Digital Commons Network^™

Obesity: Current And Potential Pharmacotherapeutics And Targets, Vidya Narayanaswami, Linda P. Dwoskin

Pharmaceutical Sciences Faculty Publications

Obesity is a global epidemic that contributes to a number of health complications including cardiovascular disease, type 2 diabetes, cancer and neuropsychiatric disorders. Pharmacotherapeutic strategies to treat obesity are urgently needed. Research over the past two decades has increased substantially our knowledge of central and peripheral mechanisms underlying homeostatic energy balance. Homeostatic mechanisms involve multiple components including neuronal circuits, some originating in hypothalamus and brain stem, as well as peripherally-derived satiety, hunger and adiposity signals that modulate neural activity and regulate eating behavior. Dysregulation of one or more of these homeostatic components results in obesity. Coincident with obesity, reward mechanisms …

Pneumocystis Infection Alters The Activation State Of Pulmonary Macrophages, Jessica M. Deckman, Cathryn J. Kurkjian, Joseph P. Mcgillis, Theodore J. Cory, Susan E. Birket, Linda M. Schutzman, Brian S. Murphy, Beth A. Garvy, David J. Feola

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Recent studies show a substantial incidence of Pneumocystis jirovecii colonization and infection in patients with chronic inflammatory lung conditions. However, little is known about the impact of Pneumocystis upon the regulation of pulmonary immunity. We demonstrate here that Pneumocystis polarizes macrophages towards an alternatively activated macrophage-like phenotype. Genetically engineered mice that lack the ability to signal through IL-4 and IL-13 were used to show that Pneumocystis alternative macrophage activation is dependent upon signaling through these cytokines. To determine whether Pneumocystis-induced macrophage polarization would impact subsequent immune responses, we infected mice with Pneumocystis and then challenged them with Pseudomonas aeruginosa 14 …

Moderating Effects Of Immunosuppressive Medications And Risk Factors For Post-Operative Joint Infection Following Total Joint Arthroplasty In Patients With Rheumatoid Arthritis Or Osteoarthritis, Elizabeth G. Salt, Amanda T. Wiggins, Mary Kay Rayens, Brent J. Morris, David M. Mannino, Andrew Hoellein, Ryan P. Donegan, Leslie J. Crofford

Nursing Faculty Publications

Objective—Inconclusive findings about infection risks, importantly the use of immunosuppressive medications, in patients who have undergone large-joint total joint arthroplasty challenge efforts to provide evidenced-based perioperative total joint arthroplasty recommendations to improve surgical outcomes. Thus, the aim of this study was to describe risk factors for developing a postoperative infection in patients undergoing TJA of a large joint [total hip arthroplasty, total knee arthroplasty, or total shoulder arthroplasty] by identifying clinical and demographic factors, including the use of high risk medications (i.e., prednisone and immunosuppressive medications) and diagnoses (i.e., rheumatoid arthritis [RA], osteoarthritis [OA], gout, obesity, diabetes mellitus), that …

Effects Of Litter On Seedling Emergence And Seed Persistence Of Three Common Species On The Loess Plateau In Northwestern China, Rui Zhang, Xiaowen Hu, Jerry M. Baskin, Carol C. Baskin, Yanrong Wang

Biology Faculty Publications

Litter accumulation resulting from land use change (enclosure) is one of the key variables influencing seedling recruitment and consequently the regeneration of plant populations and seed persistence in the soil seed bank. A better understanding of the effects of litter on seed germination and seedling emergence is crucial for developing a new set of indicators for grassland ecosystem health and for grassland management policy. We investigated the effects of seed position in litter and amount of litter covering the seed on seedling emergence and seed persistence of three common species on the Loess Plateau in northwestern China. Seed position beneath …

Identification Of Mutant Genes And Introgressed Tiger Salamander Dna In The Laboratory Axolotl, Ambystoma Mexicanum, M. Ryan Woodcock, Jennifer Vaughn-Wolfe, Alexandra Elias, David Kevin Kump, Katharina Denise Kendall, Nataliya Y. Timoshevskaya, Vladimir A. Timoshevskiy, Dustin W. Perry, Jeramiah James Smith, Jessica E. Spiewak, David M. Parichy, Stephen Randal Voss

