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| 2. |
- Betancourt, Lazaro Hiram, et al.
(författare)
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The human melanoma proteome atlas-Defining the molecular pathology
- 2021
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Ingår i: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 11:7, s. 1-20
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Tidskriftsartikel (refereegranskat)abstract
- The MM500 study is an initiative to map the protein levels in malignant melanoma tumor samples, focused on in-depth histopathology coupled to proteome characterization. The protein levels and localization were determined for a broad spectrum of diverse, surgically isolated melanoma tumors originating from multiple body locations. More than 15,500 proteoforms were identified by mass spectrometry, from which chromosomal and subcellular localization was annotated within both primary and metastatic melanoma. The data generated by global proteomic experiments covered 72% of the proteins identified in the recently reported high stringency blueprint of the human proteome. This study contributes to the NIH Cancer Moonshot initiative combining detailed histopathological presentation with the molecular characterization for 505 melanoma tumor samples, localized in 26 organs from 232 patients.
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| 3. |
- Szadai, Leticia, et al.
(författare)
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Deep proteomic analysis on biobanked paraffine-archived melanoma with prognostic/predictive biomarker read-out
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:23
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of novel protein biomarkers in melanoma is crucial. Our introduction of formalin-fixed paraffin-embedded (FFPE) tumor protocol provides new opportunities to understand the progression of melanoma and open the possibility to screen thousands of FFPE samples deposited in tumor biobanks and available at hospital pathology departments. In our retrospective biobank pilot study, 90 FFPE samples from 77 patients were processed. Protein quantitation was performed by high-resolution mass spectrometry and validated by histopathologic analysis. The global protein expression formed six sample clusters. Proteins such as TRAF6 and ARMC10 were upregulated in clusters with enrichment for shorter survival, and proteins such as AIFI1 were upregulated in clusters with enrichment for longer survival. The cohort’s heterogeneity was addressed by comparing primary and metastasis samples, as well comparing clinical stages. Within immunotherapy and targeted therapy subgroups, the upregulation of the VEGFA-VEGFR2 pathway, RNA splicing, increased activity of immune cells, extracellular matrix, and metabolic pathways were positively associated with patient outcome. To summarize, we were able to (i) link global protein expression profiles to survival, and they proved to be an independent prognostic indicator, as well as (ii) identify proteins that are potential predictors of a patient’s response to immunotherapy and targeted therapy, suggesting new opportunities for precision medicine developments.
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| 4. |
- Varga, Gábor, et al.
(författare)
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Cu(II)-amino acid–CaAl-layered double hydroxide complexes, recyclable, efficient catalysts in various oxidative transformations
- 2016
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Ingår i: Journal of Molecular Catalysis A: Chemical. - : Elsevier BV. - 1381-1169. ; 423, s. 49-60
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Tidskriftsartikel (refereegranskat)abstract
- Intercalated composite materials were prepared with CaAl-layered double hydroxide as host and Cu(II)-amino acid (L-cysteine, L-histidine and L-tyrosine) complex anions as guests. Two methods (intercalation of the ligand first followed by constructing the complex; preforming the complex first, then introducing it among the layers of the host) and optimization of the synthesis conditions were performed to obtain composites having the complex exclusively among the layers. The composite materials were structurally characterized by powder X-ray diffractometry, mid infrared (IR) spectroscopy with ATR (attenuated total reflectance) or photoacoustic detections, transmission and scanning electron microscopies and X-ray photoelectron spectroscopy. Structural features of the intercalant (coordination number, coordination sites) were elucidated by classical chemical and energy dispersive X-ray analyses, EPR (electron paramagnetic spectroscopy), X-ray absorption and far IR spectroscopies. Structural models based on these methods are also given. Catalytic activities, selectivities and recycling abilities of the substances were studied in the oxidation reactions of cyclohexene with peracetic acid and in situ formed iodosylbenzene as oxidants in the liquid phase. The catalysts were active in the Ullmann coupling reaction as well. The intercalated substances were found to be efficient and highly selective catalysts with very good recycling abilities.
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| 6. |
- Bourseau-Guilmain, Erika, et al.
