Digital Commons Network^™

Preclinical Evaluation Of Novel Fatty Acid Synthase Inhibitors In Primary Colorectal Cancer Cells And A Patient-Derived Xenograft Model Of Colorectal Cancer, Yekaterina Y. Zaytseva, Piotr G. Rychahou, Anh-Thu Le, Timothy L. Scott, Robert M. Flight, Ji Tae Kim, Jennifer Harris, Jinpeng Liu, Chi Wang, Andrew J. Morris, Theru A. Sivakumaran, Teresa Fan, Hunter Moseley, Tianyan Gao, Eun Young Lee, Heidi L. Weiss, Timothy S. Heuer, George Kemble, B. Mark Evers

Toxicology and Cancer Biology Faculty Publications

Fatty Acid Synthase (FASN), a key enzyme of de novo lipogenesis, is upregulated in many cancers including colorectal cancer (CRC); increased FASN expression is associated with poor prognosis. Potent FASN inhibitors (TVBs) developed by 3-V Biosciences demonstrate anti-tumor activity in vitro and in vivo and a favorable tolerability profile in a Phase I clinical trial.

However, CRC characteristics associated with responsiveness to FASN inhibition are not fully understood. We evaluated the effect of TVB-3664 on tumor growth in nine CRC patient-derived xenografts (PDXs) and investigated molecular and metabolic changes associated with CRC responsiveness to FASN inhibition.

CRC cells and PDXs …

Adaptation Of Microelectrode Array Technology For The Study Of Anesthesia-Induced Neurotoxicity In The Intact Piglet Brain, Emily D. Geyer, Prithvi A. Shetty, Christopher J. Suozzi, David Z. Allen, Pamela P. Benavidez, Joseph Liu, Charles N. Hollis, Greg A. Gerhardt, Jorge E. Quintero, Jason J. Burmeister, Emmett E. Whitaker

Neuroscience Faculty Publications

Every year, millions of children undergo anesthesia for a multitude of procedures. However, studies in both animals and humans have called into question the safety of anesthesia in children, implicating anesthetics as potentially toxic to the brain in development. To date, no studies have successfully elucidated the mechanism(s) by which anesthesia may be neurotoxic. Animal studies allow investigation of such mechanisms, and neonatal piglets represent an excellent model to study these effects due to their striking developmental similarities to the human brain.

This protocol adapts the use of enzyme-based microelectrode array (MEA) technology as a novel way to study the …

Serum Lipidomics Of Bovine Paratuberculosis: Disruption Of Choline-Containing Glycerophospholipids And Sphingolipids, Paul L. Wood, Erdal Erol, Glen F. Hoffsis, Margaret Steinman, Jeroen Debuck

Veterinary Science Faculty Publications

Objectives: Bovine paratuberculosis is a devastating infection with Mycobacterium avium subspecies paratuberculosis that ultimately results in death from malnutrition. While the infection is characterized by a long (2–4 years) subclinical phase with immune activation, ultimately host defense mechanisms fail and the bacteria spread from the small intestine to other organs. Since both the gastrointestinal tract and liver are essential for the biosynthesis of structural glycerophospholipids, we investigated the circulating levels of these lipids in field infections and experimentally infected cattle.

Methods: Serum lipidomics of control and M. avium subspecies paratuberculosis–infected cattle were performed utilizing high-resolution mass spectrometry.

