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Michael C Gundry, Lorenzo Brunetti, Angelique Lin, Allison E Mayle, Ayumi Kitano, Dimitrios Wagner, Joanne I Hsu, Kevin A Hoegenauer, Cliona M Rooney, Margaret A Goodell, Daisuke Nakada
Our understanding of the mechanisms that regulate hematopoietic stem/progenitor cells (HSPCs) has been advanced by the ability to genetically manipulate mice; however, germline modification is time consuming and expensive. Here, we describe fast, efficient, and cost-effective methods to directly modify the genomes of mouse and human HSPCs using the CRISPR/Cas9 system. Using plasmid and virus-free delivery of guide RNAs alone into Cas9-expressing HSPCs or Cas9-guide RNA ribonucleoprotein (RNP) complexes into wild-type cells, we have achieved extremely efficient gene disruption in primary HSPCs from mouse (>60%) and human (∼75%)...
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
Jorge Barros, Susana Morales, Orietta Echávarri, Arnol García, Jaime Ortega, Takeshi Asahi, Claudia Moya, Ronit Fischman, María P Maino, Catalina Núñez
Objective: To analyze suicidal behavior and build a predictive model for suicide risk using data mining (DM) analysis. Methods: A study of 707 Chilean mental health patients (with and without suicide risk) was carried out across three healthcare centers in the Metropolitan Region of Santiago, Chile. Three hundred forty-three variables were studied using five questionnaires. DM and machine-learning tools were used via the support vector machine technique. Results: The model selected 22 variables that, depending on the circumstances in which they all occur, define whether a person belongs in a suicide risk zone (accuracy = 0...
October 20, 2016: Revista Brasileira de Psiquiatria
Katharine Kripke, Jason Reed, Catherine Hankins, Gregory Smiley, Catey Laube, Emmanuel Njeuhmeli
BACKGROUND: The report of the Joint United Nations Programme on HIV/AIDS (UNAIDS) for World AIDS Day 2014 highlighted a Fast-Track Strategy that sets ambitious treatment and prevention targets to reduce global HIV incidence to manageable levels by 2020 and end the AIDS epidemic by 2030. The 90-90-90 treatment targets for 2020 call for 90% of people living with HIV to know their HIV status, 90% of people who know their status to receive treatment, and 90% of people on HIV treatment to be virally suppressed...
2016: PloS One
Hui-Wen Lu-Walther, Wenya Hou, Martin Kielhorn, Yoshiyuki Arai, Takeharu Nagai, Michael M Kessels, Britta Qualmann, Rainer Heintzmann
Structured illumination microscopy (SIM) is a wide-field technique in fluorescence microscopy that provides fast data acquisition and two-fold resolution improvement beyond the Abbe limit. We observed a further resolution improvement using the nonlinear emission response of a fluorescent protein. We demonstrated a two-beam nonlinear structured illumination microscope by introducing only a minor change into the system used for linear SIM (LSIM). To achieve the required nonlinear dependence in nonlinear SIM (NL-SIM) we exploited the photoswitching of the recently introduced fluorophore Kohinoor...
2016: PloS One
Han Na Kwon, Hyunjung Lim
Serum vitamin D status has been associated with prediabetes and metabolic syndrome. Evidence for the increased risk of metabolic disorders in individuals with prediabetes and a low vitamin D status is limited and uncertain. Furthermore, it has not been confirmed whether this possible relationship occurs in the Korean population. The aim of this study was to assess serum vitamin D status and to examine the relationship between serum vitamin D levels and metabolic risk factors in Korean adults with prediabetes...
2016: PloS One
Ann-Sophie Schott, Jürgen Behr, Jennifer Quinn, Rudi F Vogel
Lactic acid bacteria (LAB) are widely used as starter cultures in the manufacture of foods. Upon preparation, these cultures undergo various stresses resulting in losses of survival and fitness. In order to find conditions for the subsequent identification of proteomic biomarkers and their exploitation for preconditioning of strains, we subjected Lactobacillus (Lb.) paracasei subsp. paracasei TMW 1.1434 (F19) to different stress qualities (osmotic stress, oxidative stress, temperature stress, pH stress and starvation stress)...
2016: PloS One
Cannada Andrew Lewis, Justus Aaron Calvin, Edward F Valeev
We describe the Clustered Low Rank (CLR) framework for block-sparse and block-low-rank tensor representation and computation. The CLR framework exploits the tensor structure revealed by basis clustering; computational savings arise from low-rank compression of tensor blocks and performing block arithmetic in the low-rank form whenever beneficial. The precision is rigorously controlled by 2 parameters, avoiding ad-hoc heuristics, such as domains: one controls the CLR block rank truncation and the other controls screening of small contributions in arithmetic operations on CLR tensors to propagate sparsity through expressions...
October 26, 2016: Journal of Chemical Theory and Computation
Yanan Guo, Miaomiao Gong, Yushu Li, Yunling Liu, Xincun Dou
ZnO-CuO mesocrystal was prepared via topotactic transformation using one-step direct annealing of aqueous precursor solution and assembled into a H2S sensor. The ZnO-CuO mesocrystal-based sensor possesses good linearity and high sensitivity in the low-concentration range (10-200 ppb). Compared to pure CuO, the as-prepared ZnO-CuO mesocrystal sensor exhibited superior H2S sensing performance with a response ranging from 8.6 to 152 % towards H2S concentrations from 10 ppb to 10 ppm when applied at the optimized working temperature of 125 °C...
December 2016: Nanoscale Research Letters
Qianghua Quan, Shuwen Zhang, Xudong Wang, Qi Ouyang, Yugang Wang, Gen Yang, Chunxiong Luo
Cell migration assays for different chemical environments are important for both scientists and clinicians searching for new therapeutics. In this study, we developed a multi-well-based microfluidic chip that has multiple units for different conditions. In each unit, cells can be patterned and then released to observe their migration. Automatic image analysis and model-based data processing were developed to describe the integrated cell migration assay precisely and quickly. As a demonstration, the migration behaviors of two types of cells in eight chemical conditions were studied...
December 2016: Biomedical Microdevices
Petrina Yau-Pok Lau, Linda Katona, Peter Saghy, Kathryn Newton, Peter Somogyi, Karri P Lamsa
Long-term plasticity is well documented in synapses between glutamatergic principal cells in the cortex both in vitro and in vivo. Long-term potentiation (LTP) and -depression (LTD) have also been reported in glutamatergic connections to hippocampal GABAergic interneurons expressing parvalbumin (PV+) or nitric oxide synthase (NOS+) in brain slices, but plasticity in these cells has not been tested in vivo. We investigated synaptically-evoked suprathreshold excitation of identified hippocampal neurons in the CA1 area of urethane-anaesthetized rats...
October 25, 2016: Brain Structure & Function
Simran Chahal, Kanchan Vohra, Ashit Syngle
Peripheral artery disease (PAD) is the major risk factor for cardiovascular disease and lower extremity amputation in patients with diabetes. Autonomic neuropathy is a risk factor for cardiovascular-related morbidity and mortality. Sudomotor dysfunction is well established in type 2 diabetes mellitus (T2DM) and reflects small fibre neuropathy, cardiovascular autonomic neuropathy and peripheral sympathetic autonomic neuropathy. However, the relationship between sudomotor dysfunction and PAD remains unexplored...
October 25, 2016: Neurological Sciences
Martina Zangheri, Fabio Di Nardo, Mara Mirasoli, Laura Anfossi, Augusto Nascetti, Domenico Caputo, Giampiero De Cesare, Massimo Guardigli, Claudio Baggiani, Aldo Roda
A novel and disposable cartridge for chemiluminescent (CL)-lateral flow immunoassay (LFIA) with integrated amorphous silicon (a-Si:H) photosensors array was developed and applied to quantitatively detect human serum albumin (HSA) in urine samples. The presented analytical method is based on an indirect competitive immunoassay using horseradish peroxidase (HRP) as a tracer, which is detected by adding the luminol/enhancer/hydrogen peroxide CL cocktail. The system comprises an array of a-Si:H photosensors deposited on a glass substrate, on which a PDMS cartridge that houses the LFIA strip and the reagents necessary for the CL immunoassay was optically coupled to obtain an integrated analytical device controlled by a portable read-out electronics...
October 25, 2016: Analytical and Bioanalytical Chemistry
Si Cheng, Jie Sun, Junxing Yang, Jianqiang Lv, Feng Wu, Yanxing Lin, Lishan Liao, Yiyou Ye, Chenfu Cao, Liurong Fang, Qunyi Hua
A fast and ultrasensitive test-strip system combining quantum dots (QDs) with a lateral-flow immunoassay strip (LFIAS) was established for detection of Peste des petits ruminants virus (PPRV) antibody. The highly luminescent water-soluble carboxyl-functionalized QDs were used as the signal output and were conjugated to streptococcal protein G (SPG), which was capable of binding to immunoglobulin G (IgG) from many species through an amide bond to capture the target PPRV IgGs. The PPRV N protein, which was immobilized on the detection zone of the test strip, was expressed by transfecting recombinant Bacmid-PPRV-N with Lipofect into Sf9 insect cells...
