Regulation of G protein coupled receptors (GPCRs) looks to be not only classically lineary regulated but it is now discovered to be a complex network of interconnected proteins. Taking these in mind it is highly probable that there is multilevel system of regulation that is able to maintain control of signaling. We review here main mechanisms of GPCRs regulation.
- MeSH
- arrestin fyziologie MeSH
- fosforylace MeSH
- lidé MeSH
- proteinkinasy fyziologie MeSH
- proteiny RGS fyziologie MeSH
- receptory spřažené s G-proteiny fyziologie MeSH
- signální transdukce fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- arrestin MeSH
- proteinkinasy MeSH
- proteiny RGS MeSH
- receptory spřažené s G-proteiny MeSH
Two new species of the genus Laemostenus Bonelli sg. Antisphodrus Schaufuss of the bodemeyeri species-group are described, illustrated and compared with the related species: Laemostenus (Antisphodrus) bozdagensis sp. nov. (Type locality Manisa, Bozdağlar) and Laemostenus (Antisphodrus) binboga sp. nov. (Type locality Kayseri, Sarız, Binboğa Dağları). These new species were collected with subterranean pitfall traps in the mesovoid shallow substratum (MSS). Additional faunistic and systematic comments, identification key and check-list for Turkish species of the bodemeyeri species group are also presented. Distribution of the bodemeyeri species group is mapped.
- Klíčová slova
- Coleoptera, Taxonomy, descriptions, new species, MSS habitat, Bozdağlar, Binboğa Dağları,
- MeSH
- brouci * MeSH
- rozšíření zvířat MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Turecko MeSH
Allogeneic HSCT represents the only potentially curative treatment for very high risk (VHR) ALL. Two consecutive international prospective studies, ALL-SCT-(I)BFM 2003 and 2007 were conducted in 1150 pediatric patients. 569 presented with VHR disease leading to any kind of HSCT. All patients >2 year old were transplanted after TBI-based MAC. The median follow-up was 5 years. 463 patients were transplanted from matched donor (MD) and 106 from mismatched donor (MMD). 214 were in CR1. Stem cell source was unmanipulated BM for 330 patients, unmanipulated PBSC for 135, ex vivo T-cell depleted PBSC for 62 and cord-blood for 26. There were more advanced disease, more ex vivo T-cell depletion, and more chemotherapy based conditioning regimen for patients transplanted from MMD as compared to those transplanted from MSD or MD. Median follow up (reversed Kaplan Meier estimator) was 4.99 years, median follow up of survivals was 4.88, range (0.01-11.72) years. The 4-year CI of extensive cGvHD was 13 ± 2% and 17 ± 4% (p = NS) for the patients transplanted from MD and MMD, respectively. 4-year EFS was statistically better for patients transplanted from MD (60 ± 2% vs. 42 ± 5%, p < 0.001) for the whole cohort. This difference does not exist if considering separately patients treated in the most recent study. There was no difference in 4-year CI of relapse. The 4-year NRM was lower for patients transplanted from MD (9 ± 1% vs. 23 ± 4%, p < 0.001). In multivariate analysis, donor-type appears as a negative risk-factor for OS, EFS, and NRM. This paper demonstrates the impact of donor type on overall results of allogeneic stem cell transplantation for very-high risk pediatric acute lymphoblastic leukemia with worse results when using MMD stem cell source.
- MeSH
- akutní lymfatická leukemie * terapie MeSH
- dárci tkání MeSH
- dítě MeSH
- lidé MeSH
- nemoc štěpu proti hostiteli * MeSH
- předškolní dítě MeSH
- příprava pacienta k transplantaci MeSH
- prospektivní studie MeSH
- retrospektivní studie MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
There is still a need for synthetic approaches that are much faster, easier to scale up, more robust and efficient for generating gold(I)-thiolates that can be easily converted into gold-thiolate nanoclusters. Mechanochemical methods can offer significantly reduced reaction times, increased yields and straightforward recovery of the product, compared to the solution-based reactions. For the first time, a new simple, rapid and efficient mechanochemical redox method in a ball-mill was developed to produce the highly luminescent, pH-responsive Au(I)-glutathionate, [Au(SG)]n. The efficient productivity of the mechanochemical redox reaction afforded orange luminescent [Au(SG)]n in isolable amounts (mg scale), usually not achieved by more conventional methods in solution. Then, ultrasmall oligomeric Au10-12(SG)10-12 nanoclusters were prepared by pH-triggered dissociation of [Au(SG)]n. The pH-stimulated dissociation of the Au(I)-glutathionate complex provides a time-efficient synthesis of oligomeric Au10-12(SG)10-12 nanoclusters, it avoids high-temperature heating or the addition of harmful reducing agent (e.g., carbon monoxide). Therefore, we present herein a new and eco-friendly methodology to access oligomeric glutathione-based gold nanoclusters, already finding applications in biomedical field as efficient radiosensitizers in cancer radiotherapy.
