Úvod: Difuzní idiopatická skeletální hyperostóza (DISH) a ankylozující spondylitida (AS) jsou onemocnění různé etiologie s tvorbou hyperosifikací v oblasti páteře. Osteoprotegerin je receptor, který svou vazbou na RANKL (ligand pro receptor aktivující nukleární faktor-κB) kompetitivně ihibuje děje vedoucí k diferenciaci a aktivaci osteoklastů. Cílem studie bylo zjistit úlohu sérového osteoprotegerinu (S-OPG) v ektopické novotvorbě kosti či ve vzniku osteoporózy u nemocných s DISH a AS. Metody a materiál: Bylo vyšetřeno 44 pacientů s AS (věk 37,5 ± 13,7 let), 71 pacientů s DISH (věk 64,8 ± 9,6 let) a 116 zdravých kontrol (věk 46,5 ± 16,2 let). U pacientů i kontrol byl stanoven S-OPG metodou ELISA, hladiny sérového osteokalcinu (S-OK) a kostní alkalické fosfatázy (S-KAP) metodou EIA. U nemocných byl stanoven močový deoxypyrodinolin (U-DPD, EIA), provedeno klinické vyšetření, rtg páteře a kostní denzitometrie femuru a bederní páteře (BMD, DEXA). Aktivita AS byla hodnocena pomocí stanovení C-reaktivního proteinu v séru (CRP), sedimentace erytrocytů (FW) a indexu aktivity (BASDAI). Výsledky: Pacienti s AS byli významně mladší než s DISH, FW i CRP byly u nich vyšší a převažovali nemocní s vysokou aktivitou dle BASDAI. Po zohlednění věku nebyl přítomen rozdíl v hladinách S-OPG mezi skupinami AS, DISH a kontrolami. Podobně nebyl nalezen rozdíl mezi oběma chorobami v S-OK, S-KAP a U-DPD. U nemocných však byly zvýšeny markery kostní novotvorby S-OK (AS i DISH p<0,0005) a S-KAP (DISH p<0,0005, AS p=0,066) ve srovnáni s kontrolami. Signifikantně více pacientů mělo U-DPD nad horní hranicí referenčního rozmezí (AS: 30% a DISH: 29%). Nemocní s vyšší aktivitou AS hodnocenou podle FW měli nižší S-KAP a S-OK a podle BASDAI měli nižší S-OK proti pacientům bez známek aktivity (p<0,05). Osteoporóza nebo osteopenie byla nalezena u nemocných s AS častěji (35%) než u DISH (14%). U 50letých a mladších pacientů s AS byla přítomna negativní korelace FW se S-OK resp. S-KAP (cc= -0,476, p<0,005 resp. cc= -0,325, p=0,06) a úzká pozitivní korelace S-OPG a BMD bederní páteře i femuru (cc od 0,35 do 0,43, p<0,05). Nemocní s AS a osteoporózou měli nižší S-OPG než nemocní bez osteoporózy. Ženy s DISH měly nižší hodnoty BMD v oblasti bederní páteře i femuru a vyšší U-DPD a S-KAP než u muži. Závěr: Z nepřítomnosti změn hladin S-OPG a z nálezu zvýšení S-OK a S-KAP bez korelace S-OPG s ukazateli kostní přeměny usuzujeme, že hyperosifikační děje u obou onemocnění nejsou důsledkem nedostatečné kostní resorpce avšak jsou zřejmě výsledkem abnormální aktivity osteoblastů. Častější pokles BMD a pozitivní korelace s hladinou OPG v séru, spolu s poklesem parametrů kostní novotvorby při aktivitě onemocnění, ukazuje na možný podíl aktivity zánětu při vzniku osteoporózy u AS. Pokles BMD spolu se změnami markerů kostní přeměny u žen s DISH nejspíše souvisí s vývojem metabolicky aktivní postmenopauzální osteoporózy.

