Abstract Galectin-3 (Gal-3) is a β-galactoside-binding lectin that plays an important role in inflammatory and neurodegenerative diseases. Cuprizone (CPZ)-induced demyelination is characterized by ...the loss of mature oligodendrocytes (OLG) by apoptosis, myelin sheath degeneration and recruitment of microglia and astrocytes to the lesioned area. We compared CPZ-induced demyelination of 8-week-old Lgals3−/− vs WT mice. Lgals3−/− mice displayed a similar susceptibility to CPZ-induced demyelination up to the fifth week, as evaluated by MBP immunostaining and electronic microscopy. However, OLG progenitors (OPC) generated in CPZ-treated Lgals3−/− mice showed diminished arborization, suggesting decreased ability of these cells to differentiate. Surprisingly, while WT mice experienced spontaneous remyelination in the fifth week of CPZ treatment—even though the CPZ diet was maintained up to sixth week— Lgals3−/− mice lacked this capacity and suffered continuous demyelination up to the sixth week, accompanied by pronounced astroglial activation. Moreover, after 2 weeks of CPZ treatment, WT and Lgals3−/− mice showed lower innate anxiety as compared with respective naive mice, but only CPZ-treated Lgals3−/− mice showed decreased locomotor activity and exhibited spatial working memory impairment. Expression of Gal-3 increased during CPZ-induced demyelination in microglia but not in astrocytes. While CPZ-treated WT mice displayed heightened microglial activation associated with ED1 expression and pronounced upregulation of the phagocytic receptor TREM-2b, this effect was not observed in CPZ-treated Lgals3−/− mice which, in spite of showing an increased number of microglia, these cells evidenced caspase-3 activation. Our results indicate that Gal-3 is expressed in microglial cells to modulate their phenotype, facilitating the onset of remyelination and OLG differentiation.
Parents of children with rare diseases often face uncertainty about diagnosis, treatment, and costs associated with healthcare for their child. Health insurance status impacts each of these areas, ...but no U.S. study has explored parents' perceptions of the health insurance impacts on their child's care. This study aimed to qualitatively explore how these parents navigate the complex health insurance system for their children and their experiences in doing so.
Semi-structured interviews were conducted with parents of children with metachromatic leukodystrophy (MLD) and spinal muscular atrophy (SMA), chosen for specific disease characteristics and orphan drug status. Participants were recruited via e-mail through patient advocacy organizations between September and December 2018. Interviews were conducted via Skype, were recorded, and professionally transcribed. Modified grounded theory was utilized as a methodology to analyze transcripts in an iterative process to determine themes and sub-themes based on participant described experiences.
Major themes and subthemes that emerged across the 15 interviews included: (1) difficulties obtaining secondary insurance based on state eligibility criteria; (2) difficulty accessing needed healthcare services; and (3) need for repeated interactions with insurance representatives. The absence of clearly documented or widely recognized clinical guidelines exacerbated the difficulty accessing care identified as necessary by their healthcare team, such as therapy and equipment. An explanatory model for parent's experiences was developed from the themes and subthemes. The model includes the cyclical nature of interacting with insurance for redundant reauthorizations and the outside support and financial assistance that is often necessary to address their child's healthcare needs.
With complex health conditions, small setbacks can become costly and disruptive to the health of the child and the life of the family. This study suggests that patients with rare diseases may benefit from time limits for processing coverage decisions, increasing transparency in the claims and preauthorization processes, and more expansive authorizations for on-going needs. Additional studies are needed to understand the full scope of barriers and to inform policies that can facilitate better access for families living with rare diseases.
Context.
Abundances of beryllium in metal-poor stars scale linearly with metallicity down to Fe/H ∼ −3.0. In the stars where Be has been detected at this extremely metal-poor regime, an increased ...abundance scatter has been previously reported in the literature. This scatter could indicate a flattening of the relation between Be abundances and metallicity.
Aims.
Our aim is to perform a new investigation of Be abundances in extremely metal-poor stars and try to clarify whether a Be abundance plateau exists. We revisited the Be abundances in a sample of nine dwarfs with metallicities close to Fe/H ∼ −3.0. Additionally, we analysed the Be lines in the spectra of stars BPS BS 16968-0061 and CD-33 1173 for the first time.
Methods.
We took advantage of
Gaia
DR2 parallaxes to refine values of the surface gravity of the stars. Updated values of surface gravity can have a significant impact on the determination of Be abundances. The other atmospheric parameters were computed using photometric and spectroscopic data. Abundances of Be were determined using spectrum synthesis and model atmospheres.
Results.
Some of the stars indeed suggest a flattening. Over about a 0.5 dex range in metallicity, between Fe/H ∼ −2.70 and −3.26, the Be abundances stay mostly constant at about log(Be/H) ∼ −13.2 dex. Nevertheless, for several stars, we could only place upper limits that are below that level. Most of the sample stars are consistent with having been formed at the progenitor of the so-called
Gaia
-Enceladus merger. Two out of the three stars likely formed in-situ are the ones that deviate the most from the linear relation.
