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2014

Medical Sciences

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Full-Text Articles in Cell Biology

Arsenic Targets Neural Plate Border Specifier Cells In P19 Cells, Christopher Mccoy Dec 2014

Arsenic Targets Neural Plate Border Specifier Cells In P19 Cells, Christopher Mccoy

All Theses

Epidemiological studies have shown that arsenic exposure during early embryogenesis can cause reduced weight gain and neurological deficits later on in life. In addition, in vitro and in vivo studies have indicated that arsenic suppresses neurogenesis and myogenesis. The exact mechanism of how arsenic causes these undesired developmental outcomes is poorly understood, however both skeletal muscle and sensory neuron development require the Wnt/β-catenin signaling pathway to initiate the specific differentiation of precursor cells. We were interested in determining the target cell population of arsenic and its metabolites. Arsenic's metabolites were of interest because they have been shown to ...


Peptide Arrays For Detecting Naphthenic Acids In Oil Sands Process Affected Water, Kamaljit Kaur, Subir Bhattacharjee, Rajesh G. Pillai, Sahar Ahmed, Sarfuddin Azmi Nov 2014

Peptide Arrays For Detecting Naphthenic Acids In Oil Sands Process Affected Water, Kamaljit Kaur, Subir Bhattacharjee, Rajesh G. Pillai, Sahar Ahmed, Sarfuddin Azmi

Pharmacy Faculty Articles and Research

Naphthenic acids (NAs) are water-soluble components of petroleum. The characterization and quantification of NAs by analytical methods have proved quite challenging, whilst the toxic effects of these water-soluble compounds on a variety of organisms adversely affecting reproduction and steroid production is becoming apparent. In this study, we report a fluorescence-based competitive binding method for rapid sensing of the presence of NAs using cellulosic peptide array strips as sensors. The peptide array was designed from sequences derived from the estrogen receptor (ER). Several of these peptides were able to detect the presence of NAs at low micromolar (∼5 mg L−1 ...


Enteroendocrine Cells Support Intestinal Stem-Cell-Mediated Homeostasis In Drosophila, Alla Amcheslavsky, Wei Song, Qi Li, Yingchao Nie, Ivan Bragatto, Dominique Ferrandon, Norbert Perrimon, Y. Tony Ip Oct 2014

Enteroendocrine Cells Support Intestinal Stem-Cell-Mediated Homeostasis In Drosophila, Alla Amcheslavsky, Wei Song, Qi Li, Yingchao Nie, Ivan Bragatto, Dominique Ferrandon, Norbert Perrimon, Y. Tony Ip

UMass Center for Clinical and Translational Science Supported Publications

Intestinal stem cells in the adult Drosophila midgut are regulated by growth factors produced from the surrounding niche cells including enterocytes and visceral muscle. The role of the other major cell type, the secretory enteroendocrine cells, in regulating intestinal stem cells remains unclear. We show here that newly eclosed scute loss-of-function mutant flies are completely devoid of enteroendocrine cells. These enteroendocrine cell-less flies have normal ingestion and fecundity but shorter lifespan. Moreover, in these newly eclosed mutant flies, the diet-stimulated midgut growth that depends on the insulin-like peptide 3 expression in the surrounding muscle is defective. The depletion of Tachykinin-producing ...


Tlr Sorting By Rab11 Endosomes Maintains Intestinal Epithelial-Microbial Homeostasis, Shiyan Yu, Yingchao Nie, Y. Tony Ip, Nan Gao Sep 2014

Tlr Sorting By Rab11 Endosomes Maintains Intestinal Epithelial-Microbial Homeostasis, Shiyan Yu, Yingchao Nie, Y. Tony Ip, Nan Gao

UMass Center for Clinical and Translational Science Supported Publications

Compartmentalization of Toll-like receptors (TLRs) in intestinal epithelial cells (IECs) regulates distinct immune responses to microbes; however, the specific cellular machinery that controls this mechanism has not been fully identified. Here we provide genetic evidences that the recycling endosomal compartment in enterocytes maintains a homeostatic TLR9 intracellular distribution, supporting mucosal tolerance to normal microbiota. Genetic ablation of a recycling endosome resident small GTPase, Rab11a, a gene adjacent to a Crohn's disease risk locus, in mouse IECs and in Drosophila midgut caused epithelial cell-intrinsic cytokine production, inflammatory bowel phenotype, and early mortality. Unlike wild-type controls, germ-free Rab11a-deficient mouse intestines failed ...


