| 1. |
- Carling, Gerd, et al.
(författare)
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Diachronic Atlas of Comparative Linguistics (DiACL)—A database for ancient language typology
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- Feature stability, time and tempo of change, and the role of genealogy versus areality in creating linguistic diversity are important issues in current computational research on linguistic typology. This paper presents a database initiative, DiACL Typology, which aims to provide a resource for addressing these questions with specific of the extended Indo-European language area of Eurasia, the region with the best documented linguistic history. The database is pre-prepared for statistical and phylogenetic analyses and contains both linguistic typological data from languages spanning over four millennia, and linguistic metadata concerning geographic location, time period, and reliability of sources. The typological data has been organized according to a hierarchical model of increasing granularity in order to create datasets that are complete and representative.
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| 2. |
- Carling, Gerd, et al.
(författare)
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DiACL : Diachronic Atlas of Comparative Linguistics
- 2017
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- DiACL is an open access database with lexical and typological/morphosyntactic data for historical, comparative and phylogenetic linguistics. It contains data from 500 languages of 18 families, divided into three macro-areas: Eurasia, Pacific, and the Amazon.
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| 3. |
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| 4. |
- Claes, Filip, et al.
(författare)
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Exposure of a cryptic Hsp70 binding site determines the cytotoxicity of the ALS-associated SOD1-mutant A4V
- 2019
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Ingår i: Protein Engineering Design & Selection. - : Oxford University Press (OUP). - 1741-0126 .- 1741-0134. ; 32:10, s. 443-457
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Tidskriftsartikel (refereegranskat)abstract
- The accumulation of toxic protein aggregates is thought to play a key role in a range of degenerative pathologies, but it remains unclear why aggregation of polypeptides into non-native assemblies is toxic and why cellular clearance pathways offer ineffective protection. We here study the A4V mutant of SOD1, which forms toxic aggregates in motor neurons of patients with familial amyotrophic lateral sclerosis (ALS). A comparison of the location of aggregation prone regions (APRs) and Hsp70 binding sites in the denatured state of SOD1 reveals that ALS-associated mutations promote exposure of the APRs more than the strongest Hsc/Hsp70 binding site that we could detect. Mutations designed to increase the exposure of this Hsp70 interaction site in the denatured state promote aggregation but also display an increased interaction with Hsp70 chaperones. Depending on the cell type, in vitro this resulted in cellular inclusion body formation or increased clearance, accompanied with a suppression of cytotoxicity. The latter was also observed in a zebrafish model in vivo. Our results suggest that the uncontrolled accumulation of toxic SOD1(A4V) aggregates results from insufficient detection by the cellular surveillance network.
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| 5. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 6. |
- Rob, Filip, et al.
(författare)
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RANDOMIZED CLINICAL TRIAL COMPARING GENTAMICIN plus AZITHROMYCIN VS. CEFTRIAXONE plus AZITHROMYCIN FOR RECTAL AND PHARYNGEAL GONORRHEA
- 2019
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Ingår i: Sexually Transmitted Infections. - : BMJ Publishing Group Ltd. - 1368-4973 .- 1472-3263. ; 95:Suppl. 1, s. A286-A287
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Dual therapy including ceftriaxone plus azithromycin is currently the recommended first-line gonorrhea treatment internationally. However, for gonorrhea cases where ceftriaxone or other extended-spectrum cephalosporin can not be administered (e.g., cephalosporin resistance, allergy, or unavailability), the therapeutic options are very limited. In a previous randomized controlled clinical trial (RCT) by Kirk-caldy et al. (Clin Infect Dis. 2014), gentamicin 240 mg plus azithromycin 2 g showed 100% microbiological cure for uncomplicated gonorrhoea. However, only 10 pharyngeal infections and one rectal infection were examined. We further evaluated the efficacy and tolerability of gentamicin+azithroomycin for treatment of uncomplicated rectal and pharyngeal gonorrhea.Methods: A non-inferiority, open-label, single center RCT was conducted in Prague, Czech Republic. Patients, 18–75 years of age, diagnosed with uncomplicated rectal or pharyngeal gonorrhea by nucleic acid amplification test (NAAT) (GeneProof®) were randomized to treatment with gentamicin 240 mg intramuscularly plus azithromycin 2 g orally or ceftriaxone 500 g intramuscularly plus azithromycin 2 g orally. The primary out-come was negative culture and negative NAAT, i.e., one week and three weeks, respectively, after treatment.Results: Both clinical and microbiological cure was achieved by 100% of patients in the gentamicin+azithromycin arm (n=68; 40 rectal, 14 pharyngeal, and 14 infections in both localizations) and ceftriaxone+azithromycin arm (n=66; 36 rectal, 14 pharyngeal, and 16 infections in both localizations). Administration of gentamicin was significantly less painful than ceftriaxone according to the visual analog score (p<0.001). Gastrointestinal adverse events were slightly more common in ceftriaxone arm (50.0%) than in gentamicin arm (41.2%), but in most (64%) cases they were mild.Conclusion: Both gentamicin+azithromycin and ceftriaxone+azithromycin were 100% effective for treatment of rectal and pharyngeal gonorrhea. Gentamicin 240 mg plus azithromycin 2 g appears to be an effective alternative for treatment of both urogenital and extragenital gonorrhea in case of ceftriaxone resistance, allergy, or unavailability.
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| 7. |
- Seth-Smith, Helena M. B., et al.
(författare)
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Ongoing evolution of Chlamydia trachomatis lymphogranuloma venereum : exploring the genomic diversity of circulating strains
- 2021
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Ingår i: Microbial Genomics. - : Microbiology Society. - 2057-5858. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Lymphogranuloma venereum (LGV), the invasive infection of the sexually transmissible infection (STI) Chlamydia trachomatis, is caused by strains from the LGV biovar, most commonly represented by ompA- genotypes L2b and L2. We investigated the diversity in LGV samples across an international collection over seven years using typing and genome sequencing. LGV- positive samples (n=321) from eight countries collected between 2011 and 2017 (Spain n=97, Netherlands n=67, Switzerland n=64, Australia n=53, Sweden n=37, Hungary n=31, Czechia n=30, Slovenia n=10) were genotyped for pmpH and ompA variants. All were found to contain the 9 bp insertion in the pmpH gene, previously associated with ompA- genotype L2b. However, analysis of the ompA gene shows ompA- genotype L2b (n=83), ompA- genotype L2 (n=180) and several variants of these (n=52; 12 variant types), as well as other/mixed ompA-genotypes (n=6). To elucidate the genomic diversity, whole genome sequencing (WGS) was performed from selected samples using SureSelect target enrichment, resulting in 42 genomes, covering a diversity of ompA- genotypes and representing most of the countries sampled. A phylogeny of these data clearly shows that these ompA- genotypes derive from an ompA- genotype L2b ancestor, carrying up to eight SNPs per isolate. SNPs within ompA are overrep-resented among genomic changes in these samples, each of which results in an amino acid change in the variable domains of OmpA (major outer membrane protein, MOMP). A reversion to ompA- genotype L2 with the L2b genomic backbone is commonly seen. The wide diversity of ompA- genotypes found in these recent LGV samples indicates that this gene is under immunological selection. Our results suggest that the ompA- genotype L2b genomic backbone is the dominant strain circulating and evolving particularly in men who have sex with men (MSM) populations.
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| 8. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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