Conclusions.
The mixed origin of these extremely metal-poor stars offers a clue to understanding the flattening. We suggest that our observations can be naturally understood as a consequence of the inhomogeneous star forming conditions in the early Galaxy. Without efficient mixing, the early interstellar medium would be characterised by a large scatter in Fe abundances at a given moment. Beryllium, on the other hand, because of its origins in cosmic-ray spallation, would have more homogeneous abundances (in a Galaxy-wide sense). We therefore suggest that the observed flattening of the Be-versus-metallicity relation reflects a stronger scatter in the Galactic Fe abundances at a given age.
Magnesium hydride owns the largest share of publications on solid materials for hydrogen storage. The “Magnesium group” of international experts contributing to IEA Task 32 “Hydrogen Based Energy ...Storage” recently published two review papers presenting the activities of the group focused on magnesium hydride based materials and on Mg based compounds for hydrogen and energy storage. This review article not only overviews the latest activities on both fundamental aspects of Mg-based hydrides and their applications, but also presents a historic overview on the topic and outlines projected future developments. Particular attention is paid to the theoretical and experimental studies of Mg-H system at extreme pressures, kinetics and thermodynamics of the systems based on MgH2, nanostructuring, new Mg-based compounds and novel composites, and catalysis in the Mg based H storage systems. Finally, thermal energy storage and upscaled H storage systems accommodating MgH2 are presented.
•Historical overview of Mg-based hydrides.•Nanostructured Mg-based H storage materials prepared by mechanical alloying and reactive ball milling.•Thermodynamics and kinetics for Mg-based hydrides.•Catalysis in Mg-H system.•Mg-H system at high pressures: theoretical and experimental studies.
Aims. We report 20 new lithium-rich giants discovered within the Gaia-ESO Survey, including the first Li-rich giant with an evolutionary stage confirmed by CoRoT (Convection, Rotation and planetary ...Transits) data. We present a detailed overview of the properties of these 20 stars. Methods. Atmospheric parameters and abundances were derived in model atmosphere analyses using medium-resolution GIRAFFE or high-resolution UVES (Ultraviolet and Visual Echelle Spectrograph) spectra. These results are part of the fifth internal data release of the Gaia-ESO Survey. The Li abundances were corrected for non-local thermodynamical equilibrium effects. Other stellar properties were investigated for additional peculiarities (the core of strong lines for signs of magnetic activity, infrared magnitudes, rotational velocities, chemical abundances, and Galactic velocities). We used Gaia DR2 parallaxes to estimate distances and luminosities. Results. The giants have A(Li) > 2.2 dex. The majority of them (14 of 20 stars) are in the CoRoT fields. Four giants are located in the field of three open clusters, but are not members. Two giants were observed in fields towards the Galactic bulge, but likely lie in the inner disc. One of the bulge field giants is super Li-rich with A(Li) = 4.0 dex. Conclusions. We identified one giant with infrared excess at 22 μm. Two other giants, with large v sin i, might be Li-rich because of planet engulfment. Another giant is found to be barium enhanced and thus could have accreted material from a former asymptotic giant branch companion. Otherwise, in addition to the Li enrichment, the evolutionary stages are the only other connection between these new Li-rich giants. The CoRoT data confirm that one Li-rich giant is at the core-He burning stage. The other giants are concentrated in close proximity to the red giant branch luminosity bump, the core-He burning stages, or the early-asymptotic giant branch. This is very clear from the Gaia-based luminosities of the Li-rich giants. This is also seen when the CoRoT Li-rich giants are compared to a larger sample of 2252 giants observed in the CoRoT fields by the Gaia-ESO Survey, which are distributed throughout the red giant branch in the Teff-log g diagram. These observations show that the evolutionary stage is a major factor for the Li enrichment in giants. Other processes, such as planet accretion, contribute at a smaller scale.
In several instances chemical abundances of main-sequence and giant stars are used simultaneously under the assumption that they share the same abundance scale. It is therefore crucial to understand ...whether the metallicity or abundance differences among dwarfs and giants are real or are produced by systematic errors in the analysis. We aim to ascertain a methodology capable of producing a consistent metallicity scale for giants and dwarfs. To achieve that, we analyzed giants and dwarfs in the Hyades open cluster, under the assumption that they share the same chemical composition. All the stars in this cluster have archival high-resolution spectroscopic data obtained with HARPS and UVES. We analyzed the sample with two methods. The first method constrains the atmospheric parameters independently from spectroscopic method. We show that it is possible to obtain a consistent metallicity scale between dwarfs and giants. In our test, the metallicities derived with the well-constrained set of stellar parameters are consistent independent of the line list used.