Genomic Predictors Of Drug Response To The Alpha-Specific Phosphoinositol 3-Kinase (Pi3ka-Alpha) Inhibitor Byl719 In Head And Neck Cancers, Giananthony T. Rizzo Jul 2014

Genomic Predictors Of Drug Response To The Alpha-Specific Phosphoinositol 3-Kinase (Pi3ka-Alpha) Inhibitor Byl719 In Head And Neck Cancers, Giananthony T. Rizzo

Electronic Thesis and Dissertation Repository

PIK3CA is the only frequently mutated, druggable oncogene in head and neck squamous cell cancer (HNSCC), with PIK3CA point mutations and gene amplification rates of 17.5% and 40% respectively, with higher rates in HPV-positive disease. The objective of this research was to determine the effects of BYL719, an α-specific PI3K inhibitor in HNSCC cell lines.

All cell lines with PIK3CA hotspot point mutations or gene amplifications will be sensitive to BYL719.

Twenty-eight HNSCC cell lines were subjected to increasing concentrations of BYL719 and cell viability was measured over time. Cell lines were screened for activating PIK3CA hotspot mutations and ...


Cooperative Binding Of The Outer Arm-Docking Complex Underlies The Regular Arrangement Of Outer Arm Dynein In The Axoneme, Mikito Owa, Akane Furuta, Jiro Usukura, Fumio Arisaka, Stephen M. King, George B. Witman, Ritsu Kamiya, Ken-Ichi Wakabayashi Jul 2014

Cooperative Binding Of The Outer Arm-Docking Complex Underlies The Regular Arrangement Of Outer Arm Dynein In The Axoneme, Mikito Owa, Akane Furuta, Jiro Usukura, Fumio Arisaka, Stephen M. King, George B. Witman, Ritsu Kamiya, Ken-Ichi Wakabayashi

Cell and Developmental Biology Publications

Outer arm dynein (OAD) in cilia and flagella is bound to the outer doublet microtubules every 24 nm. Periodic binding of OADs at specific sites is important for efficient cilia/flagella beating; however, the molecular mechanism that specifies OAD arrangement remains elusive. Studies using the green alga Chlamydomonas reinhardtii have shown that the OAD-docking complex (ODA-DC), a heterotrimeric complex present at the OAD base, functions as the OAD docking site on the doublet. We find that the ODA-DC has an ellipsoidal shape approximately 24 nm in length. In mutant axonemes that lack OAD but retain the ODA-DC, ODA-DC molecules are ...


Gene Expression Profiling Identifies The Zinc-Finger Protein Charlatan As A Regulator Of Intestinal Stem Cells In Drosophila, Alla Amcheslavsky, Yingchao Nie, Qi Li, Feng He, Leo Tsuda, Michele Markstein, Y. Tony Ip Jul 2014

Gene Expression Profiling Identifies The Zinc-Finger Protein Charlatan As A Regulator Of Intestinal Stem Cells In Drosophila, Alla Amcheslavsky, Yingchao Nie, Qi Li, Feng He, Leo Tsuda, Michele Markstein, Y. Tony Ip

UMass Center for Clinical and Translational Science Supported Publications

Intestinal stem cells (ISCs) in the adult Drosophila midgut can respond to tissue damage and support repair. We used genetic manipulation to increase the number of ISC-like cells in the adult midgut and performed gene expression profiling to identify potential ISC regulators. A detailed analysis of one of these potential regulators, the zinc-finger protein Charlatan, was carried out. MARCM clonal analysis and RNAi in precursor cells showed that loss of Chn function caused severe ISC division defects, including loss of EdU incorporation, phosphorylated histone 3 staining and expression of the mitotic protein Cdc2. Loss of Charlatan also led to a ...


Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford Jun 2014

Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford

Pursuit - The Journal of Undergraduate Research at the University of Tennessee

Multiple sclerosis (MS) is a neurodegenerative disorder caused by a prolonged immune- mediated inflammatory response that targets myelin. Nearly all of the drugs approved for the treatment of MS are general immunosuppressants or only function in symptom management. The oral medication fingolimod, however, is reported to have direct therapeutic effects on cells of the central nervous system in addition to immunomodulatory functions. Fingolimod is known to interact with sphingosine-1-phosphate (S1P) receptors, and the most widely- accepted theory for its mechanism of action is functional antagonism of the receptor. This review examines significant neuromodulatory effects achieved by functional antagonism of the ...


Mnk2 Alternative Splicing Modulates The P38-Mapk Pathway And Impacts Ras-Induced Transformation, Avraham Maimon, Maxim Mogilevsky, Asaf Shilo, Regina Golan-Gerstl, Akram Obiedat, Vered Ben-Hur, Ilana Lebenthal-Loinger, Ilan Stein, Reuven Reich, Jonah Beenstock, Eldar Zehorai, Claus L. Andersen, Kasper Thorsen, Torben F. Orntoft, Roger J. Davis, Ben Davidson, David Mu, Rotem Karni Apr 2014

Mnk2 Alternative Splicing Modulates The P38-Mapk Pathway And Impacts Ras-Induced Transformation, Avraham Maimon, Maxim Mogilevsky, Asaf Shilo, Regina Golan-Gerstl, Akram Obiedat, Vered Ben-Hur, Ilana Lebenthal-Loinger, Ilan Stein, Reuven Reich, Jonah Beenstock, Eldar Zehorai, Claus L. Andersen, Kasper Thorsen, Torben F. Orntoft, Roger J. Davis, Ben Davidson, David Mu, Rotem Karni

Davis Lab Publications

The kinase Mnk2 is a substrate of the MAPK pathway and phosphorylates the translation initiation factor eIF4E. In humans, MKNK2, the gene encoding for Mnk2, is alternatively spliced yielding two splicing isoforms with differing last exons: Mnk2a, which contains a MAPK-binding domain, and Mnk2b, which lacks it. We found that the Mnk2a isoform is downregulated in breast, lung, and colon tumors and is tumor suppressive. Mnk2a directly interacts with, phosphorylates, activates, and translocates p38alpha-MAPK into the nucleus, leading to activation of its target genes, increasing cell death and suppression of Ras-induced transformation. Alternatively, Mnk2b is pro-oncogenic and does not activate ...


Photobiostimulation In C. Elegans As A Model For Low Level Light Therapy, Michael J. Spoto, Daryl D. Hurd Apr 2014

Photobiostimulation In C. Elegans As A Model For Low Level Light Therapy, Michael J. Spoto, Daryl D. Hurd

Science Scholars

Low-Level Laser Therapy (LLLT) is a developing therapeutic technique that has been gaining recognition in the scientific community in recent years. Previous experiments performed in LLLT research projects have been primarily mammalian and cell culture based. These experiments have produced results showing accelerated tissue repair. In this experiment, we introduce a new model, Caenorhabitidis elegans, a free-living soil nematode, to be used in LLLT research by testing the effects of exposure of the organism to various wavelengths and intensities of light commonly used in LLLT. C. elegans was shown to respond to photobiostimulation when exposed to specific wavelengths of Infrared ...


Smurf2 Regulates Hematopoietic Stem Cell Self-Renewal And Aging, Charusheila Ramkumar, Yahui Kong, Sally E. Trabucco, Rachel M. Gerstein, Hong Zhang Feb 2014

Smurf2 Regulates Hematopoietic Stem Cell Self-Renewal And Aging, Charusheila Ramkumar, Yahui Kong, Sally E. Trabucco, Rachel M. Gerstein, Hong Zhang

GSBS Student Publications

The age-dependent decline in the self-renewal capacity of stem cells plays a critical role in aging, but the precise mechanisms underlying this decline are not well understood. By limiting proliferative capacity, senescence is thought to play an important role in age-dependent decline of stem cell self-renewal, although direct evidence supporting this hypothesis is largely lacking. We have previously identified the E3 ubiquitin ligase Smurf2 as a critical regulator of senescence. In this study, we found that mice deficient in Smurf2 had an expanded hematopoietic stem cell (HSC) compartment in bone marrow under normal homeostatic conditions, and this expansion was associated ...


