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Paracrine Effect Of Nrg1 And Hgf Drives Resistance To Mek Inhibitors In Metastatic Uveal Melanoma., Hanyin Cheng, Mizue Terai, Ken Kageyama, Shinji Ozaki, Peter Mccue, Takami Sato, Andrew E. Aplin

Department of Cancer Biology Faculty Papers

Uveal melanoma patients with metastatic disease usually die within one year, emphasizing an urgent need to develop new treatment strategies for this cancer. MEK inhibitors improve survival in cutaneous melanoma patients but show only modest efficacy in metastatic uveal melanoma patients. In this study, we screened for growth factors that elicited resistance in newly characterized metastatic uveal melanoma cell lines to clinical-grade MEK inhibitors, trametinib and selumetinib. We show that neuregulin 1 (NRG1) and hepatocyte growth factor (HGF) provide resistance to MEK inhibition. Mechanistically, trametinib enhances the responsiveness to NRG1 and sustained HGF-mediated activation of AKT. Individually targeting ERBB3 and …

Coupling Between Cytoplasmic Concentration Gradients Through Local Control Of Protein Mobility In The Caenorhabditis Elegans Zygote, Youjun Wu, Huaiying Zhang, Erik E. Griffin

Dartmouth Scholarship

Cell polarity is characterized by the asymmetric distribution of factors at the cell cortex and in the cytoplasm. Although mechanisms that establish cortical asymmetries have been characterized, less is known about how persistent cytoplasmic asymmetries are generated. During the asymmetric division of the Caenorhabditis elegans zygote, the PAR proteins orchestrate the segregation of the cytoplasmic RNA-binding proteins MEX-5/6 to the anterior cytoplasm and PIE-1, POS-1, and MEX-1 to the posterior cytoplasm. In this study, we find that MEX-5/6 control the segregation of GFP::PIE-1, GFP::POS-1, and GFP::MEX-1 by locally increasing their mobility in the anterior cytoplasm. Remarkably, PIE-1, POS-1, and MEX-1 …

Taranis Functions With Cyclin A And Cdk1 In A Novel Arousal Center To Control Sleep In Drosophila., Dinis J.S. Afonso, Die Liu, Daniel R. Machado, Huihui Pan, James E.C. Jepson, Dragana Rogulja, Kyunghee Koh

Department of Neuroscience Faculty Papers

Sleep is an essential and conserved behavior whose regulation at the molecular and anatomical level remains to be elucidated. Here, we identify TARANIS (TARA), a Drosophila homolog of the Trip-Br (SERTAD) family of transcriptional coregulators, as a molecule that is required for normal sleep patterns. Through a forward-genetic screen, we isolated tara as a novel sleep gene associated with a marked reduction in sleep amount. Targeted knockdown of tara suggests that it functions in cholinergic neurons to promote sleep. tara encodes a conserved cell-cycle protein that contains a Cyclin A (CycA)-binding homology domain. TARA regulates CycA protein levels and genetically …

Reformed Approach To The Interactions Of Science And Religion, Tony N. Jelsma

Faculty Work Comprehensive List

"Sometimes, despite our best theological and scientific study, religion and science still seem to be in conflict."

Posting about the interactions between religion and science from In All Things - an online hub committed to the claim that the life, death, and resurrection of Jesus Christ has implications for the entire world.

http://inallthings.org/a-reformed-approach-to-the-interactions-of-science-and-religion

Comparison Of The Equine Reference Sequence With Its Sanger Source Data And New Illumina Reads, Jovan Rebolledo-Mendez, Matthew S. Hestand, Stephen J. Coleman, Zheng Zeng, Ludovic Orlando, James N. Macleod, Ted Kalbfleisch

Maxwell H. Gluck Equine Research Center Faculty Publications

The reference assembly for the domestic horse, EquCab2, published in 2009, was built using approximately 30 million Sanger reads from a Thoroughbred mare named Twilight. Contiguity in the assembly was facilitated using nearly 315 thousand BAC end sequences from Twilight's half brother Bravo. Since then, it has served as the foundation for many genome-wide analyses that include not only the modern horse, but ancient horses and other equid species as well. As data mapped to this reference has accumulated, consistent variation between mapped datasets and the reference, in terms of regions with no read coverage, single nucleotide variants, and small …

