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Olanzapine-Induced Methylation Alters Cadherin Gene Families And Associated Pathways Implicated In Psychosis, Melkaye G. Melka, Christina A Castellani, Nagalingam Rajakumar, Richard O'Reilly, Shiva M Singh

Biology Publications

BACKGROUND: The complex aetiology of most mental disorders involves gene-environment interactions that may operate using epigenetic mechanisms particularly DNA methylation. It may explain many of the features seen in mental disorders including transmission, expression and antipsychotic treatment responses. This report deals with the assessment of DNA methylation in response to an antipsychotic drug (olanzapine) on brain (cerebellum and hippocampus), and liver as a non-neural reference in a rat model. The study focuses on the Cadherin/protocadherins encoded by a multi-gene family that serve as adhesion molecules and are involved in cell-cell communication in the mammalian brain. A number of these molecules …

Cytokine Gene Expression Profiles During Initiation, Progression And Resolution Of Periodontitis, Jeffrey L. Ebersole, Sreenatha S. Kirakodu, Michael John Novak, Arnold J. Stromberg, Shu Shen, Luis Orraca, Janis Gonzalez-Martinez, Armando Burgos, Octavio A. Gonzalez

Center for Oral Health Research Faculty Publications

AIM: Variations in the expression of cytokines during the progression of periodontitis remain ill-defined. We evaluated the expression of 19 cytokine genes related to T-cell phenotype/function during initiation, progression and resolution of periodontitis, and related these to the expression of soft and bone tissue destruction genes (TDGs).

MATERIALS AND METHODS: A ligature-induced periodontitis model was used in rhesus monkeys (M. mulatta) (n = 18). Gingival tissues were taken at baseline pre-ligation, 2 weeks and 1 month (Initiation) and 3 months (progression) post ligation. Ligatures were removed and samples taken 2 months later (resolution). Total RNA was isolated and the Rhesus …

Impact Of Distinct Poxvirus Infections On The Specificities And Functionalities Of Cd4+ T Cell Responses., Nicholas A Siciliano, Adam R Hersperger, Aimee M Lacuanan, Ren-Huan Xu, John Sidney, Alessandro Sette, Luis J Sigal, Laurence C. Eisenlohr

Department of Microbiology and Immunology Faculty Papers

UNLABELLED: The factors that determine CD4+ T cell (TCD4+) specificities, functional capacity, and memory persistence in response to complex pathogens remain unclear. We explored these parameters in the C57BL/6 mouse through comparison of two highly related (>92% homology) poxviruses: ectromelia virus (ECTV), a natural mouse pathogen, and vaccinia virus (VACV), a heterologous virus that nevertheless elicits potent immune responses. In addition to elucidating several previously unidentified major histocompatibility complex class II (MHC-II)-restricted epitopes, we observed many qualitative and quantitative differences between the TCD4+ repertoires, including responses not elicited by VACV despite complete sequence conservation. In addition, we observed functional …

Fructose-2,6-Bisphosphate Synthesis By 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase 4 (Pfkfb4) Is Required For The Glycolytic Response To Hypoxia And Tumor Growth, Jason Chesney, Jennifer Clark, Alden C. Klarer, Yoannis Imbert-Fernandez, Andrew N. Lane, Sucheta Telang

Markey Cancer Center Faculty Publications

Fructose-2,6-bisphosphate (F2,6BP) is a shunt product of glycolysis that allosterically activates 6-phosphofructo-1-kinase (PFK-1) resulting in increased glucose uptake and glycolytic flux to lactate. The F2,6BP concentration is dictated by four bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4) with distinct kinase:phosphatase activities. PFKFB4 is over-expressed in human cancers, induced by hypoxia and required for survival and growth of several cancer cell lines. Although PFKFB4 appears to be a rational target for anti-neoplastic drug development, it is not clear whether its kinase or phosphatase activity is required for cancer cell survival. In this study, we demonstrate that recombinant human PFKFB4 kinase activity is 4.3-fold greater than …

