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Peter D Koch, Howard R Miller, Gary Yu, John A Tallarico, Peter K Sorger, Yuan Wang, Yan Feng, Jason R Thomas, Nathan T Ross, Timothy Mitchison
We screened a library of bioactive small molecules for activators and inhibitors of innate immune signaling through IRF3 and NFkB pathways with the goals of advancing pathway understanding and discovering probes for immunology research. We used high content screening to measure the translocation from the cytoplasm to nucleus of IRF3 and NFkB in primary human macrophages; these transcription factors play a critical role in the activation of STING and other pro-inflammatory pathways. Our pathway activator screen yielded a diverse set of hits that promoted nuclear translocation of IRF3 and/or NFkB, but the majority of these compounds did not cause activation of downstream pathways...
March 19, 2018: ACS Chemical Biology
Timm Oberwahrenbrock, Ghislaine L Traber, Sebastian Lukas, Iñigo Gabilondo, Rachel Nolan, Christopher Songster, Lisanne Balk, Axel Petzold, Friedemann Paul, Pablo Villoslada, Alexander U Brandt, Ari J Green, Sven Schippling
Objective: To evaluate the inter-rater reliability of semiautomated segmentation of spectral domain optical coherence tomography (OCT) macular volume scans. Methods: Macular OCT volume scans of left eyes from 17 subjects (8 patients with MS and 9 healthy controls) were automatically segmented by Heidelberg Eye Explorer (v1.9.3.0) beta-software (Spectralis Viewing Module v6.0.0.7), followed by manual correction by 5 experienced operators from 5 different academic centers...
May 2018: Neurology® Neuroimmunology & Neuroinflammation
Concetta Saponaro, Sara Sergio, Antonio Coluccia, Maria De Luca, Giuseppe La Regina, Luca Mologni, Valeria Famiglini, Valentina Naccarato, Daniela Bonetti, Candice Gautier, Stefano Gianni, Daniele Vergara, Michel Salzet, Isabelle Fournier, Cecilia Bucci, Romano Silvestri, Carlo Gambacorti Passerini, Michele Maffia, Addolorata Maria Luce Coluccia
Nuclear activated β-catenin plays a causative role in colorectal cancers (CRC) but remains an elusive therapeutic target. Using human CRC cells harboring different Wnt/β-catenin pathway mutations in APC/KRAS or β-catenin/KRAS genes, and both genetic and pharmacological knockdown approaches, we show that oncogenic β-catenin signaling negatively regulates the expression of NHERF1 (Na+ /H+ exchanger 3 regulating factor 1), a PDZ-adaptor protein that is usually lost or downregulated in early dysplastic adenomas to exacerbate nuclear β-catenin activity...
March 19, 2018: Oncogene
Frank Portillo, William R Branch, Werner Conradie, Mark-Oliver Rödel, Johannes Penner, Michael F Barej, Chifundera Kusamba, Wandege M Muninga, Mwenebatu M Aristote, Aaron M Bauer, Jean-François Trape, Zoltán T Nagy, Piero Carlino, Olivier S G Pauwels, Michele Menegon, Marius Burger, Tomáš Mazuch, Kate Jackson, Daniel F Hughes, Mathias Behangana, Eli Greenbaum
Members of the snake subfamily Aparallactinae occur in various habitats throughout sub-Saharan Africa. The monophyly of aparallactine snakes is well established, but relationships within the subfamily are poorly known. We sampled 158 individuals from six of eight aparallactine genera in sub-Saharan Africa. We employed concatenated gene-tree analyses, divergence dating approaches, and ancestral-area reconstructions to infer phylogenies and biogeographic patterns with a multi-locus data set consisting of three mitochondrial (16S, cyt b, and ND4) and two nuclear genes (c-mos and RAG1)...
