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https://www.readbyqxmd.com/read/28077684/targeting-aurora-kinase-a-and-jak2-prevents-gvhd-while-maintaining-treg-and-antitumor-ctl-function
#1
Brian C Betts, Anandharaman Veerapathran, Joseph Pidala, Hua Yang, Pedro Horna, Kelly Walton, Christopher L Cubitt, Steven Gunawan, Harshani R Lawrence, Nicholas J Lawrence, Said M Sebti, Claudio Anasetti
Graft-versus-host disease (GVHD) is a leading cause of nonrelapse mortality after allogeneic hematopoietic cell transplantation. T cell costimulation by CD28 contributes to GVHD, but prevention is incomplete when targeting CD28, downstream mammalian target of rapamycin (mTOR), or Aurora A. Likewise, interleukin-6 (IL-6)-mediated Janus kinase 2 (JAK2) signaling promotes alloreactivity, yet JAK2 inhibition does not eliminate GVHD. We provide evidence that blocking Aurora A and JAK2 in human T cells is synergistic in vitro, prevents xenogeneic GVHD, and maintains antitumor responses by cytotoxic T lymphocytes (CTLs)...
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28077653/characterizing-hiv-1-splicing-using-next-generation-sequencing
#2
Ann Emery, Shuntai Zhou, Elizabeth Pollom, Ronald Swanstrom
: Full-length HIV-1 RNA serves as the genome or as an mRNA, or this RNA undergoes splicing using four donors and ten acceptors to create over 50 physiologically relevant transcripts in two size classes (1.8 kb and 4 kb). We developed an assay using Primer ID-tagged deep sequencing to quantify HIV-1 splicing. Using the NL4-3 lab strain we found that A5 (env/nef) is the most commonly used acceptor (about 50%) with A3 (tat) the least used (about 3%). Two small exons are made when a splice to acceptor A1 or A2 is followed by activation of donor D2 or D3, and the high-level use of D2 and D3 dramatically reduces the amount of vif and vpr transcripts...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28067900/donor-cd19-car-t-cells-exert-potent-graft-versus-lymphoma-activity-with-diminished-graft-versus-host-activity
#3
Arnab Ghosh, Melody Smith, Scott E James, Marco L Davila, Enrico Velardi, Kimon V Argyropoulos, Gertrude Gunset, Fabiana Perna, Fabiana M Kreines, Emily R Levy, Sophie Lieberman, Hillary V Jay, Andrea Z Tuckett, Johannes L Zakrzewski, Lisa Tan, Lauren F Young, Kate Takvorian, Jarrod A Dudakov, Robert R Jenq, Alan M Hanash, Ana Carolina F Motta, George F Murphy, Chen Liu, Andrea Schietinger, Michel Sadelain, Marcel R M van den Brink
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies. However, graft-versus-host disease (GVHD) and relapse after allo-HSCT remain major impediments to the success of allo-HSCT. Chimeric antigen receptors (CARs) direct tumor cell recognition of adoptively transferred T cells. CD19 is an attractive CAR target, which is expressed in most B cell malignancies, as well as in healthy B cells. Clinical trials using autologous CD19-targeted T cells have shown remarkable promise in various B cell malignancies...
January 9, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28060070/enhancing-dmek-success-by-identifying-optimal-levels-of-trypan-blue-dye-application-to-donor-corneal-tissue
#4
Parag A Majmudar, Lauren Johnson
PURPOSE: The purpose of this study was to determine the correct concentration and duration of application of trypan blue dye to Descemet membrane endothelial keratoplasty (DMEK) donor corneal tissue before transplant to enhance visibility while minimizing damage to the tissue. METHODS: Corneas were precut for DMEK using an 8-mm punch, and each was stained with either 0.06% or 0.15% trypan blue for a duration of 1, 3, or 5 minutes. After staining, each tissue was placed in balanced salt solution and observed to determine how quickly the stain faded from the tissue using a grading system...
February 2017: Cornea
https://www.readbyqxmd.com/read/28053099/hcmv-specific-cd4-t-cells-are-poly-functional-and-can-respond-to-hcmv-infected-dendritic-cells-in-vitro
#5
Sarah E Jackson, George X Sedikides, Gavin M Mason, Georgina Okecha, Mark R Wills
: Human cytomegalovirus (HCMV) infection and periodic re-activation is generally well controlled by the HCMV-specific T cell response in healthy people. While the CD8+ T cell response to HCMV has been extensively studied, the HCMV-specific CD4+ T cell effector response is not as well understood, especially in the context of direct interactions with HCMV infected cells. We screened the IFNγ and IL-10 response to 6 HCMV peptide pools (selected as the most frequently responded to in our previous studies: pp65, pp71, IE1, IE2, gB and US3) in 84 donors, aged 23 - 74 years...
January 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28051311/versatile-self-adapting-boronic-acids-for-h-bond-recognition-from-discrete-to-polymeric-supramolecules
#6
Irene Georgiou, Simon Kervyn, Alexandre Rossignon, Federica De Leo, Johan Wouters, Gilles Bruylants, Davide Bonifazi
By taking advantage of the peculiar dynamic covalent reactivity of boronic acids to form tetraboronate derivatives, interest has risen to use the aryl derivatives in materials science and supramolecular chemistry, nevertheless their ability to form H-bonded complexes has been only marginally touched. Herein we report the first solution and solid-state binding studies of first double H-bonded DD•AA-type complexes of a series of aromatic boronic acids that adopt a synsyn conformation with suitable complementary H-bonding acceptor partners...
January 4, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28049640/cml-patients-with-deep-molecular-responses-to-tki-have-restored-immune-effectors-decreased-pd-1-and-immune-suppressors
#7
Amy Hughes, Jade Clarson, Carine Tang, Ljiljana Vidovic, Deborah L White, Timothy P Hughes, Agnes S M Yong
Immunological control may contribute to achievement of deep molecular response in chronic myeloid leukemia (CML) patients on tyrosine kinase inhibitor (TKI) therapy and may promote treatment free remission (TFR). We investigated effector and suppressor immune responses in CML patients at diagnosis (n=21), on TKI (imatinib, nilotinib, dasatinib) prior to achieving major molecular response (pre-MMR, BCR-ABL1 >0.1%, n=8), MMR (BCR-ABL1 ≤0.1%, n=20), molecular response(4.5) (MR(4.5), BCR-ABL1 ≤0.0032%, n=16) and sustained TFR (BCR-ABL1 undetectable following cessation of TKI therapy, n=13)...
January 3, 2017: Blood
https://www.readbyqxmd.com/read/28043045/continuous-removal-and-recovery-of-tellurium-in-an-upflow-anaerobic-granular-sludge-bed-reactor
#8
Joyabrata Mal, Yarlagadda V Nancharaiah, Neeraj Maheshwari, Eric D van Hullebusch, Piet N L Lens
Continuous removal of tellurite (TeO3(2-)) from synthetic wastewater and subsequent recovery in the form of elemental tellurium was studied in an upflow anaerobic granular sludge bed (UASB) reactor operated at 30°C. The UASB reactor was inoculated with anaerobic granular sludge and fed with lactate as carbon source and electron donor at an organic loading rate of 0.6g CODL(-1)d(-1). After establishing efficient and stable COD removal, the reactor was fed with 10mg TeO3(2-)L(-1) for 42 d before increasing the influent concentration to 20mg TeO3(2-)L(-1)...
December 26, 2016: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28038685/grafted-c-kit-ssea1-eye-wall-progenitor-cells-delay-retinal-degeneration-in-mice-by-regulating-neural-plasticity-and-forming-new-graft-to-host-synapses
#9
Xi Chen, Zehua Chen, Zhengya Li, Chen Zhao, Yuxiao Zeng, Ting Zou, Caiyun Fu, Xiaoli Liu, Haiwei Xu, Zheng Qin Yin
BACKGROUND: Despite diverse pathogenesis, the common pathological change observed in age-related macular degeneration and in most hereditary retinal degeneration (RD) diseases is photoreceptor loss. Photoreceptor replacement by cell transplantation may be a feasible treatment for RD. The major obstacles to clinical translation of stem cell-based cell therapy in RD remain the difficulty of obtaining sufficient quantities of appropriate and safe donor cells and the poor integration of grafted stem cell-derived photoreceptors into the remaining retinal circuitry...
December 30, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28038356/mrna-overexpression-of-the-hypoxia-inducible-factor-1-alpha-subunit-gene-hif1a-an-independent-predictor-of-poor-overall-survival-in-chronic-lymphocytic-leukemia
#10
Christos K Kontos, Sotirios G Papageorgiou, Marios A Diamantopoulos, Andreas Scorilas, Efthimia Bazani, Diamantina Vasilatou, Konstantinos Gkontopoulos, Eirini Glezou, Georgia Stavroulaki, George Dimitriadis, Vasiliki Pappa
The hypoxia inducible factor 1 (HIF1) is a heterodimeric transcription factor that ultimately regulates cellular responses to changes in oxygen tension. In this study, we examined the potential diagnostic and prognostic potential of the mRNA expression of HIF1 regulatory α-subunit (HIF1A) in chronic lymphocytic leukemia (CLL). For this purpose, total RNA was isolated from peripheral blood mononuclear cells collected from 88 CLL patients and 33 non-leukemic blood donors, and poly(A)-RNA was reversely transcribed...
November 29, 2016: Leukemia Research
https://www.readbyqxmd.com/read/28017796/analysis-of-transcriptional-variability-in-a-large-human-ipsc-library-reveals-genetic-and-non-genetic-determinants-of-heterogeneity
#11
Ivan Carcamo-Orive, Gabriel E Hoffman, Paige Cundiff, Noam D Beckmann, Sunita L D'Souza, Joshua W Knowles, Achchhe Patel, Dimitri Papatsenko, Fahim Abbasi, Gerald M Reaven, Sean Whalen, Philip Lee, Mohammad Shahbazi, Marc Y R Henrion, Kuixi Zhu, Sven Wang, Panos Roussos, Eric E Schadt, Gaurav Pandey, Rui Chang, Thomas Quertermous, Ihor Lemischka
Variability in induced pluripotent stem cell (iPSC) lines remains a concern for disease modeling and regenerative medicine. We have used RNA-sequencing analysis and linear mixed models to examine the sources of gene expression variability in 317 human iPSC lines from 101 individuals. We found that ∼50% of genome-wide expression variability is explained by variation across individuals and identified a set of expression quantitative trait loci that contribute to this variation. These analyses coupled with allele-specific expression show that iPSCs retain a donor-specific gene expression pattern...
December 2, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/28002433/a-therapeutic-uricase-with-reduced-immunogenicity-risk-and-improved-development-properties
#12
Andrew C Nyborg, Chris Ward, Anna Zacco, Benoy Chacko, Luba Grinberg, James C Geoghegan, Ryan Bean, Michaela Wendeler, Frank Bartnik, Ellen O'Connor, Flaviu Gruia, Vidyashankara Iyer, Hui Feng, Varnika Roy, Mark Berge, Jeffrey N Miner, David M Wilson, Dongmei Zhou, Simone Nicholson, Clynn Wilker, Chi Y Wu, Susan Wilson, Lutz Jermutus, Herren Wu, David A Owen, Jane Osbourn, Steven Coats, Manuel Baca
Humans and higher primates are unique in that they lack uricase, the enzyme capable of oxidizing uric acid. As a consequence of this enzyme deficiency, humans have high serum uric acid levels. In some people, uric acid levels rise above the solubility limit resulting in crystallization in joints, acute inflammation in response to those crystals causes severe pain; a condition known as gout. Treatment for severe gout includes injection of non-human uricase to reduce serum uric acid levels. Krystexxa® is a hyper-PEGylated pig-baboon chimeric uricase indicated for chronic refractory gout that induces an immunogenic response in 91% of treated patients, including infusion reactions (26%) and anaphylaxis (6...
2016: PloS One
https://www.readbyqxmd.com/read/28000672/a-small-electron-donor-in-cobalt-complex-electrolyte-significantly-improves-efficiency-in-dye-sensitized-solar-cells
#13
Yan Hao, Wenxing Yang, Lei Zhang, Roger Jiang, Edgar Mijangos, Yasemin Saygili, Leif Hammarström, Anders Hagfeldt, Gerrit Boschloo
Photoelectrochemical approach to solar energy conversion demands a kinetic optimization of various light-induced electron transfer processes. Of great importance are the redox mediator systems accomplishing the electron transfer processes at the semiconductor/electrolyte interface, therefore affecting profoundly the performance of various photoelectrochemical cells. Here, we develop a strategy-by addition of a small organic electron donor, tris(4-methoxyphenyl)amine, into state-of-art cobalt tris(bipyridine) redox electrolyte-to significantly improve the efficiency of dye-sensitized solar cells...
December 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27983801/resonance-energy-transfer-in-upconversion-nanoplatforms-for-selective-biodetection
#14
Qianqian Su, Wei Feng, Dongpeng Yang, Fuyou Li
Resonance energy transfer (RET) describes the process that energy is transferred from an excited donor to an acceptor molecule, leading to a reduction in the fluorescence emission intensity of the donor and an increase in that of the acceptor. By this technique, measurements with the good sensitivity can be made about distance within 1 to 10 nm under physiological conditions. For this reason, the RET technique has been widely used in polymer science, biochemistry, and structural biology. Recently, a number of RET systems incorporated with nanoparticles, such as quantum dots, gold nanoparticles, and upconversion nanoparticles, have been developed...
December 16, 2016: Accounts of Chemical Research
https://www.readbyqxmd.com/read/27980834/-n-n-bis-2-hy-droxy-eth-yl-di-thio-carbamato-%C3%AE%C2%BA-2-s-s-bis-tri-phenyl-phosphane-%C3%AE%C2%BAp-copper-i-chloro-form-monosolvate-crystal-structure-hirshfeld-surface-analysis-and-solution-nmr-measurements
#15
Sang Loon Tan, Chien Ing Yeo, Peter J Heard, Geoffrey R Akien, Nathan R Halcovitch, Edward R T Tiekink
The title compound, [Cu(C5H5NO2S2)(C18H15P)2]·CHCl3, features a tetra-hedrally coordinated Cu(I) atom within a P2S2 donor set defined by two phosphane P atoms and by two S atoms derived from a symmetrically coordinating di-thio-carbamate ligand. Both intra- and inter-molecular hy-droxy-O-H⋯O(hydroxy) hydrogen bonding is observed: the former closes an eight-membered {⋯HOC2NC2O} ring, whereas the latter connects centrosymmetrically related mol-ecules into dimeric aggregates via eight-membered {⋯H-O⋯H-O}2 synthons...
December 1, 2016: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/27979997/glycosyltransfer-in-mutants-of-putative-catalytic-residue-glu303-of-the-human-abo-h-a-and-b-blood-group-glycosyltransferases-gta-and-gtb-proceeds-through-a-labile-active-site
#16
Ryan J Blackler, Susannah M L Gagnon, Robert Polakowski, Natisha L Rose, Ruixiang B Zheng, James A Letts, Asha R Johal, Brock Schuman, Svetlana N Borisova, Monica M Palcic, Stephen V Evans
The homologous glycosyltransferases α-1,3-N-acetylgalactosaminyltransferase (GTA) and α-1,3-galactosyltransferase (GTB) carry out the final synthetic step of the closely related human ABO(H) blood group A and B antigens. The catalytic mechanism of these model retaining enzymes remains under debate, where Glu303 has been suggested to act as a putative nucleophile in a double displacement mechanism, a local dipole stabilizing the intermediate in an orthogonal associative mechanism or a general base to stabilize the reactive oxocarbenium ion-like intermediate in an S N i-like mechanism...
November 22, 2016: Glycobiology
https://www.readbyqxmd.com/read/27943656/decellularisation-of-human-donor-aortic-and-pulmonary-valved-conduits-using-low-concentration-sds
#17
Tayyebeh Vafaee, Daniel Thomas, Amisha Desai, Louise M Jennings, Helen Berry, Paul Rooney, John Kearney, John Fisher, Eileen Ingham
The clinical use of decellularised cardiac valve allografts is increasing. Long term data will be required to determine whether they outperform conventional cryopreserved allografts. Valves decellularised using different processes may show varied long-term outcomes. It is therefore important to understand the effects of specific decellularisation technologies on the characteristics of donor heart valves. Human cryopreserved aortic and pulmonary valved conduits were decellularised using hypotonic buffer, 0.1% (w/v) SDS and nuclease digestion...
December 12, 2016: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/27941802/influence-of-donor-age-on-induced-pluripotent-stem-cells
#18
Valentina Lo Sardo, William Ferguson, Galina A Erikson, Eric J Topol, Kristin K Baldwin, Ali Torkamani
Induced pluripotent stem cells (iPSCs) are being pursued as a source of cells for autologous therapies, many of which will be aimed at aged patients. To explore the impact of age on iPSC quality, we produced iPSCs from blood cells of 16 donors aged 21-100. We find that iPSCs from older donors retain an epigenetic signature of age, which can be reduced through passaging. Clonal expansion via reprogramming also enables the discovery of somatic mutations present in individual donor cells, which are missed by bulk sequencing methods...
January 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/27938949/dual-purpose-corneal-tissue-for-anterior-lamellar-keratoplasty-and-descemet-s-membrane-endothelial-keratoplasty
#19
C Larena Menant-Tay, Ronan Conlon, Salina Teja, Season Yeung, Joshua Teichman, Setareh Ziai, Kashif Baig
OBJECTIVE: To assess the intraoperative issues and surgical outcomes of preparing a single-donor corneal tissue for same-day use in both deep anterior lamellar keratoplasty (DALK) and Descemet's membrane endothelial keratoplasty (DMEK). DESIGN: Consecutive retrospective case series. PARTICIPANTS: Ten eyes of 10 patients who underwent DALK (5 patients) or DMEK (5 patients) surgery using dual-purpose corneal tissue. METHODS: Five dual-purpose corneoscleral rims were used to prepare tissue for 5 DMEK and 5 DALK procedures...
December 2016: Canadian Journal of Ophthalmology. Journal Canadien D'ophtalmologie
https://www.readbyqxmd.com/read/27932164/retzius-space-preservation-technique-for-robotic-assisted-laparoscopic-radical-prostatectomy-in-a-kidney-transplant-patient-first-case-in-thailand-and-our-first-experience
#20
P Jenjitranant, P Sangkum, P Sirisreetreerux, W Viseshsindh, S Patcharatrakul, W Kongcharoensombat
OBJECTIVE: The aim of this work was to report our experience in robotic-assisted laparoscopic radical prostatectomy for the treatment of localized prostate cancer in a kidney transplant recipient. METHODS: A 73-year-old man with chronic renal failure underwent living-donor kidney transplantation (KT) in 1993. His baseline creatinine after KT was ∼1.2 mg/dL. He developed lower urinary tract symptoms in 1999. He was diagnosed with benign prostatic hyperplasia and treated accordingly...
November 2016: Transplantation Proceedings
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