Nuclear actin plays an important role in such processes as chromatin remodeling, transcriptional regulation, RNA processing, and nuclear export. Recent research has demonstrated that actin in the nucleus probably exists in dynamic equilibrium between monomeric and polymeric forms, and some of the actin-binding proteins, known to regulate actin dynamics in cytoplasm, have been also shown to be present in the nucleus. In this paper, we present ultrastructural data on distribution of actin and various actin-binding proteins (alpha-actinin, filamin, p190RhoGAP, paxillin, spectrin, and tropomyosin) in nuclei of HeLa cells and resting human lymphocytes. Probing extracts of HeLa cells for the presence of actin-binding proteins also confirmed their presence in nuclei. We report for the first time the presence of tropomyosin and p190RhoGAP in the cell nucleus, and the spatial colocalization of actin with spectrin, paxillin, and alpha-actinin in the nucleolus.

• MeSH
• aktinin MeSH
• aktiny analýza   MeSH
• buněčné jádro chemie   ultrastruktura   MeSH
• financování organizované MeSH
• HeLa buňky MeSH
• jaderné proteiny analýza   MeSH
• lidé MeSH
• lymfocyty chemie   ultrastruktura   MeSH
• mikrofilamentové proteiny analýza   MeSH
• paxilin MeSH
• proteiny aktivující GTPasu MeSH
• spektrin MeSH
• tropomyosin MeSH
• Check Tag
• lidé MeSH

The activity of cyclin-dependent kinases (cdks) depends on the phosphorylation of a residue corresponding to threonine 161 in human p34cdc2. One enzyme responsible for phosphorylating this critical residue has recently been purified from Xenopus and starfish. It was termed CAK (for cdk-activating kinase), and it was shown to contain p40MO15 as its catalytic subunit. In view of the cardinal role of cdks in cell cycle control, it is important to learn if and how CAK activity is regulated during the somatic cell cycle. Here, we report a molecular characterization of a human p40MO15 homologue and its associated CAK activity. We have cloned and sequenced a cDNA coding for human p40MO15, and raised specific polyclonal and monoclonal antibodies against the corresponding protein expressed in Escherichia coli. These tools were then used to demonstrate that p40MO15 protein expression and CAK activity are constant throughout the somatic cell cycle. Gel filtration suggests that active CAK is a multiprotein complex, and immunoprecipitation experiments identify two polypeptides of 34 and 32 kD as likely complex partners of p40MO15. The association of the three proteins is near stoichiometric and invariant throughout the cell cycle. Immunocytochemistry and biochemical enucleation experiments both demonstrate that p40MO15 is nuclear at all stages of the cell cycle (except for mitosis, when the protein redistributes throughout the cell), although the p34cdc2/cyclin B complex, one of the major purported substrates of CAK, occurs in the cytoplasm until shortly before mitosis. The absence of obvious changes in CAK activity in exponentially growing cells constitutes a surprise. It suggests that the phosphorylation state of threonine 161 in p34cdc2 (and the corresponding residue in other cdks) may be regulated primarily by the availability of the cdk/cyclin substrates, and by phosphatase(s).

