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Li Cheng, Jun Zhang, Xin-Yi Li, Li Yuan, Yan-Fang Pan, Xiao-Rong Chen, Tian-Ming Gao, Jian-Tian Qiao, Jin-Shun Qi
Amyloid β protein (Aβ) plays a critical role in pathogenesis of Alzheimer's disease (AD). Our previous studies indicated that the sequence 31-35 in Aβ molecule is an effective active center responsible for Aβ neurotoxicity in vivo and in vitro. In the present study, we prepared a novel antibody specifically targeting the sequence 31-35 of amyloid β protein, and investigated the neuroprotection of the anti-Aβ31-35 antibody against Aβ1-42 -induced impairments in neuronal viability, spatial memory, and hippocampal synaptic plasticity in rats...
October 26, 2016: Hippocampus
Romain Da Costa, Carsten Röger, Jasmin Segelken, Maya Barben, Christian Grimm, John Neidhardt
Purpose: Gene therapies to treat eye disorders have been extensively studied in the past 20 years. Frequently, adeno-associated viruses were applied to the subretinal or intravitreal space of the eye to transduce retinal cells with nucleotide sequences of therapeutic potential. In this study we describe a novel intravitreal injection procedure that leads to a reproducible adeno-associated virus (AAV)2/8-mediated transduction of more than 70% of the retina. Methods: Prior to a single intravitreal injection of a enhanced green fluorescent protien (GFP)-expressing viral suspension, we performed an aspiration of vitreous tissue from wild-type C57Bl/6J mice...
October 1, 2016: Investigative Ophthalmology & Visual Science
Jarrod D Frizzell, Li Liang, Phillip J Schulte, Clyde W Yancy, Paul A Heidenreich, Adrian F Hernandez, Deepak L Bhatt, Gregg C Fonarow, Warren K Laskey
Importance: Several attempts have been made at developing models to predict 30-day readmissions in patients with heart failure, but none have sufficient discriminatory capacity for clinical use. Machine-learning (ML) algorithms represent a novel approach and may have potential advantages over traditional statistical modeling. Objective: To develop models using a ML approach to predict all-cause readmissions 30 days after discharge from a heart failure hospitalization and to compare ML model performance with models developed using "conventional" statistically based methods...
October 26, 2016: JAMA Cardiology
Peter Sandner, Peter Berger, Christoph Zenzmaier
Fibrotic diseases cause high rates of morbidity and mortality, and their incidence increases with age. Despite intense research and development efforts, effective and well-tolerated antifibrotic treatments are scarce. Transforming growth factor-β signaling, which is widely considered the most important profibrotic factor, causes a pro-oxidant shift in redox homeostasis and a concomitant decrease in nitric oxide (NO) signaling. The NO/cyclic guanosine monophosphate (cGMP) signaling cascade plays a pivotal role in the regulation of cell and organ function in whole-body hemostasis...
October 27, 2016: Gerontology
Musaffe Tuna, Christopher I Amos
Approximately 18% of all human cancers have a viral etiology, and human papillomavirus (HPV) has been identified as one of the most prevalent viruses that plays causative role in nearly all cervical cancers and, in addition, in subset of head and neck, anal, penile and vulvar cancers. The recent introduction of next generation sequencing (NGS) and other 'omics' approaches have resulted in comprehensive knowledge on the pathogenesis of HPV-driven tumors. Specifically, these approaches have provided detailed information on genomic HPV integration sites, disrupted genes and pathways, and common and distinct genetic and epigenetic alterations in different human HPV-associated cancers...
October 23, 2016: Oncotarget
Kwangwoo Park, Sungjin Park, Mi-Jin Jeon, Jinhyun Choi, Jun Won Kim, Yoon Jin Cho, Won-Seok Jang, Yo Sup Keum, Ik Jae Lee
The 3D-printed boluses were used during the radiation therapy of the chest wall in six patients with breast cancer after modified radical mastectomy (MRM). We measured the in-vivo skin doses while both conventional and 3D-printed boluses were placed on the chest wall and compared the mean doses delivered to the ipsilateral lung and the heart. The homogeneity and conformity of the dose distribution in the chest wall for both types of boluses were also evaluated. The uniformity index on the chest skin was improved when the 3D-printed boluses were used, with the overall average skin dose being closer to the prescribed one in the former case (-0...
October 23, 2016: Oncotarget
Michelle J Wilkinson, Henry G Smith, Gráinne McEntee, Joan Kyula-Currie, Tim D Pencavel, David C Mansfield, Aadil A Khan, Victoria Roulstone, Andrew J Hayes, Kevin J Harrington
Advanced extremity melanoma and sarcoma present a significant therapeutic challenge, requiring multimodality therapy to treat or even palliate disease. These aggressive tumours are relatively chemo-resistant, therefore new treatment approaches are urgently required. We have previously reported on the efficacy of oncolytic virotherapy (OV) delivered by isolated limb perfusion. In this report, we have improved therapeutic outcomes by combining OV with radiotherapy. In vitro, the combination of oncolytic vaccinia virus (GLV-1h68) and radiotherapy demonstrated synergistic cytotoxicity...