Objective: Diffuse idiopathic skeletal hyperostosis (DISH) and ankylosing spondylitis (AS) represent diseases with distinct etiological patterns that cause hyperossification of the spine. Osteoprotegerin is a decoy receptor that binds RANKL (receptor activator of nuclear factor-κB) and thereby competitively inhibits differentiation and activation of osteoclasts. The aim of this study was to find out the role of serum osteoprotegerin (S-OPG) with respect to the ectopic bone formation or osteoporosis in patients with DISH and AS, respectively. Methods and materials: Forty-four patients with AS (mean age 37.5 ± 13.7 years), 71 patients with DISH (mean age 64.8 ± 9.6 years), and 116 healthy controls (mean age 46.5 ± 16.2 years) were examined. The level of S-OPG was measured by ELISA, and serum osteocalcin (S-OC) and bone alkaline phosphatase (ALP) by EIA. The level of urine dexypyridinoline (U-DPD, EIA), and clinical assessment, spine radiography as well as bone densitometry of femur and lumber spine (BMD, DEXA) were performed in all the patients. Disease activity of AS was estimated according the C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and the mean BASDAI. Results: Patients with AS were younger than those with DISH, had higher ESR and CRP. Those with high disease activity according to BASDAI were prevalent. Age-adjusted levels of S-OPG were similar between patients with AS, DISH as well as in healthy controls. Likewise, the difference in S-OC, bone ALP, and U-DPD between those two diseases was also not observed. Moreover, the patients had significantly higher levels bone-formation markers S-OC (p<0.0005 for AS and DISH) and bone ALP (p<0.0005 and p=0.066 for DISH and AS, respectively) in contrast to healthy controls. The levels of U-DPD were above the upper reference range in significantly more patients (AS: 30% and DISH: 29%). AS patients with high disease activity according to ESR had lower bone ALP and S-OC, and according to BASDAI had lower S-OC compared to the patients with low activity (p<0.05). Prevalence of osteoporosis and osteopenia was higher in patients with AS (35%) compared to those with DISH (14%). In 50 years old and younger AS patients, ESR correlated negatively with S-OC as well as with bone ALP (cc= -0.476, p<0.005, cc= -0.325, p=0.06, respectively). Moreover, tight positive correlation between S-OPG and BMD of lumbar spine and femur (cc from 0.35 to 0.43, p<0.05) was also observed. Patients with AS and osteoporosis had lower S-OPG levels than those without osteoporosis.Women with DISH presented lower lumbar spine and femur BMD and higher U-DPD and bone ALP than men. Conclusion: With respect to similar levels of S-OPG, increased levels of S-OC as well as bone ALP, and no association between S-OPG and markers of bone turnover, we propose that hyperossification in both diseases is not the result of insufficient bone resorption but rather the result of abnormal activity of osteoblasts. Frequent decrease of BMD, positive correlation of BMD with serum levels of OPG as well as decrease of bone formation markers during the active disease indicate a putative role of inflammation in the onset of osteoporosis in AS. The decrease of BMD in the line with the changes of bone turnover markers in women with DISH is most probably related to the development of metabolically active postmenopausal osteoporosis.

• MeSH
• alkalická fosfatasa krev   MeSH
• ankylózující spondylitida diagnóza   MeSH
• biologické markery analýza   MeSH
• difuzní idiopatická skeletální hyperostóza diagnóza   MeSH
• finanční podpora výzkumu jako téma MeSH
• glykoproteiny krev   MeSH
• kostní denzita MeSH
• lidé MeSH
• osteokalcin krev   MeSH
• osteoporóza diagnóza   MeSH
• receptory cytoplazmatické a nukleární krev   MeSH
• rozložení podle pohlaví MeSH
• stupeň závažnosti nemoci MeSH
• věkové faktory MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

Interspecific competition is a fundamental process affecting community structure and evolution of interacting species. Besides direct competition, this process is also mediated by shared enemies, which can change the outcome of competition dramatically. However, previous studies investigating interactions between competing species and their parasites (parasite-mediated competition) completely overlooked the effect of 'sperm' parasites (i.e. sperm-dependent parthenogens or pseudogams) on competition. These organisms originate by interspecific hybridization, produce clonal gametes, but exploit parental species for their own reproduction, being therefore analogous to classical parasites. Here we use the reaction-diffusion model and show that pseudogams alter the outcome of interspecific competition significantly. They may either slow down competitive exclusion of the inferior competitor or even turn the outcome of competition between the species. Asexual organisms may thus have unexpectedly strong impact on community structure, and have more significant evolutionary potential than was previously thought.