• MeSH
• buněčné jádro enzymologie   MeSH
• buněčný cyklus * MeSH
• cyklin-dependentní kinasy * MeSH
• cykliny metabolismus   MeSH
• fosforylace MeSH
• G1 fáze MeSH
• gelová chromatografie MeSH
• HeLa buňky MeSH
• klonování DNA MeSH
• komplementární DNA chemie   genetika   MeSH
• lidé MeSH
• mitóza MeSH
• molekulární sekvence - údaje MeSH
• protein-serin-threoninkinasy chemie   genetika   metabolismus   MeSH
• proteinkinasa CDC2 metabolismus   MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Adipokinetic hormones (AKHs) are a group of insect metabolic neurohormones, synthesized and released from an endocrine retrocerebral gland, the corpus cardiacum (CC). Small amounts of AKH have also been identified in the brain, although their role in this organ is not clear. To address this gap in the knowledge about insect brain biology, we studied the nucleotide sequence, tissue distribution, and subcellular localization of AKHs in the brain and CC of the firebug Pyrrhocoris apterus. This insect expresses two AKHs; the octapeptides Pyrap-AKH and Peram-CAH-II, the presence of which was documented in the both studied organs. In situ hybridization and quantitative reverse-transcription (q-RT)-PCR revealed the expression of the genes encoding for both AKHs not only in the CC, but also in brain. Electron microscopy analysis of the brain revealed the presence of these hormones in specialized secretory granules localized predominantly in the cellular bodies of neurons. The hormones might be transported from the granules into the axons, where they could play a role in neuronal signaling. Under acute stress induced by the injection of 3μmol KCl, the level of AKHs in the brain increased to a greater extent than that in the CC. These results might indicate an enhanced role of brain-derived AKHs in defence reaction under acute stress situations.

• MeSH
• centrální nervový systém metabolismus   ultrastruktura   MeSH
• exprese genu MeSH
• fyziologický stres genetika   MeSH
• Heteroptera * genetika   metabolismus   ultrastruktura   MeSH
• hmyzí hormony genetika   metabolismus   MeSH
• klonování DNA MeSH
• kyselina pyrrolidonkarboxylová analogy a deriváty   metabolismus   MeSH
• molekulární sekvence - údaje MeSH
• oligopeptidy genetika   metabolismus   MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• sekvenční homologie aminokyselin MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Bacterial proteins exhibiting two or more unrelated functions, referred to as moonlighting proteins, are suggested to contribute to full virulence manifestation in pathogens. An expanding number of published studies have revealed the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to be a multitasking protein with virulence impact in a number of pathogenic bacteria. This protein can be detected on the bacterial surface or outside the bacterial cell, where it interacts with host proteins. In this way, GAPDH is able to modulate various pathogenic processes. Moreover, it has been shown to be involved in non-enzymatic processes inside the bacterial cell. In this mini review, we summarize main findings concerning the multiple localization and protein interactions of GAPDH derived from bacterial pathogens of humans. We also briefly discuss problems associated with using GAPDH as a vaccine antigen and endeavor to inspire further research to fill gaps in the existing knowledge.

• MeSH
• Bacteria enzymologie   patogenita   MeSH
• bakteriální infekce mikrobiologie   prevence a kontrola   MeSH
• bakteriální proteiny metabolismus   MeSH
• bakteriální vakcíny imunologie   MeSH
• glyceraldehyd-3-fosfátdehydrogenasy imunologie   metabolismus   MeSH
• lidé MeSH
• proteiny metabolismus   MeSH
• vazba proteinů MeSH
• virulence MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

TRAIL, a ligand of the TNFalpha family, induces upon binding to its pro-death receptors TRAIL-R1/DR4 and TRAIL-R2/DR5 the apoptosis of cancer cells. Activated receptors incite the formation of the Death-Inducing Signaling Complex followed by the activation of the downstream apoptotic signaling. TRAIL-induced apoptosis is regulated at multiple levels, one of them being the presence and relative number of TRAIL pro- and anti-apoptotic receptors on the cytoplasmic membrane. In a yeast two-hybrid search for proteins that interact with the intracellular part (ICP) of DR4, we picked ARAP1, an adapter protein with ArfGAP and RhoGAP activities. In yeast, DR4(ICP) interacts with the alternatively spliced ARAP1 lacking 11 amino acids from the PH5 domain. Transfected ARAP1 co-precipitates with DR4 and co-localizes with it in the endoplasmic reticulum/Golgi, at the cytoplasmic membrane and in early endosomes of TRAIL-treated cells. ARAP1 knockdown significantly compromises the localization of DR4 at the cell surface of several tumor cell lines and slows down their TRAIL-induced death. ARAP1 overexpressed in HEL cells does not affect their TRAIL-induced apoptosis or the membrane localization of DR4, but it enhances the cell-surface presentation of phosphatidyl serine. Our data indicate that ARAP1 is likely involved in the regulation of the cell-specific trafficking of DR4 and might thus affect the efficacy of TRAIL-induced apoptosis.