Biology Faculty Publications

The molecular genetic toolkit of the Mexican axolotl, a classic model organism, has matured to the point where it is now possible to identify genes for mutant phenotypes. We used a positional cloning–candidate gene approach to identify molecular bases for two historic axolotl pigment phenotypes: white and albino. White (d/d) mutants have defects in pigment cell morphogenesis and differentiation, whereas albino (a/a) mutants lack melanin. We identified in white mutants a transcriptional defect in endothelin 3 (edn3), encoding a peptide factor that promotes pigment cell migration and differentiation in other …

Inhibition Of The Integrin/Fak Signaling Axis And C-Myc Synergistically Disrupts Ovarian Cancer Malignancy, B. Xu, Jason R. Lefringhouse, Z. Liu, D. West, Lauren A. Baldwin, C. Ou, L. Chen, Dana L. Napier, Luksana Chaiswing, Lawrence D. Brewer, Daret K. St Clair, Olivier Thibault, John R. Van Nagell, Binhua P. Zhou, R. Drapkin, J.-A. Huang, M. L. Lu, Frederick R. Ueland, X. H. Yang

Pharmacology and Nutritional Sciences Faculty Publications

Integrins, a family of heterodimeric receptors for extracellular matrix, are promising therapeutic targets for ovarian cancer, particularly high-grade serous-type (HGSOC), as they drive tumor cell attachment, migration, proliferation and survival by activating focal adhesion kinase (FAK)-dependent signaling. Owing to the potential off-target effects of FAK inhibitors, disruption of the integrin signaling axis remains to be a challenge. Here, we tackled this barrier by screening for inhibitors being functionally cooperative with small-molecule VS-6063, a phase II FAK inhibitor. From this screening, JQ1, a potent inhibitor of Myc oncogenic network, emerged as the most robust collaborator. Treatment with a combination of VS-6063 …

Sodium-Myoinositol Cotransporter-1, Smit1, Mediates The Production Of Reactive Oxygen Species Induced By Hyperglycemia In The Heart, Anne Van Steenbergen, Magali Balteau, Audrey Ginion, Laura Ferté, Sylvain Battault, Christophe De Meester De Ravenstein, Jean-Luc Balligand, Evangelos-Panagiotis Daskalopoulos, Patrick Gilon, Florin Despa, Sanda Despa, Jean-Louis Vanoverschelde, Sandrine Horman, Hermann Koepsell, Gerard Berry, Louis Hue, Luc Bertrand, Christophe Beauloye

Pharmacology and Nutritional Sciences Faculty Publications

Hyperglycemia (HG) stimulates the production of reactive oxygen species in the heart through activation of NADPH oxidase 2 (NOX2). This production is independent of glucose metabolism but requires sodium/glucose cotransporters (SGLT). Seven SGLT isoforms (SGLT1 to 6 and sodium-myoinositol cotransporter-1, SMIT1) are known, although their expression and function in the heart remain elusive. We investigated these 7 isoforms and found that only SGLT1 and SMIT1 were expressed in mouse, rat and human hearts. In cardiomyocytes, galactose (transported through SGLT1) did not activate NOX2. Accordingly, SGLT1 deficiency did not prevent HG-induced NOX2 activation, ruling it out in the cellular response to …

Data Management Basics And Best Practices, Christie Peters

Research Data and Scholarly Communications Committee Workshops

Big data, data management, and data life cycle are all buzzwords being discussed among librarians, researchers, and campus administrators across the country and around the world. Learn the basics of these terms and what services an academic library system might be expected to offer patrons, while identifying personal opportunities for improving how you work with your own data. You will have the opportunity to explore DMPTool during this session.

The presentation slides are available by clicking the Download button on the right. Handouts as well as the video and audio files of this workshop are listed as additional files below …

Seed Dormancy-Breaking In A Cold Desert Shrub In Relation To Sand Temperature And Moisture, Huiliang Liu, Buhailiqiemu Abudureheman, Lingwei Zhang, Jerry M. Baskin, Carol C. Baskin, Daoyuan Zhang

Biology Faculty Publications

Seasonal periodicity of seed germination and its relationship to seasonal changes in temperature and soil moisture have been well studied in seeds of species with physiological dormancy. However, relatively little information is available on the role of these environmental factors in controlling germination of seeds with physical dormancy (PY). Our primary aim was to determine if seeds of the cold desert sand dune semi-shrub Eremosparton songoricum exhibits seasonal periodicity of seed germination and the relationship between seed dormancy break and soil temperature and moisture. In the laboratory, seeds incubated on dry, wet, wet-dry and dry-wet sand were exposed to a …

