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- Cabras, T., et al.
(författare)
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Top-down HPLC-ESI-MS characterization of rat gliadoralin A, a new member of the family of rat submandibular gland glutamine-rich proteins and potential substrate of transglutaminase
- 2013
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Ingår i: Journal of Separation Science. - : Wiley. - 1615-9306. ; 36:17, s. 2848-2861
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Tidskriftsartikel (refereegranskat)abstract
- During HPLC-ESI-MS/MS analysis of rat submandibular saliva secreted under isoprenaline stimulation, a protein with an experimental [M+H](1+) = 10544.24 m/z was detected (17.5 +/- 0.7 min). The MS/MS fragmentation pattern, manually investigated, allowed establishing an internal sequence in agreement with a DNA-derived sequence of an unknown rat protein coded D3Z9M3 (Swiss-Prot). To match the experimental MS/MS fragmentation pattern and protein mass with theoretical data, the removal from the N terminus of the signal peptide and from the C terminus of three amino acid (a.a.) residues (Arg-Ala-Val) and the cyclization of the N-terminal glutamine in pyroglutamic had to be supposed, resulting in a mature protein of 90 a.a. HPLC-ESI-MS/MS of the trypsin digest ensured 100% sequence coverage. For the high glutamine content (34/90 = 37.8%) we propose to name this protein rat gliadoralin A 1-90. Low amounts of five different isoforms were sporadically detected, which did not significantly change their relative amounts after stimulation. Gliadoralin A is substrate for transglutaminase-2, having Lys 60 and different Gln residues as major determinants for enzyme recognition. In silico investigation of superior structures evidenced that a small part of the protein adopts an -helical fold, whereas large segments are unfolded, suggesting an unordered conformation.
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- Alexander, Jes, et al.
(författare)
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Multimodal single-cell analysis reveals distinct radioresistant stem-like and progenitor cell populations in murine glioma
- 2020
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Ingår i: GLIA. - : Wiley. - 0894-1491 .- 1098-1136. ; 68:12, s. 2486-2502
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Tidskriftsartikel (refereegranskat)abstract
- Radiation therapy is part of the standard of care for gliomas and kills a subset of tumor cells, while also altering the tumor microenvironment. Tumor cells with stem-like properties preferentially survive radiation and give rise to glioma recurrence. Various techniques for enriching and quantifying cells with stem-like properties have been used, including the fluorescence activated cell sorting (FACS)-based side population (SP) assay, which is a functional assay that enriches for stem-like tumor cells. In these analyses, mouse models of glioma have been used to understand the biology of this disease and therapeutic responses, including the radiation response. We present combined SP analysis and single-cell RNA sequencing of genetically-engineered mouse models of glioma to show a time course of cellular response to radiation. We identify and characterize two distinct tumor cell populations that are inherently radioresistant and also distinct effects of radiation on immune cell populations within the tumor microenvironment.
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- Cabras, T., et al.
(författare)
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Marked Differences in the Submandibular Salivary Proteome between Sardinian Alcohol-Preferring and Sardinian Alcohol-Non Preferring Rats Revealed by an Integrated Top-Down-Bottom-Up Proteomic Platform
- 2018
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 17:1, s. 455-469
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Tidskriftsartikel (refereegranskat)abstract
- Sardinian alcohol-preferring (sP) and Sardinian alcohol-non preferring (sNP) rats have been selectively bred for opposite alcohol preference and consumption. Aiming to verify possible differences at the proteomics level between sP and sNP rats, we investigated the salivary proteome by a a liquid chromatography-mass spectrometry top-down-bottom-up integrated approach. For this purpose, submandibular saliva was collected from alcohol-naive sP and sNP rats under isoprenaline stimulation. A total of 200 peptides and proteins were detected and quantified in the two rat lines, 149 of which were characterized in their naturally occurring structure. The data are available via ProteomeXchange with identifier PXD006997. Surprisingly, sP rats exhibited marked quantitative and qualitative differences with respect to sNP rats, namely higher levels of proteoforms originating from submandibular gland protein C, and from submandibular rat protein 2, as well as those of several unidentified peptides and proteins. sP rats expressed some proteins not detectable in sNP rats such as the glutamine and glutamic acid-rich protein (GRP)-CB. The isoform GRP-B, detectable in both rat lines, was more abundant in sNP rats. The submandibular saliva of sNP rats was also characterized by very high levels of GRP-B proteolytic peptides and rat salivary protein 1. Whether these differences could contribute to the opposite alcohol preference and consumption of sP and sNP rats is currently unknown and requires further investigation. © 2017 American Chemical Society.
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- Fedele, Vita, et al.
(författare)
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Epigenetic Regulation of ZBTB18 Promotes Glioblastoma Progression
- 2017
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Ingår i: Molecular Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1541-7786 .- 1557-3125. ; 15:8, s. 998-1011
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma (GBM) comprises distinct subtypes characterized by their molecular profile. Mesenchymal identity in GBM has been associated with a comparatively unfavorable prognosis, primarily due to inherent resistance of these tumors to current therapies. The identification of molecular determinants of mesenchymal transformation could potentially allow for the discovery of new therapeutic targets. Zinc Finger and BTB Domain Containing 18 (ZBTB18/ZNF238/RP58) is a zinc finger transcriptional repressor with a crucial role in brain development and neuronal differentiation. Here, ZBTB18 is primarily silenced in the mesenchymal subtype of GBM through aberrant promoter methylation. Loss of ZBTB18 contributes to the aggressive phenotype of glioblastoma through regulation of poor prognosis-associated signatures. Restitution of ZBTB18 expression reverses the phenotype and impairs tumor-forming ability. These results indicate that ZBTB18 functions as a tumor suppressor in GBM through the regulation of genes associated with phenotypically aggressive properties.
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- Galletti, L., et al.
(författare)
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Influence of topological edge states on the properties of Al/Bi2Se3/Al hybrid Josephson devices
- 2014
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Ingår i: Physical Review B - Condensed Matter and Materials Physics. - 2469-9950 .- 2469-9969. ; 89:13
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Tidskriftsartikel (refereegranskat)abstract
- In superconductor-topological insulator-superconductor hybrid junctions, the barrier edge states are expected to be protected against backscattering, to generate unconventional proximity effects, and, possibly, to signal the presence of Majorana fermions. The standards of proximity modes for these types of structures have to be settled for a neat identification of possible new entities. Through a systematic and complete set of measurements of the Josephson properties we find evidence of ballistic transport in coplanar Al-Bi2Se3-Al junctions that we attribute to a coherent transport through the topological edge state. The shunting effect of the bulk only influences the normal transport. This behavior, which can be considered to some extent universal, is fairly independent of the specific features of superconducting electrodes. A comparative study of Shubnikov-de Haas oscillations and scanning tunneling spectroscopy gave an experimental signature compatible with a two-dimensional electron transport channel with a Dirac dispersion relation. A reduction of the size of the Bi2Se3 flakes to the nanoscale is an unavoidable step to drive Josephson junctions in the proper regime to detect possible distinctive features of Majorana fermions.
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