ALBERT

Description: Non-human primates provide genetic model systems biologically intermediate between humans and other mammalian model organisms. Populations of Caribbean vervet monkeys ( Chlorocebus aethiops sabaeus ) are genetically homogeneous and large enough to permit well-powered genetic mapping studies of quantitative traits relevant to human health, including expression quantitative trait loci (eQTL). Previous transcriptome-wide investigation in an extended vervet pedigree identified 29 heritable transcripts for which levels of expression in peripheral blood correlate strongly with expression levels in the brain. Quantitative trait linkage analysis using 261 microsatellite markers identified significant ( n = 8) and suggestive ( n = 4) linkages for 12 of these transcripts, including both cis - and trans -eQTL. Seven transcripts, located on different chromosomes, showed maximum linkage to markers in a single region of vervet chromosome 9; this observation suggests the possibility of a master trans -regulator locus in this region. For one cis -eQTL (at B3GALTL , beta-1,3-glucosyltransferase), we conducted follow-up single nucleotide polymorphism genotyping and fine-scale association analysis in a sample of unrelated Caribbean vervets, localizing this eQTL to a region of 〈200 kb. These results suggest the value of pedigree and population samples of the Caribbean vervet for linkage and association mapping studies of quantitative traits. The imminent whole genome sequencing of many of these vervet samples will enhance the power of such investigations by providing a comprehensive catalog of genetic variation.

Description: Vortex formation through the Rossby wave instability (RWI) in protoplanetary discs has been invoked to play a role in planet formation theory and suggested to explain the observation of large dust asymmetries in several transitional discs. However, whether or not vortex formation operates in layered accretion discs, i.e. models of protoplanetary discs including dead zones near the disc mid-plane – regions that are magnetically inactive and the effective viscosity greatly reduced – has not been verified. As a first step towards testing the robustness of vortex formation in layered discs, we present non-linear hydrodynamical simulations of global 3D protoplanetary discs with an imposed kinematic viscosity that increases away from the disc mid-plane. Two sets of numerical experiments are performed: (i) non-axisymmetric instability of artificial radial density bumps in viscous discs and (ii) vortex formation at planetary gap edges in layered discs. Experiment (i) shows that the linear instability is largely unaffected by viscosity and remains dynamical. The disc–planet simulations also show the initial development of vortices at gap edges, but in layered discs, the vortices are transient structures which disappear well into the non-linear regime. We suggest that the long-term survival of columnar vortices, such as those formed via the RWI, requires low effective viscosity throughout the vertical extent of the disc, so such vortices do not persist in layered discs.

Description: A Saskatchewan multi-incident family was clinically characterized with Parkinson disease (PD) and Lewy body pathology. PD segregates as an autosomal-dominant trait, which could not be ascribed to any known mutation. DNA from three affected members was subjected to exome sequencing. Genome alignment, variant annotation and comparative analyses were used to identify shared coding mutations. Sanger sequencing was performed within the extended family and ethnically matched controls. Subsequent genotyping was performed in a multi-ethnic case–control series consisting of 2928 patients and 2676 control subjects from Canada, Norway, Taiwan, Tunisia, and the USA. A novel mutation in receptor-mediated endocytosis 8/RME-8 (DNAJC13 p.Asn855Ser) was found to segregate with disease. Screening of cases and controls identified four additional patients with the mutation, of which two had familial parkinsonism. All carriers shared an ancestral DNAJC13 p.Asn855Ser haplotype and claimed Dutch–German–Russian Mennonite heritage. DNAJC13 regulates the dynamics of clathrin coats on early endosomes. Cellular analysis shows that the mutation confers a toxic gain-of-function and impairs endosomal transport. DNAJC13 immunoreactivity was also noted within Lewy body inclusions. In late-onset disease which is most reminiscent of idiopathic PD subtle deficits in endosomal receptor-sorting/recycling are highlighted by the discovery of pathogenic mutations VPS35 , LRRK2 and now DNAJC13 . With this latest discovery, and from a neuronal perspective, a temporal and functional ecology is emerging that connects synaptic exo- and endocytosis, vesicular trafficking, endosomal recycling and the endo-lysosomal degradative pathway. Molecular deficits in these processes are genetically linked to the phenotypic spectrum of parkinsonism associated with Lewy body pathology.

Description: It has been established that self-gravitating disc–satellite interaction can lead to the formation of a gravitationally unstable gap. Such an instability may significantly affect the orbital migration of gap-opening perturbers in self-gravitating discs. In this paper, we extend the two-dimensional hydrodynamic simulations of Lin & Papaloizou to investigate the role of the perturber or planet mass on the gravitational stability of gaps and its impact on orbital migration. We consider giant planets with planet-to-star mass ratio q M p / M * [0.3, 3.0]  x 10 –3 (so that q  = 10 –3 corresponds to a Jupiter mass planet if M * = M ), in a self-gravitating disc with disc-to-star mass ratio M d / M *  = 0.08, aspect ratio h  = 0.05 and Keplerian Toomre parameter Q k0  = 1.5 at 2.5 times the planet's initial orbital radius. These planet masses correspond to $\tilde{q}\in [0.9,\,1.7]$ , where $\tilde{q}$ is the ratio of the planet Hill radius to the local disc scale-height. Fixed-orbit simulations show that all planet masses we consider open gravitationally unstable gaps, but the instability is stronger and develops sooner with increasing planet mass. The disc-on-planet torques typically become more positive with increasing planet mass. In freely migrating simulations, we observe faster outward migration with increasing planet mass, but only for planet masses capable of opening unstable gaps early on. For q  = 0.0003 ( $\tilde{q}=0.9$ ), the planet undergoes rapid inward type III migration before it can open a gap. For q  = 0.0013 ( $\tilde{q}=1.5$ ) we find it is possible to balance the tendency for inward migration by the positive torques due to an unstable gap, but only for a few 10 s of orbital periods. We find the unstable outer gap edge can trigger outward type III migration, sending the planet to twice its initial orbital radius on dynamical time-scales. We briefly discuss the importance of our results in the context of giant planet formation on wide orbits through disc fragmentation.