| 1. |
- Vermunt, L., et al.
(författare)
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Duration of preclinical, prodromal, and dementia stages of Alzheimer's disease in relation to age, sex, and APOE genotype
- 2019
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:7, s. 888-898
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: We estimated the age-specific duration of the preclinical, prodromal, and dementia stages of Alzheimer's disease (AD) and the influence of sex, setting, apolipoprotein E (APOE) genotype, and cerebrospinal fluid tau on disease duration. Methods: We performed multistate modeling in a combined sample of 6 cohorts (n = 3268) with death as the end stage and estimated the preclinical, prodromal, and dementia stage duration. Results: The overall AD duration varied between 24 years (age 60) and 15 years (age 80). For individuals presenting with preclinical AD, age 70, the estimated preclinical AD duration was 10 years, prodromal AD 4 years, and dementia 6 years. Male sex, clinical setting, APOE epsilon 4 allele carriership, and abnormal cerebrospinal fluid tau were associated with a shorter duration, and these effects depended on disease stage. Discussion: Estimates of AD disease duration become more accurate if age, sex, setting, APOE, and cerebrospinal fluid tau are taken into account. This will be relevant for clinical practice and trial design. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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| 2. |
- Jaén-Luchoro, D., et al.
(författare)
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Complete genome sequence of Mycobacterium chelonae type strain CCUG 47445, a rapidly growing species of nontuberculous mycobacteria
- 2016
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Ingår i: Genome Announcements. - 2169-8287. ; 4:3
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Tidskriftsartikel (refereegranskat)abstract
- Mycobacterium chelonae strains are ubiquitous rapidly growing mycobacteria associated with skin and soft tissue infections, cellulitis, abscesses, osteomyelitis, catheter infections, disseminated diseases, and postsurgical infections after implants with prostheses, transplants, and even hemodialysis procedures. Here, we report the complete genome sequence of M. chelonae type strain CCUG 47445. © 2016 Jaén-Luchoro et al.
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| 3. |
- Karlsson, Roger, 1975, et al.
(författare)
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Proteotyping bacteria: Characterization, differentiation and identification of pneumococcus and other species within the Mitis Group of the genus Streptococcus by tandem mass spectrometry proteomics
- 2018
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- A range of methodologies may be used for analyzing bacteria, depending on the purpose and the level of resolution needed. The capability for recognition of species distinctions within the complex spectrum of bacterial diversity is necessary for progress in microbiological research. In clinical settings, accurate, rapid and cost-effective methods are essential for early and efficient treatment of infections. Characterization and identification of microorganisms, using, bottom-up proteomics, or "proteotyping", relies on recognition of species-unique or associated peptides, by tandem mass spectrometry analyses, dependent upon an accurate and comprehensive foundation of genome sequence data, allowing for differentiation of species, at amino acid-level resolution. In this study, the high resolution and accuracy of MS/MS-based proteotyping was demonstrated, through analyses of the three phylogenetically and taxonomically most closely-related species of the Mitis Group of the genus Streptococcus: i.e., the pathogenic species, Streptococcus pneumoniae (pneumococcus), and the commensal species, Streptococcus pseudopneumoniae and Streptococcus mitis. To achieve high accuracy, a genome sequence database used for matching peptides was created and carefully curated. Here, MS-based, bottom-up proteotyping was observed and confirmed to attain the level of resolution necessary for differentiating and identifying the most-closely related bacterial species, as demonstrated by analyses of species of the Streptococcus Mitis Group, even when S. pneumoniae were mixed with S. pseudopneumoniae and S. mitis, by matching and identifying more than 200 unique peptides for each species.
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| 4. |
- Noguera-Salva, M. A., et al.
