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Kyung-Ha Lee, Peipei Zhang, Hong Joo Kim, Diana M Mitrea, Mohona Sarkar, Brian D Freibaum, Jaclyn Cika, Maura Coughlin, James Messing, Amandine Molliex, Brian A Maxwell, Nam Chul Kim, Jamshid Temirov, Jennifer Moore, Regina-Maria Kolaitis, Timothy I Shaw, Bing Bai, Junmin Peng, Richard W Kriwacki, J Paul Taylor
Expansion of a hexanucleotide repeat GGGGCC (G4C2) in C9ORF72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Transcripts carrying (G4C2) expansions undergo unconventional, non-ATG-dependent translation, generating toxic dipeptide repeat (DPR) proteins thought to contribute to disease. Here, we identify the interactome of all DPRs and find that arginine-containing DPRs, polyGly-Arg (GR) and polyPro-Arg (PR), interact with RNA-binding proteins and proteins with low complexity sequence domains (LCDs) that often mediate the assembly of membrane-less organelles...
October 20, 2016: Cell
Annalisa Ruggeri, Yuqian Sun, Myriam Labopin, Andrea Bacigalupo, Francesca Lorentino, William Arcese, Stella Santarone, Zafar Gülbas, Didier Blaise, Giuseppe Messina, Ardeshi Ghavamzadeh, Florent Malard, Benedetto Bruno, Jose Luis Diez-Martin, Yener Koc, Fabio Ciceri, Mohamad Mohty, Arnon Nagler
Severe graft-versus-host-disease is a major barrier for non T-cell-depleted haploidentical stem cell transplantation and there is no consensus on the optimal GVHD prophylaxis. This study compared the two most commonly used graft-versus-host-disease prophylaxis regimens (post-transplant-cyclophosphamide-based (PTCY) versus the anti-thymocyte-globulin-based (ATG)) in adults with acute myeloid leukemia reported to the european society for blood and bone marrow transplantation. 308 patients were analyzed, 193 received PTCY and 115 ATG as anti- graft-versus-host-disease prophylaxis...
October 6, 2016: Haematologica
K R Anila, Nileena Nayak, K Jayasree
INTRODUCTION: Chronic lymphocytic thyroiditis [Hashimoto thyroiditis (HT)] is a common thyroid lesion diagnosed on fine-needle aspiration cytology (FNAC). Apart from FNAC, various other parameters, such as clinical features, ultrasonographic findings, antithyroid antibody levels, hormone profiles, and radionuclide thyroid scan, are also taken into consideration in making a diagnosis of HT. AIMS: To grade lymphocytic thyroiditis based on the cytomorphology and to correlate the cytological grades with the levels of antithyroid peroxidase antibody (ATPO), antithyroglobulin antibody (ATG), and thyroid stimulating hormone (TSH)...
July 2016: Journal of Cytology
Qi Zhang, Manyi Yang, Zhan Qu, Jixiang Zhou, Qin Jiang
Molecule-targeted therapy has become the research focus for hepatocellular carcinoma (HCC). Persistent PI3K-AKT activation is often detected in HCC, representing a valuable oncotarget for treatment. Here, we tested the anti-HCC activity by a potent AKT inhibitor: AKT inhibitor 1/2 (AKTi-1/2). In both established (HepG2 and Huh-7) and primary human HCC cells, treatment with AKTi-1/2 inhibited cell survival and proliferation, but induced cell apoptosis. AKTi-1/2 blocked AKT-mTOR activation, yet simultaneously provoked cytoprotective autophagy in HCC cells...
October 15, 2016: Biochemical and Biophysical Research Communications
Kirsten A M White, Li Luo, Todd A Thompson, Salina Torres, Chien-An Andy Hu, Nancy E Thomas, Jenna Lilyquist, Hoda Anton-Culver, Stephen B Gruber, Lynn From, Klaus J Busam, Irene Orlow, Peter A Kanetsky, Loraine D Marrett, Richard P Gallagher, Lidia Sacchetto, Stefano Rosso, Terence Dwyer, Anne E Cust, Colin B Begg, Marianne Berwick
Autophagy has been linked with melanoma risk and survival, but no polymorphisms in autophagy-related (ATG) genes have been investigated in relation to melanoma progression. We examined five single-nucleotide polymorphisms (SNPs) in three ATG genes (ATG5; ATG10; and ATG16L) with known or suspected impact on autophagic flux in an international population-based case-control study of melanoma. DNA from 911 melanoma patients was genotyped. An association was identified between (GG) (rs2241880) and earlier stage at diagnosis (OR 0...