March 15, 2018: Molecular Phylogenetics and Evolution
Paola Spitalieri, Rosa V Talarico, Silvia Caioli, Michela Murdocca, Annalucia Serafino, Marco Girasole, Simone Dinarelli, Giovanni Longo, Sabina Pucci, Annalisa Botta, Giuseppe Novelli, Cristina Zona, Ruggiero Mango, Federica Sangiuolo
Myotonic Dystrophy type 1 (DM1) is a multisystemic disease, autosomal dominant, caused by a CTG repeat expansion in DMPK gene. We assessed the appropriateness of patient-specific induced pluripotent stem cell-derived cardiomyocytes (CMs) as a model to recapitulate some aspects of the pathogenetic mechanism involving cardiac manifestations in DM1 patients. Once obtained in vitro, CMs have been characterized for their morphology and their functionality. CMs DM1 show intranuclear foci and transcript markers abnormally spliced respect to WT ones, as well as several irregularities in nuclear morphology, probably caused by an unbalanced lamin A/C ratio...
March 15, 2018: Journal of Molecular and Cellular Cardiology
Davar Abedini, Sajad Rashidi Monfared
A primary mechanism for controlling the development of multicellular organisms is transcriptional regulation, which carried out by transcription factors (TFs) that recognize and bind to their binding sites on promoter region. The distance from translation start site, order, orientation, and spacing between cis elements are key factors in the concentration of active nuclear TFs and transcriptional regulation of target genes. In this study, overrepresented motifs in cold and pathogenesis responsive genes were scanned via Gibbs sampling method, this method is based on detection of overrepresented motifs by means of a stochastic optimization strategy that searches for all possible sets of short DNA segments...
March 17, 2018: Molecular Biology Reports
C M Chingkoe, A Brook, A J Moser, K J Mortele
PURPOSE: At our tertiary medical center, multidisciplinary subspecialists meet twice a week during a CME-accredited conference to discuss oncologic and non-oncologic patients with pancreatic diseases at which time a subspecialized abdominal staff radiologist reinterprets the patient's relevant imaging studies. This study assesses the changes in patient management due to imaging reinterpretation during multidisciplinary pancreas conference (MPC). MATERIALS AND METHODS: In this retrospective, IRB-approved, HIPAA-compliant study, imaging studies of all patients discussed at MPC between July 1 and December 31, 2015 were assessed for technical adequacy, and original reports analyzed for congruency with reinterpretation...
March 17, 2018: Abdominal Radiology
Atefeh Rabiee, Marcus Krüger, Jacob Ardenkjær-Larsen, C Ronald Kahn, Brice Emanuelli
Insulin/IGF-1 action is driven by a complex and highly integrated signalling network. Loss-of-function studies indicate that the major insulin/IGF-1 receptor substrate (IRS) proteins, IRS-1 and IRS-2, mediate different biological functions in vitro and in vivo, suggesting specific signalling properties despite their high degree of homology. To identify mechanisms contributing to the differential signalling properties of IRS-1 and IRS-2 in the mediation of insulin/IGF-1 action, we performed comprehensive mass spectrometry (MS)-based phosphoproteomic profiling of brown preadipocytes from wild type, IRS-1-/- and IRS-2-/- mice in the basal and IGF-1-stimulated states...
March 14, 2018: Cellular Signalling
Julian Betancur, Frederic Commandeur, Mahsaw Motlagh, Tali Sharir, Andrew J Einstein, Sabahat Bokhari, Mathews B Fish, Terrence D Ruddy, Philipp Kaufmann, Albert J Sinusas, Edward J Miller, Timothy M Bateman, Sharmila Dorbala, Marcelo Di Carli, Guido Germano, Yuka Otaki, Balaji K Tamarappoo, Damini Dey, Daniel S Berman, Piotr J Slomka
OBJECTIVES: The study evaluated the automatic prediction of obstructive disease from myocardial perfusion imaging (MPI) by deep learning as compared with total perfusion deficit (TPD). BACKGROUND: Deep convolutional neural networks trained with a large multicenter population may provide improved prediction of per-patient and per-vessel coronary artery disease from single-photon emission computed tomography MPI. METHODS: A total of 1,638 patients (67% men) without known coronary artery disease, undergoing stress99m Tc-sestamibi or tetrofosmin MPI with new generation solid-state scanners in 9 different sites, with invasive coronary angiography performed within 6 months of MPI, were studied...
March 12, 2018: JACC. Cardiovascular Imaging
Takahiro Iijima, Tadashi Shimizu
The relaxation-assisted separation method was applied to overlapping2 H nuclear magnetic resonance (NMR) spectra of diamagnetic and paramagnetic solids to separate them based on the different relaxation behaviors caused by molecular motion. Carr-Purcell-Meiboom-Gill sequences for2 H NMR were adopted to build two-dimensional data sets from one-dimensional NMR experiments. For diamagnetic α-glycine, the2 H NMR spectrum collected at 198 K was separated into two components from static -CD2 - and dynamic -ND3 ...
March 8, 2018: Solid State Nuclear Magnetic Resonance
Pollyana Trigueiro, Silvia Pedetti, Baptiste Rigaud, Sebastien Balme, Jean-Marc Janot, Ieda M G Dos Santos, Régis Gougeon, Maria G Fonseca, Thomas Georgelin, Maguy Jaber
Wine chemistry inspires and challenges with its complexity and intriguing composition. In this context, the composites based on the use of a model protein, a polyphenol of interest and montmorillonite in a model hydroalcoholic solution have been studied. A set of experimental characterization techniques highlighted the interactions between the organic and the inorganic parts in the composite. The amount of the organic part was determined by ultraviolet-visible (UV-VIS) and thermal analysis. X-ray diffraction (XRD) and transmission electronic microscopy (TEM) informed about the stacking/exfoliation of the layers in the composites...
March 6, 2018: Colloids and Surfaces. B, Biointerfaces
Michael B Wayson, Wesley E Bolch
Internal radiation dose estimates for diagnostic nuclear medicine procedures are typically calculated for a reference individual. Resultantly, there is uncertainty when determining the organ doses to patients who are not at 50th percentile on either height or weight. This study aims to better personalize internal radiation dose estimates for individual patients by modifying the dose estimates calculated for reference individuals based on easily obtainable morphometric characteristics of the patient. Phantoms of different sitting heights and waist circumferences were constructed based on computational reference phantoms for the newborn, 10-year-old, and adult...
March 16, 2018: Physics in Medicine and Biology
Qingqing Wei, Ruiqi Li, Liang Zhong, Haiyuan Mu, Shaopeng Zhang, Liang Yue, Jinzhu Xiang, Enhong Li, Minglei Zhi, Suying Cao, Jianyong Han
After zygotic genome activation and lineage specification, zygotes develop into late blastocysts comprising three distinct cell types. The molecular mechanisms underlying this progress are largely unknown in pigs. Here, we intended to analyze an extensive set of regulators at the single-cell level to define the events involved in the development of the porcine blastocysts. Using a quantitative microfluidics approach in single cells, we detected mRNA levels of 96 genes known to function in early embryonic development and maintenance of stem cell pluripotency simultaneously in 480 individual cells derived from porcine preimplantation embryos...
March 13, 2018: Biology of Reproduction
Korkut Bekiroglu, Constantino Lagoa, Stephanie T Lanza, Mario Sznaier
Considerable effort has been devoted to the development of algorithms for identification of parsimonious discrete time models from noisy input/output data sets since this facilitates controller design. Several methods, such as nuclear norm minimization, have been used to provide approximate solutions to this non-convex problem. However, even though the field of continuous time system identification is now mature, results on parsimonious model identification of continuous time systems are still very limited...
