1,122 research outputs found
Lung macrophage scavenger receptor SR-A6 (MARCO) is an adenovirus type-specific virus entry receptor
<div><p>Macrophages are a diverse group of phagocytic cells acting in host protection against stress, injury, and pathogens. Here, we show that the scavenger receptor SR-A6 is an entry receptor for human adenoviruses in murine alveolar macrophage-like MPI cells, and important for production of type I interferon. Scavenger receptors contribute to the clearance of endogenous proteins, lipoproteins and pathogens. Knockout of SR-A6 in MPI cells, anti-SR-A6 antibody or the soluble extracellular SR-A6 domain reduced adenovirus type-C5 (HAdV-C5) binding and transduction. Expression of murine SR-A6, and to a lower extent human SR-A6 boosted virion binding to human cells and transduction. Virion clustering by soluble SR-A6 and proximity localization with SR-A6 on MPI cells suggested direct adenovirus interaction with SR-A6. Deletion of the negatively charged hypervariable region 1 (HVR1) of hexon reduced HAdV-C5 binding and transduction, implying that the viral ligand for SR-A6 is hexon. SR-A6 facilitated macrophage entry of HAdV-B35 and HAdV-D26, two important vectors for transduction of hematopoietic cells and human vaccination. The study highlights the importance of scavenger receptors in innate immunity against human viruses.</p></div
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Arenavirus budding resulting from viral-protein-associated cell membrane curvature
Viral replication occurs within cells, with release (and onward infection) primarily achieved through two alternative mechanisms: lysis, in which virions emerge as the infected cell dies and bursts open; or budding, in which virions emerge gradually from a still living cell by appropriating a small part of the cell membrane. Virus budding is a poorly understood process that challenges current models of vesicle formation. Here, a plausible mechanism for arenavirus budding is presented, building on recent evidence that viral proteins embed in the inner lipid layer of the cell membrane. Experimental results confirm that viral protein is associated with increased membrane curvature, whereas a mathematical model is used to show that localized increases in curvature alone are sufficient to generate viral buds. The magnitude of the protein-induced curvature is calculated from the size of the amphipathic region hypothetically removed from the inner membrane as a result of translation, with a change in membrane stiffness estimated from observed differences in virion deformation as a result of protein depletion. Numerical results are based on experimental data and estimates for three arenaviruses, but the mechanisms described are more broadly applicable. The hypothesized mechanism is shown to be sufficient to generate spontaneous budding that matches well both qualitatively and quantitatively with experimental observations
Common data elements for clinical research in mitochondrial disease: a National Institute for Neurological Disorders and Stroke project
Objectives The common data elements (CDE) project was
developed by the National Institute of Neurological
Disorders and Stroke (NINDS) to provide clinical researchers
with tools to improve data quality and allow for harmonization
of data collected in different research studies. CDEs have been
created for several neurological diseases; the aim of this project
was to develop CDEs specifically curated for mitochondrial
disease (Mito) to enhance clinical research.
Methods Nine working groups (WGs), composed of international
mitochondrial disease experts, provided recommendations
for Mito clinical research. They initially reviewed
existing NINDS CDEs and instruments, and developed new
data elements or instruments when needed. Recommendations
were organized, internally reviewed by the Mito WGs, and
posted online for external public comment for a period of eight
weeks. The final version was again reviewed by all WGs and
the NINDS CDE team prior to posting for public use
Genetics of decayed sexual traits in a parasitoid wasp with endosymbiont-induced asexuality.
Trait decay may occur when selective pressures shift, owing to changes in environment or life style, rendering formerly adaptive traits non-functional or even maladaptive. It remains largely unknown if such decay would stem from multiple mutations with small effects or rather involve few loci with major phenotypic effects. Here, we investigate the decay of female sexual traits, and the genetic causes thereof, in a transition from haplodiploid sexual reproduction to endosymbiont-induced asexual reproduction in the parasitoid wasp Asobara japonica. We take advantage of the fact that asexual females cured of their endosymbionts produce sons instead of daughters, and that these sons can be crossed with sexual females. By combining behavioral experiments with crosses designed to introgress alleles from the asexual into the sexual genome, we found that sexual attractiveness, mating, egg fertilization and plastic adjustment of offspring sex ratio (in response to variation in local mate competition) are decayed in asexual A. japonica females. Furthermore, introgression experiments revealed that the propensity for cured asexual females to produce only sons (because of decayed sexual attractiveness, mating behavior and/or egg fertilization) is likely caused by recessive genetic effects at a single locus. Recessive effects were also found to cause decay of plastic sex-ratio adjustment under variable levels of local mate competition. Our results suggest that few recessive mutations drive decay of female sexual traits, at least in asexual species deriving from haplodiploid sexual ancestors
Yeast : the soul of beer’s aroma—a review of flavour-active esters and higher alcohols produced by the brewing yeast