Orthoclust: An Orthology-Based Network Framework For Clustering Data Across Multiple Species, Koon-Kiu Yan, Daifeng Wang, Joel Rozowsky, Henry Zheng, Chao Cheng, Mark Gerstein Gerstein

Dartmouth Scholarship

Increasingly, high-dimensional genomics data are becoming available for many organisms.Here, we develop OrthoClust for simultaneously clustering data across multiple species. OrthoClust is a computational framework that integrates the co-association networks of individual species by utilizing the orthology relationships of genes between species. It outputs optimized modules that are fundamentally cross-species, which can either be conserved or species-specific. We demonstrate the application of OrthoClust using the RNA-Seq expression profiles of Caenorhabditis elegans and Drosophila melanogaster from the modENCODE consortium. A potential application of cross-species modules is to infer putative analogous functions of uncharacterized elements like non-coding RNAs based on guilt-by-association.

The Jak2 Small Molecule Inhibitor, G6, Reduces The Tumorigenic Potential Of T98g Glioblastoma Cells In Vitro And In Vivo, Rebekah Baskin, Sung O. Park, György M. Keserű, Kirpal S. Bisht, Heather L. Wamsley, Peter P. Sayeski

Chemistry Faculty Publications

Glioblastoma multiforme (GBM) is the most common and the most aggressive form of primary brain tumor. Jak2 is a non-receptor tyrosine kinase that is involved in proliferative signaling through its association with various cell surface receptors. Hyperactive Jak2 signaling has been implicated in numerous hematological disorders as well as in various solid tumors including GBM. Our lab has developed a Jak2 small molecule inhibitor known as G6. It exhibits potent efficacy in vitro and in several in vivo models of Jak2-mediated hematological disease. Here, we hypothesized that G6 would inhibit the pathogenic growth of GBM cells expressing hyperactive Jak2. To …

Applying Accelerator Mass Spectrometry For Low-Level Detection Of Complex Engineered Nanoparticles In Biological Media, Binghui Wang, George S. Jackson, Robert A. Yokel, Eric A. Grulke

Pharmaceutical Sciences Faculty Publications

Complex engineered nanoparticles (CENPs), which have different core and surface components, are being developed for medicinal, pharmaceutical and industrial applications. One of the key challenges for environmental health and safety assessments of CENPs is to identify and quantity their transformations in biological environments. This study reports the effects of in vivo exposure of citrate-coated nanoalumina with different rare isotope labels on each component. This CENP was dosed to the rat and accelerator mass spectrometry (AMS) was used to quantify ²⁶Al, ¹⁴C, and their ratio in the dosing material and tissue samples. For CENPs detected in the liver, the …

Nuclear Glycolytic Enzyme Enolase Of Toxoplasma Gondii Functions As A Transcriptional Regulator, Thomas Mouveaux, Gabrielle Oria, Elisabeth Werkmeister, Christian Slomianny, Barbara A. Fox, David J. Bzik, Stanislas Tomavo

Dartmouth Scholarship

Apicomplexan parasites including Toxoplasma gondii have complex life cycles within different hosts and their infectivity relies on their capacity to regulate gene expression. However, little is known about the nuclear factors that regulate gene expression in these pathogens. Here, we report that T. gondii enolase TgENO2 is targeted to the nucleus of actively replicating parasites, where it specifically binds to nuclear chromatin in vivo. Using a ChIP-Seq technique, we provide evidence for TgENO2 enrichment at the 5′ untranslated gene regions containing the putative promoters of 241 nuclear genes. Ectopic expression of HA-tagged TgENO1 or TgENO2 led to changes in …

Thiosulfoxide (Sulfane) Sulfur: New Chemistry And New Regulatory Roles In Biology, John Toohey, Arthur J L Cooper

