681 research outputs found
Dopamine transporter/α-synuclein complexes are altered in the post mortem caudate putamen of Parkinson’s disease: An in situ proximity ligation assay study
No full textParkinson's disease (PD) is characterized by the degeneration of the dopaminergic nigrostriatal neurons and the presence of Lewy bodies (LB) and Lewy neurites (LN) mainly composed of α-synuclein. By using the in situ proximity ligation assay (PLA), which allows for the visualization of protein-protein interactions in tissues to detect dopamine transporter (DAT)/α-synuclein complexes, we previously described that these are markedly redistributed in the striatum of human α-synuclein transgenic mice at the phenotypic stage, showing dopamine (DA) release impairment without a DAT drop and motor symptoms. Here, we used the in situ PLA to investigate DAT/α-synuclein complexes in the caudate putamen of PD patients and age-matched controls. They were found to be redistributed and showed an increased size in PD patients, where we observed several neuropil-like and neuritic-like PLA-positive structures. In the PD brains, DAT immunolabeling showed a pattern similar to that of in situ PLA in areas with abundant α-synuclein neuropathology. This notwithstanding, the in situ PLA signal was only partially retracing DAT or α-synuclein immunolabeling, suggesting that a large amount of complexes may have been lost along with the degeneration process. These findings reveal a DAT/α-synuclein neuropathological signature in PD and hint that synaptic alterations involving striatal DAT may derive from α-synuclein aggregation
Living in Promiscuity: The Multiple Partners of Alpha-Synuclein at the Synapse in Physiology and Pathology.
No full textAlpha-synuclein (α-syn) is a small protein that, in neurons, localizes predominantly to presynaptic terminals. Due to elevated conformational plasticity, which can be affected by environmental factors, in addition to undergoing disorder-to-order transition upon interaction with different interactants, α-syn is counted among the intrinsically disordered proteins (IDPs) family. As with many other IDPs, α-syn is considered a hub protein. This function is particularly relevant at synaptic sites, where α-syn is abundant and interacts with many partners, such as monoamine transporters, cytoskeletal components, lipid membranes, chaperones and synaptic vesicles (SV)-associated proteins. These protein⁻protein and protein⁻lipid membrane interactions are crucial for synaptic functional homeostasis, and alterations in α-syn can cause disruption of this complex network, and thus a failure of the synaptic machinery. Alterations of the synaptic environment or post-translational modification of α-syn can induce its misfolding, resulting in the formation of oligomers or fibrillary aggregates. These α-syn species are thought to play a pathological role in neurodegenerative disorders with α-syn deposits such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), which are referred to as synucleinopathies. Here, we aim at revising the complex and promiscuous role of α-syn at synaptic terminals in order to decipher whether α-syn molecular interactants may influence its conformational state, contributing to its aggregation, or whether they are just affected by it
Mitochondria and alpha-synuclein: Friends or foes in the pathogenesis of Parkinson's disease?
