The retention and splicing (RES) complex is a conserved spliceosome-associated module that was shown to enhance splicing of a subset of transcripts and promote the nuclear retention of unspliced pre-mRNAs in yeast. The heterotrimeric RES complex is organized around the Snu17p protein that binds to both the Bud13p and Pml1p subunits. Snu17p exhibits an RRM domain that resembles a U2AF homology motif (UHM) and Bud13p harbors a Trp residue reminiscent of an UHM-ligand motif (ULM). It has therefore been proposed that the interaction between Snu17p and Bud13p resembles canonical UHM-ULM complexes. Here, we have used biochemical and NMR structural analysis to characterize the structure of the yeast Snu17p-Bud13p complex. Unlike known UHMs that sequester the Trp residue of the ULM ligand in a hydrophobic pocket, Snu17p and Bud13p utilize a large interaction surface formed around the two helices of the Snu17p domain. In total 18 residues of the Bud13p ligand wrap around the Snu17p helical surface in an U-turn-like arrangement. The invariant Trp(232) in Bud13p is located in the center of the turn, and contacts surface residues of Snu17p. The structural data are supported by mutational analysis and indicate that Snu17p provides an extended binding surface with Bud13p that is notably distinct from canonical UHM-ULM interactions. Our data highlight structural diversity in RRM-protein interactions, analogous to the one seen for nucleic acid interactions.

• MeSH
• Escherichia coli genetika   metabolismus   MeSH
• exprese genu MeSH
• fosforylace MeSH
• fungální RNA biosyntéza   genetika   MeSH
• hydrofobní a hydrofilní interakce MeSH
• interakční proteinové domény a motivy MeSH
• malý jaderný ribonukleoprotein U2 chemie   genetika   metabolismus   MeSH
• molekulární modely MeSH
• molekulární sekvence - údaje MeSH
• prekurzory RNA biosyntéza   genetika   MeSH
• rekombinantní proteiny chemie   genetika   metabolismus   MeSH
• Saccharomyces cerevisiae - proteiny chemie   genetika   metabolismus   MeSH
• Saccharomyces cerevisiae chemie   genetika   metabolismus   MeSH
• sekundární struktura proteinů MeSH
• sekvence aminokyselin MeSH
• sekvenční seřazení MeSH
• sestřih RNA MeSH
• spliceozomy chemie   metabolismus   MeSH
• transportní proteiny chemie   genetika   metabolismus   MeSH
• tryptofan chemie   metabolismus   MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Cíl: Ošetření zlomeniny lícně-čelistního komplexu dlahovou osteosyntézou je v dnešní době považováno za standardní metodu, v odborných kruzích je však stále vedena diskuse nad počtem a umístěním osteosyntetických dlah užitých při ošetření. Ve své práci autoři hodnotí umístění kostních minidlah při ošetření zlomeniny lícně-čelistního komplexu a své závěry porovnávají s dostupnou literaturou. Materiál a metoda: Do pětileté studie bylo zahrnuto 45 pacientů s izolovanou zlomeninou lícně-čelistního komplexu ošetřených osteosyntézou, kterých bylo provedeno celkem 81; jednak z intraorálního přístupu na zygomatikoalveolární kristu a z přístupu extraorálního na dolní a zevní okraj očnice. Zhodnocení bylo provedeno na základě pooperačníno CT vyšetření, kde byl porovnán objem operované a zdravé očnice. Výsledky: Dolní okraj očnice byl zvolen jako místo první volby pro umístění kostních minidlah v 38 případech z 81, zevní okraj očnice v 31 případech, což neodpovídá dostupným literárním údajům. Závěr: I extraorální přístup k ošetření zlomenin lícně-čelistního komplexu je klinicky plně akceptovatelný, jde o kosmeticky vyhovující a funkčně plnohodnotné ošetření.

Aim of the study: Treatment of zygomaticomaxillary complex fractures with osteosynthesis is considered a standard method, however, there still exists a debate over the number and location of osteosynthesis plates used in the treatment among the professional circles. In this work, the authors evaluate the location of bone miniplates in the course of treatment of zygomaticomaxillary complex fractures, the conclusions are compared with the available literature. Material and methods: A total of 45 patients with isolated zygomaticomaxillary complex fractures treated with osteosynthesis were enrolled in the 5-year study; the total number of osteosyntheses was 81, both from intraoral approach to the zygomaticoalveolar region and extraoral approach to the lower and lateral orbital rim. Evaluation was based on postoperative CT scans used to compare the volume of the operated and the healthy orbit. Results: The lower orbital rim was selected as the place of first choice for placement of bone miniplates in 38 out of 81 cases, and the lateral orbital rim was used in 31 cases, which does not correspond with the available literature data. Conclusion: The extraoral approach to treating zygomaticomaxillary complex fractures is fully clinically acceptable, representing a cosmetically and functionally full-fledged treatment.