Gonad: Genome-Editing Via Oviductal Nucleic Acids Delivery System: A Novel Microinjection Independent Genome Engineering Method In Mice., Gou Takahashi, Channabasavaiah B. Gurumurthy, Kenta Wada, Hiromi Miura, Masahiro Sato, Masato Ohtsuka

Journal Articles: Genetics, Cell Biology & Anatomy

Microinjection is considered the gold standard technique for delivery of nucleic acids (NAs; transgenes or genome editing tools such as CRISPR/Cas9 systems) into embryos, for creating genetically modified organisms. It requires sophisticated equipment as well as well-trained and highly skilled personnel to perform the micro-injection technique. Here, we describe a novel and simple microinjection-independent technique, called Genome-editing via Oviductal Nucleic Acids Delivery (GONAD). Using GONAD, we show that NAs (e.g., eGFP mRNA or Cas9 mRNA/sgRNAs) can be effectively delivered to pre-implantation embryos within the intact mouse oviduct by a simple electroporation method, and result in the desired genetic modification in …

A Cysteine Zipper Stabilizes A Pre-Fusion F Glycoprotein Vaccine For Respiratory Syncytial Virus, Guillaume B. E. Stewart-Jones, Paul V. Thomas, Man Chen, Aliaksandr Druz, Gordon M. Joyce, Wing-Pui Kong, Mallika Sastry, Conque Soto, Yongping Yang, Baoshan Zhang, Lei Chen, Gwo-Yu Chuang, Ivelin S. Georgiev, Jason S. Mclellan

Dartmouth Scholarship

Recombinant subunit vaccines should contain minimal non-pathogen motifs to reduce potential off-target reactivity. We recently developed a vaccine antigen against respiratory syncytial virus (RSV), which comprised the fusion (F) glycoprotein stabilized in its pre-fusion trimeric conformation by “DS-Cav1” mutations and by an appended C-terminal trimerization motif or “foldon” from T4-bacteriophage fibritin. Here we investigate the creation of a cyste- ine zipper to allow for the removal of the phage foldon, while maintaining the immunogenic- ity of the parent DS-Cav1+foldon antigen. Constructs without foldon yielded RSV F monomers, and enzymatic removal of the phage foldon from pre-fusion F trimers resulted in …

Procollagen C-Endopeptidase Enhancer Protein 2 (Pcpe2) Reduces Atherosclerosis In Mice By Enhancing Scavenger Receptor Class B1 (Sr-Bi)-Mediated High-Density Lipoprotein (Hdl)-Cholesteryl Ester Uptake, Ricquita D. Pollard, Christopher N. Blesso, Manal Zabalawi, Brian Fulp, Mark Gerelus, Xuewei Zhu, Erica W. Lyons, Nebil Nuradin, Omar L. Francone, Xiang-An Li, Daisy Sahoo, Michael J. Thomas, Mary G. Sorci-Thomas

Pediatrics Faculty Publications

Studies in human populations have shown a significant correlation between procollagen C-endopeptidase enhancer protein 2 (PCPE2) single nucleotide polymorphisms and plasma HDL cholesterol concentrations. PCPE2, a 52-kDa glycoprotein located in the extracellular matrix, enhances the cleavage of C-terminal procollagen by bone morphogenetic protein 1 (BMP1). Our studies here focused on investigating the basis for the elevated concentration of enlarged plasma HDL in PCPE2-deficient mice to determine whether they protected against diet-induced atherosclerosis. PCPE2-deficient mice were crossed with LDL receptor-deficient mice to obtain LDLr^-/-, PCPE2^-/- mice, which had elevated HDL levels compared with LDLr^-/- mice with similar …

Space Environmental Factor Impacts Upon Murine Colon Microbiota And Mucosal Homeostasis, Lauren E. Ritchie, Stella S. Taddeo, Brad R. Weeks, Florence Lima, Susan A. Bloomfield, M. Andrea Azcarate-Peril, Sara R. Zwart, Scott M. Smith, Nancy D. Turner

