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Cryo-Em Structure Of The Human Ferritin–Transferrin Receptor 1 Complex, Linda Celeste Montemiglio, Claudia Testi, Pierpaolo Ceci, Elisabetta Falvo, Martina Pitea, Carmelinda Savino, Alessandro Arcovito, Giovanna Peruzzi, Paola Baiocco, Filippo Mancia, Alberto Boffi, Amédée des Georges, Beatrice Vallone 2019 Sapienza University of Rome

Cryo-Em Structure Of The Human Ferritin–Transferrin Receptor 1 Complex, Linda Celeste Montemiglio, Claudia Testi, Pierpaolo Ceci, Elisabetta Falvo, Martina Pitea, Carmelinda Savino, Alessandro Arcovito, Giovanna Peruzzi, Paola Baiocco, Filippo Mancia, Alberto Boffi, Amédée Des Georges, Beatrice Vallone

Publications and Research

Human transferrin receptor 1 (CD71) guarantees iron supply by endocytosis upon binding of iron-loaded transferrin and ferritin. Arenaviruses and the malaria parasite exploit CD71 for cell invasion and epitopes on CD71 for interaction with transferrin and pathogenic hosts were identified. Here, we provide the molecular basis of the CD71 ectodomain-human ferritin interaction by determining the 3.9 Å resolution single-particle cryo-electron microscopy structure of their complex and by validating our structural findings in a cellular context. The contact surfaces between the heavy-chain ferritin and CD71 largely overlap with arenaviruses and Plasmodium vivax binding regions in the apical part of the ...


Advances In Geometric Techniques For Analyzing Blebbing In Chemotaxing Dictyostelium Cells, Zully Santiago, John Loustau, David Meretzky, Devarshi Rawal, Derrick Brazill 2019 CUNY Hunter College

Advances In Geometric Techniques For Analyzing Blebbing In Chemotaxing Dictyostelium Cells, Zully Santiago, John Loustau, David Meretzky, Devarshi Rawal, Derrick Brazill

Publications and Research

We present a technical platform that allows us to monitor and measure cortex and membrane dynamics during bleb-based chemotaxis. Using D. discoideum cells expressing LifeAct-GFP and crawling under agarose containing RITC-dextran, we were able to simultaneously visualize the actin cortex and the cell membrane throughout bleb formation. Using these images, we then applied edge detect to generate points on the cell boundary with coordinates in a coordinate plane. Then we fitted these points to a curve with known x and y coordinate functions. The result was to parameterize the cell outline. With the parameterization, we demonstrate how to compute data ...


Optimization Of Primary Cilia Detection In Musculoskeletal Tissue, Ragen Engel 2019 The University of Akron

Optimization Of Primary Cilia Detection In Musculoskeletal Tissue, Ragen Engel

Williams Honors College, Honors Research Projects

The objective of this research project was to optimize a laboratory technique for visualizing primary cilia in musculoskeletal tissue of young swine, specifically the growth plate of long bones. This was accomplished through varying fixation procedures, antigen retrieval methods, antibody concentrations, and incubation times. By varying these parameters, a reproducible procedure was developed to examine the primary cilia in multiple tissues including ligament, fascia, and growth plate. This experiment introduced variances in fixation methods, with methanol or formalin. Paraffin and frozen embedding techniques were also varied for comparison with regards to cilia visualization. Results from the acetylated alpha tubulin (aTUB ...


The Roles Of Primary Cilia In Cardiovascular Diseases, Rajasekharreddy Pala, Maha Jamal, Qamar Alshammari, Surya M. Nauli 2018 Chapman University

The Roles Of Primary Cilia In Cardiovascular Diseases, Rajasekharreddy Pala, Maha Jamal, Qamar Alshammari, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia are microtubule-based organelles found in most mammalian cell types. Cilia act as sensory organelles that transmit extracellular clues into intracellular signals for molecular and cellular responses. Biochemical and molecular defects in primary cilia are associated with a wide range of diseases, termed ciliopathies, with phenotypes ranging from polycystic kidney disease, liver disorders, mental retardation, and obesity to cardiovascular diseases. Primary cilia in vascular endothelia protrude into the lumen of blood vessels and function as molecular switches for calcium (Ca2+) and nitric oxide (NO) signaling. As mechanosensory organelles, endothelial cilia are involved in blood flow sensing. Dysfunction in endothelial ...


