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https://www.readbyqxmd.com/read/27910942/improved-bi-allelic-modification-of-a-transcriptionally-silent-locus-in-patient-derived-ipsc-by-cas9-nickase
#1
Reto Eggenschwiler, Mohsen Moslem, Mariane Serra Fráguas, Melanie Galla, Oliver Papp, Maximilian Naujock, Ines Fonfara, Ingrid Gensch, Annabell Wähner, Abbas Beh-Pajooh, Claudio Mussolino, Marcel Tauscher, Doris Steinemann, Florian Wegner, Susanne Petri, Axel Schambach, Emmanuelle Charpentier, Toni Cathomen, Tobias Cantz
Homology directed repair (HDR)-based genome editing via selectable long flanking arm donors can be hampered by local transgene silencing at transcriptionally silent loci. Here, we report efficient bi-allelic modification of a silent locus in patient-derived hiPSC by using Cas9 nickase and a silencing-resistant donor construct that contains an excisable selection/counter-selection cassette. To identify the most active single guide RNA (sgRNA)/nickase combinations, we employed a lentiviral vector-based reporter assay to determine the HDR efficiencies in cella...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27909745/dechlorination-of-three-tetrachlorobenzene-isomers-by-contaminated-harbor-sludge-derived-enrichment-cultures-follows-thermodynamically-favorable-reactions
#2
Yue Lu, Javier Ramiro-Garcia, Pieter Vandermeeren, Steffi Herrmann, Danuta Cichocka, Dirk Springael, Siavash Atashgahi, Hauke Smidt
Dechlorination patterns of three tetrachlorobenzene isomers, 1,2,3,4-, 1,2,3,5-, and 1,2,4,5-TeCB, were studied in anoxic microcosms derived from contaminated harbor sludge. The removal of doubly, singly, and un-flanked chlorine atoms was noted in 1,2,3,4- and 1,2,3,5-TeCB fed microcosms, whereas only singly flanked chlorine was removed in 1,2,4,5-TeCB microcosms. The thermodynamically more favorable reactions were selectively followed by the enriched cultures with di- and/or mono-chlorobenzene as the main end products of the reductive dechlorination of all three isomers...
December 1, 2016: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27909647/what-is-direct-allorecognition
#3
REVIEW
Dominic A Boardman, Jacinta Jacob, Lesley A Smyth, Giovanna Lombardi, Robert I Lechler
Direct allorecognition is the process by which donor-derived major histocompatibility complex (MHC)-peptide complexes, typically presented by donor-derived 'passenger' dendritic cells, are recognised directly by recipient T cells. In this review, we discuss the two principle theories which have been proposed to explain why individuals possess a high-precursor frequency of T cells with direct allospecificity and how self-restricted T cells recognise allogeneic MHC-peptide complexes. These theories, both of which are supported by functional and structural data, suggest that T cells recognising allogeneic MHC-peptide complexes focus either on the allopeptides bound to the allo-MHC molecules or the allo-MHC molecules themselves...
2016: Current Transplantation Reports
https://www.readbyqxmd.com/read/27909435/immune-reconstitution-after-allogeneic-hematopoietic-stem-cell-transplantation
#4
REVIEW
Justyna Ogonek, Mateja Kralj Juric, Sakhila Ghimire, Pavankumar Reddy Varanasi, Ernst Holler, Hildegard Greinix, Eva Weissinger
The timely reconstitution and regain of function of a donor-derived immune system is of utmost importance for the recovery and long-term survival of patients after allogeneic hematopoietic stem cell transplantation (HSCT). Of note, new developments such as umbilical cord blood or haploidentical grafts were associated with prolonged immunodeficiency due to delayed immune reconstitution, raising the need for better understanding and enhancing the process of immune reconstitution and finding strategies to further optimize these transplant procedures...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27908288/granulocyte-macrophage-colony-stimulating-factor-receptor-%C3%AE-expression-and-its-targeting-in-antigen-induced-arthritis-and-inflammation
#5
Andrew D Cook, Cynthia Louis, Matthew J Robinson, Reem Saleh, Matthew A Sleeman, John A Hamilton
BACKGROUND: Blockade of granulocyte macrophage colony-stimulating factor (GM-CSF) and its receptor (GM-CSFRα) is being successfully tested in trials in rheumatoid arthritis (RA) with clinical results equivalent to those found with neutralization of the current therapeutic targets, TNF and IL-6. To explore further the role of GM-CSF as a pro-inflammatory cytokine, we examined the effect of anti-GM-CSFRα neutralization on myeloid cell populations in antigen-driven arthritis and inflammation models and also compared its effect with that of anti-TNF and anti-IL-6...
