The antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection

Antibiotics are widely used in the treatment of bacterial infections. Although known for their microbicidal activity, antibiotics may also interfere with the host's immune system. Here, we analyzed the effects of bedaquiline (BDQ), an inhibitor of the mycobacterial ATP synthase, on human macrophages. Genome-wide gene expression analysis revealed that BDQ reprogramed cells into potent bactericidal phagocytes. We found that 579 and 1,495 genes were respectively differentially expressed in naive- and M. tuberculosis-infected macrophages incubated with the drug, with an over-representation of lysosome-associated genes. BDQ treatment triggered a variety of antimicrobial defense mechanisms, including phagosome-lysosome fusion, and autophagy. These effects were associated with activation of transcription factor EB, involved in the transcription of lysosomal genes, resulting in enhanced intracellular killing of different bacterial species that were naturally insensitive to BDQ. Thus, BDQ could be used as a host-directed therapy against a wide range of bacterial infections

Bottom mixed layer oxygen dynamics in the Celtic Sea

The seasonally stratified continental shelf seas are highly productive, economically important environments which are under considerable pressure from human activity. Global dissolved oxygen concentrations have shown rapid reductions in response to anthropogenic forcing since at least the middle of the twentieth century. Oxygen consumption is at the same time linked to the cycling of atmospheric carbon, with oxygen being a proxy for carbon remineralisation and the release of CO2. In the seasonally stratified seas the bottom mixed layer (BML) is partially isolated from the atmosphere and is thus controlled by interplay between oxygen consumption processes, vertical and horizontal advection. Oxygen consumption rates can be both spatially and temporally dynamic, but these dynamics are often missed with incubation based techniques. Here we adopt a Bayesian approach to determining total BML oxygen consumption rates from a high resolution oxygen time-series. This incorporates both our knowledge and our uncertainty of the various processes which control the oxygen inventory. Total BML rates integrate both processes in the water column and at the sediment interface. These observations span the stratified period of the Celtic Sea and across both sandy and muddy sediment types. We show how horizontal advection, tidal forcing and vertical mixing together control the bottom mixed layer oxygen concentrations at various times over the stratified period. Our muddy-sand site shows cyclic spring-neap mediated changes in oxygen consumption driven by the frequent resuspension or ventilation of the seabed. We see evidence for prolonged periods of increased vertical mixing which provide the ventilation necessary to support the high rates of consumption observed

Carrier-mediated magnetoelectricity in complex oxide heterostructures

While tremendous success has been achieved to date in creating both single phase and composite magnetoelectric materials, the quintessential electric-field control of magnetism remains elusive. In this work, we demonstrate a linear magnetoelectric effect which arises from a novel carrier-mediated mechanism, and is a universal feature of the interface between a dielectric and a spin-polarized metal. Using first-principles density functional calculations, we illustrate this effect at the SrRuO$_3$/SrTiO$_3$ interface and describe its origin. To formally quantify the magnetic response of such an interface to an applied electric field, we introduce and define the concept of spin capacitance. In addition to its magnetoelectric and spin capacitive behavior, the interface displays a spatial coexistence of magnetism and dielectric polarization suggesting a route to a new type of interfacial multiferroic

Spectral Theory of Sparse Non-Hermitian Random Matrices

Sparse non-Hermitian random matrices arise in the study of disordered physical systems with asymmetric local interactions, and have applications ranging from neural networks to ecosystem dynamics. The spectral characteristics of these matrices provide crucial information on system stability and susceptibility, however, their study is greatly complicated by the twin challenges of a lack of symmetry and a sparse interaction structure. In this review we provide a concise and systematic introduction to the main tools and results in this field. We show how the spectra of sparse non-Hermitian matrices can be computed via an analogy with infinite dimensional operators obeying certain recursion relations. With reference to three illustrative examples --- adjacency matrices of regular oriented graphs, adjacency matrices of oriented Erd\H{o}s-R\'{e}nyi graphs, and adjacency matrices of weighted oriented Erd\H{o}s-R\'{e}nyi graphs --- we demonstrate the use of these methods to obtain both analytic and numerical results for the spectrum, the spectral distribution, the location of outlier eigenvalues, and the statistical properties of eigenvectors.Comment: 60 pages, 10 figure

A tiered approach to the use of alternatives to animal testing for the safety assessment of cosmetics: Eye irritation

AbstractThe need for alternative approaches to replace the in vivo rabbit Draize eye test for evaluation of eye irritation of cosmetic ingredients has been recognised by the cosmetics industry for many years. Extensive research has lead to the development of several assays, some of which have undergone formal validation. Even though, to date, no single in vitro assay has been validated as a full replacement for the rabbit Draize eye test, organotypic assays are accepted for specific and limited regulatory purposes. Although not formally validated, several other in vitro models have been used for over a decade by the cosmetics industry as valuable tools in a weight of evidence approach for the safety assessment of ingredients and finished products. In light of the deadlines established in the EU Cosmetics Directive for cessation of animal testing for cosmetic ingredients, a COLIPA scientific meeting was held in Brussels on 30th January, 2008 to review the use of alternative approaches and to set up a decision-tree approach for their integration into tiered testing strategies for hazard and safety assessment of cosmetic ingredients and their use in products. Furthermore, recommendations are given on how remaining data gaps and research needs can be addressed

Interlayer strain effects on the structural behavior of BiFeO3/LaFeO3 superlattices

