| 1. |
- Chng, Kern Rei, et al.
(författare)
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Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment
- 2020
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 26, s. 941-951
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Tidskriftsartikel (refereegranskat)abstract
- Although disinfection is key to infection control, the colonization patterns and resistomes of hospital-environment microbes remain underexplored. We report the first extensive genomic characterization of microbiomes, pathogens and antibiotic resistance cassettes in a tertiary-care hospital, from repeated sampling (up to 1.5 years apart) of 179 sites associated with 45 beds. Deep shotgun metagenomics unveiled distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human-microbiome-influenced environments with corresponding patterns of spatiotemporal divergence. Quasi-metagenomics with nanopore sequencing provided thousands of high-contiguity genomes, phage and plasmid sequences (>60% novel), enabling characterization of resistome and mobilome diversity and dynamic architectures in hospital environments. Phylogenetics identified multidrug-resistant strains as being widely distributed and stably colonizing across sites. Comparisons with clinical isolates indicated that such microbes can persist in hospitals for extended periods (>8 years), to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections. Spatiotemporal characterization of microbial diversity and antibiotic resistance in a tertiary-care hospital reveals broad distribution and persistence of antibiotic-resistant organisms that could cause opportunistic infections in a healthcare setting.
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| 2. |
- Danko, David, et al.
(författare)
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A global metagenomic map of urban microbiomes and antimicrobial resistance
- 2021
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 184:13, s. 3376-3393
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Tidskriftsartikel (refereegranskat)abstract
- We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities.
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| 3. |
- Chernomoretz, Ariel, et al.
(författare)
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The Metagenomics and Metadesign of the Subways and Urban Biomes (MetaSUB) International Consortium inaugural meeting report
- 2016
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Ingår i: Microbiome. - : Springer Science and Business Media LLC. - 2049-2618. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- The Metagenomics and Metadesign of the Subways and Urban Biomes (MetaSUB) International Consortium is a novel, interdisciplinary initiative comprised of experts across many fields, including genomics, data analysis, engineering, public health, and architecture. The ultimate goal of the MetaSUB Consortium is to improve city utilization and planning through the detection, measurement, and design of metagenomics within urban environments. Although continual measures occur for temperature, air pressure, weather, and human activity, including longitudinal, cross-kingdom ecosystem dynamics can alter and improve the design of cities. The MetaSUB Consortium is aiding these efforts by developing and testing metagenomic methods and standards, including optimized methods for sample collection, DNA/RNA isolation, taxa characterization, and data visualization. The data produced by the consortium can aid city planners, public health officials, and architectural designers. In addition, the study will continue to lead to the discovery of new species, global maps of antimicrobial resistance (AMR) markers, and novel biosynthetic gene clusters (BGCs). Finally, we note that engineered metagenomic ecosystems can help enable more responsive, safer, and quantified cities.
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| 4. |
- Ding, Mozhu, et al.
(författare)
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Atrial fibrillation and use of antithrombotic medications in older people : A population-based study
- 2017
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 249, s. 173-178
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Tidskriftsartikel (refereegranskat)abstract
- Background: Trends in the use of antithrombotic drugs in elderly patients with atrial fibrillation (AF) are largely unknown. We estimated the prevalence of AF in an older population, and examined whether use of anticoagulant and antiplatelet drugs in older AF patients has changed over time. Methods: Data from the population-based Swedish National study on Aging and Care in Kungsholmen (n = 3363, age = 60 years, 64.9% women) were used (2001-2004 and 2007-2010). AF cases were identified through 12-lead electrocardiogram, physician examinations, and patient register records (ICD-10 code I48). We used the CHADS(2) and CHA(2)DS(2)-VASc scores to estimate stroke risk, and an incomplete HAS-BLED score to estimate bleeding risk. Results: At baseline (2001-2004), 328 persons (9.8%) were ascertained to have AF. The prevalence of AF increased significantly with age from 2.8% in people aged 60-66 years to 21.2% in those = 90 years, and was more common in men than in women (11.2% vs. 9.0%). Among AF patients with CHADS2 score = 2 at baseline, 25% were taking anticoagulant drugs and 54% were taking antiplatelet drugs. High bleeding risk was significantly associated with not using anticoagulant drugs in AF patients (multi-adjusted OR = 2.50, p = 0.015). Between 2001-2004 and 2007-2010, use of anticoagulant drugs increased significantly, especially in AF patients with CHA2DS2-VASc score >= 2 (23% vs. 33%, p = 0.008) and in those with HAS-BLED score <3 (32% vs. 53%, p = 0.004). Conclusion: AF is common among old people. The use of anticoagulant drugs increased over time in AF patients, yet still two-thirds of those with high stroke risk remained untreated.
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| 5. |
- Hanrieder, Jörg, 1980, et al.
(författare)
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L-DOPA-induced dyskinesia is associated with regional increase of striatal dynorphin peptides as elucidated by imaging mass spectrometry.
