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Calreticulin

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https://www.readbyqxmd.com/read/29346364/mutations-in-caenorhabditis-elegans-neuroligin-like-glit-1-the-apoptosis-pathway-and-the-calcium-chaperone-crt-1-increase-dopaminergic-neurodegeneration-after-6-ohda-treatment
#1
Sarah-Lena Offenburger, Elisabeth Jongsma, Anton Gartner
The loss of dopaminergic neurons is a hallmark of Parkinson's disease, the aetiology of which is associated with increased levels of oxidative stress. We used C. elegans to screen for genes that protect dopaminergic neurons against oxidative stress and isolated glit-1 (gliotactin (Drosophila neuroligin-like) homologue). Loss of the C. elegans neuroligin-like glit-1 causes increased dopaminergic neurodegeneration after treatment with 6-hydroxydopamine (6-OHDA), an oxidative-stress inducing drug that is specifically taken up into dopaminergic neurons...
January 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29337311/dinaciclib-induces-immunogenic-cell-death-and-enhances-anti-pd-1-mediated-tumor-suppression
#2
Dewan Md Sakib Hossain, Sarah Javaid, Mingmei Cai, Chunsheng Zhang, Anandi Sawant, Marlene Hinton, Manjiri Sathe, Jeff Grein, Wendy Blumenschein, Elaine M Pinheiro, Alissa Chackerian
Blockade of the checkpoint inhibitor programmed death 1 (PD1) has demonstrated remarkable success in the clinic for the treatment of cancer; however, a majority of tumors are resistant to anti-PD1 monotherapy. Numerous ongoing clinical combination therapy studies will likely reveal additional therapeutics that complement anti-PD1 blockade. Recent studies found that immunogenic cell death (ICD) improves T cell responses against different tumors, thus indicating that ICD may further augment antitumor immunity elicited by anti-PD1...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29320819/molecular-and-biochemical-characterization-of-opisthorchis-viverrini-calreticulin
#3
Wanlapa Chaibangyang, Amornrat Geadkaew-Krenc, Suksiri Vichasri-Grams, Smarn Tesana, Rudi Grams
Calreticulin (CALR), a multifunctional protein thoroughly researched in mammals, comprises N-, P-, and C-domain and has roles in calcium homeostasis, chaperoning, clearance of apoptotic cells, cell adhesion, and also angiogenesis. In this study, the spatial and temporal expression patterns of the Opisthorchis viverrini CALR gene were analyzed, and calcium-binding and chaperoning properties of recombinant O. viverrini CALR (OvCALR) investigated. OvCALR mRNA was detected from the newly excysted juvenile to the mature parasite by RT-PCR while specific antibodies showed a wide distribution of the protein...
December 2017: Korean Journal of Parasitology
https://www.readbyqxmd.com/read/29318471/aav-mediated-gene-delivery-of-the-calreticulin-anti-angiogenic-domain-inhibits-ocular-neovascularization
#4
Leilei Tu, Jiang-Hui Wang, Veluchamy A Barathi, Selwyn M Prea, Zheng He, Jia Hui Lee, James Bender, Anna E King, Grant J Logan, Ian E Alexander, Youn-Shen Bee, Ming-Hong Tai, Gregory J Dusting, Bang V Bui, Jingxiang Zhong, Guei-Sheung Liu
Ocular neovascularization is a common pathological feature in diabetic retinopathy and neovascular age-related macular degeneration that can lead to severe vision loss. We evaluated the therapeutic efficacy of a novel endogenous inhibitor of angiogenesis, the calreticulin anti-angiogenic domain (CAD180), and its functional 112-residue fragment, CAD-like peptide 112 (CAD112), delivered using a self-complementary adeno-associated virus serotype 2 (scAAV2) in rodent models of oxygen-induced retinopathy and laser-induced choroidal neovascularization...
January 9, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29296828/gene-editing-rescue-of-a-novel-mpl-mutant-associated-with-congenital-amegakaryocytic-thrombocytopenia
#5
Cédric Cleyrat, Romain Girard, Eun H Choi, Éric Jeziorski, Thierry Lavabre-Bertrand, Sylvie Hermouet, Serge Carillo, Bridget S Wilson
Thrombopoietin (Tpo) and its receptor (Mpl) are the principal regulators of early and late thrombopoiesis and hematopoietic stem cell maintenance. Mutations in MPL can drastically impair its function and be a contributing factor in multiple hematologic malignancies, including congenital amegakaryocytic thrombocytopenia (CAMT). CAMT is characterized by severe thrombocytopenia at birth, which progresses to bone marrow failure and pancytopenia. Here we report unique familial cases of CAMT that presented with a previously unreported MPL mutation: T814C (W272R) in the background of the activating MPL G117T (K39N or Baltimore) mutation...
