OBJECTIVE: The study objectives were (i) to explore the agreement between the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and physical examination in assessing enthesitis in patients with spondyloarthritis (SpA) and (ii) to investigate the prevalence and clinical relevance of subclinical enthesitis in this population. METHODS: Twenty rheumatology centers participated in this cross-sectional study. Patients with SpA, including axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), underwent both ultrasound scan and physical examination of large lower limb entheses. The OMERACT ultrasound lesions of enthesitis were considered, along with a recently proposed definition for "active enthesitis" by our group. Subclinical enthesitis was defined as the presence of "active enthesitis" in ≥1 enthesis in patients with SpA without clinical enthesitis (ie, number of positive entheses on physical examination and Leeds Enthesitis Index score = 0). RESULTS: A total of 4,130 entheses in 413 patients with SpA (224 with axSpA and 189 with PsA) were evaluated through ultrasound and physical examination. Agreement between ultrasound and physical examination ranged from moderate (ie, enthesophytes) to almost perfect (ie, power Doppler and "active enthesitis"). Patellar tendon entheses demonstrated the highest agreement, whereas Achilles tendon insertion showed the lowest. Among 158 (38.3%) of 413 patients with SpA with clinical enthesitis, 108 (68.4%) exhibited no "active enthesitis" on ultrasound. Conversely, of those 255 without clinical enthesitis, 39 (15.3%) showed subclinical enthesitis. Subclinical enthesitis was strongly associated with local structural damage. However, no differences were observed regarding the demographic and clinical profiles of patients with SpA with and without subclinical enthesitis. CONCLUSION: Our study underscores the need for a comprehensive tool integrating ultrasound and physical examination for assessing enthesitis in patients with SpA.
- MeSH
- Achillova šlacha diagnostické zobrazování MeSH
- axiální spondyloartritida diagnostické zobrazování MeSH
- dospělí MeSH
- entezopatie * diagnostické zobrazování MeSH
- fyzikální vyšetření * MeSH
- lidé středního věku MeSH
- lidé MeSH
- průřezové studie MeSH
- psoriatická artritida diagnostické zobrazování komplikace MeSH
- spondylartritida * diagnostické zobrazování komplikace MeSH
- ultrasonografie * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
OBJECTIVES: To assess, in spondyloarthritis (SpA), the discriminative value of the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and their associations with clinical features in this population. METHODS: In this multicentre study involving 20 rheumatology centres, clinical and ultrasound examinations of the lower limb large entheses were performed in 413 patients with SpA (axial SpA and psoriatic arthritis) and 282 disease controls (osteoarthritis and fibromyalgia). 'Active enthesitis' was defined as (1) power Doppler (PD) at the enthesis grade ≥1 plus entheseal thickening and/or hypoechoic areas, or (2) PD grade >1 (independent of the presence of entheseal thickening and/or hypoechoic areas). RESULTS: In the univariate analysis, all OMERACT lesions except enthesophytes/calcifications showed a significant association with SpA. PD (OR=8.77, 95% CI 4.40 to 19.20, p<0.001) and bone erosions (OR=4.75, 95% CI 2.43 to 10.10, p<0.001) retained this association in the multivariate analysis. Among the lower limb entheses, only the Achilles tendon was significantly associated with SpA (OR=1.93, 95% CI 1.30 to 2.88, p<0.001) in the multivariate analyses. Active enthesitis showed a significant association with SpA (OR=9.20, 95% CI 4.21 to 23.20, p<0.001), and unlike the individual OMERACT ultrasound lesions it was consistently associated with most clinical measures of SpA disease activity and severity in the regression analyses. CONCLUSIONS: This large multicentre study assessed the value of different ultrasound findings of enthesitis in SpA, identifying the most discriminative ultrasound lesions and entheseal sites for SpA. Ultrasound could differentiate between SpA-related enthesitis and other forms of entheseal pathology (ie, mechanical enthesitis), thus improving the assessment of entheseal involvement in SpA.
