Medin aggregation causes cerebrovascular dysfunction in aging wild-type mice

Medin is the most common amyloid known in humans, as it can be found in blood vessels of the upper body in virtually everybody over 50 years of age. However, it remains unknown whether deposition of Medin plays a causal role in age-related vascular dysfunction. We now report that aggregates of Medin also develop in the aorta and brain vasculature of wild-type mice in an age-dependent manner. Strikingly, genetic deficiency of the Medin precursor protein, MFG-E8, eliminates not only vascular aggregates but also prevents age-associated decline of cerebrovascular function in mice. Given the prevalence of Medin aggregates in the general population and its role in vascular dysfunction with aging, targeting Medin may become a novel approach to sustain healthy aging

Large deep-sea zooplankton biomass mirrors primary production in the global ocean

The biological pump transports organic carbon produced by photosynthesis to the meso- and bathypelagic zones, the latter removing carbon from exchanging with the atmosphere over centennial time scales. Organisms living in both zones are supported by a passive flux of particles, and carbon transported to the deep-sea through vertical zooplankton migrations. Here we report globally-coherent positive relationships between zooplankton biomass in the epi-, meso-, and bathypelagic layers and average net primary production (NPP). We do so based on a global assessment of available deep-sea zooplankton biomass data and large-scale estimates of average NPP. The relationships obtained imply that increased NPP leads to enhanced transference of organic carbon to the deep ocean. Estimated remineralization from respiration rates by deep-sea zooplankton requires a minimum supply of 0.44 Pg C y(-1) transported into the bathypelagic ocean, comparable to the passive carbon sequestration. We suggest that the global coupling between NPP and bathypelagic zooplankton biomass must be also supported by an active transport mechanism associated to vertical zooplankton migration

Seasonal variations in the nitrogen isotopic composition of settling particles at station K2 in the western subarctic North Pacific

Intensive observations using hydrographical cruises and moored sediment trap deployments during 2010 and 2012 at station K2 in the North Pacific western subarctic gyre (WSG) revealed seasonal changes in δ15N of both suspended and settling particles. Suspended particles (SUS) were collected from depths between the surface and 200 m; settling particles by drifting traps (DST; 100-200 m) and moored traps (MST; 200 and 500 m). All particles showed higher δ15N values in winter and lower in summer, contrary to the expected by isotopic fractionation during phytoplankton nitrate consumption. We suggest that these observed isotopic patterns are due to ammonium consumption via light-controlled nitrification, which could induce variations in δ15N(SUS) of 0.4-3.1 ‰ in the euphotic zone (EZ). The δ15N(SUS) signature was reflected by δ15 N(DST) despite modifications during biogenic transformation from suspended particles in the EZ. δ15 N enrichment (average: 3.6 ‰) and the increase in C:N ratio (by 1.6) in settling particles suggests year-round contributions of metabolites from herbivorous zooplankton as well as TEPs produced by diatoms. Accordingly, seasonal δ15 N(DST) variations of 2.4-7.0 ‰ showed a significant correlation with primary productivity (PP) at K2. By applying the observed δ15 N(DST) vs. PP regression to δ15 N(MST) of 1.9-8.0 ‰, we constructed the first annual time-series of PP changes in the WSG. Moreover, the monthly export ratio at 500 m was calculated using both estimated PP and measured organic carbon fluxes. Results suggest a 1.6 to 1.8 times more efficient transport of photosynthetically-fixed carbon to the intermediate layers occurs in summer/autumn rather than winter/spring

European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities.</p

European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation.

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities

Spatial variation in the trophic structure of micronekton assemblages from the eastern tropical North Atlantic in two regions of differing productivity and oxygen environments

Highlights: • Micronekton ecology differed between equatorial (EQ) and low-oxygen waters (LO). • The δ15N enrichment per trophic level was lower in the productive LO than in the EQ. • Migrating fauna in the LO encounter increased competition for food resources. • The δ15N values of non-migrators increased with depth in the EQ, but not in the LO. • The δ15N values of mesopelagic micronektonivores were lower in the productive LO. Abstract: The ecology of vertically migrating mesopelagic micronekton is affected by physical properties of their environment. Increased light attenuation in particle-rich productive waters, as well as low oxygen conditions decrease the migration amplitude. This likely has implications on the trophic organisation of micronekton communities, which are predominantly governed by niche partitioning in the vertical dimension. We investigated trophic structures of pelagic communities in the eastern tropical North Atlantic by comparing micronekton species assemblages from the low-oxygen region influenced by Mauritanian upwelling between 8° and 11° N (LO) and the less productive and more oxygenated equatorial area between 0 and 4°N (EQ). We analysed stable isotopes of carbon (δ13C) and nitrogen (δ15N) in body tissues of 35 species of mesopelagic fishes, four species of cephalopods, two species of cnidarians, and two species of decapods and used these values as a proxy for their trophic niche and correlated them with the traits feeding guild, migration pattern, mean depth of occurrence and body size. Our results demonstrate significant regional differences in the food web structure and vertical trophic interactions of the investigated micronekton assemblages. Diurnally migrating fishes that predominantly feed on copepods exhibited higher δ15N values in the LO (9.6‰) than in the EQ (8.9‰), reflecting changes in baseline values of pelagic tunicates. Contrary, all other Feeding – Migrator guilds show lower or similar δ15N values in the LO compared to the EQ, indicating reduced isotopic enrichment between trophic levels (TL) in the LO compared to the EQ. Further, a generally lower δ15N enrichment between TL3 – TL4 compared to TL2 – TL3 was observed (LO: TL2 – TL3: ~2.2‰, TL3 – TL4: ~1.2‰; EQ: TL2 – TL3: ~3.5‰, TL3 – TL4: ~2.2‰). Quantitative isotopic niche metrics suggest enhanced competition in trophic niche space, whereas relative isotopic niche positions indicate an increased importance of food from lower trophic levels (non-crustacean and/or gelatinous prey resources) for fishes from the LO compared to the EQ. The absence of a depth-related increase in δ15N values of partial- and nonmigrators of the LO is contrary to results from the EQ and previously published data. Low δ15N values in partially and nonmigrating micronektonivores of the LO in comparison with those of the EQ could be due to feeding on lower trophic prey components in the LO, as is indicated by an overlap in isotopic niche with that of partially and nonmigrating mixed crustacean feeders in the LO. Alternatively, driving mechanisms could be the consumption of prey from shallower waters, regional differences in δ15N enrichment, species-specific ecological differences or a combination of these processes. Each of these explanations is likely tightly correlated to a vertical biogeochemical structuring effect of low oxygen midwater layers fuelled by high nitrate inputs from the Mauritanian upwelling region. Our study provides crucial ecological insights for a better understanding of large-scale gradients in micronekton migration patterns