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Xiaosa Li, Ying Wang, Yajing Liu, Bei Yang, Xiao Wang, Jia Wei, Zongyang Lu, Yuxi Zhang, Jing Wu, Xingxu Huang, Li Yang, Jia Chen
The targeting range of CRISPR-Cas9 base editors (BEs) is limited by their G/C-rich protospacer-adjacent motif (PAM) sequences. To overcome this limitation, we developed a CRISPR-Cpf1-based BE by fusing the rat cytosine deaminase APOBEC1 to a catalytically inactive version of Lachnospiraceae bacterium Cpf1. The base editor recognizes a T-rich PAM sequence and catalyzes C-to-T conversion in human cells, while inducing low levels of indels, non-C-to-T substitutions and off-target editing.
March 19, 2018: Nature Biotechnology
Angélique Rousseau, Stéphanie La Carbona, Aurélien Dumètre, Lucy J Robertson, Gilles Gargala, Sandie Escotte-Binet, Loïc Favennec, Isabelle Villena, Cédric Gérard, Dominique Aubert
Giardia duodenalis, Cryptosporidium spp. and Toxoplasma gondii are protozoan parasites that have been highlighted as emerging foodborne pathogens by the Food and Agriculture Organization of the United Nations and the World Health Organization. According to the European Food Safety Authority, 4786 foodborne and waterborne outbreaks were reported in Europe in 2016, of which 0.4% were attributed to parasites including Cryptosporidium, Giardia and Trichinella. Until 2016, no standardized methods were available to detect Giardia, Cryptosporidium and Toxoplasma (oo)cysts in food...
2018: Parasite: Journal de la Société Française de Parasitologie
Aisha Nazli, Sara Dizzell, Muhammad Atif Zahoor, Victor H Ferreira, Jessica Kafka, Matthew William Woods, Michel Ouellet, Ali A Ashkar, Michel J Tremblay, Dawn Me Bowdish, Charu Kaushic
More than 40% of HIV infections occur via female reproductive tract (FRT) through heterosexual transmission. Epithelial cells that line the female genital mucosa are the first line of defense against HIV-1 and other sexually transmitted pathogens. These sentient cells recognize and respond to external stimuli by induction of a range of carefully balanced innate immune responses. Previously, we have shown that in response to HIV-1 gp120, the genital epithelial cells (GECs) from upper reproductive tract induce an inflammatory response that may facilitate HIV-1 translocation and infection...
March 19, 2018: Cellular & Molecular Immunology
Damianos G Kokkinidis, Bejan Alvandi, Prio Hossain, T Raymond Foley, Caitlin E Kielhorn, Gagan D Singh, Stephen W Waldo, John R Laird, Ehrin J Armstrong
PURPOSE: To evaluate the association between a chronic total occlusion (CTO) and long-term outcomes among patients undergoing endovascular intervention to the external iliac artery (EIA). METHODS: A 2-center retrospective study was conducted of 331 patients (mean age 64.7±12.7 years; 221 men) who underwent endovascular intervention for 481 EIA atherosclerotic lesions between 2006 and 2016. A quarter of the lesions (115, 23.9%) were CTOs. The majority of patients (184, 60...
April 2018: Journal of Endovascular Therapy
Franziska Krieg, Stefan T Ochsenbein, Sergii Yakunin, Stephanie Ten Brinck, Philipp Aellen, Adrian Süess, Baptiste Clerc, Dominic Guggisberg, Olga Nazarenko, Yevhen Shynkarenko, Sudhir Kumar, Chih-Jen Shih, Ivan Infante, Maksym V Kovalenko
Colloidal lead halide perovskite nanocrystals (NCs) have recently emerged as versatile photonic sources. Their processing and optoelectronic applications are hampered by the loss of colloidal stability and structural integrity due to the facile desorption of surface capping molecules during isolation and purification. To address this issue, herein, we propose a new ligand capping strategy utilizing common and inexpensive long-chain zwitterionic molecules such as 3-( N , N -dimethyloctadecylammonio)propanesulfonate, resulting in much improved chemical durability...