Results: In …

Genome-Wide Association Meta-Analysis Of Circulating Odd-Numbered Chain Saturated Fatty Acids: Results From The Charge Consortium, Marcia C. De Oliveira Otto, Rozenn N. Lemaitre, Qi Sun, Irena B. King, Jason H. Y. Wu, Ani Manichaikul, Stephen S. Rich, Michael Y. Tsai, Y. D. Chen, Myriam Fornage, Guan Weihua, Stella Aslibekyan, Marguerite R. Irvin, Edmond K. Kabagambe, Donna K. Arnett, Majken K. Jensen, Barbara Mcknight, Bruce M. Psaty, Lyn M. Steffen, Caren E. Smith, Ulf Risérus, Lars Lind, Frank B. Hu, Eric B. Rimm, David S. Siscovick, Dariush Mozaffarian

Epidemiology and Environmental Health Faculty Publications

Background

Odd-numbered chain saturated fatty acids (OCSFA) have been associated with potential health benefits. Although some OCSFA (e.g., C15:0 and C17:0) are found in meats and dairy products, sources and metabolism of C19:0 and C23:0 are relatively unknown, and the influence of non-dietary determinants, including genetic factors, on circulating levels of OCSFA is not established.

Objective

To elucidate the biological processes that influence circulating levels of OCSFA by investigating associations between genetic variation and OCSFA.

Design

We performed a meta-analysis of genome-wide association studies (GWAS) of plasma phospholipid/erythrocyte levels of C15:0, C17:0, C19:0, and C23:0 among 11,494 individuals of European …

Synaptic Phospholipids As A New Target For Cortical Hyperexcitability And E/I Balance In Psychiatric Disorders, Carine Thalman, Guilherme Horta, Lianyong Qiao, Heiko Endle, Irmgard Tegeder, Hong Cheng, Gregor Laube, Torfi Sigurdsson, Maria Jelena Hauser, Stefan Tenzer, Ute Distler, Junken Aoki, Andrew J. Morris, Gerd Geisslinger, Jochen Röper, Sergei Kirischuk, Heiko J. Luhmann, Konstantin Radyushkin, Robert Nitsch, Johannes Vogt

Internal Medicine Faculty Publications

Lysophosphatidic acid (LPA) is a synaptic phospholipid, which regulates cortical excitation/inhibition (E/I) balance and controls sensory information processing in mice and man. Altered synaptic LPA signaling was shown to be associated with psychiatric disorders. Here, we show that the LPA-synthesizing enzyme autotaxin (ATX) is expressed in the astrocytic compartment of excitatory synapses and modulates glutamatergic transmission. In astrocytes, ATX is sorted toward fine astrocytic processes and transported to excitatory but not inhibitory synapses. This ATX sorting, as well as the enzymatic activity of astrocyte-derived ATX are dynamically regulated by neuronal activity via astrocytic glutamate receptors. Pharmacological and genetic ATX inhibition …

Historical And Cross-Cultural Perspectives On Parkinson's Disease, Lee Xenakis Blonder

Sanders-Brown Center on Aging Faculty Publications

Parkinson’s disease (PD) is a common neurodegenerative disorder, affecting up to 10 million people worldwide according to the Parkinson’s Disease Foundation. Epidemiological and genetic studies show a preponderance of idiopathic cases and a subset linked to genetic polymorphisms of a familial nature. Traditional Chinese medicine and Ayurveda recognized and treated the illness that Western Medicine terms PD millennia ago, and descriptions of Parkinson’s symptomatology by Europeans date back 2000 years to the ancient Greek physician Galen. However, the Western nosological classification now referred to in English as “Parkinson’s disease” and the description of symptoms that define it, are accredited to …

Gwas For Fusarium Head Blight Related Traits In Winter Wheat (Triticum Aestivum L.) In An Artificially Warmed Treatment, Elisane W. Tessmann, David A. Van Sanford

Plant and Soil Sciences Faculty Publications

Global temperature increases will affect Fusarium head blight (FHB) levels in wheat (Triticum aestivum L.). A pressing question is whether current sources of resistance will be effective in a warmer environment. We evaluated phenotypic response to disease in 238 soft winter wheat breeding lines and cultivars grown in 2015–2016 and 2016–2017 under control and warmed (+3 °C) conditions. Warming was achieved with heating cables buried 3 cm in the rhizosphere. We measured heading date, plant height, yield, FHB rating, Fusarium damaged kernels (FDK), deoxynivalenol (DON), leaf blotch rating, powdery mildew rating and leaf rust rating. There were significant ( …

