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- Durso, M., et al.
(author)
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Biomimetic graphene for enhanced interaction with the external membrane of astrocytes
- 2018
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In: Journal of Materials Chemistry B. - : Royal Society of Chemistry (RSC). - 2050-7518 .- 2050-750X. ; 6:33, s. 5335-5342
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Journal article (peer-reviewed)abstract
- Graphene and graphene substrates display huge potential as material interfaces for devices and biomedical tools targeting the modulation or recovery of brain functionality. However, to be considered reliable neural interfaces, graphene-derived substrates should properly interact with astrocytes, favoring their growth and avoiding adverse gliotic reactions. Indeed, astrocytes are the most abundant cells in the human brain and they have a crucial physiological role to maintain its homeostasis and modulate synaptic transmission. In this work, we describe a new strategy based on the chemical modification of graphene oxide (GO) with a synthetic phospholipid (PL) to improve interaction of GO with brain astroglial cells. The PL moieties were grafted on GO sheets through polymeric brushes obtained by atom-transfer radical-polymerization (ATRP) between acryloyl-modified PL and GO nanosheets modified with a bromide initiator. The adhesion of primary rat cortical astrocytes on GO-PL substrates increased by about three times with respect to that on glass substrates coated with standard adhesion agents (i.e. poly-d-lysine, PDL) as well as with respect to that on non-functionalized GO. Moreover, we show that astrocytes seeded on GO-PL did not display significant gliotic reactivity, indicating that the material interface did not cause a detrimental inflammatory reaction when interacting with astroglial cells. Our results indicate that the reported biomimetic approach could be applied to neural prosthesis to improve cell colonization and avoid glial scar formation in brain implants. Additionally, improved adhesion could be extremely relevant in devices targeting neural cell sensing/modulation of physiological activity.
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- Saracino, S., et al.
(author)
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Updated radial velocities and new constraints on the nature of the unseen source in NGC1850 BH1
- 2023
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 521:2, s. 3162-3171
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Journal article (peer-reviewed)abstract
- A black hole candidate orbiting a luminous star in the Large Magellanic Cloud young cluster NGC 1850 (∼100 Myr) has recently been reported based on radial velocity and light-curve modelling. Subsequently, an alternative explanation has been suggested for the system: a bloated post-mass transfer secondary star (Minitial ∼ 4–5 M⊙ and Mcurrent ∼ 1–2 M⊙) with a more massive, yet luminous companion (the primary). Upon reanalysis of the MUSE spectra, we found that the radial velocity variations originally reported were underestimated (K2, revised = 176 ± 3 km s−1 versus K2, original = 140 ± 3 km s−1) because of the weighting scheme adopted in the full-spectrum fitting analysis. The increased radial velocity semi-amplitude translates into a system mass function larger than previously deduced (frevised = 2.83 M⊙versus foriginal = 1.42 M⊙). By exploiting the spectral disentangling technique, we place an upper limit of 10 per cent of a luminous primary source to the observed optical light in NGC1850 BH1, assuming that the primary and secondary are the only components contributing to the system. Furthermore, by analysing archival near-infrared data, we find clues to the presence of an accretion disc in the system. These constraints support a low-mass post-mass transfer star but do not provide a definitive answer whether the unseen component in NGC1850 BH1 is indeed a black hole. These results predict a scenario where, if a primary luminous source of mass M ≥ 4.7 M⊙ is present in the system (given the inclination and secondary mass constraints), it must be hidden in a optically thick disc to be undetected in the MUSE spectra
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- Baselli, Guido A, et al.
(author)
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Rare ATG7 genetic variants predispose patients to severe fatty liver disease.