NYMC Faculty Publications

The understanding of sulfur bonding is undergoing change. Old theories on hypervalency of sulfur and the nature of the chalcogen-chalcogen bond are now questioned. At the same time, there is a rapidly expanding literature on the effects of sulfur in regulating biological systems. The two fields are inter-related because the new understanding of the thiosulfoxide bond helps to explain the newfound roles of sulfur in biology. This review examines the nature of thiosulfoxide (sulfane, S0) sulfur, the history of its regulatory role, its generation in biological systems, and its functions in cells. The functions include synthesis of cofactors (molybdenum cofactor, …

Relating Gene Expression Evolution With Cpg Content Changes, Huan Yang, Dawei Li, Chao Cheng

Dartmouth Scholarship

Background:

Previous studies have shown that CpG dinucleotides are enriched in a subset of promoters and the CpG content of promoters is positively correlated with gene expression levels. But the relationship between divergence of CpG content and gene expression evolution has not been investigated. Here we calculate the normalized CpG (nCpG) content in DNA regions around transcription start site (TSS) and transcription terminal site (TTS) of genes in nine organisms, and relate them with expression levels measured by RNA-seq.

Results:

The nCpG content of TSS shows a bimodal distribution in all organisms except platypus, whereas the nCpG content of TTS …

Adrenergic Signaling Regulates Mitochondrial Ca2+ Uptake Through Pyk2-Dependent Tyrosine Phosphorylation Of The Mitochondrial Ca2+ Uniporter., Jin O-Uchi, Bong Sook Jhun, Shangcheng Xu, Stephen Hurst, Anna Raffaello, Xiaoyun Liu, Bing Yi, Huiliang Zhang, Polina Gross, Jyotsna Mishra, Alina Ainbinder, Sarah Kettlewell, Godfrey L Smith, Robert T Dirksen, Wang Wang, Rosario Rizzuto, Shey-Shing Sheu

Department of Medicine Faculty Papers

AIMS: Mitochondrial Ca2+ homeostasis is crucial for balancing cell survival and death. The recent discovery of the molecular identity of the mitochondrial Ca2+ uniporter pore (MCU) opens new possibilities for applying genetic approaches to study mitochondrial Ca2+ regulation in various cell types, including cardiac myocytes. Basal tyrosine phosphorylation of MCU was reported from mass spectroscopy of human and mouse tissues, but the signaling pathways that regulate mitochondrial Ca2+ entry through posttranslational modifications of MCU are completely unknown. Therefore, we investigated α1-adrenergic-mediated signal transduction of MCU posttranslational modification and function in cardiac cells.

RESULTS: α1-adrenoceptor (α1-AR) signaling translocated activated proline-rich tyrosine …

Mitochondrial Ion Channels/Transporters As Sensors And Regulators Of Cellular Redox Signaling., Jin O-Uchi, Shin-Young Ryu, Bong Sook Jhun, Stephen Hurst, Shey-Shing Sheu

Department of Medicine Faculty Papers

SIGNIFICANCE: Mitochondrial ion channels/transporters and the electron transport chain (ETC) serve as key sensors and regulators for cellular redox signaling, the production of reactive oxygen species (ROS) and nitrogen species (RNS) in mitochondria, and balancing cell survival and death. Although the functional and pharmacological characteristics of mitochondrial ion transport mechanisms have been extensively studied for several decades, the majority of the molecular identities that are responsible for these channels/transporters have remained a mystery until very recently.

RECENT ADVANCES: Recent breakthrough studies uncovered the molecular identities of the diverse array of major mitochondrial ion channels/transporters, including the mitochondrial Ca2+ uniporter pore, …

Loss Of 4e-Bp1 Function Induces Emt And Promotes Cancer Cell Migration And Invasion Via Cap-Dependent Translational Activation Of Snail, Weijia Cai, Qing Ye, Qing-Bai She

Markey Cancer Center Faculty Publications

The cap-dependent translation is frequently deregulated in a variety of cancers associated with tumor progression. However, the molecular basis of the translation activation for metastatic progression of cancer remains largely elusive. Here, we demonstrate that activation of cap-dependent translation by silencing the translational repressor 4E-BP1 causes cancer epithelial cells to undergo epithelial-mesenchymal transition (EMT), which is associated with selective upregulation of the EMT inducer Snail followed by repression of E-cadherin expression and promotion of cell migratory and invasive capabilities as well as metastasis. Conversely, inhibition of cap-dependent translation by a dominant active mutant 4E-BP1 effectively downregulates Snail expression and suppresses …