- Klíčová slova
- bioactive molecules, glutathione, gold nanocluster, gold thiolate, mechanochemistry,
- Publikační typ
- časopisecké články MeSH
Legionnaires' disease is a severe form of lung infection caused by bacteria belonging to the genus Legionella. The disease severity depends on both host immunity and L. pneumophila virulence. The objective of this study was to describe the pathological spectrum of acute pneumonia caused by a virulent clinical isolate of L. pneumophila serogroup 1, sequence type 62. In A/JOlaHsd mice, we compared two infectious doses, namely, 104 and 106 CFU, and their impact on the mouse status, bacterial clearance, lung pathology, and blood count parameters was studied. Acute pneumonia resembling Legionnaires' disease has been described in detail.
- Klíčová slova
- A/J mouse, histopathology, inflammatory, legionellosis, lung infection, mouse model,
- Publikační typ
- časopisecké články MeSH
The article deals with the analysis of chromium layer grinding on a steel substrate, where this issue was addressed with regard to the requirements of the manufacturing sector, specifically in the aerospace industry. The experimental samples were chromium-plated and ground under different cutting conditions by the grooving method of grinding. Two types of grinding wheels for grinding were used, grinding wheel based on SG (solgel) a grinding wheel based on SiC. The resulting microstructure and microhardness in the machined layer were evaluated with using of confocal laser microscopy, inverted materials microscopy, and hardness testing. Based on the results, recommendations were made regarding a suitable approach to grinding the chromium coating. We used a confocal laser microscope and hardness tester for the evaluation of presented values. It was found that, on the base of analyses values, with both grinding wheel and using cutting conditions used, good results have been achieved. This could be stated, because the analysis of the samples microstructure after grinding for the given cutting conditions showed that it is possible that a small influence is completely acceptable from the point of the final product view and there are no major negative phenomena. Measurements of surface microhardness after grinding showed similar results for all samples. The SiC-based grinding wheel showed slightly better results, but both grinding wheels can be used without problems for the presented cutting conditions, and the presented cutting conditions with both grinding wheels can be recommended for the grinding of the given material.
- Klíčová slova
- SG, SiC, cutting speed, grinding, microstructure,
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: Although a number of human Legionnaires' disease in tourists are recorded annually in Europe, there are few cases where a direct link can be made between the infected person and the source of infection (hotel or other accommodation). We present a scheme followed in order to track down and identify the source of infection in a tourist suffering from L. pneumophila sg 5 infection, who was accommodated in seven different hotels during his holidays in the island of Crete, and we comment on various difficulties and draw-backs of the process. METHOD: Water samples were collected from the seven hotels where the patient had resided and analyzed at the regional public health laboratory using cultivation and molecular tests. RESULTS: Of 103 water samples analyzed, 19 (18.4%) were positive for Legionella non-pneumophila and 8 (7.8%) were positive for L. pneumophila. A successful L. pneumophila sg 5 match was found between the clinical and environmental sample, which led us to the final identification of the liable hotel. CONCLUSION: Timely notification of the case, within the the European Legionnaires' Disease Surveillance Network (ELDSNet) of the partners involved, is crucial during a course of travel associated with Legionella case investigation. Moreover, the urinary antigen test alone cannot provide sufficient information for the source identification. However, acquiring clinical as well as environmental isolates for serogroup and SBT identification is highly important for the successful matching.
