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https://www.readbyqxmd.com/read/28821454/low-dose-anti-thymocyte-globulin-for-graft-versus-host-disease-prophylaxis-in-matched-unrelated-allogeneic-hematopoietic-stem-cell-transplant
#1
A Bryant, R Mallick, L Huebsch, D Allan, H Atkins, G Anstee, M Sabloff, N Scrivens, D Maze, C Bredeson, N Kekre
Graft-versus-host disease (GVHD) is a leading cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (alloHCT). Prophylactic in-vivo T-Cell depletion with antithymocyte globulin (ATG) has been associated with decreased GVHD rates many alloHCT settings. Despite decades of clinical study, optimal ATG dosing has not been established. Understanding that higher rates of GVHD are observed with matched unrelated (MUD) versus matched related donor (MRD) alloHCT, at our institution MUD alloHSCT recipients have historically had low dose thymoglobulin (total dose 2...
August 15, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28820317/ulk1-ubiquitylation-is-regulated-by-phosphorylation-on-its-carboxy-terminus
#2
Francesca Nazio, Marianna Carinci, Francesco Cecconi
Autophagy is a highly conserved process that acts sequestering cytoplasmic components for their degradation by the lysosomes. It consists of several sequential steps that have to be finely regulated to ensure both its progression and termination. Post-translational modifications (PTMs) play an important role in regulating ATG proteins function in different stages of autophagy. Recently, we demonstrated that, during prolonged starvation, ULK1 protein is specifically ubiquitylated by NEDD4L, and that this regulation is important to protect cells against excessive autophagy...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28820286/autophagy-monitoring-and-autophagy-deficient-mice
#3
Akiko Kuma, Masaaki Komatsu, Noboru Mizushima
Discovery of yeast autophagy-related (ATG) genes and subsequent identification of their homologs in other organisms have enabled researchers to investigate physiological functions of macroautophagy/autophagy using genetic techniques. Specific identification of autophagy-related structures is important to evaluate autophagic activity, and specific ablation of autophagy-related genes is a critical means to determine the requirements of autophagy. Here, we review currently available mouse models, particularly focusing on autophagy (and mitophagy) indicator models and systemic autophagy-related gene-knockout mouse models...
August 18, 2017: Autophagy
https://www.readbyqxmd.com/read/28819706/generation-of-a-functional-humanized-delta-like-ligand-4-transgenic-mouse-model
#4
John Wiseman, Pernilla Gregersson, Johan Johansson, Kerstin Magnell, Fernanda Pilataxi, Chris Morehouse, Philip Brohawn, Nicholas Holoweckyj, Patrick Strout, Song Cho
Humanized mouse models are important tools in many areas of biological drug development including, within oncology research, the development of antagonistic antibodies that have the potential to block tumor growth by controlling vascularization and are key to the generation of in vivo proof-of-concept efficacy data. However, due to cross reactivity between human antibodies and mouse target such studies regularly require mouse models expressing only the human version of the target molecule. Such humanized knock-in/knock-out, KIKO, models are dependent upon the generation of homozygous mice expressing only the human molecule, compensating for loss of the mouse form...
August 17, 2017: Transgenic Research
https://www.readbyqxmd.com/read/28816597/the-ulk-complex-initiates-autophagosome-formation-at-phosphatidylinositol-synthase-enriched-er-subdomains
#5
Taki Nishimura, Noboru Mizushima
In our recent paper, we biochemically analyzed autophagosome-related membranes at the initiation stage of macroautophagy/autophagy using atg knockout (KO) cells and demonstrated that the ULK complex is recruited to 2 distinct membranes: the ER membrane and ATG9A-positive autophagosome precursors. We have also identified phosphatidylinositol synthase (PIS)-enriched ER subdomains as the initiation site of autophagosome formation. Based on these findings, we propose that the ULK complex, the PIS-enriched ER subdomain, and ATG9A vesicles together initiate autophagosome formation...
