Publications search

Tetherin encodes an interferon-inducible antiviral protein that traps a broad spectrum of enveloped viruses at infected cell surfaces. Despite the absence of any clearly related gene or activity, we describe possible scenarios by which tetherin arose that exemplify how protein modularity, evolvability, and robustness can create and preserve new functions. We find that tetherin genes in various organisms exhibit no sequence similarity and share only a common architecture and location in modern genomes. Moreover, tetherin is part of a cluster of three potential sister genes encoding proteins of similar architecture, some variants of which exhibit antiviral activity while others can be endowed with antiviral activity by a simple modification. Only in slowly evolving species (e.g., coelacanths) does tetherin exhibit sequence similarity to one potential sister gene. Neofunctionalization, drift, and genetic conflict appear to have driven a near complete loss of sequence similarity among modern tetherin genes and their sister genes.

Psoriasis is a chronic inflammatory disease associated with a variety of co-morbid conditions, including cardiovascular disease. Advancements in our understanding of the cellular and molecular mechanisms of psoriasis have led to a better understanding regarding its pathogenesis, which in turn has stimulated ongoing research to identify the underlying pathophysiology responsible for the increased risk of cardiovascular events associated with psoriasis. Although not yet fully elucidated, emerging evidence points to immune-mediated inflammation as a process that contributes to endothelial cell dysfunction, dyslipidemia, and atherosclerosis as key processes influencing cardiovascular disease in psoriasis. In particular, the dyslipidemia present in psoriasis may be associated with altered lipoprotein function and increased atherogenicity. Here, we review how the cytokine networks involved in lipoprotein metabolism and inflammation could impact on the cardiovascular disease risk for patients with psoriasis. Published by Elsevier Inc.

The persistence of tick-borne encephalitis virus (TBEV) in nature is maintained by numerous species of reservoir hosts, multiple transmissions between vertebrates and invertebrates, and the virus adaptation to its hosts. Our Aim: was to compare TBEV isolates from ticks and small wild mammals to estimate their roles in the circulation of the viral subtypes. Methods: TBEV isolates from two species of ixodid ticks, four species of rodents, and one species of shrews in the Novosibirsk region, South-Western Siberia, Russia, were analyzed using bioassay, hemagglutination, hemagglutination inhibition, neutralization tests, ELISA, reverse transcription with real-time PCR, and phylogenetic analysis. Results: TBEV RNA and/or protein E were found in 70.9% +/- 3.0% of mammals and in 3.8% +/- 0.4% of ticks. The TBEV infection rate, main subtypes, and neurovirulence were similar between ixodid tick species. However, the proportions of the virus that were pathogenic for laboratory mice and of the Far-Eastern (FE) subtype, as well as the viral loads with the Siberian and the European subtypes for the TBEV in Ixodes pavlovskyi Pomerantsev, 1946 were higher than in Ixodes persulcatus (P. Schulze, 1930). Percentages of infected Myodes rutilus, Sicista betulina, and Sorex araneus exceeded those of Apodemus agrarius and Myodes rufocanus. Larvae and nymphs of ticks were found mainly on rodents, especially on Myodes rufocanus and S. betulina. The proportion of TBEV-mixed infections with different subtypes in the infected ticks (55.9% +/- 6.5%) was higher than in small mammals (36.1% +/- 4.0%) (p < 0.01). Conclusions: Molecular typing revealed mono-or mixed infection with three main subtypes of TBEV in ticks and small mammals. The Siberian subtype was more common in ixodid ticks, and the FE subtype was more common in small mammals (p < 0.001). TBEV isolates of the European subtype were rare. TBEV infection among different species of small mammals did not correlate with their infestation rate with ticks in the Novosibirsk region, Russia.

A search for a narrow baryonic state in the pK(S)(0) and (p) over barK(S)(0) system has been performed in ep collisions at HERA with the ZEUS detector using an integrated luminosity of 358 pb(-1) taken in 2003-2007. The search was performed with deep inelastic scattering events at an ep centre-of-mass energy of 318 GeV for exchanged photon virtuality, Q(2), between 20 and 100 GeV2. Contrary to evidence presented for such a state around 1.52 GeV in a previous ZEUS analysis using a sample of 121 pb(-1) taken in 1996-2000, no resonance peak was found in the p((p) over bar )K-S(0) invariant-mass distribution in the range 1.45-1.7 GeV. Upper limits on the production cross section are set. (C) 2016 The Author(s). Published by Elsevier B.V.

Joubert Syndrome (JS) is an inherited ciliopathy associated with mutations in genes essential in primary cilium function. Whole exome sequencing in a multiplex consanguineous family from India revealed a KIAA0556 homozygous single base pair deletion mutation (c.4420del; p.Met1474Cysfs*11). Knockdown of the gene in zebrafish resulted in a ciliopathy phenotype, rescued by co-injection of wildtype cDNA. Affected siblings present a mild and classical form of Joubert syndrome allowing for further delineation of the JS associated genotypic spectrum.

Polyamines play important roles in a range of cellular processes. In this issue of Cell Host & Microbe, Mounce et al. (2016) link polyamine metabolism to the interferon response and demonstrate proviral effects for polyamines. The study points to the pathway as a potential novel pan-viral therapeutic target.

Atopic dermatitis (AD) is a complex skin disease frequently associated with other diseases of the atopic diathesis. Recent evidence supports the concept that AD can also recognize other comorbidities, such as chronic inflammatory bowel or cardiovascular diseases. These comorbidities might result from chronic cutaneous inflammation or from a common, yet-to-bedefined immunologic background leading to immune deviations. The activation of immune cells and their migration to the skin play an essential role in the pathogenesis of AD. In patients with AD, an underlying immune deviation might result in higher susceptibility of the skin to environmental factors. There is a high unmet medical need to define immunologic endotypes of AD because it has significant implications on upcoming stratification of the phenotype of AD and the resulting targeted therapies in the development of precision medicine. This review article emphasizes studies on environmental factors affecting AD development and novel biological agents used in the treatment of AD. Best evidence of the clinical efficacy of novel immunologic approaches using biological agents in patients with AD is available for the anti-IL-4 receptor alpha-chain antibody dupilumab, but a number of studies are currently ongoing with other specific antagonists to immune system players. These targeted molecules can be expressed on or drive the cellular players infiltrating the skin (eg, T lymphocytes, dendritic cells, or eosinophils). Such approaches can have immunomodulatory and thereby beneficial clinical effects on the overall skin condition, as well as on the underlying immune deviation that might play a role in comorbidities. An effect of these immunologic treatments on pruritus and the disturbed microbiome in patients with AD has other potential consequences for treatment.

BackgroundChronic hand and foot eczema (CHFE), a prevalent debilitating disorder affecting approximately 15% of the population, presents a socioeconomic and psychosocial burden for patients and often follows a chronic course, refractory to conventional therapies. Thus, a large need exists for more effective therapeutics; the excimer laser (308 nm) is effective for some inflammatory skin diseases, but its efficacy has not been evaluated for CHFE. MethodsThe study is a retrospective chart review conducted on 30 patients with recalcitrant CHFE (19 with hand involvement, four with foot involvement, and seven with both) treated twice weekly with excimer laser (308 nm) single wavelength ultraviolet (UV)B radiation between January 2013 and December 2014. ResultsImprovements in clinical scores included a 69% reduction in average physician's global assessment (PGA) scores (from 2.77 at baseline to 0.87 after treatment, P < 0.0001) with a parallel reduction in average modified total lesion/symptom scores of 70% (from 10.2 to 3.1, P < 0.0001). Only mild sunburn-like reactions were observed. ConclusionThis report evaluates excimer laser for patients with refractory CHFE and shows excellent and sustained efficacy for this treatment. Compared to other UV therapies, excimer laser offers lower cumulative doses of UV radiation by targeting specific areas. This effective treatment should be considered alone or in combination with other established or newer therapies.

We show here that the Saccharomyces cerevisiae GARP complex and the Cog1-4 subcomplex of the COG complex, both members of the complexes associated with tethering containing helical rods (CATCHR) family of multisubunit tethering complexes, share the same subunit organization. We also show that HOPS, a tethering complex acting in the endolysosomal pathway, shares a similar architecture, thus suggesting that multisubunit tethering complexes use related structural frameworks.

The decorrelation in the azimuthal angle between the most forward and the most backward jets (Mueller-Navelet jets) is measured in data collected in pp collisions with the CMS detector at the LHC at root s = 7 TeV. The measurement is presented in the form of distributions of azimuthal-angle differences, Delta phi, between the Mueller-Navelet jets, the average cosines of (pi - Delta phi), 2(pi - Delta phi), and 3(pi - Delta phi), and ratios of these cosines. The jets are required to have transverse momenta, p(T), in excess of 35 GeV and rapidities, |y|, of less than 4.7. The results are presented as a function of the rapidity separation, Delta y, between the Mueller-Navelet jets, reaching Delta y up to 9.4 for the first time. The results are compared to predictions of various Monte Carlo event generators and to analytical predictions based on the DGLAP and BFKL parton evolution schemes.