- Klíčová slova
- Arthritis, Psoriatic, Fibromyalgia, Osteoarthritis, Spondylitis, Ankylosing, Ultrasonography,
- MeSH
- Achillova šlacha diagnostické zobrazování patologie MeSH
- dospělí MeSH
- entezopatie * diagnostické zobrazování MeSH
- lidé středního věku MeSH
- lidé MeSH
- psoriatická artritida diagnostické zobrazování komplikace MeSH
- spondylartritida * diagnostické zobrazování komplikace MeSH
- studie případů a kontrol MeSH
- stupeň závažnosti nemoci MeSH
- ultrasonografie dopplerovská * metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
The seventh iteration of the reference genome assembly for Rattus norvegicus-mRatBN7.2-corrects numerous misplaced segments and reduces base-level errors by approximately 9-fold and increases contiguity by 290-fold compared with its predecessor. Gene annotations are now more complete, improving the mapping precision of genomic, transcriptomic, and proteomics datasets. We jointly analyzed 163 short-read whole-genome sequencing datasets representing 120 laboratory rat strains and substrains using mRatBN7.2. We defined ∼20.0 million sequence variations, of which 18,700 are predicted to potentially impact the function of 6,677 genes. We also generated a new rat genetic map from 1,893 heterogeneous stock rats and annotated transcription start sites and alternative polyadenylation sites. The mRatBN7.2 assembly, along with the extensive analysis of genomic variations among rat strains, enhances our understanding of the rat genome, providing researchers with an expanded resource for studies involving rats.
- Klíčová slova
- Rnor_6.0, genetic map, heterogeneous stock, hybrid rat diversity panel, inbred strains, mRatBN7.2, phylogenetic tree, rat, recombinant inbred, reference genome,
- MeSH
- anotace sekvence MeSH
- genetická variace genetika MeSH
- genom * genetika MeSH
- genomika * MeSH
- krysa rodu Rattus MeSH
- sekvenování celého genomu MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Protein lipidation is a post-translational modification that confers hydrophobicity on protein substrates to control their cellular localization, mediate protein trafficking, and regulate protein function. In particular, protein prenylation is a C-terminal modification on proteins bearing canonical motifs catalyzed by prenyltransferases. Prenylated proteins have been of interest due to their numerous associations with various diseases. Chemical proteomic approaches have been pursued over the last decade to define prenylated proteomes (prenylome) and probe their responses to perturbations in various cellular systems. Here, we describe the discovery of prenylation of a non-canonical prenylated protein, ALDH9A1, which lacks any apparent prenylation motif. This enzyme was initially identified through chemical proteomic profiling of prenylomes in various cell lines. Metabolic labeling with an isoprenoid probe using overexpressed ALDH9A1 revealed that this enzyme can be prenylated inside cells but does not respond to inhibition by prenyltransferase inhibitors. Site-directed mutagenesis of the key residues involved in ALDH9A1 activity indicates that the catalytic C288 bears the isoprenoid modification likely through an NAD+-dependent mechanism. Furthermore, the isoprenoid modification is also susceptible to hydrolysis, indicating a reversible modification. We hypothesize that this modification originates from endogenous farnesal or geranygeranial, the established degradation products of prenylated proteins and results in a thioester form that accumulates. This novel reversible prenoyl modification on ALDH9A1 expands the current paradigm of protein prenylation by illustrating a potentially new type of protein-lipid modification that may also serve as a novel mechanism for controlling enzyme function.
- Publikační typ
- časopisecké články MeSH
The seventh iteration of the reference genome assembly for Rattus norvegicus-mRatBN7.2-corrects numerous misplaced segments and reduces base-level errors by approximately 9-fold and increases contiguity by 290-fold compared to its predecessor. Gene annotations are now more complete, significantly improving the mapping precision of genomic, transcriptomic, and proteomics data sets. We jointly analyzed 163 short-read whole genome sequencing datasets representing 120 laboratory rat strains and substrains using mRatBN7.2. We defined ~20.0 million sequence variations, of which 18.7 thousand are predicted to potentially impact the function of 6,677 genes. We also generated a new rat genetic map from 1,893 heterogeneous stock rats and annotated transcription start sites and alternative polyadenylation sites. The mRatBN7.2 assembly, along with the extensive analysis of genomic variations among rat strains, enhances our understanding of the rat genome, providing researchers with an expanded resource for studies involving rats.
