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Articles 1 - 21 of 21
Full-Text Articles in Medicine and Health Sciences
Multiple Subject Barycentric Discriminant Analysis (Musubada): How To Assign Scans To Categories Without Using Spatial Normalization, Hervé Abdi, Lynne J. Williams, Andrew C. Connolly, M. Ida Gobbini
Multiple Subject Barycentric Discriminant Analysis (Musubada): How To Assign Scans To Categories Without Using Spatial Normalization, Hervé Abdi, Lynne J. Williams, Andrew C. Connolly, M. Ida Gobbini
Dartmouth Scholarship
We present a new discriminant analysis (DA) method called Multiple Subject Barycentric Discriminant Analysis (MUSUBADA) suited for analyzing fMRI data because it handles datasets with multiple participants that each provides different number of variables (i.e., voxels) that are themselves grouped into regions of interest (ROIs). Like DA, MUSUBADA (1) assigns observations to predefined categories, (2) gives factorial maps displaying observations and categories, and (3) optimally assigns observations to categories. MUSUBADA handles cases with more variables than observations and can project portions of the data table (e.g., subtables, which can represent participants or ROIs) on the factorial maps. Therefore MUSUBADA can …
Quantitative, Spectrally-Resolved Intraoperative Fluorescence Imaging, Pablo A. Valdés, Frederic Leblond, Valerie L. Jacobs, Brian C. Wilson, Keith D. Paulsen, David W. Roberts
Quantitative, Spectrally-Resolved Intraoperative Fluorescence Imaging, Pablo A. Valdés, Frederic Leblond, Valerie L. Jacobs, Brian C. Wilson, Keith D. Paulsen, David W. Roberts
Dartmouth Scholarship
Intraoperative visual fluorescence imaging (vFI) has emerged as a promising aid to surgical guidance, but does not fully exploit the potential of the fluorescent agents that are currently available. Here, we introduce a quantitative fluorescence imaging (qFI) approach that converts spectrally-resolved data into images of absolute fluorophore concentration pixel-by-pixel across the surgical field of view (FOV). The resulting estimates are linear, accurate, and precise relative to true values, and spectral decomposition of multiple fluorophores is also achieved. Experiments with protoporphyrin IX in a glioma rodent model demonstrate in vivo quantitative and spectrally-resolved fluorescence imaging of infiltrating tumor margins for the …
Thr 163 Phosphorylation Causes Mcl-1 Stabilization When Degradation Is Independent Of The Adjacent Gsk3-Targeted Phosphodegron, Promoting Drug Resistance In Cancer, Shanna K. Nifoussi, Julie A. Vrana, Aaron M. Domina, Alfredo De Biasio, Jingang Gui, Mark A. Gregory, Stephen R. Hann, Ruth W. Craig
Thr 163 Phosphorylation Causes Mcl-1 Stabilization When Degradation Is Independent Of The Adjacent Gsk3-Targeted Phosphodegron, Promoting Drug Resistance In Cancer, Shanna K. Nifoussi, Julie A. Vrana, Aaron M. Domina, Alfredo De Biasio, Jingang Gui, Mark A. Gregory, Stephen R. Hann, Ruth W. Craig
Dartmouth Scholarship
The antiapoptotic Bcl-2 family member Mcl-1 is a PEST protein (containing sequences enriched in proline, glutamic acid, serine, and threonine) and is subject to rapid degradation via multiple pathways. Impaired degradation leading to the maintenance of Mcl-1 expression is an important determinant of drug resistance in cancer. Phosphorylation at Thr 163 in the PEST region, stimulated by 12-O-tetradecanoylphorbol acetic acid (TPA)-induced activation of extracellular signal-regulated kinase (ERK), is associated with Mcl-1 stabilization in BL41-3 Burkitt lymphoma cells. This contrasts with the observation that Thr 163 phosphorylation in normal fibroblasts primes glycogen synthase kinase (GSK3)-induced phosphorylation at Ser 159, producing a …