Following spinal cord injury (SCI), semaphorin 3A (Sema3A) prevents axonal regeneration through binding to the neuropilin-1 (NRP-1)/PlexinA4 receptor complex. Here, we show that galectin-1 (Gal-1), ...an endogenous glycan-binding protein, selectively bound to the NRP-1/PlexinA4 receptor complex in injured neurons through a glycan-dependent mechanism, interrupts the Sema3A pathway and contributes to axonal regeneration and locomotor recovery after SCI. Although both Gal-1 and its monomeric variant contribute to de-activation of microglia, only high concentrations of wild-type Gal-1 (which co-exists in a monomer-dimer equilibrium) bind to the NRP-1/PlexinA4 receptor complex and promote axonal regeneration. Our results show that Gal-1, mainly in its dimeric form, promotes functional recovery of spinal lesions by interfering with inhibitory signals triggered by Sema3A binding to NRP-1/PlexinA4 complex, supporting the use of this lectin for the treatment of SCI patients.
Organisms that accumulate calcium carbonate structures are particularly vulnerable to ocean warming (OW) and ocean acidification (OA), potentially reducing the socioeconomic benefits of ecosystems ...reliant on these taxa. Since rising atmospheric CO
is responsible for global warming and increasing ocean acidity, to correctly predict how OW and OA will affect marine organisms, their possible interactive effects must be assessed. Here we investigate, in the field, the combined temperature (range: 16-26 °C) and acidification (range: pH
8.1-7.4) effects on mortality and growth of Mediterranean coral species transplanted, in different seasonal periods, along a natural pH gradient generated by a CO
vent. We show a synergistic adverse effect on mortality rates (up to 60%), for solitary and colonial, symbiotic and asymbiotic corals, suggesting that high seawater temperatures may have increased their metabolic rates which, in conjunction with decreasing pH, could have led to rapid deterioration of cellular processes and performance. The net calcification rate of the symbiotic species was not affected by decreasing pH, regardless of temperature, while in the two asymbiotic species it was negatively affected by increasing acidification and temperature, suggesting that symbiotic corals may be more tolerant to increasing warming and acidifying conditions compared to asymbiotic ones.
Microglia (MG) play a crucial role as the predominant myeloid cells in the central nervous system and are commonly activated in multiple sclerosis. They perform essential functions under normal ...conditions, such as actively surveying the surrounding parenchyma, facilitating synaptic remodeling, engulfing dead cells and debris, and protecting the brain against infectious pathogens and harmful self-proteins. Extracellular vesicles (EVs) are diverse structures enclosed by a lipid bilayer that originate from intracellular endocytic trafficking or the plasma membrane. They are released by cells into the extracellular space and can be found in various bodily fluids. EVs have recently emerged as a communication mechanism between cells, enabling the transfer of functional proteins, lipids, different RNA species, and even fragments of DNA from donor cells. MG act as both source and recipient of EVs. Consequently, MG-derived EVs are involved in regulating synapse development and maintaining homeostasis. These EVs also directly influence astrocytes, significantly increasing the release of inflammatory cytokines like IL-1β, IL-6, and TNF-α, resulting in a robust inflammatory response. Furthermore, EVs derived from inflammatory MG have been found to inhibit remyelination, whereas Evs produced by pro-regenerative MG effectively promote myelin repair. This review aims to provide an overview of the current understanding of MG-derived Evs, their impact on neighboring cells, and the cellular microenvironment in normal conditions and pathological states, specifically focusing on demyelination and remyelination processes.
For the past six years we have carried out a search for massive planets around main sequence and evolved stars in the open cluster M 67, using radial velocity (RV) measurements obtained with HARPS at ...ESO (La Silla), SOPHIE at OHP and HRS at HET. Additional RV data come from CORALIE at the Euler Swiss Telescope. We aim to perform a long-term study on giant planet formation in open clusters and determine how it depends on stellar mass and chemical composition. We report the detection of three new extrasolar planets: two in orbit around the two G dwarfs YBP1194 and YBP1514, and one around the evolved star S364. The orbital solution for YBP1194 yields a period of 6.9 days, an eccentricity of 0.24, and a minimum mass of 0.34 MJup. YBP1514 shows periodic RV variations of 5.1 days, a minimum mass of 0.40 MJup, and an eccentricity of 0.39. The best Keplerian solution for S364 yields a period of 121.7 days, an eccentricity of 0.35 and a minimum mass of 1.54 MJup. An analysis of Hα core flux measurements as well as of the line bisectors spans revealed no correlation with the RV periods, indicating that the RV variations are best explained by the presence of a planetary companion. Remarkably, YBP1194 is one of the best solar twins identified so far, and YBP1194b is the first planet found around a solar twin that belongs to a stellar cluster. In contrast with early reports and in agreement with recent findings, our results show that massive planets around stars of open clusters are as frequent as those around field stars.
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