• MeSH
• apoptóza účinky léků   MeSH
• buněčná membrána metabolismus   MeSH
• buněčné linie MeSH
• down regulace MeSH
• financování organizované MeSH
• lidé MeSH
• malá interferující RNA farmakologie   MeSH
• mapování interakce mezi proteiny MeSH
• nádorové buněčné linie MeSH
• protein TRAIL metabolismus   MeSH
• proteiny aktivující GTPasu fyziologie   MeSH
• receptory TNF metabolismus   MeSH
• techniky dvojhybridového systému MeSH
• transport proteinů fyziologie   MeSH
• transportní proteiny fyziologie   MeSH
• Check Tag
• lidé MeSH

• MeSH
• acidobazická rovnováha MeSH
• aminy MeSH
• anestetika lokální chemie   MeSH
• fosfolipidy MeSH
• membrány MeSH
• povrchově aktivní látky MeSH
• vodní a elektrolytová rovnováha MeSH

This study explored unmet mental health and social care needs in the Slovak Republic and their adverse human rights consequences. We estimated treatment gap for persons aged 15-64 years in year 2015 affected by depressive, anxiety, substance use and schizophrenic disorders by comparing local treated prevalence rates with population estimated rates for Europe. Two-thirds of people with depressive disorders and over 80% of those with anxiety disorders and alcohol dependence were not receiving treatment. There was no treatment gap for persons with schizophrenia. Fifty-one percent of those eligible for disability pension on the grounds of mental disorders failed to receive it. We discuss the implications of the estimated gaps in mental health and social care and consequent human rights violations that may result from the current system of mental health care in Slovakia.

• MeSH
• databáze faktografické MeSH
• disparity zdravotní péče * MeSH
• dospělí MeSH
• duševní poruchy MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidská práva zákonodárství a právo   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• odhad potřeb * MeSH
• senioři MeSH
• služby péče o duševní zdraví * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Slovenská republika MeSH

The mammalian ventricular myocardium forms a functional syncytium due to flow of electrical current mediated in part by gap junctions localized within intercalated disks. The connexin (Cx) subunit of gap junctions have direct and indirect roles in conduction of electrical impulse from the cardiac pacemaker via the cardiac conduction system (CCS) to working myocytes. Cx43 is the dominant isoform in these channels. We have studied the distribution of Cx43 junctions between the CCS and working myocytes in a transgenic mouse model, which had the His-Purkinje portion of the CCS labeled with green fluorescence protein. The highest number of such connections was found in a region about one-third of ventricular length above the apex, and it correlated with the peak proportion of Purkinje fibers (PFs) to the ventricular myocardium. At this location, on the septal surface of the left ventricle, the insulated left bundle branch split into the uninsulated network of PFs that continued to the free wall anteriorly and posteriorly. The second peak of PF abundance was present in the ventricular apex. Epicardial activation maps correspondingly placed the site of the first activation in the apical region, while some hearts presented more highly located breakthrough sites. Taken together, these results increase our understanding of the physiological pattern of ventricular activation and its morphological underpinning through detailed CCS anatomy and distribution of its gap junctional coupling to the working myocardium.

• MeSH
• konexin 43 fyziologie   MeSH
• mezerový spoj fyziologie   MeSH
• mezibuněčná komunikace * MeSH
• myši MeSH
• perikard cytologie   fyziologie   MeSH
• Purkyňova vlákna cytologie   fyziologie   MeSH
• srdeční komory patologie   MeSH
• svalové buňky cytologie   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• acidobazická rovnováha účinky záření   MeSH
• anestetika lokální toxicita   MeSH
• dýchání účinky léků   MeSH
• králíci MeSH
• Check Tag
• králíci MeSH
• Publikační typ
• srovnávací studie MeSH