Cryo-EM structure of the mature dengue virus at 3.5-Å resolution.

Regulated by pH, membrane-anchored proteins E and M function during dengue virus maturation and membrane fusion. Our atomic model of the whole virion from cryo-electron microscopy at 3.5-Å resolution reveals that in the mature virus at neutral extracellular pH, the N-terminal 20-amino-acid segment of M (involving three pH-sensing histidines) latches and thereby prevents spring-loaded E fusion protein from prematurely exposing its fusion peptide. This M latch is fastened at an earlier stage, during maturation at acidic pH in the trans-Golgi network. At a later stage, to initiate infection in response to acidic pH in the late endosome, M releases the latch and exposes the fusion peptide. Thus, M serves as a multistep chaperone of E to control the conformational changes accompanying maturation and infection. These pH-sensitive interactions could serve as targets for drug discovery

Cryo-EM model of the bullet-shaped vesicular stomatitis virus.

Vesicular stomatitis virus (VSV) is a bullet-shaped rhabdovirus and a model system of negative-strand RNA viruses. Through direct visualization by means of cryo-electron microscopy, we show that each virion contains two nested, left-handed helices: an outer helix of matrix protein M and an inner helix of nucleoprotein N and RNA. M has a hub domain with four contact sites that link to neighboring M and N subunits, providing rigidity by clamping adjacent turns of the nucleocapsid. Side-by-side interactions between neighboring N subunits are critical for the nucleocapsid to form a bullet shape, and structure-based mutagenesis results support this description. Together, our data suggest a mechanism of VSV assembly in which the nucleocapsid spirals from the tip to become the helical trunk, both subsequently framed and rigidified by the M layer

Four Levels of Hierarchical Organization, Including Noncovalent Chainmail, Brace the Mature Tumor Herpesvirus Capsid against Pressurization

SummaryLike many double-stranded DNA viruses, tumor gammaherpesviruses Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus withstand high internal pressure. Bacteriophage HK97 uses covalent chainmail for this purpose, but how this is achieved noncovalently in the much larger gammaherpesvirus capsid is unknown. Our cryoelectron microscopy structure of a gammaherpesvirus capsid reveals a hierarchy of four levels of organization: (1) Within a hexon capsomer, each monomer of the major capsid protein (MCP), 1,378 amino acids and six domains, interacts with its neighboring MCPs at four sites. (2) Neighboring capsomers are linked in pairs by MCP dimerization domains and in groups of three by heterotrimeric triplex proteins. (3) Small (∼280 amino acids) HK97-like domains in MCP monomers alternate with triplex heterotrimers to form a belt that encircles each capsomer. (4) One hundred sixty-two belts concatenate to form noncovalent chainmail. The triplex heterotrimer orchestrates all four levels and likely drives maturation to an angular capsid that can withstand pressurization

Combined effects of ultrasound and immobilization protocol on butyl acetate synthesis catalyzed by CALB

It is well established that the performance of lipase B from Candida antarctica (CALB) as catalyst for esterification reactions may be improved by the use of ultrasound technology or by its immobilization on styrene-divinylbenzene beads (MCI-CALB). The present research evaluated the synthesis of butyl acetate using MCI-CALB under ultrasonic energy, comparing the results against those obtained using the commercial preparation, Novozym 435. The optimal conditions were determined using response surface methodology (RSM) evaluating the following parameters: reaction temperature, substrate molar ratio, amount of biocatalyst, and added water. The optimal conditions for butyl acetate synthesis catalyzed by MCI-CALB were: Temperature, 48.8 °C; substrate molar ratio, 3.46:1 alcohol: Acid; amount of biocatalyst, 7.5%; and added water 0.28%, both as substrate mass. Under these conditions, 90% of conversion was reached in 1.5 h. In terms of operational stability, MCI-CALB was reused in seven cycles while keeping 70% of its initial activity under ultrasonic energy. The support pore size and resistance are key points for the enzyme activity and stability under mechanical stirring. The use of ultrasound improved both activity and stability because of better homogeneity and reduced mechanical stress to the immobilized system.This work was supported by grants from CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), and CTQ2013-41507-R from Spanish MINECO. We would like to thank Novozymes Spain for its comprehensive support of this research, in special Ramiro Martínez (Novozymes, Spain) for kindly supplying the enzymes used in the work. We also thank CNPq (Brazil) for a fellowship to A.M. Silva and FAPERGS (Brazil) for a fellowship to J.S. Alves. A Ph D. fellowship from Spanish Goberment to Miss Garcia-Galan is also acknowledged The help and suggestions from Ángel Berenguer-Murcia (Instituto de Materiales, Universidad de Alicante) are gratefully recognized. We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI)Peer Reviewe

Temperature and Field Dependence of the Mobility in Liquid-Crystalline Conjugated Polymer Films

The transport properties of organic light-emitting diodes in which the emissive layer is composed of conjugated polymers in the liquid-crystalline phase have been investigated. We have performed simulations of the current transient response to an illumination pulse via the Monte Carlo approach, and from the transit times we have extracted the mobility of the charge carriers as a function of both the electric field and the temperature. The transport properties of such films are different from their disordered counterparts, with charge carrier mobilities exhibiting only a weak dependence on both the electric field and temperature. We show that for spatially ordered polymer films, this weak dependence arises for thermal energy being comparable to the energetic disorder, due to the combined effect of the electrostatic and thermal energies. The inclusion of spatial disorder, on the other hand, does not alter the qualitative behaviour of the mobility, but results in decreasing its absolute value.Comment: 9 pages, 8 figures, submitted to Phys. Rev.

Pre-HEAT: submillimeter site testing and astronomical spectra from Dome A, Antarctica

Pre-HEAT is a 20 cm aperture submillimeter-wave telescope with a 660 GHz (450 micron) Schottky diode heterodyne receiver and digital FFT spectrometer for the Plateau Observatory (PLATO) developed by the University of New South Wales. In January 2008 it was deployed to Dome A, the summit of the Antarctic plateau, as part of a scientific traverse led by the Polar Research Institute of China and the Chinese Academy of Sciences. Dome A may be one of the best sites in the world for ground based Terahertz astronomy, based on the exceptionally cold, dry and stable conditions which prevail there. Pre-HEAT is measuring the 450 micron sky opacity at Dome A and mapping the Galactic Plane in the ^(13)CO J=6-5 line, constituting the first submillimeter measurements from Dome A. It is field-testing many of the key technologies for its namesake -- a successor mission called HEAT: the High Elevation Antarctic Terahertz telescope. Exciting prospects for submillimeter astronomy from Dome A and the status of Pre-HEAT will be presented

Déjà vu: a database of highly similar citations in the scientific literature

In the scientific research community, plagiarism and covert multiple publications of the same data are considered unacceptable because they undermine the public confidence in the scientific integrity. Yet, little has been done to help authors and editors to identify highly similar citations, which sometimes may represent cases of unethical duplication. For this reason, we have made available Déjà vu, a publicly available database of highly similar Medline citations identified by the text similarity search engine eTBLAST. Following manual verification, highly similar citation pairs are classified into various categories ranging from duplicates with different authors to sanctioned duplicates. Déjà vu records also contain user-provided commentary and supporting information to substantiate each document's categorization. Déjà vu and eTBLAST are available to authors, editors, reviewers, ethicists and sociologists to study, intercept, annotate and deter questionable publication practices. These tools are part of a sustained effort to enhance the quality of Medline as ‘the’ biomedical corpus. The Déjà vu database is freely accessible at http://spore.swmed.edu/dejavu. The tool eTBLAST is also freely available at http://etblast.org

Fair play:Perceived fairness in crowdsourcing competitions and the customer relationship-related consequences

TeleRehab enables the rehabilitation services to be delivered in distance by providing information exchange between patient with disabilities and the clinical professionals. The readiness step in any adoption of healthcare services should always be one of the requirements for a successful implementation of an innovation. However, little scholarly has been undertaken to study its influence on TeleRehab and the various barrier factors that influence its adoption. This research explores the barrier factors that influence the readiness of healthcare institution to adopt TeleRehab. This paper presents a semi-structured interview involving 23 clinical professionals of a case study on the issues of TeleRehab readiness in one rehabilitation centre in Malaysia. By applying thematic analysis, the study uncovers seven barriers that affect the TeleRehab readiness. This includes barriers of no urgency to change, less awareness, less involvement in planning, not enough exposure on e-Healthcare knowledge, resistance to change, low usage of hardware and software, and less connectivity. The study contributes to both TeleRehab management and technology readiness research in hospitals

Identifying duplicate content using statistically improbable phrases

Motivation: Document similarity metrics such as PubMed's ‘Find related articles’ feature, which have been primarily used to identify studies with similar topics, can now also be used to detect duplicated or potentially plagiarized papers within literature reference databases. However, the CPU-intensive nature of document comparison has limited MEDLINE text similarity studies to the comparison of abstracts, which constitute only a small fraction of a publication's total text. Extending searches to include text archived by online search engines would drastically increase comparison ability. For large-scale studies, submitting short phrases encased in direct quotes to search engines for exact matches would be optimal for both individual queries and programmatic interfaces. We have derived a method of analyzing statistically improbable phrases (SIPs) for assistance in identifying duplicate content

Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown