New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Quantifying the effect of turbulent magnetic diffusion on the growth rate of the magneto-rotational instability

VK: resolve; Karhunen, J.; ReSoLVEContext. In astrophysics, turbulent diffusion is often used in place of microphysical diffusion to avoid resolving the small scales. However, we expect this approach to break down when time and length scales of the turbulence become comparable with other relevant time and length scales in the system. Turbulent diffusion has previously been applied to the magneto-rotational instability (MRI), but no quantitative comparison of growth rates at different turbulent intensities has been performed. Aims. We investigate to what extent turbulent diffusion can be used to model the effects of small-scale turbulence on the kinematic growth rates of the MRI, and how this depends on angular velocity and magnetic field strength. Methods. We use direct numerical simulations in three-dimensional shearing boxes with periodic boundary conditions in the spanwise direction and additional random plane-wave volume forcing to drive a turbulent flow at a given length scale. We estimate the turbulent diffusivity using a mixing length formula and compare with results obtained with the test-field method. Results. It turns out that the concept of turbulent diffusion is remarkably accurate in describing the effect of turbulence on the growth rate of the MRI. No noticeable breakdown of turbulent diffusion has been found, even when time and length scales of the turbulence become comparable with those imposed by the MRI itself. On the other hand, quenching of turbulent magnetic diffusivity by the magnetic field is found to be absent. Conclusions. Turbulence reduces the growth rate of the MRI in the same way as microphysical magnetic diffusion does.Peer reviewe

Doppler images of DI Piscium during 2004-2006

VK: resolve; Karhunen, J.; ReSoLVEAims. DI Psc (HD 217352) is a Li-rich, rapidly rotating single K giant. We set out to study the spot configuration and activity level by calculating surface temperature maps of the star. Methods. We apply the Doppler imaging method on high-resolution optical spectroscopy obtained during 2004–2006. Results. In July–August 2004, no clear spot structures were visible, but the spot coverage increased in July 2005, and cool spots emerged, especially at intermediate latitudes. Later on in September 2006, the spot coverage increased and cool spots were visible on both sides of the equator. However, the map of 2006 suffers from bad phase coverage, meaning it is not possible to draw definite conclusions on the spot locations during that season. Conclusions. Compared with earlier Doppler maps of DI Psc and temperature maps obtained for other late-type stars with similar rotation rates, DI Psc seems to be in a low activity state especially during the observing season of July–August 2004. During the 2005 and 2006 observing seasons, the spot activity seen in the spectral line profiles and inferred from Doppler images increases, and the temperature contrast in our last map is more comparable to what was reported in an earlier study. Therefore, it can be concluded that the spot activity level of the star is variable over time. However, the present and previous Doppler images form too short a time series to draw conclusions about a possible activity cycle in DI Psc.Peer reviewe

High-resolution ammonia mapping of the very young protostellar core Chamaeleon-MMS1

VK: resolve; Karhunen, J.; ReSoLVEAims. The aim of this study is to investigate the structure and kinematics of the nearby candidate first hydrostatic core Cha-MMS1. Methods. Cha-MMS1 was mapped in the NH3(1,1) line and the 1.2 cm continuum using the Australia Telescope Compact Array (ATCA). The angular resolution of the ATCA observations is 7″ (~1000 AU), and the velocity resolution is 50 m s-1. The core was also mapped with the 64 m Parkes Telescope in the NH3(1,1) and (2,2) lines. Observations from Herschel Space Observatory and Spitzer Space Telescope were used to help interpretation. The ammonia spectra were analysed using Gaussian fits to the hyperfine structure. A two-layer model was applied in the central parts of the core where the ATCA spectra show signs of self-absorption. Results. A compact high column density core with a steep velocity gradient (~20 km s-1 pc-1) is detected in ammonia. We derive a high gas density (~106 cm-3) in this region, and a fractional ammonia abundance compatible with determinations towards other dense cores (~10-8). This suggests that the age of the high density core is comparable to the freeze-out timescale of ammonia in these conditions, on the order of 104 years. The direction of the velocity gradient agrees with previous single-dish observations, and the overall velocity distribution can be interpreted as rotation. The rotation axis goes through the position of a compact far-infrared source detected by Spitzer and Herschel. The specific angular momentum of the core, ~10-3km s-1 pc, is typical for protostellar envelopes. A string of 1.2 cm continuum sources is tentatively detected near the rotation axis. The ammonia spectra suggest the presence of warm embedded gas in its vicinity. An hourglass-shaped structure is seen in ammonia at the cloud’s average LSR velocity, also aligned with the rotation axis. Although this structure resembles a pair of outflow lobes the ammonia spectra show no indications of shocked gas. Conclusions. The observed ammonia structure mainly delineates the inner envelope around the central source. The velocity gradient is likely to originate in the angular momentum of the contracting core, although influence of the outflow from the neighbouring young star IRS4 is possibly visible on one side of the core. The tentative continuum detection and the indications of a warm background component near the rotation axis suggest that the core contains a deeply embedded outflow which may have been missed in previous single-dish CO surveys owing to beam dilution.Peer reviewe

Call for action: Designing for harmony in creative teams

Competitive markets force diverse organizations to intensively manage innovation. Many of them set up multifunctional teams responsible for generating novel and original ideas. Such teams often face higher risk of conflicts and tensions, being an inherent part of creative processes. Impact of this phenomena on creative performance of teams, even though extensively addressed in research, remains unclarified. We approach this issue while providing a novel interpretation framework inspired by the concept of harmony in jazz improvisation. We apply it to observations made with project teams in an organizational setting, and use it to inform design of a supporting collaborative solution. We postulate the need for further work on team harmony and creativity

Observing Dynamos in Cool Stars

The main aim of this paper is to introduce the most important observables that help us to investigate stellar dynamos and compare those to the modeling results. We give an overview of the available observational methods and data processing techniques that are suitable for such purposes, with touching upon examples of inadequate interpretations as well. Stellar observations are compared to the solar data in such a way, which ensures that the measurements are comparable in dimension, wavelength, and timescale. A brief outlook is given to the future plans and possibilities. A thorough review of this topic was published nearly a decade ago (Berdyugina 2005), now we focus on the experience that have been gathered since that time.Comment: 47 pages, accepted for publication in Space Science Review

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele. © 2022, The Author(s)