Predicting Disease-Related Genes Using Integrated Biomedical Networks, Jiajie Peng, Kun Bai, Xuequn Shang, Guohua Wang, Hansheng Xue, Shuilin Jin, Liang Cheng, Yadong Wang, Jin Chen

Institute for Biomedical Informatics Faculty Publications

Background: Identifying the genes associated to human diseases is crucial for disease diagnosis and drug design. Computational approaches, esp. the network-based approaches, have been recently developed to identify disease-related genes effectively from the existing biomedical networks. Meanwhile, the advance in biotechnology enables researchers to produce multi-omics data, enriching our understanding on human diseases, and revealing the complex relationships between genes and diseases. However, none of the existing computational approaches is able to integrate the huge amount of omics data into a weighted integrated network and utilize it to enhance disease related gene discovery.

Results: We propose a new network-based disease …

Mono Quaternary Ammonium Salts And Methods For Modulating Neuronal Nicotinic Acetylcholine Receptors, Peter A. Crooks, Linda P. Dwoskin, Guangrong Zheng, Sangeetha Sumithran, Zhenfa Zheng

Pharmaceutical Sciences Faculty Patents

Provided are monoquaternary ammonium compounds which are modulators of nicotinic acetylcholine receptors. Also provided are methods of using the compounds for modulating the function of a nicotinic acetylcholine receptor, and for the prevention and/or treatment of central nervous system disorders, substance use and/or abuse, and gastrointestinal tract disorders.

Transforming Growth Factor-Β In Thoracic Aortic Aneurysms: Good, Bad, Or Irrelevant?, Alan Daugherty, Zheying Chen, Hisashi Sawada, Debra L. Rateri, Mary B. Sheppard

Physiology Faculty Publications

No abstract provided.

Phlpp Regulates Hexokinase 2-Dependent Glucose Metabolism In Colon Cancer Cells, Xiaopeng Xiong, Yang-An Wen, Mihail I. Mitov, Mary C. Oaks, Shigeki Miyamoto, Tianyan Gao

Markey Cancer Center Faculty Publications

Increased glucose metabolism is considered as one of the most important metabolic alterations adapted by cancer cells in order to generate energy as well as high levels of glycolytic intermediates to support rapid proliferation. PH domain leucine-rich repeat protein phosphatase (PHLPP) belongs to a novel family of Ser/Thr protein phosphatases that function as tumor suppressors in various types of human cancer. Here we determined the role of PHLPP in regulating glucose metabolism in colon cancer cells. Knockdown of PHLPP increased the rate of glucose consumption and lactate production, whereas overexpression of PHLPP had the opposite effect. Bioenergetic analysis using Seahorse …

Promote Growth And Animal Health With Isoflavones In Red Clover And Other Legumes, Michael D. Flythe, Glen E. Aiken

Forage Symposium at the Kentucky Cattlemen’s Convention

The field of nutrition has continued to expand since the 18th century. We once thought that the only important components in foods and feeds were proteins, carbohydrates, fats and salts. Evidence was slowly pieced together to show that certain minor components were essential for life, and the vitamins were discovered. Like the doctors that first suspected vitamins were essential, some cattlemen have long noted advantages in animal performance and health on certain diets in ways that cannot be explained by a simple forage analysis. Today, we are learning the roles that phenolic plant secondary metabolites, sometimes called polyphenols, play in …

Microbial Interactions In The Phyllosphere Increase Plant Performance Under Herbivore Biotic Stress, Muhammad Saleem, Nicole Meckes, Zahida H. Pervaiz, Milton B. Traw

Plant and Soil Sciences Faculty Publications

The phyllosphere supports a tremendous diversity of microbes and other organisms. However, little is known about the colonization and survival of pathogenic and beneficial bacteria alone or together in the phyllosphere across the whole plant life-cycle under herbivory, which hinders our ability to understand the role of phyllosphere bacteria on plant performance. We addressed these questions in experiments using four genetically and biogeographically diverse accessions of Arabidopsis thaliana, three ecologically important bacterial strains (Pseudomonas syringae DC3000, Xanthomonas campestris, both pathogens, and Bacillus cereus, plant beneficial) under common garden conditions that included fungus gnats (Bradysia spp.). …

Grazing Panel, Jeff Beasley, Trevor Toland, Ted Krauskopf

Kentucky Grazing Conference

No abstract provided.

