2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modelling

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), affect millions of people every year and so far, there are no therapeutic cures available. Even though animal and histological models have been of great aid in understanding disease mechanisms and identifying possible therapeutic strategies, in order to find disease-modifying solutions there is still a critical need for systems that can provide more predictive and physiologically relevant results. One possible avenue is the development of patient-derived models, e.g. by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), which can then be differentiated into any cell type for modelling. These systems contain key genetic information from the donors, and therefore have enormous potential as tools in the investigation of pathological mechanisms underlying disease phenotype, and progression, as well as in drug testing platforms. hiPSCs have been widely cultured in 2D systems, but in order to mimic human brain complexity, 3D models have been proposed as a more advanced alternative. This review will focus on the use of patient-derived hiPSCs to model AD, PD, HD and ALS. In brief, we will cover the available stem cells, types of 2D and 3D culture systems, existing models for neurodegenerative diseases, obstacles to model these diseases in vitro, and current perspectives in the field

Essential Noninvasive Multimodality Neuromonitoring for the Critically Ill Patient

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2020. Other selected articles can be found online at . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from

Body Context and Posture Affect Mental Imagery of Hands

Different visual stimuli have been shown to recruit different mental imagery strategies. However the role of specific visual stimuli properties related to body context and posture in mental imagery is still under debate. Aiming to dissociate the behavioural correlates of mental processing of visual stimuli characterized by different body context, in the present study we investigated whether the mental rotation of stimuli showing either hands as attached to a body (hands-on-body) or not (hands-only), would be based on different mechanisms. We further examined the effects of postural changes on the mental rotation of both stimuli. Thirty healthy volunteers verbally judged the laterality of rotated hands-only and hands-on-body stimuli presented from the dorsum- or the palm-view, while positioning their hands on their knees (front postural condition) or behind their back (back postural condition). Mental rotation of hands-only, but not of hands-on-body, was modulated by the stimulus view and orientation. Additionally, only the hands-only stimuli were mentally rotated at different speeds according to the postural conditions. This indicates that different stimulus-related mechanisms are recruited in mental rotation by changing the bodily context in which a particular body part is presented. The present data suggest that, with respect to hands-only, mental rotation of hands-on-body is less dependent on biomechanical constraints and proprioceptive input. We interpret our results as evidence for preferential processing of visual- rather than kinesthetic-based mechanisms during mental transformation of hands-on-body and hands-only, respectively

Gut Flora Metabolism of Phosphatidylcholine Promotes Cardiovascular Disease

Metabolomics studies hold promise for the discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. Here we used a metabolomics approach to generate unbiased small-molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine—choline, trimethylamine N-oxide (TMAO) and betaine—were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted upregulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary-choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases, an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidaemic mice. Discovery of a relationship between gut-flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for the development of new diagnostic tests and therapeutic approaches for atherosclerotic heart disease

Submillimeter Polarization Spectrum of the Carina Nebula

Linear polarization maps of the Carina Nebula were obtained at 250, 350, and 500 μm during the 2012 flight of the Balloon-borne Large Aperture Submillimeter Telescope for Polarimetry (BLASTPol). These measurements are combined with Planck 850 μm data in order to produce a submillimeter spectrum of the polarization fraction of the dust emission, averaged over the cloud. This spectrum is flat to within ±15% (relative to the 350 μm polarization fraction). In particular, there is no evidence for a pronounced minimum of the spectrum near 350 μm, as suggested by previous ground-based measurements of other molecular clouds. This result of a flat polarization spectrum in Carina is consistent with recently published BLASTPol measurements of the Vela C molecular cloud and also agrees with a published model for an externally illuminated, dense molecular cloud by Bethell and collaborators. The shape of the spectrum in Carina does not show any dependence on the radiative environment of the dust, as quantified by the Planck-derived dust temperature or dust optical depth at 353 GHz

Relative Alignment between the Magnetic Field and Molecular Gas Structure in the Vela C Giant Molecular Cloud Using Low- and High-density Tracers

We compare the magnetic field orientation for the young giant molecular cloud Vela C inferred from 500 μm polarization maps made with the BLASTPol balloon-borne polarimeter to the orientation of structures in the integrated line emission maps from Mopra observations. Averaging over the entire cloud we find that elongated structures in integrated line-intensity or zeroth-moment maps, for low-density tracers such as 12CO and 13CO J → 1 – 0, are statistically more likely to align parallel to the magnetic field, while intermediate- or high-density tracers show (on average) a tendency for alignment perpendicular to the magnetic field. This observation agrees with previous studies of the change in relative orientation with column density in Vela C, and supports a model where the magnetic field is strong enough to have influenced the formation of dense gas structures within Vela C. The transition from parallel to no preferred/perpendicular orientation appears to occur between the densities traced by 13CO and by C18O J → 1 – 0. Using RADEX radiative transfer models to estimate the characteristic number density traced by each molecular line, we find that the transition occurs at a molecular hydrogen number density of approximately 103 cm−3 . We also see that the Centre Ridge (the highest column density and most active star-forming region within Vela C) appears to have a transition at a lower number density, suggesting that this may depend on the evolutionary state of the cloud

The transcriptional regulator BBX24 impairs DELLA activity to promote shade avoidance in Arabidopsis thaliana

[EN] In response to canopy shade, plant vegetative structures elongate to gain access to light. However, the mechanism that allows a plastic transcriptional response to canopy shade light is not fully elucidated. Here we propose that the activity of PIF4, a key transcription factor in the shade signalling network, is modulated by the interplay between the BBX24 transcriptional regulator and DELLA proteins, which are negative regulators of the gibberellin (GA) signalling pathway. We show that GA-related targets are enriched among genes responsive to BBX24 under shade and that the shade-response defect in bbx24 mutants is rescued by a GA treatment that promotes DELLA degradation. BBX24 physically interacts with DELLA proteins and alleviates DELLA-mediated repression of PIF4 activity. 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