• MeSH
• fraktury čelisti * diagnostické zobrazování   terapie   MeSH
• fraktury lícní kosti * diagnostické zobrazování   terapie   MeSH
• fraktury očnice diagnostické zobrazování   terapie   MeSH
• klinické zkoušky jako téma MeSH
• kostní destičky využití   MeSH
• lidé MeSH
• vnitřní fixace fraktury * metody   MeSH
• Check Tag
• lidé MeSH

The developmental and epileptic encephalopathies (DEEs) are heterogeneous disorders with a strong genetic contribution, but the underlying genetic etiology remains unknown in a significant proportion of individuals. To explore whether statistical support for genetic etiologies can be generated on the basis of phenotypic features, we analyzed whole-exome sequencing data and phenotypic similarities by using Human Phenotype Ontology (HPO) in 314 individuals with DEEs. We identified a de novo c.508C>T (p.Arg170Trp) variant in AP2M1 in two individuals with a phenotypic similarity that was higher than expected by chance (p = 0.003) and a phenotype related to epilepsy with myoclonic-atonic seizures. We subsequently found the same de novo variant in two individuals with neurodevelopmental disorders and generalized epilepsy in a cohort of 2,310 individuals who underwent diagnostic whole-exome sequencing. AP2M1 encodes the μ-subunit of the adaptor protein complex 2 (AP-2), which is involved in clathrin-mediated endocytosis (CME) and synaptic vesicle recycling. Modeling of protein dynamics indicated that the p.Arg170Trp variant impairs the conformational activation and thermodynamic entropy of the AP-2 complex. Functional complementation of both the μ-subunit carrying the p.Arg170Trp variant in human cells and astrocytes derived from AP-2μ conditional knockout mice revealed a significant impairment of CME of transferrin. In contrast, stability, expression levels, membrane recruitment, and localization were not impaired, suggesting a functional alteration of the AP-2 complex as the underlying disease mechanism. We establish a recurrent pathogenic variant in AP2M1 as a cause of DEEs with distinct phenotypic features, and we implicate dysfunction of the early steps of endocytosis as a disease mechanism in epilepsy.

• MeSH
• adaptorový proteinový komplex - mu-podjednotky genetika   MeSH
• adaptorový proteinový komplex 2 genetika   MeSH
• dítě MeSH
• endocytóza * MeSH
• epilepsie etiologie   patologie   MeSH
• klathrin genetika   metabolismus   MeSH
• kojenec MeSH
• lidé MeSH
• missense mutace * MeSH
• mladiství MeSH
• myši knockoutované MeSH
• myši MeSH
• nemoci mozku etiologie   patologie   MeSH
• neurovývojové poruchy etiologie   patologie   MeSH
• předškolní dítě MeSH
• sekvenování exomu MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• myši MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

In this study, we focused on an analysis of biguanides effects on mitochondrial enzyme activities, mitochondrial membrane potential and membrane permeability transition pore function. We used phenformin, which is more efficient than metformin, and evaluated its effect on rat liver mitochondria and isolated hepatocytes. In contrast to previously published data, we found that phenformin, after a 5 min pre-incubation, dose-dependently inhibits not only mitochondrial complex I but also complex II and IV activity in isolated mitochondria. The enzymes complexes inhibition is paralleled by the decreased respiratory control index and mitochondrial membrane potential. Direct measurements of mitochondrial swelling revealed that phenformin increases the resistance of the permeability transition pore to Ca(2+) ions. Our data might be in agreement with the hypothesis of Schäfer (1976) that binding of biguanides to membrane phospholipids alters membrane properties in a non-specific manner and, subsequently, different enzyme activities are modified via lipid phase. However, our measurements of anisotropy of fluorescence of hydrophobic membrane probe diphenylhexatriene have not shown a measurable effect of membrane fluidity with the 1 mM concentration of phenformin that strongly inhibited complex I activity. Our data therefore suggest that biguanides could be considered as agents with high efficacy but low specifity.

• MeSH
• biguanidy farmakologie   MeSH
• fenformin farmakologie   MeSH
• inhibitory enzymů farmakologie   MeSH
• jaterní mitochondrie účinky léků   enzymologie   MeSH
• krysa rodu rattus MeSH
• metformin farmakologie   MeSH
• potkani Wistar MeSH
• respirační komplex I antagonisté a inhibitory   fyziologie   MeSH
• respirační komplex II antagonisté a inhibitory   fyziologie   MeSH
• respirační komplex IV antagonisté a inhibitory   fyziologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Studie se zúčastnilo osmnáct probandů - nemocných RS. Experimentální skupina byla po dobu šesti týdnů podrobena komplexnímu fyzioterapeutickému programu, jehož součástí byla aerobní zátěž. Kontrolní skupina dodržovala dosavadní zvyklosti. U probandů experimentální skupiny došlo ke zvýšení fyzické kondice (zátěžové vyšetření na rumpálovém ergometru) a snížení únavy (Modified Fatigue hnpact Scale).

18 patients with multiple sclerosis had participated on this study. Experiemtnal group underwent during a period of 6 weeks to a complex physiotherapeutic program, parts of which was aerobic load. Increasing of physical shape (investigation of load with the help of ergometer) and fatigue decrease (Modified Fatigue Impact Scale) were observed in members of control group.

• MeSH
• dospělí MeSH
• ergometrie metody   MeSH
• lidé MeSH
• roztroušená skleróza MeSH
• tělesná výkonnost MeSH
• únava diagnóza   rehabilitace   terapie   MeSH
• zátěžový test metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• srovnávací studie MeSH

Light quality significantly influences plant metabolism, growth and development. Recently, we have demonstrated that leaves of barley and other plant species grown under monochromatic green light (500-590 nm) accumulated a large pool of chlorophyll a (Chl a) intermediates with incomplete hydrogenation of their phytyl chains. In this work, we studied accumulation of these geranylgeranylated Chls a and b in pigment-protein complexes (PPCs) of Arabidopsis plants acclimated to green light and their structural-functional consequences on the photosynthetic apparatus. We found that geranylgeranylated Chls are present in all major PPCs, although their presence was more pronounced in light-harvesting complex II (LHCII) and less prominent in supercomplexes of photosystem II (PSII). Accumulation of geranylgeranylated Chls hampered the formation of PSII and PSI super- and megacomplexes in the thylakoid membranes as well as their assembly into chiral macrodomains; it also lowered the temperature stability of the PPCs, especially that of LHCII trimers, which led to their monomerization and an anomaly in the photoprotective mechanism of non-photochemical quenching. Role of geranylgeranylated Chls in adverse effects on photosynthetic apparatus of plants acclimated to green light is discussed.

• MeSH
• adaptace oční fyziologie   MeSH
• Arabidopsis metabolismus   MeSH
• chlorofyl metabolismus   MeSH
• fotosystém II (proteinový komplex) metabolismus   MeSH
• prenylace MeSH
• světlosběrné proteinové komplexy metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH

The extrinsic PsbU and PsbV proteins are known to play a critical role in stabilizing the Mn4CaO5 cluster of the PSII oxygen-evolving complex (OEC). However, most isolates of the marine cyanobacterium Prochlorococcus naturally miss these proteins, even though they have kept the main OEC protein, PsbO. A structural homology model of the PSII of such a natural deletion mutant strain (P. marinus MED4) did not reveal any obvious compensation mechanism for this lack. To assess the physiological consequences of this unusual OEC, we compared oxygen evolution between Prochlorococcus strains missing psbU and psbV (PCC 9511 and SS120) and two marine strains possessing these genes (Prochlorococcus sp. MIT9313 and Synechococcus sp. WH7803). While the low light-adapted strain SS120 exhibited the lowest maximal O2 evolution rates (Pmax per divinyl-chlorophyll a, per cell or per photosystem II) of all four strains, the high light-adapted strain PCC 9511 displayed even higher PChlmax and PPSIImax at high irradiance than Synechococcus sp. WH7803. Furthermore, thermoluminescence glow curves did not show any alteration in the B-band shape or peak position that could be related to the lack of these extrinsic proteins. This suggests an efficient functional adaptation of the OEC in these natural deletion mutants, in which PsbO alone is seemingly sufficient to ensure proper oxygen evolution. Our study also showed that Prochlorococcus strains exhibit negative net O2 evolution rates at the low irradiances encountered in minimum oxygen zones, possibly explaining the very low O2 concentrations measured in these environments, where Prochlorococcus is the dominant oxyphototroph.

