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https://www.readbyqxmd.com/read/29233943/atg-dependent-phagocytosis-in-dendritic-cells-drives-myelin-specific-cd4-t-cell-pathogenicity-during-cns-inflammation
#1
Christian W Keller, Christina Sina, Monika B Kotur, Giulia Ramelli, Sarah Mundt, Isaak Quast, Laure-Anne Ligeon, Patrick Weber, Burkhard Becher, Christian Münz, Jan D Lünemann
Although reactivation and accumulation of autoreactive CD4+ T cells within the CNS are considered to play a key role in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), the mechanisms of how these cells recognize their target organ and induce sustained inflammation are incompletely understood. Here, we report that mice with conditional deletion of the essential autophagy protein ATG5 in classical dendritic cells (DCs), which are present at low frequencies in the nondiseased CNS, are completely resistant to EAE development following adoptive transfer of myelin-specific T cells and show substantially reduced in situ CD4+ T cell accumulation during the effector phase of the disease...
December 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29233870/the-mammalian-ulk1-complex-and-autophagy-initiation
#2
REVIEW
Maria Zachari, Ian G Ganley
Autophagy is a vital lysosomal degradation pathway that serves as a quality control mechanism. It rids the cell of damaged, toxic or excess cellular components, which if left to persist could be detrimental to the cell. It also serves as a recycling pathway to maintain protein synthesis under starvation conditions. A key initial event in autophagy is formation of the autophagosome, a unique double-membrane organelle that engulfs the cytosolic cargo destined for degradation. This step is mediated by the serine/threonine protein kinase ULK1 (unc-51-like kinase 1), which functions in a complex with at least three protein partners: FIP200 (focal adhesion kinase family interacting protein of 200 kDa), ATG (autophagy-related protein) 13 (ATG13), and ATG101...
December 12, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/29230587/arterial-wall-hypertrophy-is-ameliorated-by-%C3%AE-2-adrenergic-receptor-antagonist-or-aliskiren-in-kidneys-of-angiotensinogen-knockout-mice
#3
Haruka Nakamori, Shin-Ichiro Yoshida, Hiroaki Ishiguro, Shota Suzuki, Hiroaki Yasuzaki, Tatsuo Hashimoto, Tomoaki Ishigami, Nobuhito Hirawa, Yoshiyuki Toya, Satoshi Umemura, Kouichi Tamura
BACKGROUND: Arterial hypertrophy and interstitial fibrosis are important characteristics in kidneys of angiotensinogen-knockout (Atg -/-) mice. In these mice, which exhibit polyuria and hypotension, sympathetic nerve signaling is estimated to be compensatorily hyperactive. Furthermore, transforming growth factor (TGF)-β1 is overexpressed in mice kidneys. To determine whether sympathetic nerve signaling and TGF-β1 exacerbate arterial hypertrophy and interstitial fibrosis, intervention studies of such signaling are required...
December 11, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/29228741/autophagy-inhibition-sensitizes-ly3023414-induced-anti-glioma-cell-activity-in-vitro-and-in-vivo
#4
Lan Zheng, Huanyin Li, Yanqing Mo, Gong Qi, Bin Liu, Jing Zhao
PI3K-AKT-mTOR signaling is a valuable treatment target for human glioma. LY3023414 is a novel, highly-potent and pan PI3K-AKT-mTOR inhibitor. Here, we show that LY3023414 efficiently inhibited survival and proliferation of primary and established human glioma cells. Meanwhile, apoptosis activation was observed in LY3023414-treated glioma cells. LY3023414 blocked AKT-mTOR activation in human glioma cells. Further studies show that LY3023414 induced feedback activation of autophagy in U251MG cells. On the other hand, autophagy inhibition via adding pharmacological inhibitors or silencing Beclin-1/ATG-5 significantly potentiated LY3023414-induced glioma cell apoptosis...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29225252/reactivation-of-hemophagocytic-lymphohistiocytosis-triggered-by-antithymocyte-globulin
#5
Kensuke Matsuda, Kazuhiro Toyama, Takashi Toya, Masako Ikemura, Fumihiko Nakamura, Mineo Kurokawa
A 16-year-old boy with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (HLH) underwent allogeneic hematopoietic stem cell transplantation after conditioning with fludarabine, melphalan, total body irradiation, and rabbit antithymocyte globulin (ATG). A severe, persistent infusion reaction occurred after the initial administration of ATG. Investigations showed a rapid increase in the levels of liver enzymes and ferritin, and the reactivation of HLH was confirmed by marked hemophagocytosis in the bone marrow...
December 8, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29223072/alteration-of-autophagy-related-proteins-in-peripheral-blood-mononuclear-cells-of-patients-with-parkinson-s-disease
#6
Yasuo Miki, Shuji Shimoyama, Tomoya Kon, Tatsuya Ueno, Ryo Hayakari, Kunikazu Tanji, Tomoh Matsumiya, Eiki Tsushima, Fumiaki Mori, Koichi Wakabayashi, Masahiko Tomiyama
Previous postmortem studies demonstrated dysregulation of autophagy in patients with Parkinson's disease (PD). To clarify whether this alteration reflects a fundamental aspect of PD or represents the final stage of autophagy dysregulation resulting from a long neurodegenerative process, we focused on basal autophagy in peripheral blood mononuclear cells (PBMCs) of PD patients (n = 35) and controls (n = 23). The whole-transcriptome assay revealed downregulation of mRNAs for 6 core regulators of autophagy (UNC-51-like kinase [ULK] 3, autophagy-related [Atg] 2A, Atg4B, Atg5, Atg16L1, and histone deacetylase 6)...
November 21, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29218765/deregulation-of-autophagy-in-postmortem-brains-of-machado-joseph-disease-patients
#7
Annie Sittler, Marie-Paule Muriel, Martina Marinello, Alexis Brice, Wilfred den Dunnen, Sandro Alves
Autophagy, the major pathway for protein turnover, is critical to maintain cellular homeostasis and has been implicated in neurodegenerative diseases. The aim of this research was to analyze the expression of autophagy markers in postmortem brains from Machado-Joseph disease (MJD) patients. The expression of autophagy markers in the cerebellum and the oculomotor nucleus from MJD patients and age-matched controls with no signs of neuropathology was inspected postmortem by immunohistochemistry (IHC) and Western blot...
December 8, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/29218074/autophagy-in-endometriosis
#8
REVIEW
Hui-Li Yang, Jie Mei, Kai-Kai Chang, Wen-Jie Zhou, Li-Qing Huang, Ming-Qing Li
Endometriosis (EMS) is a common gynecologic disease that causes chronic pelvic pain, dysmenorrhea, and infertility in women. The doctrine of menstruation back flow planting and defects in the immune system are well known and widely accepted. In recent years, increasing studies have been focused on the role of autophagy in EMS, and have shown that autophagy plays a vital role in EMS. Autophagy, which is known as the non-apoptotic form of programmed cell death induced by a large number of intracellular/extracellular stimuli, is the major cellular pathway for the degradation of long-lived proteins and cytoplasmic organelles in eukaryotic cells...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29217388/impact-of-cytomegalovirus-cmv-viral-load-on-probability-of-spontaneous-clearance-and-response-to-pre-emptive-therapy-in-allogeneic-stem-cell-transplant-recipients
#9
Jose F Camargo, Erik Kimble, Rossana Rosa, Luis A Shimose, Maria X Bueno, Nikeshan Jeyakumar, Michele I Morris, Lilian M Abbo, Jacques Simkins, Maritza C Alencar, Cara Benjamin, Eric Wieder, Antonio Jimenez, Amer Beitinjaneh, Mark Goodman, John J Byrnes, Lazaros J Lekakis, Denise Pereira, Krishna V Komanduri
The optimal viral load threshold to initiate pre-emptive cytomegalovirus (CMV) therapy in hematopoietic cell transplant (HCT) recipients remains to be defined. In an effort to address this question we conducted a retrospective study of 174 allogeneic HCT recipients transplanted at a single center between August 2012 and April 2016. During this period, pre-emptive therapy started at the discretion of the treating clinician. 109 (63%) patients developed CMV viremia. Median time to reactivation was 17 (IQR, 7-30) days post-HCT...
December 4, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29211764/identification-expression-and-functional-characterization-of-m4l-a-muscarinic-acetylcholine-m4-receptor-splice-variant
#10
Douglas A Schober, Carrie H Croy, Cara L Ruble, Ran Tao, Christian C Felder
Rodent genomic alignment sequences support a 2-exon model for muscarinic M4 receptor. Using this model a novel N-terminal extension was discovered in the human muscarinic acetylcholine M4 receptor. An open reading frame was discovered in the human, mouse and rat with a common ATG (methionine start codon) that extended the N-terminus of the muscarinic acetylcholine M4 receptor subtype by 155 amino acids resulting in a longer variant. Transcriptional evidence for this splice variant was confirmed by RNA-Seq and RT-PCR experiments performed from human donor brain prefrontal cortices...
2017: PloS One
https://www.readbyqxmd.com/read/29210476/delayed-revascularization-of-islets-after-transplantation-by-il-6-blockade-in-pig-to-non-human-primate-islet-xenotransplantation-model
#11
Byoung-Hoon Min, Jun-Seop Shin, Jong-Min Kim, Seong-Jun Kang, Hyun-Je Kim, Il-Hee Yoon, Su-Kyoung Park, Ji-Won Choi, Min-Suk Lee, Chung-Gyu Park
BACKGROUND: Pancreatic islet transplantation is currently proven as a promising treatment for type 1 diabetes patients with labile glycemic control and severe hypoglycemia unawareness. Upon islet transplantation, revascularization is essential for proper functioning of the transplanted islets. As IL-6 is important for endothelial cell survival and systemic inflammation related to xenograft, the effect of IL-6 receptor antagonist, tocilizumab, on revascularization of the transplanted islets was examined in pig to non-human primate islet xenotransplantation model...
December 6, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29210078/mdatg18a-overexpression-improves-tolerance-to-nitrogen-deficiency-and-regulates-anthocyanin-accumulation-through-increased-autophagy-in-transgenic-apple
#12
Xun Sun, Xin Jia, Liuqing Huo, Runmin Che, Xiaoqing Gong, Ping Wang, Fengwang Ma
Nitrogen (N) availability is an essential factor for plant growth. Recycling and remobilization of N have strong impacts on crop yield and quality under N deficiency. Autophagy is a critical nutrient-recycling process that facilitates remobilization under starvation. We previously showed that an important AuTophaGy (ATG) protein from apple, MdATG18a, has a positive role in drought tolerance. In this study, we explored its biological role in response to low-N. Overexpression of MdATG18a in both Arabidopsis and apple improved tolerance to N-depletion and caused a greater accumulation of anthocyanin...
December 5, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/29207601/dissecting-the-mechanisms-involved-in-anti-human-t-lymphocyte-immunoglobulin-atg-induced-tolerance-in-the-setting-of-allogeneic-stem-cell-transplantation-potential-implications-for-graft-versus-host-disease
#13
Katia Beider, David Naor, Valeria Voevoda, Olga Ostrovsky, Hanna Bitner, Evgenia Rosenberg, Nira Varda-Bloom, Victoria Marcu-Malina, Jonathan Canaani, Ivetta Danilesko, Avichai Shimoni, Arnon Nagler
Polyclonal anti-human thymocyte globulins (ATG) have been recently shown to significantly reduce the incidence of graft versus host disease (GVHD) post allogeneic stem cell transplantation (HSCT) from both sibling and unrelated donors. Induction of regulatory T cells has been suggested as one of the possible mechanisms. The aim of current study was to further characterize the T cell populations induced by ATG treatment and to delineate the mechanisms involved in ATG-induced tolerance. Phenotypic characterization revealed a significant increase in the expression of FoxP3, GITR, CD95, PD-1 and ICOS as well as the complement inhibitory molecules CD55, CD58 and CD59 on CD4+CD25+ T cells upon ATG treatment...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207540/herpesvirus-and-autophagy-all-right-everybody-be-cool-this-is-a-robbery
#14
REVIEW
Marion Lussignol, Audrey Esclatine
Autophagy is an essential vacuolar process of the cell, leading to lysosomal degradation and recycling of proteins and organelles, which is extremely important in maintaining homeostasis. Multiple roles have been now associated with autophagy, in particular a pro-survival role in nutrient starvation or in stressful environments, a role in life span extension, in development, or in innate and adaptive immunity. This cellular process can also take over microorganisms or viral proteins inside autophagosomes and degrade them directly in autolysosomes and is then called xenophagy and virophagy, respectively...
December 4, 2017: Viruses
https://www.readbyqxmd.com/read/29199482/low-dose-anti-thymocyte-globulin-reduces-chronic-graft-versus-host-disease-incidence-rates-after-matched-unrelated-donor-transplantation
#15
Anand Tandra, Fahrettin Covut, Brenda Cooper, Richard Creger, Lauren Brister, Bernadette McQuigg, Paolo Caimi, Ehsan Malek, Ben Tomlinson, Hillard M Lazarus, Folashade Otegbeye, Merle Kolk, Marcos de Lima, Leland Metheny
Anti-thymocyte globulin (ATG) is often added to hematopoietic stem cell transplant conditioning regimens to prevent graft rejection and reduce graft-versus-host disease (GVHD). Doses used in retrospective and prospective clinical trials have ranged from 2.5 to 20 mg/kg with rates of grade II-IV acute GVHD and chronic GVHD up to 40 and 60%, respectively. We retrospectively compared outcomes in recipients of matched unrelated donor (MUD) grafts given low dose rabbit ATG IV 3 mg/kg (n = 52) versus recipients of matched related donor (MRD) grafts (n = 48) without ATG...