(författare)
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Hypoxia regulates global membrane protein endocytosis through caveolin-1 in cancer cells
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Hypoxia promotes tumour aggressiveness and resistance of cancers to oncological treatment. The identification of cancer cell internalizing antigens for drug targeting to the hypoxic tumour niche remains a challenge of high clinical relevance. Here we show that hypoxia down-regulates the surface proteome at the global level and, more specifically, membrane proteome internalization. We find that hypoxic down-regulation of constitutive endocytosis is HIF-independent, and involves caveolin-1-mediated inhibition of dynamin-dependent, membrane raft endocytosis. Caveolin-1 overexpression inhibits protein internalization, suggesting a general negative regulatory role of caveolin-1 in endocytosis. In contrast to this global inhibitory effect, we identify several proteins that can override caveolin-1 negative regulation, exhibiting increased internalization at hypoxia. We demonstrate antibody-mediated cytotoxin delivery and killing specifically of hypoxic cells through one of these proteins, carbonic anhydrase IX. Our data reveal that caveolin-1 modulates cell-surface proteome turnover at hypoxia with potential implications for specific targeting of the hypoxic tumour microenvironment.
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| 7. |
- Horvatovich, Peter, et al.
(författare)
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Quest for Missing Proteins : Update 2015 on Chromosome-Centric Human Proteome Project
- 2015
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 14:9, s. 3415-3431
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- This paper summarizes the recent activities of the Chromosome-Centric Human Proteome Project (C-HPP) consortium, which develops new technologies to identify yet-to-be annotated proteins (termed "missing proteins") in biological samples that lack sufficient experimental evidence at the protein level for confident protein identification. The C-HPP also aims to identify new protein forms that may be caused by genetic variability, post-translational modifications, and alternative splicing. Proteogenomic data integration forms the basis of the C-HPP's activities; therefore, we have summarized some of the key approaches and their roles in the project. We present new analytical technologies that improve the chemical space and lower detection limits coupled to bioinformatics tools and some publicly available resources that can be used to improve data analysis or support the development of analytical assays. Most of this paper's content has been compiled from posters, slides, and discussions presented in the series of C-HPP workshops held during 2014. All data (posters, presentations) used are available at the C-HPP Wild (http://c-hpp.webhosting.rug.nl/) and in the Supporting Information.
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| 8. |
- Jakli, Antal, et al.
(författare)
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Method for preparing anisotropic particles and devices thereof
- 2010
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Patent (populärvet., debatt m.m.)abstract
- The invention provides a simple and cost-effective method for preparing particles such as anisotropic semiconductor nanoparticles (e.g. CdS) and devices thereof. The method comprises (i) dispersing at least part of particle-forming reactants in a self-organized medium such as surfactant-aqueous solution system, and (ii) conducting a particle-forming reaction using the particle-forming reactants dispersed in the self-organized medium under shear condition to form the particles. The anisotropic property of the particles is controlled at least partially by the shear condition. The invention may be used to prepare quantum dots in a liquid crystal, and various devices such as nonlinear optics, optoelectronic devices, and solar cells, among others.
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| 9. |
- Mogren, Anna, et al.
