End Stage Renal Disease Predicts Increased Risk of Death in First Degree Relatives in the Norwegian Population

BackgroundIncreased risk of end stage renal disease (ESRD) and death in Norwegian living kidney donors has been reported, most of the donors were related to the recipient. The present study investigates risk of death in first degree relatives of ESRD patients.MethodsThe Norwegian Population Registry, The Norwegian Cause of Death Registry and the Norwegian Renal Registry were linked. All citizens born in Norway, alive in 1960 and with at least one registered first degree relative were included; individuals who died during the first year of life were excluded. A cohort-design was used, ESRD in a first degree relative was the main exposure variable and death and causes of death were the main outcome variables. Cox regression statistics were used to investigate mortality risks.Results5 130 600 individuals were included, 27 508 had at least one first degree relative with ESRD. 828 022 died during follow-up, of whom 4105 had a first degree relative with ESRD. Adjusted hazard ratio (aHR) for death was 1.13 (1.09–1.16) in individuals with a relative with ESRD compared to those without a relative with ESRD. Excluding known hereditary renal disease, aHR decreased to 1.12 (1.09–1.15). Cardiovascular death aHR was 1.15 (1.10–1.21), of which cerebrovascular death 1.34 (1.22–1.50). aHR for death due to non-hereditary renal/ureteric disease was 2.29 (1.81–2.91) with renal failure 1.80 (1.26–2.56) and glomerular disease 5.69 (3.88–8.34) as main contributors. Diabetes mellitus death aHR was 1.68 (1.35–2.10). Absolute mortality risks increased most for the oldest cohorts with excess mortality of 148 per 100.000 person years for the cohort born 1920–39 and 218 for the cohort born 1900–1919.ConclusionsESRD in first degree relatives was associated with increased hazard ratio for death. Death due to cardiovascular disease, renal disease and diabetes mellitus increased the most.     

Spatial evolutionary and ecological vicariance analysis (SEEVA), a novel approach to biogeography and speciation research,with an example from Brazilian Gentianaceae

Aim Spatial evolutionary and ecological vicariance analysis (SEEVA) is a simple analytical method that evaluates environmental or ecological divergence associated with evolutionary splits. It integrates evolutionary hypotheses, phylogenetic data, and spatial, temporal, environmental and geographical information to elucidate patterns. Using a phylogeny of Prepusa Mart. and Senaea Taub. (Angiospermae: Gentianaceae), SEEVA is used to describe the radiation and ecological patterns of this basal gentian group across south‐eastern Brazil. Location Latin America, global. Methods Environmental data for 151 geolocated botanical collections, associated with specimens from seven species, were compiled with Arc GIS, and were matched with geolocated base layers of eight climatological variables, as well as one each of geological, soil type, elevational and vegetation variables. Sister groups were defined on the basis of the six nested nodes that defined the phylogenetic tree of these two genera. A (0, 1)‐scaled divergence index (D) was defined and tested for each of 12 environmental and for each of the six phylogenetic nodes, by means of contingency analyses. We contrast divergence indices of nested clades, allopatric and sympatric sister clades. Results The level of ecological divergence between sister clades/species, defined in terms of D measures, was substantial for five of six nodes, with 21 of 72 environmental comparisons having D > 0.75. Soil types and geological age of bedrock were strongly divergent only for basal nodes in the phylogeny, by contrast with temperature and precipitation, which exhibited strong divergence at all nodes. There has been strong divergence and progressive occupation of wetter and colder habitats throughout the history of Prepusa. Nodes separating allopatric sister clades exhibited larger niche divergence than did those separating sympatric sister clades. Main conclusions SEEVA provides a multi‐source, direct analysis method for correlating field collections, phylogenetic hypotheses, species distributions and georeferenced environmental data. Using SEEVA, it was possible to quantify and test the divergence between sister lineages, illustrating both niche conservatism and ecological specialization. SEEVA permits elucidation of historical and ecological vicariance for evolutionary lineages, and is amenable to wide application, taxonomically, geographically and ecologically.     

Antibody Uptake into Neurons Occurs Primarily via Clathrin-dependent Fcγ Receptor Endocytosis and Is a Prerequisite for Acute Tau Protein Clearance

Tau immunotherapy is effective in transgenic mice, but the mechanisms of Tau clearance are not well known. To this end, Tau antibody uptake was analyzed in brain slice cultures and primary neurons. Internalization was rapid (<1 h), saturable, and substantial compared with control mouse IgG. Furthermore, temperature reduction to 4 °C, an excess of unlabeled mouse IgG, or an excess of Tau antibodies reduced uptake in slices by 63, 41, and 62%, respectively (p = 0.002, 0.04, and 0.005). Uptake strongly correlated with total and insoluble Tau levels (r² = 0.77 and 0.87 and p = 0.002 and 0.0002), suggesting that Tau aggregates influence antibody internalization and/or retention within neurons. Inhibiting phagocytosis did not reduce uptake in slices or neuronal cultures, indicating limited microglial involvement. In contrast, clathrin-specific inhibitors reduced uptake in neurons (≤78%, p < 0.0001) and slices (≤35%, p = 0.03), demonstrating receptor-mediated endocytosis as the primary uptake pathway. Fluid phase endocytosis accounted for the remainder of antibody uptake in primary neurons, based on co-staining with internalized dextran. The receptor-mediated uptake is to a large extent via low affinity FcγII/III receptors and can be blocked in slices (43%, p = 0.04) and neurons (53%, p = 0.008) with an antibody against these receptors. Importantly, antibody internalization appears to be necessary for Tau reduction in primary neurons. Overall, these findings clarify that Tau antibody uptake is primarily receptor-mediated, that these antibodies are mainly found in neurons with Tau aggregates, and that their intracellular interaction leads to clearance of Tau pathology, all of which have major implications for therapeutic development of this approach.     

Hepatic CYP1A induction in rainbow trout (Oncorhynchus mykiss) after exposure to benzo[a]pyrene in water

Juvenile rainbow trout were exposed to unlabelled benzo[a]pyrene BaP and ³H benzo a pyrene (³H BaP), in a static exposure system for 2 days. The initial concentration was 30 μg l^-1 and 0.625 μCi l^-1, corresponding to 6 mg kg^-1 body weight and 125 μCi kg^-1 body weight. Hepatic 7-ethoxyresorufin-O-deethylase (EROD) activity was measured during the exposure and depuration periods, elucidating the time course pattern of CYP1A induction. Maximum induction (11-fold) of EROD activity was observed on day 2 after addition of BaP to the water. Tissue distribution of ³H-BaP was studied by liquid scintillation counting and whole body autoradiography. The concentration of ³H-BaP-derived radioactivity was highest in the bile at all sampling times. High levels of radiolabelled compound were also present in the gills, liver and the olfactory organ. There was an overall decrease in all tissues during the depuration period. The elimination of ³H-BaP-derived radioactivity from the gills, however, was slow compared with liver and blood (6.2 days vs 2.7 and 2.9 days, respectively).     

GENETIC VARIABILITY AND MOLECULAR PHYLOGENY OF DINOPHYSIS SPECIES (DINOPHYCEAE) FROM NORWEGIAN WATERS INFERRED FROM SINGLE CELL ANALYSES OF rDNA1

The objectives of this study were to determine rDNA sequences of the most common Dinophysis species in Scandinavian waters and to resolve their phylogenetic relationships within the genus and to other dinoflagellates. A third aim was to examine the intraspecific variation in D. acuminata and D. norvegica, because these two species are highly variable in both morphology and toxicity. We obtained nucleotide sequences of coding (small subunit [SSU], partial large subunit [LSU], 5.8S) and noncoding (internal transcribed spacer [ITS]1, ITS2) parts of the rRNA operon by PCR amplification of one or two Dinophysis cells isolated from natural water samples. The three photosynthetic species D. acuminata, D. acuta, and D. norvegica differed in only 5 to 8 of 1802 base pairs (bp) within the SSU rRNA gene. The nonphotosynthetic D. rotundata (synonym Phalacroma rotundatum[Claparède et Lachmann] Kofoid et Michener), however, differed in approximately 55 bp compared with the three photosynthetic species. In the D1 and D2 domains of LSU rDNA, the phototrophic species differed among themselves by 3 to 12 of 733 bp, whereas they differed from D. rotundata by more than 100 bp. This supports the distinction between Dinophysis and Phalacroma. In the phylogenetic analyses based on SSU rDNA, all Dinophysis species were grouped into a common clade in which D. rotundata diverged first. The results indicate an early divergence of Dinophysis within the Dinophyta. The LSU phylogenetic analyses, including 4 new and 11 Dinophysis sequences from EMBL, identified two major clades within the phototrophic species. Little or no intraspecific genetic variation was found in the ITS1–ITS2 region of single cells of D. norvegica and D. acuminata from Norway, but the delineation between these two species was not always clear.     

Effect of fish length and nutritional condition on the fecundity of distressed Atlantic cod Gadus morhua from the Baltic Sea

The disappearance of larger individuals and the decrease in individual body condition suffered by Atlantic cod Gadus morhua in the eastern Baltic during the past two decades can be expected to affect the stock reproductive output. To investigate this, female G. morhua were collected during the spawning and pre‐spawning period in 2015?2016. The current individual potential fecundity (F_P) of eastern Baltic G. morhua was estimated and analysed in relation to total length (L_T) and indices of nutritional status such as body condition (K) and hepato‐somatic index (I_H) using generalized linear models. In addition, the current prevalence of atresia and its potential relation to K were investigated. Moreover, a calibration curve to estimate F_P from oocyte diameter, based on the autodiametric oocyte counting method, was established for the first time for eastern Baltic G. morhua and can be used for future fecundity studies on this stock. The results showed that F_P was mainly positively related to fish length, but K and I_H also contributed significantly to the variation in F_P. The model predicted that fish with K = 1·2 have a F_P 51% higher than fish of the same L_T with K = 0·8. The prevalence of fecundity regulation by atresia was 5·8%, but it was found only in fish in the pre‐spawning maturity stage and with low K. Temporal changes in biological features such as the length composition and individual body condition of eastern Baltic G. morhua, should be accounted for when estimating stock reproductive potential.     

Lipooligosaccharide Structures of Invasive and Carrier Isolates of Neisseria meningitidis Are Correlated with Pathogenicity and Carriage

The degree of phosphorylation and phosphoethanolaminylation of lipid A on neisserial lipooligosaccharide (LOS), a major cell-surface antigen, can be correlated with inflammatory potential and the ability to induce immune tolerance in vitro. On the oligosaccharide of the LOS, the presence of phosphoethanolamine and sialic acid substituents can be correlated with in vitro serum resistance. In this study, we analyzed the structure of the LOS from 40 invasive isolates and 25 isolates from carriers of Neisseria meningitidis without disease. Invasive strains were classified as groups 1–3 that caused meningitis, septicemia without meningitis, and septicemia with meningitis, respectively. Intact LOS was analyzed by high resolution matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Prominent peaks for lipid A fragment ions with three phosphates and one phosphoethanolamine were detected in all LOS analyzed. LOS from groups 2 and 3 had less abundant ions for highly phosphorylated lipid A forms and induced less TNF-α in THP-1 monocytic cells compared with LOS from group 1. Lipid A from all invasive strains was hexaacylated, whereas lipid A of 6/25 carrier strains was pentaacylated. There were fewer O-acetyl groups and more phosphoethanolamine and sialic acid substitutions on the oligosaccharide from invasive compared with carrier isolates. Bioinformatic and genomic analysis of LOS biosynthetic genes indicated significant skewing to specific alleles, dependent on the disease outcome. Our results suggest that variable LOS structures have multifaceted effects on homeostatic innate immune responses that have critical impact on the pathophysiology of meningococcal infections.