December 4, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29198930/induction-regimen-and-survival-in-simultaneous-heart-kidney-transplant-recipients
#16
Venkatesh K Ariyamuthu, Alpesh A Amin, Mark H Drazner, Faris Araj, Pradeep P A Mammen, Mehmet Ayvaci, Mutlu Mete, Fatih Ozay, Mythili Ghanta, Sumit Mohan, Prince Mohan, Bekir Tanriover
BACKGROUND: Induction therapy in simultaneous heart-kidney transplantation (SHKT) is not well studied in the setting of contemporary maintenance immunosuppression consisting of tacrolimus (TAC), mycophenolic acid (MPA), and prednisone (PRED). METHODS: We analyzed the Organ Procurement and Transplant Network registry from January 1, 2000, to March 3, 2015, for recipients of SHKT (N = 623) maintained on TAC/MPA/PRED at hospital discharge. The study cohort was further stratified into 3 groups by induction choice: induction (n = 232), rabbit anti-thymoglobulin (r-ATG; n = 204), and interleukin-2 receptor-α (n = 187) antagonists...
November 15, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/29198169/stress-response-transcription-factors-msn2-and-msn4-couple-torc2-ypk1-signaling-and-mitochondrial-respiration-to-atg8-gene-expression-and-autophagy
#17
Ariadne Vlahakis, Nerea Lopez Muniozguren, Ted Powers
Macroautophagy/autophagy is a starvation and stress-induced catabolic process critical for cellular homeostasis and adaptation. Several Atg proteins are involved in the formation of the autophagosome and subsequent degradation of cytoplasmic components, a process termed autophagy flux. Additionally, the expression of several Atg proteins, in particular Atg8, is modulated transcriptionally, yet the regulatory mechanisms involved remain poorly understood. Here we demonstrate that the AGC kinase Ypk1, target of the rapamycin-insensitive TORC2 signaling pathway, controls ATG8 expression by repressing the heterodimeric Zinc-finger transcription factors Msn2 and Msn4...
December 4, 2017: Autophagy
https://www.readbyqxmd.com/read/29190168/the-effect-of-anti-thyroid-antibodies-positivity-on-children-with-primary-immune-thrombocytopenia
#18
Suzan O Mousa, Gamal T Soliman, Ahmed A-F Saedii, Emad N Hameed
Primary immune thrombocytopenia (ITP) is the most common cause of acquired thrombocytopenia in children. Anti-thyroid antibodies (aTA) have previously been found to be present in various autoimmune diseases. Our aim was to study the effect of aTA positivity (which are anti-thyroid peroxidase (aTPo) and/or anti-thyroglobulin (aTg)) on children with primary immune thrombocytopenia and their relation to treatment response. Sixty-one children with primary ITP were enrolled in the present study. They were further subdivided into: ND&P group (newly diagnosed and persistent) and chronic ITP group...
November 30, 2017: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/29186076/the-role-of-anti-thymocyte-globulin-or-alemtuzumab-based-serotherapy-in-the-prophylaxis-and-management-of-graft-versus-host-disease
#19
REVIEW
Robert Ali, Jeremy Ramdial, Sandra Algaze, Amer Beitinjaneh
Allogeneic hematopoietic stem cell transplant is an established treatment modality for hematologic and non-hematologic diseases. However, it is associated with acute and long-term sequelae which can translate into mortality. Graft-versus-host disease (GVHD) remains a glaring obstacle, especially with the advent of reduced-intensity conditioning. Serotherapy capitalizes on antibodies which target T cells and other immune cells to mitigate this effect. This article focuses on the utility of two such agents: anti-thymocyte globulin (ATG) and alemtuzumab...
November 29, 2017: Biomedicines
https://www.readbyqxmd.com/read/29181673/relative-transcription-of-autophagy-related-genes-in-amblyomma-sculptum-and-rhipicephalus-microplus-ticks
#20
Nicole O Moura-Martiniano, Erik Machado-Ferreira, Gilberto S Gazêta, Carlos Augusto Gomes Soares
Ticks endure stressful off-host periods and perform as vectors of a diversity of infectious agents, thus engaging pathways that expectedly demand for autophagy. Little is known of ticks' autophagy, a conserved eukaryotic machinery assisting in homeostasis processes that also participates in tissue-dependent metabolic functions. Here, the autophagy-related ATG4 (autophagin-1), ATG6 (beclin-1) and ATG8 (LC3) mRNAs from the human diseases vector Amblyomma sculptum and the cattle-tick Rhipicephalus microplus were identified...
November 27, 2017: Experimental & Applied Acarology
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