March 9, 2018: ACS Energy Letters
Zhongzhen Yi, Brooke L Prinzing, Felicia Cao, Stephen Gottschalk, Giedre Krenciute
Glioblastoma is the most aggressive primary brain tumor in humans and is virtually incurable with conventional therapies. Chimeric antigen receptor (CAR) T cell therapy targeting the glioblastoma antigen EphA2 is an attractive approach to improve outcomes because EphA2 is expressed highly in glioblastoma but only at low levels in normal brain tissue. Building upon our previous findings in this area, we generated and evaluated a panel of EphA2-specific CARs. We demonstrate here that T cells expressing CD28...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
Henrieta Fraser, Niloufar Safinia, Nathali Grageda, Sarah Thirkell, Katie Lowe, Laura J Fry, Cristiano Scottá, Andrew Hope, Christopher Fisher, Rachel Hilton, David Game, Paul Harden, Andrew Bushell, Kathryn Wood, Robert I Lechler, Giovanna Lombardi
The concept of regulatory T cell (Treg)-based immunotherapy has enormous potential for facilitating tolerance in autoimmunity and transplantation. Clinical translation of Treg cell therapy requires production processes that satisfy the rigors of Good Manufacturing Practice (GMP) standards. In this regard, we report our findings on the implementation of a robust GMP compliant process for the ex vivo expansion of clinical grade Tregs, demonstrating the feasibility of this developed process for the manufacture of a final product for clinical application...
March 16, 2018: Molecular Therapy. Methods & Clinical Development
John E Mullinax, MacLean Hall, Sangeetha Prabhakaran, Jeffrey Weber, Nikhil Khushalani, Zeynep Eroglu, Andrew S Brohl, Joseph Markowitz, Erica Royster, Allison Richards, Valerie Stark, Jonathan S Zager, Linda Kelley, Cheryl Cox, Vernon K Sondak, James J Mulé, Shari Pilon-Thomas, Amod A Sarnaik
Purpose: Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) for metastatic melanoma can be highly effective, but attrition due to progression before TIL administration (32% in prior institutional experience) remains a limitation. We hypothesized that combining ACT with cytotoxic T lymphocyte-associated antigen 4 blockade would decrease attrition and allow more patients to receive TIL. Experimental design: Thirteen patients with metastatic melanoma were enrolled...
2018: Frontiers in Oncology
Jungeun Won, Guillermo L Monroy, Pin-Chieh Huang, Roshan Dsouza, Malcolm C Hill, Michael A Novak, Ryan G Porter, Eric Chaney, Ronit Barkalifa, Stephen A Boppart
Pneumatic otoscopy to assess the mobility of the tympanic membrane (TM) is a highly recommended diagnostic method of otitis media (OM), a widespread middle ear infection characterized by the fluid accumulation in the middle ear. Nonetheless, limited depth perception and subjective interpretation of small TM displacements have challenged the appropriate and efficient examination of TM dynamics experienced during OM. In this paper, a pneumatic otoscope integrated with low coherence interferometry (LCI) was adapted with a controlled pressure-generating system to record the pneumatic response of the TM and to estimate middle ear pressure (MEP)...
February 1, 2018: Biomedical Optics Express
Cecilia T Costiniuk, Vikram Mehraj, Jean-Pierre Routy, Christina de Castro, Natale Wasef, Mohammad-Ali Jenabian, Syim Salahuddin, Bertrand Lebouché, Joseph Cox, Jason Szabo, Marina Klein, Larry Lands, Adam J Shapiro
Introduction: Low levels of nasal NO have been associated with increased propensity to rhinosinusitis and respiratory tract infections. Our objective was to describe nasal NO levels in HIV-infected individuals versus healthy controls and determine possible risk factors for reduced nasal NO levels. Materials and Methods: HIV-infected individuals and healthy controls were recruited. Participants underwent nasal NO testing by standardized methods using a CLD88 chemiluminescence analyzer and completed the Sinonasal Outcome Test-20 (SNOT-20) on symptoms of rhinosinusitis...
