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The genetic component of Alzheimer’s disease (AD) has been mainly assessed using Genome Wide Association Studies (GWAS), which do not capture the risk contributed by rare variants. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals —16,036 AD cases and 16,522 controls— in a two-stage analysis. Next to known genes TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Next to these genes, the rare variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential driver genes in AD-GWAS loci. Rare damaging variants in these genes, and in particular loss-of-function variants, have a large effect on AD-risk, and they are enriched in early onset AD cases. The newly identified AD-associated genes provide additional evidence for a major role for APP-processing, Aβ-aggregation, lipid metabolism and microglial function in AD.

We reconstruct the geometry and strength of the Atlantic meridional overturning circulation during the Heinrich stadial 2 and three Greenland interstadials of the 20–50 ka period based on the comparison of new and published sedimentary 231Pa / 230Th data with simulated sedimentary 231Pa / 230Th. We show that the deep Atlantic circulation during these interstadials was very different from that of the Holocene. Northern-sourced waters likely circulated above 2500 m depth, with a flow rate lower than that of the present-day North Atlantic deep water (NADW). Southern-sourced deep waters most probably flowed northwards below 4000 m depth into the North Atlantic basin and then southwards as a return flow between 2500 and 4000 m depth. The flow rate of this southern-sourced deep water was likely larger than that of the modern Antarctic bottom water (AABW). Our results further show that during Heinrich stadial 2, the deep Atlantic was probably directly affected by a southern-sourced water mass below 2500 m depth, while a slow, southward-flowing water mass originating from the North Atlantic likely influenced depths between 1500 and 2500 m down to the equator.

The genus Profundiconus Kuroda, 1956 is reviewed. The morphological characters of the shell, radular tooth and internal anatomy of species in Profundiconus are discussed. In particular, we studied Profundiconus material collected by dredging in deep water during different scientific campaigns carried out in the Solomon Islands, Madagascar, Papua New Guinea and New Caledonia. We reconstructed a phylogeny of 55 individuals based on partial mitochondrial cox1 gene sequences. The phylogeny shows several clades containing individuals that do not match any of the known species of Profundiconus based on their shell and radular morphologies, and are introduced here as five new species: Profundiconus maribelae sp. nov. from the Solomon Islands; P. virginiae sp. nov. from Chesterfield Plateau (New Caledonia); P. barazeri sp. nov. from Chesterfield Plateau and the Grand Passage area (New Caledonia); P. puillandrei sp. nov. from Norfolk Ridge (New Caledonia), Kermadec Ridge (New Zealand) and possibly Balut Island (Philippines); and P. neocaledonicus sp. nov. from New Caledonia. Furthermore, Profundiconus teramachii forma neotorquatus (da Motta, 1984) is raised to specific status as P. neotorquatus (da Motta, 1984).

Dansgaard–Oeschger oscillations constitute one of the most enigmatic features of the last glacial cycle. Their cold atmospheric phases have been commonly associated with cold sea-surface temperatures and expansion of sea ice in the North Atlantic and adjacent seas. Here, based on dinocyst analyses from the 48–30 ka interval of four sediment cores from the northern Northeast Atlantic and southern Norwegian Sea, we provide direct and quantitative evidence of a regional paradoxical seesaw pattern: cold Greenland and North Atlantic phases coincide with warmer sea-surface conditions and shorter seasonal sea-ice cover durations in the Norwegian Sea as compared to warm phases. Combined with additional palaeorecords and multi-model hosing simulations, our results suggest that during cold Greenland phases, reduced Atlantic meridional overturning circulation and cold North Atlantic sea-surface conditions were accompanied by the subsurface propagation of warm Atlantic waters that re-emerged in the Nordic Seas and provided moisture towards Greenland summit.

The pairwise comparison of RNA secondary structures is a fundamental problem, with direct application in mining databases for annotating putative noncoding RNA candidates in newly sequenced genomes. An increasing number of software tools are available for comparing RNA secondary structures, based on different models (such as ordered trees or forests, arc annotated sequences, and multilevel trees) and computational principles (edit distance, alignment). We describe here the website BRASERO that offers tools for evaluating such software tools on real and synthetic datasets.

The Stratosphere–troposphere Processes And their Role in Climate (SPARC) Quasi-Biennial Oscillation initiative (QBOi) aims to improve the fidelity of tropical stratospheric variability in general circulation and Earth system models by conducting coordinated numerical experiments and analysis. In the equatorial stratosphere, the QBO is the most conspicuous mode of variability. Five coordinated experiments have therefore been designed to (i) evaluate and compare the verisimilitude of modelled QBOs under present-day conditions, (ii) identify robustness (or alternatively the spread and uncertainty) in the simulated QBO response to commonly imposed changes in model climate forcings (e.g. a doubling of CO2 amounts), and (iii) examine model dependence of QBO predictability. This paper documents these experiments and the recommended output diagnostics. The rationale behind the experimental design and choice of diagnostics is presented. To facilitate scientific interpretation of the results in other planned QBOi studies, consistent descriptions of the models performing each experiment set are given, with those aspects particularly relevant for simulating the QBO tabulated for easy comparison.