- 2011
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Ingår i: Molecular & cellular proteomics : MCP. - 1535-9484 .- 1535-9476. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- Opioid peptides are involved in various pathophysiological processes, including algesia, epilepsy, and drug dependence. A strong association between L-DOPA-induced dyskinesia (LID) and elevated prodynorphin mRNA levels has been established in both patients and in animal models of Parkinson's disease, but to date the endogenous prodynorphin peptide products have not been determined. Here, matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) was used for characterization, localization, and relative quantification of striatal neuropeptides in a rat model of LID in Parkinson's disease. MALDI IMS has the unique advantage of high sensitivity and high molecular specificity, allowing comprehensive detection of multiple molecular species in a single tissue section. Indeed, several dynorphins and enkephalins could be detected in the present study, including dynorphin A(1-8), dynorphin B, α-neoendorphin, MetEnkRF, MetEnkRGL, PEnk (198-209, 219-229). IMS analysis revealed elevated levels of dynorphin B, α-neoendorphin, substance P, and PEnk (220-229) in the dorsolateral striatum of high-dyskinetic animals compared with low-dyskinetic and lesion-only control rats. Furthermore, the peak-intensities of the prodynorphin derived peptides, dynorphin B and α-neoendorphin, were strongly and positively correlated with LID severity. Interestingly, these LID associated dynorphin peptides are not those with high affinity to κ opioid receptors, but are known to bind and activate also μ- and Δ-opioid receptors. In addition, the peak intensities of a novel endogenous metabolite of α-neoendorphin lacking the N-terminal tyrosine correlated positively with dyskinesia severity. MALDI IMS of striatal sections from Pdyn knockout mice verified the identity of fully processed dynorphin peptides and the presence of endogenous des-tyrosine α-neoendorphin. Des-tyrosine dynorphins display reduced opioid receptor binding and this points to possible novel nonopioid receptor mediated changes in the striatum of dyskinetic rats. Because des-tyrosine dynorphins can only be detected by mass spectrometry, as no antibodies are available, these findings highlight the importance of MALDI IMS analysis for the study of molecular dynamics in neurological diseases.
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| 6. |
- Hägglund, Maria G. A., et al.
(författare)
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Characterization of the transporterB0AT3 (Slc6a17) in the rodent central nervous system
- 2013
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Ingår i: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 14, s. 54-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The vesicular B(0)AT3 transporter (SLC6A17), one of the members of the SLC6 family, is a transporter for neutral amino acids and is exclusively expressed in brain. Here we provide a comprehensive expression profile of B(0)AT3 in mouse brain using in situ hybridization and immunohistochemistry. Results: We confirmed previous expression data from rat brain and used a novel custom made antibody to obtain detailed co-labelling with several cell type specific markers. B(0)AT3 was highly expressed in both inhibitory and excitatory neurons. The B(0)AT3 expression was highly overlapping with those of vesicular glutamate transporter 2 (VGLUT2) and vesicular glutamate transporter 1 (VGLUT1). We also show here that Slc6a17mRNA is up-regulated in animals subjected to short term food deprivation as well as animals treated with the serotonin reuptake inhibitor fluoxetine and the dopamine/noradrenaline reuptake inhibitor bupropion. Conclusions: This suggests that the B(0)AT3 transporter have a role in regulation of monoaminergic as well as glutamatergic synapses.
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| 7. |
- Ljungdahl, Anna, et al.
(författare)
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Imaging mass spectrometry reveals elevated nigral levels of dynorphin neuropeptides in L-DOPA-induced dyskinesia in rat model of Parkinson's disease.
- 2011
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 6:9
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Tidskriftsartikel (refereegranskat)abstract
- L-DOPA-induced dyskinesia is a troublesome complication of L-DOPA pharmacotherapy of Parkinson's disease and has been associated with disturbed brain opioid transmission. However, so far the results of clinical and preclinical studies on the effects of opioids agonists and antagonists have been contradictory at best. Prodynorphin mRNA levels correlate well with the severity of dyskinesia in animal models of Parkinson's disease; however the identities of the actual neuroactive opioid effectors in their target basal ganglia output structures have not yet been determined. For the first time MALDI-TOF imaging mass spectrometry (IMS) was used for unbiased assessment and topographical elucidation of prodynorphin-derived peptides in the substantia nigra of a unilateral rat model of Parkinson's disease and L-DOPA induced dyskinesia. Nigral levels of dynorphin B and alpha-neoendorphin strongly correlated with the severity of dyskinesia. Even if dynorphin peptide levels were elevated in both the medial and lateral part of the substantia nigra, MALDI IMS analysis revealed that the most prominent changes were localized to the lateral part of the substantia nigra. MALDI IMS is advantageous compared with traditional molecular methods, such as radioimmunoassay, in that neither the molecular identity analyzed, nor the specific localization needs to be predetermined. Indeed, MALDI IMS revealed that the bioconverted metabolite leu-enkephalin-arg also correlated positively with severity of dyskinesia. Multiplexing DynB and leu-enkephalin-arg ion images revealed small (0.25 by 0.5 mm) nigral subregions with complementing ion intensities, indicating localized peptide release followed by bioconversion. The nigral dynorphins associated with L-DOPA-induced dyskinesia were not those with high affinity to kappa opioid receptors, but consisted of shorter peptides, mainly dynorphin B and alpha-neoendorphin that are known to bind and activate mu and delta opioid receptors. This suggests that mu and/or delta subtype-selective opioid receptor antagonists may be clinically relevant for reducing L-DOPA-induced dyskinesia in Parkinson's disease.
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| 8. |
- Vaïopoulou, Maria, et al.
(författare)
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The 2016–2018 Greek-Swedish archaeological project at Thessalian Vlochos, Greece
- 2020
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Ingår i: Opuscula: Annual of the Swedish Institutes at Athens and Rome. - : Editorial Committee of the Swedish Institutes at Athens and Rome (ECSI). - 2000-0898. ; 13, s. 7-72
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Tidskriftsartikel (refereegranskat)abstract
- The Vlochos Archaeological Project (2016–2018) was a Greek-Swedish archaeological investigation of the remains of the ancient urban site at Vlochos in western Thessaly, Greece. Employing a wide array of non-invasive methods, the project succeeded in completely mapping the visible remains, which had previously not been systematically investigated. The extensive remains of multi-period urban fortifications, a Classical-Hellenistic city, a Roman town, and a Late Antique fortress were identified, evidence of the long history of habitation on this site. Since comparatively little fieldwork has been conducted in the region, the results significantly increase our knowledge of the history and archaeology of Thessaly.
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