No full textParkinson’s disease (PD) is a movement disorder characterized by dopaminergic nigrostriatal neuron degeneration and the formation of Lewy bodies (LB), pathological inclusions containing fibrils that are mainly composed of α-synuclein. Dopaminergic neurons, for their intrinsic characteristics, have a high energy demand that relies on the efficiency of the mitochondria respiratory chain. Dysregulations of mitochondria, deriving from alterations of complex I protein or oxidative DNA damage, change the trafficking, size and morphology of these organelles. Of note, these mitochondrial bioenergetics defects have been related to PD. A series of experimental evidence supports that α-synuclein physiological action is relevant for mitochondrial homeostasis, while its pathological aggregation can negatively impinge on mitochondrial function. It thus appears that imbalances in the equilibrium between the reciprocal modulatory action of mitochondria and α-synuclein can contribute to PD onset by inducing neuronal impairment. This review will try to highlight the role of physiological and pathological α-synuclein in the modulation of mitochondrial functions
La strada maestra del Master
No full textIl volume raccoglie una serie di contributi sui temi e sui problemi dell’alta formazione nel settore nel campo della comunicazione, da parte di studiosi, docenti, professionisti, collaboratori e allievi, italiani e stranieri, del Master in Comunicazione e Media della Facoltà di Scienze Politiche “Cesare Alfieri” dell’Università degli Studi di Firenze. L’intervento di Gaia Peruzzi riflette sulle modalità formative e sul valore del suddetto master a partire dall’esperienza che l’autrice vi ha fatto, nella duplice veste prima di allieva, poi di collaboratrice alla progettazione e all’organizzazione didattica.The essay is a report on the educational value of the Masters in Communication and Media at the Faculty of Political Science "Cesare Alfieri" of the University of Florence, starting from the experience of the author, in the double role first as student, then as a collaborator to the planning and didactic organisation
Gaia Early Data Release 3: The celestial reference frame (Gaia-CRF3)
No full textContext. Gaia-CRF3 is the celestial reference frame for positions and proper motions in the third release of data from the Gaia mission, Gaia DR3 (and for the early third release, Gaia EDR3, which contains identical astrometric results). The reference frame isdefined by the positions and proper motions at epoch 2016.0 for a specific set of extragalactic sources in the (E)DR3 catalogue. Aims. We describe the construction of Gaia-CRF3 and its properties in terms of the distributions in magnitude, colour, and astrometricquality. Methods. Compact extragalactic sources in Gaia DR3 were identified by positional cross-matching with 17 external catalogues of quasi-stellar objects (QSO) and active galactic nuclei (AGN), followed by astrometric filtering designed to remove stellar contaminants. Selecting a clean sample was favoured over including a higher number of extragalactic sources. For the final sample, the random and systematic errors in the proper motions are analysed, as well as the radio–optical offsets in position for sources in the third realisation of the International Celestial Reference Frame (ICRF3). Results. Gaia-CRF3 comprises about 1.6 million QSO-like sources, of which 1.2 million have five-parameter astrometric solutions in Gaia DR3 and 0.4 million have six-parameter solutions. The sources span the magnitude range G = 13–21 with a peak density at 20.6 mag, at which the typical positional uncertainty is about 1 mas. The proper motions show systematic errors on the level of 12 μas yr−1 on angular scales greater than 15 deg. For the 3142 optical counterparts of ICRF3 sources in the S/X frequency bands, the median offset from the radio positions is about 0.5 mas, but it exceeds 4 mas in either coordinate for 127 sources. We outline the future of Gaia-CRF in the next Gaia data releases. Appendices give further details on the external catalogues used, how to extract information about the Gaia-CRF3 sources, potential (Galactic) confusion sources, and the estimation of the spin and orientation of an astrometric solution
Changes in α-Synuclein Posttranslational Modifications in an AAV-Based Mouse Model of Parkinson’s Disease