In Defense Of Soil Health, Allen R. Williams

Kentucky Grazing Conference

Soil health is a hot topic today in sustainable agriculture circles and is even becoming more popular in conventional agriculture. However, the term is often thrown around loosely, and sometimes the meaning gets muddled.

Oviposition Traits Generate Extrinsic Postzygotic Isolation Between Two Pine Sawfly Species, Emily E. Bendall, Kim L. Vertacnik, Catherine R. Linnen

Biology Faculty Publications

Background: Although empirical data indicate that ecological speciation is prevalent in nature, the relative importance of different forms of reproductive isolation and the traits generating reproductive isolation remain unclear. To address these questions, we examined a pair of ecologically divergent pine-sawfly species: while Neodiprion pinetum specializes on a thin-needled pine (Pinus strobus), N. lecontei utilizes thicker-needled pines. We hypothesized that extrinsic postzygotic isolation is generated by oviposition traits. To test this hypothesis, we assayed ovipositor morphology, oviposition behavior, and host-dependent oviposition success in both species and in F1 and backcross females.

Results: Compared to N. lecontei, N. …

Transcriptomic Response Of Wolf Spider, Pardosa Pseudoannulata, To Transgenic Rice Expressing Bacillus Thuringiensis Cry1ab Protein, Juan Wang, Yuande Peng, Kaifu Xiao, Baoyang Wei, Jilin Hu, Zhi Wang, Qisheng Song, Xuguo Zhou

Entomology Faculty Publications

Background: Bacillum thuringiensis (Bt) toxin produced in Cry1-expressing genetically modified rice (Bt rice) is highly effective to control lepidopteran pests, which reduces the needs for synthetic insecticides. Non-target organisms can be exposed to Bt toxins through direct feeding or trophic interactions in the field. The wolf spider Pardosa pseudoannulata, one of the dominant predators in South China, plays a crucial role in the rice agroecosystem. In this study, we investigated transcriptome responses of the 5th instar spiders fed on preys maintained on Bt- and non-Bt rice.

Results: Comparative transcriptome analysis resulted in 136 differentially expressed genes (DEGs) …

Crispr-Cas9 Mediated Nox4 Knockout Inhibits Cell Proliferation And Invasion In Hela Cells, Naser Jafari, Hyunju Kim, Rackhyun Park, Liqing Li, Minsu Jang, Andrew J. Morris, Junsoo Park, Cai Huang

Markey Cancer Center Faculty Publications

Increased expression of NOX4 protein is associated with cancer progression and metastasis but the role of NOX4 in cell proliferation and invasion is not fully understood. We generated NOX4 knockout HeLa cell lines using the CRISPR-Cas9 gene editing system to explore the cellular functions of NOX4. After transfection of CRISPR-Cas9 construct, we performed T7 endonuclease 1 assays and DNA sequencing to generate and identify insertion and deletion of the NOX4 locus. We confirmed the knockout of NOX4 by Western blotting. NOX4 knockout cell lines showed reduced cell proliferation with an increase of sub-G1 cell population and the decrease of S/G2/M …

Association Of Body Mass Index With Dna Methylation And Gene Expression In Blood Cells And Relations To Cardiometabolic Disease: A Mendelian Randomization Approach, Michael M. Mendelson, Riccardo E. Marioni, Roby Joehanes, Chunyu Liu, Åsa K. Hedman, Stella Aslibekyan, Ellen W. Demerath, Weihua Guan, Degui Zhi, Chen Yao, Tianxiao Huan, Christine Willinger, Brian Chen, Paul Courchesne, Michael Multhaup, Marguerite R. Irvin, Ariella Cohain, Eric E. Schadt, Megan L. Grove, Jan Bressler, Kari North, Johan Sundström, Stefan Gustafsson, Sonia Shah, Allan F. Mcrae, Sarah E. Harris, Jude Gibson, Paul Redmond, Janie Corley, Lee Murphy, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background

The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain.