Internal Medicine Faculty Publications

Astronaut intestinal health may be impacted by microgravity, radiation, and diet. The aim of this study was to characterize how high and low linear energy transfer (LET) radiation, microgravity, and elevated dietary iron affect colon microbiota (determined by 16S rDNA pyrosequencing) and colon function. Three independent experiments were conducted to achieve these goals: 1) fractionated low LET γ radiation (¹³⁷Cs, 3 Gy, RAD), high Fe diet (IRON) (650 mg/kg diet), and a combination of low LET γ radiation and high Fe diet (IRON+RAD) in male Sprague-Dawley rats; 2) high LET ³⁸Si particle exposure (0.050 Gy), 1/6 G …

Something To Fear: Perception Of Defining Characteristics Of Animals, Evaluation Of Animals, And The Moderating Role Of Speciesism, Allison Elaine Waters

Theses and Dissertations

Speciesism, a form of prejudice wherein a person gives or takes value away from an organism based upon how he or she categorizes living things, is most likely a form of flexible evolutionary adaptation. However, with increasing awareness of humanity's impact on the environment and growing morality, speciesism is increasingly becoming a disadvantage. Speciesism can be reflected in actions from unethical breeding habits to outright attacks on certain animals. The purpose of this study was to examine if altering the physical appearance of animals affects the person's attitudes towards those animals. It was hypothesized that altering physical characteristics of some …

Spatial Heterogeneity, Host Movement And Mosquito-Borne Disease Transmission, Miguel A. Acevedo, Olivia Prosper, Kenneth Lopiano, Nick Ruktanonchai, T. Trevor Caughlin, Maia Martcheva, Craig W. Osenberg, David L. Smith

Dartmouth Scholarship

Mosquito-borne diseases are a global health priority disproportionately affecting low-income populations in tropical and sub-tropical countries. These pathogens live in mosquitoes and hosts that interact in spatially heterogeneous environments where hosts move between regions of varying transmission intensity. Although there is increasing interest in the implications of spatial processes for mosquito-borne disease dynamics, most of our understanding derives from models that assume spatially homogeneous transmission. Spatial variation in contact rates can influence transmission and the risk of epidemics, yet the interaction between spatial heterogeneity and movement of hosts remains relatively unexplored. Here we explore, analytically and through numerical simulations, how …

Selection Of Reference Genes For Rt-Qpcr Analysis In The Monarch Butterfly, Danaus Plexippus (L.), A Migrating Bio-Indicator, Huipeng Pan, Xiaowei Yang, Keith Bidne, Richard L. Hellmich, Blair D. Siegfried, Xuguo Zhou

Entomology Faculty Publications

Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) is a powerful technique to quantify gene expression. To facilitate gene expression study and obtain accurate results, normalization relative to stably expressed reference genes is crucial. The monarch butterfly, Danaus plexippus (L.), is one of the most recognized insect species for its spectacular annual migration across North America. Besides its great voyages, D. plexippus has drawn attention to its role as a bio-indicator, ranging from genetically modified organisms (GMOs) to natural ecosystems. In this study, nine reference genes from D. plexippus genome were selected as the candidate reference genes. The expression profiles of these …

New Functions For Alpha-Catenins In Health And Disease: From Cancer To Heart Regeneration., Alexia Vite, Jifen Li, Glenn L. Radice

Center for Translational Medicine Faculty Papers

Strong cell-cell adhesion mediated by adherens junctions is dependent on anchoring the transmembrane cadherin molecule to the underlying actin cytoskeleton. To do this, the cadherin cytoplasmic domain interacts with catenin proteins, which include α-catenin that binds directly to filamentous actin. Originally thought to be a static structure, the connection between the cadherin/catenin adhesion complex and the actin cytoskeleton is now considered to be dynamic and responsive to both intercellular and intracellular signals. Alpha-catenins are mechanosensing proteins that undergo conformational change in response to cytoskeletal tension thus modifying the linkage between the cadherin and the actin cytoskeleton. There are three α-catenin …

Understanding Nucleus Pulposus Cell Phenotype: A Prerequisite For Stem Cell Based Therapies To Treat Intervertebral Disc Degeneration., Hyowon Choi, Zariel I. Johnson, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Intervertebral disc (IVD) degeneration and associated low back pain (LBP) remains a major burden to our society without significant improvements in treatment strategies or patient's quality of life. While the recent cell-transplantation studies for treatment of degenerative disc disease have shown promising results, to better gauge the success and functional outcomes of these therapies, it is crucial to understand if transplanted cells give rise to healthy nucleus pulposus (NP) tissue. NP cell phenotype is unique and is defined by expression of a characteristic set of markers that reflect specialized physiology and function. This review summarizes phenotypic markers that mirror the …

Discovery Of A Polyomavirus In European Badgers (Meles Meles) And The Evolution Of Host Range In The Family Polyomaviridae, Sarah C. Hill, Aisling A. Murphy, Matthew Cotten, Anne L. Palser, Phillip Benson, Sandrine Lesellier, Eamonn Gormley, Céline Richomme, Sylvia Grierson, Deirdre Ni Bhuachalla, Mark Chambers, Paul Kellam, María Laura Boschiroli, Bernhard Ehlers, Michael A. Jarvis, Oliver G. Pybus

School of Biomedical Sciences

Polyomaviruses infect a diverse range of mammalian and avian hosts, and are associated with a variety of symptoms. However, it is unknown whether the viruses are found in all mammalian families and the evolutionary history of the polyomaviruses is still unclear. Here, we report the discovery of a novel polyomavirus in the European badger (Meles meles), which to our knowledge represents the first polyomavirus to be characterized in the family Mustelidae, and within a European carnivoran. Although the virus was discovered serendipitously in the supernatant of a cell culture inoculated with badger material, we subsequently confirmed its presence in wild …

Is Autologous Or Heterologous Pericardium Better For Valvuloplasty? A Comparative Study Of Calcification Propensity, Wen-Jian Jiang, Yong-Chao Cui, Jin-Hua Li, Xiu-Hui Zhang, Huan-Huan Ding, Yong-Qiang Lai, Hong-Jia Zhang

The Texas Heart Institute Journal

Pericardial calcification is detrimental to the long-term durability of valvuloplasty. However, whether calcification susceptibility differs between heterologous and autologous pericardium is unclear. In this study, we compared the progression of calcification in vivo between autologous and heterologous pericardium.

We randomly divided 28 rabbits into 4 equal groups. Resected rabbit pericardium served as autologous pericardium, and commercial bovine pericardium served as heterologous pericardium. We subcutaneously embedded one of each pericardial patch in the abdominal walls of 21 of the rabbits. The 7 control rabbits (group A) received no implants. The embedded samples were removed at 2 months in group B, at …

Preclinical Characterization Of Duoc-01, A Cell Therapy Product Derived From Banked Umbilical Cord Blood For Use As An Adjuvant To Umbilical Cord Blood Transplantation For Treatment Of Inherited Metabolic Diseases., Joanne Kurtzberg, Susan Buntz, Tracy Gentry, Pamela Noeldner, April Ozamiz, Benjamin Rusche, Robert W. Storms, Amy Wollish, David A Wenger, Andrew E. Balber

Department of Neurology Faculty Papers

BACKGROUND AIMS: Cord blood (CB) transplantation slows neurodegeneration during certain inherited metabolic diseases. However, the number of donor cells in the brain of patients does not appear to be sufficient to provide benefit until several months after transplant. We developed the cell product DUOC-01 to provide therapeutic effects in the early post-transplant period.

METHODS: DUOC-01 cultures initiated from banked CB units were characterized by use of time-lapse photomicroscopy during the 21-day manufacturing process. Antigen expression was measured by means of flow cytometry and immunocytochemistry; transcripts for cytokines and enzymes by quantitative real-time polymerase chain reaction; activities of lysosomal enzymes by …

Genetic Heterogeneity Of Pseudoxanthoma Elasticum: The Chinese Signature Profile Of Abcc6 And Enpp1 Mutations., Liang Jin, Qiujie Jiang, Zhengsheng Wu, Changxia Shao, Yong Zhou, Luting Yang, Jouni Uitto, Gang Wang

Department of Dermatology and Cutaneous Biology Faculty Papers

Pseudoxanthoma elasticum (PXE), an autosomal recessive disorder characterized by ectopic mineralization, is caused by mutations in the ABCC6 gene. We examined clinically 29 Chinese PXE patients from unrelated families, so far the largest cohort of Asian PXE patients. In a subset of 22 patients, we sequenced ABCC6 and another candidate gene, ENPP1, and conducted pathogenicity analyses for each variant. We identified a total of 17 distinct mutations in ABCC6, 15 of them being, to our knowledge, previously unreported, including 5 frameshift and 10 missense variants. In addition, a missense mutation in combination with a recurrent nonsense mutation in ENPP1 was …

Haemophilus Influenzae Responds To Glucocorticoids Used In Asthma Therapy By Modulation Of Biofilm Formation And Antibiotic Resistance, Chris S. Earl, Tee Wooi Keong, Shi-Qi An, Sarah Murdoch, Yvonne Mccarthy, Junkal Garmendia, Joseph Ward, J Maxwell Dow, Liang Yang, George A. O'Toole, Robert P. Ryan

Dartmouth Scholarship

Glucocorticosteroids are used as a main treatment to reduce airway inflammation in people with asthma who suffer from neutrophilic airway inflammation, a condition frequently associ- ated with Haemophilus influenzae colonization. Here we show that glucocorticosteroids have a direct influence on the behavior of H. influenzae that may account for associated difficulties with therapy. Using a mouse model of infection, we show that cortico- steroid treatment promotes H. influenzae persistence. Transcrip- tomic analysis of bacteria either isolated from infected mouse airway or grown in laboratory medium identified a number of genes encoding regulatory factors whose expression responded to the presence of …

The Endogenous Cell-Fate Factor Dachshund Restrains Prostate Epithelial Cell Migration Via Repression Of Cytokine Secretion Via A Cxcl Signaling Module., Ke Chen, Kongming Wu, Xuanmao Jiao, Liping Wang, Xiaoming Ju, Min Wang, Gabriele Disante, Shaohua Xu, Qiong Wang, Kevin Li, Xin Sun, Chongwen Xu, Zhiping Li, Mathew C. Casimiro, Adam Ertel, Sankar Addya, Peter Mccue, Michael P. Lisanti, Chenguang Wang, Richard J. Davis, Graeme Mardon, Richard Pestell

Department of Cancer Biology Faculty Papers

Prostate cancer is the second leading form of cancer-related death in men. In a subset of prostate cancer patients, increased chemokine signaling IL8 and IL6 correlates with castrate-resistant prostate cancer (CRPC). IL8 and IL6 are produced by prostate epithelial cells and promote prostate cancer cell invasion; however, the mechanisms restraining prostate epithelial cell cytokine secretion are poorly understood. Herein, the cell-fate determinant factor DACH1 inhibited CRPC tumor growth in mice. Using Dach1(fl/fl)/Probasin-Cre bitransgenic mice, we show IL8 and IL6 secretion was altered by approximately 1,000-fold by endogenous Dach1. Endogenous Dach1 is shown to serve as a key endogenous restraint to …

Preventing Farnesylation Of The Dynein Adaptor Spindly Contributes To The Mitotic Defects Caused By Farnesyltransferase Inhibitors, Andrew J. Holland, Rita M. Reis, Sherry Niessen, Cláudia Pereira, Douglas A. Andres, H. Peter Spielmann, Don W. Cleveland, Arshad Desai, Reto Gassmann

Molecular and Cellular Biochemistry Faculty Publications

The clinical interest in farnesyltransferase inhibitors (FTIs) makes it important to understand how these compounds affect cellular processes involving farnesylated proteins. Mitotic abnormalities observed after treatment with FTIs have so far been attributed to defects in the farnesylation of the outer kinetochore proteins CENP-E and CENP-F, which are involved in chromosome congression and spindle assembly checkpoint signaling. Here we identify the cytoplasmic dynein adaptor Spindly as an additional component of the outer kinetochore that is modified by farnesyltransferase (FTase). We show that farnesylation of Spindly is essential for its localization, and thus for the proper localization of dynein and its …

Proteasome-Mediated Proteolysis Of The Polyglutamine-Expanded Androgen Receptor Is A Late Event In Spinal And Bulbar Muscular Atrophy (Sbma) Pathogenesis., Erin M Heine, Tamar R Berger, Anna Pluciennik, Christopher R Orr, Lori Zboray, Diane E Merry

Department of Biochemistry and Molecular Biology Faculty Papers

Proteolysis of polyglutamine-expanded proteins is thought to be a required step in the pathogenesis of several neurodegenerative diseases. The accepted view for many polyglutamine proteins is that proteolysis of the mutant protein produces a "toxic fragment" that induces neuronal dysfunction and death in a soluble form; toxicity of the fragment is buffered by its incorporation into amyloid-like inclusions. In contrast to this view, we show that, in the polyglutamine disease spinal and bulbar muscular atrophy, proteolysis of the mutant androgen receptor (AR) is a late event. Immunocytochemical and biochemical analyses revealed that the mutant AR aggregates as a full-length protein, …

Social Communication Of Predator-Induced Changes In Drosophila Behavior And Germ Line Physiology, Balint Z. Kacsoh, Julianna Bozler, Mani Ramaswami, Giovanni Bosco

Dartmouth Scholarship

Behavioral adaptation to environmental threats and subsequent social transmission of adaptive behavior has evolutionary implications. In Drosophila, exposure to parasitoid wasps leads to a sharp decline in oviposition. We show that exposure to predator elicits both an acute and learned oviposition depression, mediated through the visual system. However, long-term persistence of oviposition depression after predator removal requires neuronal signaling functions, a functional mushroom body, and neurally driven apoptosis of oocytes through effector caspases. Strikingly, wasp-exposed flies (teachers) can transmit egg-retention behavior and trigger ovarian apoptosis in naive, unexposed flies (students). Acquisition and behavioral execution of this socially learned behavior …

Cytoskeletal Dynamics: A View From The Membrane, Magdalena Bezanilla, Amy S. Gladfelter, David R. Kovar, Wei-Lih Lee

Dartmouth Scholarship

Many aspects of cytoskeletal assembly and dynamics can be recapitulated in vitro; yet, how the cytoskeleton integrates signals in vivo across cellular membranes is far less understood. Recent work has demonstrated that the membrane alone, or through membrane-associated proteins, can effect dynamic changes to the cytoskeleton, thereby impacting cell physiology. Having identified mechanistic links between membranes and the actin, microtubule, and septin cytoskeletons, these studies highlight the membrane’s central role in coordinating these cytoskeletal systems to carry out essential processes, such as endocytosis, spindle positioning, and cellular compartmentalization.

Metformin Prevents Aggressive Ovarian Cancer Growth Driven By High-Energy Diet: Similarity With Calorie Restriction, Zaid Al-Wahab, Ismail Mert, Calvin Tebbe, Jasdeep Chhina, Miriana Hijaz, Robert T. Morris, Rouba Ali-Fehmi, Shailendra Giri, Adnan R. Munkarah, Ramandeep Rattan

Hematology/Oncology Articles

Caloric restriction (CR) was recently demonstrated by us to restrict ovarian cancer growth in vivo. CR resulted in activation of energy regulating enzymes adenosine monophosphate activated kinase (AMPK) and sirtuin 1 (SIRT1) followed by downstream inhibition of Akt-mTOR. In the present study, we investigated the effects of metformin on ovarian cancer growth in mice fed a high energy diet (HED) and regular diet (RD) and compared them to those seen with CR in an immunocompetent isogeneic mouse model of ovarian cancer. Mice either on RD or HED diet bearing ovarian tumors were treated with 200 mg/kg metformin in drinking water. …

The Zoological Paradox, Thorfun Chutchawanjumrut

Architecture Senior Theses

Through on-site field investigation, studies of animal behaviors,

and Jon Coe’s zoo enrichment principles, this thesis proposes

that zoo architec-ture should prioritize the needs of the animals

by incorporating behavioral and environmental enrichments

into its design. Enrichments refer to the pro- cess of providing the

appropriate behav-ioral and environmental stimuli that foster the

animals to exhibit their own natural behaviors.