Among the most important factors influencing beer quality is the presence of well-adjusted amounts of higher alcohols and esters. Thus, a heavy body of literature focuses on these substances and on the parameters influencing their production by the brewing yeast. Additionally, the complex metabolic pathways involved in their synthesis require special attention. More than a century of data, mainly in genetic and proteomic fields, has built up enough information to describe in detail each step in the pathway for the synthesis of higher alcohols and their esters, but there is still place for more. Higher alcohols are formed either by anabolism or catabolism (Ehrlich pathway) of amino acids. Esters are formed by enzymatic condensation of organic acids and alcohols. The current paper reviews the up-to-date knowledge in the pathways involving the synthesis of higher alcohols and esters by brewing yeasts. Fermentation parameters affecting yeast response during biosynthesis of these aromatic substances are also fully reviewed.Eduardo Pires gratefully acknowledges the Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) for the PhD fellowship support (SFRH/BD/61777/2009). The financial contributions of the EU FP7 project Ecoefficient Biodegradable Composite Advanced Packaging (EcoBioCAP, grant agreement no. 265669) as well as of the Grant Agency of the Czech Republic (project GACR P503/12/1424) are also gratefully acknowledged. The authors thank the Ministry of Education, Youth and Sports of the Czech Republic (MSM 6046137305) for their financial support
Real-time and post-processed georeferencing for hyperpspectral drone remote sensing
The use of drones and photogrammetric technologies are increasing rapidly in different applications. Currently, drone processing workflow is in most cases based on sequential image acquisition and post-processing, but there are great interests towards real-time solutions. Fast and reliable real-time drone data processing can benefit, for instance, environmental monitoring tasks in precision agriculture and in forest. Recent developments in miniaturized and low-cost inertial measurement systems and GNSS sensors, and Real-time kinematic (RTK) position data are offering new perspectives for the comprehensive remote sensing applications. The combination of these sensors and light-weight and low-cost multi- or hyperspectral frame sensors in drones provides the opportunity of creating near real-time or real-time remote sensing data of target object. We have developed a system with direct georeferencing onboard drone to be used combined with hyperspectral frame cameras in real-time remote sensing applications. The objective of this study is to evaluate the real-time georeferencing comparing with post-processing solutions. Experimental data sets were captured in agricultural and forested test sites using the system. The accuracy of onboard georeferencing data were better than 0.5 m. The results showed that the real-time remote sensing is promising and feasible in both test sites. © Authors 2018. CC BY 4.0 License.Peer reviewe
Mosaic dysfunction of mitophagy in mitochondrial muscle disease
Mitophagy is a quality control mechanism that eliminates damaged mitochondria, yet its significance in mammalian pathophysiology and aging has remained unclear. Here, we report that mitophagy contributes to mitochondrial dysfunction in skeletal muscle of aged mice and human patients. The early disease stage is characterized by muscle fibers with central nuclei, with enhanced mitophagy around these nuclei. However, progressive mitochondrial dysfunction halts mitophagy and disrupts lysosomal homeostasis. Interestingly, activated or halted mitophagy occur in a mosaic manner even in adjacent muscle fibers, indicating cell-autonomous regulation. Rapamycin restores mitochondrial turnover, indicating mTOR-dependence of mitochondrial recycling in advanced disease stage. Our evidence suggests that (1) mitophagy is a hallmark of age-related mitochondrial pathology in mammalian muscle, (2) mosaic halting of mitophagy is a mechanism explaining mosaic respiratory chain deficiency and accumulation of pathogenic mtDNA variants in adult-onset mitochondrial diseases and normal aging, and (3) augmenting mitophagy is a promising therapeutic approach for muscle mitochondrial dysfunction.Peer reviewe
Arts-Aided Recognition of Citizens' Perceptions for Urban Open Space Management
Urban open spaces of local natural environments can promote the health and well-being of both ecosystems and humans, and the management of the urban spaces can benefit from knowledge of individuals’/citizens’ perceptions of such environments. However, such knowledge is scarce and contemporary inquiries are often limited to cognitive observations and focused on built environmental elements rather than encouraged to recognize and communicate comprehensive perceptions. This paper investigates whether arts-based methods can facilitate recognition and understanding perceptions of urban open spaces. Two arts-based methods were used to capture perceptions: drifting, which is a walking method, and theatrical images, which is a still image method and three reflective methods to recognize and communicate the perceptions. The results show related sensations and perceptions enabled by arts-based methods comparing them to a sticker map method. The main findings were perceptions, which included information about human–environment interaction, about relations to other people and about ‘sense of place’ in urban open spaces. The hitherto unidentified perceptions about urban open space were associations, metaphors and memories. The methods used offer initial practical implications for future use
Isolation of dental stem cell-enriched populations from continuously growing mouse incisors
Continuous growth of the rodent incisor is enabled by epithelial and mesenchymal stem cells (ESCs and MSCs) which unceasingly replenish enamel and dentin, respectively, that wear by persistent animal gnawing. Lineage tracing studies have provided evidence that ESCs contribute to all epithelial lineages of the tooth in vivo. Meanwhile, in the mouse incisor, MSCs continuously contribute to odontoblast lineage and tooth growth. However, in vitro manipulation of ESCs has shown little progress, mainly due to lack of appropriate protocol to successfully isolate, culture, expand, and differentiate ESCs in vitro without using the co-culture system. In this chapter we describe the isolation of the Sox2-GFP+ cell population that is highly enriched in ESCs. Isolated cells can be used for various types of analyses, including in vitro culture, single cell-related analyses, etc. Furthermore, we describe ways to obtain populations enriched in the incisor MSCs using FACS sorting of antibody-labeled cells. Easily accessible FACS sorting enables easy and relatively fast isolation of the cells labeled by the fluorescent protein. © Springer Science+Business Media, LLC, part of Springer Nature 2019.Peer reviewe
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