• MeSH
• bakteriální proteiny chemie   genetika   fyziologie   MeSH
• chlorofyl metabolismus   MeSH
• fotosyntéza fyziologie   MeSH
• fotosystém II (proteinový komplex) chemie   genetika   fyziologie   MeSH
• genom bakteriální MeSH
• kyslík metabolismus   MeSH
• molekulární modely MeSH
• průtoková cytometrie MeSH
• sinice genetika   metabolismus   MeSH
• světlo MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

The major light-harvesting complex of Amphidinium (A.) carterae, chlorophyll-a-chlorophyll-c 2-peridinin-protein complex (acpPC), was studied using ultrafast pump-probe spectroscopy at low temperature (60 K). An efficient peridinin-chlorophyll-a energy transfer was observed. The stimulated emission signal monitored in the near-infrared spectral region was stronger when redder part of peridinin pool was excited, indicating that these peridinins have the S1/ICT (intramolecular charge-transfer) state with significant charge-transfer character. This may lead to enhanced energy transfer efficiency from "red" peridinins to chlorophyll-a. Contrary to the water-soluble antenna of A. carterae, peridinin-chlorophyll-a protein, the energy transfer rates in acpPC were slower under low-temperature conditions. This fact underscores the influence of the protein environment on the excited-state dynamics of pigments and/or the specificity of organization of the two pigment-protein complexes.

• MeSH
• blízká infračervená spektroskopie * MeSH
• časové faktory MeSH
• chlorofyl metabolismus   MeSH
• Dinoflagellata metabolismus   MeSH
• elektrony MeSH
• karotenoidy metabolismus   MeSH
• kinetika MeSH
• nízká teplota * MeSH
• přenos energie MeSH
• světlosběrné proteinové komplexy metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Metastatic cancer remains a formidable challenge in anticancer therapy. Despite efforts to develop effective antimetastasis drugs over the past half-century, currently approved treatments fall short of expectations. This report highlights the promising antiproliferative activity of a ruthenium-based therapeutic agent, namely dichlorido(p-cymene)[2-amino-4-(pyridin-3-yl)-4H-benzo[h]-chromene-3-carbonitrile]ruthenium(II) (complex 1) against metastatic cell lines. Complex 1 shows significant efficacy in metastatic LoVo and Du-145 cell lines at nanomolar concentrations, being markedly more active than clinically used anticancer cisplatin. Studies on the MDA-MB-231 cell line, which displays invasive characteristics, demonstrated that 1 significantly reduces cell invasion. This efficacy was confirmed by its impact on matrix metalloproteinase production in MDA-MB-231 cells. Given that cell migration drives cancer invasion and metastasis, complex 1's effect on MDA-MB-231 cell migration was evaluated via wound healing assay and vimentin network analysis. Results indicated a strong reduction in migration. A re-adhesion assay further demonstrated that 1 significantly lowers the re-adhesion ability of MDA-MB-231 cells compared to cisplatin. To better simulate the human body environment, a 3D spheroid invasion assay was used. This method showed that 1 effectively inhibits tumor spheroids from infiltrating the surrounding extracellular matrix. This study underscores the potential of (arene)ruthenium(II) complexes with naphthopyran ligands as potent antimetastatic agents for chemotherapy.

• MeSH
• buněčná adheze účinky léků   MeSH
• komplexní sloučeniny * farmakologie   chemie   terapeutické užití   MeSH
• lidé MeSH
• metastázy nádorů prevence a kontrola   farmakoterapie   MeSH
• nádorové buněčné linie MeSH
• pohyb buněk * účinky léků   MeSH
• proliferace buněk účinky léků   MeSH
• protinádorové látky * farmakologie   chemie   terapeutické užití   MeSH
• ruthenium * chemie   farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The functional role of CD36 protein detected in mitochondrial fractions in long chain fatty acid (LCFA) oxidation is unclear due to conflicting results obtained in Cd36 knockout mice and experiments using sulfo-N-succinimidyl oleate (SSO) for inhibition of CD36 mediated LCFA transport. We investigated effect of SSO on mitochondrial respiration and found that SSO substantially inhibits not only LCFA oxidation, but also oxidation of flavoprotein- and NADH-dependent substrates and generation of mitochondrial membrane potential. Experiments in rat liver, heart and kidney mitochondria demonstrated a direct effect on mitochondrial respiratory chain with the most pronounced inhibition of the complex III (IC(50) 4microM SSO). The results presented here show that SSO is a potent and irreversible inhibitor of mitochondrial respiratory chain. Copyright 2010. Published by Elsevier Inc.

• MeSH
• antigeny CD36 genetika   metabolismus   účinky léků   MeSH
• biologický transport účinky léků   MeSH
• buněčné dýchání účinky léků   MeSH
• krysa rodu rattus MeSH
• kyseliny olejové farmakologie   MeSH
• mastné kyseliny metabolismus   MeSH
• membránový potenciál mitochondrií účinky léků   MeSH
• mitochondrie enzymologie   účinky léků   MeSH
• myši knockoutované MeSH
• myši MeSH
• potkani inbrední WKY MeSH
• respirační komplex III antagonisté a inhibitory   MeSH
• sukcinimidy farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH