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Bhupathiraju NVSDK, Rizvi W, Batteas JD, Drain CM
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Fluorinated porphyrinoids as efficient platforms for new photonic materials, sensors, and therapeutics
ORGANIC & BIOMOLECULAR CHEMISTRY 2016; 14(2):389-408
Porphyrinoids are robust heterocyclic dyes studied extensively for their applications in medicine and as photonic materials because of their tunable photophysical properties, diverse means of modifying the periphery, and the ability to chelate most transition metals. Commercial applications include their use as phthalocyanine dyes in optical discs, porphyrins in photodynamic therapy, and as oxygen sensors. Most applications of these dyes require exocyclic moieties to improve solubility, target diseases, modulate photophysical properties, or direct the self-organization into architectures with desired photonic properties. The synthesis of the porphyrinoid depends on the desired application, but the de novo synthesis often involves several steps, is time consuming, and results in low isolated yields. Thus, the application of core porphyrinoid platforms that can be rapidly and efficiently modified to evaluate new molecular architectures allows researchers to focus on the design concepts rather than the synthesis methods, and opens porphyrinoid chemistry to a broader scientific community. We have focused on several widely available, commercially viable porphyrinoids as platforms: meso-perfluorophenylporphyrin, perfluorophthalocyanine, and meso-perfluorophenylcorrole. The perfluorophenylporphyrin is readily converted to the chlorin, bacteriochlorin, and isobacteriochlorin. Derivatives of all six of these core platforms can be efficiently and controllably made via mild nucleophilic aromatic substitution reactions using primary S, N, and O nucleophiles bearing a wide variety of functional groups. The remaining fluoro groups enhance the photo and oxidative stability of the dyes and can serve as spectroscopic signatures to characterize the compounds or in imaging applications using F-19 NMR. This review provides an overview of the chemistry of fluorinated porphyrinoids that are being used as a platform to create libraries of photo-active compounds for applications in medicine and materials.
Fins JJ
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In Remembrance, with Thanks to Voltaire
CAMBRIDGE QUARTERLY OF HEALTHCARE ETHICS 2016 JAN; 25(1):107-109
Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, Brandstetter J, Brondolin E, Dragicevic M, Eroe J, Flechl M, Friedl M, Fruehwirth R, Ghete VM, Hartl C, Hoermann N, Hrubec J, Jeitler M, Knuenz V, Koenig A, Krammer M, Kraetschmer I, Liko D, Matsushita T, Mikulec I, Rabady D, Rahbaran B, Rohringer H, Schieck J, Schoefbeck R, Strauss J, Treberer-Treberspurg W, Waltenberger W, Wulz CE, Mossolov V, Shumeiko N, Gonzalez JS, Alderweireldt S, Cornelis T, De Wolf EA, Janssen X, Knutsson A, Lauwers J, Luyckx S, Ochesanu S, Rougny R, De Klundert MV, Van Haevermaet H, Van Mechelen P, Van Remortel N, Van Spilbeeck A, Abu Zeid S, Blekman F, D'Hondt J, Daci N, De Bruyn I, Deroover K, Heracleous N, Keaveney J, Lowette S, Moreels L, Olbrechts A, Python Q, Strom D, Tavernier S, Van Doninck W, Van Mulders P, Van Onsem GP, Van Parijs I, Barria P, Brun H, Caillol C, Clerbaux B, De Lentdecker G, Delannoy