Bursts And Heavy Tails In Temporal And Sequential Dynamics Of Foraging Decisions, Kanghoon Jung, Hyeran Jang, Jerald D. D. Kralik, Jaeseung Jeong

Dartmouth Scholarship

A fundamental understanding of behavior requires predicting when and what an individual will choose. However, the actual temporal and sequential dynamics of successive choices made among multiple alternatives remain unclear. In the current study, we tested the hypothesis that there is a general bursting property in both the timing and sequential patterns of foraging decisions. We conducted a foraging experiment in which rats chose among four different foods over a continuous two-week time period. Regarding when choices were made, we found bursts of rapidly occurring actions, separated by time-varying inactive periods, partially based on a circadian rhythm. Regarding what was …

Cc2d1a Regulates Human Intellectual And Social Function As Well As Nf-Κb Signaling Homeostasis., M. Chiara Manzini, Lan Xiong, Ranad Shaheen, Dimira E Tambunan, Stefania Di Costanzo, Vanessa Mitisalis, +15 Additional Authors

Pharmacology and Physiology Faculty Publications

Autism spectrum disorder (ASD) and intellectual disability (ID) are often comorbid, but the extent to which they share common genetic causes remains controversial. Here, we present two autosomal-recessive "founder" mutations in the CC2D1A gene causing fully penetrant cognitive phenotypes, including mild-to-severe ID, ASD, as well as seizures, suggesting shared developmental mechanisms. CC2D1A regulates multiple intracellular signaling pathways, and we found its strongest effect to be on the transcription factor nuclear factor κB (NF-κB). Cc2d1a gain and loss of function both increase activation of NF-κB, revealing a critical role of Cc2d1a in homeostatic control of intracellular signaling. Cc2d1a knockdown in neurons …

D-Beta-Hydroxybutyrate Extends Lifespan In , Clare Edwards, John Canfield, Neil Copes, Muhammad Rehan, David Lipps, Patrick C. Bradshaw

Molecular Biosciences Faculty Publications

The ketone body beta-hydroxybutyrate (βHB) is a histone deacetylase (HDAC) inhibitor and has been shown to be protective in many disease models, but its effects on aging are not well studied. Therefore we determined the effect of βHB supplementation on the lifespan ofC. elegans nematodes. βHB supplementation extended mean lifespan by approximately 20%. RNAi knockdown of HDACs hda-2 or hda-3 also increased lifespan and further prevented βHB-mediated lifespan extension. βHB-mediated lifespan extension required the DAF-16/FOXO and SKN-1/Nrf longevity pathways, the sirtuin SIR-2.1, and the AMP kinase subunit AAK-2. βHB did not extend lifespan in a genetic model of dietary restriction …

Cyclic Di-Gmp-Dependent Signaling Pathways In The Pathogenic Firmicute Listeria Monocytogenes, Li-Hong Chen, Volkan K. Köseoğlu, Zehra T. Güvener, Tanya Myers-Morales, Joseph M. Reed, Sarah E. F. D'Orazio, Kurt W. Miller, Mark Gomelsky

Microbiology, Immunology, and Molecular Genetics Faculty Publications

We characterized key components and major targets of the c-di-GMP signaling pathways in the foodborne pathogen Listeria monocytogenes, identified a new c-di-GMP-inducible exopolysaccharide responsible for motility inhibition, cell aggregation, and enhanced tolerance to disinfectants and desiccation, and provided first insights into the role of c-di-GMP signaling in listerial virulence. Genome-wide genetic and biochemical analyses of c-di-GMP signaling pathways revealed that L. monocytogenes has three GGDEF domain proteins, DgcA (Lmo1911), DgcB (Lmo1912) and DgcC (Lmo2174), that possess diguanylate cyclase activity, and three EAL domain proteins, PdeB (Lmo0131), PdeC (Lmo1914) and PdeD (Lmo0111), that possess c-di-GMP phosphodiesterase activity. Deletion of all …