October 22, 2016: Oncotarget
Luca Antonio Dimuccio, Nelson Rodrigues, Felice Larocca, João Pratas, Ana Margarida Amado, Luís A E Batista de Carvalho
This study examines the geochemical and mineralogical variations in the ferruginous mineralisations that crop out within Grotta della Monaca, which is considered to be the most striking and best known example of a prehistoric iron mine-cave from the southern Apennines (Calabria, Italy). Previous archaeological research identified three local and distinct ancient exploitation phases of these ferruginous mineralisations: (1) an Upper Palaeolithic phase; (2) a Late Neolithic phase; and (3) a post-Medieval phase...
October 17, 2016: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Justin T Clapp, Jody A Roberts, Britt Dahlberg, Lee Sullivan Berry, Lisa M Jacobs, Edward A Emmett, Frances K Barg
Research on community responses to environmental toxicity has richly described the struggles of citizens to identify unrecognized toxins, collect their own environmental health facts, and use them to lobby authorities for recognition and remediation. Much of this literature is based on an empiricist premise: it is concerned with exploring differences in how laypeople and experts perceive what is presumed to be a singular toxic reality that preexists these varying perspectives. Here, we seek to reexamine this topic by shifting the focus from facts to facticity-that is, by exploring the many types of knowledge that communities develop about toxicity and how these knowledges articulate with the ideas of scientific and governmental authorities about what kinds of information are valid bases for policymaking...
October 20, 2016: Social Science & Medicine
Ehud Chorin, Eyal Ben-Assa, Maayan Konigstein, May-Tal Rofe, Aviram Hochstadt, Naama Galli, Michael Schnapper, Yaron Arbel, Ilan Rabey, Jeremy Ben Shoshan, Amir Halkin, Itzhak Herz, Ariel Finkelstein, Samuel Bazan, Gad Keren, Shmuel Banai
BACKGROUND: Radiologists and cardiologists have a remarkably different approach to the clinical importance and to the need for prophylactic treatment of contrast-induced acute kidney injury (CI-AKI). OBJECTIVES: To evaluate the efficacy of forced diuresis with matched controlled hydration (FMH) in a real-world, high risk population. METHODS: This is an investigator-driven, single-center, retrospective analysis of prospectively collected data...
October 11, 2016: International Journal of Cardiology
Joseph O Okeme, Eva M Webster, J Mark Parnis, Miriam L Diamond
Partition coefficients between polyurethane foam (PUF) and air (KPUF-Air) are important when using PUF as a passive air sampler for semi-volatile organic compounds (SVOCs) and when considering the fate of SVOCs indoors where PUF is a common material. Here, KPUF-Air for selected SVOCs was estimated using published methods, since measured data are unavailable for most of these compounds. Estimates of KPUF-Air were within one order of magnitude for SVOCs having values of log octanol-air partition coefficient (KOA) of 5, but differed by nearly three orders of magnitude for SVOCs with log KOA of 12...
October 23, 2016: Chemosphere
A Di Gilio, G Ventrella, P Giungato, M Tutino, R Giua, G Assennato, G de Gennaro
This study provided a useful approach for assessing the impact of industrial sources on surrounding, especially in a sensitive industrial area as Taranto (South of Italy). Taranto is one of the most industrialized Italian towns, where several emission sources operate simultaneously in proximity to the urban settlement. An intensive monitoring campaign of PAHs was carried out from January 28th to July 30th, 2011, in seven sites located in residential settlement around the industrial area and in the city center...
October 23, 2016: Chemosphere
Judd F Hultquist, Kathrin Schumann, Jonathan M Woo, Lara Manganaro, Michael J McGregor, Jennifer Doudna, Viviana Simon, Nevan J Krogan, Alexander Marson
New genetic tools are needed to understand the functional interactions between HIV and human host factors in primary cells. We recently developed a method to edit the genome of primary CD4(+) T cells by electroporation of CRISPR/Cas9 ribonucleoproteins (RNPs). Here, we adapted this methodology to a high-throughput platform for the efficient, arrayed editing of candidate host factors. CXCR4 or CCR5 knockout cells generated with this method are resistant to HIV infection in a tropism-dependent manner, whereas knockout of LEDGF or TNPO3 results in a tropism-independent reduction in infection...
October 25, 2016: Cell Reports
Jeremy A Goettel, Roopali Gandhi, Jessica E Kenison, Ada Yeste, Gopal Murugaiyan, Sharmila Sambanthamoorthy, Alexandra E Griffith, Bonny Patel, Dror S Shouval, Howard L Weiner, Scott B Snapper, Francisco J Quintana
Existing therapies for inflammatory bowel disease that are based on broad suppression of inflammation result in variable clinical benefit and unwanted side effects. A potential therapeutic approach for promoting immune tolerance is the in vivo induction of regulatory T cells (Tregs). Here we report that activation of the aryl hydrocarbon receptor using the non-toxic agonist 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) induces human Tregs in vitro that suppress effector T cells through a mechanism mediated by CD39 and Granzyme B...