(författare)
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Role of the C-terminal basic amino acids and the lipid anchor of the G gamma(2) protein in membrane interactions and cell localization
- 2017
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Ingår i: Biochimica Et Biophysica Acta-Biomembranes. - : Elsevier BV. - 0005-2736. ; 1859:9, s. 1536-1547
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Tidskriftsartikel (refereegranskat)abstract
- Heterotrimeric G proteins are peripheral membrane proteins that frequently localize to the plasma membrane where their presence in molar excess over G protein coupled receptors permits signal amplification. Their distribution is regulated by protein-lipid interactions, which has a clear influence on their activity. G beta gamma dimer drives the interaction between G protein heterotrimers with cell membranes. We focused our study on the role of the C-terminal region of the G gamma(2) protein in G protein interactions with cell membranes. The G gamma(2) subunit is modified at cysteine (Cys) 68 by the addition of an isoprenyl lipid, which is followed by the proteolytic removal of the last three residues that leaves an isoprenylated and carboxyl methylated Cys-68 as the terminal amino acid. The role of Cys isoprenylation of the CAAX box has been defined for other proteins, yet the importance of proteolysis and carboxyl methylation of isoprenylated proteins is less clear. Here, we showed that not only geranylgeranylation but also proteolysis and carboxyl methylation are essential for the correct localization of G gamma(2) in the plasma membrane. Moreover, we showed the importance of electrostatic interactions between the inner leaflet of the plasma membrane and the positively charged C-terminal domain of the G gamma(2) subunit (amino acids Arg-62, Lys-64 and Lys-65) as a second signal to reach the plasma membrane. Indeed, single or multiple point mutations at G gamma(2) C-terminal amino acids have a significant effect on G gamma(2) protein-plasma membrane interactions and its localization to charged Ld (liquid disordered) membrane microdomains. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escriba. (C) 2017 Published by Elsevier B.V.
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| 5. |
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| 6. |
- Undabarrena, A., et al.
(författare)
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Complete genome sequence of the marine Rhodococcus sp H-CA8f isolated from Comau fjord in Northern Patagonia, Chile
- 2018
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Ingår i: Marine Genomics. - : Elsevier BV. - 1874-7787. ; 40, s. 13-17
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Tidskriftsartikel (refereegranskat)abstract
- Rhodococcus sp. H-CA8f was isolated from marine sediments obtained from the Comau fjord, located in Northern Chilean Patagonia. Whole-genome sequencing was achieved using PacBio RS II platform, comprising one closed, complete chromosome of 6,19 Mbp with a 62.45% G + C content. The chromosome harbours several metabolic pathways providing a wide catabolic potential, where the upper biphenyl route is described. Also, Rhodococcus sp. H-CA8f bears one linear mega-plasmid of 301 Kbp and 62.34% of G + C content, where genomic analyses demonstrated that it is constituted mostly by putative ORFs with unknown functions, representing a novel genetic feature. These genetic characteristics provide relevant insights regarding Chilean marine actinobacterial strains.
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| 7. |
- Gonzales-Siles, Lucia, et al.
(författare)
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Mass Spectrometry Proteotyping of Streptococcus pneumoniae and commensal Streptococcus: identification of biomarkers for infectious strain characterization
- 2016
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Ingår i: 26th ECCMID 2016 Amsterdam, The Netherlands. 9 - 12 April 2016.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Streptococcus pneumoniae (pneumococcus) is the leading cause of community-acquired pneumonia, with morbidity and mortality worldwide. S. pneumoniae belongs to the S. mitis-Group (viridans streptococci), phenotypically and genotypically similar to commensal species of the upper respiratory tract, S. mitis, S. oralis, and S. pseudopneumoniae, causing problems for identifications in clinical laboratories. In this project, we apply state-of-the-art proteomics for Streptococcus spp. 'proteotyping'; identifying and characterizing protein biomarkers for species-level identification, antibiotic resistance, virulence and strain typing for epidemiological analyses (1). Material/methods: Bacterial proteins, from intact bacteria or cell fractions, are bound to a membrane surface, using patented (WO2006068619) FlowCell (LPITM) technology. Peptides are generated from the bound proteins, by enzymatic digestion, separated and analyzed, using LC-MS/MS. The mass spectra profiles are compared to reference peptide sequences and whole genome sequence (wgs) data of the NCBI RefSeq Database. The S. mitis-Group specie, S. pneumoniae, S. mitis, S. oralis, S. psedopneumoniae, as well as the more distantly-related, Group A Streptococcus (GAS) species, S. pyogenes , were analyzed individually and in mixtures, to demonstrate the resolution of proteotyping for differentiating bacteria. Results: Using proteotyping protocols, S. pneumoniae were detected