Caveolin-1 deficiency alters plasma lipid and lipoprotein profiles in mice.

Caveolae are specialized membrane microdomains formed as the result of local accumulation of cholesterol, glycosphingolipids, and the structural protein caveolin-1 (Cav-1). To further elucidate the role of Cav-1 in lipid homeostasis in-vivo, we analyzed fasting and post-prandial plasma from Cav-1 deficient mice on low or on high fat diet. In total plasma analysis, an increase in ceramide and hexosylceramide was observed. In cholesteryl ester (CE), we found an increased saturated+monounsaturated/polyunsaturated fatty acid ratio in fasting plasma of low fat fed Cav-1(-/-) mice with increased proportions of CE16:1, CE18:1, CE20:3, and decreased proportions of CE18:2 and CE22:6. Under high fat diet HDL-CE, free cholesterol and pre-beta-HDL were increased accompanied by a shift from slow to fast migrating alpha-HDL and expansion of apoE containing HDL. Our results demonstrate a significant role of Cav-1 in HDL-cholesterol metabolism and may reflect a variety of Cav-1 functions including modulation of ACAT activity and SR-BI function

Functional compartmentalization and metabolic separation in a prokaryotic cell

The prokaryotic cell is traditionally seen as a “bag of enzymes,” yet its organization is much more complex than in this simplified view. By now, various microcompartments encapsulating metabolic enzymes or pathways are known for Bacteria. These microcompartments are usually small, encapsulating and concentrating only a few enzymes, thus protecting the cell from toxic intermediates or preventing unwanted side reactions. The hyperthermophilic, strictly anaerobic Crenarchaeon Ignicoccus hospitalis is an extraordinary organism possessing two membranes, an inner and an energized outer membrane. The outer membrane (termed here outer cytoplasmic membrane) harbors enzymes involved in proton gradient generation and ATP synthesis. These two membranes are separated by an intermembrane compartment, whose function is unknown. Major information processes like DNA replication, RNA synthesis, and protein biosynthesis are located inside the “cytoplasm” or central cytoplasmic compartment. Here, we show by immunogold labeling of ultrathin sections that enzymes involved in autotrophic CO2 assimilation are located in the intermembrane compartment that we name (now) a peripheric cytoplasmic compartment. This separation may protect DNA and RNA from reactive aldehydes arising in the I. hospitalis carbon metabolism. This compartmentalization of metabolic pathways and information processes is unprecedented in the prokaryotic world, representing a unique example of spatiofunctional compartmentalization in the second domain of life

Global aerosol modeling with MADE3 (v3.0) in EMAC (based on v2.53): model description and evaluation

Recently, the aerosol microphysics submodel MADE3 (Modal Aerosol Dynamics model for Europe, adapted for global applications, third generation) was introduced as a successor to MADE and MADE-in. It includes nine aerosol species and nine lognormal modes to represent aerosol particles of three different mixing states throughout the aerosol size spectrum. Here, we describe the implementation of the most recent version of MADE3 into the ECHAM/MESSy Atmospheric Chemistry (EMAC) general circulation model, including a detailed evaluation of a 10-year aerosol simulation with MADE3 as part of EMAC.We compare simulation output to station network measurements of near-surface aerosol component mass concentrations, to airborne measurements of aerosol mass mixing ratio and number concentration vertical profiles, to ground-based and airborne measurements of particle size distributions, and to station network and satellite measurements of aerosol optical depth. Furthermore, we describe and apply a new evaluation method, which allows a comparison of model output to size-resolved electron microscopy measurements of particle composition. Although there are indications that fine-mode particle deposition may be underestimated by the model, we obtained satisfactory agreement with the observations. Remaining deviations are of similar size to those identified in other global aerosol model studies.Thus, MADE3 can be considered ready for application within EMAC. Due to its detailed representation of aerosol mixing state, it is especially useful for simulating wet and dry removal of aerosol particles, aerosol-induced formation of cloud droplets and ice crystals as well as aerosol–radiation interactions. Besides studies on these fundamental processes, we also plan to use MADE3 for a reassessment of the climate effects of anthropogenic aerosol perturbations.</p

NASA Image eXchange (NIX)

This paper discusses the technical aspects of and the project background for the NASA Image exchange (NIX). NIX, which provides a single entry point to search selected image databases at the NASA Centers, is a meta-search engine (i.e., a search engine that communicates with other search engines). It uses these distributed digital image databases to access photographs, animations, and their associated descriptive information (meta-data). NIX is available for use at the following URL: http://nix.nasa.gov./NIX, which was sponsored by NASAs Scientific and Technical Information (STI) Program, currently serves images from seven NASA Centers. Plans are under way to link image databases from three additional NASA Centers. images and their associated meta-data, which are accessible by NIX, reside at the originating Centers, and NIX utilizes a virtual central site that communicates with each of these sites. Incorporated into the virtual central site are several protocols to support searches from a diverse collection of database engines. The searches are performed in parallel to ensure optimization of response times. To augment the search capability, browse functionality with pre-defined categories has been built into NIX, thereby ensuring dissemination of 'best-of-breed' imagery. As a final recourse, NIX offers access to a help desk via an on-line form to help locate images and information either within the scope of NIX or from available external sources