Recent Shifts In The Occurrence, Cause, And Magnitude Of Animal Mass Mortality Events, Samuel B. Fey, Adam M. Siepielski, Sébastien Nusslé, Kristina Cervantes-Yoshida, Jason L. Hwan, Eric R. Huber, Maxfield J. Fey, Alessandro Catenazzi, Stephanie M. Carlson

Dartmouth Scholarship

Mass mortality events (MMEs) are rapidly occurring catastrophic demographic events that punctuate background mortality levels. Individual MMEs are staggering in their observed magnitude: re- moving more than 90% of a population, resulting in the death of more than a billion individuals, or producing 700 million tons of dead biomass in a single event. Despite extensive documentation of individual MMEs, we have no understanding of the major features characterizing the occurrence and magnitude of MMEs, their causes, or trends through time. Thus, no framework exists for contextualizing MMEs in the wake of ongoing global and regional perturbations to natural systems. Here …

Rapidly Self-Renewing Human Multipotent Marrow Stromal Cells (Hmsc) Express Sialyl Lewis X And Actively Adhere To Arterial Endothelium In A Chick Embryo Model System, Harris E. Mcferrin, Scott D. Olson, Miriam V. Gutschow, Julie A. Semon, Deborah E. Sullivan, Darwin J. Prockop

Biological Sciences Faculty Research & Creative Works

Background: There have been conflicting observations regarding the receptors utilized by human multipotent mesenchymal bone marrow stromal cells (hMSC) to adhere to endothelial cells (EC). To address the discrepancies, we performed experiments with cells prepared with a standardized, low-density protocol preserving a sub-population of small cells that are rapidly self-renewing.

Methods: Sialyl Lewis X (SLeX) and α4 integrin expression were determined by flow cytometry. Fucosyltransferase expression was determined by quantitative realtime RT-PCR. Cell adhesion assays were carried out with a panel of endothelial cells from arteries, veins and the microvasculature in vitro. In Vivo experiments were performed to determine …

The Overwintering Biology Of The Acorn Weevil, Curculio Glandium In Southwestern Ontario., Hiroko Udaka, Brent J Sinclair

Biology Publications

The acorn weevil, Curculio glandium, is a widespread predator of acorns in eastern North America that overwinters in the soil as a larva. It is possible that low temperatures limit its northern geographic range, so we determined the cold tolerance strategy, seasonal variation in cold tolerance, and explored the physiological plasticity of overwintering larvae. Weevil larvae were collected from acorns of red and bur oak from Pelee Island, southwestern Ontario in fall 2010 and 2011. C. glandium larvae are freeze avoidant and larvae collected from bur oak acorns had lower supercooling points (SCPs: -7.6±0.36°C, LT50: -7.2°C) than those collected from …

Breach Of Tolerance: Primary Biliary Cirrhosis., Lifeng Wang, Fu-Sheng Wang, Christopher Chang, M Eric Gershwin

Department of Medical Genetics Faculty Papers

In primary biliary cirrhosis (PBC), the breach of tolerance that leads to active disease involves a disruption in several layers of control, including central tolerance, peripheral anergy, a "liver tolerance effect," and the action of T regulatory cells and their related cytokines. Each of these control mechanisms plays a role in preventing an immune response against self, but all of them act in concert to generate effective protection against autoimmunity without compromising the ability of the host immune system to mount an effective response to pathogens. At the same time, genetic susceptibility, environmental factors, including infection agents and xenobiotics, play …

Paramyxovirus Glycoprotein Incorporation, Assembly And Budding: A Three Way Dance For Infectious Particle Production, Farah El Najjar, Anthony P. Schmitt, Rebecca Ellis Dutch