Abcg5 And Abcg8: More Than A Defense Against Xenosterols, Shailendra B. Patel, Gregory A. Graf, Ryan E. Temel

Pharmaceutical Sciences Faculty Publications

The elucidation of the molecular basis of the rare disease, sitosterolemia, has revolutionized our mechanistic understanding of how dietary sterols are excreted and how cholesterol is eliminated from the body. Two proteins, ABCG5 and ABCG8, encoded by the sitosterolemia locus, work as obligate dimers to pump sterols out of hepatocytes and enterocytes. ABCG5/ABCG8 are key in regulating whole-body sterol trafficking, by eliminating sterols via the biliary tree as well as the intestinal tract. Importantly, these transporters keep xenosterols from accumulating in the body. The sitosterolemia locus has been genetically associated with lipid levels and downstream atherosclerotic disease, as well as …

Matrix Metalloproteinase-Mediated Blood-Brain Barrier Dysfunction In Epilepsy, Ralf G. Rempe, Anika M. S. Hartz, Emma L. B. Soldner, Brent S. Sokola, Satya R. Alluri, Erin L. Abner, Richard J. Kryscio, Anton Pekcec, Juli Schlichtiger, Björn Bauer

Pharmaceutical Sciences Faculty Publications

The blood-brain barrier is dysfunctional in epilepsy, thereby contributing to seizure genesis and resistance to antiseizure drugs. Previously, several groups reported that seizures increase brain glutamate levels, which leads to barrier dysfunction. One critical component of barrier dysfunction is brain capillary leakage. Based on our preliminary data, we hypothesized that glutamate released during seizures mediates an increase in matrix-metalloproteinase (MMP) expression and activity levels, thereby contributing to barrier leakage. To test this hypothesis, we exposed isolated brain capillaries from male Sprague Dawley rats to glutamate ex vivo and used an in vivo/ex vivo approach of isolated brain capillaries …

Forage News [2018-05], Department Of Plant And Soil Sciences, University Of Kentucky

Forage News

• Value of Cutting Hay Earlier
• Guide to successfully replacing endophyte-infected KY-31 pastures with Novel Endophyte Tall Fescue
• Alfalfa – Third Most Valuable Field Crop in U.S.

Amylin And Diabetic Cardiomyopathy – Amylin-Induced Sarcolemmal Ca2+ Leak Is Independent Of Diabetic Remodeling Of Myocardium, Miao Liu, Amanda Hoskins, Nirmal Verma, Donald M. Bers, Sanda Despa, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

Amylin is a pancreatic β-cell hormone co-secreted with insulin, plays a role in normal glucose homeostasis, and forms amyloid in the pancreatic islets of individuals with type-2 diabetes. Aggregated amylin is also found in blood and extra-pancreatic tissues, including myocardium. Myocardial amylin accumulation is associated with myocyte Ca²⁺ dysregulation in diabetic rats expressing human amylin. Whether deposition of amylin in the heart is a consequence of or a contributor to diabetic cardiomyopathy remains unknown. We used amylin knockout (AKO) mice intravenously infused with either human amylin (i.e, the aggregated form) or non-amyloidogenic (i.e., monomeric) rodent amylin to test the …

Physiologically Based Pharmacokinetic Modeling Of Nanoceria Systemic Distribution In Rats Suggests Dose- And Route-Dependent Biokinetics, Ulrika Carlander, Tshepo Paulsen Moto, Anteneh Assefa Desalegn, Robert A. Yokel, Gunnar Johanson

Pharmaceutical Sciences Faculty Publications

Background: Cerium dioxide nanoparticles (nanoceria) are increasingly being used in a variety of products as catalysts, coatings, and polishing agents. Furthermore, their antioxidant properties make nanoceria potential candidates for biomedical applications. To predict and avoid toxicity, information about their biokinetics is essential. A useful tool to explore such associations between exposure and internal target dose is physiologically based pharmacokinetic (PBPK) modeling. The aim of this study was to test the appropriateness of our previously published PBPK model developed for intravenous (IV) administration when applied to various sizes of nanoceria and to exposure routes relevant for humans.