July 2017: Proceedings of the IFAC World Congress
Timothy Kwang Yong Tay, Aye Aye Thike, Nirmala Pathmanathan, Ana Richelia Jara-Lazaro, Jabed Iqbal, Adeline Shi Hui Sng, Heng Seow Ye, Jeffrey Chun Tatt Lim, Valerie Cui Yun Koh, Jane Sie Yong Tan, Joe Poh Sheng Yeong, Zi Long Chow, Hui Hua Li, Chee Leong Cheng, Puay Hoon Tan
Background: Ki67 positivity in invasive breast cancers has an inverse correlation with survival outcomes and serves as an immunohistochemical surrogate for molecular subtyping of breast cancer, particularly ER positive breast cancer. The optimal threshold of Ki67 in both settings, however, remains elusive. We use computer assisted image analysis (CAIA) to determine the optimal threshold for Ki67 in predicting survival outcomes and differentiating luminal B from luminal A breast cancers...
February 20, 2018: Oncotarget
Zsofia Miskolczi, Michael P Smith, Emily J Rowling, Jennifer Ferguson, Jorge Barriuso, Claudia Wellbrock
Despite the general focus on an invasive and de-differentiated phenotype as main driver of cancer metastasis, in melanoma patients many metastatic lesions display a high degree of pigmentation, indicative for a differentiated phenotype. Indeed, studies in mice and fish show that melanoma cells switch to a differentiated phenotype at secondary sites, possibly because in melanoma differentiation is closely linked to proliferation through the lineage-specific transcriptional master regulator MITF. Importantly, while a lot of effort has gone into identifying factors that induce the de-differentiated/invasive phenotype, it is not well understood how the switch to the differentiated/proliferative phenotype is controlled...
March 16, 2018: Oncogene
Pushp Bajaj, Xiao-Gang Wang, Tucker Carrington, Francesco Paesani
Full-dimensional vibrational spectra are calculated for both X- (H2 O) and X- (D2 O) dimers (X = F, Cl, Br, I) at the quantum-mechanical level. The calculations are carried out on two sets of recently developed potential energy functions (PEFs), namely, Thole-type model energy (TTM-nrg) and many-body energy (MB-nrg), using the symmetry-adapted Lanczos algorithm with a product basis set including all six vibrational coordinates. Although both TTM-nrg and MB-nrg PEFs are derived from coupled-cluster single double triple-F12 data obtained in the complete basis set limit, they differ in how many-body effects are represented at short range...
March 14, 2018: Journal of Chemical Physics
Milad Rayka, Mohammad Goli, Shant Shahbazian
A set of effective electronic-only Kohn-Sham (EKS) equations are derived for the muonic molecules (containing a positively charged muon), which are completely equivalent to the coupled electronic-muonic Kohn-Sham equations derived previously within the framework of the nuclear-electronic orbital density functional theory (NEO-DFT). The EKS equations contain effective non-coulombic external potentials depending on parameters describing the muon's vibration, which are optimized during the solution of the EKS equations making the muon's KS orbital reproducible...
March 15, 2018: Physical Chemistry Chemical Physics: PCCP
Mamta Gupta, Anna Laury, Marisa R Nucci, Bradley J Quade
AIMS: Current WHO classification defines smooth muscle tumors of uncertain malignant potential (STUMP) as neoplasms that cannot be diagnosed reliably as benign or malignant using generally accepted criteria. This has led to application of various criteria sets; consequently, consistent and reliable outcome data is lacking. The aims of this study were: 1) to compare the frequency of adverse outcome in STUMP based on enhanced criteria; and 2) to perform failure analysis to identify feature(s) helpful in predicting outcome...
March 14, 2018: Histopathology
David M Spooner, Holly Ruess, Carlos I Arbizu, Flor Rodríguez, Claudia Solís-Lemus
PREMISE OF THE STUDY: The species boundaries of wild and cultivated potatoes are controversial, with most of the taxonomic problems in the cultivated potato clade. We here provide the first in-depth phylogenetic study of the cultivated potato clade to explore possible causes of these problems. METHODS: We examined 131 diploid accessions, using 12 nuclear orthologs, producing an aligned data set of 14,072 DNA characters, 2171 of which are parsimony-informative. We analyzed the data to produce phylogenies and perform concordance analysis and goodness-of-fit tests...
January 2018: American Journal of Botany
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