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- Keddie, Stephen, et al.
(författare)
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Peripherin is a biomarker of axonal damage in peripheral nervous system disease
- 2023
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Ingår i: Brain. - 0006-8950 .- 1460-2156. ; 146:11, s. 4562-4573
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Tidskriftsartikel (refereegranskat)abstract
- Valid, responsive blood biomarkers specific to peripheral nerve damage would improve management of peripheral nervous system (PNS) diseases. Neurofilament light chain (NfL) is sensitive for detecting axonal pathology but is not specific to PNS damage, as it is expressed throughout the PNS and CNS. Peripherin, another intermediate filament protein, is almost exclusively expressed in peripheral nerve axons. We postulated that peripherin would be a promising blood biomarker of PNS axonal damage. We demonstrated that peripherin is distributed in sciatic nerve, and to a lesser extent spinal cord tissue lysates, but not in brain or extra-neural tissues. In the spinal cord, anti-peripherin antibody bound only to the primary cells of the periphery (anterior horn cells, motor axons and primary afferent sensory axons). In vitro models of antibody-mediated axonal and demyelinating nerve injury showed marked elevation of peripherin levels only in axonal damage and only a minimal rise in demyelination. We developed an immunoassay using single molecule array technology for the detection of serum peripherin as a biomarker for PNS axonal damage. We examined longitudinal serum peripherin and NfL concentrations in individuals with Guillain-Barr © syndrome (GBS, n = 45, 179 time points), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP, n = 35, 70 time points), multiple sclerosis (n = 30), dementia (as non-inflammatory CNS controls, n = 30) and healthy individuals (n = 24). Peak peripherin levels were higher in GBS than all other groups (median 18.75 pg/ml versus < 6.98 pg/ml, P < 0.0001). Peak NfL was highest in GBS (median 220.8 pg/ml) and lowest in healthy controls (median 5.6 pg/ml), but NfL did not distinguish between CIDP (17.3 pg/ml), multiple sclerosis (21.5 pg/ml) and dementia (29.9 pg/ml). While peak NfL levels were higher with older age (rho = +0.39, P < 0.0001), peak peripherin levels did not vary with age. In GBS, local regression analysis of serial peripherin in the majority of individuals with three or more time points of data (16/25) displayed a rise-and-fall pattern with the highest value within the first week of initial assessment. Similar analysis of serial NfL concentrations showed a later peak at 16 days. Group analysis of serum peripherin and NfL levels in GBS and CIDP patients were not significantly associated with clinical data, but in some individuals with GBS, peripherin levels appeared to better reflect clinical outcome measure improvement. Serum peripherin is a promising new, dynamic and specific biomarker of acute PNS axonal damage.
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2. |
- Gasman, Danny, et al.
(författare)
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MINDS Abundant water and varying C/O across the disk of Sz 98 as seen by JWST/MIRI
- 2023
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 679
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Tidskriftsartikel (refereegranskat)abstract
- Context. The Mid-InfraRed Instrument (MIRI) Medium Resolution Spectrometer (MRS) on board the James Webb Space Telescope (JWST) allows us to probe the inner regions of protoplanetary disks, where the elevated temperatures result in an active chemistry and where the gas composition may dictate the composition of planets forming in this region. The disk around the classical T Tauri star Sz 98, which has an unusually large dust disk in the millimetre with a compact core, was observed with the MRS, and we examine its spectrum here.Aims. We aim to explain the observations and put the disk of Sz 98 in context with other disks, with a focus on the H2O emission through both its ro-vibrational and pure rotational emission. Furthermore, we compare our chemical findings with those obtained for the outer disk from Atacama Large Millimeter/submillimeter Array (ALMA) observations.Methods. In order to model the molecular features in the spectrum, the continuum was subtracted and local thermodynamic equilibrium (LTE) slab models were fitted. The spectrum was divided into different wavelength regions corresponding to H2O lines of different excitation conditions, and the slab model fits were performed individually per region.Results. We confidently detect CO, H2O, OH, CO2, and HCN in the emitting layers. Despite the plethora of H2O lines, the isotopo-logue (H2O)-O-18 is not detected. Additionally, no other organics, including C2H2, are detected. This indicates that the C/O ratio could be substantially below unity, in contrast with the outer disk. The H2O emission traces a large radial disk surface region, as evidenced by the gradually changing excitation temperatures and emitting radii. Additionally, the OH and CO2 emission is relatively weak. It is likely that H2O is not significantly photodissociated, either due to self-shielding against the stellar irradiation, or UV shielding from small dust particles. While H2O is prominent and OH is relatively weak, the line fluxes in the inner disk of Sz 98 are not outliers compared to other disks.Conclusions. The relative emitting strength of the different identified molecular features points towards UV shielding of H2O in the inner disk of Sz 98, with a thin layer of OH on top. The majority of the organic molecules are either hidden below the dust continuum, or not present. In general, the inferred composition points to a sub-solar C/O ratio (<0.5) in the inner disk, in contrast with the larger than unity C/O ratio in the gas in the outer disk found with ALMA.
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3. |
- Henning, Thomas, et al.
(författare)
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MINDS : The JWST MIRI Mid-INfrared Disk Survey
- 2024
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Ingår i: Publications of the Astronomical Society of the Pacific. - 0004-6280 .- 1538-3873. ; 136:5
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Tidskriftsartikel (refereegranskat)abstract
- The study of protoplanetary disks has become increasingly important with the Kepler satellite finding that exoplanets are ubiquitous around stars in our galaxy and the discovery of enormous diversity in planetary system architectures and planet properties. High-resolution near-IR and ALMA images show strong evidence for ongoing planet formation in young disks. The JWST MIRI mid-INfrared Disk Survey (MINDS) aims to (1) investigate the chemical inventory in the terrestrial planet-forming zone across stellar spectral type, (2) follow the gas evolution into the disk dispersal stage, and (3) study the structure of protoplanetary and debris disks in the thermal mid-IR. The MINDS survey will thus build a bridge between the chemical inventory of disks and the properties of exoplanets. The survey comprises 52 targets (Herbig Ae stars, T Tauri stars, very low-mass stars and young debris disks). We primarily obtain MIRI/MRS spectra with high signal-to-noise ratio (∼100–500) covering the complete wavelength range from 4.9 to 27.9 μm. For a handful of selected targets we also obtain NIRSpec IFU high resolution spectroscopy (2.87–5.27 μm). We will search for signposts of planet formation in thermal emission of micron-sized dust—information complementary to near-IR scattered light emission from small dust grains and emission from large dust in the submillimeter wavelength domain. We will also study the spatial structure of disks in three key systems that have shown signposts for planet formation, TW Hya and HD 169142 using the MIRI coronagraph at 15.5 μm and 10.65 μm respectively and PDS 70 using NIRCam imaging in the 1.87 μm narrow and the 4.8 μm medium band filter. We provide here an overview of the MINDS survey and showcase the power of the new JWST mid-IR molecular spectroscopy with the TW Hya disk spectrum where we report the detection of the molecular ion CH3+ and the robust confirmation of HCO+ earlier detected with Spitzer.
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4. |
- Kamp, Inga, et al.
(författare)
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The chemical inventory of the inner regions of planet-forming disks - the JWST/MINDS program
- 2023
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Ingår i: Faraday discussions. - 1359-6640 .- 1364-5498. ; 245, s. 112-137
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Tidskriftsartikel (refereegranskat)abstract
- The understanding of planet formation has changed recently, embracing the new idea of pebble accretion. This means that the influx of pebbles from the outer regions of planet-forming disks to their inner zones could determine the composition of planets and their atmospheres. The solid and molecular components delivered to the planet-forming region can be best characterized by mid-infrared spectroscopy. With Spitzer low-resolution (R = 100, 600) spectroscopy, this approach was limited to the detection of abundant molecules, such as H2O, C2H2, HCN and CO2. This contribution will present the first results of the MINDS (MIRI mid-INfrared Disk Survey, PI:Th Henning) project. Due do the sensitivity and spectral resolution provided by the James Webb Space Telescope (JWST), we now have a unique tool to obtain the full inventory of chemistry in the inner disks of solar-type stars and brown dwarfs, including also less-abundant hydrocarbons and isotopologues. The Integral Field Unit (IFU) capabilities will enable at the same time spatial studies of the continuum and line emission in extended sources such as debris disks, the flying saucer and also the search for mid-IR signatures of forming planets in systems such as PDS 70. These JWST observations are complementary to ALMA and NOEMA observations of outer-disk chemistry; together these datasets will provide an integral view of the processes occurring during the planet-formation phase.
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