| 1. |
- Petkova, Maya, 1990, et al.
(author)
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Kinematics of Galactic Centre clouds shaped by shear-seeded solenoidal turbulence
- 2023
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In: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 525:1, s. 962-968
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Journal article (peer-reviewed)abstract
- The Central Molecular Zone (CMZ; the central ∼500 pc of the Galaxy) is a kinematically unusual environment relative to the Galactic disc, with high-velocity dispersions and a steep size-linewidth relation of the molecular clouds. In addition, the CMZ region has a significantly lower star formation rate (SFR) than expected by its large amount of dense gas. An important factor in explaining the low SFR is the turbulent state of the star-forming gas, which seems to be dominated by rotational modes. However, the turbulence driving mechanism remains unclear. In this work, we investigate how the Galactic gravitational potential affects the turbulence in CMZ clouds. We focus on the CMZ cloud G0.253+0.016 ('the Brick'), which is very quiescent and unlikely to be kinematically dominated by stellar feedback. We demonstrate that several kinematic properties of the Brick arise naturally in a cloud-scale hydrodynamics simulation, that takes into account the Galactic gravitational potential. These properties include the line-of-sight velocity distribution, the steepened size-linewidth relation, and the predominantly solenoidal nature of the turbulence. Within the simulation, these properties result from the Galactic shear in combination with the cloud's gravitational collapse. This is a strong indication that the Galactic gravitational potential plays a crucial role in shaping the CMZ gas kinematics, and is a major contributor to suppressing the SFR, by inducing predominantly solenoidal turbulent modes.
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| 2. |
- Petkova, Maya, 1990, et al.
(author)
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The complex multiscale structure in simulated and observed emission maps of the proto-cluster cloud G0.253+0.016 ('the Brick')
- 2023
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 520:2, s. 2245-2268
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Journal article (peer-reviewed)abstract
- The Central Molecular Zone (the central ∼500 pc of the Milky Way) hosts molecular clouds in an extreme environment of strong shear, high gas pressure and density, and complex chemistry. G0.253+0.016, also known as 'the Brick', is the densest, most compact, and quiescent of these clouds. High-resolution observations with the Atacama Large Millimetre/submillimetre Array (ALMA) have revealed its complex, hierarchical structure. In this paper we compare the properties of recent hydrodynamical simulations of the Brick to those of the ALMA observations. To facilitate the comparison, we post-process the simulations and create synthetic ALMA maps of molecular line emission from eight molecules. We correlate the line emission maps to each other and to the mass column density and find that HNCO is the best mass tracer of the eight emission lines within the simulations. Additionally, we characterize the spatial structure of the observed and simulated cloud using the density probability distribution function (PDF), spatial power spectrum, fractal dimension, and moments of inertia. While we find good agreement between the observed and simulated data in terms of power spectra and fractal dimensions, there are key differences in the density PDFs and moments of inertia, which we attribute to the omission of magnetic fields in the simulations. This demonstrates that the presence of the Galactic potential can reproduce many cloud properties, but additional physical processes are needed to fully explain the gas structure.
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| 3. |
- Kam, K., et al.
(author)
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Sleep oscillation-specific associations with Alzheimer's disease CSF biomarkers: novel roles for sleep spindles and tau
- 2019
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In: Molecular Neurodegeneration. - : Springer Science and Business Media LLC. - 1750-1326. ; 14
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Journal article (peer-reviewed)abstract
- BackgroundBased on associations between sleep spindles, cognition, and sleep-dependent memory processing, here we evaluated potential relationships between levels of CSF A(42), P-tau, and T-tau with sleep spindle density and other biophysical properties of sleep spindles in a sample of cognitively normal elderly individuals.MethodsOne-night in-lab nocturnal polysomnography (NPSG) and morning to early afternoon CSF collection were performed to measure CSF A(42), P-tau and T-tau. Seven days of actigraphy were collected to assess habitual total sleep time.ResultsSpindle density during NREM stage 2 (N2) sleep was negatively correlated with CSF A(42), P-tau and T-tau. From the three, CSF T-tau was the most significantly associated with spindle density, after adjusting for age, sex and ApoE4. Spindle duration, count and fast spindle density were also negatively correlated with T-tau levels. Sleep duration and other measures of sleep quality were not correlated with spindle characteristics and did not modify the associations between sleep spindle characteristics and the CSF biomarkers of AD.ConclusionsReduced spindles during N2 sleep may represent an early dysfunction related to tau, possibly reflecting axonal damage or altered neuronal tau secretion, rendering it a potentially novel biomarker for early neuronal dysfunction. Given their putative role in memory consolidation and neuroplasticity, sleep spindles may represent a mechanism by which tau impairs memory consolidation, as well as a possible target for therapeutic interventions in cognitive decline.
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| 4. |
- Antzutkin, Oleg, et al.
(author)
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Binding of Aluminium(III)-Citrate Complexes, [Al3(H-1Cit)3(OH)]-4 and [Al3(H-1Cit)3(OH)4]-7, to Alzheimer's A-beta(1-40) Peptides : In situ Atomic Force, Electron Microscopy and Solid State 13C and 27Al NMR Studies
- 2005
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In: Sixth Keele Meeting on Aluminium. - : Centro de Estudos do Ambiente e Mar, Universidade de Aveiro. ; , s. 16-
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Conference paper (other academic/artistic)abstract
- It is believed that Alzheimer's disease (AD) amyloid-β-peptide (Aβ) deposits contribute directly to the disease's progressive neurodegeneration. Aggregation cascade for Aβ peptides, its relevance to neurotoxicity in the course of AD, various factors modulating Aβ aggregation kinetics and experimental methods useful for these studies were recently discussed [1]. Al(III), Zn(II), Cu(II) and Fe(III) ions are often colocalized at the center of the core of Alzheimer's amyloid plaques [2] and are suggested to promote aggregation of physiological concentrations of Aβ [3]. It has also been suggested that Al can block calcium permeable putative Aβ-peptide channels in bilayer membranes [4]. Therefore studies of complexation of metal ions with Aβ-oligomers and fibrils are important in the search for the causes of and potential treatments for AD.We studied effects of highly soluble and biologically relevant aluminium(III)-citrate compounds, [Al3(H-1Cit)3(OH)]-4 and [Al3(H-1Cit)3(OH)4]-7, on the fibrillogenesis of Aβ(1-40). All resonances in 156.37 MHz 27Al and 90.52 MHz 13C MAS NMR spectra of powder Al(III)-citrate complexes were assigned. 27Al MAS NMR of dialysed samples of Aβ(1-40) co-incubated with the Al(III)-citrate complexes at different concentrations in TRIS buffer solutions, pH 7.4, shows that Al(III)-citrates bind to Aβ(1-40) as [Al3(H-1Cit)3(OH)]-4 and either accelerate ([Al3(H-1Cit)3(OH)]-4 complex) or retard ([Al3(H-1Cit)3(OH)4]-7 compound) aggregation of Aβ(1-40) as revealed by AFM. [1] ON Antzutkin, Magn. Reson. Chem. 42 (2004) 231; [2] MA Lovell et al., J. Neurol. Sci. 158 (1998) 47; Ch Exley et al., Al and Alzheimer's disease, Ch Exley (Ed)1998) 47; Ch Exley , Ch Exley (Ed) Elsevier Science, 2001, 421; [3] PW Mantyh et al., J. Neurochem. 61 (1993) 1171; [4] N Arispe et al, PNAS 90 (1993) 567.
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| 5. |
- Martinez-Corral, Ines, et al.
(author)
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Blockade of VEGF-C signaling inhibits lymphatic malformations driven by oncogenic PIK3CA mutation
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- Lymphatic malformations (LMs) are debilitating vascular anomalies presenting with large cysts (macrocystic) or lesions that infiltrate tissues (microcystic). Cellular mechanisms underlying LM pathology are poorly understood. Here we show that the somatic PIK3CA(H1047R) mutation, resulting in constitutive activation of the p110 alpha PI3K, underlies both macrocystic and microcystic LMs in human. Using a mouse model of PIK3CA(H1047R)-driven LM, we demonstrate that both types of malformations arise due to lymphatic endothelial cell (LEC)-autonomous defects, with the developmental timing of p110 alpha activation determining the LM subtype. In the postnatal vasculature, PIK3CA(H1047R) promotes LEC migration and lymphatic hypersprouting, leading to microcystic LMs that grow progressively in a vascular endothelial growth factor C (VEGF-C)-dependent manner. Combined inhibition of VEGF-C and the PI3K downstream target mTOR using Rapamycin, but neither treatment alone, promotes regression of lesions. The best therapeutic outcome for LM is thus achieved by co-inhibition of the upstream VEGF-C/VEGFR3 and the downstream PI3K/mTOR pathways. Lymphatic malformation (LM) is a debilitating often incurable vascular disease. Using a mouse model of LM driven by a disease-causative PIK3CA mutation, the authors show that vascular growth is dependent on the upstream lymphangiogenic VEGF-C signalling, permitting effective therapeutic intervention.
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| 6. |
- Petkova, Aneta T., et al.
(author)
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A structural model for Alzheimer's β-amyloid fibrils based on experimental constraints from solid state NMR
- 2002
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 99:26, s. 16742-16747
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Journal article (peer-reviewed)abstract
- We present a structural model for amyloid fibrils formed by the 40-residue β-amyloid peptide associated with Alzheimer's disease (Aβ1-40), based on a set of experimental constraints from solid state NMR spectroscopy. The model additionally incorporates the cross-β structural motif established by x-ray fiber diffraction and satisfies constraints on Aβ1-40 fibril dimensions and mass-per-length determined from electron microscopy. Approximately the first 10 residues of Aβ1-40 are structurally disordered in the fibrils. Residues 12-24 and 30-40 adopt β-strand conformations and form parallel β-sheets through intermolecular hydrogen bonding. Residues 25-29 contain a bend of the peptide backbone that brings the two β-sheets in contact through sidechain-sidechain interactions. A single cross-β unit is then a double-layered β-sheet structure with a hydrophobic core and one hydrophobic face. The only charged sidechains in the core are those of D23 and K28, which form salt bridges. Fibrils with minimum mass-per-length and diameter consist of two cross-β units with their hydrophobic faces juxtaposed.
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| 7. |
- Pomara, Nunzio, et al.
(author)
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Lower CSF amyloid beta peptides and higher F2-isoprostanes in cognitively intact elderly individuals with major depressive disorder.
- 2012
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In: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 169:5, s. 523-30
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Journal article (peer-reviewed)abstract
- Major depressive disorder is common in the elderly, and symptoms are often not responsive to conventional antidepressant treatment, especially in the long term. Soluble oligomeric and aggregated forms of amyloid beta peptides, especially amyloid beta 42, impair neuronal and synaptic function. Amyloid beta 42 is the main component of plaques and is implicated in Alzheimer's disease. Amyloid beta peptides also induce a depressive state in rodents and disrupt major neurotransmitter systems linked to depression. The authors assessed whether major depression was associated with CSF levels of amyloid beta, tau protein, and F2-isoprostanes in elderly individuals with major depressive disorder and age-matched nondepressed comparison subjects.
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| 8. |
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