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https://www.readbyqxmd.com/read/28345006/genome-wide-specificity-of-highly-efficient-talens-and-crispr-cas9-for-t-cell-receptor-modification
#1
Friederike Knipping, Mark J Osborn, Karl Petri, Jakub Tolar, Hanno Glimm, Christof von Kalle, Manfred Schmidt, Richard Gabriel
In T cells with transgenic high-avidity T cell receptors (TCRs), endogenous and transferred TCR chains compete for surface expression and may pair inappropriately, potentially causing autoimmunity. To knock out endogenous TCR expression, we assembled 12 transcription activator-like effector nucleases (TALENs) and five guide RNAs (gRNAs) from the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas9) system. Using TALEN mRNA, TCR knockout was successful in up to 81% of T cells...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28314239/likelihood-ratio-and-posterior-odds-in-forensic-genetics-two-sides-of-the-same-coin
#2
Amke Caliebe, Susan Walsh, Fan Liu, Manfred Kayser, Michael Krawczak
It has become widely accepted in forensics that, owing to a lack of sensible priors, the evidential value of matching DNA profiles in trace donor identification or kinship analysis is most sensibly communicated in the form of a likelihood ratio (LR). This restraint does not abate the fact that the posterior odds (PO) would be the preferred basis for returning a verdict. A completely different situation holds for Forensic DNA Phenotyping (FDP), which is aimed at predicting externally visible characteristics (EVCs) of a trace donor from DNA left behind at the crime scene...
March 6, 2017: Forensic Science International. Genetics
https://www.readbyqxmd.com/read/28256086/males-without-apparent-alloimmunization-could-have-hla-antibodies-that-recognize-target-hla-specificities-expressed-on-cells
#3
J Nakamura, F Nakajima, H Kamada, K Tadokoro, T Nagai, M Satake
BACKGROUND AND OBJECTIVES: Human leukocyte antigen (HLA) antibodies, which are involved in the development of transfusion-related side effects such as transfusion-related lung injury, are sometimes found in males without a history of alloimmunization (eg, transplantation and transfusion). Whether HLA antibodies in male donors can interact with their target HLA specificities expressed on cells have not been completely investigated. MATERIALS AND METHODS: The HLA antibodies detected in 7 male donors were characterized...
March 2, 2017: HLA
https://www.readbyqxmd.com/read/28252969/in-vitro-and-in-silico-tools-to-assess-extent-of-cellular-uptake-and-lysosomal-sequestration-of-respiratory-drugs-in-human-alveolar-macrophages
#4
Ayşe Ufuk, Frauke Assmus, Laura Francis, Jonathan Plumb, Valeriu Damian, Michael Gertz, J Brian Houston, Aleksandra Galetin
Accumulation of respiratory drugs in human alveolar macrophages (AMs) has not been extensively studied in vitro and in silico despite its potential impact on therapeutic efficacy and/or occurrence of phospholipidosis. The current study aims to characterize the accumulation and subcellular distribution of drugs with respiratory indication in human AMs and to develop an in silico mechanistic AM model to predict lysosomal accumulation of investigated drugs. The data set included 9 drugs previously investigated in rat AM cell line NR8383...
March 20, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28252345/evidence-of-stress-in-%C3%AE-cells-obtained-with-laser-capture-microdissection-from-pancreases-of-brain-dead-donors
#5
Aref Ebrahimi, Min-Ho Jung, Jonathan M Dreyfuss, Hui Pan, Dennis Sgroi, Susan Bonner-Weir, Gordon C Weir
Isolated islets used for transplantation are known to be stressed, which can result from the circumstances of death, in particular brain death, the preservation of the pancreas with its warm and cold ischemia, from the trauma of the isolation process, and the complex events that occur during tissue culture. The current study focused upon the events that occur before the islet isolation procedure. Pancreases were obtained from brain dead donors (n = 7) with mean age 50 (11) and normal pancreatic tissue obtained at surgery done for pancreatic neoplasms (n = 7), mean age 69 (9)...
March 4, 2017: Islets
https://www.readbyqxmd.com/read/28249957/a-case-based-analysis-of-whether-living-related-donors-listed-for-transplant-share-esrd-causes-with-their-recipients
#6
Arthur J Matas, Rebecca E Hays, Hassan N Ibrahim
BACKGROUND AND OBJECTIVES: Two recent studies reported increased risk of ESRD after kidney donation. In both, the majority of ESRD was seen in those donating to a relative. Confounding this observation is that, in the absence of donation, relatives of those with ESRD are at increased risk for ESRD. Understanding the pathogenesis and risk factors for postdonation ESRD is critical for both donor selection and counseling. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We hypothesized that if familial relationship was an important consideration in pathogenesis, the donor and linked recipient would share ESRD etiology...
March 1, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28248094/a-multidimensional-view-of-charge-transfer-excitons-at-organic-donor-acceptor-interfaces
#7
Ti Wang, Tika R Kafle, Bhupal Kattel, Wai-Lun Chan
How tightly bound charge transfer (CT) excitons dissociate at organic donor-acceptor interfaces has been a long-standing question in the organic photovoltaics community. Recently, it has been proposed that exciton delocalization reduces the exciton binding energy and promotes exciton dissociation. In order to understand this mechanism, it is critical to resolve the evolution of the exciton's binding energy and coherent size with femtosecond time resolution. However, because the coherent size is just a few nanometers, it presents a major experimental challenge to capture the CT process simultaneously in the energy, spatial, and temporal domains...
March 10, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28238510/piperazines-as-nootropic-agents-new-derivatives-of-the-potent-cognition-enhancer-dm235-carrying-hydrophilic-substituents
#8
Maria Vittoria Martino, Luca Guandalini, Lorenzo Di Cesare Mannelli, Marta Menicatti, Gianluca Bartolucci, Silvia Dei, Dina Manetti, Elisabetta Teodori, Carla Ghelardini, Maria Novella Romanelli
The piperazine ring of the potent nootropic drug DM235 has been decorated with H-bond donor and acceptor groups (CH2OH, CH2OMe, CH2OCOMe, COOEt); the aim was to insert new functional groups, suitable for further chemical manipulation. The influence of these modifications on nootropic activity was assessed by means of the mouse passive avoidance test; some of the newly synthesized molecules (alcohol 7b, acetate 8b and ester 10d) showed interesting in vivo potency. This makes it possible to use these functional groups for adding other residues, in order to increase molecular diversity, or for anchoring a biotin group, to obtain compounds useful to capture the biological target...
February 16, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28223278/impact-of-genetic-alterations-in-stem-cell-transplantation-for-myelodysplasia-and-secondary-acute-myeloid-leukemia
#9
Tetsuichi Yoshizato, Yasuhito Nannya, Yoshiko Atsuta, Yusuke Shiozawa, Yuka Iijima-Yamashita, Kenichi Yoshida, Yuichi Shiraishi, Hiromichi Suzuki, Yasunobu Nagata, Yusuke Sato, Nobuyuki Kakiuchi, Keitaro Matsuo, Makoto Onizuka, Keisuke Kataoka, Kenichi Chiba, Hiroko Tanaka, Hiroo Ueno, Masahiro M Nakagawa, Bartlomiej Przychodzen, Claudia Haferlach, Wolfgang Kern, Kosuke Aoki, Hidehiro Itonaga, Yoshinobu Kanda, Mikkael A Sekeres, Jaroslaw P Maciejewski, Torsten Haferlach, Yasushi Miyazaki, Keizo Horibe, Masashi Sanada, Satoru Miyano, Hideki Makishima, Seishi Ogawa
Genetic alterations, including mutations and copy number alterations, are central to the pathogenesis of myelodysplastic syndromes and related diseases (myelodysplasia), but their roles in allogeneic stem-cell transplantation have not fully been studied in a large cohort of patients. We enrolled 797 patients who had been diagnosed with myelodysplasia at initial presentation and received transplantation via the Japan Marrow Donor Program. Targeted-capture sequencing was performed to identify mutations in 69 genes, together with copy number alterations, whose effects on transplantation outcomes were investigated...
February 21, 2017: Blood
https://www.readbyqxmd.com/read/28219249/enhanced-photoelectrochemical-method-for-sensitive-detection-of-protein-kinase-a-activity-using-tio2-g-c3n4-pamam-dendrimer-and-alkaline-phosphatase
#10
Xue Li, Lusheng Zhu, Yunlei Zhou, Huanshun Yin, Shiyun Ai
A novel photoelectrochemical (PEC) assay is developed for sensitive detection of protein kinase A (PKA) activity based on PKA-catalyzed phosphorylation reaction in solution and signal amplification strategy triggered by PAMAM dendrimer and alkaline phosphatase (ALP). In this strategy, it is noteworthy at this point that PKA phosphorylation was achieved in solution instead of on the surface of the electrode, which has advantages of the good contact in reactants and simple experimental procedure. For immobilizing the phosphorylated peptide (P-peptide) on electrode surface, graphite-like carbon nitride (g-C3N4) and titanium dioxide (TiO2) complex is synthesized and characterized, which plays a significant role for TiO2 conjugating phosphate groups and g-C3N4 providing PEC signal...
February 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28218505/theoretically-manipulating-quantum-dots-on-two-dimensional-tio2-monolayer-for-effective-visible-light-absorption
#11
Ting Liao, Ziqi Sun, Shi Xue Dou
Low solar energy harvesting and conversion efficiency has become a major problem in solar energy science and engineering owing to the difficulty in capturing solar energy across the wide solar spectrum, especially in the visible light range. Inspired by the extraordinary properties of materials arising from decreased dimensions, in this study, we explore a nanocontact system formed by a two-dimensional (2D) TiO2 monolayer and II-VI semiconductor (CdX)13 (X = S, Se, and Te) nanocages for engineering the visible light absorption...
February 27, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28217846/enhanced-peroxidase-like-performance-of-gold-nanoparticles-by-hot-electrons
#12
Xinghua Xia, Chen Wang, Yi Shi, Xing-Guo Nie, Yuan-Yuan Dan, Jian Li
Enzyme mimics have been widely used as alternatives to natural enzymes. However, the catalytic performances of enzyme mimics are often decreased due to different spatial structures or absence of functional groups compared to natural enzymes. Herein, we report a highly efficient enzyme-like catalytic performance of gold nanoparticles (AuNPs) by visible light stimulation. The enzyme-like reaction is evaluated by the catalytic reaction of AuNPs oxidizing a typical chromogenic substrate 3, 3', 5, 5'-tetramethylbenzydine (TMB) with hydrogen peroxide as an oxidant...
February 20, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28216236/elimination-of-falsely-reactive-results-in-a-commercially-available-west-nile-virus-igm-capture-enzyme-linked-immunosorbent-assay-by-heterophilic-antibody-blocking-reagents
#13
Harry E Prince, Mary Lapé-Nixon, Tara S Givens, Tiffany Bradshaw, Marek J Nowicki
All sera initially reactive in the Focus Diagnostics West Nile virus IgM capture enzyme-linked immunosorbent assay (WNV IgM ELISA) must be retested with background subtraction to identify falsely-reactive (FR) samples due to antibodies that bind to immunoglobulins of other animal species (heterophilic antibodies). In some settings, such as pre-transplant testing of organ donors, the reporting delay associated with retesting can have an adverse impact on donor procurement and organ placement. We sought to determine if inclusion of heterophilic antibody blockers in assay conjugate could eliminate the nonspecific reactivity of FR samples...
February 16, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28214703/polyester-fabric-sheet-layers-functionalized-with-graphene-oxide-for-sensitive-isolation-of-circulating-tumor-cells
#14
Jiyoon Bu, Young Jun Kim, Yoon-Tae Kang, Tae Hee Lee, Jeongsuk Kim, Young-Ho Cho, Sae-Won Han
The metastasis of cancer is strongly associated with the spread of circulating tumor cells (CTCs). Based on the microfluidic devices, which offer rapid recovery of CTCs, a number of studies have demonstrated the potential of CTCs as a diagnostic tool. However, not only the insufficient specificity and sensitivity derived from the rarity and heterogeneity of CTCs, but also the high-cost fabrication processes limit the use of CTC-based medical devices in commercial. Here, we present a low-cost fabric sheet layers for CTC isolation, which are composed of polyester monofilament yarns...
February 12, 2017: Biomaterials
https://www.readbyqxmd.com/read/28213526/structural-and-mechanistic-insights-into-hemoglobin-catalyzed-hydrogen-sulfide-oxidation-and-the-fate-of-polysulfide-products
#15
Victor Vitvitsky, Pramod K Yadav, Sojin An, Javier Seravalli, Uhn-Soo Cho, Ruma Banerjee
Hydrogen sulfide is a cardioprotective signaling molecule but is toxic at elevated concentrations. Red blood cells can synthesize H2S but lacking organelles, cannot dispose off H2S via the mitochondrial sulfide oxidation pathway. We have recently shown that at high sulfide concentrations, ferric hemoglobin oxidizes H2S to a mixture of thiosulfate and iron-bound polysulfides in which the latter species predominates. Here, we report the crystal structure of human hemoglobin containing low-spin ferric sulfide, the first intermediate in heme-catalyzed sulfide oxidation...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28213525/conformational-profiling-of-the-at1-angiotensin-ii-receptor-reflects-biased-agonism-g-protein-coupling-and-cellular-context
#16
Dominic Devost, Rory Sleno, Darlaine Petrin, Alice Zhang, Yuji Shinjo, Rakan Okde, Junken Aoki, Asuka Inoue, Terence E Hebert
Here, we report the design and use of GPCR-based biosensors to monitor ligand-mediated conformational changes in receptors in intact cells. These biosensors use Bioluminescence Resonance Energy Transfer (BRET) with Renilla luciferase (RlucII) as an energy donor, placed at the distal end of the receptor C-tail and the small fluorescent molecule FlAsH, as an energy acceptor, its binding site inserted at different positions throughout the intracellular loops and carboxy-terminal tail of the angiotensin II type I receptor (AT1R)...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28211267/efficient-and-selective-uptake-of-tco4-by-a-cationic-metal-organic-framework-material-with-open-ag-sites
#17
Daopeng Sheng, Lin Zhu, Chao Xu, Chengliang Xiao, Yanlong Wang, Yaxing Wang, Lanhua Chen, Juan Diwu, Jing Chen, Zhifang Chai, Thomas E Albrecht-Schmitt, Shuao Wang
(99)Tc is one of the most problematic radioisotopes in used nuclear fuel owing to its combined features of high fission yield, long half-life, and high environmental mobility. There are only a handful of functional materials that can remove TcO4(-) anion from aqueous solution and identifying for new, stable materials with high anion-exchange capacities, fast kinetics, and good selectivity remains a challenge. We report here an 8-fold interpenetrated three-dimensional cationic metal-organic framework material, SCU-100, which is assembled from a tetradentate neutral nitrogen-donor ligand and two-coordinate Ag(+) cations as potential open metal sites...
March 21, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28177218/ultrasensitive-photoelectrochemical-biosensing-of-cell-surface-n-glycan-expression-based-on-the-enhancement-of-nanogold-assembled-mesoporous-silica-amplified-by-graphene-quantum-dots-and-hybridization-chain-reaction
#18
Shenguang Ge, Feifei Lan, Linlin Liang, Na Ren, Li Li, Haiyun Liu, Mei Yan, Jinghua Yu
An ultrasensitive photoelectrochemical (PEC) biosensor for N-glycan expression based on the enhancement of nanogold-assembled mesoporous silica nanoparticles (GMSNs) was fabricated, which also combined with multibranched hybridization chain reaction (mHCR) and graphene quantum dots (GQDs). In this work, the localized surface plasmon resonance, mHCR and GQDs-induced signal amplification strategies were integrated exquisitely and applied sufficiently. In the fabrication, after porous ZnO spheres immobilized on the Au nanorod-modified paper working electrode were sensitized by CdTe QDs, the GMSNs were assembled on the CdTe QDs...
March 1, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28167878/commercial-separation-systems-designed-for-preparation-of-platelet-rich-plasma-yield-differences-in-cellular-composition
#19
Ryan M Degen, Johnathan A Bernard, Kristin S Oliver, Joshua S Dines
BACKGROUND: The role of platelet-rich plasma (PRP) in the treatment of sport-related injuries is unclear, largely due to the heterogeneity of clinical results. This may relate to compositional differences in PRP from different separation systems. QUESTIONS/PURPOSES: This study aims to compare the composition of PRP produced with five different commercially available systems, focusing on cellular concentrations and pH. METHODS: Seven donors (41 ± 12 years) provided blood for PRP preparation using five systems (Arthrex Angel, Emcyte Genesis CS, Arteriocyte Magellan, Harvest SmartPrep, and Biomet GPS III)...
February 2017: HSS Journal: the Musculoskeletal Journal of Hospital for Special Surgery
https://www.readbyqxmd.com/read/28151033/graft-immunocomplex-capture-fluorescence-analysis-to-detect-donor-specific-antibodies-and-hla-antigen-complexes-in-the-allograft
#20
Tsukasa Nakamura, Hidetaka Ushigome, Kiyoko Watabe, Yui Imanishi, Koji Masuda, Takehisa Matsuyama, Shumpei Harada, Katsuhiro Koshino, Taku Iida, Shuji Nobori, Norio Yoshimura
BACKGROUND: Immunocomplex capture fluorescence analysis (ICFA) is an attractive method to detect donor-specific anti-HLA antibodies (DSA) and HLA antigen complexes. Currently, antibody-mediated rejection (AMR) due to DSA is usually diagnosed by C4d deposition and serological DSA detection. Conversely, there is a discrepancy between these findings frequently. Thereupon, our graft ICFA technique may contribute to establish the diagnosis of AMR. METHODS: Graft samples were obtained by a percutaneous needle biopsy...
February 2, 2017: Immunological Investigations
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