Modified Cantilever Arrays Improve Sensitivity And Reproducibility Of Nanomechanical Sensing In Living Cells, Samadhan B. Patil, Rajai M. Al-Jehani, Hashem Etayash, Valerian Turbe, Keren Jiang, Joe Bailey, Walid Al-Akkad, Rania Soudy, Kamaljit Kaur, Rachel A. McKendry, Thomas Thundat, Joseph W. Ndieyira 2018 University College London

Modified Cantilever Arrays Improve Sensitivity And Reproducibility Of Nanomechanical Sensing In Living Cells, Samadhan B. Patil, Rajai M. Al-Jehani, Hashem Etayash, Valerian Turbe, Keren Jiang, Joe Bailey, Walid Al-Akkad, Rania Soudy, Kamaljit Kaur, Rachel A. Mckendry, Thomas Thundat, Joseph W. Ndieyira

Pharmacy Faculty Articles and Research

Mechanical signaling involved in molecular interactions lies at the heart of materials science and biological systems, but the mechanisms involved are poorly understood. Here we use nanomechanical sensors and intact human cells to provide unique insights into the signaling pathways of connectivity networks, which deliver the ability to probe cells to produce biologically relevant, quantifiable and reproducible signals. We quantify the mechanical signals from malignant cancer cells, with 10 cells per ml in 1000-fold excess of non-neoplastic human epithelial cells. Moreover, we demonstrate that a direct link between cells and molecules creates a continuous connectivity which acts like a percolating ...


Unravelling The Structure Of Glycosyl Cations Via Cold-Ion Infrared Spectroscopy, Eike Mucha, Mateusz Marianski, Fei-Fei Xu, Daniel A. Thomas, Gerard Meijer, Gert von Helden, Peter H. Seeberger, Kevin Pagel 2018 Max Planck Society

Unravelling The Structure Of Glycosyl Cations Via Cold-Ion Infrared Spectroscopy, Eike Mucha, Mateusz Marianski, Fei-Fei Xu, Daniel A. Thomas, Gerard Meijer, Gert Von Helden, Peter H. Seeberger, Kevin Pagel

Publications and Research

Glycosyl cations are the key intermediates during the glycosylation reaction that covalently links building blocks during the synthetic assembly of carbohydrates. The exact structure of these ions remained elusive due to their transient and short-lived nature. Structural insights into the intermediate would improve our understanding of the reaction mechanism of glycosidic bond formation. Here, we report an in-depth structural analysis of glycosyl cations using a combination of cold-ion infrared spectroscopy and first-principles theory. Participating C2 protective groups form indeed a covalent bond with the anomeric carbon that leads to C1-bridged acetoxonium-type structures. The resulting bicyclic structure strongly distorts the ring ...


Characterizing The Cognitive And Emotional Effects Of Delta-9-Tetrahydrocannabinol In Distinct Hippocampal Sub-Regions, Dinat Khan 2018 The University of Western Ontario

Characterizing The Cognitive And Emotional Effects Of Delta-9-Tetrahydrocannabinol In Distinct Hippocampal Sub-Regions, Dinat Khan

Electronic Thesis and Dissertation Repository

The objective of this study is to determine the potential differential effects of THC in the DH or VH sub-regions, as well as the upstream effects on PFC neuronal activity and oscillations. Rodents used for electrophysiology were infused with THC or vehicle in the DH or VH regions, combined with PFC recordings. Additionally, a battery of behavioural paradigms was performed. Deficits in short-term memory when THC was infused into both regions was observed, however working memory was impaired with VH infusions only. This could be due to THC-induced dysregulation in the PFC, as beta oscillations were significantly decreased selectively in ...


“Do We Know Jack” About Jak? A Closer Look At Jak/Stat Signaling Pathway, Emira Bousoik, Hamidreza Montazeri Aliabadi 2018 Chapman University

“Do We Know Jack” About Jak? A Closer Look At Jak/Stat Signaling Pathway, Emira Bousoik, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Janus tyrosine kinase (JAK) family of proteins have been identified as crucial proteins in signal transduction initiated by a wide range of membrane receptors. Among the proteins in this family JAK2 has been associated with important downstream proteins, including signal transducers and activators of transcription (STATs), which in turn regulate the expression of a variety of proteins involved in induction or prevention of apoptosis. Therefore, the JAK/STAT signaling axis plays a major role in the proliferation and survival of different cancer cells, and may even be involved in resistance mechanisms against molecularly targeted drugs. Despite extensive research focused on ...


Lim Protein Ajuba Associates With The Rpa Complex Through Direct Cell Cycle-Dependent Interaction With The Rpa70 Subunit, Sandy Fowler, Pascal Maguin, Sampada Kalan, Diego Loayza 2018 CUNY Hunter College

Lim Protein Ajuba Associates With The Rpa Complex Through Direct Cell Cycle-Dependent Interaction With The Rpa70 Subunit, Sandy Fowler, Pascal Maguin, Sampada Kalan, Diego Loayza

Publications and Research

DNA damage response pathways are essential for genome stability and cell survival. Specifically, the ATR kinase is activated by DNA replication stress. An early event in this activation is the recruitment and phosphorylation of RPA, a single stranded DNA binding complex composed of three subunits, RPA70, RPA32 and RPA14. We have previously shown that the LIM protein Ajuba associates with RPA, and that depletion of Ajuba leads to potent activation of ATR. In this study, we provide evidence that the Ajuba-RPA interaction occurs through direct protein contact with RPA70, and that their association is cell cycle-regulated and is reduced upon ...


Reconstitution Of Gabaergic Postsynapses In Host Cells, Karthik Kanamalla 2018 University of Connecticut

Reconstitution Of Gabaergic Postsynapses In Host Cells, Karthik Kanamalla

Honors Scholar Theses

Type A GABA receptors (GABAARs) can be found embedded in postsynaptic membranes or in a variety of extrasynaptic locations. Receptors with synaptic function are recruited to the postsynapse by submembranous scaffolds composed of gephyrin and collybistin (CB). This study was aimed at assessing whether the ability to interact with the scaffold differentiates synaptic from non-synaptic receptors. Using HEK293 cells as an expression system, and indirect immunofluorescence (IF), co-localization of extrasynaptic receptors α1β3δ and α4β3δ with the CB-gephyrin scaffold was assessed and compared with that of the synaptic receptor α1β3γ2. Results indicated that both extrasynaptic receptors were able to colocalize with ...


Sodium Bicarbonate Cotransporter Nbce2 Gene Variants Increase Sodium And Bicarbonate Transport In Human Renal Proximal Tubule Cells., John J Gildea, Peng Xu, Brandon A Kemp, Julia M Carlson, Hanh T Tran, Dora Bigler Wang, Christophe J Langouët-Astrié, Helen E McGrath, Robert M Carey, Pedro A Jose, Robin A Felder 2018 George Washington University

Sodium Bicarbonate Cotransporter Nbce2 Gene Variants Increase Sodium And Bicarbonate Transport In Human Renal Proximal Tubule Cells., John J Gildea, Peng Xu, Brandon A Kemp, Julia M Carlson, Hanh T Tran, Dora Bigler Wang, Christophe J Langouët-Astrié, Helen E Mcgrath, Robert M Carey, Pedro A Jose, Robin A Felder

Medicine Faculty Publications

RATIONALE: Salt sensitivity of blood pressure affects >30% of the hypertensive and >15% of the normotensive population. Variants of the electrogenic sodium bicarbonate cotransporter NBCe2 gene, SLC4A5, are associated with increased blood pressure in several ethnic groups. SLC4A5 variants are also highly associated with salt sensitivity, independent of hypertension. However, little is known about how NBCe2 contributes to salt sensitivity, although NBCe2 regulates renal tubular sodium bicarbonate transport. We hypothesized that SLC4A5 rs10177833 and rs7571842 increase NBCe2 expression and human renal proximal tubule cell (hRPTC) sodium transport and may be a cause of salt sensitivity of blood pressure.

OBJECTIVE: To ...


Validation Of Minimally-Invasive Sample Collection Methods For Measurement Of Telomere Length, Stephanie A. Stout, Jue Lin, Natalie Hernandez, Elyssia Poggi Davis, Judith E. Carroll, Laura M. Glynn 2017 University of Denver

Validation Of Minimally-Invasive Sample Collection Methods For Measurement Of Telomere Length, Stephanie A. Stout, Jue Lin, Natalie Hernandez, Elyssia Poggi Davis, Judith E. Carroll, Laura M. Glynn

Psychology Faculty Articles and Research

Objective: The discovery of telomere length (TL) as a biomarker of cellular aging and correlate of age-related disease has generated a new field of research in the biology of healthy aging. Although the most common method of sample collection for TL is venous blood draw, less-invasive DNA collection methods are becoming more widely used. However, how TL relates across tissues derived from these sample collection methods is poorly understood. The current study is the first to characterize the associations in TL across three sample collection methods: venous whole blood, finger prick dried blood spot and saliva.

Methods: TL was measured ...


Heads And Tails, Julie Simons 2017 The California Maritime Academy

Heads And Tails, Julie Simons

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.


Microstructure Of Attachment Mechanisms Of Newly Hatched Larvae Of Four Cyprinid Species With Comments On Terminology, George E. Maurakis, Eugene G. Maurakis 2017 College of Science, Virginia Tech

Microstructure Of Attachment Mechanisms Of Newly Hatched Larvae Of Four Cyprinid Species With Comments On Terminology, George E. Maurakis, Eugene G. Maurakis

Virginia Journal of Science

An adhesive organ is a prominent, protruding mucus secreting gland that is used by newly hatched tadpoles and larvae of some fishes to attach to aquatic vegetation. The objective of this research is to test the hypothesis that newly hatched cyprinid larvae of Hybognathus hankinsoni, Notemigonus crysoleucas, Cyprinus carpio and Gila atraria contain cephalic adhesive organs. Newly hatched larvae of Semotilus atromaculatus, which do not attach to submerged aquatic vegetation, were used as the control. SEM examination of newly hatched larvae indicate there were no adhesive organs on the control species (S. atromaculatus) or test species (H. hankinsoni, N. crysoleucas ...


The Effect Of Pericyte Cell Therapy On Postischemic Neovascularization In Wild Type And Type 2 Diabetic Mice, Katherine E. Hayes 2017 University of Massachusetts Amherst

The Effect Of Pericyte Cell Therapy On Postischemic Neovascularization In Wild Type And Type 2 Diabetic Mice, Katherine E. Hayes

Doctoral Dissertations

Peripheral artery disease is an atherosclerotic disease that causes limb ischemia and has few effective treatments. Stem cell therapy is a promising treatment option, but concomitant diabetes may limit its effectiveness. The purpose of this study was to evaluate the therapeutic potential of skeletal muscle pericytes to augment postischemic neovascularization following the induction of limb ischemia in wild type and type 2 diabetic (T2DM) mice. The hypothesis was that diabetes impairs the ability of skeletal muscle pericytes to augment postischemic neovascularization and differentiate in vivo. Pericytes were isolated via fluorescence activated cell sorting for CD45-CD34-CD146+ ­­cells, and pericyte ...


Impact Of The C-Mybe308g Mutation On Mouse Myelopoiesis And Dendritic Cell Development, Peter Papathanasiou, Sawang Petvises, Ying-Ying Hey, Andrew C Perkins, Helen C O'Neill 2017 Australian National University

Impact Of The C-Mybe308g Mutation On Mouse Myelopoiesis And Dendritic Cell Development, Peter Papathanasiou, Sawang Petvises, Ying-Ying Hey, Andrew C Perkins, Helen C O'Neill

Helen O'Neill

Booreana mice carrying the c-Myb308G point mutation were analyzed to determine changes in early hematopoiesis in the bone marrow and among mature cells in the periphery. This point mutation led to increased numbers of early hematopoietic stem and progenitor cells (HSPCs), with a subsequent reduction in the development of B cells, erythroid cells, and neutrophils, and increased numbers of myeloid cells and granulocytes. Myelopoiesis was further investigated by way of particular subsets affected. A specific question addressed whether booreana mice contained increased numbers of dendritic-like cells (L-DC subset) recently identified in the spleen, since L-DCs arise in vitro by direct ...