No full textParkinson’s disease (PD) pathology is characterized by the loss of dopaminergic neurons of the nigrostriatal system and accumulation of Lewy bodies (LB) and Lewy neurites (LN), inclusions mainly composed of alpha-synuclein (α-Syn) fibrils. Studies linking the occurrence of mutations and multiplications of the α-Syn gene (SNCA) to the onset of PD support that α-Syn deposition may play a causal role in the disease, in line with the hypothesis that disease progression may correlate with the spreading of LB pathology in the brain. Interestingly, LB accumulate posttranslationally modified forms of α-Syn, suggesting that α-Syn posttranslational modifications impinge on α-Syn aggregation and/or toxicity. Here, we aimed at investigating changes in α-Syn phosphorylation, nitration and acetylation in mice subjected to nigral stereotaxic injections of adeno-associated viral vectors inducing overexpression of human α-Syn (AAV-hα-Syn), that model genetic PD with SNCA multiplications. We detected a mild increase of serine (Ser) 129 phosphorylated α-Syn in the substantia nigra (SN) of AAV-hα-Syn-injected mice in spite of the previously described marked accumulation of this PTM in the striatum. Following AAV-hα-Syn injection, tyrosine (Tyr) 125/136 nitrated α-Syn accumulation in the absence of general 3-nitrotirosine (3NT) or nitrated-Tyr39 α-Syn changes and augmented protein acetylation abundantly overlapping with α-Syn immunopositivity were also detected
The Contribution of -Synuclein Spreading to Parkinson’s Disease Synaptopathy
No full textSynaptopathies are diseases with synapse defects as shared pathogenic features, encompassing neurodegenerative disorders such
as Parkinson’s disease (PD). In sporadic PD, the most common age-related neurodegenerative movement disorder, nigrostriatal
dopaminergic deficits are responsible for the onset of motor symptoms that have been related to -synuclein deposition at
synaptic sites. Indeed, -synuclein accumulation can impair synaptic dopamine release and induces the death of nigrostriatal
neurons. While in physiological conditions the protein can interact with and modulate synaptic vesicle proteins and membranes,
numerous experimental evidences have confirmed that its pathological aggregation can compromise correct neuronal functioning.
In addition, recent findings indicate that -synuclein pathology spreads into the brain and can affect the peripheral autonomic and
somatic nervous system. Indeed, monomeric, oligomeric, and fibrillary -synuclein can move from cell to cell and can trigger the
aggregation of the endogenous protein in recipient neurons. This novel “prion-like” behavior could further contribute to synaptic
failure in PD and other synucleinopathies. This review describes the major findings supporting the occurrence of -synuclein
pathology propagation in PD and discusses how this phenomenon could induce or contribute to synaptic injury and degeneration
Gaia Data Release 3: The extragalactic content
No full textThe Gaia Galactic survey mission is designed and optimized to obtain astrometry, photometry, and spectroscopy of nearly two billion stars in our Galaxy. Yet as an all-sky multi-epoch survey, Gaia also observes several million extragalactic objects down to a magnitude of G 21 mag. Due to the nature of the Gaia onboard-selection algorithms, these are mostly point-source-like objects. Using data provided by the satellite, we have identified quasar and galaxy candidates via supervised machine learning methods, and estimate their redshifts using the low resolution BP/RP spectra. We further characterise the surface brightness profiles of host galaxies of quasars and of galaxies from pre-defined input lists. Here we give an overview of the processing of extragalactic objects, describe the data products in Gaia DR3, and analyse their properties. Two integrated tables contain the main results for a high completeness, but low purity (50-70%), set of 6.6 million candidate quasars and 4.8 million candidate galaxies. We provide queries that select purer sub-samples of these containing 1.9 million probable quasars and 2.9 million probable galaxies (both 95% purity). We also use high quality BP/RP spectra of 43 thousand high probability quasars over the redshift range 0.05-4.36 to construct a composite quasar spectrum spanning restframe wavelengths from 72 1000 nm.Astrodynamics & Space Mission
Gaia Data Release 3: Summary of the content and survey properties
No full textContext. We present the third data release of the European Space Agency's Gaia mission, Gaia DR3. This release includes a large variety of new data products, notably a much expanded radial velocity survey and a very extensive astrophysical characterisation of Gaia sources. Aims. We outline the content and the properties of Gaia DR3, providing an overview of the main improvements in the data processing in comparison with previous data releases (where applicable) and a brief discussion of the limitations of the data in this release. Methods. The Gaia DR3 catalogue is the outcome of the processing of raw data collected with the Gaia instruments during the first 34 months of the mission by the Gaia Data Processing and Analysis Consortium. Results. The Gaia DR3 catalogue contains the same source list, celestial positions, proper motions, parallaxes, and broad band photometry in the G, GBP, and GRP pass-bands already present in the Early Third Data Release, Gaia EDR3. Gaia DR3 introduces an impressive wealth of new data products. More than 33 million objects in the ranges GRVS'<'14 and 3100'<'Teff'<'14'500, have new determinations of their mean radial velocities based on data collected by Gaia. We provide GRVS magnitudes for most sources with radial velocities, and a line broadening parameter is listed for a subset of these. Mean Gaia spectra are made available to the community. The Gaia DR3 catalogue includes about 1 million mean spectra from the radial velocity spectrometer, and about 220 million low-resolution blue and red prism photometer BP/RP mean spectra. The results of the analysis of epoch photometry are provided for some 10 million sources across 24 variability types. Gaia DR3 includes astrophysical parameters and source class probabilities for about 470 million and 1500 million sources, respectively, including stars, galaxies, and quasars. Orbital elements and trend parameters are provided for some 800'000 astrometric, spectroscopic and eclipsing binaries. More than 150'000 Solar System objects, including new discoveries, with preliminary orbital solutions and individual epoch observations are part of this release. Reflectance spectra derived from the epoch BP/RP spectral data are published for about 60 000 asteroids. Finally, an additional data set is provided, namely the Gaia Andromeda Photometric Survey, consisting of the photometric time series for all sources located in a 5.5 degree radius field centred on the Andromeda galaxy. Conclusions. This data release represents a major advance with respect to Gaia DR2 and Gaia EDR3 because of the unprecedented quantity, quality, and variety of source astrophysical data. To date this is the largest collection of all-sky spectrophotometry, radial velocities, variables, and astrophysical parameters derived from both low- and high-resolution spectra and includes a spectrophotometric and dynamical survey of SSOs of the highest accuracy. The non-single star content surpasses the existing data by orders of magnitude. The quasar host and galaxy light profile collection is the first such survey that is all sky and space based. The astrophysical information provided in Gaia DR3 will unleash the full potential of Gaia's exquisite astrometric, photometric, and radial velocity surveys.Astrodynamics & Space Mission
Revisiting the Gaia hypothesis: Maximum Entropy, Kauffman's 'Fourth Law' and physiosemeiosis
No full textRecently, Kleidon suggested a restatement of the Gaia hypothesis based on Maximum Entropy approaches to the Earth system. Refuting conceptions of Gaia as a homeostatic system, Gaia is seen as a non-equilibrium thermodynamic system which continuously moves away from equilibrium, driven by maximum entropy production which materializes in hierarchically coupled mechanisms of energetic flows via dissipation and physical work. I propose to relate this view with Kauffman's 'Fourth Law of Thermodynamics', which I interprete as a proposition about the accumulation of information in evolutionary processes. Then, beyond its use in the Kleidon model, the concept of physical work is expanded to including work directed at the capacity to work: I offer a twofold specification of Kauffman's concept of an 'autonomous agent', one as a 'self-referential heat engine', and the other in terms of physiosemeiosis, which is a naturalized application of Peirce's theory of signs emerging from recent biosemiotic research. I argue that the conjunction of these three theoretical sources, Maximum Entropy, Kauffman's Fourth Law, and physiosemeiosis, allows to show that the Kleidon restatement of the Gaia hypothesis is equivalent to the proposition that the biosphere is a system of generating, processing and storing information, thus directly treating information as a physical phenomenon. I substantiate this argument by proposing a more detailed analysis of the notion of hierarchy in the Kleidon model. In this view, there is a fundamental ontological continuity between the biological processes and the human economy, as both are seen as information processing and entropy producing systems. As with other previous transitions in evolution, the human economy leverages the mechanisms by which Gaia moves further away from equilibrium. This implies that information and natural resources or energy are not substitutes, i.e. the knowledge economy continues to build on the same physical principles as the biosphere, with energy and information being two aspects of the same underlying physical process. --Gaia,non-equilibrium systems,Fourth Law,work,Peirce,triadism,hierarchy,economic growth
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