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Beta cell mass

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https://www.readbyqxmd.com/read/29781950/report-of-the-key-opinion-leaders-meeting-on-stem-cell-derived-beta-cells
#1
Jon Odorico, James Markmann, Douglas Melton, Julia Greenstein, Albert Hwa, Cristina Nostro, Alireza Rezania, Jose Oberholzer, Daniel Pipeleers, Luhan Yang, Chad Cowan, Danwei Huangfu, Dieter Egli, Uri Ben-David, Ludovic Vallier, Shane T Grey, Qizhi Tang, Bart Roep, Camilo Ricordi, Ali Naji, Giuseppe Orlando, Daniel G Anderson, Mark Poznansky, Barbara Ludwig, Alice Tomei, Dale L Greiner, Melanie Graham, Melissa Carpenter, Giovanni Migliaccio, Kevin D'Amour, Bernhard Hering, Lorenzo Piemonti, Thierry Berney, Mike Rickels, Thomas Kay, Ann Adams
Beta cell replacement has the potential to restore euglycemia in patients with insulin dependent diabetes. While great progress has been made in establishing allogeneic islet transplantation from deceased donors as the standard of care for those with the most labile diabetes, it is also clear that the deceased donor organ supply cannot possibly treat all those who could benefit from restoration of a normal beta cell mass, especially if immunosuppression were not required. Against this background, the International Pancreas and Islet Transplant Association (IPITA) in collaboration with the Harvard Stem Cell Institute (HSCI), the Juvenile Diabetes Research Foundation (JDRF), and the Helmsley Foundation held a 2-day Key Opinion Leaders Meeting in Boston in 2016 to bring together experts in generating and transplanting beta cells derived from stem cells...
April 30, 2018: Transplantation
https://www.readbyqxmd.com/read/29775289/mass-spectral-detection-of-diethoxyphospho-tyrosine-adducts-on-proteins-from-hek293-cells-using-monoclonal-antibody-depy-for-enrichment
#2
Seda Onder, Lawrence M Schopfer, Ozden Tacal, Thomas A Blake, Rudolph C Johnson, Oksana Lockridge
Chronic illness from exposure to organophosphorus toxicants is hypothesized to involve modification of unknown proteins. Tyrosine in proteins that have no active site serine readily reacts with organophosphorus toxicants. We developed a monoclonal antibody, depY, that specifically recognizes diethoxyphospho-tyrosine in proteins and peptides, independent of the surrounding amino acid sequence. Our goal in the current study was to identify diethoxyphosphorylated proteins in human HEK293 cell lysate treated with chlorpyrifos oxon...
May 18, 2018: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29774025/co-stimulation-impaired-bone-marrow-derived-dendritic-cells-prevent-dextran-sodium-sulfate-induced-colitis-in-mice
#3
Carl Engman, Yesica Garciafigueroa, Brett Eugene Phillips, Massimo Trucco, Nick Giannoukakis
Dendritic cells (DC) are important in the onset and severity of inflammatory bowel disease (IBD). Tolerogenic DC induce T-cells to become therapeutic Foxp3+ regulatory T-cells (Tregs). We therefore asked if experimental IBD could be prevented by administration of bone marrow-derived DC generated under conventional GM-CSF/IL-4 conditions but in the presence of a mixture of antisense DNA oligonucleotides targeting the primary transcripts of CD40, CD80, and CD86. These cell products (which we call AS-ODN BM-DC) have demonstrated tolerogenic activity in preventing type 1 diabetes and preserving beta cell mass in new-onset type 1 diabetes in the NOD mouse strain, in earlier studies...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29770603/t-cell-tracking-using-cerenkov-and-radioluminescence-imaging
#4
F Boschi, F De Sanctis, S Ugel, A E Spinelli
Cancer immunotherapy is a promising strategy based on the ability of the immune system to kill selected cells. In the development of an effective T-cell therapy the non-invasive cell tracking methods play a crucial role. Here we investigate the potentialities of T-cell marked with radionuclides in order to detect their localization with imaging techniques in small animal rodents. A protocol to label T-cells with 32 P-ATP was tested and evaluated. The homing of 32 P-ATP labeled T lymphocytes was investigated by Cerenkov luminescence imaging and radioluminescence imaging The first approach relies on the acquisition of Cerenkov photons produced by the beta particles emitted by the 32 P internalized by lymphocytes; the second one on the detection of photons coming from the conversion of radioactive energy in light done by scintillator crystals layered on the animals...
May 16, 2018: Journal of Biophotonics
https://www.readbyqxmd.com/read/29770421/quantitative-proteomics-and-systems-analysis-of-cultured-h9c2-cardiomyoblasts-during-differentiation-over-time-supports-a-function-follows-form-model-of-differentiation
#5
Cynthia Kankeu, Kylie Clarke, Delphi Van Haver, Kris Gevaert, Francis Impens, Anna Dittrich, H Llewelyn Roderick, Egle Passante, Heinrich J Huber
The rat cardiomyoblast cell line H9C2 has emerged as a valuable tool for studying cardiac development, mechanisms of disease and toxicology. We present here a rigorous proteomic analysis that monitored the changes in protein expression during differentiation of H9C2 cells into cardiomyocyte-like cells over time. Quantitative mass spectrometry followed by gene ontology (GO) enrichment analysis revealed that early changes in H9C2 differentiation are related to protein pathways of cardiac muscle morphogenesis and sphingolipid synthesis...
May 17, 2018: Molecular omics
https://www.readbyqxmd.com/read/29768729/adaptive-changes-in-pancreas-post-roux-en-y-gastric-bypass-induced-weight-loss
#6
A Lautenbach, M Wernecke, N Riedel, J Veigel, J Yamamura, S Keller, R Jung, P Busch, O Mann, F K Knop, J J Holst, J J Meier, J Aberle
AIMS: Obesity has been shown to trigger adaptive increases in pancreas parenchymal and fat volume. Consecutively, pancreatic steatosis may lead to beta-cell dysfunction. However, it is not known, whether the pancreatic tissue components decrease with weight loss and pancreatic steatosis is reversible following RYGB. Therefore, the objective of the study was to investigate the effects of RYGB-induced weight loss on pancreatic volume and glucose homeostasis. MATERIALS AND METHODS: 11 patients were recruited in the Obesity Centre of the University Medical Centre Hamburg-Eppendorf...
May 16, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29768513/increased-mitochondrial-fission-is-critical-for-hypoxia-induced-pancreatic-beta-cell-death
#7
Da Zhang, Yanfang Liu, Yao Tang, Xiaofeng Wang, Zhichao Li, Rui Li, Zhenyu Ti, Weidong Gao, Jigang Bai, Yi Lv
Hypoxia-mediated pancreatic beta cell death is one of the main causes of pancreatic beta celldeath, which leads to the loss of functional pancreatic beta cell mass and type 1 diabetes andtype 2 diabetes.However, the molecular mechanisms that control life and death of pancreatic beta cells remain poorly understood. Here we showed that mitochondrial fission was strongly induced in pancreatic beta cellsmainly due to an elevation of DRP1S616 phosphorylation through HIF-1αactivation and subsequent DRP1 mitochondrial translocation...
2018: PloS One
https://www.readbyqxmd.com/read/29768427/differential-effects-of-tnf-%C3%AE-and-il-1%C3%AE-on-the-control-of-metal-metabolism-and-cadmium-induced-cell-death-in-chronic-inflammation
#8
Paola Bonaventura, Aline Lamboux, Francis Albarède, Pierre Miossec
OBJECTIVE: Interleukin-1-beta (IL-1β) and tumour necrosis factor-alpha (TNF-α) are both monocyte-derived cytokines. Both cytokines have been previously described to exert a role in rheumatoid arthritis (RA) pathogenesis synergizing with other pro-inflammatory mediators, such as interleukin-17 (IL-17) on target cells, for the perpetuation of the inflammatory response (e.g. IL-6 production). In the context of experimental RA, Cd addition has an anti-proliferative and anti-inflammatory effect when associated to IL-17/TNF-α stimulation, due to its accumulation in synoviocytes...
2018: PloS One
https://www.readbyqxmd.com/read/29767307/virus-vector-mediated-genetic-modification-of-brain-tumor-stromal-cells-after-intravenous-delivery
#9
Adrienn Volak, Stanley G LeRoy, Jeya Shree Natasan, David J Park, Pike See Cheah, Andreas Maus, Zachary Fitzpatrick, Eloise Hudry, Kelsey Pinkham, Sheetal Gandhi, Bradley T Hyman, Dakai Mu, Dwijit GuhaSarkar, Anat O Stemmer-Rachamimov, Miguel Sena-Esteves, Christian E Badr, Casey A Maguire
The malignant primary brain tumor, glioblastoma (GBM) is generally incurable. New approaches are desperately needed. Adeno-associated virus (AAV) vector-mediated delivery of anti-tumor transgenes is a promising strategy, however direct injection leads to focal transgene spread in tumor and rapid tumor division dilutes out the extra-chromosomal AAV genome, limiting duration of transgene expression. Intravenous (IV) injection gives widespread distribution of AAV in normal brain, however poor transgene expression in tumor, and high expression in non-target cells which may lead to ineffective therapy and high toxicity, respectively...
May 16, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29763908/connexin-43-modulates-osteogenic-differentiation-of-bone-marrow-stromal-cells-through-gsk-3beta-beta-catenin-signaling-pathways
#10
Fei-Xiang Lin, Gui-Zhou Zheng, Bo Chang, Rong-Chun Chen, Qi-Hao Zhang, Peng Xie, Da Xie, Guo-Yong Yu, Qin-Xiao Hu, De-Zhong Liu, Shi-Xin Du, Xue-Dong Li
BACKGROUND/AIMS: Bone marrow stromal cells (BMSCs) are multipotent precursors that give rise to osteoblasts, and contribute directly to bone formation. Connexin 43 (Cx43) is the most ubiquitous gap junction protein expressed in bone cell types, and plays crucial roles in regulating intercellular signal transmission for bone development, differentiation and pathology. However, the precise role and mechanism of Cx43 in BMSCs are less known. Here, we investigate the function of Cx43 in osteogenic differentiation of BMSCs in vitro...
May 10, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29760957/simulated-microgravity-induces-a-cellular-regression-of-the-mature-phenotype-in-human-primary-osteoblasts
#11
Magda Gioia, Anna Michaletti, Manuel Scimeca, Mario Marini, Umberto Tarantino, Lello Zolla, Massimo Coletta
Decreased mechanical loading on bones, such as prolonged bed rest and microgravity during space flights, leads to the development of an osteoporotic-like phenotype. Although osteoblast hypo-functionality is reported to be involved in the progression of bone pathological conditions, the cellular mechanisms of this process remain largely unknown. The combined application of mass spectrometry "-omics" and histochemical and ultrastructural approaches have been employed to investigate the effects of the gravitational unloading on human bone-cell biology...
2018: Cell Death Discovery
https://www.readbyqxmd.com/read/29755708/growth-and-endocrine-function-in-tunisian-thalassemia-major-patients
#12
Naouel Guirat Dhouib, Monia Ben Khaled, Monia Ouederni, Habib Besbes, Ridha Kouki, Fethi Mellouli, Mohamed Bejaoui
β-thalassemia major (β-TM) is among the most common hereditary disorders imposing high expenses on health-care system worldwide. The patient's survival is dependent on lifetime blood transfusion which leads to iron overload and its toxicity in various organs including endocrine glands. This article provides an overview of endocrine disorders in beta-TM patients. This single center investigation enrolled 28 β-TM patients (16 males, 12 females) regularly transfused with packed red cell since early years of life...