- Klíčová slova
- Legionella pneumophila sg 5, biotyping, surveillance, travel associated disease, urinary antigen test,
- MeSH
- cestování * MeSH
- Legionella pneumophila izolace a purifikace MeSH
- legionelóza diagnóza moč MeSH
- lidé MeSH
- mikrobiologie vody * MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Geografické názvy
- Francie etnologie MeSH
- Řecko MeSH
BACKGROUND: A retrospective study was undertaken to define the efficacy of both mini gastric bypass or one anastomosis gastric bypass (MGB/OAGB) and sleeve gastrectomy (SG) in type 2 diabetes mellitus (T2DM) remission in morbidly obese patients (pts). METHODS: Eight European centers were involved in this survey. T2DM was preoperatively diagnosed in 313/3252 pts (9.62%). In 175/313 patients, 55.9% underwent MGB/OAGB, while in 138/313 patients, 44.1% received SG between January 2006 and December 2014. RESULTS: Two hundred six out of 313 (63.7 %) pts reached 1 year of follow-up. The mean body mass index (BMI) for MGB/OAGB pts was 33.1 ± 6.6, and the mean BMI for SG pts was 35.9 ± 5.9 (p < 0.001). Eighty-two out of 96 (85.4%) MGB/OAGB pts vs. 67/110 (60.9%) SG pts are in remission (p < 0.001). No correlation was found in the % change vs. baseline values for hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) in relation to BMI reduction, for both MGB/OAGB or SG (ΔFPG 0.7 and ΔHbA1c 0.4 for MGB/OAGB; ΔFPG 0.7 and ΔHbA1c 0.1 for SG). At multivariate analysis, high baseline HbA1c [odds ratio (OR) = 0.623, 95% confidence interval (CI) 0.419-0.925, p = 0.01], preoperative consumption of insulin or oral antidiabetic agents (OR = 0.256, 95% CI 0.137-0.478, p = <0.001), and T2DM duration >10 years (OR = 0.752, 95% CI 0.512-0.976, p = 0.01) were negative predictors whereas MGB/OAGB resulted as a positive predictor (OR = 3.888, 95% CI 1.654-9.143, p = 0.002) of diabetes remission. CONCLUSIONS: A significant BMI decrease and T2DM remission unrelated from weight loss were recorded for both procedures if compared to baseline values. At univariate and multivariate analyses, MGB/OAGB seems to outperform significantly SG. Four independent variables able to influence T2DM remission at 12 months have been identified.
- Klíčová slova
- Bariatric surgery, European multicenter survey, MGB/OAGB, Mini gastric bypass/one anastomosis gastric bypass, Remission, SG, Sleeve gastrectomy, T2DM, Type 2 diabetes mellitus,
- MeSH
- diabetes mellitus 2. typu komplikace chirurgie MeSH
- dospělí MeSH
- gastrektomie metody MeSH
- hmotnostní úbytek MeSH
- lidé středního věku MeSH
- lidé MeSH
- morbidní obezita komplikace chirurgie MeSH
- následné studie MeSH
- retrospektivní studie MeSH
- výsledek terapie MeSH
- žaludeční bypass metody MeSH
- zdravotnické přehledy MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: Differentiating Parkinson's disease (PD) from atypical parkinsonian disorders (APD) such as Multiple System Atrophy, parkinsonian type (MSA-p) or Progressive Supranuclear Palsy (PSP-RS) can be challenging. Early signs of postural Instability and gait disability (PIGD) are considered clues that may signal presence of APD. However, it remains unknown which PIGD test - or combination of tests - can best distinguish PD from APD. We evaluated the discriminative value of several widely-used PIGD tests, and aimed to develop a short PIGD evaluation that can discriminate parkinsonian disorders. METHODS: In this multicentre cohort study patients were recruited by 11 European MSA Study sites. Patients were diagnosed using standardized criteria. Postural instability and gait disability was evaluated using interviews and several clinical tests. RESULTS: Nineteen PD, 21 MSA-p and 25 PSP-RS patients were recruited. PIGD was more common in APD compared to PD. There was no significant difference in axial symptoms between PSP-RS and MSA-p, except for self-reported falls (more frequent in PSP-RS patients). The test with the greatest discriminative power to distinguish APD from PD was the ability to perform tandem gait (AUC 0.83; 95% CI 71-94; p < 0.001), followed by the retropulsion test (AUC 0.8; 95% CI 0.69-0.91; p < 0.001) and timed-up-and-go test (TUG) (AUC 0.77; 95% CI 0.64-0.9; p = 0.001). The combination of these three tests yielded highest diagnostic accuracy (AUC 0.96; 95% CI 0.92-1.0; p < 0.001). CONCLUSIONS: Our study suggests that simple "bedside" PIGD tests - particularly the combination of tandem gait performance, TUG and retropulsion test - can discriminate APD from PD.
