DNA-protein crosslinks (DPCs) are highly toxic DNA lesions represented by proteins covalently bound to the DNA. Persisting DPCs interfere with fundamental genetic processes such as DNA replication and transcription. Cytidine analog zebularine (ZEB) has been shown to crosslink DNA METHYLTRANSFERASE1 (MET1). Recently, we uncovered a critical role of the SMC5/6-mediated SUMOylation in the repair of DPCs. In an ongoing genetic screen, we identified two additional candidates, HYPERSENSITIVE TO ZEBULARINE 2 and 3, that were mapped to REGULATOR OF TELOMERE ELONGATION 1 (RTEL1) and polymerase TEBICHI (TEB), respectively. By monitoring the growth of hze2 and hze3 plants in response to zebularine, we show the importance of homologous recombination (HR) factor RTEL1 and microhomology-mediated end-joining (MMEJ) polymerase TEB in the repair of MET1-DPCs. Moreover, genetic interaction and sensitivity assays showed the interdependency of SMC5/6 complex, HR, and MMEJ in the homology-directed repair of MET1-DPCs in Arabidopsis. Altogether, we provide evidence that MET1-DPC repair in plants is more complex than originally expected.
- Klíčová slova
- Arabidopsis thaliana, DNA damage repair, DNA–protein crosslink, RTEL1, SMC5/6 complex, TEBICHI, genome stability, replicative stress,
- MeSH
- Arabidopsis * genetika metabolismus MeSH
- cytidin * analogy a deriváty metabolismus farmakologie MeSH
- DNA rostlinná genetika metabolismus MeSH
- oprava DNA MeSH
- poškození DNA MeSH
- proteiny huseníčku * metabolismus genetika MeSH
- rekombinační oprava DNA MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cytidin * MeSH
- DNA rostlinná MeSH
- proteiny huseníčku * MeSH
- pyrimidin-2-one beta-ribofuranoside MeSH Prohlížeč
INTRODUCTION: IL-40 is a novel cytokine associated with autoimmune connective tissue disorders such as rheumatoid arthritis (RA) or Sjögren syndrome. We have previously shown an accumulation of IL-40 in the RA joint and its expression by immune cells and fibroblasts. Therefore, we aimed to assess the role of IL-40 in association with hyaline cartilage and chondrocyte activity. METHODS: Immunohistochemistry was employed to detect IL-40 in paired samples of loaded and unloaded regions of osteoarthritis (OA) cartilage (n=5). Synovial fluid IL-40 was analysed by ELISA in OA (n=31) and control individuals after knee injury (n=34). The impact of IL-40 on chondrocytes was tested in vitro. RESULTS: IL-40 was found in chondrocytes of the superficial zone of the OA cartilage, both in loaded and unloaded explants. Additionally, only biopsies from loaded explants showed significant IL-40 positivity in transitional zone chondrocytes. Levels of IL-40 were significantly elevated in the synovial fluid from OA patients compared to controls (p<0.0009) and correlated with synovial fluid leukocyte counts in OA (r=0.444, p=0.014). Chondrocytes exposed to IL-40 dose dependently increased in the secretion of pro-inflammatory cytokines IL-6 (p<0.0001) and IL-8 (p=0.004). Moreover, a dose dependent up-regulation of matrix degrading metalloproteinases MMP-1 (p=0.004), MMP-3 (p=0.031) and MMP-13 (p=0.0002) upon IL-40 treatment was observed in contrast to untreated chondrocytes. CONCLUSION: This study is the first to demonstrate the accumulation of IL-40 in OA cartilage and its up-regulation in the synovial fluid of OA patients compared to controls. In addition, extracellular IL-40 appears to play a role in promoting inflammation and cartilage destruction by driving chondrocyte behaviour towards a more aggressive phenotype.
- Klíčová slova
- Cartilage, Chondrocytes, Interleukin 40, Osteoarthritis,
- MeSH
- chondrocyty * metabolismus patologie MeSH
- dospělí MeSH
- ELISA MeSH
- fenotyp MeSH
- imunohistochemie MeSH
- interleukiny * metabolismus MeSH
- kloubní chrupavka metabolismus patologie MeSH
- kultivované buňky MeSH
- lidé středního věku MeSH
- lidé MeSH
- osteoartróza * metabolismus patologie MeSH
- senioři MeSH
- synoviální tekutina * metabolismus MeSH
- upregulace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- C17orf99 protein, human MeSH Prohlížeč
- interleukiny * MeSH
OBJECTIVES: We aimed to evaluate cardiovascular (CV) risk in patients with idiopathic inflammatory myopathies (IIM) compared with healthy controls (HC) and to assess its association with disease-specific features. METHODS: Ninety IIM patients and 180 age-/sex-matched HC were included. Subjects with a history of CV disease (angina pectoris, myocardial infarction and cerebrovascular/peripheral arterial vascular events) were excluded. All participants were prospectively recruited and underwent examinations of carotid intima-media thickness (CIMT), pulse wave velocity (PWV), ankle-brachial index (ABI), and body composition. The risk of fatal CV events was evaluated by the Systematic COronary Risk Evaluation (SCORE) and its modifications. RESULTS: Compared with HC, IIM patients had a significantly higher prevalence of traditional CV risk factors, carotid artery disease (CARD), abnormal ABI and PWV. After propensity score matching (using traditional CV risk factors), the prevalence of CARD and pathological PWV remained significantly higher in IIM than HC. No significant difference in SCORE was observed. The most unfavourable CV risk profile was observed in patients with necrotizing myopathy, especially in statin-induced anti-HMGCR+ patients. The calculated CV risk scores by SCORE, SCORE2 and SCORE multiplied by the coefficient 1.5 (mSCORE) were reclassified according to CIMT and the presence of carotid plaques. SCORE was demonstrated to be most inaccurate in predicting CV risk in IIM. Age, disease activity, lipid profile, body composition parameters and blood pressure were the most significant predictors of CV risk in IIM patients. CONCLUSION: Significantly higher prevalence of traditional risk factors and subclinical atherosclerosis was observed in IIM patients compared with HC.
- Klíčová slova
- atherosclerosis, cardiovascular risk, inflammation, myositis,
- MeSH
- analýza pulzové vlny MeSH
- intimomediální šíře tepenné stěny MeSH
- kardiovaskulární nemoci * epidemiologie etiologie MeSH
- lidé MeSH
- myozitida * epidemiologie MeSH
- nemoci arterie carotis * MeSH
- rizikové faktory kardiovaskulárních chorob MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
TiO2 aerogels doped with Ni, Co, Cu, and Fe were prepared, and their structure and photocatalytic activity during the decomposition of a model pollutant, acid orange (AO7), were studied. After calcination at 500 °C and 900 °C, the structure and composition of the doped aerogels were evaluated and analyzed. XRD analysis revealed the presence of anatase/brookite and rutile phases in the aerogels along with other oxide phases from the dopants. SEM and TEM microscopy showed the nanostructure of the aerogels, and BET analysis showed their mesoporosity and high specific surface area of 130 to 160 m2·g-1. SEM-EDS, STEM-EDS, XPS, EPR methods and FTIR analysis evaluated the presence of dopants and their chemical state. The concentration of doped metals in aerogels varied from 1 to 5 wt.%. The photocatalytic activity was evaluated using UV spectrophotometry and photodegradation of the AO7 pollutant. Ni-TiO2 and Cu-TiO2 aerogels calcined at 500 °C showed higher photoactivity coefficients (kaap) than aerogels calcined at 900 °C, which were ten times less active due to the transformation of anatase and brookite to the rutile phase and the loss of textural properties of the aerogels.
- Klíčová slova
- aerogels, anatase, brookite, photocatalytic properties, transition metal ions,
- Publikační typ
- časopisecké články MeSH
This study investigated the effect of glycerol added in different phases of sperm equilibration on CASA and flow cytometry parameters of thawed ram spermatozoa. Sperm was collected from adult Wallachian rams. The freezing extender was glycerol-free ANDROMED® (Minitub GmbH, Tiefenbach, Germany) supplied by 6% exogenous glycerol at different stages of the cryopreservation process. The purpose of this study was to compare two strategies of glycerol addition for sperm cryopreservation. The first strategy included the use of a glycerol-free extender for the procedure of glycerol-free equilibration and chilling, with the glycerolation of the extender by 6% glycerol shortly before sperm slow freezing (GFA). The second strategy included the use of a freezing extender already glycerolated by 6% glycerol before the equilibration and chilling of sperm and following slow freezing (GA). Sperm samples were analyzed after equilibration (but before freezing) and after thawing (at T0, T1 h, and T2 h time points). iSperm® mCASA (Aidmics Biotechnology Co., LTD., Taipei, Taiwan) was used for the evaluation of sperm kinematics. Flow cytometry was used to measure sperm viability (plasma membrane/acrosome intactness) and mitochondrial membrane potential. The obtained results significantly demonstrated that the glycerol-free equilibration with the addition of glycerol shortly before freezing is a perspective strategy for cryopreservation of Wallachian ram sperm.
- Klíčová slova
- cryopreservation capacity, mitochondrial membrane potential, plasma membrane and acrosome intactness, sperm motility,
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Although the tick-borne pathogen Anaplasma phagocytophilum is currently described as a single species, studies using genetic markers can distinguish groups of variants associated with different hosts, pathogenicity, zoonotic potential and biotic and geographic niches. The objective of our study was to investigate the genetic diversity of A. phagocytophilum and Ixodes ricinus ticks attached to people. METHODS: In collaboration with a commercial diagnostic company, a total of 52 DNA samples were obtained from ticks that tested positive for A. phagocytophilum by quantitative PCR. The genetic profile of each sample was determined using the groEL and ankA genes. Identification of the tick species was confirmed by partial sequencing of the COI subunit and a portion of the TROSPA gene. RESULTS: All 52 ticks were identified as I. ricinus. Two protocols of nested PCR amplifying 1293- and 407-bp fragments of groEL of A. phagocytophilum yielded amplicons of the expected size for all 52 samples. Among all sequences, we identified 10 unique genetic variants of groEL belonging to ecotype I and ecotype II. The analysis targeting ankA was successful in 46 of 52 ticks. Among all sequences, we identified 21 unique genetic variants phylogenetically belonging to three clusters. CONCLUSIONS: Our results indicate that ticks attached to people harbor distant genetic variants of A. phagocytophilum, some of which are not recognized as zoonotic. Further studies are needed to determine the risk of human infection by genetic variants other than those designated as zoonotic.
- Klíčová slova
- Anaplasma phagocytophilum, Anaplasmosis, Genetic diversity, Infectious diseases, Ixodes ricinus,
- MeSH
- Anaplasma phagocytophilum * genetika MeSH
- ekotyp MeSH
- klíště * MeSH
- lidé MeSH
- polymerázová řetězová reakce MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The reconstruction of the settlement´s hinterland and acquisition of plant resources is one of the crucial questions in the field of environmental archaeology. Our study is focused on the reconstruction of the settlement's structure and character of the environment from which the site drew resources. These research questions were addressed by the interpretation of plant macroremains, charcoals, and the results of the spatial model. We have focused on the maximum size of the settlement that the surrounding countryside was able to withstand. Our results clearly demonstrated significant deforestation and intensive land use in the vicinity of the Late Bronze Age study site. As the weed taxa showed, a wide range of crops was grown in rather dry or less often in damp fields. Based on our archaeobotanical results, we were able to reconstruct several types of grasslands: dry pastures and fallow fields on plateaus and slopes, wet pastures or meadows in the floodplain. Acidophilous oak forests, alluvial forests, and shrubs were reconstructed as the most common forest habitats in the vicinity of the study site. Based on the archaeological knowledge of the region, we assume relatively low population density during the Late Bronze Age, and thus only a small part of the more or less forested landscape was significantly affected by human activities.
- MeSH
- ekosystém MeSH
- lesy MeSH
- lidé MeSH
- stromy * MeSH
- zachování přírodních zdrojů * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
OBJECTIVES: To date, there is almost no information concerning the sexual health of patients with idiopathic inflammatory myopathies (IIM). This cross-sectional study aimed to compare sexual function in patients with IIM to age-/sex-matched healthy controls (HC) and determine the potential impact of clinical features on sexual function. METHODS: In total, 122 women (61 with IIM, 61 age-matched HC) and 22 men (11 with IIM, 11 age-matched HC) aged 18-80 years completed gender-specific selection of 7 well-established and validated questionnaires assessing sexual health and function (Female Sexual Function Index, Brief Index of Sexual Function for Women, Sexual Function Questionnaire, Sexual Quality of Life Questionnaire-Female, International Index of Erectile Function, Male Sexual Health Questionnaire, Sexual Quality of Life Questionnaire-Male). Results were compared between patients and HC and correlated with selected disease-related features. RESULTS: The prevalence of sexual dysfunction in IIM was 59% in women (vs 40% in HC), and 64% (vs 9% in HC) in men. Men and women with IIM reported significantly impaired sexual function compared with sex-/age-matched HC. Decreased sexual function was associated with muscle weakness, disability, physical inactivity, fatigue, depression and decreased quality of life. CONCLUSIONS: Our results suggest that sexual dysfunction is common among IIM patients and more attention should be paid to this aspect of the disease.
