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Chiricozzi A, Suarez-Farinas M, Fuentes-Duculan J, Cueto I, Li K, Tian S, Brodmerkel C, Krueger JG
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Increased expression of interleukin-17 pathway genes in nonlesional skin of moderate-to-severe psoriasis vulgaris
BRITISH JOURNAL OF DERMATOLOGY 2016 JAN; 174(1):136-145
Background Psoriasis vulgaris is an inflammatory immune-mediated disease, with lesional skin characterized by sharply demarcated, erythematous scaly plaques. Uninvolved psoriatic skin appears clinically similar to normal skin. However, it has been hypothesized that inflammatory cytokines, e.g. interleukin (IL)-17, may affect any organ or tissue having a vascular supply; thus, distant uninvolved skin could be exposed to increased circulating IL-17. Objectives To establish comparative genomic profiles between noninvolved skin and normal skin, in particular, determining immune abnormalities in distant uninvolved skin. Methods We performed a meta-analysis on three gene array studies, comparing the nonlesional (NL) psoriatic skin transcriptome with normal gene expression. We investigated immunological features of noninvolved skin, particularly linked to IL-17 signalling. Results We detected 252 differentially expressed gene transcripts in uninvolved skin compared with normal skin; multiple immune-related genes, including IL-17-downstream genes, were upregulated. Increased expression of IL-17-signature genes (e.g. DEFB4 and S100A7) was associated with an increased number of CD3+, CD8+ and DC-LAMP+ cells in NL skin vs. normal controls. Inducible T-cell costimulator (ICOS) expression was detected only in a few T-cells within NL skin. Conclusions Our data described the genomic profile in NL skin, characterizing the immune activation that was mainly attributed to IL-17 signalling.
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Q, Arenton MW, Boutle S, Cox B, Francis B, Goodell J, Hirosky R, Ledovskoy A, Li H, Lin C, Neu C, Wolfe E, Wood J, Xia F, Clarke C, Harr R, Karchin PE, Don CKK, Lamichhane P, Sturdy J, Belknap DA, Carlsmith D, Cepeda M, Christian A, Dasu S, Dodd L, Duric S, Friis E, Gomber B, Hall-Wilton R, Herndon M, Herve A, Klabbers P, Lanaro A, Levine A, Long K, Loveless R, Mohapatra A, Ojalvo I, Perry T, Pierro GA, Polese G, Ross I, Ruggles T, Sarangi T, Savin A, Sharma A, Smith N, Smith WH, Taylor D, Woods N
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Measurement of differential cross sections for Higgs boson production in the diphoton decay channel in pp collisions at root s=8TeV
EUROPEAN PHYSICAL JOURNAL C 2016 JAN 11; 76(1):? Article 13
A measurement is presented of differential cross sections for Higgs boson (H) production in pp collisions at root s = 8 TeV. The analysis exploits the H -> gamma gamma decay in data corresponding to an integrated luminosity of 19.7 fb(-1) collected by the CMS experiment at the LHC. The cross section is measured as a function of the kinematic properties of the diphoton system and of the associated jets. Results corrected for detector effects are compared with predictions at next-to-leading order and next-to-next-to-leading order in perturbative quantum chromodynamics, as well as with predictions beyond the standard model. For isolated photons with pseudorapidities vertical bar eta vertical bar < 2.5, and with the photon of largest and next-to-largest transverse momentum (p(T)(gamma)) divided by the diphoton mass m(gamma gamma) satisfying the respective conditions of p(T)(gamma)/m(gamma gamma) > 1/3 and > 1/4, the total fiducial cross section is 32 +/- 10 fb.
Schwiedrzik CM, Bernstein B, Melloni L
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Motion along the mental number line reveals shared representations for numerosity and space
ELIFE 2016 JAN 15; 5(?):? Article e10806
Perception of number and space are tightly intertwined. It has been proposed that this is due to 'cortical recycling', where numerosity processing takes over circuits originally processing space. Do such 'recycled' circuits retain their original functionality? Here, we investigate interactions between numerosity and motion direction, two functions that both localize to parietal cortex. We describe a new phenomenon in which visual motion direction adapts nonsymbolic numerosity perception, giving rise to a repulsive aftereffect: motion to the left adapts small numbers, leading to overestimation of numerosity, while motion to the right adapts large numbers, resulting in underestimation. The reference frame of this effect is spatiotopic. Together with the tuning properties of the effect this suggests that motion direction-numerosity cross-adaptation may occur in a homolog of area LIP. 'Cortical recycling' thus expands but does not obliterate the functions originally performed by the recycled circuit, allowing for shared computations across domains.