Tryptophan Hydroxylase-1 Regulates Immune Tolerance And Inflammation, Elizabeth C. Nowak, Victor C. De Vries, Anna Wasiuk, Cory Ahonen, Kathryn A. Bennett, Isabelle Le Mercier, Dae-Gon Ha, Randolph J. Noelle
Tryptophan Hydroxylase-1 Regulates Immune Tolerance And Inflammation, Elizabeth C. Nowak, Victor C. De Vries, Anna Wasiuk, Cory Ahonen, Kathryn A. Bennett, Isabelle Le Mercier, Dae-Gon Ha, Randolph J. Noelle
Dartmouth Scholarship
Nutrient deprivation based on the loss of essential amino acids by catabolic enzymes in the microenvironment is a critical means to control in ammatory responses and immune tolerance. Here we report the novel nding that Tph-1 (tryptophan hydroxylase-1), a synthase which catalyses the conversion of tryptophan to serotonin and exhausts tryptophan, is a potent regulator of immunity. In models of skin allograft tolerance, tumor growth, and experimental autoimmune encephalomyelitis, Tph-1 de ciency breaks allograft tolerance, induces tumor remission, and intensi es neuroin ammation, respectively. All of these effects of Tph-1 de ciency are independent of its downstream product serotonin. Because …
Murine Gammaherpesvirus 68 Lana Acts On Terminal Repeat Dna To Mediate Episome Persistence, Aline C. Habison, Chantal Beauchemin, J. Pedro Simas, Edward J. Usherwood
Murine Gammaherpesvirus 68 Lana Acts On Terminal Repeat Dna To Mediate Episome Persistence, Aline C. Habison, Chantal Beauchemin, J. Pedro Simas, Edward J. Usherwood
Dartmouth Scholarship
Murine gammaherpesvirus 68 (MHV68) ORF73 (mLANA) has sequence homology to Kaposi’s sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA). LANA acts on the KSHV terminal repeat (TR) elements to mediate KSHV episome maintenance. Disruption of mLANA expression severely reduces the ability of MHV68 to establish latent infection in mice, consistent with the possibility that mLANA mediates episome persistence. Here we assess the roles of mLANA and MHV68 TR (mTR) elements in episome persistence. mTR-associated DNA persisted as an episome in latently MHV68-infected tumor cells, demonstrating that the mTR elements can serve as a cis-acting element for MHV68 episome maintenance. In some …
Two Boundaries Separate Borrelia Burgdorferi Populations In North America, Gabriele Margos, Jean I. Tsao, Santiago Castillo-Ramirez, Yvette A. Girard, Anne G. Hoen
Two Boundaries Separate Borrelia Burgdorferi Populations In North America, Gabriele Margos, Jean I. Tsao, Santiago Castillo-Ramirez, Yvette A. Girard, Anne G. Hoen
Dartmouth Scholarship
Understanding the spread of infectious diseases is crucial for implementing effective control measures. For this, it is important to obtain information on the contemporary population structure of a disease agent and to infer the evolutionary processes that may have shaped it. Here, we investigate on a continental scale the population structure of Borrelia burgdorferi, the causative agent of Lyme borreliosis (LB), a tick-borne disease, in North America. We test the hypothesis that the observed d population structure is congruent with recent population expansions and that these were preceded by bottlenecks mostly likely caused by the near extirpation in the 1900s …
Cofactor Molecules Maintain Infectious Conformation And Restrict Strain Properties In Purified Prions, Nathan R. Deleault, Daniel J. Walsh, Justin R. Piro, Fei Wang, Xinhe Wang, Jiyan Ma, Judy R. Rees, Surachai Supattapone
Cofactor Molecules Maintain Infectious Conformation And Restrict Strain Properties In Purified Prions, Nathan R. Deleault, Daniel J. Walsh, Justin R. Piro, Fei Wang, Xinhe Wang, Jiyan Ma, Judy R. Rees, Surachai Supattapone
Dartmouth Scholarship
No abstract provided.
