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https://www.readbyqxmd.com/read/28320958/p97-vcp-promotes-degradation-of-crbn-substrate-glutamine-synthetase-and-neosubstrates
#1
Thang Van Nguyen, Jing Li, Chin-Chun Jean Lu, Jennifer L Mamrosh, Gang Lu, Brian E Cathers, Raymond J Deshaies
Glutamine synthetase (GS) plays an essential role in metabolism by catalyzing the synthesis of glutamine from glutamate and ammonia. Our recent study showed that CRBN, a direct protein target for the teratogenic and antitumor activities of immunomodulatory drugs such as thalidomide, lenalidomide, and pomalidomide, recognizes an acetyl degron of GS, resulting in ubiquitylation and degradation of GS in response to glutamine. Here, we report that valosin-containing protein (VCP)/p97 promotes the degradation of ubiquitylated GS, resulting in its accumulation in cells with compromised p97 function...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28318487/a-high-resolution-map-of-transcriptional-repression
#2
Ziwei Liang, Karen Brown, Thomas Carroll, Benjamin Taylor, Isabel Ferreirós Vidal, Brian Hendrich, David Rueda, Amanda G Fisher, Matthias Merkenschlager
Turning genes on and off is essential for development and homeostasis, yet little is known about the sequence and causal role of chromatin state changes during the repression of active genes. This is surprising, as defective gene silencing underlies developmental abnormalities and disease. Here we delineate the sequence and functional contribution of transcriptional repression mechanisms at high temporal resolution. Inducible entry of the NuRD-interacting transcriptional regulator Ikaros into mouse pre-B cell nuclei triggered immediate binding to target gene promoters...
March 20, 2017: ELife
https://www.readbyqxmd.com/read/28289717/retinoic-acid-orphan-receptor-c-inhibition-suppresses-th17-cells-and-induces-thymic-aberrations
#3
Christine Guntermann, Alessandro Piaia, Marie-Laure Hamel, Diethilde Theil, Tina Rubic-Schneider, Alberto Del Rio-Espinola, Linda Dong, Andreas Billich, Klemens Kaupmann, Janet Dawson, Klemens Hoegenauer, David Orain, Samuel Hintermann, Rowan Stringer, Dhavalkumar D Patel, Arno Doelemeyer, Mark Deurinck, Jens Schümann
Retinoic-acid-orphan-receptor-C (RORC) is a master regulator of Th17 cells, which are pathogenic in several autoimmune diseases. Genetic Rorc deficiency in mice, while preventing autoimmunity, causes early lethality due to metastatic thymic T cell lymphomas. We sought to determine whether pharmacological RORC inhibition could be an effective and safe therapy for autoimmune diseases by evaluating its effects on Th17 cell functions and intrathymic T cell development. RORC inhibitors effectively inhibited Th17 differentiation and IL-17A production, and delayed-type hypersensitivity reactions...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28270875/prevalence-of-helicobacter-pylori-infection-in-samples-of-gastric-biopsies
#4
Leda Maria Delmondes Freitas Trindade, Lania Barreto de Oliveira Menezes, Adozina Marques de Souza Neta, Paulo Candido Leite Rolemberg, Lais Dantas Souza, Ikaro Daniel de Carvalho Barreto, Luise Meurer
BACKGROUND: Helicobacter pylori (H. pylori) infection affects about 50% of the world population and its association with environmental factors and host properties is involved in gastric carcinogenesis. The study aimed to estimate the prevalence of H. pylori in samples of gastric mucosa biopsies, correlate the presence of the bacteria in the sample with the variables age, sex and origin, to identify the types of lesions found in patients with H. pylori, and to evaluate the association of the lesions with the region of the gastric mucosa...
