An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo

Molecular characterization and antiviral activity test of common drugs against echovirus 18 isolated in Korea

Genetic diversity and antiviral activity for five common antiviral drugs of echovirus (ECV) 5 isolated in Korea have been described. The present study extended these tests to a Korean ECV 18 isolate. An outbreak of aseptic meningitis caused by the ECV 18 isolate was reported in Korea in 2005, marking the first time this virus had been identified in the country since enterovirus surveillance began in 1993. Using a sample isolated from stool specimen of a 5-year-old male patient with aseptic meningitis, the complete genome sequence was obtained and was compared it with the Metcalf prototype strain. Unlike the ECV5 isolate, the 3' untranslated region had the highest identity value (94.2%) at the nucleotide level, while, at the amino acid level, the P2 region displayed the highest identity value (96.9%). These two strains shared all cleavage sites, with the exception of the 2B/2C site, which was RQ/NN in the Metcalf strain but RQ/NS in the Korean ECV 18 isolate. In Vero cells infected with the Korean ECV 18 isolate, no cytotoxicity was observed in the presence of azidothymidine, acyclovir, amantadine, lamivudine, or ribavirin, when the drugs were administered at a CC50 value >100 μg/mL. Of the five drugs, only amantadine (IC50: 4.97 ± 0.77 μg/mL, TI: 20.12) and ribavirin (IC50: 7.63 ± 0.87 μg/mL, TI: 13.11) had any antiviral activity against the Korean ECV 18 isolate in the five antiviral drugs. These antiviral activity effects were similar with results of the Korean ECV5 isolate

The mimetic politics of lone-wolf terrorism

Written at a time of crisis in the project of social and political modernity, Fyodor Dostoevsky’s 1864 novel Notes from Underground offers an intriguing parallel for the twenty-first century lone-wolf; it portrays an abject, outcast, spiteful unnamed anti-hero boiling with rage, bitter with resentment and on the verge of radicalisation. A Girardian reading of the poetic truths contained in Dostoevsky’s work is able to provide important keys to explain the contemporary transformation from ‘fourth-wave’ religious terrorism to ‘fifth-wave’ lone-wolf terrorism. Such a reading argues that it is mimetic rivalry – rather than much-trumpeted forms of religious violence or cultural differences – that fuels the triangular relation between governments, terrorists and civilian victims at heart of terrorist acts. This approach is further able to blend social inquiry with an account of the individual, in fact anthropological, conditions of lone-wolf terrorism by tracing the globalisation of resentment and the individualisation of violence to the hyper-mimeticism characterising the globalisation of late modernity. Finally, a mimetic reading of ‘fifth-wave’ terrorism accounts for the turbulence of a global politics in which victimhood and scapegoating no longer have the ability to stabilise social order and warns against a future where violence proliferates and escalates unchecked

Mineralogy of a Mudstone at Yellowknife Bay, Gale Crater, Mars

Sedimentary rocks at Yellowknife Bay (Gale Crater) on Mars include mudstone sampled by the Curiosity rover. The samples, John Klein and Cumberland, contain detrital basaltic minerals, Ca-sulfates, Fe oxide/hydroxides, Fe-sulfides, amorphous material, and trioctahedral smectites. The John Klein smectite has basal spacing of ~10 Å indicating little interlayer hydration. The Cumberland smectite has basal spacing at ~13.2 Å as well as ~10 Å. The ~13.2 Å spacing suggests a partially chloritized interlayer or interlayer Mg or Ca facilitating H_2O retention. Basaltic minerals in the mudstone are similar to those in nearby eolian deposits. However, the mudstone has far less Fe-forsterite, possibly lost with formation of smectite plus magnetite. Late Noachian/Early Hesperian or younger age indicates that clay mineral formation on Mars extended beyond Noachian time