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https://www.readbyqxmd.com/read/28716709/isolation-and-characterization-of-the-5-flanking-region-of-the-human-pdxk-gene
#1
ShuoHao Huang, ZhengQing Liu, ZhenQiao Ma, JianYun Zhang, LongQuan Huang
Pyridoxal kinase is a key enzyme for the biosynthesis of pyridoxal 5'-phosphate. Pyridoxal 5'-phosphate is the catalytically active form of vitamin B6, and acts as a cofactor in >140 different enzyme reactions. It is still unknown how the kinase synthesis is regulated in the cells, and nothing has been reported about the gene promoter. In the present study, based on the bioinformatics analysis of the 5'-flanking region of the human PDXK gene, we cloned the promoter region by PCR. Through the construction of a series of luciferase expression vectors containing the human PDXK promoter region, we characterized the promoter in terms of its structure and function...
July 14, 2017: Gene
https://www.readbyqxmd.com/read/28716402/the-role-of-low-dose-anti-thymocyte-globulin-as-standard-prophylaxis-in-mismatched-and-matched-unrelated-hematopoietic-peripheral-stem-cell-transplantation-for-hematologic-malignancies
#2
Ioanna Sakellari, Ioannis Batsis, Zoi Bousiou, Despina Mallouri, Varnavas Constantinou, Eleni Gavriilaki, Christos Smias, Evangelia Yannaki, Panayotis Kaloyannidis, Giorgos Papaioannou, Niki Stavroyianni, Antonia Syrigou, Damianos Sotiropoulos, Asimina Fylaktou, Aliki Tsompanakou, Riad Saloum, Achilles Anagnostopoulos
INTRODUCTION: Anti-thymocyte globulin (ATG)-based immunosuppressive therapy is often used in allogeneic hematopoietic cell transplantation to reduce incidence and severity of graft-versus-host disease (GVHD). PATIENTS AND METHODS: In our observational study, ATG (rabbit, Thymoglobulin; Sanofi, 5 mg/kg) was administered as a standardized part of the conditioning in 97 patients with a median age of 34 years (range, 14-58 years), allotransplanted for hematologic malignancies from matched (8/8; n = 52) and allele or antigen mismatched (7/8; n = 43 and 6/8; n = 2) unrelated donors...
June 29, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28714944/impact-of-the-presence-of-hla-1-locus-mismatch-and-the-use-of-low-dose-antithymocyte-globulin-in-unrelated-bone-marrow-transplantation
#3
K Kawamura, J Kanda, S Fuji, M Murata, K Ikegame, K Yoshioka, T Fukuda, Y Ozawa, N Uchida, K Iwato, T Sakura, M Hidaka, H Hashimoto, T Ichinohe, Y Atsuta, Y Kanda
HLA 1-locus-mismatched unrelated donors (1MMUD) have been used in allogeneic hematopoietic stem cell transplantation (allo-HCT) for patients who lack an HLA-matched donor. We retrospectively analyzed 3313 patients with acute leukemia or myelodysplastic syndrome who underwent bone marrow transplantation from an HLA allele-matched unrelated donor (MUD) or 1MMUD between 2009 and 2014. We compared the outcomes of MUD (n=2089) and 1MMUD with antithymocyte globulin (ATG) (1MM-ATG(+); n=109) with those of 1MMUD without ATG (1MM-ATG(-); n=1115)...
July 17, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28713249/crispr-cas9-mediated-zebrafish-knock-in-as-a-novel-strategy-to-study-midbrain-hindbrain-boundary-development
#4
Gokul Kesavan, Avinash Chekuru, Anja Machate, Michael Brand
The midbrain-hindbrain boundary (MHB) acts as an organizer and controls the fate of neighboring cells to develop into either mesencephalic (midbrain) or metencephalic (hindbrain) cells by secreting signaling molecules like Wnt1 and Fgf8. The zebrafish is an excellent vertebrate model for studying MHB development due to the ease of gene manipulation and the possibility of following cellular dynamics and morphogenetic processes using live imaging. Currently, only very few reporter and/or Cre-driver lines are available to study gene expression at the MHB, hampering the understanding of MHB development, and traditional transgenic technologies using promoter/enhancer fragments or bacterial artificial chromosome (BAC)-mediated transgenesis often do not faithfully recapitulate endogenous expression patterns...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28712572/centriolar-satellites-control-gabarap-ubiquitination-and-gabarap-mediated-autophagy
#5
Justin Joachim, Minoo Razi, Delphine Judith, Martina Wirth, Emily Calamita, Vesela Encheva, Brian D Dynlacht, Ambrosius P Snijders, Nicola O'Reilly, Harold B J Jefferies, Sharon A Tooze
Autophagy maintains cellular health and homeostasis during stress by delivering cytosolic material captured by autophagosomes to lysosomes for degradation. Autophagosome formation is complex: initiated by the recruitment of autophagy (Atg) proteins to the formation site, it is sustained by activation of Atg proteins to allow growth and closure of the autophagosome. How Atg proteins are translocated to the forming autophagosome is not fully understood. Transport of the ATG8 family member GABARAP from the centrosome occurs during starvation-induced autophagosome biogenesis, but how centrosomal proteins regulate GABARAP localization is unknown...
July 10, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28711727/a-chemotherapy-only-regimen-of-busulfan-melphalan-and-fludarabine-and-rabbit-atg-followed-by-allogeneic-t-cell-depleted-hematopoietic-stem-cell-transplants-for-the-treatment-of-myeloid-malignancies
#6
Barbara Spitzer, Ann A Jakubowski, Esperanza B Papadopoulos, Kirsten Fuller, Patrick D Hilden, James W Young, Juliet Barker, Guenther Koehne, Miguel-Angel Perales, Katharine C Hsu, Marcel R M van den Brink, Nancy A Kernan, Susan E Prockop, Andromachi Scaradavou, Hugo Castro-Malaspina, Richard J O'Reilly, Farid Boulad
We sought to develop a myeloablative chemotherapeutic regimen to secure consistent engraftment of T-cell depleted (TCD) hematopoietic stem cell transplants (HSCT) without the need for total body irradiation, thereby reducing toxicity, while maintaining low rates of GvHD and without increasing relapse. We investigated the myeloablative combination of busulfan and melphalan, with the immunosuppressive agents fludarabine and rabbit anti-thymocyte gloubin (r-ATG) as cytoreduction prior to a T-cell depleted HSCT...
July 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28710132/autophagy-deficiency-compromises-alternative-pathways-of-respiration-following-energy-deprivation
#7
Jessica As Barros, João Henrique F Cavalcanti, David B Medeiros, Adriano Nunes-Nesi, Tamar Avin-Wittenberg, Alisdair R Fernie, Wagner Araujo
Under heterotrophic conditions carbohydrate oxidation inside the mitochondria is the primary energy source for cellular metabolism. However, during energy-limited conditions, alternative substrates are required to support respiration. Amino acid oxidation in plant cells plays a key role in this by generating electrons that can be transferred to the mitochondrial electron transport chain via the electron transfer flavoprotein/ubiquinone oxidoreductase system. Autophagy, a catabolic mechanism for macromolecule and protein recycling, allows the maintenance of amino acid pools and nutrient remobilization...
July 14, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28708266/belatacept-conversion-in-an-hiv-positive-kidney-transplant-recipient-following-anti-thymocyte-globulin-induction
#8
Samatha A Kuten, Samir J Patel, Ashvin Baru, A Osama Gaber, Rustin D Crutchley, Venkataraman Ramanathan, Richard J Knight
Herein, we describe a case of early belatacept conversion in a human immunodeficiency virus (HIV)-positive kidney transplant recipient in an effort to improve suboptimal graft function and avoid drug interactions following anti-thymocyte globulin (ATG) administration. We observed improvement in renal function without HIV disease progression or opportunistic infections. Donor-specific antibodies appeared shortly after conversion but cleared without intervention. This case highlights belatacept as a means to improve renal function and avoid significant drug interactions even following ATG induction...
July 14, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28705935/forkhead-box-o3-foxo3-regulates-kidney-tubular-autophagy-following-urinary-tract-obstruction
#9
Ling Li, Ronald Zviti, Catherine Ha, Zhao V Wang, Joseph A Hill, Fangming Lin
Autophagy has been shown to be important for normal homeostasis and adaptation to stress in the kidney. Yet, the molecular mechanisms regulating renal epithelial autophagy are not fully understood. Here, we explored the role of the stress-responsive transcription factor forkhead box O3 (FoxO3) in mediating injury-induced proximal tubular autophagy in mice with unilateral ureteral obstruction (UUO). We show that following UUO, FoxO3 is activated and displays nuclear expression in the hypoxic proximal tubules exhibiting high levels of autophagy...
July 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28704456/atg4-plays-an-important-role-in-efficient-expansion-of-autophagic-isolation-membranes-by-cleaving-lipidated-atg8-in-saccharomyces-cerevisiae
#10
Eri Hirata, Yoshikazu Ohya, Kuninori Suzuki
Autophagy, an intracellular degradation system, is highly conserved among eukaryotes from yeast to mammalian cells. In the yeast Saccharomyces cerevisiae, most Atg (autophagy-related) proteins, which are essential for autophagosome formation, are recruited to a restricted region close to the vacuole, termed the vacuole-isolation membrane contact site (VICS), upon induction of autophagy. Subsequently, the isolation membrane (IM) expands and sequesters cytoplasmic materials to become a closed autophagosome. In S...
2017: PloS One
https://www.readbyqxmd.com/read/28703794/impaired-autophagosome-clearance-contributes-to-neuronal-death-in-a-piglet-model-of-neonatal-hypoxic-ischemic-encephalopathy
#11
Derong Cui, Dawei Sun, Xintao Wang, Liye Yi, Ewa Kulikowicz, Michael Reyes, Junchao Zhu, Zeng-Jin Yang, Wei Jiang, Raymond C Koehler
To examine the temporal relationship of cortical autophagic flux with delayed neuronal cell death after hypoxia-ischemia (HI) in neonatal piglets. HI was produced with 45-min hypoxia and 7-min airway occlusion in 3-5-day-old piglets. Markers of autophagic, lysosomal and cell death signaling were studied via immunohistochemistry, immunoblotting, and histochemistry in piglet brains. In vitro, autophagy was impaired in cultured mouse cortical neurons treated with chloroquine with or without rapamycin for 1 d in the presence of Z-VAD-fmk, cyclosporine A, or vehicle control, and cell viability was assessed with the MTT assay...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28703297/neither-eosinophils-nor-neutrophils-require-atg5-dependent-autophagy-for-extracellular-dna-trap-formation
#12
Nina Germic, Darko Stojkov, Kevin Oberson, Shida Yousefi, Hans-Uwe Simon
The importance of extracellular traps (ETs) in innate immunity is well established, but the molecular mechanisms responsible for their formation remain unclear and in scientific dispute. ETs have been defined as extracellular DNA scaffolds associated with the granule proteins of eosinophils or neutrophils. They are capable of killing bacteria extracellularly. Based mainly on results with phosphoinositide 3-kinase (PI3K) inhibitors such as 3-methyladenine (3-MA) and wortmannin which are commonly used to inhibit autophagy, several groups have reported that autophagy is required for neutrophil extracellular trap (NET) formation...
July 13, 2017: Immunology
https://www.readbyqxmd.com/read/28700465/alemtuzumab-versus-antithymocyte-globulin-induction-therapies-in-kidney-transplantation-patients-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#13
Jianming Zheng, Wenli Song
Alemtuzumab (ALEM) is widely used as an induction therapy for organ transplantation, and numerous randomized controlled trials (RCTs) have been published to evaluate its efficacy and safety in kidney transplantation as compared with antithymocyte globulin (ATG). The purpose of this study was to compare the benefits and safety of ALEM with those of ATG for induction therapy.A systematic literature search in three electronic databases, including PubMed, EmBase, and Cochrane Library, since inception through October 2016, was conducted to identify potential RCTs for inclusion...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28692028/in-search-of-the-optimal-platform-for-post-allogeneic-sct-immunotherapy-in-relapsed-multiple-myeloma-a-systematic-review
#14
REVIEW
R Oostvogels, S M U Venema, M de Witte, R Raymakers, J Kuball, N Kröger, M C Minnema
Allogeneic stem cell transplantation (allo-SCT) has the potential to induce sustained remissions in patients with multiple myeloma (MM). Currently, allo-SCT is primarily performed in high-risk MM patients, most often in the setting of early relapse after first-line therapy with autologous SCT. However, the implementation of allo-SCT for MM is jeopardized by high treatment-related mortality (TRM) rates as well as high relapse rates. In this systematic review, we aimed to identify a safe allo-SCT strategy that has optimal 1-year results regarding mortality, relapse and severe GvHD, creating opportunities for post-transplantation strategies to maintain remissions in the high-risk group of relapsed MM patients...
July 10, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28689811/ampk-activation-ameliorates-d-galn-lps-induced-acute-liver-failure-by-upregulating-foxo3a-to-induce-autophagy
#15
Yan-Min Liu, Jun Lv, Qing-Lei Zeng, Shen Shen, Ji-Yuan Xing, Ying-Ying Zhang, Zhi-Hao Zhang, Zu-Jiang Yu
BACKGROUND AND AIM: Acute liver failure (ALF) is an uncommon but serious disease still carrying a high mortality. This study aimed to investigate the mechanism of AMPK on D-GalN/LPS-induced ALF. METHODS: In this study, we utilized intraperitoneal injection of D-GalN/LPS to induce ALF model, and analyzed the expression of AMPK, inflammatory cytokines (TNF-α, IL-1β and IL-6), Foxo3A and autophagy-related genes (Atg-5, Beclin-1, Atg-7) by real-time quantitative polymerase chain reaction (RT-PCR) in liver tissue...
July 6, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28683827/expanding-landscapes-of-the-diversified-mcr-1-bearing-plasmid-reservoirs
#16
Qingjing Wang, Jian Sun, Jun Li, Youfa Ding, Xing-Ping Li, Jingxia Lin, Bachar Hassan, Youjun Feng
BACKGROUND: Polymyxin is a cationic polypeptide antibiotic that can disrupt bacterial cell membrane by interacting with its lipopolysaccharide molecules and is used as a last resort drug against lethal infections by the carbapenem-resistant superbugs (like NDM-1). However, global discovery of the MCR-1 colistin resistance dramatically challenges the newly renewed interest in colistin for clinical use. METHODS: The mcr-1-harboring plasmids were acquired from swine and human Escherichia coli isolated in China, from 2015 to 2016, and subjected to Illumina PacBio RSII and Hi-Seq2000 for full genome sequencing...
July 6, 2017: Microbiome
https://www.readbyqxmd.com/read/28677782/nicd-inhibits-cell-proliferation-and-promotes-apoptosis-and-autophagy-in-pc12-cells
#17
Bo Li, Ping Duan, Xuefei Han, Wenhai Yan, Ying Xing
Pheochromocytoma is a tumor of the adrenal medulla for which surgical resection is the only therapy. Though the Notch1 signaling pathway has been suggested as a target for pheochromocytoma treatment, the effect of Notch1 intracellular domain (NICD) on pheochromocytoma cell growth remains unknown. In the present study, the effect of NICD on pheochromocytoma cell growth was examined, by use of a tetracycline‑inducible system for NICD overexpression in the PC12 pheochromocytoma cell line. Flow cytometry was used to determine the effect of NICD on cell cycle phase distribution and apoptosis in PC12 cells...
June 29, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28676397/feedback-autophagy-activation-as-a-key-resistance-factor-of-ku-0060648-in-colorectal-cancer-cells
#18
Mintao Mao, Yumei Liu, Xinhai Gao
The current study evaluated the potential anti-colorectal cancer (CRC) activity by Ku-0060648, a novel DNA-PKcs and PI3K duel inhibitor. In both CRC cell lines (HCT-116 and HT-29) and primary human colon cancer cells, Ku-0060648 exposure at nM concentrations efficiently inhibited cell proliferation. Meanwhile, Ku-0060648 provoked apoptosis in CRC cells. Ku-0060648 was yet ineffective to the normal colon epithelial cells. Ku-0060648 blocked PI3K-AKT-mTOR cascade and in-activated DNA-PKcs in CRC cells. Intriguingly, Ku-0060648 treatment induced feedback autophagy activation in HCT-116 cells...
July 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28670945/coinheritance-of-hb-bristol-alesha-%C3%AE-67-e11-val%C3%A2-met-hbb-c-202g-a-and-the-%C3%AE-212-patchwork-allele-in-a-brazilian-child-with-severe-congenital-hemolytic-anemia
#19
Gisele A Pedroso, Elza M Kimura, Magnun N N Santos, Dulcinéia M Albuquerque, Jucilane L H Ferruzzi, Susan E Jorge, Fernando F Costa, Sara T O Saad, Maria F Sonati
Hb Bristol-Alesha [HBB: c.202G>A; β 67 Val>Met] is a rare structural variant of hemoglobin (Hb) resulting from a GTG>ATG substitution at codon 67 of the β-globin gene that leads to the replacement of valine by methionine in the corresponding position of the β-globin chain. The methionine residue is subsequently modified to aspartic acid [β67(E11)Val-Met→Asp], possibly by autoxidation mechanisms. This substitution prevents normal non-polar binding of Val67 to the heme group, resulting in molecular instability and severe hemolysis...
July 3, 2017: Hemoglobin
https://www.readbyqxmd.com/read/28668491/validation-of-the-hematopoietic-cell-transplantation-specific-comorbidity-index-in-non-myeloablative-allogeneic-stem-cell-transplantation
#20
Muthu Veeraputhiran, Lingyao Yang, Vandana Sundaram, Sally Arai, Robert Lowsky, David Miklos, Everett Meyer, Lori Muffly, Robert Negrin, Andrew Rezvani, Judith Shizuru, Wen Kai Weng, Laura Johnston
The Hematopoietic cell transplant-comorbidity index (HCT-CI) has been extensively studied in myeloablative (MA) and reduced intensity conditioning (RIC) regimens with less available data regarding the validity of HCT-CI in non-myeloablative (NMA) allogeneic transplant. We conducted a retrospective analysis to evaluate the association between HCT-CI and non-relapse mortality (NRM) and all-cause mortality (ACM) in patients receiving the Total Lymphoid Irradiation and Anti-thymocyte Globulin (TLI/ATG) NMA transplant preparative regimen...
June 28, 2017: Biology of Blood and Marrow Transplantation
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