2018: AIDS Research and Treatment
Tong-Yun Wang, Yong-Gang Liu, Liang Li, Gang Wang, Hai-Ming Wang, Hong-Liang Zhang, Shi-Fei Zhao, Jia-Cong Gao, Tong-Qing An, Zhi-Jun Tian, Yan-Dong Tang, Xue-Hui Cai
Porcine reproductive and respiratory syndrome virus (PRRSV) is a problematic virus that is difficult to control. The principal target cells for PRRSV infection are porcine alveolar macrophages (PAMs). Increasing evidence has demonstrated that CD163 is the determinant receptor for PRRSV infection. However, the relationship between CD163 abundance and PRRSV infection is unclear. In this study, we first generated primary immortalized PAMs (iPAMs) using SV40 large T antigen and demonstrated that CD163 expression is suppressed by the alternative splicing of mRNA in iPAMs...
February 23, 2018: Oncotarget
Weili Wang, Kuansong Wang, Zihua Chen, Ling Chen, Wei Guo, Ping Liao, Daniel Rotroff, Todd C Knepper, Zhaoqian Liu, Wei Zhang, Howard L Mcleod, Yijing He
Background: Gastric cancer (GC) is a major cause of cancer deaths, especially in Eastern Asia. Current classification systems, including the WHO, Lauren, and TCGA, have clarified the pathological and molecular profiles of GC. However, these classifications lack an association with clinical outcome and guidance for medication selection. Objective: We aimed to identify a new immunoclassification for GC to better predict patient prognosis and aid in patient selection for immunotherapy...
February 23, 2018: Oncotarget
Bihong Xu, Chunyu Huang, Xianzi Yang, Xiangzhao Li, Liang Li, Yanqing Ding
Human epidermal growth factor receptor 2 (HER-2) has an important clinical role in various cancers. However, the prognostic impact of HER-2 in gastric cancer (GC) is controversial. RAB1A is an important small molecule in the mechanistic target of rapamycin signalling pathway, which is one of the downstream signalling pathways of the epidermal growth factor receptor family. In recent years, the aberrant expression of RAB1A has been reported in a number of tumours, but its regulation in GC has not been extensively examined...
April 2018: Oncology Letters
Srikant Rangaraju, Syed Ali Raza, Noel Xiang'An Li, Ranjita Betarbet, Eric B Dammer, Duc Duong, James J Lah, Nicholas T Seyfried, Allan I Levey
In the central nervous system (CNS), microglia are innate immune mononuclear phagocytes (CNS MPs) that can phagocytose infectious particles, apoptotic cells, neurons, and pathological protein aggregates, such as Aβ in Alzheimer's disease (AD). While CD11b+ CD45low microglia account for the majority of CNS MPs, a small population of CD11b+ CD45high CNS MPs is also recognized in AD that surround Aβ plaques. These transcriptionally and pathologically unique CD45high cells have unclear origin and undefined phagocytic characteristics...
2018: Frontiers in Immunology
Barbara Diana, Valentino Zurloni, Massimiliano Elia, Cesare Cavalera, Olivia Realdon, Gudberg K Jonsson, M Teresa Anguera
Deception has evolved to become a fundamental aspect of human interaction. Despite the prolonged efforts in many disciplines, there has been no definite finding of a univocally "deceptive" signal. This work proposes an approach to deception detection combining cognitive load manipulation and T-pattern methodology with the objective of: (a) testing the efficacy of dual task-procedure in enhancing differences between truth tellers and liars in a low-stakes situation; (b) exploring the efficacy of T-pattern methodology in discriminating truthful reports from deceitful ones in a low-stakes situation; (c) setting the experimental design and procedure for following research...