February 2017: Gastroenterology Research
https://www.readbyqxmd.com/read/28269619/a-wearable-computing-platform-for-developing-cloud-based-machine-learning-models-for-health-monitoring-applications
#5
Shyamal Patel, Ryan S McGinnis, Ikaro Silva, Steve DiCristofaro, Nikhil Mahadevan, Elise Jortberg, Jaime Franco, Albert Martin, Joseph Lust, Milan Raj, Bryan McGrane, Paolo DePetrillo, A J Aranyosi, Melissa Ceruolo, Jesus Pindado, Roozbeh Ghaffari
Wearable sensors have the potential to enable clinical-grade ambulatory health monitoring outside the clinic. Technological advances have enabled development of devices that can measure vital signs with great precision and significant progress has been made towards extracting clinically meaningful information from these devices in research studies. However, translating measurement accuracies achieved in the controlled settings such as the lab and clinic to unconstrained environments such as the home remains a challenge...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28269456/skin-mounted-accelerometer-system-for-measuring-knee-range-of-motion
#6
Ryan S McGinnis, Shyamal Patel, Ikaro Silva, Nikhil Mahadevan, Steve DiCristofaro, Elise Jortberg, Melissa Ceruolo, A J Aranyosi
Sufficient range of motion of the knee joint is necessary for performing many activities of daily living. Ambulatory monitoring of knee function can provide valuable information about progression of diseases like knee osteoarthritis and recovery after surgical interventions like total knee arthroplasty. In this paper, we describe a skin-mounted, conformal, accelerometer-based system for measuring knee angle and range of motion that does not require a skilled operator to apply devices. We establish the accuracy of this technique with respect to clinical gold standard goniometric measurements on a dataset collected from normative subjects during the performance of repeated bouts of knee flexion and extension tests...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28241063/role-of-dna-methylation-in-expression-control-of-the-ikzf3-gsdma-region-in-human-epithelial-cells
#7
Sanny Moussette, Abeer Al Tuwaijri, Hamid-Reza Kohan-Ghadr, Samar Elzein, Raquel Farias, Julie Bérubé, Bianca Ho, Catherine Laprise, Cynthia G Goodyer, Simon Rousseau, Anna K Naumova
Chromosomal region 17q12-q21 is associated with asthma and harbors regulatory polymorphisms that influence expression levels of all five protein-coding genes in the region: IKAROS family zinc finger 3 (Aiolos) (IKZF3), zona pellucida binding protein 2 (ZPBP2), ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3), and gasdermins A and B (GSDMA, GSDMB). Furthermore, DNA methylation in this region has been implicated as a potential modifier of the genetic risk of asthma development. To further characterize the effect of DNA methylation, we examined the impact of treatment with DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) that causes DNA demethylation, on expression and promoter methylation of the five 17q12-q21 genes in the human airway epithelium cell line NuLi-1, embryonic kidney epithelium cell line 293T and human adenocarcinoma cell line MCF-7...
2017: PloS One
https://www.readbyqxmd.com/read/28227877/a-wearable-computing-platform-for-developing-cloud-based-machine-learning-models-for-health-monitoring-applications
#8
Shyamal Patel, Ryan S McGinnis, Ikaro Silva, Steve DiCristofaro, Nikhil Mahadevan, Elise Jortberg, Jaime Franco, Albert Martin, Joseph Lust, Milan Raj, Bryan McGrane, Paolo DePetrillo, A J Aranyosi, Melissa Ceruolo, Jesus Pindado, Roozbeh Ghaffari, Shyamal Patel, Ryan S McGinnis, Ikaro Silva, Steve DiCristofaro, Nikhil Mahadevan, Elise Jortberg, Jaime Franco, Albert Martin, Joseph Lust, Milan Raj, Bryan McGrane, Paolo DePetrillo, A J Aranyosi, Melissa Ceruolo, Jesus Pindado, Roozbeh Ghaffari
Wearable sensors have the potential to enable clinical-grade ambulatory health monitoring outside the clinic. Technological advances have enabled development of devices that can measure vital signs with great precision and significant progress has been made towards extracting clinically meaningful information from these devices in research studies. However, translating measurement accuracies achieved in the controlled settings such as the lab and clinic to unconstrained environments such as the home remains a challenge...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28227706/skin-mounted-accelerometer-system-for-measuring-knee-range-of-motion
#9
Ryan S McGinnis, Shyamal Patel, Ikaro Silva, Nikhil Mahadevan, Steve DiCristofaro, Elise Jortberg, Melissa Ceruolo, A J Aranyosi, Ryan S McGinnis, Shyamal Patel, Ikaro Silva, Nikhil Mahadevan, Steve DiCristofaro, Elise Jortberg, Melissa Ceruolo, A J Aranyosi, A J Aranyosi, Melissa Ceruolo, Ikaro Silva, Steve DiCristofaro, Elise Jortberg, Ryan S McGinnis, Shyamal Patel, Nikhil Mahadevan
Sufficient range of motion of the knee joint is necessary for performing many activities of daily living. Ambulatory monitoring of knee function can provide valuable information about progression of diseases like knee osteoarthritis and recovery after surgical interventions like total knee arthroplasty. In this paper, we describe a skin-mounted, conformal, accelerometer-based system for measuring knee angle and range of motion that does not require a skilled operator to apply devices. We establish the accuracy of this technique with respect to clinical gold standard goniometric measurements on a dataset collected from normative subjects during the performance of repeated bouts of knee flexion and extension tests...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226048/fetal-and-neonatal-deaths-of-children-of-patients-classified-as-near-miss
#10
Daniele Marin Nardello, Alzira Maria D Avila Nery Guimarães, Ikaro Daniel de Carvalho Barreto, Ricardo Queiroz Gurgel, Eleonora Ramos de Oliveira Ribeiro, Cristiane Franca Lisboa Gois
Objective: identify the epidemiological aspects of early fetal and neonatal deaths in children of patients classified with near miss and the factors associated with this outcome. Method: a cross-sectional study of 79 women identified with near miss and their newborns. The variables were analyzed using Fisher's exact test. Risk factors were estimated based on unadjusted and adjusted odds ratios, and by means of multiple correspondence analysis, with significance for p <0...