• MeSH
• biologická evoluce * MeSH
• biologické modely MeSH
• interakce hostitele a parazita genetika   MeSH
• kompetitivní chování fyziologie   MeSH
• rozmnožování genetika   MeSH
• sexuální chování fyziologie   MeSH
• spermie růst a vývoj   mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Yeast form complex highly organized colonies in which cells undergo spatiotemporal phenotypic differentiation in response to local gradients of nutrients, metabolites, and specific signaling molecules. Colony fitness depends on cell interactions, cooperation, and the division of labor between differentiated cell subpopulations. Here, we describe the regulation and dynamics of the expansion of papillae that arise during colony aging, which consist of cells that overcome colony regulatory rules and disrupt the synchronized colony structure. We show that papillae specifically expand within the U cell subpopulation in differentiated colonies. Papillae emerge more frequently in some strains than in others. Genomic analyses further revealed that the Whi2p-Psr1p/Psr2p complex (WPPC) plays a key role in papillae expansion. We show that cells lacking a functional WPPC have a sizable interaction-specific fitness advantage attributable to production of and resistance to a diffusible compound that inhibits growth of other cells. Competitive superiority and high relative fitness of whi2 and psr1psr2 strains are particularly pronounced in dense spatially structured colonies and are independent of TORC1 and Msn2p/Msn4p regulators previously associated with the WPPC function. The WPPC function, described here, might be a regulatory mechanism that balances cell competition and cooperation in dense yeast populations and, thus, contributes to cell synchronization, pattern formation, and the expansion of cells with a competitive fitness advantage.

• MeSH
• membránové proteiny genetika   metabolismus   MeSH
• proliferace buněk fyziologie   MeSH
• proteinfosfatasy genetika   metabolismus   MeSH
• regulace genové exprese u hub fyziologie   MeSH
• Saccharomyces cerevisiae - proteiny genetika   metabolismus   MeSH
• Saccharomyces cerevisiae genetika   metabolismus   MeSH
• signální transdukce fyziologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Allogeneic transplantation (allo-HCT) is a curative treatment in CLL whose efficacy including the most severe forms had led to the 2006 EBMT recommendations. The advent after 2014 of targeted therapies has revolutionized CLL management, allowing prolonged control to patients who have failed immunochemotherapy and/or have TP53 alterations. We analysed the pre COVID pandemic 2009-2019 EBMT registry. The yearly number of allo-HCT raised to 458 in 2011 yet dropped from 2013 onwards to an apparent plateau above 100. Within the 10 countries who were under the EMA for drug approval and performed 83.5% of those procedures, large initial differences were found but the annual number converged to 2-3 per 10 million inhabitants during the 3 most recent years suggesting that allo-HCT remains applied in selected patients. Long-term follow-up on targeted therapies shows that most patients relapse, some early, with risk factors and resistance mechanisms being described. The treatment of patients exposed to both BCL2 and BTK inhibitors and especially those with double refractory disease will become a challenge in which allo-HCT remains a solid option in competition with emerging therapies that have yet to demonstrate their long-term effectiveness.

• MeSH
• chronická lymfatická leukemie * terapie   MeSH
• COVID-19 * etiologie   MeSH
• homologní transplantace metody   MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• příprava pacienta k transplantaci metody   MeSH
• retrospektivní studie MeSH
• transplantace hematopoetických kmenových buněk * metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The 14-3-3 protein family is a highly conserved and widely distributed group of proteins consisting of multiple isoforms in eukaryotes. Ubiquitously expressed, 14-3-3 proteins play key roles in DNA replication, cell cycle regulation, and apoptosis. The function of 14-3-3 proteins is mediated by interaction with a large number of other proteins and with DNA. It has been demonstrated that 14-3-3γ protein binds strongly to cruciform structures and is crucial for initiating replication. In this study, we analyzed DNA binding properties of the 14-3-3γ isoform to linear and supercoiled DNA. We demonstrate that 14-3-3γ protein binds strongly to long DNA targets, as evidenced by electrophoretic mobility shift assay on agarose gels. Binding of 14-3-3γ to DNA target results in the appearance of blurry, retarded DNA bands. Competition experiments with linear and supercoiled DNA on magnetic beads show very strong preference for supercoiled DNA. We also show by confocal microscopy that 14-3-3 protein in the HCT-116 cell line is co-localized with DNA cruciforms. This implies a role for the 14-3-3γ protein in its binding to local DNA structures which are stabilized by DNA supercoiling.