September 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29290768/modulated-electro-hyperthermia-induced-loco-regional-and-systemic-tumor-destruction-in-colorectal-cancer-allografts
#6
Tamas Vancsik, Csaba Kovago, Eva Kiss, Edina Papp, Gertrud Forika, Zoltan Benyo, Nora Meggyeshazi, Tibor Krenacs
Background: Modulated electro-hyperthermia (mEHT), a non-invasive intervention using 13.56 MHz radiofrequency, can selectively target cancers due to their elevated glycolysis (Warburg-effect), extracellular ion concentration and conductivity compared to normal tissues. We showed earlier that mEHT alone can provoke apoptosis and damage associated molecular pattern (DAMP) signals in human HT29 colorectal cancer xenografts of immunocompromised mice. Materials: Here we tested the mEHT induced stress and immune responses in C26 colorectal cancer allografts of immunocompetent (BALB/c) mice between 12-72 h post-treatment...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29288169/defining-the-requirements-for-the-pathogenic-interaction-between-mutant-calreticulin-and-mpl-in-mpn
#7
Shannon Elf, Nouran S Abdelfattah, April J Baral, Danielle Beeson, Jeanne F Rivera, Amy Ko, Natalie Florescu, Gabriel Birrane, Edwin Chen, Ann Mullally
Mutations in calreticulin (CALR) are phenotypic drivers in the pathogenesis of myeloproliferative neoplasms (MPN). Mechanistic studies have demonstrated that mutant CALR binds to the thrombopoietin receptor MPL, and that the positive electrostatic charge of the mutant CALR C-terminus is required for mutant CALR-mediated activation of JAK-STAT signaling. Here we demonstrate that although binding between mutant CALR and MPL is required for mutant CALR to transform hematopoietic cells, binding alone is insufficient for cytokine independent growth...
December 29, 2017: Blood
https://www.readbyqxmd.com/read/29286412/basic-research-in-plasma-medicine-a-throughput-approach-from-liquids-to-cells
#8
Sander Bekeschus, Anke Schmidt, Felix Niessner, Torsten Gerling, Klaus-Dieter Weltmann, Kristian Wende
In plasma medicine, ionized gases with temperatures close to that of vertebrate systems are applied to cells and tissues. Cold plasmas generate reactive species known to redox regulate biological processes in health and disease. Pre-clinical and clinical evidence points to beneficial effects of plasma treatment in the healing of chronic ulcer of the skin. Other emerging topics, such as plasma cancer treatment, are receiving increasing attention. Plasma medical research requires interdisciplinary expertise in physics, chemistry, and biomedicine...
November 17, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29284148/itraq-based-comparative-proteome-analysis-for-molecular-mechanism-of-defense-against-acute-ammonia-toxicity-in-pacific-white-shrimp-litopenaeus-vannamei
#9
Xia Lu, Sheng Luan, Ping Dai, Xianhong Meng, Baoxiang Cao, Kun Luo, Jie Kong
In the practical farming of Litopenaeus vannamei, the intensive culture system and environmental pollution usually results in a high concentration of ammonia, which brings large detrimental effects to shrimp, such as increasing the susceptibility to pathogens and even causing high mortality. We have revealed that the survival time under acute ammonia stress varied substantially among different families and obtained ammonia-tolerant (LV_T) and ammonia-sensitive (LV_S) families. In order to understand the molecular mechanism of defense against ammonia toxicity in shrimp, we performed iTRAQ LC-MS/MS proteomic analysis between LV_T and LV_S groups of L...