Effects Of Low-Dose Drinking Water Arsenic On Mouse Fetal And Postnatal Growth And Development, Courtney D. Kozul-Horvath, Fokko Zandbergen, Brian P. Jackson, Richard I. Enelow, Joshua W. Hamilton
Effects Of Low-Dose Drinking Water Arsenic On Mouse Fetal And Postnatal Growth And Development, Courtney D. Kozul-Horvath, Fokko Zandbergen, Brian P. Jackson, Richard I. Enelow, Joshua W. Hamilton
Dartmouth Scholarship
Background: Arsenic (As) exposure is a significant worldwide environmental health concern. Chronic exposure via contaminated drinking water has been associated with an increased incidence of a number of diseases, including reproductive and developmental effects. The goal of this study was to identify adverse outcomes in a mouse model of early life exposure to low-dose drinking water As (10 ppb, current U.S. EPA Maximum Contaminant Level). Methodology and Findings: C57B6/J pups were exposed to 10 ppb As, via the dam in her drinking water, either in utero and/or during the postnatal period. Birth outcomes, the growth of the F1 offspring, and …
Isolation Of Phosphatidylethanolamine As A Solitary Cofactor For Prion Formation In The Absence Of Nucleic Acids, Nathan R. Deleault, Justin R. Piro, Daniel J. Walsh, Fei Wang, Jiyan Ma, James C. Geoghegan, Surachai Supattapone
Isolation Of Phosphatidylethanolamine As A Solitary Cofactor For Prion Formation In The Absence Of Nucleic Acids, Nathan R. Deleault, Justin R. Piro, Daniel J. Walsh, Fei Wang, Jiyan Ma, James C. Geoghegan, Surachai Supattapone
Dartmouth Scholarship
Infectious prions containing the pathogenic conformer of the mammalian prion protein (PrP(Sc)) can be produced de novo from a mixture of the normal conformer (PrP(C)) with RNA and lipid molecules. Recent reconstitution studies indicate that nucleic acids are not required for the propagation of mouse prions in vitro, suggesting the existence of an alternative prion propagation cofactor in brain tissue. However, the identity and functional properties of this unique cofactor are unknown. Here, we show by purification and reconstitution that the molecule responsible for the nuclease-resistant cofactor activity in brain is endogenous phosphatidylethanolamine (PE). Synthetic PE alone facilitates conversion of …
Propentofylline Targets Troy, A Novel Microglial Signaling Pathway, Valerie L. Jacobs, Yingna Liu, Joyce A. De Leo
Propentofylline Targets Troy, A Novel Microglial Signaling Pathway, Valerie L. Jacobs, Yingna Liu, Joyce A. De Leo
Dartmouth Scholarship
Glioblastoma multiforme (GBM) is the most common and aggressive primary brain cancer, with a median survival of less than 2 years after diagnosis with current available therapies. The tumor microenvironment serves a critical role in tumor invasion and progression, with microglia as a critical player. Our laboratory has previously demonstrated that propentofylline, an atypical methylxanthine with central nervous system glial modulating and anti-inflammatory actions, significantly decreases tumor growth in a GBM rodent model by preferentially targeting microglia. In the present study, we used the CNS-1 rat glioma model to elucidate the mechanisms of propentofylline. Here we demonstrate that propentofylline targets …
Improved Tumor Contrast Achieved By Single Time Point Dual-Reporter Fluorescence Imaging, Kenneth M. Tichauer, Kimberley S. Samkoe, Kristian J. Sexton, Jason R. Gunn, Tayyaba Hasan, Brian W. Pogue
Improved Tumor Contrast Achieved By Single Time Point Dual-Reporter Fluorescence Imaging, Kenneth M. Tichauer, Kimberley S. Samkoe, Kristian J. Sexton, Jason R. Gunn, Tayyaba Hasan, Brian W. Pogue
Dartmouth Scholarship
