During the past two decades, tissue engineering and the regenerative medicine field have invested in the regeneration and reconstruction of pathologically altered tissues, such as cartilage, bone, ...skin, heart valves, nerves and tendons, and many others. The 3D structured scaffolds and hydrogels alone or combined with bioactive molecules or genes and cells are able to guide the development of functional engineered tissues, and provide mechanical support during in vivo implantation. Naturally derived and synthetic polymers, bioresorbable inorganic materials, and respective hybrids, and decellularized tissue have been considered as scaffolding biomaterials, owing to their boosted structural, mechanical, and biological properties. A diversity of biomaterials, current treatment strategies, and emergent technologies used for 3D scaffolds and hydrogel processing, and the tissue-specific considerations for scaffolding for Tissue engineering (TE) purposes are herein highlighted and discussed in depth. The newest procedures focusing on the 3D behavior and multi-cellular interactions of native tissues for further use for in vitro model processing are also outlined. Completed and ongoing preclinical research trials for TE applications using scaffolds and hydrogels, challenges, and future prospects of research in the regenerative medicine field are also presented.
The current coronavirus disease (COVID‐19) outbreak, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has raised the possibility of potential neurotropic properties ...of this virus. Indeed, neurological sequelae of SARS‐CoV‐2 infection have already been reported and highlight the relevance of considering the neurological impact of coronavirus (CoV) from a translational perspective. Animal models of SARS and Middle East respiratory syndrome, caused by structurally similar CoVs during the 2002 and 2012 epidemics, have provided valuable data on nervous system involvement by CoVs and the potential for central nervous system spread of SARS‐CoV‐2. One key finding that may unify these pathogens is that all require angiotensin‐converting enzyme 2 as a cell entry receptor. The CoV spike glycoprotein, by which SARS‐CoV‐2 binds to cell membranes, binds angiotensin‐converting enzyme 2 with a higher affinity compared with SARS‐CoV. The expression of this receptor in neurons and endothelial cells hints that SARS‐CoV‐2 may have higher neuroinvasive potential compared with previous CoVs. However, it remains to be determined how such invasiveness might contribute to respiratory failure or cause direct neurological damage. Both direct and indirect mechanisms may be of relevance. Clinical heterogeneity potentially driven by differential host immune‐mediated responses will require extensive investigation. Development of disease models to anticipate emerging neurological complications and to explore mechanisms of direct or immune‐mediated pathogenicity in the short and medium term is therefore of great importance. In this brief review, we describe the current knowledge from models of previous CoV infections and discuss their potential relevance to COVID‐19.
A majority of current disease-modifying therapeutic approaches for age-related neurodegenerative diseases target their characteristic proteopathic lesions (α-synuclein, Tau, Aβ). To monitor such ...treatments, fluid biomarkers reflecting the underlying disease process are crucial. We found robust increases of neurofilament light chain (NfL) in CSF and blood in murine models of α-synucleinopathies, tauopathy, and β-amyloidosis. Blood and CSF NfL levels were strongly correlated, and NfL increases coincided with the onset and progression of the corresponding proteopathic lesions in brain. Experimental induction of α-synuclein lesions increased CSF and blood NfL levels, while blocking Aβ lesions attenuated the NfL increase. Consistently, we also found NfL increases in CSF and blood of human α-synucleinopathies, tauopathies, and Alzheimer’s disease. Our results suggest that CSF and particularly blood NfL can serve as a reliable and easily accessible biomarker to monitor disease progression and treatment response in mouse models and potentially in human proteopathic neurodegenerative diseases.
•Increased NfL in CSF and blood of proteopathic neurodegenerative diseases•Increased NfL in CSF and blood coincides with onset of proteopathic lesions in brain•NfL as disease progression and treatment response marker•Translational value and predictability of current mouse models in clinical settings
Bacioglu et al. (2016) report NfL increases in CSF and blood of murine models and human α-synucleinopathies, tauopathies, and β-amyloidosis. NfL in bodily fluid constitutes a biomarker of neurodegeneration reflecting the translational value and potential impact of current mouse models in clinical settings.