Candida Albicans Als5p Amyloid In Host-Microbe Interactions: A Ceanorhabditis Elegans Study, Michael Bois Feb 2014

Candida Albicans Als5p Amyloid In Host-Microbe Interactions: A Ceanorhabditis Elegans Study, Michael Bois

All Dissertations, Theses, and Capstone Projects

Candida albicans, a dimorphic fungus and an opportunistic pathogen, possesses a myriad of adherence factors including members of the agglutinin-like sequence (Als) family of mannoproteins. The adhesin Als5p mediates adhesion to many substrates, and is upregulated during commensal interactions, but is downregulated during active C. albicans infections[1]. An amyloid forming core sequence at residues 325-331 has been shown to be important for Als5p function, because a single amino acid substitution at position 326 (V326N) greatly reduces Als5p-mediated adherence[2]. We evaluated the role of Als5p in host-microbe interactions, using Caenorhabditis elegans as a host model and feeding them Saccharomyces ...


The Role Of Oxygen Tension And Insulin-Like Growth Factor Signaling In The Placental Mesenchymal Stem Cell Fate, Amer Youssef Jan 2014

The Role Of Oxygen Tension And Insulin-Like Growth Factor Signaling In The Placental Mesenchymal Stem Cell Fate, Amer Youssef

Electronic Thesis and Dissertation Repository

The human placenta of different gestational ages is a readily available source for isolation of adult mesenchymal stem cell (MSC) for potential use in regenerative therapies. The chorionic villous region, the largest component of a placenta that interfaces with the maternal circulation, is a rich source of placental MSCs (PMSCs). To remain multipotent, PMSCs are best maintained in culture conditions that mimic the in vivo microenvironment. Insulin like growth factors (IGFs, IGF-I and -II) and oxygen tension are two of the most important microenvironmental factors in the placenta. They are of low concentration or tension respectively, at early gestation, and ...


Effect Of A 10 Day Decrease In Physical Activity On Circulating Angiogenic Cells, Gayatri Guhanarayan Jan 2014

Effect Of A 10 Day Decrease In Physical Activity On Circulating Angiogenic Cells, Gayatri Guhanarayan

Masters Theses 1911 - February 2014

Circulating angiogenic cells (CACs) are early predictors of cardiovascular health and are inversely proportional to related outcomes. Increased number and function of CACs is seen in healthy individuals compared with individuals with cardiovascular disease (CVD). Exercise increases CAC number and function in CVD populations, through a nitric oxide-mediated mechanism. Inactivity is a growing concern in industrialized nations; it is an independent risk factor for CVD and is linked to increased mortality. The purpose of this study was to understand the effect of reduced physical activity (rPA) on two CAC populations (CFU-Hill and CD34+) in highly active individuals. We examined the ...


Roles Of Dendritic Cells In Immunity To Toxoplasma Gondii, Christopher David Dupont Jan 2014

Roles Of Dendritic Cells In Immunity To Toxoplasma Gondii, Christopher David Dupont

Publicly Accessible Penn Dissertations

Toxoplasma gondii is an intracellular protozoan parasite that actively invades host cells. During toxoplasmosis, dendritic cells (DCs) promote CD4+ and CD8+ T cell responses, which are critical for long-term immunity. Despite this critical role of DCs, questions remain regarding how this population is regulated during infection, and the specific types of interactions (phagocytosis or active invasion) between parasites and DCs that are necessary to induce T cell responses.

Previous studies have observed an infection-induced expansion of DC populations during toxoplasmosis, but the factors that regulate this expansion are currently unknown. Mice deficient in the cytokine Flt3L, which promotes the proliferation ...


