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- Cartelli, Daniele, et al.
(författare)
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α-Synuclein is a Novel Microtubule Dynamase
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- α-Synuclein is a presynaptic protein associated to Parkinson's disease, which is unstructured when free in the cytoplasm and adopts α helical conformation when bound to vesicles. After decades of intense studies, α-Synuclein physiology is still difficult to clear up due to its interaction with multiple partners and its involvement in a pletora of neuronal functions. Here, we looked at the remarkably neglected interplay between α-Synuclein and microtubules, which potentially impacts on synaptic functionality. In order to identify the mechanisms underlying these actions, we investigated the interaction between purified α-Synuclein and tubulin. We demonstrated that α-Synuclein binds to microtubules and tubulin α2β2 tetramer; the latter interaction inducing the formation of helical segment(s) in the α-Synuclein polypeptide. This structural change seems to enable α-Synuclein to promote microtubule nucleation and to enhance microtubule growth rate and catastrophe frequency, both in vitro and in cell. We also showed that Parkinson's disease-linked α-Synuclein variants do not undergo tubulin-induced folding and cause tubulin aggregation rather than polymerization. Our data enable us to propose α-Synuclein as a novel, foldable, microtubule-dynamase, which influences microtubule organisation through its binding to tubulin and its regulating effects on microtubule nucleation and dynamics.
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- Silvestri, M, et al.
(författare)
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Detection of Genomically Aberrant Cells within Circulating Tumor Microemboli (CTMs) Isolated from Early-Stage Breast Cancer Patients
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Circulating tumor microemboli (CTMs) are clusters of cancer cells detached from solid tumors, whose study can reveal mechanisms underlying metastatization. As they frequently comprise unknown fractions of leukocytes, the analysis of copy number alterations (CNAs) is challenging. To address this, we titrated known numbers of leukocytes into cancer cells (MDA-MB-453 and MDA-MB-36, displaying high and low DNA content, respectively) generating tumor fractions from 0–100%. After low-pass sequencing, ichorCNA was identified as the best algorithm to build a linear mixed regression model for tumor fraction (TF) prediction. We then isolated 53 CTMs from blood samples of six early-stage breast cancer patients and predicted the TF of all clusters. We found that all clusters harbor cancer cells between 8 and 48%. Furthermore, by comparing the identified CNAs of CTMs with their matched primary tumors, we noted that only 31–71% of aberrations were shared. Surprisingly, CTM-private alterations were abundant (30–63%), whereas primary tumor-private alterations were rare (4–12%). This either indicates that CTMs are disseminated from further progressed regions of the primary tumor or stem from cancer cells already colonizing distant sites. In both cases, CTM-private mutations may inform us about specific metastasis-associated functions of involved genes that should be explored in follow-up and mechanistic studies.
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- Spolaor, Andrea, et al.
(författare)
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Climate change is rapidly deteriorating the climatic signal in Svalbard glaciers
- 2024
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Ingår i: CRYOSPHERE. - 1994-0416 .- 1994-0424. ; 18:1, s. 307-320
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Tidskriftsartikel (refereegranskat)abstract
- The Svalbard archipelago is particularly sensitive to climate change due to the relatively low altitude of its main ice fields and its geographical location in the higher North Atlantic, where the effect of Arctic amplification is more significant. The largest temperature increases have been observed during winter, but increasing summer temperatures, above the melting point, have led to increased glacier melt. Here, we evaluate the impact of this increased melt on the preservation of the oxygen isotope ( delta 18 O) signal in firn records. delta 18 O is commonly used as a proxy for past atmospheric temperature reconstructions, and, when preserved, it is a crucial parameter to date and align ice cores. By comparing four different firn cores collected in 2012, 2015, 2017 and 2019 at the top of the Holtedahlfonna ice field (1100 m a.s.l.), we show a progressive deterioration of the isotope signal, and we link its degradation to the increased occurrence and intensity of melt events. Our findings indicate that, starting from 2015, there has been an escalation in melting and percolation resulting from changes in the overall atmospheric conditions. This has led to the deterioration of the climate signal preserved within the firn or ice. Our observations correspond with the model's calculations, demonstrating an increase in water percolation since 2014, potentially reaching deeper layers of the firn. Although the delta 18 O signal still reflects the interannual temperature trend, more frequent melting events may in the future affect the interpretation of the isotopic signal, compromising the use of Svalbard ice cores. Our findings highlight the impact and the speed at which Arctic amplification is affecting Svalbard's cryosphere.
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