Methods: Experimental biokinetic data …

Downregulation Of Microrna Eca-Mir-128 In Seminal Exosomes And Enhanced Expression Of Cxcl16 In The Stallion Reproductive Tract Are Associated With Long-Term Persistence Of Equine Arteritis Virus, Mariano Carossino, Pouya Dini, Theodore S. Kalbfleisch, Alan T. Loynachan, Igor F. Canisso, Kathleen M. Shuck, Peter J. Timoney, R. Frank Cook, Udeni B. R. Balasuriya

Maxwell H. Gluck Equine Research Center Faculty Publications

Equine arteritis virus (EAV) can establish long-term persistent infection in the reproductive tract of stallions and is shed in the semen. Previous studies showed that long-term persistence is associated with a specific allele of the CXCL16 gene (CXCL16S) and that persistent infection is maintained despite the presence of a local inflammatory and humoral and mucosal antibody responses. In this study, we demonstrated that equine seminal exosomes (SEs) are enriched in a small subset of microRNAs (miRNAs). Most importantly, we demonstrated that long-term EAV persistence is associated with the downregulation of an SE-associated miRNA (eca-mir-128) and with an enhanced …

Advancing The Understanding Of Environmental Transformations, Bioavailability And Effects Of Nanomaterials, An International Us Environmental Protection Agency—Uk Environmental Nanoscience Initiative Joint Program, Mitch M. Lasat, Kian Fan Chung, Jamie Lead, Steve Mcgrath, Richard J. Owen, Sophie Rocks, Jason M. Unrine, Junfeng Zhang

Plant and Soil Sciences Faculty Publications

Nanotechnology has significant economic, health, and environmental benefits, including renewable energy and innovative environmental solutions. Manufactured nanoparticles have been incorporated into new materials and products because of their novel or enhanced properties. These very same properties also have prompted concerns about the potential environmental and human health hazard and risk posed by the manufactured nanomaterials. Appropriate risk management responses require the development of models capable of predicting the environmental and human health effects of the nanomaterials. Development of predictive models has been hampered by a lack of information concerning the environmental fate, behavior and effects of manufactured nanoparticles. The United …

Knockout Of Pannexin-1 Induces Hearing Loss, Jin Chen, Chun Liang, Liang Zong, Yan Zhu, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

Mutations of gap junction connexin genes induce a high incidence of nonsyndromic hearing loss. Pannexin genes also encode gap junctional proteins in vertebrates. Recent studies demonstrated that Pannexin-1 (Panx1) deficiency in mice and mutation in humans are also associated with hearing loss. So far, several Panx1 knockout (KO) mouse lines were established. In general, these Panx1 KO mouse lines demonstrate consistent phenotypes in most aspects, including hearing loss. However, a recent study reported that a Panx1 KO mouse line, which was created by Genentech Inc., had no hearing loss as measured by the auditory brainstem response (ABR) threshold at low-frequency …

Restoration Of Legacy Trees As Roosting Habitat For Myotis Bats In Eastern North American Forests, Michael J. Lacki

Forestry and Natural Resources Faculty Publications

Most eastern North American Myotis roost in forests during summer, with species forming maternity populations, or colonies, in cavities or crevices or beneath the bark of trees. In winter, these bats hibernate in caves and are experiencing overwinter mortalities due to infection from the fungus Pseudogymnoascus destructans, which causes white-nose syndrome (WNS). Population recovery of WNS-affected species is constrained by the ability of survivors to locate habitats suitable for rearing pups in summer. Forests in eastern North America have been severely altered by deforestation, land-use change, fragmentation and inadvertent introduction of exotic insect pests, resulting in shifts in tree …

Ketogenic Diet Enhances Neurovascular Function With Altered Gut Microbiome In Young Healthy Mice, David Ma, Amy C. Wang, Ishita Parikh, Stefan J. Green, Jared D. Hoffman, George Chlipala, M. Paul Murphy, Brent S. Sokola, Björn Bauer, Anika M. S. Hartz, Ai-Ling Lin

Sanders-Brown Center on Aging Faculty Publications

Neurovascular integrity, including cerebral blood flow (CBF) and blood-brain barrier (BBB) function, plays a major role in determining cognitive capability. Recent studies suggest that neurovascular integrity could be regulated by the gut microbiome. The purpose of the study was to identify if ketogenic diet (KD) intervention would alter gut microbiome and enhance neurovascular functions, and thus reduce risk for neurodegeneration in young healthy mice (12–14 weeks old). Here we show that with 16 weeks of KD, mice had significant increases in CBF and P-glycoprotein transports on BBB to facilitate clearance of amyloid-beta, a hallmark of Alzheimer’s disease (AD). These neurovascular …

Screening Of Multimeric Β-Xylosidases From The Gut Microbiome Of A Higher Termite, Globitermes Brachycerastes, Chunyan Liu, Gen Zou, Xing Yan, Xuguo Zhou

Entomology Faculty Publications

Termite gut microbiome is a rich reservoir for glycoside hydrolases, a suite of enzymes critical for the degradation of lignocellulosic biomass. To search for hemicellulases, we screened 12,000 clones from a fosmid gut library of a higher termite, Globitermes brachycerastes. As a common Southeastern Asian genus, Globitermes distributes predominantly in tropical rain forests and relies on the lignocellulases from themselves and bacterial symbionts to digest wood. In total, 22 positive clones with β-xylosidase activity were isolated, in which 11 representing different restriction fragment length polymorphism (RFLP) patterns were pooled and subjected to 454 pyrosequencing. As a result, eight putative β-xylosidases …

Evaluation Of A Novel Finite Element Model Of Active Contraction In The Heart, Xiaoyan Zhang, Zhan-Qiu Liu, Kenneth S. Campbell, Jonathan F. Wenk

Mechanical Engineering Faculty Publications

Finite element (FE) modeling is becoming a widely used approach for the investigation of global heart function. In the present study, a novel model of cellular-level systolic contraction, which includes both length- and velocity-dependence, was implemented into a 3D non-linear FE code. To validate this new FE implementation, an optimization procedure was used to determine the contractile parameters, associated with sarcomeric function, by comparing FE-predicted pressure and strain to experimental measures collected with magnetic resonance imaging and catheterization in the ventricles of five healthy rats. The pressure-volume relationship generated by the FE models matched well with the experimental data. Additionally, …

First-Year Vitality Of Reforestation Plantings In Response To Herbivore Exclusion On Reclaimed Appalachian Surface-Mined Land, Zachary J. Hackworth, John M. Lhotka, John J. Cox, Christopher D. Barton, Matthew T. Springer

Forestry and Natural Resources Faculty Publications

Conventional Appalachian surface-mine reclamation techniques repress natural forest regeneration, and tree plantings are often necessary for reforestation. Reclaimed Appalachian surface mines harbor a suite of mammal herbivores that forage on recently planted seedlings. Anecdotal reports across Appalachia have implicated herbivory in the hindrance and failure of reforestation efforts, yet empirical evaluation of herbivory impacts on planted seedling vitality in this region remains relatively uninitiated. First growing-season survival, height growth, and mammal herbivory damage of black locust (Robinia pseudoacacia L.), shortleaf pine (Pinus echinata Mill.), and white oak (Quercus alba L.) are presented in response to varying intensities …

Role Of Protein Charge Density On Hepatitis B Virus Capsid Formation, Xinyu Sun, Dong Li, Zhaoshuai Wang, Panchao Yin, Rundong Hu, Rundong Hu, Hui Li, Qiao Liu, Yunyi Gao, Baiping Ren, Jie Zheng, Yinan Wei, Tianbo Liu

Chemistry Faculty Publications

The role of electrostatic interactions in the viral capsid assembly process was studied by comparing the assembly process of a truncated hepatitis B virus capsid protein Cp149 with its mutant protein D2N/D4N, which has the same conformational structure but four fewer charges per dimer. The capsid protein self-assembly was investigated under a wide range of protein surface charge densities by changing the protein concentration, buffer pH, and solution ionic strength. Lowering the protein charge density favored the capsid formation. However, lowering charge beyond a certain point resulted in capsid aggregation and precipitation. Interestingly, both the wild-type and D2N/D4N mutant displayed …

Human Cancer And Platelet Interaction, A Potential Therapeutic Target, Shike Wang, Zhenyu Li, Ren Xu

Markey Cancer Center Faculty Publications

Cancer patients experience a four-fold increase in thrombosis risk, indicating that cancer development and progression are associated with platelet activation. Xenograft experiments and transgenic mouse models further demonstrate that platelet activation and platelet-cancer cell interaction are crucial for cancer metastasis. Direct or indirect interaction of platelets induces cancer cell plasticity and enhances survival and extravasation of circulating cancer cells during dissemination. In vivo and in vitro experiments also demonstrate that cancer cells induce platelet aggregation, suggesting that platelet-cancer interaction is bidirectional. Therefore, understanding how platelets crosstalk with cancer cells may identify potential strategies to inhibit cancer metastasis and to reduce …

Effective Room-Temperature Ammonia-Sensitive Composite Sensor Based On Graphene Nanoplates And Pani, Zongbiao Ye, Yan Chen, Bohao Liu, Yuanjie Su, Zhi Chen, Huiling Tai, Yadong Jiang

Electrical and Computer Engineering Faculty Publications

The graphene nanoplate (GN)-polyaniline (PANI) composite was developed via in-situ polymerization method and simultaneously assembled on interdigital electrodes (IDEs) at low temperature for ammonia (NH₃) detection. The assembled composite sensor showed excellent sensing performance toward different concentrations of NH₃, 1.5 of response value and 123 s/204 s for the response/recovery time to 15 ppm NH₃. Meanwhile, an interesting supersaturation phenomenon was observed at high concentration of NH₃. A reasonable speculation was proposed for this special sensing behavior and the mechanism for enhanced sensing properties was also analyzed.

Psychopathy To Altruism: Neurobiology Of The Selfish–Selfless Spectrum, James W. H. Sonne, Don M. Gash

Neuroscience Faculty Publications

The age-old philosophical, biological, and social debate over the basic nature of humans as being “universally selfish” or “universally good” continues today highlighting sharply divergent views of natural social order. Here we analyze advances in biology, genetics and neuroscience increasing our understanding of the evolution, features and neurocircuitry of the human brain underlying behavior in the selfish–selfless spectrum. First, we examine evolutionary pressures for selection of altruistic traits in species with protracted periods of dependence on parents and communities for subsistence and acquisition of learned behaviors. Evidence supporting the concept that altruistic potential is a common feature in human populations …

In Vivo Structures Of The Helicobacter Pylori Cag Type Iv Secretion System, Yi-Wei Chang, Carrie L. Shaffer, Lee A. Rettberg, Debnath Ghosal, Grant J. Jensen

Veterinary Science Faculty Publications

The type IV secretion system (T4SS) is a versatile nanomachine that translocates diverse effector molecules between microbes and into eukaryotic cells. Here, using electron cryotomography, we reveal the molecular architecture of the Helicobacter pylori cag T4SS. Although most components are unique to H. pylori, the cag T4SS exhibits remarkable architectural similarity to other T4SSs. Our images revealed that, when H. pylori encounters host cells, the bacterium elaborates membranous tubes perforated by lateral ports. Sub-tomogram averaging of the cag T4SS machinery revealed periplasmic densities associated with the outer membrane, a central stalk, and peripheral wing-like densities. Additionally, we resolved pilus-like …