Adapting Jon Coe’s strategies and Heini Hediger’s concept of

territory as precedents, “A Zoological Paradox” proposes the reimagining

of the zoo typology by integrating existing enrich-ment

methodologies, as well as allowing human visitors to interact and

engage in the process …

Establishing The Dance Floor: Frame Manipulation Experiments, Peter D. Suich

Undergraduate Honors Theses

Past studies of honey bee populations, in both natural and laboratory settings have allowed researchers to elucidate the dance language of honey bees within the hive. While the intent and meaning of the waggle dance is thoroughly understood, the area within the hive on which the bees dance is poorly understood. Several factors that may contribute to waggle dancing were studied: substrate, scent and hive entrance proximity. Two separate honey bee colonies were placed in three-frame observation hives. After establishing the dance floor, new experimental conditions were introduced by changing the position of the frames and watching for three days …

Isolation Housing Exacerbates Alzheimer's Disease-Like Pathophysiology In Aged App/Ps1 Mice, Huang Huang, Linmei Wang, Min Cao, Charles Marshall, Junying Gao, Na Xiao, Gang Hu, Ming Xiao

Center of Excellence in Rural Health Faculty Publications

BACKGROUND: Alzheimer's disease is a neurodegenerative disease characterized by gradual declines in social, cognitive, and emotional functions, leading to a loss of expected social behavior. Social isolation has been shown to have adverse effects on individual development and growth as well as health and aging. Previous experiments have shown that social isolation causes an early onset of Alzheimer's disease-like phenotypes in young APP695/PS1-dE9 transgenic mice. However, the interactions between social isolation and Alzheimer's disease still remain unknown.

METHODS: Seventeen-month-old male APP695/PS1-dE9 transgenic mice were either singly housed or continued group housing for 3 months. Then, Alzheimer's disease-like pathophysiological changes were …

Alternating Magnetic Field-Induced Hyperthermia Increases Iron Oxide Nanoparticle Cell Association/Uptake And Flux In Blood-Brain Barrier Models, Mo Dan, Younsoo Bae, Thomas A. Pittman, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

PURPOSE: Superparamagnetic iron oxide nanoparticles (IONPs) are being investigated for brain cancer therapy because alternating magnetic field (AMF) activates them to produce hyperthermia. For central nervous system applications, brain entry of diagnostic and therapeutic agents is usually essential. We hypothesized that AMF-induced hyperthermia significantly increases IONP blood-brain barrier (BBB) association/uptake and flux.

METHODS: Cross-linked nanoassemblies loaded with IONPs (CNA-IONPs) and conventional citrate-coated IONPs (citrate-IONPs) were synthesized and characterized in house. CNA-IONP and citrate-IONP BBB cell association/uptake and flux were studied using two BBB Transwell^® models (bEnd.3 and MDCKII cells) after conventional and AMF-induced hyperthermia exposure.

RESULTS: …

Increasing Adipocyte Lipoprotein Lipase Improves Glucose Metabolism In High Fat Diet-Induced Obesity, R. Grace Walton, Beibei Zhu, Resat Unal, Michael Spencer, Manjula Sunkara, Andrew J. Morris, Richard Charnigo, Wendy S. Katz, Alan Daugherty, Deborah A. Howatt, Philip A. Kern, Brian S. Finlin

Barnstable Brown Diabetes Center Faculty Publications

Lipid accumulation in liver and skeletal muscle contributes to co-morbidities associated with diabetes and obesity. We made a transgenic mouse in which the adiponectin (Adipoq) promoter drives expression of lipoprotein lipase (LPL) in adipocytes to potentially increase adipose tissue lipid storage. These mice (Adipoq-LPL) have improved glucose and insulin tolerance as well as increased energy expenditure when challenged with a high fat diet (HFD). To identify the mechanism(s) involved, we determined whether the Adipoq-LPL mice diverted dietary lipid to adipose tissue to reduce peripheral lipotoxicity, but we found no evidence for this. Instead, characterization …