Comparison of serological assays in human Middle East respiratory syndrome (MERS)-coronavirus infection

Plaque reduction neutralisation tests (PRNT), microneutralisation (MN), Middle East respiratory syndrome (MERS)-spike pseudoparticle neutralisation (ppNT) and MERS S1-enzyme-linked immunosorbent assay (ELISA) antibody titres were compared using 95 sera from 17 patients with MERS, collected two to 46 days after symptom onset. Neutralisation tests correlated well with each other and moderately well with S1 ELISA. Moreover to compare antigenic similarity of genetically diverse MERS-CoV clades, the response of four sera from two patients sampled at two time periods during the course of illness were tested by 90% PRNT. Genetically diverse MERS-CoV clades were antigenically homogenous.published_or_final_versio

MERS-CoV antibody responses 1 Year after symptom onset, South Korea, 2015

We investigated the kinetics of the Middle East respiratory syndrome coronavirus (MERS-CoV) neutralizing and spike protein antibody titers over the course of 1 year in 11 patients who were confirmed by reverse transcription PCR to have been infected during the outbreak in South Korea in 2015. Robust antibody responses were detected in all survivors who had severe disease; responses remained detectable, albeit with some waning, for <1 year. The duration of viral RNA detection (but not viral load) in sputum significantly correlated with the antibody response magnitude. The MERS S1 ELISA antibody titers correlated well with the neutralizing antibody response. Antibody titers in 4 of 6 patients who had mild illness were undetectable even though most had evidence of pneumonia. This finding implies that MERS-CoV seroepidemiologic studies markedly underestimate the extent of mild and asymptomatic infection. Obtaining convalescent-phase plasma with high antibody titers to treat MERS will be challenging.published_or_final_versio

An Efficient Representation of Euclidean Gravity I

We explore how the topology of spacetime fabric is encoded into the local structure of Riemannian metrics using the gauge theory formulation of Euclidean gravity. In part I, we provide a rigorous mathematical foundation to prove that a general Einstein manifold arises as the sum of SU(2)_L Yang-Mills instantons and SU(2)_R anti-instantons where SU(2)_L and SU(2)_R are normal subgroups of the four-dimensional Lorentz group Spin(4) = SU(2)_L x SU(2)_R. Our proof relies only on the general properties in four dimensions: The Lorentz group Spin(4) is isomorphic to SU(2)_L x SU(2)_R and the six-dimensional vector space of two-forms splits canonically into the sum of three-dimensional vector spaces of self-dual and anti-self-dual two-forms. Consolidating these two, it turns out that the splitting of Spin(4) is deeply correlated with the decomposition of two-forms on four-manifold which occupies a central position in the theory of four-manifolds.Comment: 31 pages, 1 figur

Chicken genome analysis reveals novel genes encoding biotin-binding proteins related to avidin family

BACKGROUND: A chicken egg contains several biotin-binding proteins (BBPs), whose complete DNA and amino acid sequences are not known. In order to identify and characterise these genes and proteins we studied chicken cDNAs and genes available in the NCBI database and chicken genome database using the reported N-terminal amino acid sequences of chicken egg-yolk BBPs as search strings. RESULTS: Two separate hits showing significant homology for these N-terminal sequences were discovered. For one of these hits, the chromosomal location in the immediate proximity of the avidin gene family was found. Both of these hits encode proteins having high sequence similarity with avidin suggesting that chicken BBPs are paralogous to avidin family. In particular, almost all residues corresponding to biotin binding in avidin are conserved in these putative BBP proteins. One of the found DNA sequences, however, seems to encode a carboxy-terminal extension not present in avidin. CONCLUSION: We describe here the predicted properties of the putative BBP genes and proteins. Our present observations link BBP genes together with avidin gene family and shed more light on the genetic arrangement and variability of this family. In addition, comparative modelling revealed the potential structural elements important for the functional and structural properties of the putative BBP proteins

On the Temperature Dependence of the Shear Viscosity and Holography

We examine the structure of the shear viscosity to entropy density ratio eta/s in holographic theories of gravity coupled to a scalar field, in the presence of higher derivative corrections. Thanks to a non-trivial scalar field profile, eta/s in this setup generically runs as a function of temperature. In particular, its temperature behavior is dictated by the shape of the scalar potential and of the scalar couplings to the higher derivative terms. We consider a number of dilatonic setups, but focus mostly on phenomenological models that are QCD-like. We determine the geometric conditions needed to identify local and global minima for eta/s as a function of temperature, which translate to restrictions on the signs and ranges of the higher derivative couplings. Finally, such restrictions lead to an holographic argument for the existence of a global minimum for eta/s in these models, at or above the deconfinement transition.Comment: references adde

Management model for the logistics and competitiveness of SMEs in the city of Barranquilla

In Colombia, small and medium-sized enterprises (SMEs) are the most powerful engines of economic development, since they generate a high volume of jobs in the national territory, while diversifying productive, commercial, and service activities. In order to propose a model for logistics management as a component for the competitiveness of SMEs, a qualitative study is proposed that will allow us to collect from a structured review of recent literature, identifying the elements to be taken into account for logistics management in order to provide timely support and open space for continuous improvement. The proposed model is structured in six main blocks: characterization of processes according to the activity of the SME, external factors of influence, internal factors of influence, feeding of information, monitoring and control of operations, and feedback between support areas. The above elements have been analyzed and suggested taking into account the specific aspects of SMEs in the country, and taking into account the peculiarities of these small productive cells

Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions

During meiosis, Structural Maintenance of Chromosome (SMC) complexes underpin two fundamental features of meiosis: homologous recombination and chromosome segregation. While meiotic functions of the cohesin and condensin complexes have been delineated, the role of the third SMC complex, Smc5/6, remains enigmatic. Here we identify specific, essential meiotic functions for the Smc5/6 complex in homologous recombination and the regulation of cohesin. We show that Smc5/6 is enriched at centromeres and cohesin-association sites where it regulates sister-chromatid cohesion and the timely removal of cohesin from chromosomal arms, respectively. Smc5/6 also localizes to recombination hotspots, where it promotes normal formation and resolution of a subset of joint-molecule intermediates. In this regard, Smc5/6 functions independently of the major crossover pathway defined by the MutLγ complex. Furthermore, we show that Smc5/6 is required for stable chromosomal localization of the XPF-family endonuclease, Mus81-Mms4Eme1. Our data suggest that the Smc5/6 complex is required for specific recombination and chromosomal processes throughout meiosis and that in its absence, attempts at cell division with unresolved joint molecules and residual cohesin lead to severe recombination-induced meiotic catastroph

Inflammatory cytokines and biofilm production sustain Staphylococcus aureus outgrowth and persistence: A pivotal interplay in the pathogenesis of Atopic Dermatitis

Individuals with Atopic dermatitis (AD) are highly susceptible to Staphylococcus aureus colonization. However, the mechanisms driving this process as well as the impact of S. aureus in AD pathogenesis are still incompletely understood. In this study, we analysed the role of biofilm in sustaining S. aureus chronic persistence and its impact on AD severity. Further we explored whether key inflammatory cytokines overexpressed in AD might provide a selective advantage to S. aureus. Results show that the strength of biofilm production by S. aureus correlated with the severity of the skin lesion, being significantly higher (P < 0.01) in patients with a more severe form of the disease as compared to those individuals with mild AD. Additionally, interleukin (IL)-β and interferon γ (IFN-γ), but not interleukin (IL)-6, induced a concentration-dependent increase of S. aureus growth. This effect was not observed with coagulase-negative staphylococci isolated from the skin of AD patients. These findings indicate that inflammatory cytokines such as IL1-β and IFN-γ, can selectively promote S. aureus outgrowth, thus subverting the composition of the healthy skin microbiome. Moreover, biofilm production by S. aureus plays a relevant role in further supporting chronic colonization and disease severity, while providing an increased tolerance to antimicrobials

Study of cosolvent-induced α-chymotrypsin fibrillogenesis: Does protein surface hydrophobicity trigger early stages of aggregation reaction?

The misfolding of specific proteins is often associated with their assembly into fibrillar aggregates, commonly termed amyloid fibrils. Despite the many efforts expended to characterize amyloid formation in vitro, there is no deep knowledge about the environment (in which aggregation occurs) as well as mechanism of this type of protein aggregation. Alpha-chymotrypsin was recently driven toward amyloid aggregation by the addition of intermediate concentrations of trifluoroethanol. In the present study, approaches such as turbidimetric, thermodynamic, intrinsic fluorescence and quenching studies as well as chemical modification have been successfully used to elucidate the underlying role of hydrophobic interactions (involved in early stages of amyloid formation) in α-chymotrypsin-based experimental system. © 2009 Springer Science+Business Media, LLC