October 17, 2016: Cancer Medicine
Mona Pazhouhi, Reyhaneh Sariri, Arezou Rabzia, Mozafar Khazaei
OBJECTIVES: Glioblastoma multiforme (GBM) is one of the most lethal forms of human cancer and temozolomide (TMZ) is currently part of the standard treatment for this disease. Combination therapy using natural substances can enhance the anti-cancer activity of TMZ. The purpose of this study was to evaluate the effect of TMZ in combination with thymoquinone (TQ) on human GBM cell line (U87MG). MATERIALS AND METHODS: The cell line was treated with TMZ and/or TQ. Cell viability was assessed using trypan blue and MTT assay...
August 2016: Iranian Journal of Basic Medical Sciences
L V Kroth, F F Barreiro, D Saitovitch, M A Traesel, D O L d'Avila, C E Poli-de-Figueiredo
Acute graft pyelonephritis is a very common infection in renal transplantation. The impact of acute graft pyelonephritis (AGPN) on graft and patient outcome has not yet been established. Eight hundred seventy kidney and kidney-pancreas transplants were retrospectively studied, over last 13 years, to verify occurrence of AGPN in the first 30 days post-transplantation. We found that 112 patients (15.8%) presented post-transplantatiom AGPN up to 30 days after a kidney transplantation. The occurrence was higher in older patients (P = ...
September 2016: Transplantation Proceedings
L V Kroth, F F Barreiro, D Saitovitch, M A Traesel, D O L d'Avila, C E Poli-de-Figueiredo
BACKGROUND: Solid organ transplant recipients are susceptible to antibiotic-resistant infections and carbapenem-resistant Acinetobacter baumannii (CRAB) has recently been recognized as a serious complication in solid organ recipients. High mortality rates have been described. METHODS: We retrospectively analyzed 807 transplantations and detected 10 patients who died 24 hours after the diagnosis of septicemia, all with CRAB-positive blood cultures. Recipients were followed up for at least 1 year and were stratified into the following groups: Group 1, patients alive; Group 2, patients that died due to other causes except Acinetobacter infection; and Group 3, patients who died within 24 hours of CRAB diagnosis...
September 2016: Transplantation Proceedings
Zeng Xiaowei, Liu Cuicui, Han Ning, Bian Hongwu, Zhu Muyuan
Autophagy is an evolutionarily highly conserved catabolic pathway among eukaryotic cells that protects the organisms against environmental stress. Normally, autophagy is mainly involved with autophagy-related proteins(ATGs) and autophagic regulators including a series of cytoplasmic proteins and small molecules. Besides, the selective autophagy, which targets damaged organalles or protein aggregates, is mediated by the additional receptors to help the ATGs recognize different substrates. In this review, we summarize recent advances in autophagic regulators like ROS(Reactive oxygen species), TOR(Target of rapamycin) and receptors like NBR1(Neighbor of BRCA1 gene protein), RPN10(Regulatory particle non-ATPase 10) as well as their functional mechanisms mainly in Arabidopsis thaliana...
July 20, 2016: Yi Chuan, Hereditas
Weiwei Li, Ming Chen, Erhui Wang, Liqin Hu, Malcolm J Hawkesford, Li Zhong, Zhu Chen, Zhaoshi Xu, Liancheng Li, Yongbin Zhou, Changhong Guo, Youzhi Ma
BACKGROUND: Autophagy is a cellular degradation process that is highly evolutionarily-conserved in yeast, plants, and animals. In plants, autophagy plays important roles in regulating intracellular degradation and recycling of amino acids in response to nutrient starvation, senescence, and other environmental stresses. Foxtail millet (Setaria italica) has strong resistance to stresses and has been proposed as an ideal material for use in the study of the physiological mechanisms of abiotic stress tolerance in plants...
October 12, 2016: BMC Genomics
Thomas Westergard, Brigid K Jensen, Xinmei Wen, Jingli Cai, Elizabeth Kropf, Lorraine Iacovitti, Piera Pasinelli, Davide Trotti
Aberrant hexanucleotide repeat expansions in C9orf72 are the most common genetic change underlying amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). RNA transcripts containing these expansions undergo repeat-associated non-ATG translation (RAN-T) to form five dipeptide repeat proteins (DPRs). DPRs are found as aggregates throughout the CNS of C9orf72-ALS/FTD patients, and some cause degeneration when expressed in vitro in neuronal cultures and in vivo in animal models. The spread of characteristic disease-related proteins drives the progression of pathology in many neurodegenerative diseases...
October 11, 2016: Cell Reports
Qing-Hua Cao, Fang Liu, Zu-Li Yang, Xin-Hui Fu, Zi-Huan Yang, Quentin Liu, Lei Wang, Xiang-Bo Wan, Xin-Juan Fan
Autophagy-related (ATG) genes contributed to tumorigenesis and cancer progression. This study aims to investigate the expression of ATG proteins and their clinicopathological significance in gastric cancer. Nine well-known ATG proteins, (ULK1, Beclin 1, ATG3, ATG5, ATG7, ATG9, ATG10, ATG12 and LC3B) and p62/SQSTM1, which represented key regulators that participated in whole autophagosomes stepwise processes, were detected in a large cohort of 352 primary gastric cancer patients. Among these 352 patients, 117 cases were randomly assigned to the training set to detect the clinicopathological value of ATG proteins, and another 235 patients were used as the testing set for further validation...
2016: American Journal of Translational Research
Rajeeve Sivadasan, Daniel Hornburg, Carsten Drepper, Nicolas Frank, Sibylle Jablonka, Anna Hansel, Xenia Lojewski, Jared Sterneckert, Andreas Hermann, Pamela J Shaw, Paul G Ince, Matthias Mann, Felix Meissner, Michael Sendtner
Intronic hexanucleotide expansions in C9ORF72 are common in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, but it is unknown whether loss of function, toxicity by the expanded RNA or dipeptides from non-ATG-initiated translation are responsible for the pathophysiology. We determined the interactome of C9ORF72 in motor neurons and found that C9ORF72 was present in a complex with cofilin and other actin binding proteins. Phosphorylation of cofilin was enhanced in C9ORF72-depleted motor neurons, in patient-derived lymphoblastoid cells, induced pluripotent stem cell-derived motor neurons and post-mortem brain samples from ALS patients...
October 10, 2016: Nature Neuroscience
Hironori Suzuki, Takuo Osawa, Yuko Fujioka, Nobuo N Noda
In autophagy, which is an intracellular degradation system that is conserved among eukaryotes, degradation targets are sequestered through the de novo synthesis of a double-membrane organelle, the autophagosome, which delivers them to the lysosomes for degradation. The core autophagy machinery comprising 18 autophagy-related (Atg) proteins in yeast plays an essential role in autophagosome formation; however, the molecular role of each Atg factor and the mechanism of autophagosome formation remain elusive. Recent years have seen remarkable progress in structural biological studies on the core autophagy machinery, opening new avenues for autophagy research...
October 7, 2016: Current Opinion in Structural Biology
Giuseppe Ronzitti, Giulia Bortolussi, Remco van Dijk, Fanny Collaud, Severine Charles, Christian Leborgne, Patrice Vidal, Samia Martin, Bernard Gjata, Marcelo Simon Sola, Laetitia van Wittenberghe, Alban Vignaud, Philippe Veron, Piter J Bosma, Andres F Muro, Federico Mingozzi
Crigler-Najjar syndrome is a severe metabolic disease of the liver due to a reduced activity of the UDP Glucuronosyltransferase 1A1 (UGT1A1) enzyme. In an effort to translate to the clinic an adeno-associated virus vector mediated liver gene transfer approach to treat Crigler-Najjar syndrome, we developed and optimized a vector expressing the UGT1A1 transgene. For this purpose, we designed and tested in vitro and in vivo multiple codon-optimized UGT1A1 transgene cDNAs. We also optimized noncoding sequences in the transgene expression cassette...
2016: Molecular Therapy. Methods & Clinical Development
X X Li, M Wang, Y Q Shao, N Nie, J Shi, Z D Huang, J Zhang, M L Ge, J B Huang, Y Z Zheng
Objective: To assess the clinical feature and outcomes of severe aplastic anemia (SAA) patients suffered from bacteremia following antithymocyte globulin (ATG). Methods: A total of 264 cases hospitalized in our hospital between Jan 2000 and July 2011 were enrolled into this study. We evaluated the associated pathogens of bacteremia, analyzed the risk factors by Logistic regression and estimated the overall survival (OS) by Kaplan-Meier method for the cohort of patients. Results: Bloodstream infections occurred in 49 patients, with a median age of 20 (4-62) years, including 38 cases with very SAA (VSAA) and 11 SAA patients...
September 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Hong-Hua Li, Fei Li, Chun-Ji Gao, Wen-Rong Huang, Jian Bo, Li-Ping Dou, Li-Li Wang, Yu Jing, Lu Wang, Wen-Jun Li, Li Yu, Dai-Hong Liu
The features of graft-versus-host disease (GVHD) were compared between patients who underwent myeloablative conditioning and received a peripheral blood stem cell transplant (PBSCT) from either a haploidentical donor (HID) or a matched sibling donor (MSD) during the same period of time. The HID group included more patients with advanced disease. Both groups received the same GVHD prophylaxis with the addition of antithymoglobulin (ATG) in HID group. Higher cumulative incidences (CI) of acute GVHD grade 2-4 (35·1% vs...
October 7, 2016: British Journal of Haematology
Yoko Karube, Yoshiyuki Ito, Morimichi Nishihira, Takashi Inoue, Osamu Araki, Sumiko Maeda, Satoshi Kobayashi, Masayuki Chida
A 58-year-old male underwent right lung transplantation from a brain-dead donor, after which acute rejection developed that was resistant to steroid pulse therapy. Rabbit-derived anti-thymocyte globulin (rATG) therapy was successful for controlling the rejection. However, following that therapy, the patient was affected by an opportunistic infection and suffered from repeated empyema. It is important to pay attention to immunosuppressive agent levels in blood following treatment, because ATG is a potent immunosuppressive drug and its effects can continue for more than 6 months after administration...
October 2016: Kyobu Geka. the Japanese Journal of Thoracic Surgery
Zhi Guo, Hong-Yan Gao, Tian-Yan Zhang, Xiao-Dong Liu, Kai Yang, Jing-Xing Lou, Xue-Peng He, Yuan Zhang, Peng Chen, Hui-Ren Chen
The study was aimed to explore the efficacy and safety of allo-HSCT with high-dose cyclophosphamide-induced immune tolerance for SAA. In the present study, 20 cases (12 male, 8 female; average age = 17.8 years) received reduced-intensity conditioning allo-HSCT from August 2012 to August 2014 in the Beijing Military Region General Hospital. All were HLA mismatched and received CSA; 11 received ATG-intensive immune therapy. Donors underwent mobilization with cell colony-stimulating factor. The modified preconditioning regimen included reduced-strength fludarabine combined with Busulfex and cytarabine, cyclophosphamide...
October 5, 2016: International Journal of Hematology
M Águila Ruiz-Sola, M Victoria Barja, David Manzano, Briardo Llorente, Bert Schipper, Jules Beekwilder, Manuel Rodriguez-Concepcion
A wide diversity of isoprenoids is produced in different plant compartments. Most groups of isoprenoids synthesized in plastids and some produced elsewhere in the plant cell derive from geranylgeranyl diphosphate (GGPP) synthesized by GGPP synthase (GGPPS) enzymes. In Arabidopsis thaliana, 5 genes appear to encode GGPPS isoforms localized in plastids (2), the endoplasmic reticulum (2), and mitochondria (1). However, the loss of function of the plastid-targeted GGPPS11 isoform (referred to as G11) is sufficient to cause lethality...
October 5, 2016: Plant Physiology
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