Methods and Findings

We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs …

Fatigue Properties And Damage Mechanism Of A Cr-Mn Austenite Steel, Z. Q. Lv, Pei Cai, T. Yu, Yan Jin, H. F. Zhang, Tongguang Zhai, W. T. Fu

Chemical and Materials Engineering Faculty Publications

The fatigue properties and the damage mechanism of a Cr-Mn austenite steel were investigated using four-point bend fatigue testing. The stress-number of cycles to failure (S-N) curve of the Cr-Mn austenite steel was measured at room temperature, at the frequency of f=20 Hz and the stress ratio of R=0.1. The fatigue strength of this Cr-Mn austenite steel was measured to be 503 MPa in the maximum stress. Multiple cracks are initiated on the sample surface after fatigue failure tests, and usually only one or two of them can lead to the final failure of the samples. Most of the cracks …

Novel Interconnections In Lipid Metabolism Revealed By Overexpression Of Sphingomyelin Synthase-1, Gergana M. Deevska, Patrick P. Dotson Ii, Alexander A. Karakashian, Giorgis Isaac, Mark Wrona, Samuel B. Kelly, Alfred H. Merrill Jr., Mariana N. Nikolova‑Karakashian

Physiology Faculty Publications

This study investigates the consequences of elevating sphingomyelin synthase 1 (SMS1) activity, which generates the main mammalian sphingolipid, sphingomyelin. HepG2 cells stably transfected with SMS1 (HepG2-SMS1) exhibit elevated enzyme activity in vitro and increased sphingomyelin content (mainly C22:0- and C24:0-sphingomyelin) but lower hexosylceramide (Hex-Cer) levels. HepG2-SMS1 cells have fewer triacylglycerols than controls but similar diacylglycerol acyltransferase activity, triacylglycerol secretion, and mitochondrial function. Treatment with 1 mm palmitate increases de novo ceramide synthesis in both cell lines to a similar degree, causing accumulation of C16:0-ceramide (and some C18:0-, C20:0-, and C22:0-ceramides) as well as C16:0- and C18:0-Hex-Cers. In these experiments, the …

Radiation Induced Apoptosis Of Murine Bone Marrow Cells Is Independent Of Early Growth Response 1 (Egr1), Karine Z. Oben, Beth W. Gachuki, Sara S. Alhakeem, Mary Kathryn Mckenna, Ying Liang, Daret K. St. Clair, Vivek M. Rangnekar, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

An understanding of how each individual 5q chromosome critical deleted region (CDR) gene contributes to malignant transformation would foster the development of much needed targeted therapies for the treatment of therapy related myeloid neoplasms (t-MNs). Early Growth Response 1 (EGR1) is a key transcriptional regulator of myeloid differentiation located within the 5q chromosome CDR that has been shown to regulate HSC (hematopoietic stem cell) quiescence as well as the master regulator of apoptosis—p53. Since resistance to apoptosis is a hallmark of malignant transformation, we investigated the role of EGR1 in apoptosis of bone marrow cells; a cell population from which …

Longitudinal Measurement And Hierarchical Classification Framework For The Prediction Of Alzheimer's Disease, Meiyan Huang, Wei Yang, Qianjin Feng, Wufan Chen, Michael Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack Jr., William Jagust, John Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew Saykin, John Morris, Leslie M. Shaw, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Beccera, Liberty Teodoro, Bryan Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Charles D. Smith, Greg A. Jicha, Peter A. Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad

Neurology Faculty Publications

Accurate prediction of Alzheimer’s disease (AD) is important for the early diagnosis and treatment of this condition. Mild cognitive impairment (MCI) is an early stage of AD. Therefore, patients with MCI who are at high risk of fully developing AD should be identified to accurately predict AD. However, the relationship between brain images and AD is difficult to construct because of the complex characteristics of neuroimaging data. To address this problem, we present a longitudinal measurement of MCI brain images and a hierarchical classification method for AD prediction. Longitudinal images obtained from individuals with MCI were investigated to acquire important …

Omecamtiv Mecarbil Enhances The Duty Ratio Of Human Β-Cardiac Myosin Resulting In Increased Calcium Sensitivity And Slowed Force Development In Cardiac Muscle, Anja M. Swenson, Wanjian Tang, Cheavar A. Blair, Christopher M. Fetrow, William C. Unrath, Michael J. Previs, Kenneth S. Campbell, Christopher M. Yengo