Molecular and Cellular Biochemistry Faculty Publications

Paramyxoviruses are a family of negative sense RNA viruses whose members cause serious diseases in humans, such as measles virus, mumps virus and respiratory syncytial virus; and in animals, such as Newcastle disease virus and rinderpest virus. Paramyxovirus particles form by assembly of the viral matrix protein, the ribonucleoprotein complex and the surface glycoproteins at the plasma membrane of infected cells and subsequent viral budding. Two major glycoproteins expressed on the viral envelope, the attachment protein and the fusion protein, promote attachment of the virus to host cells and subsequent virus-cell membrane fusion. Incorporation of the surface glycoproteins into infectious …

Neurotrophic Factor Gdnf Promotes Survival Of Salivary Stem Cells, Nan (Tori) Xiao, Yuan Lin, Hongbin Cao, Davud Sirjani, Amato J. Giaccia, Albert C. Koong, Christina S. Kong, Maximilian Diehn, Quynh-Thu Le

All Dugoni School of Dentistry Faculty Articles

Stem cell-based regenerative therapy is a promising treatment for head and neck cancer patients that suffer from chronic dry mouth (xerostomia) due to salivary gland injury from radiation therapy. Current xerostomia therapies only provide temporary symptom relief, while permanent restoration of salivary function is not currently feasible. Here, we identified and characterized a stem cell population from adult murine submandibular glands. Of the different cells isolated from the submandibular gland, this specific population, Lin-CD24+c-Kit+Sca1+, possessed the highest capacity for proliferation, self renewal, and differentiation during serial passage in vitro. Serial transplantations of this stem cell population into the submandibular gland …

Rorα Binds To E2f1 To Inhibit Cell Proliferation And Regulate Mammary Gland Branching Morphogenesis, Gaofeng Xiong, Ren Xu

Markey Cancer Center Faculty Publications

Retinoic acid receptor-related orphan nuclear receptor alpha (RORα) is a potent tumor suppressor that reduces cell proliferation and inhibits tumor growth. However, the molecular mechanism by which it inhibits cell proliferation remains unknown. We demonstrate a noncanonical nuclear receptor pathway in which RORα binds to E2F1 to inhibit cell cycle progression. We showed that RORα bound to the heptad repeat and marked box region of E2F1 and suppressed E2F1-regulated transcription in epithelial cells. Binding of RORα inhibited E2F1 acetylation and its DNA-binding activity by recruiting histone deacetylase 1 (HDAC1) to the protein complexes. Knockdown of HDAC1 or inhibition of HDAC …

Differentiation State-Specific Mitochondrial Dynamic Regulatory Networks Are Revealed By Global Transcriptional Analysis Of The Developing Chicken Lens., Daniel Chauss, Subhasree Basu, Suren Rajakaruna, Zhiwei Ma, Victoria Gau, Sara Anastas, Lisa A. Brennan, J. Fielding Hejtmancik, A. Sue Menko, Marc Kantorow

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The mature eye lens contains a surface layer of epithelial cells called the lens epithelium that requires a functional mitochondrial population to maintain the homeostasis and transparency of the entire lens. The lens epithelium overlies a core of terminally differentiated fiber cells that must degrade their mitochondria to achieve lens transparency. These distinct mitochondrial populations make the lens a useful model system to identify those genes that regulate the balance between mitochondrial homeostasis and elimination. Here we used an RNA sequencing and bioinformatics approach to identify the transcript levels of all genes expressed by distinct regions of the lens epithelium …

Persistent Hepatic Structural Alterations Following Nanoceria Vascular Infusion In The Rat, Michael T. Tseng, Qiang Fu, Khoua Lor, G. Rafael Fernandez-Botran, Zhong-Bin Deng, Uschi M. Graham, D. Allan Butterfield, Eric A. Grulke, Robert A. Yokel

Chemistry Faculty Publications

Understanding the long-term effects and possible toxicity of nanoceria, a widely utilized commercial metal oxide, is of particular importance as it is poised for development as a therapeutic agent based on its autocatalytic redox behavior. We show here evidence of acute and subacute adverse hepatic responses, after a single infusion of an aqueous dispersion of 85 mg/kg, 30 nm nanoceria into Sprague Dawley rats. Light and electron microscopic evidence of avid uptake of nanoceria by Kupffer cells was detected as early as 1 hr after infusion. Biopersistent nanoceria stimulated cluster of differentiation 3⁺ lymphocyte proliferation that intermingled with nanoceria-containing …

