice by local application of an alkali solution (0.75 N NaOH). Corneal nerve architecture, morphology, density, and length were studied. Eye-wiping was evaluated before and after CSI in response to hypertonic saline (2 M NaCl). Naltrexone (NTX) or Naloxone-methiodide (NLX-me), opioid receptor antagonists, were given subcutaneously (s.c., 3 mg/kg) or …


Pilot Study On The Efficiency Of Water-Only Decontamination For Firefighters’ Turnout Gear, Anthony Calvillo, Erin N. Haynes, Jeff Burkle, Kenny Schroeder, Angelo Calvillo, Julie Reese, Tiina Reponen Mar 2019

Pilot Study On The Efficiency Of Water-Only Decontamination For Firefighters’ Turnout Gear, Anthony Calvillo, Erin N. Haynes, Jeff Burkle, Kenny Schroeder, Angelo Calvillo, Julie Reese, Tiina Reponen

Epidemiology and Environmental Health Faculty Publications

Firefighters are exposed to toxic environments upon entering burning structures. Many structures contain synthetic materials which release toxic chemicals when on fire. These chemicals can enter the body through multiple routes of exposure, including inhalation and skin absorption. Thus, according to the fire departments included in this study, firefighters now conduct on-site decontamination procedures to remove hazardous chemicals, including polycyclic aromatic hydrocarbons from the surface of firefighter turnout gear. Several methods are being practiced at the local level, including decontamination with soap and water, and decontamination with water alone. The water-only decontamination method requires less time and supplies yet has …


Sphk2−/− Mice Are Protected From Obesity And Insulin Resistance, Shwetha Ravichandran, Brian S. Finlin, Philip A. Kern, Sabire Özcan Mar 2019

Sphk2−/− Mice Are Protected From Obesity And Insulin Resistance, Shwetha Ravichandran, Brian S. Finlin, Philip A. Kern, Sabire Özcan

Clinical and Translational Science Faculty Publications

Sphingosine kinases phosphorylate sphingosine to sphingosine 1‑phosphate (S1P), which functions as a signaling molecule. We have previously shown that sphingosine kinase 2 (Sphk2) is important for insulin secretion. To obtain a better understanding of the role of Sphk2 in glucose and lipid metabolism, we have characterized 20- and 52-week old Sphk2−/− mice using glucose and insulin tolerance tests and by analyzing metabolic gene expression in adipose tissue. A detailed metabolic characterization of these mice revealed that aging Sphk2−/− mice are protected from metabolic decline and obesity compared to WT mice. Specifically, we found that 52-week old …