and differentiated from other streptococci, S. mitis, S. oralis, S. psedopneumoniae and the more distant relative, S. pyogenes, by identification of unique discriminatory peptides. Metabolic protein biomarkers were identified, including for antibiotic resistance and virulence. It was possible to find discriminatory biomarkers for a target species when analyzing 1:1 mixes of S. pneumoniae and other species from the S. mitis-Group. The different strains of S. pneumoniae, analyzed in different ratio combinations, were successfully differentiated and identified. For successful proteotyping, a comprehensive and accurate genomic database was observed to be key for obtaining reliable peptide matching and proteotyping data. Importantly, because of observed high rates of misclassified wgs data in the public databases, the taxonomic classifications of genomes in GenBank were analyzed against reference type strain genomes of target species by calculating wgs similarities, using Average Nucleotide Identity with BLAST (ANIb). While wgs data for S. pneumoniae were confirmed to be classified correctly, approximately one-third of wgs data for other species of the S. mitis-Group were determined to be misclassified. Streptococci strains that could not be identified, using standard genotypic and phenotypic approaches, were characterized by proteotyping and genome sequencing to establish their taxonomy and biomarker features to enhance species database matching. Conclusions: Proteotyping enables differentiation, identification and characterization of pneumococcus from the most closely related species attaining, as well, strain-level discrimination from single LC-MS/MS analyses. The protocol enhances identification and characterization of pathogenic bacterial isolates through identifications of expressed biomarkers, ultimately for cultivation-independent analyses of clinical samples. 1) Karlsson et al., 2015. Syst Appl Microbiol. 38:246-257.
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| 8. |
- Jaen-Luchoro, Daniel, et al.
(författare)
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First insights into a type II toxin-antitoxin system from the clinical isolate Mycobacterium sp MHSD3, similar to epsilon/zeta systems
- 2017
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- A putative type II toxin-antitoxin (TA) system was found in the clinical isolate Mycobacterium sp. MHSD3, a strain closely related to Mycobacterium chelonae. Further analyses of the protein sequences of the two genes revealed the presence of domains related to a TA system. BLAST analyses indicated the presence of closely related proteins in the genomes of other recently published M. chelonae strains. The functionality of both elements of the TA system was demonstrated when expressed in Escherichia coli cells, and the predicted structure of the toxin is very similar to those of well-known zeta-toxins, leading to the definition of a type II TA system similar to epsilon/zeta TA systems in strains that are closely related to M. chelonae.
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| 9. |
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| 10. |
- Salvà-Serra, Francisco, 1989, et al.
(författare)
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Proteotyping for Rapid Identifications of Clinically-Relevant Infectious Bacteria
- 2016
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Ingår i: Programme of the XXXV ECCO Meeting 2016.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Aims The development and application of novel identifications and diagnostics of pathogenic bacteria, virulence and antibiotic resistance factors, to enhance treatment of infectious diseases and to address the pandemic of antimicrobial resistance (1). To apply mass spectrometry (MS)-based ‘proteotyping’, a rapid proteomic-genomic method to identify and use cell biomarkers for pathogen identification and detection of targeted metabolic functions (www.tailored-treatment.eu/). Methods and results The proteins of intact bacterial cells or cell-fractions are bound to a membrane surface, using the patented (WO2006068619) Lipid-based Protein Immobilization (LPI) technology. Peptides are generated from bound proteins, using enzymatic digestion, separated and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The MS profiles are compared to those of reference peptide sequences and the peptide sequences are compared against a curated in-house database of genome sequences. Conclusions Analyses of bacterial cell peptides identified protein biomarkers of infectious bacteria, at the species-level, virulence and antibiotic resistance factors. Model samples have been ‘proteotyped’, using well-characterized reference strains, and an enhanced whole-genome sequence database, to demonstrate ‘proof-of-concept’, and the method been applied directly to the analyses of clinical samples, without prior cultivation. Significance of study Proteotyping demonstrates the potential for proteomics-based analyses for detecting expressed genomic markers of bacterial species, virulence and antibiotic resistance, for the identifications and diagnostics of infectious microorganisms. References Cohen A, Bont L, Engelhard D, Moore E, Fernández D, Kreisberg-Greenblatt R, Oved K, Eden E, Hayes J (2015). A multifaceted 'omics' approach for addressing the challenge of antimicrobial resistance. Future Microbiol. 10:365-376
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