December 25, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29282219/mutant-calreticulin-knock-in-mice-develop-thrombocytosis-and-myelofibrosis-without-a-stem-cell-self-renewal-advantage
#10
Juan Li, Daniel Prins, Hyun Jung Park, Jacob Grinfeld, Carlos Gonzalez-Arias, Stephen Loughran, Oliver M Dovey, Thorsten Klampfl, Cavan Bennett, Tina L Hamilton, Dean C Pask, Rachel Sneade, Matthew Williams, Juliet Aungier, Cedric Ghevaert, George S Vassiliou, David G Kent, Anthony R Green
Somatic mutations in the endoplasmic reticulum chaperone calreticulin (CALR) are detected in approximately 40% of patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF). Multiple different mutations have been reported, but all result in a +1bp frame shift and generate a novel protein C-terminus. In this study, we generated a conditional mouse knock-in model of the most common CALR mutation, a 52bp deletion. The mutant novel human C-terminal sequence is integrated into the otherwise intact mouse CALR gene and results in mutant CALR expression under the control of the endogenous mouse locus...
December 27, 2017: Blood
https://www.readbyqxmd.com/read/29277359/soho-state-of-the-art-update-and-next-questions-mpn
#11
REVIEW
Prithviraj Bose, Jason Gotlib, Claire N Harrison, Srdan Verstovsek
The discovery of the activating Janus kinase (JAK)2V617F mutation in 2005 in most patients with the classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) spurred intense interest in research into these disorders, culminating in the identification of activating mutations in MPL in 2006 and indels in the gene encoding calreticulin (CALR) in 2013, thus providing additional mechanistic explanations for the universal activation of JAK-signal transducer and activator of transcription (JAK-STAT) observed in these conditions, and the success of the JAK1/2 inhibitor ruxolitinib, which first received regulatory approval in 2011...
January 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29258411/calreticulin-affects-hematopoietic-stem-progenitor-cell-fate-by-impacting-erythroid-and-megakaryocytic-differentiation
#12
Simona Salati, Zelia Prudente, Elena Genovese, Valentina Pennucci, Sebastiano Rontauroli, Niccolo' Bartalucci, Carmela Mannarelli, Samantha Ruberti, Roberta Zini, Chiara Rossi, Elisa Bianchi, Paola Guglielmelli, Enrico Tagliafico, Alessandro M Vannucchi, Rossella Manfredini
Calreticulin (CALR) is a chaperone protein that localizes primarily to the endoplasmic reticulum (ER) lumen where it is responsible for the control of proper folding of neo-synthesized glycoproteins and for the retention of calcium. Recently, mutations affecting exon 9 of the CALR gene have been described in approximately 40% of patients with myeloproliferative neoplasms (MPNs). Although the role of mutated CALR in the development of MPNs has begun to be clarified, there are still no data available on the function of wild-type (WT) CALR during physiological hematopoiesis...
December 19, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/29246810/a-new-l-type-lectin-lvltlc1-from-the-shrimp-litopenaeus-vannamei-facilitates-the-clearance-of-vibrio-harveyi
#13
Yushun Tian, Ting Chen, Wen Huang, Peng Luo, Da Huo, Long Yun, Chaoqun Hu, Yiming Cai
According to structures and functions of lectins found in shrimp, they are classified into seven types, namely, L-type, C-type, P-type, M-type, galectins, fibrinogen-like domain lectins, and calnexin/calreticulin. Until now, the researches of shrimp lectins are mainly focused on C-type lectins. In this study, we identified a new L-type lectin, designated as LvLTLC1, from the shrimp Litopenaeus vannamei. The cDNA of LvLTLC1 is 1184 bp with an open reading frame of 990 bp encoding a protein of 329 amino acids...
December 12, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29228584/combination-of-calr-and-pdia3-is-a-potential-prognostic-biomarker-for-non-small-cell-lung-cancer
#14
Ke Wang, Hao Li, Ruo Chen, Yang Zhang, Xiu-Xuan Sun, Wan Huang, Huijie Bian, Zhi-Nan Chen
Proteomic-based approaches for biomarker discovery are promising strategies used in cancer research. In this study, we performed quantitative proteomic analysis on 16 paired samples of non-small cell lung cancer (NSCLC) and adjacent non-tumor lung tissues using label-free quantitative proteomics and liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS) to identify differentially expressed proteins. A total of 91 proteins were differentially expressed in NSCLC compared with adjacent non-tumor lung tissues among 4047 identified proteins (fold change > 1...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29222295/myeloproliferative-neoplasms-from-origins-to-outcomes
#15
REVIEW
Jyoti Nangalia, Anthony R Green
Substantial progress has been made in our understanding of the pathogenetic basis of myeloproliferative neoplasms. The discovery of mutations in JAK2 over a decade ago heralded a new age for patient care as a consequence of improved diagnosis and the development of therapeutic JAK inhibitors. The more recent identification of mutations in calreticulin brought with it a sense of completeness, with most patients with myeloproliferative neoplasm now having a biological basis for their excessive myeloproliferation...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29221829/constitutive-expression-of-the-active-fragment-of-human-vasostatin-vs30-in-pichia-pastoris-smd1168
#16
Sergio Calderon-Salais, Prisiliana Velazquez-Bernardino, Victor E Balderas-Hernandez, Ana P Barba-de la Rosa, Antonio De Leon-Rodriguez
Vasostatin 30 (Vs30) is an active fragment derived from the N-terminal region (135-164aa) of human calreticulin (hCALR) and has the ability to inhibit angiogenesis. In this work, the expression of Vs30 was performed using a protease-deficient strain of the methylotrophic yeast Pichia pastoris. The vs30 gene was optimized for P. pastoris preferential codon usage and inserted into constitutive expression vector pGAPZαA. In addition, a multi-copy strain was obtained using an in vitro multimerization approach...
December 5, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/29218307/calreticulin-challenges-posed-by-the-intrinsically-disordered-nature-of-calreticulin-to-the-study-of-its-function
#17
Lilian Varricchio, Mario Falchi, Massimiliano Dall'Ora, Caterina De Benedittis, Alessandra Ruggeri, Vladimir N Uversky, Anna Rita Migliaccio
Calreticulin is a Ca2+-binding chaperone protein, which resides mainly in the endoplasmic reticulum but also found in other cellular compartments including the plasma membrane. In addition to Ca2+, calreticulin binds and regulates almost all proteins and most of the mRNAs deciding their intracellular fate. The potential functions of calreticulin are so numerous that identification of all of them is becoming a nightmare. Still the recent discovery that patients affected by the Philadelphia-negative myeloproliferative disorders essential thrombocytemia or primary myelofibrosis not harboring JAK2 mutations carry instead calreticulin mutations disrupting its C-terminal domain has highlighted the clinical need to gain a deeper understanding of the biological activity of this protein...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29214350/co-culture-of-human-fibroblasts-and-borrelia-burgdorferi-enhances-collagen-and-growth-factor-mrna
#18
Elisabeth Aberer, Milana Surtov-Pudar, Daniel Wilfinger, Alexander Deutsch, Gerd Leitinger, Helmut Schaider
Skin fibrosis has been reported in Borrelia burgdorferi infection in Europe, but has been questioned by several authors. The objective of the present study was to examine the interaction of skin fibroblasts with B. burgdorferi sensu stricto B31 (BB) and B. afzelii (BA) in vitro by electron microscopy. We also determined the expression of collagen type I, TGF-β, FGF-1, calreticulin (CALR), decorin (DCN), and PDGF-α at the mRNA level in Borrelia/fibroblast co-cultures. Intact Borrelia attach to and transmigrate fibroblasts, and undergo cystic transformation outside the fibroblasts...
December 6, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/29212804/myeloproliferative-neoplasms-from-origins-to-outcomes
#19
REVIEW
Jyoti Nangalia, Anthony R Green
Substantial progress has been made in our understanding of the pathogenetic basis of myeloproliferative neoplasms. The discovery of mutations in JAK2 over a decade ago heralded a new age for patient care as a consequence of improved diagnosis and the development of therapeutic JAK inhibitors. The more recent identification of mutations in calreticulin brought with it a sense of completeness, with most patients with myeloproliferative neoplasm now having a biological basis for their excessive myeloproliferation...
December 7, 2017: Blood
https://www.readbyqxmd.com/read/29203952/effect-of-intra-tumoral-magnetic-nanoparticle-hyperthermia-and-viral-nanoparticle-immunogenicity-on-primary-and-metastatic-cancer
#20
P Jack Hoopes, Courtney M Mazur, Bjorn Osterberg, Ailin Song, David J Gladstone, Nicole F Steinmetz, Frank A Veliz, Alicea A Bursey, Robert J Wagner, Steven N Fiering
Although there is long association of medical hyperthermia and immune stimulation, the relative lack of a quantifiable and reproducible effect has limited the utility and advancement of this relationship in preclinical/clinical cancer and non-cancer settings. Recent cancer-based immune findings (immune checkpoint modulators etc.) including improved mechanistic understanding and biological tools now make it possible to modify and exploit the immune system to benefit conventional cancer treatments such as radiation and hyperthermia...
January 2017: Proceedings of SPIE
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