Assessing SNP-markers to study population mixing and ecological adaptation in Baltic cod

Atlantic cod (Gadus morhua) is a species of great ecological and economical importance in the Baltic Sea. Here, two genetically differentiated stocks, the western and the eastern Baltic cod, display substantial mechanical mixing, hampering our understanding of cod ecology and impeding stock assessments and management. Based on whole-genome re-sequencing data from reference samples obtained from the study area, we designed two different panels of Single Nucleotide Polymorphisms markers (SNPs), which take into account the exceptional genome architecture of cod. A minimum panel of 20 diagnostic SNPs and an extended panel (20 diagnostic and 18 biologically informative SNPs, 38 in total) were developed and validated to distinguish unambiguously between the western and the eastern Baltic cod stocks and to enable studies of local adaptation to the specific environment in the Baltic Sea, respectively. We tested both panels on cod sampled from the southern Baltic Sea (n = 603) caught in 2015 and 2016. Genotyping results showed that catches from the mixing zone in the Arkona Sea, were composed of similar proportions of individuals of the western and the eastern stock. Catches from adjacent areas to the east, the Bornholm Basin and Gdańsk Deep, were exclusively composed of eastern Baltic cod, whereas catches from adjacent western areas (Belt Sea and Öresund) were composed of western Baltic cod. Interestingly, the two Baltic cod stocks showed strong genetic differences at loci associated with life-history trait candidate genes, highlighting the species’ potential for ecological adaptation even at small geographical scales. The minimum and the extended panel of SNP markers presented in this study provide powerful tools for future applications in research and fisheries management to further illuminate the mixing dynamics of cod in the Baltic Sea and to better understand Baltic cod ecology

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Aerosol and cloud top height information of Envisat MIPAS measurements

Infrared limb emission instruments have a long history in measuring clouds and aerosol. In particular, the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) instrument aboard ESA's Envisat provides 10 years of altitude-resolved global measurements. Previous studies found systematic overestimations and underestimations of cloud top heights for cirrus and polar stratospheric clouds. To assess the cloud top height information and to characterise its uncertainty for the MIPAS instrument we performed simulations for ice clouds, volcanic ash, and sulfate aerosol. From the simulation results we found that in addition to the known effects of the field-of-view that can lead to a cloud top height overestimation, and broken cloud conditions that can lead to underestimation, the cloud extinction also plays an important role. While for optically thick clouds the possible cloud top height overestimation for MIPAS reaches up to 1.6 km due to the field-of-view, for optically thin clouds and aerosol the systematic underestimation reaches 5.1 km. For the detection sensitivity and the degree of underestimation of the MIPAS measurements, the cloud layer thickness also plays a role; 1 km thick clouds are detectable down to extinctions of 5×10−4 km−1 and 6 km thick clouds are detectable down to extinctions of 1×10−4 km−1, where the largest underestimations of the cloud top height occur for the optically thinnest clouds with a vertical extent of 6 km. The relation between extinction coefficient, cloud top height estimate, and layer thickness is confirmed by a comparison of MIPAS cloud top heights of the volcanic sulfate aerosol from the Nabro eruption in 2011 with space- and ground-based lidar measurements and twilight measurements between June 2011 and February 2012. For plumes up to 2 months old, where the extinction was between 1×10−4 and 7×10−4 km−1 and the layer thickness mostly below 4 km, we found for MIPAS an average underestimation of 1.1 km. In the aged plume with extinctions down to 5×10−5 km−1 and layer thicknesses of up to 9.5 km, the underestimation was higher, reaching up to 7.2 km. The dependency of the cloud top height overestimations or underestimations on the extinction coefficient can explain seemingly contradictory results of previous studies. In spite of the relatively large uncertainty range of the cloud top height, the comparison of the detection sensitivity towards sulfate aerosol between MIPAS and a suite of widely used UV/VIS limb and IR nadir satellite aerosol measurements shows that MIPAS provides complementary information in terms of detection sensitivity

Aerosol and cloud top height information of Envisat MIPAS measurements

Infrared limb emission instruments have a long history in measuring clouds and aerosol. In particular, the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) instrument aboard ESA's Envisat provides 10 years of altitude-resolved global measurements. Previous studies found systematic overestimations and underestimations of cloud top heights for cirrus and polar stratospheric clouds. To assess the cloud top height information and to characterise its uncertainty for the MIPAS instrument we performed simulations for ice clouds, volcanic ash, and sulfate aerosol. From the simulation results we found that in addition to the known effects of the field-of-view that can lead to a cloud top height overestimation, and broken cloud conditions that can lead to underestimation, the cloud extinction also plays an important role. While for optically thick clouds the possible cloud top height overestimation for MIPAS reaches up to 1.6 km due to the field-of-view, for optically thin clouds and aerosol the systematic underestimation reaches 5.1 km. For the detection sensitivity and the degree of underestimation of the MIPAS measurements, the cloud layer thickness also plays a role; 1 km thick clouds are detectable down to extinctions of 5×10-4 km-1 and 6 km thick clouds are detectable down to extinctions of 1×10-4 km-1, where the largest underestimations of the cloud top height occur for the optically thinnest clouds with a vertical extent of 6 km. The relation between extinction coefficient, cloud top height estimate, and layer thickness is confirmed by a comparison of MIPAS cloud top heights of the volcanic sulfate aerosol from the Nabro eruption in 2011 with space-and ground-based lidar measurements and twilight measurements between June 2011 and February 2012. For plumes up to 2 months old, where the extinction was between 1×10-4 and 7×10-4 km-1 and the layer thickness mostly below 4 km, we found for MIPAS an average underestimation of 1.1 km. In the aged plume with extinctions down to 5 × 10-5 km-1 and layer thicknesses of up to 9.5 km, the underestimation was higher, reaching up to 7.2 km. The dependency of the cloud top height overestimations or underestimations on the extinction coefficient can explain seemingly contradictory results of previous studies. In spite of the relatively large uncertainty range of the cloud top height, the comparison of the detection sensitivity towards sulfate aerosol between MIPAS and a suite of widely used UV/VIS limb and IR nadir satellite aerosol measurements shows that MIPAS provides complementary information in terms of detection sensitivity. © Author(s) 2020