H, Fasanella G, Favart L, Gay APR, Grebenyuk A, Karapostoli G, Lenzi T, Leonard A, Maerschalk T, Marinov A, Pernie L, Randle-conde A, Reis T, Seva T, Vander Velde C, Vanlaer P, Yonamine R, Zenoni F, Zhang F, Beernaert K, Benucci L, Cimmino A, Crucy S, Dobur D, Fagot A, Garcia G, Gul M, Mccartin J, Rios AAO, Poyraz D, Ryckbosch D, Salva S, Sigamani M, Strobbe N, Tytgat M, Van Driessche W, Yazgan E, Zaganidis N, Basegmez S, Beluffi C, Bondu O, Brochet S, Bruno G, Castello R, Caudron A, Ceard L, Da Silveira GG, Delaere C, Favart D, Forthomme L, Giammanco A, Hollar J, Jafari A, Jez P, Komm M, Lemaitre V, Mertens A, Nuttens C, Perrini L, Pin A, Piotrzkowski K, Popov A, Quertenmont L, Selvaggi M, Marono MV, Beliy N, Hammad GH, Alda WL, Alves GA, Brito L, Martins MC, Hamer M, Hensel C, Herrera CM, Moraes A, Pol ME, Teles PR, Das Chagas EBB, Carvalho W, Chinellato J, Custodio A, Da Costa EM, Damiao DD, Martins CD, De Souza SF, Guativa LMH, Malbouisson H, Figueiredo DM, Mundim L, Nogima H, Da Silva WLP, Santoro A, Sznajder A, Manganote EJT, Pereira AV, Ahuja S, Bernardes CA, Santos AD, Dogra S, Tomei TRFP, Gregores EM, Mercadante PG, Moon CS, Novaes SF, Padula SS, Abad DR, Vargas JCR, Aleksandrov A, Hadjiiska R, Iaydjiev P, Rodozov M, Stoykova S, Sultanov G, Vutova M, Dimitrov A, Glushkov I, Litov L, Pavlov B, Petkov P, Ahmad M, Bian JG, Chen GM, Chen HS, Chen M, Cheng T, Du R, Jiang CH, Plestina R, Romeo F, Shaheen SM, Tao J, Wang C, Wang Z, Zhang H, Asawatangtrakuldee C, Ban Y, Li Q, Liu S, Mao Y, Qian SJ, Wang D, Xu Z, Zou W, Avila C, Cabrera A, Sierra LFC, Florez C, Gomez JP, Moreno BG, Sanabria JC, Godinovic N, Lelas D, Puljak I, Cipriano PMR, Antunovic Z, Kovac M, Brigljevic V, Kadija K, Luetic J, Micanovic S, Sudic L, Attikis A, Mavromanolakis G, Mousa J, Nicolaou C, Ptochos F, Razis PA, Rykaczewski H, Bodlak M, Finger M, Finger M, Abdelalim AA, Awad A, El Sawy M, Mahrous A, Mohamed A, Radi A, Calpas B, Kadastik M, Murumaa M, Raidal M, Tiko A, Veelken C, Eerola P, Pekkanen J, Voutilainen M, Harkonen J, Karimaki V, Kinnunen R, Lampen T, 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GN, Kim MS, Kong DJ, Lee S, Oh YD, Sakharov A, Son DC, Cifuentes JAB, Kim H, Kim TJ, Ryu MS, Song S, Choi S, Go Y, Gyun D, Hong B, Jo M, Kim H, Kim Y, Lee B, Lee K, Lee KS, Lee S, Park SK, Roh Y, Yoo HD, Choi M, Kim H, Kim JH, Lee JSH, Park IC, Ryu G, Choi Y, Choi YK, Goh J, Kim D, Kwon E, Lee J, Yu I, Juodagalvis A, Vaitkus J, Ahmed I, Ibrahim ZA, Komaragiri JR, Ali MABM, Idris FM, Abdullah WATW, Yusli MN, Linares EC, Castilla-Valdez H, De La Cruz-Burelo E, Heredia-de La Cruz I, Hernandez-Almada A, Lopez-Fernandez R, Sanchez-Hernandez A, Moreno SC, Valencia FV, Pedraza I, Ibarguen HAS, Pineda AM, Krofcheck D, Butler PH, Ahmad A, Ahmad M, Hassan Q, Hoorani HR, Khan WA, Khurshid T, Shoaib M, Bialkowska H, Bluj M, Boimska B, Frueboes T, Gorski M, Kazana M, Nawrocki K, Romanowska-Rybinska K, Szleper M, Zalewski P, Brona G, Bunkowski K, Doroba K, Kalinowski A, Konecki M, Krolikowski J, Misiura M, Olszewski M, Walczak M, Bargassa P, Silva CBDE, Di Francesco A, Faccioli P, Parracho PGF, 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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, 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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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.