ABSTRACT
We report the discovery of 25 new open clusters resulting from a search in dense low Galactic latitude fields. We also provide, for the first time, structural and astrophysical parameters ...for the new findings and 34 other recently discovered open clusters using Gaia Data Release 2 (DR2) data. The candidates were confirmed by jointly inspecting the vector point diagrams and spatial distribution. The discoveries were validated by matching near known objects and comparing their mean astrometric parameters with the available literature. A decontamination algorithm was applied to the three-dimensional astrometric space to derive membership likelihoods for clusters stars. By rejecting stars with low membership likelihoods, we built decontaminated colour–magnitude diagrams and derived the clusters astrophysical parameters by isochrone fitting. The structural parameters were also derived by King-profile fittings over the stellar distributions. The investigated clusters are mainly located within 3 kpc from the Sun, with ages ranging from 30 Myr to 3.2 Gyr and reddening limited to E(B − V) = 2.5. On average, our cluster sample presents less concentrated structures than Gaia DR2 confirmed clusters, since the derived core radii are larger while the tidal radii are not significantly different. Most of them are located in the IV quadrant of the Galactic disc at low latitudes, therefore, they are immersed in dense fields characteristic of the inner Milky Way.
Since liver transplant (LT) was introduced to treat patients with familial amyloid polyneuropathy carrying the V30M mutation (ATTR-V30M), ocular and cardiac complications have developed. Long-term ...central nervous system (CNS) involvement was not investigated. Our goals were to: (1) identify and characterise focal neurological episodes (FNEs) due to CNS dysfunction in ATTR-V30M patients; (2) characterise neuropathological features and temporal profile of CNS transthyretin amyloidosis.
We monitored the presence and type of FNEs in 87 consecutive ATTR-V30M and 35 non-ATTR LT patients. FNEs were investigated with CT scan, EEG and extensive neurovascular workup. MRI studies were not performed because all patients had cardiac pacemakers as part of the LT protocol. We characterised transthyretin amyloid deposition in the brains of seven ATTR-V30M patients, dead 3-13 years after polyneuropathy onset.
FNEs occurred in 31% (27/87) of ATTR-V30M and in 5.7% (2/35) of the non-ATTR transplanted patients (OR=7.0, 95% CI 1.5 to 33.5). FNEs occurred on average 14.6 years after disease onset (95% CI 13.3 to 16.0) in ATTR-V30M patients, which is beyond the life expectancy of non-transplanted ATTR-V30M patients (10.9, 95% CI 10.5 to 11.3). ATTR-V30M patients with FNEs had longer disease duration (OR=1.24; 95% CI 1.07 to 1.43), renal dysfunction (OR=4.65; 95% CI 1.20 to 18.05) and were men (OR=3.57; 95% CI 1.02 to 12.30). CNS transthyretin amyloidosis was already present 3 years after polyneuropathy onset and progressed from the meninges and its vessels towards meningocortical vessels and the superficial brain parenchyma, as disease duration increased.
Our findings indicate that CNS clinical involvement occurs in ATTR-V30M patients regardless of LT. Longer disease duration after LT can provide the necessary time for transthyretin amyloidosis to progress until it becomes clinically relevant. Highly sensitive imaging methods are needed to identify and monitor brain ATTR. Disease modifying therapies should consider brain TTR as a target.
ABSTRACT
We report the discovery of 34 new open clusters and candidates as a result of a systematic search carried out in 200 adjacent fields of 1 × 1 deg2 area projected towards the Galactic bulge, ...using Gaia DR2 data. The objects were identified and characterized by a joint analysis of their photometric, kinematic, and spatial distribution that has been consistently used and proved to be effective in our previous works. The discoveries were validated by cross-referencing the objects position and astrometric parameters with the available literature. Besides their coordinates and astrometric parameters, we also provide sizes, ages, distances, and reddening for the discovered objects. In particular, 32 clusters are closer than 2 kpc from the Sun, which represents an increment of nearly $39{{\ \rm per\ cent}}$ of objects with astrophysical parameters determined in the nearby inner disc. Although these objects fill an important gap in the open clusters distribution along the Sagittarius arm, this arm, traced by known clusters, appears to be interrupted, which may be an artefact due to the incompleteness of the cluster census.
Several processing technologies and engineering strategies have been combined to create scaffolds with superior performance for efficient tissue regeneration. Cartilage tissue is a good example of ...that, presenting limited self-healing capacity together with a high elasticity and load-bearing properties. In this work, novel porous silk fibroin (SF) scaffolds derived from horseradish peroxidase (HRP)-mediated crosslinking of highly concentrated aqueous SF solution (16 wt%) in combination with salt-leaching and freeze-drying methodologies were developed for articular cartilage tissue engineering (TE) applications. The HRP-crosslinked SF scaffolds presented high porosity (89.3 ± 0.6%), wide pore distribution and high interconnectivity (95.9 ± 0.8%). Moreover, a large swelling capacity and favorable degradation rate were observed up to 30 days, maintaining the porous-like structure and β-sheet conformational integrity obtained with salt-leaching and freeze-drying processing. The in vitro studies supported human adipose-derived stem cells (hASCs) adhesion, proliferation, and high glycosaminoglycans (GAGs) synthesis under chondrogenic culture conditions. Furthermore, the chondrogenic differentiation of hASCs was assessed by the expression of chondrogenic-related markers (collagen type II, Sox-9 and Aggrecan) and deposition of cartilage-specific extracellular matrix for up to 28 days. The cartilage engineered constructs also presented structural integrity as their mechanical properties were improved after chondrogenic culturing. Subcutaneous implantation of the scaffolds in CD-1 mice demonstrated no necrosis or calcification, and deeply tissue ingrowth. Collectively, the structural properties and biological performance of these porous HRP-crosslinked SF scaffolds make them promising candidates for cartilage regeneration.