• MeSH
• Escherichia coli genetika   MeSH
• HCT116 buňky MeSH
• klonování DNA MeSH
• kompetitivní vazba MeSH
• křížová struktura DNA genetika   metabolismus   MeSH
• lidé MeSH
• plazmidy genetika   MeSH
• proteiny 14-3-3 genetika   metabolismus   MeSH
• rekombinantní fúzní proteiny genetika   metabolismus   MeSH
• replikace DNA genetika   MeSH
• retardační test MeSH
• superhelikální DNA genetika   metabolismus   MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• imunodifuze MeSH
• protilátky virové MeSH
• radioimunoanalýza MeSH
• virové proteiny MeSH

BACKGROUND AND AIM: The cytogenetic and diagnostic hallmark of mantle cell lymphoma (MCL) is translocation t(11;14)(q13;q32), resulting in overexpression of cyclin D1. Cyclin D1 expression was analysed in 32 cases of MCL. METHODS: The t(11;14) translocation was detected by fluorescence in situ hybridisation, level of cyclin D1 mRNA by competitive RT-PCR, and level of cyclin D1 and D2 proteins by immunohistochemistry and/or immunoblotting. RESULTS: In 30 cases, the presence of translocation t(11;14), a high level of cyclin D1 mRNA, and a high level of the cyclin D1 protein were confirmed. Two cyclin D1-negative cases overexpressing cyclin D2 were detected by immunoblotting. CONCLUSIONS: There are rare cyclin D1-negative cases of MCL overexpressing cyclin D2. Anti-cyclin D1 antibodies with low specificity can bind both cyclin D1 and cyclin D2, thus providing false cyclin D1-positive signals in immunohistochemical analysis.

• MeSH
• cyklin D1 metabolismus   MeSH
• cyklin D2 metabolismus   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 11 genetika   MeSH
• lidské chromozomy, pár 14 genetika   MeSH
• lymfom z plášťových buněk genetika   metabolismus   MeSH
• nádorové biomarkery metabolismus   MeSH
• nádorové proteiny metabolismus   MeSH
• senioři MeSH
• translokace genetická MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH

The patients with mantle cell lymphoma (MCL) have translocation t(11;14) associated with cyclin D1 overexpression. We observed that iron (an essential cofactor of dioxygenases including prolyl hydroxylases [PHDs]) depletion by deferoxamine blocked MCL cells' proliferation, increased expression of DNA damage marker γH2AX, induced cell cycle arrest and decreased cyclin D1 level. Treatment of MCL cell lines with dimethyloxalylglycine, which blocks dioxygenases involving PHDs by competing with their substrate 2-oxoglutarate, leads to their decreased proliferation and the decrease of cyclin D1 level. We then postulated that loss of EGLN2/PHD1 in MCL cells may lead to down-regulation of cyclin D1 by blocking the degradation of FOXO3A, a cyclin D1 suppressor. However, the CRISPR/Cas9-based loss-of-function of EGLN2/PHD1 did not affect cyclin D1 expression and the loss of FOXO3A did not restore cyclin D1 levels after iron chelation. These data suggest that expression of cyclin D1 in MCL is not controlled by ENGL2/PHD1-FOXO3A pathway and that chelation- and 2-oxoglutarate competition-mediated down-regulation of cyclin D1 in MCL cells is driven by yet unknown mechanism involving iron- and 2-oxoglutarate-dependent dioxygenases other than PHD1. These data support further exploration of the use of iron chelation and 2-oxoglutarate-dependent dioxygenase inhibitors as a novel therapy of MCL.