Sela U, Park CG, Park A, Olds P, Wang S, Steinman RM, Fischetti VA
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Dendritic Cells Induce a Subpopulation of IL-12R beta 2-Expressing Treg that Specifically Consumes IL-12 to Control Th1 Responses
PLOS ONE 2016 JAN 8; 11(1):? Article e0146412
Cytokines secreted from dendritic cells (DCs) play an important role in the regulation of T helper (Th) cell differentiation and activation into effector cells. Therefore, controlling cytokine secretion from DCs may potentially regulate Th differentiation/activation. DCs also induce de-novo generation of regulatory T cells (Treg) that modulate the immune response. In the current study we used the mixed leukocyte reaction (MLR) to investigate the effect of allospecific Treg on IL-12, TNF alpha and IL-6 secretion by DCs. Treg cells were found to markedly down-regulate IL-12 secretion from DCs following stimulation with TLR7/8 agonist. This down-regulation of IL-12 was neither due to a direct suppression of its production by the DCs nor a result of marked DC death. We found that IL-12 was rather actively consumed by Treg cells. IL-12 consumption was mediated by a subpopulation of IL-12R beta 2-expressing Treg cells and was dependent on MHC class-II expressed on dendritic cells. Furthermore, IL-12 consumption by Tregs increased their suppressive effect on T cell proliferation and Th1 activation. These results provide a new pathway of Th1 response regulation where IL-12 secreted by DCs is consumed by a sub-population of IL-12R beta 2-expressing Treg cells. Consumption of IL-12 by Tregs not only reduces the availability of IL-12 to Th effector cells but also enhances the Treg immunosuppressive effect. This DC-induced IL12R beta 2-expressing Treg subpopulation may have a therapeutic advantage in suppressing Th1 mediated autoimmunity.
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Observation of top quark pairs produced in association with a vector boson in pp collisions at root s=8 TeV
JOURNAL OF HIGH ENERGY PHYSICS 2016 JAN 18; ?(1):? Article 096
Measurements of the cross sections for top quark pairs produced in association with a W or Z boson are presented, using 8 TeV pp collision data corresponding to an integrated luminosity of 19.5 fb(-1), collected by the CMS experiment at the LHC. Final states are selected in which the associated W boson decays to a charged lepton and a neutrino or the Z boson decays to two charged leptons. Signal events are identified by matching reconstructed objects in the detector to specific final state particles from t (t) over barW or t (t) over barZ decays. The t (t) over barW cross section is measured to be 382(-102)(+117) fb with a significance of 4.8 standard deviations from the background-only hypothesis. The t (t) over barZ cross section is measured to be 242(-55)(+65) fb with a significance of 6.4 standard deviations from the background-only hypothesis. These measurements are used to set bounds on five anomalous dimension-six operators that would affect the t (t) over barW and t (t) over barZ cross sections.
Conceicao T, Coelho C, Silva IS, de Lencastre H, Aires-de-Sousa M
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Methicillin-Resistant Staphylococcus aureus in the Community in Luanda, Angola: Blurred Boundaries with the Hospital Setting
MICROBIAL DRUG RESISTANCE 2016 JAN 1; 22(1):22-27
Although the nosocomial prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in Angola is over 60% and one of the highest in Africa, the extent of MRSA in the community is unknown. To fill this gap, we conducted a hospital-based study in which 158 children attending the emergency ward and ambulatory services of a pediatric hospital in Luanda, the capital of Angola, were screened for S. aureus nasal colonization. Overall, 70 (44.3%) individuals were colonized with S. aureus, of which 20 (28.6%) carried MRSA, resulting in a prevalence of 12.7% (20/158) of MRSA in the population screened. Molecular characterization by pulsed-field gel electrophoresis (PFGE), spa typing, multilocus sequence typing, and SCCmec typing distributed the isolates into two major MRSA clones and one dominant methicillin-susceptible S. aureus (MSSA) lineage, corresponding to the main clones circulating in hospitals in Luanda. The MRSA isolates mainly belonged to clones A (PFGE type A, spa type t105, ST5-IVa-65%) and B (PFGE B, t3869, ST88-IVa-30%), while MSSA isolates mainly belonged to clone L (PFGE type L, t861, ST508-42%). S. aureus isolates showed resistance to penicillin (96%), rifampin (87%), and trimethoprim-sulfamethoxazole (21%). In conclusion, the prevalence of MRSA among children in the community in Luanda is high and seems to originate from hospitals, warranting continuous monitoring and implementation of additional infection control measures.
Guttman-Yassky E, Ungar B, Noda S, Suprun M, Shroff A, Dutt R, Khattri S, Min M, Mansouri Y, Zheng XZ, Estrada YD, Singer GK, Suarez-Farinas M, Krueger JG, Lebwohl MG
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Extensive alopecia areata is reversed by IL-12/IL-23p40 cytokine antagonism
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 2016 JAN; 137(1):301-304
Levran O, Peles E, Randesi M, da Rosa JC, Ott J, Rotrosen J, Adelson M, Kreek MJ
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Glutamatergic and GABAergic susceptibility loci for heroin and cocaine addiction in subjects of African and European ancestry
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY 2016 JAN 4; 64(?):118-123
Background: Drug addiction, a leading health problem, is a chronic brain disease with a significant genetic component. Animal models and clinical studies established the involvement of glutamate and GABA neurotransmission in drug addiction. This study was designed to assess if 258 variants in 27 genes of these systems contribute to the vulnerability to develop drug addiction. Methods: Four independent analyses were conducted in a sample of 1860 subjects divided according to drug of abuse (heroin or cocaine) and ancestry (African and European). Results: A total of 11 SNPs in eight genes showed nominally significant associations (P < 0.01) with heroin and/or cocaine addiction in one or both ancestral groups but the associations did not survive correction for multiple testing. Of these SNPs, the GAD1 upstream SNP rs1978340 is potentially functional as it was shown to affect GABA concentrations in the cingulate cortex. In addition, SNPs GABRB3 rs7165224; DBI rs12613135; GAD1 SNPs rs2058725, rs1978340, rs2241164; and GRIN2A rs1650420 were previously reported in associations with drug addiction or related phenotypes. Conclusions: The study supports the involvement of genetic variation in the glutamatergic and GABAergic systems in drug addiction with partial overlap in susceptibility loci between cocaine and heroin addiction. (C) 2015 Elsevier Inc. All rights reserved.
Evering TH, Applebaum A, La Mar M, Garmon D, Dorfman D, Markowitz M
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Rates of non-confounded HIV-associated neurocognitive disorders in men initiating combination antiretroviral therapy during primary infection
AIDS 2016 JAN; 30(2):203-210
Objective:To determine the prevalence of HIV-associated neurocognitive disorders (HAND) in HIV-infected participants who initiated combination antiretroviral therapy (cART) during primary infection.Design:Cross-sectional observational study.Methods:HIV-infected men without neuropsychiatric confounds who had initiated cART during primary infection were administered a neuropsychological battery as well as questionnaires evaluating depression and quality of life. Eligibility was determined by a medical examination with history and review of records.Results:Twenty-six primarily non-Hispanic white (73%), male (100%) participants were enrolled and underwent neurocognitive assessment. Mean age was 43 (28-71) years, with a median of 17 years of education (13-24). Median current and nadir CD4(+) T-cell counts were 828 (506-1411) and 359 (150-621) cells/l. All participants had plasma HIV-1 RNA less than 50copies/ml. Median duration of cART prior to enrolment was 5.7 years (2.2-9.9). Median global deficit score was 0.17 (0.00-0.60). Only one (4%) participant was impaired.Conclusion:Rates of HAND in this cohort of HIV-infected men without comorbid conditions who initiated early cART are low. Our findings suggest a possible neuroprotective benefit of early cART and an important contribution of comorbidities to observed HAND prevalence.
Fuchs E
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Epithelial Skin Biology: Three Decades of Developmental Biology, a Hundred Questions Answered and a Thousand New Ones to Address
ESSAYS ON DEVELOPMENTAL BIOLOGY, PT A 2016; 116(?):357-374
The mammalian skin epidermis and its hair and sweat gland appendages provide a protective barrier that retains essential body fluids, guards against invasion by harmful microbes, and regulates body temperature through the ability to sweat. At the interface between the external environment and the body, skin is constantly subjected to physical trauma and must also be primed to repair wounds in response to injury. In adults, the skin maintains epidermal homeostasis, hair regeneration, and wound repair through the use of its stem cells. This essay focuses on when stem cells become established during skin development and where these cells reside in adult epithelial tissues of the skin. I explore how skin stem cells maintain tissue homeostasis and repair wounds and how they regulate the delicate balance between proliferation and differentiation. Finally, I tackle the relation between skin cancer and mutations that perturb the regulation of stem cells.