Larval size-distributions of Ariosoma balearicum cryptic species during the March–April season in the Sargasso Sea Subtropical Convergence Zone

Leptocephali of the shallow-water congrid eel Ariosoma balearicum are abundant during February–April in the Sargasso Sea, and larval and adult meristic data indicates this species includes several regional subpopulations/cryptic species. Four multiple-transect larval surveys (2011, 2014, 2015, 2017) were used to examine the geographic size distribution of two myomere-count types of A. balearicum leptocephali. High-count (HC) larvae were consistently mostly between 80 and 100 mm in size (60–132 mm; 87.9 ± 6.8 mm) as observed previously, and frequently had narrow size ranges. The usually larger LC larvae (78–176 mm; 111.4 ± 26.7 mm) were more abundant in western or central areas. HC larvae tended to decrease in size from west to east and increase from south to north. Catch rates were geographically variable relative to hydrographic structure/frontal positions across the wide 2015 sampling area. Mitochondrial 16 s rRNA sequences of HC and LC larvae show species-level differences, providing evidence of the existence of two cryptic species with different larval dispersal strategies in the Sargasso Sea subtropical gyre region. The HC larvae disperse widely into the gyre, seemingly through Gulf Stream recirculation or eastward frontal-jet flows, and apparently must use directional swimming to cross the Florida Current to recruit into the South Atlantic Bight. LC leptocephali may mostly be retained near the Bahamas, with few larvae dispersing into the gyre. This seems to indicate natural selection occurred for spawning location and larval behavior due to the powerful Florida Current/Gulf Stream, resulting in two completely different spawning and larval dispersal strategies within a local geographic region

Evidence of hybridization between genetically distinct Baltic cod stocks during peak population abundance(s)

Abstract Range expansions can lead to increased contact of divergent populations, thus increasing the potential of hybridization events. Whether viable hybrids are produced will most likely depend on the level of genomic divergence and associated genomic incompatibilities between the different entities as well as environmental conditions. By taking advantage of historical Baltic cod (Gadus morhua) otolith samples combined with genotyping and whole genome sequencing, we here investigate the genetic impact of the increased spawning stock biomass of the eastern Baltic cod stock in the mid 1980s. The eastern Baltic cod is genetically highly differentiated from the adjacent western Baltic cod and locally adapted to the brackish environmental conditions in the deeper Eastern basins of the Baltic Sea unsuitable for its marine counterparts. Our genotyping results show an increased proportion of eastern Baltic cod in western Baltic areas (Mecklenburg Bay and Arkona Basin)—indicative of a range expansion westwards—during the peak population abundance in the 1980s. Additionally, we detect high frequencies of potential hybrids (including F1, F2 and backcrosses), verified by whole genome sequencing data for a subset of individuals. Analysis of mitochondrial genomes further indicates directional gene flow from eastern Baltic cod males to western Baltic cod females. Our findings unravel that increased overlap in distribution can promote hybridization between highly divergent populations and that the hybrids can be viable and survive under specific and favourable environmental conditions. However, the observed hybridization had seemingly no long‐lasting impact on the continuous separation and genetic differentiation between the unique Baltic cod stocks

ADAP Promotes Degranulation and Migration of NK Cells Primed During vivo Listeria monocytogenes Infection in Mice.

The adhesion and degranulation-promoting adaptor protein (ADAP) serves as a multifunctional scaffold and is involved in the formation of immune signaling complexes. To date only limited and moreover conflicting data exist regarding the role of ADAP in NK cells. To extend existing knowledge we investigated ADAP-dependency of NK cells in the context of in vivo infection with the intracellular pathogen Listeria monocytogenes (Lm). Ex vivo analysis of infection-primed NK cells revealed impaired cytotoxic capacity in NK cells lacking ADAP as indicated by reduced CD107a surface expression and inefficient perforin production. However, ADAP-deficiency had no global effect on NK cell morphology or intracellular distribution of CD107a-containing vesicles. Proteomic definition of ADAPko and wild type NK cells did not uncover obvious differences in protein composition during the steady state and moreover, similar early response patterns were induced in NK cells upon infection independent of the genotype. In line with protein network analyses that suggested an altered migration phenotype in naïve ADAPko NK cells, in vitro migration assays uncovered significantly reduced migration of both naïve as well as infection-primed ADAPko NK cells compared to wild type NK cells. Notably, this migration defect was associated with a significantly reduced expression of the integrin CD11a on the surface of splenic ADAP-deficient NK cells 1 day post-Lm infection. We propose that ADAP-dependent alterations in integrin expression might account at least in part for the fact that during in vivo infection significantly lower numbers of ADAPko NK cells accumulate in the spleen i.e., the site of infection. In conclusion, we show here that during systemic Lm infection in mice ADAP is essential for efficient cytotoxic capacity and migration of NK cells