October 25, 2016: Analytical and Bioanalytical Chemistry
Li Li, Zhiyuan Zhang
The emergence of bioorthogonal reactions has greatly broadened the scope of biomolecule labeling and detecting. Of all the bioorthogonal reactions that have been developed, the copper-catalyzed azide-alkyne cycloaddition (CuAAC) is the most widely applied one, mainly because of its relatively fast kinetics and high efficiency. However, the introduction of copper species to in vivo systems raises the issue of potential toxicity. In order to reduce the copper-induced toxicity and further improve the reaction kinetics and efficiency, different strategies have been adopted, including the development of diverse copper chelating ligands to assist the catalytic cycle and the development of chelating azides as reagents...
October 24, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Christian Brinkmann, Benedikt Schulte-Körne, Marijke Grau, Sinja Obels, Roman Kemmerling, Thorsten Schiffer, Wilhelm Bloch, Klara Brixius
BACKGROUND: Increases in the amount of inducible nitric oxide synthase (iNOS) protein and abnormal production of nitric oxide (NO) in skeletal muscle have been suggested to be associated with peripheral insulin resistance in patients with type 2 diabetes mellitus (T2DM). This pilot study analyzed whether a 3-month endurance training can affect iNOS protein and NO metabolite levels in the vastus lateralis muscle of insulin-independent T2DM men, thereby affecting the patients` glycemic control...
October 26, 2016: Metabolic Syndrome and related Disorders
Lior Weizman, Yonina C Eldar, Dafna Ben Bashat
PURPOSE: In many clinical MRI scenarios, existing imaging information can be used to significantly shorten acquisition time or to improve Signal to Noise Ratio (SNR). In this paper the authors present a framework, referred to as FASTMER, for fast MRI by exploiting a reference image. METHODS: The proposed approach utilizes the possible similarity of the reference image to the acquired image, which exists in many clinical MRI imaging scenarios. Examples include similarity between adjacent slices in high resolution MRI, similarity between various contrasts in the same scan and similarity between different scans of the same patient...
October 2016: Medical Physics
A Neubert, Z Yang, C Engstrom, Y Xia, M W Strudwick, S S Chandra, J Fripp, S Crozier
PURPOSE: Magnetic resonance (MR) imaging plays a key role in investigating early degenerative disorders and traumatic injuries of the glenohumeral cartilages. Subtle morphometric and biochemical changes of potential relevance to clinical diagnosis, treatment planning, and evaluation can be assessed from measurements derived from in vivo MR segmentation of the cartilages. However, segmentation of the glenohumeral cartilages, using approaches spanning manual to automated methods, is technically challenging, due to their thin, curved structure and overlapping intensities of surrounding tissues...
October 2016: Medical Physics
Maxence Borot de Battisti, Baudouin Denis de Senneville, Metha Maenhout, Jan J W Lagendijk, Marco van Vulpen, Gilion Hautvast, Dirk Binnekamp, Marinus A Moerland
PURPOSE: The development of MR-guided high dose rate (HDR) brachytherapy is under investigation due to the excellent tumor and organs at risk visualization of MRI. However, MR-based localization of needles (including catheters or tubes) has inherently a low update rate and the required image interpretation can be hampered by signal voids arising from blood vessels or calcifications limiting the precision of the needle guidance and reconstruction. In this paper, a new needle tracking prototype is investigated using fiber Bragg gratings (FBG)-based sensing: this prototype involves a MR-compatible stylet composed of three optic fibers with nine sets of embedded FBG sensors each...
October 2016: Medical Physics
Peng Wang, Jochen Cammin, Francesca Bisello, Timothy D Solberg, James E McDonough, Timothy C Zhu, David Menichelli, Boon-Keng Kevin Teo
PURPOSE: Proton radiography (PR) and proton computed tomography (PCT) can be used to measure proton stopping power directly. However, practical and cost effective proton imaging detectors are not widely available. In this study, the authors investigated the feasibility of proton imaging using a silicon diode array. METHODS: A one-dimensional silicon diode detector array (1DSDA) was aligned with the central axis (CAX) of the proton beam. Polymethyl methacrylate (PMMA) slabs were used to find the correspondence between the water equivalent thickness (WET) and 1DSDA channel number...
October 2016: Medical Physics
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