In this study, we demonstrate a method to quantify biomarker expression that uses an exogenous dual-reporter imaging approach to improve tumor signal detection. The uptake of two fluorophores, one nonspecific and one targeted to the epidermal growth factor receptor (EGFR), were imaged at 1 h in three types of xenograft tumors spanning a range of EGFR expression levels (n = 6 in each group). Using this dual-reporter imaging methodology, tumor contrast-to-noise ratio was amplified by >6 times at 1 h postinjection and >2 times at 24 h. Furthermore, by as early as 20 min postinjection, the dual-reporter imaging signal …
Spatial Frequency Domain Tomography Of Protoporphyrin Ix Fluorescence In Preclinical Glioma Models, Soren D. Konecky, Chris M. Owen, Tyler Rice, Pablo A. ValdéS, Chris M. Owen, Pablo A. Valdes, David W. Roberts, Kolbein Kolste, Frederic Leblond, Keith D. Paulsen, Brian C. Wilson
Spatial Frequency Domain Tomography Of Protoporphyrin Ix Fluorescence In Preclinical Glioma Models, Soren D. Konecky, Chris M. Owen, Tyler Rice, Pablo A. ValdéS, Chris M. Owen, Pablo A. Valdes, David W. Roberts, Kolbein Kolste, Frederic Leblond, Keith D. Paulsen, Brian C. Wilson
Dartmouth Scholarship
Multifrequency (0 to 0.3 mm−1), multiwavelength (633, 680, 720, 800, and 820 nm) spatial frequency domain imaging (SFDI) of 5-aminolevulinic acid-induced protoporphyrin IX (PpIX) was used to recover absorption, scattering, and fluorescence properties of glioblastoma multiforme spheroids in tissue-simulating phantoms and in vivo in a mouse model. Three-dimensional tomographic reconstructions of the frequency-dependent remitted light localized the depths of the spheroids within 500 μm, and the total amount of PpIX in the reconstructed images was constant to within 30% when spheroid depth was varied. In vivo tumor-to-normal contrast was greater than ∼ 1.5 in reduced scattering coefficient for all wavelengths …
Corneal Replication Is An Interferon Response-Independent Bottleneck For Virulence Of Herpes Simplex Virus 1 In The Absence Of Virion Host Shutoff, Tracy J. Pasieka, Vineet D. Menachery, Pamela C. Rosato, David A. Leib
Corneal Replication Is An Interferon Response-Independent Bottleneck For Virulence Of Herpes Simplex Virus 1 In The Absence Of Virion Host Shutoff, Tracy J. Pasieka, Vineet D. Menachery, Pamela C. Rosato, David A. Leib
Dartmouth Scholarship
Herpes simplex viruses lacking the virion host shutoff function (Δvhs) are avirulent and hypersensitive to type I and type II interferon (IFN). In this study, we demonstrate that even in the absence of IFN responses in AG129 (IFN-αβγR−/−) mice, Δvhs remains highly attenuated via corneal infection but is fully virulent via intracranial infection. The data demonstrate that the interferon-independent inherent replication defect of Δvhs has a significant impact upon peripheral replication and neuroinvasion.
Pv1 Down-Regulation Via Shrna Inhibits The Growth Of Pancreatic Adenocarcinoma Xenografts, Sophie J. Deharvengt, Dan Tse, Olga Sideleva, Caitlin Mcgarry, Jason R. Gunn, Daniel S. Longnecker, Catherine Carriere, Radu V. Stan
Pv1 Down-Regulation Via Shrna Inhibits The Growth Of Pancreatic Adenocarcinoma Xenografts, Sophie J. Deharvengt, Dan Tse, Olga Sideleva, Caitlin Mcgarry, Jason R. Gunn, Daniel S. Longnecker, Catherine Carriere, Radu V. Stan
Dartmouth Scholarship
PV1 is an endothelial-specific protein with structural roles in the formation of diaphragms in endothelial cells of normal vessels. PV1 is also highly expressed on endothelial cells of many solid tumours. On the basis of in vitro data, PV1 is thought to actively participate in angiogenesis. To test whether or not PV1 has a function in tumour angiogenesis and in tumour growth in vivo, we have treated pancreatic tumour-bearing mice by single-dose intratumoural delivery of lentiviruses encoding for two different shRNAs targeting murine PV1. We find that PV1 down-regulation by shRNAs inhibits the growth of established tumours derived from two …
Mitogen Activated Protein Kinase Phosphatase-1 Prevents The Development Of Tactile Sensitivity In A Rodent Model Of Neuropathic Pain, Christian Ndong, Russell P. Landry, Joyce A. Deleo, Edgar A. Romero-Sandoval
Mitogen Activated Protein Kinase Phosphatase-1 Prevents The Development Of Tactile Sensitivity In A Rodent Model Of Neuropathic Pain, Christian Ndong, Russell P. Landry, Joyce A. Deleo, Edgar A. Romero-Sandoval
Dartmouth Scholarship
Neuropathic pain due to nerve injury is one of the most difficult types of pain to treat. Following peripheral nerve injury, neuronal and glial plastic changes contribute to central sensitization and perpetuation of mechanical hypersensitivity in rodents. The mitogen activated protein kinase (MAPK) family is pivotal in this spinal cord plasticity. MAPK phosphatases (MKPs) limit inflammatory processes by dephosphorylating MAPKs. For example, MKP-1 preferentially dephosphorylates p-p38. Since spinal p-p38 is pivotal for the development of chronic hypersensitivity in rodent models of pain, and p-p38 inhibitors have shown clinical potential in acute and chronic pain patients, we hypothesize that induction of …
Chromosomal Instability And Cancer: A Complex Relationship With Therapeutic Potential, Samuel F. Bakhoum, Duane A. Compton
Chromosomal Instability And Cancer: A Complex Relationship With Therapeutic Potential, Samuel F. Bakhoum, Duane A. Compton
Dartmouth Scholarship
Chromosomal instability (CIN) is a hallmark of human neoplasms. Despite its widespread prevalence, knowledge of the mechanisms and contributions of CIN in cancer has been elusive. It is now evident that the role of CIN in tumor initiation and growth is more complex than previously thought. Furthermore, distinguishing CIN, which consists of elevated rates of chromosome missegregation, from aneuploidy, which is a state of abnormal chromosome number, is crucial to understanding their respective contributions in cancer. Collectively, experimental evidence suggests that CIN enables tumor adaptation by allowing tumors to constantly sample the aneuploid fitness landscape. This complex relationship, together with …
Caveolae, Fenestrae And Transendothelial Channels Retain Pv1 On The Surface Of Endothelial Cells, Eugene Tkachenko, Dan Tse, Olga Sideleva, Sophie J. Deharvengt, Marcus R. Luciano, Yan Xu, Caitlin L. Mcgarry, John Chidlow, Paul F. Pilch, William C. Sessa, Derek K. Toomre, Radu V. Stan
Caveolae, Fenestrae And Transendothelial Channels Retain Pv1 On The Surface Of Endothelial Cells, Eugene Tkachenko, Dan Tse, Olga Sideleva, Sophie J. Deharvengt, Marcus R. Luciano, Yan Xu, Caitlin L. Mcgarry, John Chidlow, Paul F. Pilch, William C. Sessa, Derek K. Toomre, Radu V. Stan
Dartmouth Scholarship
PV1 protein is an essential component of stomatal and fenestral diaphragms, which are formed at the plasma membrane of endothelial cells (ECs), on structures such as caveolae, fenestrae and transendothelial channels. Knockout of PV1 in mice results in in utero and perinatal mortality. To be able to interpret the complex PV1 knockout phenotype, it is critical to determine whether the formation of diaphragms is the only cellular role of PV1. We addressed this question by measuring the effect of complete and partial removal of structures capable of forming diaphragms on PV1 protein level. Removal of caveolae in mice by knocking …
Ovarian Cancer Progression Is Controlled By Phenotypic Changes In Dendritic Cells, Uciane K. Scarlett, Melanie R. Rutkowski, Adam M. Rauwerdink, Jennifer Fields, Ximena Escovar-Fadul, Jason Baird, Juan R. Cubillos-Ruiz, Ana C. Jacobs, Jorge L. Gonzalez, John Weaver, Steven Fiering, Jose R. Conejo-Garcia
Ovarian Cancer Progression Is Controlled By Phenotypic Changes In Dendritic Cells, Uciane K. Scarlett, Melanie R. Rutkowski, Adam M. Rauwerdink, Jennifer Fields, Ximena Escovar-Fadul, Jason Baird, Juan R. Cubillos-Ruiz, Ana C. Jacobs, Jorge L. Gonzalez, John Weaver, Steven Fiering, Jose R. Conejo-Garcia