- Klíčová slova
- Genetic Map, Heterogeneous Stock, Hybrid Rat Diversity Panel, Inbred Strains, Phylogenetic Tree, Rat, Recombinant Inbred, Reference Genome, Rnor_6.0, mRatBN7.2,
- Publikační typ
- časopisecké články MeSH
- preprinty MeSH
OBJECTIVES: To investigate the reliability of the OMERACT US Task Force definition of US enthesitis in SpA. METHODS: In this web exercise, based on the evaluation of 101 images and 39 clips of the main entheses of the lower limbs, the elementary components included in the OMERACT definition of US enthesitis in SpA (hypoechoic areas, entheseal thickening, power Doppler signal at the enthesis, enthesophytes/calcifications, bone erosions) were assessed by 47 rheumatologists from 37 rheumatology centres in 15 countries. Inter- and intra-observer reliability of the US components of enthesitis was calculated using Light's kappa, Cohen's kappa, Prevalence And Bias Adjusted Kappa (PABAK) and their 95% CIs. RESULTS: Bone erosions and power Doppler signal at the enthesis showed the highest overall inter-reliability [Light's kappa: 0.77 (0.76-0.78), 0.72 (0.71-0.73), respectively; PABAK: 0.86 (0.86-0.87), 0.73 (0.73-0.74), respectively], followed by enthesophytes/calcifications [Light's kappa: 0.65 (0.64-0.65), PABAK: 0.67 (0.67-0.68)]. This was moderate for entheseal thickening [Light's kappa: 0.41 (0.41-0.42), PABAK: 0.41 (0.40-0.42)], and fair for hypoechoic areas [Light's kappa: 0.37 (0.36-0.38); PABAK: 0.37 (0.37-0.38)]. A similar trend was observed in the intra-reliability exercise, although this was characterized by an overall higher degree of reliability for all US elementary components compared with the inter-observer evaluation. CONCLUSIONS: The results of this multicentre, international, web-based study show a good reliability of the OMERACT US definition of bone erosions, power Doppler signal at the enthesis and enthesophytes/calcifications. The low reliability of entheseal thickening and hypoechoic areas raises questions about the opportunity to revise the definition of these two major components for the US diagnosis of enthesitis.
- Klíčová slova
- PsA, enthesitis, multicenter international study, power Doppler signal, reliability, seronegative spondyloarthritis, ultrasound,
- MeSH
- entezopatie * diagnostické zobrazování MeSH
- internet MeSH
- lidé MeSH
- reprodukovatelnost výsledků MeSH
- ultrasonografie dopplerovská metody MeSH
- ultrasonografie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
Some familial platelet disorders are associated with predisposition to leukemia, myelodysplastic syndrome (MDS) or dyserythropoietic anemia. We identified a family with autosomal dominant thrombocytopenia, high erythrocyte mean corpuscular volume (MCV) and two occurrences of B cell-precursor acute lymphoblastic leukemia (ALL). Whole-exome sequencing identified a heterozygous single-nucleotide change in ETV6 (ets variant 6), c.641C>T, encoding a p.Pro214Leu substitution in the central domain, segregating with thrombocytopenia and elevated MCV. A screen of 23 families with similar phenotypes identified 2 with ETV6 mutations. One family also had a mutation encoding p.Pro214Leu and one individual with ALL. The other family had a c.1252A>G transition producing a p.Arg418Gly substitution in the DNA-binding domain, with alternative splicing and exon skipping. Functional characterization of these mutations showed aberrant cellular localization of mutant and endogenous ETV6, decreased transcriptional repression and altered megakaryocyte maturation. Our findings underscore a key role for ETV6 in platelet formation and leukemia predisposition.
