| 1. |
- Kovacs, Gabor G., et al.
(författare)
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Aging-related tau astrogliopathy (ARTAG) : harmonized evaluation strategy
- 2016
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 131:1, s. 87-102
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Tidskriftsartikel (refereegranskat)abstract
- Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of astroglial tau pathology in the aged brain, facilitating communication among neuropathologists and researchers, and informing interpretation of clinical biomarkers and imaging studies that focus on tau-related indicators.
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| 2. |
- Boccaletti, Anthony, et al.
(författare)
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Fast-moving features in the debris disk around AU Microscopii
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7572, s. 230-
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Tidskriftsartikel (refereegranskat)abstract
- In the 1980s, excess infrared emission was discovered around main-sequence stars; subsequent direct-imaging observations revealed orbiting disks of cold dust to be the source(1). These 'debris disks' were thought to be by-products of planet formation because they often exhibited morphological and brightness asymmetries that may result from gravitational perturbation by planets. This was proved to be true for the beta Pictoris system, in which the known planet generates an observable warp in the disk(2-5). The nearby, young, unusually active late-type star AU Microscopii hosts a well-studied edge-on debris disk; earlier observations in the visible and near-infrared found asymmetric localized structures in the form of intensity variations along the midplane of the disk beyond a distance of 20 astronomical units(6-9). Here we report high-contrast imaging that reveals a series of five large-scale features in the southeast side of the disk, at projected separations of 10-60 astronomical units, persisting over intervals of 1-4 years. All these features appear to move away from the star at projected speeds of 4-10 kilometres per second, suggesting highly eccentric or unbound trajectories if they are associated with physical entities. The origin, localization, morphology and rapid evolution of these features are difficult to reconcile with current theories.
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| 3. |
- Crary, John F., et al.
(författare)
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Primary age-related tauopathy (PART) : a common pathology associated with human aging
- 2014
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 128:6, s. 755-766
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Tidskriftsartikel (refereegranskat)abstract
- We recommend a new term, "primary age-related tauopathy" (PART), to describe a pathology that is commonly observed in the brains of aged individuals. Many autopsy studies have reported brains with neurofibrillary tangles (NFTs) that are indistinguishable from those of Alzheimer's disease (AD), in the absence of amyloid (A beta) plaques. For these "NFT+/A beta-aEuroe brains, for which formal criteria for AD neuropathologic changes are not met, the NFTs are mostly restricted to structures in the medial temporal lobe, basal forebrain, brainstem, and olfactory areas (bulb and cortex). Symptoms in persons with PART usually range from normal to amnestic cognitive changes, with only a minority exhibiting profound impairment. Because cognitive impairment is often mild, existing clinicopathologic designations, such as "tangle-only dementia" and "tangle-predominant senile dementia", are imprecise and not appropriate for most subjects. PART is almost universally detectable at autopsy among elderly individuals, yet this pathological process cannot be specifically identified pre-mortem at the present time. Improved biomarkers and tau imaging may enable diagnosis of PART in clinical settings in the future. Indeed, recent studies have identified a common biomarker profile consisting of temporal lobe atrophy and tauopathy without evidence of A beta accumulation. For both researchers and clinicians, a revised nomenclature will raise awareness of this extremely common pathologic change while providing a conceptual foundation for future studies. Prior reports that have elucidated features of the pathologic entity we refer to as PART are discussed, and working neuropathological diagnostic criteria are proposed.
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| 4. |
- Harakawa, Hiroki, et al.
(författare)
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A super-Earth orbiting near the inner edge of the habitable zone around the M4.5 dwarf Ross 508
- 2022
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Ingår i: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 74:4, s. 904-922
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Tidskriftsartikel (refereegranskat)abstract
- We report the near-infrared radial velocity (RV) discovery of a super-Earth planet on a 10.77 d orbit around the M4.5 dwarf Ross 508 (Jmag = 9.1). Using precision RVs from the Subaru Telescope IRD (InfraRed Doppler) instrument, we derive a semi-amplitude of 3.92ms−1, corresponding to a planet with a minimum mass msini=4.00M⊕. We find no evidence of significant signals at the detected period in spectroscopic stellar activity indicators or MEarth photometry. The planet, Ross 508 b, has a semi-major axis of 0.05366au. This gives an orbit-averaged insolation of ≈1.4 times the Earth’s value, placing Ross 508 b near the inner edge of its star’s habitable zone. We have explored the possibility that the planet has a high eccentricity and its host is accompanied by an additional unconfirmed companion on a wide orbit. Our discovery demonstrates that the near-infrared RV search can play a crucial role in finding a low-mass planet around cool M dwarfs like Ross 508.
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| 5. |
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| 6. |
- Abdelfattah, Ahmed, et al.
(författare)
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Evidence for host-microbiome co-evolution in apple
- 2022
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Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 234:6, s. 2088-2100
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Tidskriftsartikel (refereegranskat)abstract
- Plants evolved in association with a diverse community of microorganisms. The effect of plant phylogeny and domestication on host–microbiome co-evolutionary dynamics are poorly understood.Here we examined the effect of domestication and plant lineage on the composition of the endophytic microbiome of 11 Malus species, representing three major groups: domesticated apple (M. domestica), wild apple progenitors, and wild Malus species.The endophytic community of M. domestica and its wild progenitors showed higher microbial diversity and abundance than wild Malus species. Heirloom and modern cultivars harbored a distinct community composition, though the difference was not significant. A community-wide Bayesian model revealed that the endophytic microbiome of domesticated apple is an admixture of its wild progenitors, with clear evidence for microbiome introgression, especially for the bacterial community. We observed a significant correlation between the evolutionary distance of Malus species and their microbiome.This study supports co-evolution between Malus species and their microbiome during domestication. This finding has major implications for future breeding programs and our understanding of the evolution of plants and their microbiomes.
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| 7. |
- Akiyama, Eiji, et al.
(författare)
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SPIRAL STRUCTURE AND DIFFERENTIAL DUST SIZE DISTRIBUTION IN THE LkH alpha 330 DISK
- 2016
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 152:6
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Tidskriftsartikel (refereegranskat)abstract
- Dust trapping accelerates the coagulation of dust particles, and, thus, it represents an initial step toward the formation of planetesimals. We report H-band (1.6 mu m) linear polarimetric observations and 0.87 mm interferometric continuum observations toward a transitional disk around LkH alpha 330. As a. result, a pair of spiral arms were detected in the H-band emission, and an asymmetric (potentially arm-like) structure was detected in the 0.87 mm continuum emission. We discuss the origin of the spiral arm and the asymmetric structure. and suggest that a massive unseen planet is the most plausible explanation. The possibility of dust trapping and grain growth causing the asymmetric structure was also investigated through the opacity index (beta) by plotting the observed spectral energy distribution slope between 0.87 mm from our Submillimeter Array observation and 1.3 mm from literature. The results imply that grains are indistinguishable from interstellar medium-like dust in the east side (beta = 2.0 +/- 0.5) but are much smaller in the west side beta = 0.7(-0.4)(+0.5), indicating differential dust size distribution between the two sides of the disk. Combining the results of near-infrared and submillimeter observations, we conjecture that the spiral arms exist at the upper surface and an asymmetric structure resides in the disk interior. Future observations at centimeter wavelengths and differential polarization imaging in other bands (Y-K) with extreme AO imagers are required to understand how large dust grains form and to further explore the dust distribution in the disk.
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| 8. |
- Botvinik-Nezer, Rotem, et al.
(författare)
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Variability in the analysis of a single neuroimaging dataset by many teams
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
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Tidskriftsartikel (refereegranskat)abstract
- Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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| 9. |
- Boutajangout, Allal, et al.
(författare)
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Affibody-Mediated Sequestration of Amyloid beta Demonstrates Preventive Efficacy in a Transgenic Alzheimer's Disease Mouse Model
- 2019
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media S.A.. - 1663-4365 .- 1663-4365. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Different strategies for treatment and prevention of Alzheimer's disease (AD) are currently under investigation, including passive immunization with anti-amyloid beta (anti-A beta) monoclonal antibodies (mAbs). Here, we investigate the therapeutic potential of a novel type of A beta-targeting agent based on an affibody molecule with fundamentally different properties to mAbs. We generated a therapeutic candidate, denoted Z(SYM73)-albumin-binding domain (ABD; 16.8 kDa), by genetic linkage of the dimeric Z(SYM73) affibody for sequestering of monomeric A beta-peptides and an ABD for extension of its in vivo half-life. Amyloid precursor protein (APP)/PS1 transgenic AD mice were administered with Z(SYM73)-ABD, followed by behavioral examination and immunohistochemistry. Results demonstrated rescued cognitive functions and significantly lower amyloid burden in the treated animals compared to controls. No toxicological symptoms or immunology-related side-effects were observed. To our knowledge, this is the first reported in vivo investigation of a systemically delivered scaffold protein against monomeric A beta, demonstrating a therapeutic potential for prevention of AD.
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| 10. |
- Currie, Thayne, et al.
(författare)
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Direct imaging and astrometric detection of a gas giant planet orbiting an accelerating star
- 2023
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Ingår i: Science. - 0036-8075 .- 1095-9203. ; 380:6641, s. 198-203
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Tidskriftsartikel (refereegranskat)abstract
- Direct imaging of gas giant exoplanets provides information on their atmospheres and the architectures of planetary systems. However, few planets have been detected in blind surveys with direct imaging. Using astrometry from the Gaia and Hipparcos spacecraft, we identified dynamical evidence for a gas giant planet around the nearby star HIP 99770. We confirmed the detection of this planet with direct imaging using the Subaru Coronagraphic Extreme Adaptive Optics instrument. The planet, HIP 99770 b, orbits 17 astronomical units from its host star, receiving an amount of light similar to that reaching Jupiter. Its dynamical mass is 13.9 to 16.1 Jupiter masses. The planet-to-star mass ratio [(7 to 8) × 10−3] is similar to that of other directly imaged planets. The planet’s atmospheric spectrum indicates an older, less cloudy analog of the previously imaged exoplanets around HR 8799.
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