Neutral Sphingomyelinase-3 Mediates Tnf-Stimulated Oxidant Activity In Skeletal Muscle, Jennifer S. Moylan, Jeffrey D. Smith, Erin M. Wolf Horrell, Julie B. Mclean, Gergana M. Deevska, Mark R. Bonnell, Mariana N. Nikolova‑Karakashian, Michael B. Reid

Physiology Faculty Publications

AIMS: Sphingolipid and oxidant signaling affect glucose uptake, atrophy, and force production of skeletal muscle similarly and both are stimulated by tumor necrosis factor (TNF), suggesting a connection between systems. Sphingolipid signaling is initiated by neutral sphingomyelinase (nSMase), a family of agonist-activated effector enzymes. Northern blot analyses suggest that nSMase3 may be a striated muscle-specific nSMase. The present study tested the hypothesis that nSMase3 protein is expressed in skeletal muscle and functions to regulate TNF-stimulated oxidant production.

RESULTS: We demonstrate constitutive nSMase activity in skeletal muscles of healthy mice and humans and in differentiated C2C12 myotubes. nSMase3 ( …

Novel Role Of Pancreatic Differentiation 2 In Facilitating Self-Renewal And Drug Resistance Of Pancreatic Cancer Stem Cells., Arokia P. Vaz, Moorthy P. Ponnusamy, Satyanarayana Rachagani, P Dey, Apar Kishor Ganti, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Cancer stem cells (CSCs) contribute towards disease aggressiveness and drug resistance. Specific identification of CSC maintenance genes and targeting can improve the efficiency of currently available treatment modalities. Pancreatic differentiation 2 (PD2) has a major role in the self-renewal of mouse embryonic stem cells. In the present study, we investigated the role of PD2 in pancreatic CSCs.

METHODS: Characterisation of CSCs and non-CSCs from mouse models, pancreatic cancer cells and human tissues by CSC and self-renewal marker analysis using confocal assay. Effect of PD2 knockdown in CSCs (after gemcitabine treatment) was studied by immunoblot and apoptosis assays.

RESULTS: A …

Structured Light Scatteroscopy, Venkataramanan Krishnaswamy, Jonathan T. Elliott, David M. Mcclatchy, Richard J. Barth Jr., Wendy A. Wells, Brian W. Pogue, Keith D. Paulsen

Dartmouth Scholarship

A new imaging approach, structured light scatteroscopy (SLS), is demonstrated, which offers rapid wide-field imaging of microscopic morphological variations in bulk tissue surfaces. Elastic scattering of light offers exquisite sensitivity to ultrastructural changes at multiple size scales ranging from nanometers to millimeters, but in bulk tissues the confounding effects of molecular absorption and strong multiple scattering of light often lead to a dramatic reduction in scatter contrast and specificity. It is demonstrated that the SLS using structured high spatial frequency illumination and detection to probe the tissue achieves direct, absorption-independent, high-resolution maps of the scattering response. The scattering response is …

Cell Type-Dependent Rna Recombination Frequency In The Japanese Encephalitis Virus, Wei-Wei Chiang, Chingkai Chuang, Mei Chao, Wei-June Chen

Plant Pathology Faculty Publications

Japanese encephalitis virus (JEV) is one of approximately 70 flaviviruses, frequently causing symptoms involving the central nervous system. Mutations of its genomic RNA frequently occur during viral replication, which is believed to be a force contributing to viral evolution. Nevertheless, accumulating evidences show that some JEV strains may have actually arisen from RNA recombination between genetically different populations of the virus. We have demonstrated that RNA recombination in JEV occurs unequally in different cell types. In the present study, viral RNA fragments transfected into as well as viral RNAs synthesized in mosquito cells were shown not to be stable, especially …