- 2022
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In: Journal of hepatology. - : Elsevier BV. - 1600-0641 .- 0168-8278. ; 77:3, s. 596-606
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Journal article (peer-reviewed)abstract
- Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disorders and has a strong heritable component. The aim of this study was to identify new loci contributing to severe NAFLD by examining rare variants.We performed whole-exome sequencing in individuals with NAFLD and advanced fibrosis or hepatocellular carcinoma (n=301) and examined the enrichment of likely pathogenic rare variants vs. the general population, followed by validation at gene level.In patients with severe NAFLD, we observed an enrichment of the p.P426L variant (rs143545741 C>T; OR 5.26, 2.1-12.6; p=0.003) of autophagy-related 7 (ATG7), which we characterized as a loss-of-function, vs. the general population, and an enrichment in rare variants affecting the catalytic domain (OR 13.9, 1.9-612; p=0.002). In the UK Biobank cohort, loss-of-function ATG7 variants increased the risk of cirrhosis and hepatocellular carcinoma (OR 3.30, 1.1-7.5 and OR 12.30, 2.6-36, respectively; p<0.001 for both). The low-frequency loss-of-function p.V471A variant (rs36117895 T>C) was also associated with severe NAFLD in the clinical cohort (OR=1.7, 1.2-2.5; p=0.003), predisposed to hepatocellular ballooning (p=0.007) evolving to fibrosis in a Liver biopsy cohort (n=2268), and was associated with liver injury in the UK Biobank (AST levels, p<0.001), with a larger effect in severely obese individuals where it was linked to hepatocellular carcinoma (p=0.009). ATG7 protein localized to periportal hepatocytes, more so in the presence of ballooning. In the Liver Transcriptomic cohort (n=125) ATG7 expression correlated with suppression of the TNFα pathway, which was conversely upregulated in p.V471A carriers.We identified rare and low-frequency ATG7 loss-of-function variants as modifiers of NAFLD progression by impairing autophagy and facilitating ballooning and inflammation.•We found that rare mutations in a gene called autophagy related (ATG7) increase the risk of developing severe liver disease in individuals with dysmetabolism. •These mutations cause an alteration in protein function and impairment of self-renewal of cellular content, leading to liver damage and inflammation.
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- Ladegaard-Pedersen, P., et al.
(author)
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Constraining a bioavailable strontium isotope baseline for the Lake Garda region, Northern Italy: A multi-proxy approach
- 2022
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In: Journal of Archaeological Science: Reports. - : Elsevier BV. - 2352-409X. ; 41
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Journal article (peer-reviewed)abstract
- The evidence of prehistoric long-distance exchange networks in northern Italy is overwhelming, attested by several finds of non-local raw materials in Bronze Age pile-dwelling settlements of Lake Garda and eastern Po plain, like amber beads and bronze artefacts. Metals are dispersed throughout Bronze Age Europe from mining communities within the Alpine regions, and possibly local artefacts, like the Peschiera-type daggers, are known from archaeological records throughout Europe. This positions the region as part of organized networks of trade and communication connecting prehistoric Europe from north to south. This, however, does not in itself indicate a similar long-distance mobility of prehistoric individuals. To investigate individual, human provenance and mobility, the strontium (Sr) isotope methodology compares strontium isotope analysis of human remains to bioavailable strontium isotope baselines characterizing the regions of interest. We present here environmentally based, multi-proxy (water, soil leachates and plants) Sr baselines from the Lake Garda region. Our results show two separate baselines, roughly corresponding to the geographical distribution of rock types and erosional products thereof. One baseline is valid for the Lake Garda region, where Mesozoic carbonates are a dominant surface-near strontium source, and for the central Po plain north of River Po. We constrain this to 87Sr/86Sr = 0.7088 ± 0.0014 (2σ; n = 44) when including 9 compatible samples reported previously. The second Sr-baseline is valid for Alpine areas dominated by magmatic (basalts excluded) and metamorphic bedrock around the Fersina valley. We constrain this to 87Sr/86Sr = 0.7146 ± 0.0058 (2σ; n = 22) when including 11 compatible samples reported in previous studies. The baselines are compatible with previously reported results of other Sr proxies such as snails, archaeological fauna, and agricultural soils and products from the region. © 2022 Elsevier Ltd
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