Artificial (BiFeO3)0.5Λ/(LaFeO3)0.5Λ superlattices have been grown by pulsed laser deposition. The periodicity Λ was varied from 150 Å to 25 Å and the relative ratio between BiFeO3 (BFO) and LaFeO3 (LFO) is kept constant in each period. X-ray diffraction, transmission electron microscopy, and Raman spectroscopy investigations indicate antiferroelectric-like structures for large periodicity (Λ ≥ 76 Å), while Pnma LaFeO3-like structures are observed for small periodicity Λ ≤ 50 Å. Room temperature magnetic measurements were obtained by vibrating sample magnetometry and suggest antiferromagnetic ordering with weak ferromagnetism. Temperature dependent x-ray diffraction studies show an important shift of paraelectric-antiferroelectric phase transition scaling with BFO thickness. Strain and size effects explain this behavior and discussion is also made on the possible role of the oxygen octahedral rotation/tilt degree of freedom

Forest microclimates and climate change: importance, drivers and future research agenda

Forest microclimates contrast strongly with the climate outside forests. To fully understand and better predict how forests' biodiversity and functions relate to climate and climate change, microclimates need to be integrated into ecological research. Despite the potentially broad impact of microclimates on the response of forest ecosystems to global change, our understanding of how microclimates within and below tree canopies modulate biotic responses to global change at the species, community and ecosystem level is still limited. Here, we review how spatial and temporal variation in forest microclimates result from an interplay of forest features, local water balance, topography and landscape composition. We first stress and exemplify the importance of considering forest microclimates to understand variation in biodiversity and ecosystem functions across forest landscapes. Next, we explain how macroclimate warming (of the free atmosphere) can affect microclimates, and vice versa, via interactions with land-use changes across different biomes. Finally, we perform a priority ranking of future research avenues at the interface of microclimate ecology and global change biology, with a specific focus on three key themes: (1) disentangling the abiotic and biotic drivers and feedbacks of forest microclimates; (2) global and regional mapping and predictions of forest microclimates; and (3) the impacts of microclimate on forest biodiversity and ecosystem functioning in the face of climate change. The availability of microclimatic data will significantly increase in the coming decades, characterizing climate variability at unprecedented spatial and temporal scales relevant to biological processes in forests. This will revolutionize our understanding of the dynamics, drivers and implications of forest microclimates on biodiversity and ecological functions, and the impacts of global changes. In order to support the sustainable use of forests and to secure their biodiversity and ecosystem services for future generations, microclimates cannot be ignored.Peer reviewe

Seasonality and spatial heterogeneity of the surface ocean carbonate system in the northwest European continental shelf

In 2014–5 the UK NERC sponsored an 18 month long Shelf Sea Biogeochemistry research programme which collected over 1500 nutrient and carbonate system samples across the NW European Continental shelf, one of the largest continental shelves on the planet. This involved the cooperation of 10 different Institutes and Universities, using 6 different vessels. Additional carbon dioxide (CO2) data were obtained from the underway systems on three of the research vessels. Here, we present and discuss these data across 9 ecohydrodynamic regions, adapted from those used by the EU Marine Strategy Framework Directive (MSFD). We observed strong seasonal and regional variability in carbonate chemistry around the shelf in relation to nutrient biogeochemistry. Whilst salinity increased (and alkalinity decreased) out from the near-shore coastal waters offshore throughout the year nutrient concentrations varied with season. Spatial and seasonal variations in the ratio of DIC to nitrate concentration were seen that could impact carbon cycling. A decrease in nutrient concentrations and a pronounced under-saturation of surface pCO2 was evident in the spring in most regions, especially in the Celtic Sea. This decrease was less pronounced in Liverpool Bay and to the North of Scotland, where nutrient concentrations remained measurable throughout the year. The near-shore and relatively shallow ecosystems such as the eastern English Channel and southern North Sea were associated with a thermally driven increase in pCO2 to above atmospheric levels in summer and an associated decrease in pH. Non-thermal processes (such as mixing and the remineralisation of organic material) dominated in winter in most regions but especially in the northwest of Scotland and in Liverpool Bay. The large database collected will improve understanding of carbonate chemistry over the North-Western European Shelf in relation to nutrient biogeochemistry, particularly in the context of climate change and ocean acidification

Trait‐based analysis of subpolar North Atlantic phytoplankton and plastidic ciliate communities using automated flow cytometer

Plankton are an extremely diverse and polyphyletic group, exhibiting a large range in morphological and physiological traits. Here, we apply automated optical techniques, provided by the pulse‐shape recording automated flow cytometer—CytoSense—to investigate trait variability of phytoplankton and plastidic ciliates in Arctic and Atlantic waters of the subpolar North Atlantic. We used the bio‐optical descriptors derived from the CytoSense (light scattering [forward and sideward] and fluorescence [red, yellow/green and orange from chlorophyll a, degraded pigments, and phycobiliproteins, respectively]) and translated them into functional traits to demonstrate ecological trait variability along an environmental gradient. Cell size was the master trait varying in this study, with large photosynthetic microplankton (> 20 μm in cell diameter), including diatoms as single cells and chains, as well as plastidic ciliates found in Arctic waters, while small‐sized phytoplankton groups, such as the picoeukaryotes (< 4 μm) and the cyanobacteria Synechococcus were dominant in Atlantic waters. Morphological traits, such as chain/colony formation and structural complexity (i.e., cellular processes, setae, and internal vacuoles), appear to favor buoyancy in highly illuminated and stratified Arctic waters. In Atlantic waters, small cell size and spherical cell shape, in addition to photo‐physiological traits, such as high internal pigmentation, offer chromatic adaptation for survival in the low nutrient and dynamic mixing waters of the Atlantic Ocean. The use of automated techniques that quantify ecological traits holds exciting new opportunities to unravel linkages between the structure and function of plankton communities and marine ecosystems

Estimation des rejets en azote, phosphore et coliformes fécaux à l'aval d'un parcours de volailles

National audienc