Physiology Faculty Publications

The small molecule drug omecamtiv mecarbil (OM) specifically targets cardiac muscle myosin and is known to enhance cardiac muscle performance, yet its impact on human cardiac myosin motor function is unclear. We expressed and purified human β-cardiac myosin subfragment 1 (M2β-S1) containing a C-terminal Avi tag. We demonstrate that the maximum actin-activated ATPase activity of M2β-S1 is slowed more than 4-fold in the presence of OM, whereas the actin concentration required for half-maximal ATPase was reduced dramatically (30-fold). We find OM does not change the overall actin affinity. Transient kinetic experiments suggest that there are …

A Comparative Genomic Analysis Of Putative Pathogenicity Genes In The Host-Specific Sibling Species Colletotrichum Graminicola And Colletotrichum Sublineola, Ester A. S. Buiate, Katia Viana Xavier, Neil Moore, Maria F. Torres, Mark L. Farman, Christopher L. Schardl, Lisa J. Vaillancourt

Plant Pathology Faculty Publications

Background: Colletotrichum graminicola and C. sublineola cause anthracnose leaf and stalk diseases of maize and sorghum, respectively. In spite of their close evolutionary relationship, the two species are completely host-specific. Host specificity is often attributed to pathogen virulence factors, including specialized secondary metabolites (SSM), and small-secreted protein (SSP) effectors. Genes relevant to these categories were manually annotated in two co-occurring, contemporaneous strains of C. graminicola and C. sublineola. A comparative genomic and phylogenetic analysis was performed to address the evolutionary relationships among these and other divergent gene families in the two strains.

Results: Inoculation of maize with C. sublineola …

Bis-Quaternary Ammonium Salts And Methods For Modulating Neuronal Nicotinic Acetylcholine Receptors, Peter A. Crooks, Linda P. Dwoskin, Guangrong Zheng, Sangeetha Sumithran

Pharmaceutical Sciences Faculty Patents

Provided are bis-quaternary ammonium compounds which are modulators of nicotinic acetylcholine receptors. Also provided are methods of using the compounds for modulating the function of a nicotinic acetylcholine receptor, and for the prevention and/or treatment of central nervous system disorders, substance use and/or abuse, and or gastrointestinal tract disorders.

Effect Of Seed Morph And Light Level On Growth And Reproduction Of The Amphicarpic Plant Amphicarpaea Edgeworthii (Fabaceae), Keliang Zhang, Jerry M. Baskin, Carol C. Baskin, Xuejun Yang, Zhenying Huang

Biology Faculty Publications

Amphicarpic plants produce aerial and subterranean fruits on an individual plant, and these heteromorphic diaspores give rise to plants that differ in growth and ecology. Amphicarpaea edgeworthii is a summer annual amphicarpic species that grows over a range of light levels. We aimed to compare the response to shading intensity of plants of A. edgeworthii grown throughout their life cycle from aerial seeds (ASP) and from subterranean seeds (SSP). We hypothesized that vegetative and reproductive growth of plants from ASP and SSP respond differently to light. Plants were grown from ASP and SSP under 0, 46, 71 and 90% shading …

Chloroquine-Inducible Par-4 Secretion Is Essential For Tumor Cell Apoptosis And Inhibition Of Metastasis, Ravshan Burikhanov, Nikhil Hebbar, Sunil K. Noothi, Nidhi Shukla, James Sledziona, Nathália Araujo, Meghana Kudrimoti, Qing Jun Wang, David S. Watt, Danny R. Welch, Jodi Maranchie, Akihiro Harada, Vivek M. Rangnekar

Radiation Medicine Faculty Publications

The induction of tumor suppressor proteins capable of cancer cell apoptosis represents an attractive option for the re-purposing of existing drugs. We report that the anti-malarial drug, chloroquine (CQ), is a robust inducer of Par-4 secretion from normal cells in mice and cancer patients in a clinical trial. CQ-inducible Par-4 secretion triggers paracrine apoptosis of cancer cells and also inhibits metastatic tumor growth. CQ induces Par-4 secretion via the classical secretory pathway that requires the activation of p53. Mechanistically, p53 directly induces Rab8b, a GTPase essential for vesicle transport of Par-4 to the plasma membrane prior to secretion. Our findings …