January 2017: Revista Brasileira de Enfermagem
https://www.readbyqxmd.com/read/28191591/plasmacytoid-dendritic-cell-proliferations-and-neoplasms-involving-the-bone-marrow-summary-of-the-workshop-cases-submitted-to-the-18th-meeting-of-the-european-association-for-haematopathology-eahp-organized-by-the-european-bone-marrow-working-group-basel-2016
#11
Alexandar Tzankov, Konnie Hebeda, Markus Kremer, Roos Leguit, Attilio Orazi, Jon van der Walt, Umberto Gianelli
Two distinct forms of neoplasms derived from plasmacytoid dendritic cells (PDC) exist: mature PDC proliferations associated with myeloid neoplasms and blastic PDC neoplasms (BPDCN). Ten cases of PDC proliferations and neoplasms in the bone marrow have been submitted to the bone marrow workshop held at the 18th EAHP meeting. Based on observations from the submitted cases, scattered PDC (≤1% of cells) and PDC aggregates (≤10 PDC/HPF) reflect the normal bone marrow composition, while in myelodysplastic syndromes (MDS), there is a propensity for larger/more PDC aggregates (1-5% and 35 PDC/HPF)...
February 12, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28188716/-immunological-alterations-in-common-variable-immunodeficiency
#12
Laura Berrón-Ruiz
Common variable immunodeficiency (CVID) is the largest group of symptomatic primary immune deficiencies; it is characterized by hypogammaglobulinemia, poor response to vaccines and increased susceptibility to infections. Cellular phenotypes and abnormalities have been described both in adaptive and innate immune response. Several classifications of common variable immunodeficiency are based on defects found on T and B cells, which have been correlated with clinical manifestations. In recent years, significant progress has been made in elucidating the genetic mechanisms that result in a IDCV phenotype...
January 2017: Revista Alergia Mexico: Organo Oficial de la Sociedad Mexicana de Alergia e Inmunología, A.C
https://www.readbyqxmd.com/read/28152014/apigenin-selective-ck2-inhibitor-increases-ikaros-expression-and-improves-t-cell-homeostasis-and-function-in-murine-pancreatic-cancer
#13
Nadine Nelson, Karoly Szekeres, Cristina Iclozan, Ivannie Ortiz Rivera, Andrew McGill, Gbemisola Johnson, Onyekachi Nwogu, Tomar Ghansah
Pancreatic cancer (PC) evades immune destruction by favoring the development of regulatory T cells (Tregs) that inhibit effector T cells. The transcription factor Ikaros is critical for lymphocyte development, especially T cells. We have previously shown that downregulation of Ikaros occurs as a result of its protein degradation by the ubiquitin-proteasome system in our Panc02 tumor-bearing (TB) mouse model. Mechanistically, we observed a deregulation in the balance between Casein Kinase II (CK2) and protein phosphatase 1 (PP1), which suggested that increased CK2 activity is responsible for regulating Ikaros' stability in our model...
2017: PloS One
https://www.readbyqxmd.com/read/28096536/germline-ikaros-mutation-associated-with-primary-immunodeficiency-that-progressed-to-t-cell-acute-lymphoblastic-leukemia
#14
N Yoshida, H Sakaguchi, H Muramatsu, Y Okuno, C Song, S Dovat, A Shimada, M Ozeki, H Ohnishi, T Teramoto, T Fukao, N Kondo, Y Takahashi, K Matsumoto, K Kato, S Kojima
Leukemia accepted article preview online, 18 January 2017. doi:10.1038/leu.2017.25.
January 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28074872/corrigendum-targeting-high-dynamin-2-dnm2-expression-by-restoring-ikaros-function-in-acute-lymphoblastic-leukemia
#15
Zheng Ge, Yan Gu, Qi Han, Gang Zhao, Min Li, Jianyong Li, Baoan Chen, Tianyu Sun, Sinisa Dovat, Robert Peter Gale, Chunhua Song
No abstract text is available yet for this article.