In cartilage tissue engineering (TE), several processing technologies have been combined to create scaffolds for efficient tissue repair. In our study, we propose novel silk fibroin (SF) scaffolds derived from enzymatically crosslinked SF hydrogels processed by salt-leaching and freeze-drying technologies, for articular cartilage applications. Though these scaffolds, we were able to combine the elastic properties of hydrogel-based systems, with the stability, resilience and controlled porosity of scaffolds processed via salt-leaching and freeze-drying technologies. SF protein has been extensively explored for TE applications, as a result of its mechanical strength, elasticity, biocompatibility, and biodegradability. Thus, the structural, mechanical and biological performance of the proposed scaffolds potentiates their use as three-dimensional matrices for cartilage regeneration.
We provide a new view on the Cygnus-X north complex by accessing for the first time the low mass content of young stellar populations in the region. Canada–France–Hawaii Telescope/Wide-Field Infrared ...Camera was used to perform a deep near-infrared survey of this complex, sampling stellar masses down to ∼0.1 M⊙. Several analysis tools, including a extinction treatment developed in this work, were employed to identify and uniformly characterize a dozen unstudied young star clusters in the area. Investigation of their mass distributions in low-mass domain revealed a relatively uniform log-normal initial mass function (IMF) with a characteristic mass of 0.32 ± 0.08 M⊙ and mass dispersion of 0.40 ± 0.06. In the high-mass regime, their derived slopes showed that while the youngest clusters (age < 4 Myr) presented slightly shallower values with respect to the Salpeter's, our older clusters (4 Myr < age < 18 Myr) showed IMF compliant values and a slightly denser stellar population. Although possibly evidencing a deviation from an ‘universal’ IMF, these results also supports a scenario where these gas-dominated young clusters gradually ‘build up’ their IMF by accreting low-mass stars formed in their vicinity during their first ∼3 Myr, before the gas expulsion phase, emerging at the age of ∼4 Myr with a fully fledged IMF. Finally, the derived distances to these clusters confirmed the existence of at least three different star-forming regions throughout Cygnus-X north complex, at distances of 500–900 pc, 1.4–1.7 and 3.0 kpc, and revealed evidence of a possible interaction between some of these stellar populations and the Cygnus OB2 association.
ABSTRACT
A number of stellar open cluster (OC) pairs in the Milky Way occupy similar positions in the phase space (coordinates, parallax, and proper motions) and therefore may constitute physically ...interacting systems. The characterization of such objects based on observational data is a fundamental step towards a proper understanding of their physical status and to investigate cluster pair formation in the Galaxy. In this work, we employed the Gaia EDR3 data to investigate a set of 16 OCs distributed as 7 stellar aggregates. We determined structural parameters and applied a decontamination technique that allowed us to obtain unambiguous lists of member stars. The studied OCs span Galactocentric distances and ages in the ranges of $7\lesssim \, R_\mathrm{ G}(\textrm {kpc})\lesssim 11$ and $7.3\le \textrm {log}\, t\le 9.2$. Eight OCs were found to constitute four gravitationally bound pairs (NGC 5617–Trumpler 22, Collinder 394–NGC 6716, Ruprecht 100–Ruprecht 101, and NGC 659–NGC 663, the latter being a dynamically unevolved binary) and other four clusters constitute two interacting, but gravitationally unbound, pairs (King 16–Berkeley 4 and NGC 2383–NGC 2384, the latter being a dissolving OC). Other four OCs (Dias 1, Pismis 19, Czernik 20, and NGC 1857) seem not associated with any stellar aggregates. Apparently, clusters within bound and dynamically evolved pairs tend to present ratios of half-light to tidal radius larger than single clusters located at similar RG, suggesting that mutual tidal interactions may possibly affect their structural parameters. Unbound or dynamically unevolved systems seem to present less noticeable signature of tidal forces on their structure. Moreover, the core radius seems more importantly correlated with the clusters’ internal dynamical relaxation process.
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