2018: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/29755469/urinary-peptides-as-a-novel-source-of-t-cell-allergen-epitopes
#13
Ricardo da Silva Antunes, John Pham, Curtis McMurtrey, William H Hildebrand, Elizabeth Phillips, Simon Mallal, John Sidney, Paula Busse, Bjoern Peters, Véronique Schulten, Alessandro Sette
Mouse allergy in both laboratory workers and in inner-city children is associated with allergic rhinitis and asthma, posing a serious public health concern. Urine is a major source of mouse allergens, as mice spray urine onto their surroundings, where the proteins dry up and become airborne on dust particles. Here, we tested whether oligopeptides that are abundant in mouse urine may contribute to mouse allergic T cell response. Over 1,300 distinct oligopeptides were detected by mass spectrometry analysis of the low molecular weight filtrate fraction of mouse urine (LoMo)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29747653/inactivation-of-the-tight-junction-gene-cldn11-by-aberrant-hypermethylation-modulates-tubulins-polymerization-and-promotes-cell-migration-in-nasopharyngeal-carcinoma
#14
Hsin-Pai Li, Chen-Ching Peng, Chih-Ching Wu, Chien-Hsun Chen, Meng-Jhe Shih, Mei-Yuan Huang, Yi-Ru Lai, Yung-Li Chen, Ting-Wen Chen, Petrus Tang, Yu-Sun Chang, Kai-Ping Chang, Cheng-Lung Hsu
BACKGROUND: Aberrant hypermethylation of cellular genes is a common phenomenon to inactivate genes and promote tumorigenesis in nasopharyngeal carcinoma (NPC). METHODS: Methyl binding domain (MBD)-ChIP sequencing of NPC cells, microarray data of NPC biopsies and gene ontology analysis were conducted to identify a potential tumor suppressor gene CLDN11 that was both hypermethylated and downregulated in NPC. Bisulfite sequencing, qRT-PCR, immunohistochemistry staining of the NPC clinical samples and addition of methylation inhibitor, 5'azacytidine, in NPC cells were performed to verify the correlation between DNA hypermethylation and expression of CLDN11...
May 10, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29730309/a-single-point-mutation-on-the-cucumber-mosaic-virus-surface-induces-an-unexpected-and-strong-interaction-with-the-f1-complex-of-the-atp-synthase-in-nicotiana-clevelandii-plants
#15
Ákos Gellért, Tímea Pósa, Attila Fábián, László Szabó, Károly Bóka, Barbara Forró, Katalin Salánki, László Drahos, Eszter Tóth, Angéla Juhász, Ervin Balázs
A previous study showed that a single amino acid difference in the cucumber mosaic virus (CMV) capsid protein (CP) elicits unusual symptoms. The wild-type strain (CMV-R) induces green mosaic symptoms and malformation while the mutant strain (CMV-R3E79R) causes chlorotic lesions on inoculated leaves and strong stunting with necrosis on systemic leaves. Virion preparations of CMV-R and CMV-R3E79R were partially purified from Nicotiana clevelandii A. Gray and analysed by two-dimensional gel electrophoresis. Their separated protein patterns showed remarkable differences at the 50-75 kDa range, both in numbers and intensity of spots, with more protein spots for the mutant CMV...
May 3, 2018: Virus Research
https://www.readbyqxmd.com/read/29729484/high-efficiency-dual-cycle-conversion-system-using-kr-85
#16
Mark A Prelas, Modeste Tchakoua Tchouaso
This paper discusses the use of one of the safest isotopes known isotopes, Kr-85, as a candidate fuel source for deep space missions. This isotope comes from 0.286% of fission events. There is a vast quantity of Kr-85 stored in spent fuel and it is continually being produced by nuclear reactors. In using Kr-85 with a novel Dual Cycle Conversion System (DCCS) it is feasible to boost the system efficiency from 26% to 45% over a single cycle device while only increasing the system mass by less than 1%. The Kr-85 isotope is the ideal fuel for a Photon Intermediate Direct Energy Conversion (PIDEC) system...