August 17, 2017: Autophagy
https://www.readbyqxmd.com/read/28815305/predictors-of-early-mortality-after-rabbit-antithymocyte-globulin-as-first-line-treatment-in-severe-aplastic-anemia
#6
Elias H Atta, Carlos B L Lima, Danielle S P Dias, Diego V Clé, Mariana M Bonduel, Gabriela B Sciuccati, Larissa A Medeiros, Michel M Oliveira, Marco A Salvino, Marlene P Garanito, Patricia B Blum Fonseca, Sara Teresinha O Saad, Rodrigo T Calado, Phillip Scheinberg
Despite being recommended as first-line immunosuppressive therapy in severe aplastic anemia (SAA), horse antithymocyte globulin (ATG) is still unavailable in many countries outside the USA. Rabbit ATG is more lymphocytoxic than horse ATG, and this might result in a higher incidence of severe infections and early mortality. This study was designed to identify the risk factors for early mortality and overall survival (OS) after rabbit ATG in patients with SAA. We retrospectively reviewed 185 patients with SAA who underwent rabbit ATG and cyclosporine...
August 16, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28806108/the-composition-of-a-protein-aggregate-modulates-the-specificity-and-efficiency-of-its-autophagic-degradation
#7
Gangming Zhang, Long Lin, Di Qi, Hong Zhang
The mechanism underlying autophagic degradation of a protein aggregate remains largely unknown. A family of receptor proteins that simultaneously bind to the cargo and the Atg8 family of autophagy proteins (such as the MAP1LC3/LC3 subfamily) has been shown to confer cargo selectivity. The selectivity and efficiency of protein aggregate removal is also modulated by scaffold proteins that interact with receptor proteins and ATG proteins. During C. elegans embryogenesis, autophagic clearance of the cargoes PGL-1 and PGL-3 requires the receptor protein SEPA-1 and the scaffold protein EPG-2...
August 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28799202/immune-tolerance-induced-by%C3%A2-platelet-targeted-factor-viii-gene-therapy-in-hemophilia-a-mice-is-cd4%C3%A2-t-cell-mediated
#8
Y Chen, X Luo, J A Schroeder, J Chen, C K Baumgartner, J Hu, Q Shi
BACKGROUND: Immune responses are a major concern in gene therapy. Our previous studies demonstrated that platelet-targeted FVIII (2bF8) gene therapy together with in vivo drug-selection of transduced cells can rescue the bleeding diathesis and induce immune tolerance in FVIII(null) mice. OBJECTIVE: To investigate whether non-selectable 2bF8 lentiviral vector (LV) for the induction of platelet-FVIII expression is sufficient to induce immune tolerance and how immune tolerance is induced after 2bF8LV gene therapy...
August 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28792688/uncritical-request-of-thyroid-laboratory-tests-may-result-in-a-major-societal-economic-burden-results-from-a-large-population-study-in-spain
#9
Maria Salinas, Maite Lopez-Garrigos, Emilio Flores, Carlos Leiva-Salinas
BACKGROUND: Our aim is to study the regional variability in the request of thyroid laboratory tests from primary care facilities in Spain and to investigate a potential inappropriate request and its economic societal impact. METHODS: Spain is divided into 17 autonomous communities (AACCs) which are in turn divided in Health Departments that cover a geographic area and its population and a laboratory that attends the needs of every inhabitant. Each participating laboratory was required to report the number of thyroid tests requested from primary care during year 2014 and to provide organizational data...
July 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28780238/tcr%C3%AE-%C3%AE-and-cd19-cell-depleted-haploidentical-and-mismatched-hematopoietic-stem-cell-transplantation-in-primary-immune-deficiency
#10
Ravi M Shah, Reem Elfeky, Zohreh Nademi, Waseem Qasim, Persis Amrolia, Robert Chiesa, Kanchan Rao, Giovanna Lucchini, Juliana M F Silva, Austen Worth, Dawn Barge, David Ryan, Jane Conn, Andrew J Cant, Roderick Skinner, Intan Juliana Abd Hamid, Terence Flood, Mario Abinun, Sophie Hambleton, Andrew R Gennery, Paul Veys, Mary Slatter
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is used as a therapeutic approach for primary immunodeficiencies (PIDs). The best outcomes have been achieved using HLA-matched donors, but when a matched donor is not available, a haploidentical or mismatched unrelated donor (mMUD) can be useful. Various strategies are used to mitigate the risk of graft versus host disease (GvHD) and rejection associated with such transplants. OBJECTIVE: We sought to evaluate the outcomes of haploidentical or mMUD HSCT after depleting GvHD causing TCRαβCD3+ cells from the graft...
August 2, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28777843/-genetic-and-prenatal-diagnosis-for-a-haemophilia-a-family-with-two-novel-mutations-of-f8-gene
#11
Tao Li, Qiaofang Hou, Hongyan Liu, Hai Xiao, Bo Zhang, Shiling Liu, Yanli Yang, Chaoyang Zhang, Xuebing Ding, Shixiu Liao
OBJECTIVE: To conduct genetic diagnosis for a family affected with hamophilia A. METHODS: Potential mutations of the F8 gene were analyzed with PCR and Sanger sequencing. Carriers of the mutation were identified through linkage analysis using short tandem repeat (STR) markers. Suspected mutations were verified among 100 healthy controls to rule out genetic polymorphism. Prenatal diagnosis was provided based on the above results. RESULTS: Sequencing analysis has identified two mutations, c...
August 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/28776957/hla-dpb1-519-01-a-new-allele-identified-by-sequence-based-typing-in-a-korean-individual
#12
Hyun-Jung Choi, Jisu Im, Jun-Hyung Lee, Soo-Hyun Kim, Myung-Geun Shin
The new allele DPB1*519:01 showed one nucleotide difference with DPB1*13:01:01 at codon 234 (GTG/ATG).
August 4, 2017: HLA
https://www.readbyqxmd.com/read/28752968/-effects-of-triptolide-on-the-autophagy-in-synovial-spleen-and-thymus-of-rats-with-adjuvant-arthritis
#13
Lei Wan, Jian Liu, Chuan-Bing Huang, Xiao-Jun Zhang, Ya-Li Wang, Ping-Heng Zhang, Yue Sun, Lei Liu
OBJECTIVE: To determine the effect of triptolide (TP) on the expression of ATG /LC3-Ⅱ Beclin1 in synovial, spleen, and thymusof rats with adjuvant arthritis (AA). METHODS: Rats were divided for four groups: normal control (NC), model control (MC), leflunomide (LEF) treatment, and triptolide (TP)treatment, with 12 rats in each group.The AA model was established through Freund's complete adjuvant (0.1 mL each) injection into the right foot plantar skin to introduce inflammation and 10 days of tail root injection of 0...
July 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28751901/functional-characterization-of-tasnrk2-8-promoter-in-response-to-abiotic-stresses-by-deletion-analysis-in-transgenic-arabidopsis
#14
Hongying Zhang, Ruilian Jing, Xinguo Mao
Drought, salinity, and cold are the major factors limiting wheat quality and productivity; it is thus highly desirable to characterize the abiotic-stress-inducible promoters suitable for the genetic improvement of plant resistance. The sucrose non-fermenting 1-related protein kinase 2 (SnRK2) family genes show distinct regulatory properties in response to abiotic stresses. The present study characterized the approximately 3000-bp upstream sequence (the 313 bp upstream of the ATG was the transcription start site) of the Triticum aestivum TaSnRK2...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28744965/expression-of-brpa-in-streptococcus-mutans-is-regulated-by-fnr-box-mediated-repression
#15
Sumei Liao, Arpan De, Tatyana Thompson, Lynne Chapman, Jacob P Bitoun, Xin Yao, Qingzhao Yu, Fangrui Ma, Zezhang T Wen
Our previous studies showed that brpA in S. mutans, which encodes a member of the LytR-CpsA-Psr family of proteins, can be cotranscribed with brpB upstream as a bicistronic operon, while the intergenic region also has strong promoter activity. To elucidate how brpA expression is regulated, the promoter regions were analyzed using PCR-based deletions and site-directed mutagenesis and a promoterless luciferase gene as a reporter. Allelic exchange mutagenesis was also used to examine genes encoding putative trans-acting factors, and the impact of such mutations on brpA expression was analyzed by reporter assays...
July 26, 2017: Molecular Oral Microbiology
https://www.readbyqxmd.com/read/28734275/low-level-of-autophagy-related-gene-10-atg10-expression-in-the-6-hydroxydopamine-rat-model-of-parkinson-s-disease
#16
Marzieh Shams Nooraei, Ali Noori-Zadeh, Shahram Darabi, Farzad Rajaei, Zohreh Golmohammadi, Hojjat Allah Abbaszadeh
Background: Autophagy is a mechanism disassembling the damaged organelles from the cell. This study attempted to examine the expression of several autophagy-related genes in Parkinson’s disease (PD) rat model. Methods: The male Wistar rats were divided into three groups as control, sham, and lesion. In the latter group, the PD rat model was induced by the injection of 6-hydroxydopamine in the striatum.The behavioral test was conducted one (baseline) and four weeks after the surgery through apomorphine hydrochloride...
July 23, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28734047/preselection-of-recombinant-gene-integration-sites-enabling-high-transcription-rates-in-cho-cells-using-alternate-start-codons-and-recombinase-mediated-cassette-exchange
#17
Martina Baumann, Elisabeth Gludovacz, Natalie Sealover, Scott Bahr, Henry George, Nan Lin, Kevin Kayser, Nicole Borth
Site-specific Recombinase Mediated Cassette Exchange (RMCE) enables the transfer of the gene of interest (GOI) into pre-selected genomic locations with defined expression properties. For the generation of recombinant production cell lines this has the advantage that screening for high transcription rates at the genome integration site would be required only once, with the possibility to reuse the selected site for new products. Here we describe a strategy that aims at the selection of transcriptionally active genome integration sites in Chinese Hamster Ovary (CHO) cells by using alternate start codons in the surface reporter protein CD4, in combination with FACS sorting for high expressers...
July 22, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28733114/targeting-heat-shock-factor-1-as-an-antiviral-strategy-against-dengue-virus-replication-in%C3%A2-vitro-and-in%C3%A2-vivo
#18
Tsung-Ting Tsai, Chia-Ling Chen, Cheng-Chieh Tsai, Chiou-Feng Lin
Fever onset is correlated with viremia in dengue virus (DENV) patients. Heat shock factor 1 (HSF1), a heat stress response host transcription factor, plays a crucial role in regulating multiple cellular functions, as well as the onset of infectious diseases. This study evaluated the role of HSF1 in DENV replication as a means of regulating DENV infection in vitro and in vivo. DENV infection activated HSF1 in both Ca(2+) and protein kinase A-dependent manners. Inhibiting HSF1 effectively reduced DENV replication, not only in THP-1 cells but also in primary human monocytes...
July 18, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28731207/polyclonal-and-monoclonal-antibodies-for-treating-acute-rejection-episodes-in-kidney-transplant-recipients
#19
REVIEW
Angela C Webster, Sunny Wu, Krishna Tallapragada, Min Young Park, Jeremy R Chapman, Sue J Carr
BACKGROUND: Registry data shows that the incidence of acute rejection has been steadily falling. Approximately 10% to 35% of kidney recipients will undergo treatment for at least one episode of acute rejection within the first post-transplant year. Treatment options include pulsed steroid therapy, the use of an antibody preparation, the alteration of background immunosuppression, or combinations of these options. Over recent years, new treatment strategies have evolved, and in many parts of the world there has been an increase in use of tacrolimus and mycophenolate and a reduction in the use of cyclosporin and azathioprine use as baseline immunosuppression to prevent acute rejection...
July 20, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28731173/anacardic-acid-induces-cell-apoptosis-of-prostatic-cancer-through-autophagy-by-er-stress-dapk3-akt-signaling-pathway
#20
Jing Tan, Xianzhen Jiang, Guangming Yin, Leye He, Jianye Liu, Zhi Long, Zhiqiang Jiang, Kun Yao
Anacardic acid, which is commonly seen in plants of Anacardiaceae, is an important composition of cashew, ginkgo leaf and fruit, and it has been suggested in previous research to show antitumor activity. The main aim of the present study was to evaluate the anticancer effects of anacardic acid on cell apoptosis of prostatic cancer and molecular mechanisms of this phenomenon. In this study we found that anacardic acid inhibited cell proliferation, induced apoptosis and caspase-3/9 activities and Bax protein expression of prostatic cancer...
July 20, 2017: Oncology Reports
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