2018: Frontiers in Psychology
David McDougal, Daisuke Nakashima, Travis J Tenner, Noriko T Kita, John W Valley, Takaaki Noguchi
High precision oxygen three-isotope ratios were measured for four mineral phases (olivine, low-Ca and high-Ca pyroxene, and plagioclase) in equilibrated ordinary chondrites (EOC) using a secondary ion mass spectrometer. Eleven EOCs were studied that cover all groups (H, L, LL) and petrologic types (4, 5, 6), including S1-S4 shock stages, as well as unbrecciated and brecciated meteorites. SIMS analyses of multiple minerals were made in close proximity (mostly <100 μm) from several areas in each meteorite thin section, to evaluate isotope exchange among minerals...
November 2017: Meteoritics & Planetary Science
Colette S Inaba, Christina Y Koh, Sarath Sujatha-Bhaskar, Jack P Silva, Yanjun Chen, Danh V Nguyen, Ninh T Nguyen
BACKGROUND: Contemporary mortality after bariatric surgery is low and has been decreasing over the past two decades. Most studies have reported inpatient or 30-day mortality, which may not represent the true risk of bariatric surgery. The objective of this study was to examine 1-year mortality and factors predictive of 1-year mortality after contemporary laparoscopic bariatric surgery. STUDY DESIGN: Using the 2008-2012 Bariatric Outcomes Longitudinal Database (BOLD), data from 158,606 operations were analyzed, including 128,349 (80...
March 15, 2018: Journal of the American College of Surgeons
Wen Hao, Shutian Shi, Shenghui Zhou, Xiao Wang, Shaoping Nie
This study aimed to examine the effects of aspirin on the growth and cardiomyocyte differentiation grade of bone marrow mesenchymal stem cells (BMMSCs). BMMSCs were divided into five differentiation groups with different concentrations of aspirin (0mM, 0.5mM, 1mM, 2mM, or 5mM), and a undifferentiated control group. Cell growth was measured by cell proliferation, apoptosis assays and DNA cycle analysis. The differentiation grade of BMMSC-derived cardiomyocyte-like cells was examined by measuring the levels of cardiac-specific proteins with cyto-immunofluorescence staining, flow cytometry, and Western blotting...
March 15, 2018: European Journal of Pharmacology
Camila Rubio-Patiño, Jozef P Bossowski, Gian Marco De Donatis, Laura Mondragón, Elodie Villa, Lazaro E Aira, Johanna Chiche, Rana Mhaidly, Cynthia Lebeaupin, Sandrine Marchetti, Konstantinos Voutetakis, Aristotelis Chatziioannou, Florence A Castelli, Patricia Lamourette, Emeline Chu-Van, François Fenaille, Tony Avril, Thierry Passeron, John B Patterson, Els Verhoeyen, Béatrice Bailly-Maitre, Eric Chevet, Jean-Ehrland Ricci
Dietary restriction (DR) was shown to impact on tumor growth with very variable effects depending on the cancer type. However, how DR limits cancer progression remains largely unknown. Here, we demonstrate that feeding mice a low-protein (Low PROT) isocaloric diet but not a low-carbohydrate (Low CHO) diet reduced tumor growth in three independent mouse cancer models. Surprisingly, this effect relies on anticancer immunosurveillance, as depleting CD8+ T cells, antigen-presenting cells (APCs), or using immunodeficient mice prevented the beneficial effect of the diet...
March 1, 2018: Cell Metabolism
Katja Sauerstein, Jan Liebelt, Barbara Namer, Roland Schmidt, Roman Rukwied, Jürgen Sandkühler, Martin Schmelz
Secondary mechanical hyperalgesia to punctate mechanical stimuli and light touch (allodynia) are prominent symptoms in neuropathic pain states. In a combined microneurographic and psychophysical study, we investigated the role of mechano-insensitive (silent) nociceptors regarding induction. Electrical thresholds of mechano-sensitive and silent nociceptors were assessed by microneurography with two closely spaced intracutaneous electrodes (i.c.) and a transcutaneous configuration (t.c.) in the foot dorsum. For t...
March 15, 2018: Neuroscience
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