• MeSH
• aminokyseliny dikarboxylové farmakologie   MeSH
• chelátory železa farmakologie   MeSH
• cyklin D1 metabolismus   MeSH
• deferoxamin farmakologie   MeSH
• deficit železa MeSH
• dioxygenasy antagonisté a inhibitory   metabolismus   MeSH
• down regulace účinky léků   MeSH
• hydroxylace MeSH
• hypoxie buňky účinky léků   MeSH
• inhibitory enzymů farmakologie   MeSH
• kyseliny ketoglutarové farmakologie   MeSH
• lidé MeSH
• lymfom z plášťových buněk enzymologie   MeSH
• messenger RNA genetika   metabolismus   MeSH
• nádorové buněčné linie MeSH
• poškození DNA MeSH
• prolyl-4-hydroxylasy HIF metabolismus   MeSH
• protein FOXO3 genetika   metabolismus   MeSH
• železo MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Bacteria grown on semi-solid media can build two types of multicellular structures, depending on the circumstances. Bodies (colonies) arise when a single clone is grown axenically (germ-free), whereas multispecies chimeric consortia contain monoclonal microcolonies of participants. Growth of an axenic colony, mutual interactions of colonies, and negotiation of the morphospace in consortial ecosystems are results of intricate regulatory and metabolic networks. Multicellular structures developed by Serratia sp. are characteristically shaped and colored, forming patterns that reflect their growth conditions (in particular medium composition and the presence of other bacteria). RESULTS: Building on our previous work, we developed a model system for studying ontogeny of multicellular bacterial structures formed by five Serratia sp. morphotypes of two species grown in either "germ-free" or "gnotobiotic" settings (i.e. in the presence of bacteria of other conspecific morphotype, other Serratia species, or E. coli). Monoclonal bodies show regular and reproducible macroscopic appearance of the colony, as well as microscopic pattern of its growing margin. Standard development can be modified in a characteristic and reproducible manner in close vicinity of other bacterial structures (or in the presence of their products). Encounters of colonies with neighbors of a different morphotype or species reveal relationships of dominance, cooperation, or submission; multiple interactions can be summarized in "rock - paper - scissors" network of interrelationships. Chimerical (mixed) plantings consisting of two morphotypes usually produced a "consortium" whose structure is consistent with the model derived from interaction patterns observed in colonies. CONCLUSIONS: Our results suggest that development of a bacterial colony can be considered analogous to embryogenesis in animals, plants, or fungi: to proceed, early stages require thorough insulation from the rest of the biosphere. Only later, the newly developing body gets connected to the ecological interactions in the biosphere. Mixed "anlagen" cannot accomplish the first, germ-free phase of development; hence, they will result in the consortium of small colonies. To map early development and subsequent interactions with the rest of the biospheric web, simplified gnotobiotic systems described here may turn to be of general use, complementing similar studies on developing multicellular eukaryots under germ-free or gnotobiotic conditions.

• MeSH
• Escherichia coli růst a vývoj   fyziologie   MeSH
• kultivační média chemie   MeSH
• mikrobiální interakce * MeSH
• Serratia růst a vývoj   fyziologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The diffusive gradient in the film technique (DGT) is a new approach to the in-situ determinations of labile metal species in aquatic systems. The DGT device accumulates labile species from solution and therefore contamination problems associated with conventional collection and filtration procedures are eliminated. The technique employs a hydrogel layer to control the diffusive transport of metals to a cation-exchange resin, which is selective for free or weakly complexed metal ion species. This study deals with the use of a new resin based on the Spheron-Oxin® ion exchanger in the DGT technique. The resin with a selectivity for trace metal species higher than Chelex 100 could provide more information on metal speciation in aquatic systems. Its performance was tested for Cd, Cu, Ni and Pb under laboratory conditions. The new resin provides reliable results in the pH range 6-8, independently of ionic strength (25 mmol l-1- 0.6 mol l-1) and also in the presence of Mg(NO3)2 (10 µmol l-1 - 0.05 mol l-1). The effect of iminodiacetic acid, as a model competitive ligand on the metal uptake measured by DGT probe was also assessed.

• MeSH
• financování organizované MeSH
• gely MeSH
• iontoměniče MeSH
• kovy analýza   MeSH
• látky znečišťující životní prostředí analýza   MeSH