Perry M, Simon J, Gareau D, Glassberg J
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Bayesian analyses demonstrate tissue blood volume is not decreased during acute sickle cell pain episodes: A preliminary study
CLINICAL HEMORHEOLOGY AND MICROCIRCULATION 2016; 62(1):19-26
BACKGROUND: Pain is the most common complication of Sickle Cell Disease (SCD). Tissue oximetry properties in SCD during steady state and acute pain are not well described. METHODS: This was a cross sectional study of tissue oximetry properties in individuals with SCD during steady state, acute pain and healthy controls without SCD. A novel tissue oximetry device was used to better account for tissue pigmentation interference. We hypothesized that during acute SCD pain, blood volume to painful areas would be at least 10% less than steady state. Bayesian analyses of the data (with flat piors) were planned a priori because of the small projected sample size. RESULTS: The sample included 14 individuals (4 during crisis, 5 steady state, and 5 controls). In individuals with SCD, blood volume to the lower back was higher during crisis (0.18% of tissue volume vs. 0.14%). Bayesian analyses yielded a 3% probability that our hypothesis (that blood volume would decrease by 10%) was correct. CONCLUSIONS: During acute SCD pain, blood volume to painful areas is not decreased. Bayesian analyses were useful for interpretation of small sample data and may have utility in early phase trials for rare diseases.
Tian H, Sakmar TP, Huber T
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A simple method for enhancing the bioorthogonality of cyclooctyne reagent
CHEMICAL COMMUNICATIONS 2016; 52(31):5451-5454
The cross-reactivity between some cyclooctynes and thiols limits the bioorthogonality of the strain-promoted azide-alkyne cycloaddition reaction. We show that a low concentration of beta-mercaptoethanol significantly reduces the undesirable side reaction between bicyclononyne (BCN) and cysteine and while preserving free cysteines. We site-specifically label a genetically-encoded azido group in the visual photoreceptor rhodopsin to demonstrate the utility of the strategy.
Lee AJ, Moncada-Velez M, Picard C, Llanora G, Huang CH, Abel L, Chan SM, Lee BW, Casanova JL, Bustamante J, Shek LPC, Boisson-Dupuis S
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Severe Mycobacterial Diseases in a Patient with GOF I kappa B alpha Mutation Without EDA
JOURNAL OF CLINICAL IMMUNOLOGY 2016 JAN; 36(1):12-15
Musazzi L, Marrocco J
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The Many Faces of Stress: Implications for Neuropsychiatric Disorders
NEURAL PLASTICITY 2016; ?(?):? Article 8389737
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M, Garcia-Bellido A, Goldenzweig P, Han J, Harel A, Hindrichs O, Khukhunaishvili A, Petrillo G, Verzetti M, Demortier L, Arora S, Barker A, Chou JP, Contreras-Campana C, Contreras-Campana E, Duggan D, Ferencek D, Gershtein Y, Gray R, Halkiadakis E, Hidas D, Hughes E, Kaplan S, Elayavalli RK, Lath A, Panwalkar S, Park M, Salur S, Schnetzer S, Sheffield D, Somalwar S, Stone R, Thomas S, Thomassen P, Walker M, Foerster M, Riley G, Rose K, Spanier S, York A, Bouhali O, Hernandez AC, Dalchenko M, De Mattia M, Delgado A, Dildick S, Eusebi R, Flanagan W, Gilmore J, Kamon T, Krutelyov V, Montalvo R, Mueller R, Osipenkov I, Pakhotin Y, Patel R, Perloff A, Roe J, Rose A, Safonov A, Tatarinov A, Ulmer KA, Akchurin N, Cowden C, Damgov J, Dragoiu C, Dudero PR, Faulkner J, Kunori S, Lamichhane K, Lee SW, Libeiro T, Undleeb S, Volobouev I, Appelt E, Delannoy AG, Greene S, Gurrola A, Janjam R, Johns W, Maguire C, Mao Y, Melo A, Sheldon P, Snook B, Tuo S, Velkovska J, Xu Q, Arenton MW, Boutle S, Cox B, Francis B, Goodell J, Hirosky R, Ledovskoy A, Li H, Lin C, Neu C, Wolfe E, Wood J, Xia F, Clarke C, Harr R, Karchin PE, Don CKK, Lamichhane P, Sturdy J, Belknap DA, Carlsmith D, Cepeda M, Christian A, Dasu S, Dodd L, Duric S, Friis E, Gomber B, Grothe M, Hall-Wilton R, Herndon M, Herve A, Klabbers P, Lanaro A, Levine A, Long K, Loveless R, Mohapatra A, Ojalvo I, Perry T, Pierro GA, Polese G, Ross I, Ruggles T, Sarangi T, Savin A, Smith N, Smith WH, Taylor D, Woods N