April 26, 2018: Applied Radiation and Isotopes
https://www.readbyqxmd.com/read/29725943/in-vitro-monitoring-of-the-mitochondrial-beta-oxidation-flux-of-palmitic-acid-and-investigation-of-its-pharmacological-alteration-by-therapeutics
#17
Renata Murgasova, Ester Tor Carreras, Julien Bourgailh
BACKGROUND AND OBJECTIVE: The present study was designed to validate the functional assay that enables rapid screening of therapeutic candidates for their effect on mitochondrial fatty acid oxidation. METHODS: The two whole-cell systems (tissue homogenates and hepatocytes) have been evaluated to monitor the total beta-oxidation flux of physiologically important 3 H-palmitic acid by measurement of tritiated water enrichment in incubations using UPLC coupled on-line to radioactivity monitoring and mass spectrometry...
May 3, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29725251/glucagon-like-peptide-1-receptor-agonist-and-glucagon-increase-glucose-stimulated-insulin-secretion-in-beta-cells-via-distinct-adenylyl-cyclases
#18
Young-Sun Lee, Hee-Sook Jun
Diabetes mellitus is a chronic disease in which the pancreas no longer produces enough insulin. Pancreatic alpha cell mass increases in response to insufficient insulin secretion. However, the reason for this increase is not clear. It is possible that the increased alpha-cells may stimulate compensatory insulin release in response to the insufficient insulin such as insulin resistance. In this study, we investigated whether glucagon and glucagon-like peptide-1 (GLP-1), hormones produced by alpha cells, contribute to insulin secretion in INS-1 cells, a beta cell line...
2018: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29724825/deletion-of-ferroportin-in-murine-myeloid-cells-increases-iron-accumulation-and-stimulates-osteoclastogenesis-in-vitro-and-in-vivo
#19
Lei Wang, Bin Fang, Toshifumi Fujiwara, Kimberly Krager, Akshita Gorantla, Chaoyuan Li, Jian Q Feng, Michael L Jennings, Jian Zhou, Nukhet Aykin-Burns, Haibo Zhao
Osteoporosis, osteopenia, and pathological bone fractures are frequent complications of iron-overload conditions such as hereditary hemochromatosis, thalassemia, and sickle cell disease. Moreover, animal models of iron overload have revealed increased bone resorption and decreased bone formation. Although systemic iron overload affects multiple organs and tissues, leading to significant changes on bone modeling and remodeling, the cell autonomous effects of excessive iron on bone cells remain unknown. Here, to elucidate the role of cellular iron homeostasis in osteoclasts, we generated two mouse strains in which solute carrier family 40 member 1 (Slc40a1), a gene encoding ferroportin (FPN), the sole iron exporter in mammalian cells, were specifically deleted in myeloid osteoclast precursors or mature cells...
May 3, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29721633/decreased-vmat2-in-the-pancreas-of-humans-with-type-2-diabetes-mellitus-measured-in-vivo-by-pet-imaging
#20
Gary W Cline, Mika Naganawa, Laigao Chen, Kristin Chidsey, Santos Carvajal-Gonzalez, Sylvester Pawlak, Michelle Rossulek, Yanwei Zhang, Jason Bini, Timothy J McCarthy, Richard E Carson, Roberto A Calle
AIMS/HYPOTHESIS: The progressive loss of beta cell function is part of the natural history of type 2 diabetes. Autopsy studies suggest that this is, in part, due to loss of beta cell mass (BCM), but this has not been confirmed in vivo. Non-invasive methods to quantify BCM may contribute to a better understanding of type 2 diabetes pathophysiology and the development of therapeutic strategies. In humans, the localisation of vesicular monoamine transporter type 2 (VMAT2) in beta cells and pancreatic polypeptide cells, with minimal expression in other exocrine or endocrine pancreatic cells, has led to its development as a measure of BCM...
May 2, 2018: Diabetologia
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