Super Resolution Fluorescence Microscopy and Tracking of Bacterial Flotillin (Reggie) Paralogs Provide Evidence for Defined-Sized Protein Microdomains within the Bacterial Membrane but Absence of Clusters Containing Detergent-Resistant Proteins

Biological membranes have been proposed to contain microdomains of a specific lipid composition, in which distinct groups of proteins are clustered. Flotillin-like proteins are conserved between pro—and eukaryotes, play an important function in several eukaryotic and bacterial cells, and define in vertebrates a type of so-called detergent-resistant microdomains. Using STED microscopy, we show that two bacterial flotillins, FloA and FloT, form defined assemblies with an average diameter of 85 to 110 nm in the model bacterium Bacillus subtilis. Interestingly, flotillin microdomains are of similar size in eukaryotic cells. The soluble domains of FloA form higher order oligomers of up to several hundred kDa in vitro, showing that like eukaryotic flotillins, bacterial assemblies are based in part on their ability to self-oligomerize. However, B. subtilis paralogs show significantly different diffusion rates, and consequently do not colocalize into a common microdomain. Dual colour time lapse experiments of flotillins together with other detergent-resistant proteins in bacteria show that proteins colocalize for no longer than a few hundred milliseconds, and do not move together. Our data reveal that the bacterial membrane contains defined-sized protein domains rather than functional microdomains dependent on flotillins. Based on their distinct dynamics, FloA and FloT confer spatially distinguishable activities, but do not serve as molecular scaffolds

Interactive Visual Labelling versus Active Learning: An Experimental Comparison

Methods from supervised machine learning allow the classification of new data automatically and are tremendously helpful for data analysis. The quality of supervised maching learning depends not only on the type of algorithm used, but also on the quality of the labelled dataset used to train the classifier. Labelling instances in a training dataset is often done manually relying on selections and annotations by expert analysts, and is often a tedious and time-consuming process. Active learning algorithms can automatically determine a subset of data instances for which labels would provide useful input to the learning process. Interactive visual labelling techniques are a promising alternative, providing effective visual overviews from which an analyst can simultaneously explore data records and select items to a label. By putting the analyst in the loop, higher accuracy can be achieved in the resulting classifier. While initial results of interactive visual labelling techniques are promising in the sense that user labelling can improve supervised learning, many aspects of these techniques are still largely unexplored. This paper presents a study conducted using the mVis tool to compare three interactive visualisations, similarity map, scatterplot matrix (SPLOM), and parallel coordinates, with each other and with active learning for the purpose of labelling a multivariate dataset. The results show that all three interactive visual labelling techniques surpass active learning algorithms in terms of classifier accuracy, and that users subjectively prefer the similarity map over SPLOM and parallel coordinates for labelling. Users also employ different labelling strategies depending on the visualisation used

Towards low‐cost community networks in rural communities: The impact of context using the case study of Beitbridge, Zimbabwe

Most rural communities in developing countries such as Zimbabwe are underserved and/or unserved with regard to telecommunication connectivity. Governments in developing countries are also under‐resourced to provide adequate digital infrastructure. Thus, community networks are increasingly seen as viable alternatives to bridge the infrastructure gap in Africa. However, new infrastructure interventions in developing countries face many challenges including complex interventions stemming from complex policies inserted into complex sociopolitical environments. The success of community networks in other African countries prompts this investigation into the potential of transferring the community network approach to Zimbabwe. The objective of this article is to frame how context impacts development of digital infrastructure. Zimbabwe's telecommunication regulatory framework is on the verge of countenancing the development of community networks, and for this reason, there is need for research to inform would‐be investors, policy makers, and other stakeholders such as academia, NGOs, and communities themselves, on how the sociopolitical and economic environment impact these efforts. This is important because successful deployment of a community network may result in improved community development, eg, in food security, health, and education

miR449 Protects Airway Regeneration by Controlling AURKA/HDAC6-Mediated Ciliary Disassembly

Airway mucociliary regeneration and function are key players for airway defense and are impaired in chronic obstructive pulmonary disease (COPD). Using transcriptome analysis in COPD-derived bronchial biopsies, we observed a positive correlation between cilia-related genes and microRNA-449 (miR449). In vitro, miR449 was strongly increased during airway epithelial mucociliary differentiation. In vivo, miR449 was upregulated during recovery from chemical or infective insults. miR0449−/− mice (both alleles are deleted) showed impaired ciliated epithelial regeneration after naphthalene and Haemophilus influenzae exposure, accompanied by more intense inflammation and emphysematous manifestations of COPD. The latter occurred spontaneously in aged miR449−/− mice. We identified Aurora kinase A and its effector target HDAC6 as key mediators in miR449-regulated ciliary homeostasis and epithelial regeneration. Aurora kinase A is downregulated upon miR449 overexpression in vitro and upregulated in miR449−/− mouse lungs. Accordingly, imaging studies showed profoundly altered cilia length and morphology accompanied by reduced mucociliary clearance. Pharmacological inhibition of HDAC6 rescued cilia length and coverage in miR449−/− cells, consistent with its tubulin-deacetylating function. Altogether, our study establishes a link between miR449, ciliary dysfunction, and COPD pathogenesis