- Klíčová slova
- Atypical parkinsonian disorders, Multiple system atrophy, Parkinson's disease, Parkinsonian type, Postural instability and gait disability, Progressive supranuclear palsy,
- MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- neurologické poruchy chůze diagnóza epidemiologie patofyziologie MeSH
- Parkinsonova nemoc diagnóza epidemiologie patofyziologie MeSH
- parkinsonské poruchy diagnóza epidemiologie patofyziologie MeSH
- posturální rovnováha fyziologie MeSH
- prospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa epidemiologie MeSH
BACKGROUND: Eukaryotic translation initiation factor 4E (eIF4E) plays a pivotal role in the control of cap-dependent translation initiation, modulates the fate of specific mRNAs, occurs in processing bodies (PBs) and is required for formation of stress granules (SGs). In this study, we focused on the subcellular localization of a representative compendium of eIF4E protein isoforms, particularly on the less studied members of the human eIF4E protein family, eIF4E2 and eIF4E3. RESULTS: We showed that unlike eIF4E1, its less studied isoform eIF4E3_A, encoded by human chromosome 3, localized to stress granules but not PBs upon both heat shock and arsenite stress. Furthermore, we found that eIF4E3_A interacts with human translation initiation factors eIF4G1, eIF4G3 and PABP1 in vivo and sediments into the same fractions as canonical eIF4E1 during polysome analysis in sucrose gradients. Contrary to this finding, the truncated human eIF4E3 isoform, eIF4E3_B, showed no localization to SGs and no binding to eIF4G. We also highlighted that eIF4E2 may exhibit distinct functions under different stresses as it readily localizes to P-bodies during arsenite and heat stresses, whereas it is redirected to stress granules only upon heat shock. We extended our study to a number of protein variants, arising from alternative mRNA splicing, of each of the three eIF4E isoforms. Our results surprisingly uncovered differences in the ability of eIF4E1_1 and eIF4E1_3 to form stress granules in response to cellular stresses. CONCLUSION: Our comparison of all three human eIF4E isoforms and their protein variants enriches the intriguing spectrum of roles attributed to the eukaryotic initiation translation factors of the 4E family, which exhibit a distinctive localization within different RNA granules under different stresses. The localization of eIF4E3_A to stress granules, but not to processing bodies, along with its binding to eIF4G and PABP1 suggests a role of human eIF4E3_A in translation initiation rather than its involvement in a translational repression and mRNA decay and turnover. The localization of eIF4E2 to stress granules under heat shock but not arsenite stress indicates its distinct function in cellular response to these stresses and points to the variable protein content of SGs as a consequence of different stress insults.
- Klíčová slova
- Arsenite, Eukaryotic translation initiation factor 4E (eIF4E), Heat shock, PB, Processing body (P-body), SG, Stress granule, Translation control, Translation initiation factor, eIF4E2, eIF4E3,
- MeSH
- buněčné linie MeSH
- cytosol metabolismus MeSH
- eukaryotický iniciační faktor 4E analýza genetika metabolismus MeSH
- HEK293 buňky MeSH
- klonování DNA MeSH
- lidé MeSH
- messenger RNA genetika MeSH
- oxidační stres * MeSH
- poly(A)-vazebný protein I analýza metabolismus MeSH
- proteiny vázající čepičku mRNA analýza genetika metabolismus MeSH
- reakce na tepelný šok * MeSH
- sekvence aminokyselin MeSH
- sekvenční seřazení MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- EIF4E2 protein, human MeSH Prohlížeč
- eIF4E3 protein, human MeSH Prohlížeč
- eukaryotický iniciační faktor 4E MeSH
- messenger RNA MeSH
- poly(A)-vazebný protein I MeSH
- proteiny vázající čepičku mRNA MeSH