Dartmouth Scholarship
We characterized the initiation and evolution of the immune response against a new inducible p53-dependent model of aggressive ovarian carcinoma that recapitulates the leukocyte infiltrates and cytokine milieu of advanced human tumors. Unlike other models that initiate tumors before the development of a mature immune system, we detect measurable antitumor immunity from very early stages, which is driven by infiltrating dendritic cells (DCs) and prevents steady tumor growth for prolonged periods. Coinciding with a phenotypic switch in expanding DC infiltrates, tumors aggressively progress to terminal disease in a comparatively short time. Notably, tumor cells remain immunogenic at advanced stages, but …
Quantitative Cherenkov Emission Spectroscopy For Tissue Oxygenation Assessment, Johan Axelsson, Adam K. Glaser, David J. Gladstone, Brian W. Pogue
Quantitative Cherenkov Emission Spectroscopy For Tissue Oxygenation Assessment, Johan Axelsson, Adam K. Glaser, David J. Gladstone, Brian W. Pogue
Dartmouth Scholarship
Measurements of Cherenkov emission in tissue during radiation therapy are shown to enable estimation of hemoglobin oxygen saturation non-invasively, through spectral fitting of the spontaneous emissions from the treated tissue. Tissue oxygenation plays a critical role in the efficacy of radiation therapy to kill tumor tissue. Yet in-vivo measurement of this has remained elusive in routine use because of the complexity of oxygen measurement techniques. There is a spectrally broad emission of Cherenkov light that is induced during the time of irradiation, and as this travels through tissue from the point of the radiation deposition, the tissue absorption and scatter …
The Formin Fmnl3 Is A Cytoskeletal Regulator Of Angiogenesis, Clare Hetheridge, Alice N. Scott, Rajeeb K. Swain, John W. Copeland, Henry N. Higgs
The Formin Fmnl3 Is A Cytoskeletal Regulator Of Angiogenesis, Clare Hetheridge, Alice N. Scott, Rajeeb K. Swain, John W. Copeland, Henry N. Higgs
Dartmouth Scholarship
The process of angiogenesis requires endothelial cells (ECs) to undergo profound changes in shape and polarity. Although this must involve remodelling of the EC cytoskeleton, little is known about this process or the proteins that control it. We used a co-culture assay of angiogenesis to examine the cytoskeleton of ECs actively undergoing angiogenic morphogenesis. We found that elongation of ECs during angiogenesis is accompanied by stabilisation of microtubules and their alignment into parallel arrays directed at the growing tip. In other systems, similar microtubule alignments are mediated by the formin family of cytoskeletal regulators. We screened a library of human …
Seg1 Controls Eisosome Assembly And Shape, Karen E. Moreira, Sebastian Schuck, Bianca Schrul, Florian Fröhlich, James B. Moseley
Seg1 Controls Eisosome Assembly And Shape, Karen E. Moreira, Sebastian Schuck, Bianca Schrul, Florian Fröhlich, James B. Moseley
Dartmouth Scholarship
Eisosomes are stable domains at the plasma membrane of the budding yeast Saccharomyces cerevisiae and have been proposed to function in endocytosis. Eisosomes are composed of two main cytoplasmic proteins, Pil1 and Lsp1, that form a scaffold around furrow-like plasma membrane invaginations. We show here that the poorly characterized eisosome protein Seg1/Ymr086w is important for eisosome biogenesis and architecture. Seg1 was required for efficient incorporation of Pil1 into eisosomes and the generation of normal plasma membrane furrows. Seg1 preceded Pil1 during eisosome formation and established a platform for the assembly of other eisosome components. This platform was further shaped and …