(författare)
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Conceptual work on ESD from a school improvement perspective
- 2018
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Konferensbidrag (refereegranskat)abstract
- Chair: Anna Mogren, PhD, Karlstad University SwedenDiscussant: Professor Arjen Wals, Wageningen University, The Netherlands & Gothenburg University,SwedenThis symposium places Education for Sustainable Development ( ESD) within the field of school improvementtheory and research. In a number of studies, the Whole school approach in ESD is suggested and referred toas the work of embedding ESD into existing school visions and action plans (Breiting, Mayer & Mogensen2005 “Quality Criteria for ESD-schools”; Hargreaves 2008; Scott 2013.) The symposium therefore focuses onhow the research field of school improvement – which investigates, how efforts to help schools becomeincreasingly effective learning environments for the full range of their students have been more or lesssuccessful – might inform and challenge ESD and the ESD the Whole school approach.If ESD is to be framed and studied from a “within perspective” as an ongoing school improvement processrather than as an add-on activity to existing organisational arrangements and educational practices, it isnecessary to discuss models of school improvement in terms of their contribution to ESD. It is also importantto identify models of school improvement that can identify drivers and barriers for ESD implementation atorganisational level as well as on teaching and learning level (see Scherp 2013; Reezigt & Creemers 2005“Comprehensive framework for effective school improvement” ; Rolff 2010 “Trias of school development”;Rolff 2002 “P.dagogische Qualit.tsmanagement (PQM)”.In school improvement theory, a school’s organisation is commonly understood as reflexive in relation tocontext and supportive to the action of all members of the school community and their cooperation.Further, research suggests there are basic mechanisms contributing to effective school improvement such asgoal setting for improvement, pressures to improve, cyclical improvement processes and autonomy (seeScheerens & Demeuse 2005). Further, the school culture ought to be build up on dialogue supported byschool leadership. By this definition of school organisation, school improvement refers to collectivelysupporting factors in the organisation, to the end that students’ possibilities for learning in relation to acomplex surrounding world are enhanced.The recognition of multiple perspectives within the school organisation, e.g. cultural, structural, political andtransformational is central in investing possible models of school improvement. The search for schoolimprovement models that can discern those perspectives that are closely linked to ESD is crucial. Suchmodels of school improvement have the potential to constitute the link between the research fields of ESDand school improvement. They could serve as a tool for further research on how the Whole school approachis constructed in formal education, which is searched for in the practical work on ESD implementation.In this symposium examples from ongoing research projects on ESD where models of school improvementare used, considered or asked for in a German, Swedish and Hungarian context are presented. Thesymposium will explore the potential of integrating, adapting and rejecting theoretical perspectives andempirical evidence from school improvement into the ESD research field through intention papers with thegoal of developing knowledge about- how selected conceptual work on the Whole school approach in ESD draw on models andperspectives from school improvement theory,- how in an empirical case study a school improvement model was used to measure the ESD Wholeschool approach,- how school improvement has informed efforts and plan for upscaling ESD implementation in Eco-Schools to a larger number of public schools.Following questions from the audience, Arjen Wals (Wageningen University, The Netherlands & GothenburgUniversity, Sweden) will draw together the discussion and to explore implications for research in ESD.
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| 10. |
- Velásquez, Erika, et al.
(författare)
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Topological Dissection of Proteomic Changes Linked to the Limbic Stage of Alzheimer’s Disease
- 2021
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common cause of dementia worldwide. In AD, neurodegeneration spreads throughout different areas of the central nervous system (CNS) in a gradual and predictable pattern, causing progressive memory decline and cognitive impairment. Deposition of neurofibrillary tangles (NFTs) in specific CNS regions correlates with the severity of AD and constitutes the basis for disease classification into different Braak stages (I-VI). Early clinical symptoms are typically associated with stages III-IV (i.e., limbic stages) when the involvement of the hippocampus begins. Histopathological changes in AD have been linked to brain proteome alterations, including aberrant posttranslational modifications (PTMs) such as the hyperphosphorylation of Tau. Most proteomic studies to date have focused on AD progression across different stages of the disease, by targeting one specific brain area at a time. However, in AD vulnerable regions, stage-specific proteomic alterations, including changes in PTM status occur in parallel and remain poorly characterized. Here, we conducted proteomic, phosphoproteomic, and acetylomic analyses of human postmortem tissue samples from AD (Braak stage III-IV, n=11) and control brains (n=12), covering all anatomical areas affected during the limbic stage of the disease (total hippocampus, CA1, entorhinal and perirhinal cortices). Overall, ~6000 proteins, ~9000 unique phosphopeptides and 221 acetylated peptides were accurately quantified across all tissues. Our results reveal significant proteome changes in AD brains compared to controls. Among others, we have observed the dysregulation of pathways related to the adaptive and innate immune responses, including several altered antimicrobial peptides (AMPs). Notably, some of these changes were restricted to specific anatomical areas, while others altered according to disease progression across the regions studied. Our data highlights the molecular heterogeneity of AD and the relevance of neuroinflammation as a major player in AD pathology. Data are available via ProteomeXchange with identifier PXD027173.
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