Compartmentalized Camp Responses To Prostaglandin Ep2 Receptor Activation In Human Airway Smooth Muscle Cells, Shailesh R. Agarwal, Kathryn Miyashiro, Htun Latt, Rennolds S. Ostrom, Robert D. Harvey 2017 University of Nevada, Reno

Compartmentalized Camp Responses To Prostaglandin Ep2 Receptor Activation In Human Airway Smooth Muscle Cells, Shailesh R. Agarwal, Kathryn Miyashiro, Htun Latt, Rennolds S. Ostrom, Robert D. Harvey

Pharmacy Faculty Articles and Research

Background and Purpose

Previous studies indicate that prostaglandin EP2 receptors (EP2Rs) selectively couple to adenylyl cyclase type 2 (AC2) in non-lipid raft domains of airway smooth muscle (ASM) cells, where they regulate specific cAMP-dependent responses. The goal of the present study was to identify the cellular microdomains where EP2Rs stimulate cAMP production.

Experimental Approach

FRET-based cAMP biosensors were targeted to different subcellular locations of primary human ASM cells. The Epac2-camps biosensor, which expresses throughout the cell, was used to measure bulk cytoplasmic responses. Epac2-MyrPalm and Epac2-CAAX were used to measure responses associated with lipid raft and non-raft regions of the ...


Differentiation And Containment Of Derived Pancreatic Beta Cells, Caden Duffy, Alonzo Cook Ph.D. 2017 Brigham Young University - Provo

Differentiation And Containment Of Derived Pancreatic Beta Cells, Caden Duffy, Alonzo Cook Ph.D.

Biomedical Engineering Western Regional Conference

Currently, the only permanent cure for Type 1 Diabetes is a pancreatic or islet transplant. With the shortage of donors, we are progressing research towards alternative therapies by differentiating induced pluripotent stem cells into derived pancreatic β-cells that can be transplanted and used as treatment for Type 1 Diabetes. We are investigating methods to increase the yield of fully derived, insulin producing pancreatic β-cells and are additionally researching the use of hydrophilized expanded polytetrafluoroethylene for use in cell containment devices. These devices could offer a future alternative for islet transplantation in human patients.


The Localization And Function Of Novel Tetrahymena Thermophila Cytoskeletal Genes Bbc29 And Bbc39, Emily K. Moore, Nicole C. Zanolli 2017 Washington University in St. Louis

The Localization And Function Of Novel Tetrahymena Thermophila Cytoskeletal Genes Bbc29 And Bbc39, Emily K. Moore, Nicole C. Zanolli

Undergraduate Research Symposium Posters

Ciliary function is known to play an important role in many human conditions, including chronic sinus and pulmonary diseases and problems with infertility. Cilia are cytoskeletal structures that protrude from the cell body to facilitate movement. Ciliary structure is conserved throughout eukaryotes, from unicellular to multicellular organisms, including humans. A clear understanding the proteins that compose cilia and how they interact with one another will increase our knowledge about important cytoskeletal elements. Because cilia are difficult to study in multicellular organisms, the unicellular eukaryote Tetrahymena thermophila serves as a useful model for the study of cytoskeletal genes, due to their ...


Origins Of Thalamic And Cortical Projections To The Posterior Auditory Field In Congenitally Deaf Cats., Blake E Butler, Nicole Chabot, Andrej Kral, Stephen G Lomber 2017 Western University

Origins Of Thalamic And Cortical Projections To The Posterior Auditory Field In Congenitally Deaf Cats., Blake E Butler, Nicole Chabot, Andrej Kral, Stephen G Lomber

Psychology Publications

Crossmodal plasticity takes place following sensory loss, such that areas that normally process the missing modality are reorganized to provide compensatory function in the remaining sensory systems. For example, congenitally deaf cats outperform normal hearing animals on localization of visual stimuli presented in the periphery, and this advantage has been shown to be mediated by the posterior auditory field (PAF). In order to determine the nature of the anatomical differences that underlie this phenomenon, we injected a retrograde tracer into PAF of congenitally deaf animals and quantified the thalamic and cortical projections to this field. The pattern of projections from ...


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