October 25, 2016: Cell Reports
Jocelyn P Wong, Jason R Todd, Martina A Finetti, Frank McCarthy, Malgorzata Broncel, Simon Vyse, Maciej T Luczynski, Stephen Crosier, Karen A Ryall, Kate Holmes, Leo S Payne, Frances Daley, Patty Wai, Andrew Jenks, Barbara Tanos, Aik-Choon Tan, Rachael C Natrajan, Daniel Williamson, Paul H Huang
Subunits of the SWI/SNF chromatin remodeling complex are mutated in a significant proportion of human cancers. Malignant rhabdoid tumors (MRTs) are lethal pediatric cancers characterized by a deficiency in the SWI/SNF subunit SMARCB1. Here, we employ an integrated molecular profiling and chemical biology approach to demonstrate that the receptor tyrosine kinases (RTKs) PDGFRα and FGFR1 are coactivated in MRT cells and that dual blockade of these receptors has synergistic efficacy. Inhibitor combinations targeting both receptors and the dual inhibitor ponatinib suppress the AKT and ERK1/2 pathways leading to apoptosis...
October 25, 2016: Cell Reports
Alexandre Fisette, Stephanie Tobin, Léa Décarie-Spain, Khalil Bouyakdan, Marie-Line Peyot, S R Murthy Madiraju, Marc Prentki, Stephanie Fulton, Thierry Alquier
α/β-Hydrolase domain 6 (ABHD6) is a monoacylglycerol hydrolase that degrades the endocannabinoid 2-arachidonoylglycerol (2-AG). Although complete or peripheral ABHD6 loss of function is protective against diet-induced obesity and insulin resistance, the role of ABHD6 in the central control of energy balance is unknown. Using a viral-mediated knockout approach, targeted endocannabinoid measures, and pharmacology, we discovered that mice lacking ABHD6 from neurons of the ventromedial hypothalamus (VMH(KO)) have higher VMH 2-AG levels in conditions of endocannabinoid recruitment and fail to physiologically adapt to key metabolic challenges...
October 25, 2016: Cell Reports
C Buratti, F Fantozzi, M Barbanera, E Lascaro, M Chiorri, L Cecchini
Beef cattle production is a widespread activity in Italy in the agricultural field and determines an important impact on environment and resources consumption. Carbon footprint evaluation is thus necessary to evaluate the contributions of the different stages and the possible improvements of the production chain. In this study, two typical Italian beef production systems, a conventional and an organic one are investigated in order to evaluate the greenhouse gas emissions from "cradle to gate farm" by a Life Cycle Assessment (LCA) approach; the carbon footprint (CF) per 1kg of live weight meat is calculated...
October 23, 2016: Science of the Total Environment
Michael D Besmer, Frederik Hammes
Short-term fluctuations in bacterial concentrations in drinking water systems, occurring on time scales of hours-to-weeks, are essentially unexplored due to a lack of microbial monitoring tools that allow high frequency measurements. Here, we applied fully automated online flow cytometry to measure the total cell concentrations (TCC) in both raw water (karstic groundwater) and treated water (flocculation - ultrafiltration (UF) - ozonation - granular active carbon (GAC) filtration) during a period of 70 days at high temporal resolution (n > 4000 for both water types)...
October 18, 2016: Water Research
Uri Landes, Alon Barsheshet, Ariel Finkelstein, Victor Guetta, Abid Assali, Amir Halkin, Hanna Vaknin-Assa, Amit Segev, Tamir Bental, Jeremy Ben-Shoshan, Israel M Barbash, Ran Kornowski
BACKGROUND: About a decade past the first transcatheter aortic valve implantation (TAVI), data are limited regarding temporal trends accompanying its evolution from novel technology to mainstream therapy. We evaluated these trends in a large multicenter TAVI registry. HYPOTHESIS: TAVI is changing and improving with time. METHODS: Patients who underwent TAVI between January 2008 and December 2014 at 3 high-volume Israeli centers were divided into 5 time quintiles according to procedure date...
October 26, 2016: Clinical Cardiology
Patrick T Walsh, Padraic G Fallon
The recently discovered interleukin (IL)-36 family of cytokines form part of the broader IL-1 family and are emerging as important mediators of inflammatory disease. The IL-36 subfamily consists of three ligands-IL-36α, IL-36β, and IL-36γ-and the natural antagonist IL-36Ra. The cytokines exert their effects through a specific IL-36 receptor consisting of IL-36R and IL-1RAcP chains. IL-36 cytokines can direct both innate and adaptive immune responses by acting on parenchymal, stromal, and specific immune cell subsets...
October 26, 2016: Annals of the New York Academy of Sciences
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