Sensor Technologies For Intelligent Transportation Systems, Juan Guerrero-Ibáñez, Sherali Zeadally, Juan Contreras-Castillo

Information Science Faculty Publications

Modern society faces serious problems with transportation systems, including but not limited to traffic congestion, safety, and pollution. Information communication technologies have gained increasing attention and importance in modern transportation systems. Automotive manufacturers are developing in-vehicle sensors and their applications in different areas including safety, traffic management, and infotainment. Government institutions are implementing roadside infrastructures such as cameras and sensors to collect data about environmental and traffic conditions. By seamlessly integrating vehicles and sensing devices, their sensing and communication capabilities can be leveraged to achieve smart and intelligent transportation systems. We discuss how sensor technology can be integrated with the …

Differential Effects Of Linkers On The Activity Of Amphiphilic Tobramycin Antifungals, Marina Y. Fosso, Sanjib K. Shrestha, Nishad Thamban Chandrika, Emily K. Dennis, Keith D. Green, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

As the threat associated with fungal infections continues to rise and the availability of antifungal drugs remains a concern, it becomes obvious that the need to bolster the antifungal armamentarium is urgent. Building from our previous findings of tobramycin (TOB) derivatives with antifungal activity, we further investigate the effects of various linkers on the biological activity of these aminoglycosides. Herein, we analyze how thioether, sulfone, triazole, amide, and ether functionalities affect the antifungal activity of alkylated TOB derivatives against 22 Candida, Cryptococcus, and Aspergillus species. We also evaluate their impact on the hemolysis of murine erythrocytes and the …

Bilateral Carotid Artery Stenosis Causes Unexpected Early Changes In Brain Extracellular Matrix And Blood-Brain Barrier Integrity In Mice, Jill M. Roberts, Michael E. Maniskas, Gregory J. Bix

Neuroscience Faculty Publications

Bilateral carotid artery stenosis (BCAS) is one experimental model of vascular dementia thought to preferentially impact brain white matter. Indeed, few studies report hippocampal and cortical pathology prior to 30 days post-stenosis; though it is unclear whether those studies examined regions outside the white matter. Since changes in the blood-brain barrier (BBB) permeability precede more overt brain pathology in various diseases, we hypothesized that changes within the BBB and/or BBB-associated extracellular matrix (ECM) could occur earlier after BCAS in the hippocampus, cortex and striatum and be a precursor of longer term pathology. Here, C57Bl/6 mice underwent BCAS or sham surgeries …

Rational Reasoning On Ractopamine: Kentucky Regulators Reach Appropriate Responses To Inconsequential Trace-Level Environmental Substance Identifications, Theodore F. Shults, Kimberly Brewer, Jake Machin, Eric Hamelback, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

No abstract provided.

Twist Promotes Tumor Metastasis In Basal-Like Breast Cancer By Transcriptionally Upregulating Ror1, Jingying Cao, Xin Wang, Tao Dai, Yuanzhong Wu, Meifang Zhang, Renxian Cao, Ruhua Zhang, Gang Wang, Rou Jiang, Binhua P. Zhou, Jian Shi, Tiebang Kang

Markey Cancer Center Faculty Publications

Rationale: Twist is a key transcription factor for induction of epithelial-mesenchymal transition (EMT), which promotes cell migration, invasion, and cancer metastasis, confers cancer cells with stem cell-like characteristics, and provides therapeutic resistance. However, the functional roles and targeted genes of Twist in EMT and cancer progression remain elusive.

Methods: The potential targeted genes of Twist were identified from the global transcriptomes of T47D/Twist cells by microarray analysis. EMT phenotype was detected by western blotting and immunofluorescence of marker proteins. The dual-luciferase reporter and chromatin immunoprecipitation assays were employed to observe the direct transcriptional induction of ROR1 by Twist. A lung …