December 1, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27907920/aneuploidy-detection-and-mtdna-quantification-in-bovine-embryos-with-different-cleavage-onset-using-a-next-generation-sequencing-based-protocol
#6
Miroslav Hornak, David Kubicek, Petr Broz, Pavlina Hulinska, Katerina Hanzalova, Darren Griffin, Marie Machatkova, Jiri Rubes
Bovine embryos are now routinely used in agricultural systems as a means of disseminating superior genetics worldwide, ultimately with the aim of feeding an ever-growing population. Further investigations, common for human IVF embryos, thus have priority to improve cattle IVF, as has screening for aneuploidy (abnormal chromosome number). Although the incidence and consequences of aneuploidy are well documented in human preimplantation embryos, they are less well known for the embryos of other animals. To address this, we assessed aneuploidy levels in thirty-one 2-cell bovine embryos derived from early- and late-cleaving zygotes...
December 2, 2016: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/27907906/senescent-fibroblast-derived-chemerin-promotes-squamous-cell-carcinoma-migration
#7
Vida Farsam, Abhijit Basu, Martina Gatzka, Nicolai Treiber, Lars A Schneider, Medhanie A Mulaw, Tanja Lucas, Stefan Kochanek, Reinhard Dummer, Mitchell P Levesque, Meinhard Wlaschek, Karin Scharffetter-Kochanek
Aging is associated with a rising incidence of cutaneous squamous cell carcinoma (cSCC), an aggressive skin cancer with the potential for local invasion and metastasis. Acquisition of a senescence-associated secretory phenotype (SASP) in dermal fibroblasts has been postulated to promote skin cancer progression in elderly individuals. The underlying molecular mechanisms are largely unexplored. We show that Chemerin, a previously unreported SASP factor released from senescent human dermal fibroblasts, promotes cSCC cell migration, a key feature driving tumor progression...
November 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27907157/human-bone-derived-collagen-for-the-development-of-an-artificial-corneal-endothelial-graft-in-vivo-results-in-a-rabbit-model
#8
Natalia Vázquez, Manuel Chacón, Carlos A Rodríguez-Barrientos, Jesús Merayo-Lloves, Miguel Naveiras, Begoña Baamonde, Jose F Alfonso, Iriana Zambrano-Andazol, Ana C Riestra, Álvaro Meana
Corneal keratoplasty (penetrating or lamellar) using cadaveric human tissue, is nowadays the main treatment for corneal endotelial dysfunctions. However, there is a worldwide shortage of donor corneas available for transplantation and about 53% of the world's population have no access to corneal transplantation. Generating a complete cornea by tissue engineering is still a tough goal, but an endothelial lamellar graft might be an easier task. In this study, we developed a tissue engineered corneal endothelium by culturing human corneal endothelial cells on a human purified type I collagen membrane...
2016: PloS One
https://www.readbyqxmd.com/read/27906585/birth-of-cloned-microminipigs-derived-from-somatic-cell-nuclear-transfer-embryos-that-have-been-transiently-treated-with-valproic-acid
#9
Kazuchika Miyoshi, Hiroaki Kawaguchi, Kosuke Maeda, Masahiro Sato, Kohei Akioka, Michiko Noguchi, Masahisa Horiuchi, Akihide Tanimoto
In our previous study, we found that treatment of miniature pig somatic cell nuclear transfer (SCNT) embryos with 4 mM valproic acid (VPA), a histone deacetylase inhibitor, for 48 hours after activation enhanced blastocyst formation rate and octamer-binding transcription factor-3/4 (Oct-3/4) gene expression at the late blastocyst stage; however, the production of viable cloned pups failed, when those VPA-treated SCNT embryos were transferred to recipients. This failure suggests that the present VPA treatment is suboptimal...
November 2016: Cellular Reprogramming
https://www.readbyqxmd.com/read/27906583/isolation-of-bovine-skin-derived-precursor-cells-and-their-developmental-potential-after-nuclear-transfer
#10
Jiajia Xiao, Qiaoqiao Li, Pengxiang Qu, Zihan Zhang, Shaohui Pan, Yongsheng Wang, Yong Zhang
Nuclei from less differentiated stem cells yield high cloning efficiency. However, pluripotent stem cells are rather difficult to obtain from bovines. Skin-derived precursor (SKPs) cells exhibit a certain degree of pluripotency, which has been shown to enhance the efficiency of nuclear transfer (NT) in pigs. In this study, bovine SKPs were isolated and characterized. Results showed that bovine SKPs expressed nestin, fibronectin, vimentin, pluripotency-related genes, and characteristic neural crest markers, such as NGFR, PAX3, SOX9, SNAI2, and OCT4...
November 2016: Cellular Reprogramming
https://www.readbyqxmd.com/read/27906075/nuclear-bodies-reorganize-during-myogenesis-in-vitro-and-are-differentially-disrupted-by-expression-of-fshd-associated-dux4
#11
Sachiko Homma, Mary Lou Beermann, Bryant Yu, Frederick M Boyce, Jeffrey Boone Miller
BACKGROUND: Nuclear bodies, such as nucleoli, PML bodies, and SC35 speckles, are dynamic sub-nuclear structures that regulate multiple genetic and epigenetic processes. Additional regulation is provided by RNA/DNA handling proteins, notably TDP-43 and FUS, which have been linked to ALS pathology. Previous work showed that mouse cell line myotubes have fewer but larger nucleoli than myoblasts, and we had found that nuclear aggregation of TDP-43 in human myotubes was induced by expression of DUX4-FL, a transcription factor that is aberrantly expressed and causes pathology in facioscapulohumeral dystrophy (FSHD)...
December 1, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906005/the-role-of-nk-cells-in-hiv-1-protection-autologous-allogeneic-or-both
#12
REVIEW
Jef Hens, Wim Jennes, Luc Kestens
Natural killer (NK) cells specialize in killing virally infected- or tumor cells and are part of the innate immune system. The activational state of NK cells is determined by the balance of incoming activating and inhibitory signals mediated by receptor-ligand binding with the target cell. These receptor-ligand bonds mainly consist of the killer immunoglobulin-like receptors (KIR), which are expressed at the cell surface of NK cells, and their ligands: the highly variable human leukocyte antigen -class I molecules (HLA)...
March 18, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27904979/experimental-and-theoretical-studies-of-the-spectroscopic-properties-of-chalcone-derivatives
#13
Marek Pietrzak, Marek Józefowicz, Agnieszka Bajorek, Janina R Heldt
Newly synthesized, differently substituted chalcones (1,3-diaryl-2-propen-1-ones) have been studied using steady-state and time-resolved techniques combined with quantum-chemical modelling. To explore spectroscopic structure - property relationships the substituent (acceptor moiety) was chosen according to systematic variation in the Hammett parameter. It was shown that photophysical properties of the studied donor-acceptor (D-A) molecules can be predicted in terms of a simple model from the properties of individual chromophores (composite-model of decoupled moieties: donor (D) and acceptor (A))...
November 30, 2016: Journal of Fluorescence
https://www.readbyqxmd.com/read/27904085/antiviral-activity-and-molecular-geometry-of-some-new-symmetrical-tris-aminoalkyl-amine-derivatives
#14
Nobuko Mibu, Kazumi Yokomizo, Kana Murakami, Yurika Ono, Masato Ishimaru, Marie Otsubo, Hiroshi Inao, Yutaro Ono, Jian-Rong Zhou, Kunihiro Sumoto
We report the preparation of new tripodal receptor-type C3- and CS-symmetrical molecules constructed on a tris(2-aminoethyl)amine (TAEA) template. Both the anti-herpes simplex virus type 1 (anti-HSV-1) activity and cytotoxic activity of synthesized receptor-type derivatives were evaluated in order to find a characteristic structural feature for these bioactivities of compounds. Among the compounds of synthesized symmetrical TAEA-related derivatives, compound 13k showed high anti-HSV-1 activity (50% effective concentration (EC50)=16...
2016: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27903591/platelet-rich-plasma-powder-a-new-preparation-method-for-the-standardization-of-growth-factor-concentrations
#15
Matthias Kieb, Frank Sander, Cornelia Prinz, Stefanie Adam, Anett Mau-Möller, Rainer Bader, Kirsten Peters, Thomas Tischer
BACKGROUND: Platelet-rich plasma (PRP) is widely used in sports medicine. Available PRP preparations differ in white blood cell, platelet, and growth factor concentrations, making standardized research and clinical application challenging. PURPOSE: To characterize a newly standardized procedure for pooled PRP that provides defined growth factor concentrations. STUDY DESIGN: Controlled laboratory study. METHODS: A standardized growth factor preparation (lyophilized PRP powder) was prepared using 12 pooled platelet concentrates (PCs) derived from different donors via apheresis...
November 30, 2016: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/27901642/a-generic-rna-pulsed-dc-based-approach-for-developing-therapeutic-intervention-against-nasopharyngeal-carcinoma
#16
Rajeev K Tyagi, Rajesh Parmar, Naisargee Patel
The recurrent nasopharyngeal carcinoma of head-and-neck cancers pathology showed unique symptoms and clinical characteristics. The complexity of pathology poses challenges for developing therapeutic interventional approaches against nasopharyngeal carcinoma (NPC). The conventional treatment regimens offer limited local control and survival, which, leads to adverse delayed complications. Our study present a generic monocyte derived dendritic cell (MoDC) vaccine strategy for NPC in which RNA is used as a source of tumor-associated antigens (TAAgs)...
November 30, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27900891/chondrogenesis-of-human-adipose-derived-stem-cells-for-future-microtia-repair-using-co-culture-technique
#17
Bee See Goh, Siti Nurhadis Che Omar, Muhammad Azhan Ubaidah, Lokman Saim, Shamsul Sulaiman, Kien Hui Chua
CONCLUSION: In conclusion, these result showed HADSCs could differentiate into chondrocytes-like cells, dependent on signaling induced by TGF-β3 and chondrocytes. This is a promising result and showed that HADSCs is a potential source for future microtia repair. The technique of co-culture is a positive way forward to assist the microtia tissue. OBJECTIVE: Reconstructive surgery for the repair of microtia still remains the greatest challenge among the surgeons...
November 30, 2016: Acta Oto-laryngologica
https://www.readbyqxmd.com/read/27900319/spleen-dependent-immune-protection-elicited-by-cpg-adjuvanted-reticulocyte-derived-exosomes-from-malaria-infection-is-associated-with-changes-in-t-cell-subsets-distribution
#18
Lorena Martín-Jaular, Armando de Menezes-Neto, Marta Monguió-Tortajada, Aleix Elizalde-Torrent, Míriam Díaz-Varela, Carmen Fernández-Becerra, Francesc E Borras, Maria Montoya, Hernando A Del Portillo
Reticulocyte-derived exosomes (rex) are 30-100 nm membrane vesicles of endocytic origin released during the maturation of reticulocytes to erythrocytes upon fusion of multivesicular bodies with the plasma membrane. Combination of CpG-ODN with rex obtained from BALB/c mice infected with the reticulocyte-prone non-lethal P. yoelii 17X malaria strain (rexPy), had been shown to induce survival and long lasting protection. Here, we show that splenectomized mice are not protected upon rexPy+CpG inmunizations and that protection is restored upon passive transfer of splenocytes obtained from animals immunized with rexPy+CpG...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27898464/donor-derived-exosomes-the-trick-behind-the-semidirect-pathway-of-allorecognition
#19
Adrian E Morelli, William Bracamonte-Baran, William J Burlingham
PURPOSE OF REVIEW: The passenger leukocyte hypothesis predicts that after transplantation, donor antigen-presenting cells (APCs) from the graft present donor MHC molecules to directly alloreactive T cells in lymphoid organs. However, in certain transplantation models, recent evidence contradicts this long-standing concept. New findings demonstrate that host, instead of donor, APCs play a prominent role in allosensitization against donor MHC molecules via the semidirect pathway. A similar mechanism operates in development of T-cell split tolerance to noninherited maternal antigens...
November 24, 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27898462/recent-advances-in-allograft-vasculopathy
#20
Jonathan Merola, Daniel D Jane-Wit, Jordan S Pober
PURPOSE OF REVIEW: Despite considerable advances in controlling acute rejection, the longevity of cardiac and renal allografts remains significantly limited by chronic rejection in the form of allograft vasculopathy. This review discusses recently reported mechanistic insights of allograft vasculopathy pathogenesis as well as recent clinical evaluations of new therapeutic approaches. RECENT FINDINGS: Although adaptive immunity is the major driver of allograft vasculopathy, natural killer cells mediate vasculopathic changes in a transplanted mouse heart following treatment with donor-specific antibody (DSA)...
November 24, 2016: Current Opinion in Organ Transplantation
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