- MeSH
- abnormální erytrocyty MeSH
- akutní lymfatická leukemie genetika MeSH
- dospělí MeSH
- exom MeSH
- genetická predispozice k nemoci MeSH
- genetické asociační studie MeSH
- HEK293 buňky MeSH
- krevní nemoci genetika MeSH
- lidé MeSH
- missense mutace MeSH
- mutační analýza DNA MeSH
- předškolní dítě MeSH
- protein ETS, translokační varianta 6 MeSH
- protoonkogenní proteiny c-ets genetika MeSH
- represorové proteiny genetika MeSH
- rodokmen MeSH
- trombocytopenie genetika MeSH
- zárodečné mutace MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- protoonkogenní proteiny c-ets MeSH
- represorové proteiny MeSH
Sulfate is frequently found in the influent of subsurface-flow constructed wetlands (SSF CWs) used as tertiary treatments. To reveal the effects of plants and litters on sulfate removal, as well as the competition for organic carbon among microorganisms in SSF CWs, five laboratory-scale SSF CW microcosms were set up and were operated as a batch system with HRT 5 d. The results showed that the presence of Typha latifolia had little effect on sulfate removal in CWs, with or without additional carbon sources. Cattail litter addition greatly improved sulfate removal in SSF CWs. This improvement was linked to the continuous input of labile organic carbon, which lowers the redox level and supplies a habitat for sulfate reducing bacteria (SRB). The presence of SRB in cattail litter indicated the possibility of sulfate removal around the carbon supplier, but the quantity of microbes in cattail litter was much lower than that in gravel. Stoichiometry calculations showed that the contribution of SRB to COD removal (21-26%) was less than that of methane-producing bacteria (MPB) (47-61%) during the initial stage but dominated COD removal (42-65%) during the terminal stage. The contributions of aerobic bacteria (AB) and denitrification bacteria (DB) to COD removal were always lower than that of SRB. It was also observed that the variations in COD: S ratio had a great influence on the relative abundance of genes between SRB and MPB and both of them could be used as good predictors of carbon competition between SRB and MPB in CWs.
- Klíčová slova
- Carbon competition, Cattail litter, Subsurface flow constructed wetlands (SSF CWs), Sulfate, Sulfate reducing bacteria (SRB),
- MeSH
- Bacteria metabolismus MeSH
- biomasa MeSH
- chemické látky znečišťující vodu chemie metabolismus MeSH
- čištění vody metody MeSH
- mokřady * MeSH
- odpad tekutý - odstraňování * MeSH
- orobincovité fyziologie MeSH
- RNA ribozomální 16S MeSH
- sírany chemie metabolismus MeSH
- uhlík chemie metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- chemické látky znečišťující vodu MeSH
- RNA ribozomální 16S MeSH
- sírany MeSH
- uhlík MeSH
The removal efficiencies and the kinetics of disinfection byproducts (DBPs) were studied in six greenhouse laboratory-scale SSF CWs. Cattail (Typha latifolia) and its litter (collected from the aboveground samples of cattail in autumn) were used as a potential phytoremediation technology and as a primary substrate, respectively, for DBP removal. Results showed that most of the 11 DBPs (except chloroform and 1, 1-dichloropropanone) were efficiently removed (>90%) in six SSF CWs with hydraulic retention time of 5 d and there were no significant differences among the systems. Under the batch mode, the removal of DBPs in SSF CWs followed first-order kinetics with half-lives of 1.0-770.2 h. As a primary DBP in wastewater effluent, removal efficiencies for chloroform were higher in planted systems than in unplanted ones and plant uptake accounted for more than 23.8% of the removal. Plant litter greatly enhanced the removal of trihalomethanes (THMs) by supplying primary substrates and reducing conditions, and the formation of dichloromethane supported the anaerobic biodegradation of THMs via reductive dechlorination in SSF CWs. Trichloroacetonitrile was completely removed within 10 h in each system and hydrolysis was considered to be the dominant process as there was a rapid formation of the hydrolysis byproduct, trichloroacetamide.
- Klíčová slova
- Cattail litter, Disinfection byproducts, Subsurface-flow constructed wetlands (SSF CWs), Tertiary treatment, Typha latifolia,
- MeSH
- anaerobní bakterie metabolismus MeSH
- biodegradace MeSH
- chemické látky znečišťující vodu analýza metabolismus MeSH
- čištění vody metody MeSH
- dezinfekce metody MeSH
- kinetika MeSH
- mokřady * MeSH
- odpadní produkty analýza MeSH
- orobincovité MeSH
- podzemní voda chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- chemické látky znečišťující vodu MeSH
- odpadní produkty MeSH