- Klíčová slova
- erectile dysfunction, female sexual dysfunction, idiopathic inflammatory myopathies, sexual health,
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- myozitida patofyziologie psychologie MeSH
- pánevní dno patofyziologie MeSH
- průřezové studie MeSH
- senioři MeSH
- sexuální chování fyziologie MeSH
- sexuální zdraví * MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Milk fat is an important nutritional compound in the human diet. From the health point of view, some fatty acids (FAs), particularly long-chain PUFAs such as EPA and DHA, have been at the forefront of interest due to their antibacterial, antiviral, anti-inflammatory, and anti-tumor properties, which play a positive role in the prevention of cardiovascular diseases (CVD), as well as linoleic and γ-linolenic acids, which play an important role in CVD treatment as essential components of phospholipids in the mitochondria of cell membranes. Thus, the modification of the FA profile-especially an increase in the concentration of polyunsaturated FAs and n-3 FAs in bovine milk fat-is desirable. The most effective way to achieve this goal is via dietary manipulations. The effects of various strategies in dairy nutrition have been thoroughly investigated; however, there are some alternative or unconventional feedstuffs that are often used for purposes other than basic feeding or modifying the fatty acid profiles of milk, such as tanniferous plants, herbs and spices, and algae. The use of these foods in dairy diets and their effects on milk fatty acid profile are reviewed in this article. The contents of selected individual FAs (atherogenic, rumenic, linoleic, α-linolenic, eicosapentaenoic, and docosahexaenoic acids) and their combinations; the contents of n3 and n6 FAs; n6/n3 ratios; and atherogenic, health-promoting and S/P indices were used as criteria for assessing the effect of these feeds on the health properties of milk fat.
- Klíčová slova
- algae, camelina, dairy cows, health, herbs and spices, indices, milk fat quality, okara, tannins,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Temperature passively affects biological processes involved in plant growth. Therefore, it is challenging to study the dedicated temperature signalling pathways that orchestrate thermomorphogenesis, a suite of elongation growth-based adaptations that enhance leaf-cooling capacity. We screened a chemical library for compounds that restored hypocotyl elongation in the pif4-2-deficient mutant background at warm temperature conditions in Arabidopsis thaliana to identify modulators of thermomorphogenesis. The small aromatic compound 'Heatin', containing 1-iminomethyl-2-naphthol as a pharmacophore, was selected as an enhancer of elongation growth. We show that ARABIDOPSIS ALDEHYDE OXIDASES redundantly contribute to Heatin-mediated hypocotyl elongation. Following a chemical proteomics approach, the members of the NITRILASE1-subfamily of auxin biosynthesis enzymes were identified among the molecular targets of Heatin. Our data reveal that nitrilases are involved in promotion of hypocotyl elongation in response to high temperature and Heatin-mediated hypocotyl elongation requires the NITRILASE1-subfamily members, NIT1 and NIT2. Heatin inhibits NIT1-subfamily enzymatic activity in vitro and the application of Heatin accordingly results in the accumulation of NIT1-subfamily substrate indole-3-acetonitrile in vivo. However, levels of the NIT1-subfamily product, bioactive auxin (indole-3-acetic acid), were also significantly increased. It is likely that the stimulation of hypocotyl elongation by Heatin might be independent of its observed interaction with NITRILASE1-subfamily members. However, nitrilases may contribute to the Heatin response by stimulating indole-3-acetic acid biosynthesis in an indirect way. Heatin and its functional analogues present novel chemical entities for studying auxin biology.
- Klíčová slova
- 1-iminomethyl-2-naphthol, Arabidopsis, Heatin, IAN, NIT1-subfamily, PIF4, aldehyde oxidase, chemical genetics, indole-3-acetonitrile, nitrilases, thermomorphogenesis,
- MeSH
- aldehydoxidasa genetika metabolismus MeSH
- aminohydrolasy genetika metabolismus MeSH
- apomorfin analogy a deriváty farmakologie MeSH
- Arabidopsis účinky léků růst a vývoj MeSH
- herbicidy farmakologie MeSH
- hypokotyl účinky léků růst a vývoj MeSH
- inhibitory enzymů aplikace a dávkování chemie farmakologie MeSH
- kyseliny indoloctové MeSH
- molekulární struktura MeSH
- pikloram farmakologie MeSH
- proteiny huseníčku genetika metabolismus MeSH
- regulace genové exprese u rostlin účinky léků MeSH
- transkriptom účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 10,11-dihydroxy-N-n-propylnorapomorphine MeSH Prohlížeč
- AAO1 protein, Arabidopsis MeSH Prohlížeč
- aldehydoxidasa MeSH
- aminohydrolasy MeSH
- apomorfin MeSH
- herbicidy MeSH
- inhibitory enzymů MeSH
- kyseliny indoloctové MeSH
- nitrilase MeSH Prohlížeč
- pikloram MeSH
- proteiny huseníčku MeSH