Ebna1-Specific T Cell Responses During Persistent Rhesus Lcv Infection And The Development Of A Novel Therapeutic Prototype Vaccine For Ebv-Associated Diseases, Rachel Mandy Leskowitz Jan 2014

Ebna1-Specific T Cell Responses During Persistent Rhesus Lcv Infection And The Development Of A Novel Therapeutic Prototype Vaccine For Ebv-Associated Diseases, Rachel Mandy Leskowitz

Publicly Accessible Penn Dissertations

The impact of EBV on human health is substantial, but vaccines that prevent primary EBV infections or treat EBV-associated diseases are not yet available. The Epstein-Barr nuclear antigen 1 (EBNA1) is an important target for vaccination because it is the only protein expressed in all forms of latency and in all EBV-associated malignancies. The overarching goal throughout this dissertation was to determine if EBNA1 is a suitable target for vaccine development. This was addressed in two ways. First, because an improved understanding of EBNA1-specific T cell responses benefits EBV vaccine development, we characterized responses against EBNA1 of the EBV-homologous rhesus ...


Opposing Actin Networks Modulate The Mechano-Activation Of The Integrin Lfa-1 During Immunological Synapse Formation, William Andrew Comrie Jan 2014

Opposing Actin Networks Modulate The Mechano-Activation Of The Integrin Lfa-1 During Immunological Synapse Formation, William Andrew Comrie

Publicly Accessible Penn Dissertations

Formation of a functional immune response requires the regulated transfer of information between T cells, and APCs, which leads to a variety of functional outcomes. In many cases this information transfer occurs at a regulated area of cell - cell contact termed the immunological synapse (IS). In T cells responding to APCs there is a robust accumulation of F-actin on the T cell side of the synapse. This F-actin response is characterized by robust polymerization at the periphery of the contact site followed by centripetal flow of the network towards the center of the IS. While it is well known that ...


A Potential Mechanism For Extracellular Matrix Induction Of Breast Cancer Cell Normality, Robert D. Bruno, Gilbert H. Smith Jan 2014

A Potential Mechanism For Extracellular Matrix Induction Of Breast Cancer Cell Normality, Robert D. Bruno, Gilbert H. Smith

Medical Diagnostics & Translational Sciences Faculty Publications

Extracellular matrix proteins from embryonic mesenchyme have a normalizing effect on cancer cells in vitro and slow tumor growth in vivo. This concept is suggestive of a new method for controlling the growth and spread of existing cancer cells in situ and indicates the possibility that extracellular proteins and/or embryonic mesenchymal fibroblasts may represent a fertile subject for study of new anti-cancer treatments.


Recirculation Of Innate Lymphocyte Subsets In The Skin, Skye Geherin Jan 2014

Recirculation Of Innate Lymphocyte Subsets In The Skin, Skye Geherin

Publicly Accessible Penn Dissertations

The trafficking of innate-like lymphocytes, such as γδ T cells and B-1 B cells, has garnered comparatively little attention from the immunological community relative to conventional T and B cells. However, recent studies have shown that innate-like cell subsets are critical for immune regulation and host defense. In this study, we use a classic ovine lymph cannulation model to describe the phenotype and function of γδ T cells migrating through the skin. We find that γδ T cells traveling in the skin-draining afferent lymph are IFN-γ- and/or IL-17-producing effector cells that express high levels of the skin- and inflammation-seeking ...


Role Of Cytoskeletal Remodeling In T Cell Receptor Signaling And Integrin Activation At The Immunological Synapse, Alexander Babich Jan 2014

Role Of Cytoskeletal Remodeling In T Cell Receptor Signaling And Integrin Activation At The Immunological Synapse, Alexander Babich

Publicly Accessible Penn Dissertations

The efficiency of an immune response critically depends on the ability of T cells to respond to antigens. Upon encountering cognate antigenic peptides on the surface of antigen-presenting cells, T cells form a specialized interface, termed the immunological synapse (IS), which serves as the site of information transfer between the cells. This contact zone is characterized by the enrichment of signaling receptors, kinases and adaptor proteins, and is the site of extensive cytoskeletal remodeling. The versatile nature and spatio-temporal regulation of signaling cascades at the IS has long been recognized but the exact mechanisms that coordinate these processes remain poorly ...