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Search for resonant t(t)over-bar production in proton-proton collisions at root s=8 TeV
PHYSICAL REVIEW D 2016 JAN 8; 93(1):? Article 012001
A search is performed for the production of heavy resonances decaying into top-antitop quark pairs in proton-proton collisions at root s = 8 TeV. Data used for the analyses were collected with the CMS detector and correspond to an integrated luminosity of 19.7 fb(-1). The search is performed using events with three different final states, defined by the number of leptons (electrons and muons) from the t (t) over bar. WbWb decay. The analyses are optimized for reconstruction of top quarks with high Lorentz boosts, where jet substructure techniques are used to enhance the sensitivity. Results are presented for all channels and a combination is performed. No significant excess of events relative to the expected yield from standard model processes is observed. Upper limits on the production cross section of heavy resonances decaying to t (t) over bar are calculated. A narrow leptophobic topcolor Z' resonance with a mass below 2.4 TeV is excluded at 95% confidence level. Limits are also derived for a broad Z' resonance with a 10% width relative to the resonance mass, and a Kaluza-Klein excitation of the gluon in the Randall-Sundrum model. These are the most stringent limits to date on heavy resonances decaying into top-antitop quark pairs.
Roberts WM, Augustine SB, Lawton KJ, Lindsay TH, Thiele TR, Izquierdo EJ, Faumont S, Lindsay RA, Britton MC, Pokala N, Bergmann CI, Lockery SR
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A stochastic neuronal model predicts random search behaviors at multiple spatial scales in C. elegans
ELIFE 2016 JAN 29; 5(?):? Article e12572
Random search is a behavioral strategy used by organisms from bacteria to humans to locate food that is randomly distributed and undetectable at a distance. We investigated this behavior in the nematode Caenorhabditis elegans, an organism with a small, well-described nervous system. Here we formulate a mathematical model of random search abstracted from the C. elegans connectome and fit to a large-scale kinematic analysis of C. elegans behavior at submicron resolution. The model predicts behavioral effects of neuronal ablations and genetic perturbations, as well as unexpected aspects of wild type behavior. The predictive success of the model indicates that random search in C. elegans can be understood in terms of a neuronal flip-flop circuit involving reciprocal inhibition between two populations of stochastic neurons. Our findings establish a unified theoretical framework for understanding C. elegans locomotion and a testable neuronal model of random search that can be applied to other organisms.
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Study of B Meson Production in p plus Pb Collisions at root s(NN)=5.02 TeV Using Exclusive Hadronic Decays
PHYSICAL REVIEW LETTERS 2016 JAN 22; 116(3):? Article 032301
The production cross sections of the B+, B-0, and B-s(0) mesons, and of their charge conjugates, are measured via exclusive hadronic decays in p + Pb collisions at the center-of-mass energy root s(NN) = 5.02 TeV with the CMS detector at the CERN LHC. The data set used for this analysis corresponds to an integrated luminosity of 34.6 nb(-1). The production cross sections are measured in the transverse momentum range between 10 and 60 GeV/c. No significant modification is observed compared to proton-proton perturbative QCD calculations scaled by the number of incoherent nucleon-nucleon collisions. These results provide a baseline for the study of in-medium b quark energy loss in Pb + Pb collisions.