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28052520/ikaros-expression-in-distinct-bone-marrow-cell-populations-as-a-candidate-biomarker-for-outcome-with-lenalidomide-dexamethasone-therapy-in-multiple-myeloma
#16
Arnold Bolomsky, Wolfgang Hübl, Stefano Spada, Ercan Müldür, Karin Schlangen, Daniel Heintel, Alberto Rocci, Adalbert Weißmann, Veronique Fritz, Martin Willheim, Niklas Zojer, Antonio Palumbo, Heinz Ludwig
Immunomodulatory drugs (IMiDs) are a cornerstone in the treatment of multiple myeloma (MM), but specific markers to predict outcome are still missing. Recent work pointed to a prognostic role for IMiD target genes (e.g. CRBN). Moreover, indirect activity of IMiDs on immune cells correlated with outcome, raising the possibility that cell populations in the bone marrow (BM) microenvironment could serve as biomarkers. We therefore analysed gene expression levels of six IMiD target genes in whole BM samples of 44 myeloma patients treated with lenalidomide-dexamethasone...
March 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28038358/il-22-promotes-fas-expression-in-oligodendrocytes-and-inhibits-foxp3-expression-in-t-cells-by-activating-the-nf-%C3%AE%C2%BAb-pathway-in-multiple-sclerosis
#17
Jin Zhen, Jun Yuan, Yongwang Fu, Runxiu Zhu, Meiling Wang, Hong Chang, Yan Zhao, Dong Wang, Zuneng Lu
Multiple sclerosis (MS) is characterized by an increase in interleukin-22 and Fas, and a decrease in FOXP3, among other factors. In this study, we examined patients with MS and healthy control subjects and used the experimental autoimmune encephalomyelitis (EAE) animal model to identify the effects of IL-22 on oligodendrocytes and T cells in MS development. In MS, the expression of Fas in oligodendrocytes and IL-22 in CD4(+)CCR4(+)CCR6(+)CCR10(+) T cells was enhanced. Ikaros and FOXP3 were both decreased in T cells...
December 27, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/28030830/ikaros-regulation-of-the-bcl6-bach2-axis-and-its-clinical-relevance-in-acute-lymphoblastic-leukemia
#18
Zheng Ge, Xilian Zhou, Yan Gu, Qi Han, Jianyong Li, Baoan Chen, Qinyu Ge, Elanora Dovat, Jonathon L Payne, Tianyu Sun, Chunhua Song, Sinisa Dovat
B-Cell CLL/Lymphoma 6 (BCL6) is a proto-oncogene that is highly expressed in acute lymphoblastic leukemia (ALL). BTB and CNC Homology 1 Basic Leucine Zipper Transcription Factor 2 (BACH2) is a suppressor of transcription. The BACH2-BCL6 balance controls selection at the pre-B cell receptor checkpoint by regulating p53 expression. However, the underlying mechanism and the clinical relevance of the BCL6/BACH2 axis are unknown. Here, we found that Ikaros, a tumor suppressor encoded by IKZF1, directly binds to both the BCL6 and BACH2 promoters where it suppresses BCL6 and promotes BACH2 expression in B-cell ALL (B-ALL) cells...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28017969/ikzf1-expression-is-a-prognostic-marker-in-newly-diagnosed-standard-risk-multiple-myeloma-treated-with-lenalidomide-and-intensive-chemotherapy-a-study-of-the-german-myeloma-study-group-dsmm
#19
J Krönke, F Kuchenbauer, M Kull, V Teleanu, L Bullinger, D Bunjes, A Greiner, S Kolmus, S Köpff, M Schreder, L-O Mügge, C Straka, M Engelhardt, H Döhner, H Einsele, F Bassermann, R Bargou, S Knop, C Langer
Lenalidomide is an immunomodulatory compound with high clinical activity in multiple myeloma. Lenalidomide binding to the Cereblon (CRBN) E3 ubiquitin ligase results in targeted ubiquitination and degradation of the lymphoid transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) leading to growth inhibition of multiple myeloma cells. Recently, Basigin (BSG) was identified as another protein regulated by CRBN that is involved in the activity of lenalidomide. Here, we analyzed the prognostic value of IKZF1, IKZF3, CRBN and BSG mRNA expression levels in pretreatment plasma cells from 60 patients with newly diagnosed multiple myeloma uniformly treated with lenalidomide in combination with intensive chemotherapy within a clinical trial...
January 20, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28001429/single-crystalline-hexagonal-silicon-germanium
#20
Håkon Ikaros T Hauge, Sonia Conesa-Boj, Marcel A Verheijen, Sebastian Koelling, Erik P A M Bakkers
Group IV materials with the hexagonal diamond crystal structure have been predicted to exhibit promising optical and electronic properties. In particular, hexagonal silicon-germanium (Si1-xGex) should be characterized by a tunable direct band gap with implications ranging from Si-based light-emitting diodes to lasers and quantum dots for single photon emitters. Here we demonstrate the feasibility of high-quality defect-free and wafer-scale hexagonal Si1-xGex growth with precise control of the alloy composition and layer thickness...
December 27, 2016: Nano Letters
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