In mammals, RNA interference (RNAi) was historically studied as a cytoplasmic event; however, in the last decade, a growing number of reports convincingly show the nuclear localization of the Argonaute (AGO) proteins. Nevertheless, the extent of nuclear RNAi and its implication in biological mechanisms remain to be elucidated. We found that reduced Lamin A levels significantly induce nuclear influx of AGO2 in SHSY5Y neuroblastoma and A375 melanoma cancer cell lines, which normally have no nuclear AGO2. Lamin A KO manifested a more pronounced effect in SHSY5Y cells compared to A375 cells, evident by changes in cell morphology, increased cell proliferation, and oncogenic miRNA expression. Moreover, AGO fPAR-CLIP in Lamin A KO SHSY5Y cells revealed significantly reduced RNAi activity. Further exploration of the nuclear AGO interactome by mass spectrometry identified FAM120A, an RNA-binding protein and known interactor of AGO2. Subsequent FAM120A fPAR-CLIP, revealed that FAM120A co-binds AGO targets and that this competition reduces the RNAi activity. Therefore, loss of Lamin A triggers nuclear AGO2 translocation, FAM120A mediated RNAi impairment, and upregulation of oncogenic miRNAs, facilitating cancer cell proliferation.

• MeSH
• aktivní transport - buněčné jádro MeSH
• Argonaut proteiny * metabolismus   genetika   MeSH
• buněčné jádro * metabolismus   MeSH
• lamin typ A * metabolismus   genetika   MeSH
• lidé MeSH
• melanom genetika   metabolismus   patologie   MeSH
• mikro RNA * metabolismus   genetika   MeSH
• nádorové buněčné linie MeSH
• proliferace buněk * genetika   MeSH
• proteiny vázající RNA metabolismus   genetika   MeSH
• RNA interference * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• gestalt teorie MeSH
• psychologie MeSH

• Konspekt
• Psychologie
• NLK Obory
• psychologie, klinická psychologie
• NLK Publikační typ
• učebnice vysokých škol

The authors obtained behavioral observations and personality ratings for 27 free-ranging Hanuman langur males. Subjects were rated using a questionnaire based on the human Five-Factor Model (FFM). Behavioral observations were taken over 5 months using an ethogram that included 50 behaviors. Principal Component Analysis (PCA) of ratings revealed Agreeableness_(R), Confidence_(R), and Extraversion_(R) components. Each personality dimension was associated with a unique set of observed behaviors. PCA of 36 behavioral indices revealed Dominance_(B), Involvement_(B), and Activity_(B) components. Bivariate correlations showed that Agreeableness_(R) was negatively correlated with Dominance_(B); Confidence_(R) was positively correlated with Dominance_(B) and Involvement_(B) but negatively correlated with Activity_(B); and Extraversion_(R) was positively correlated with Activity_(B). Dominance rank was positively correlated with Confidence_(R) and Dominance_(B) but negatively correlated with Agreeableness_(R) and Activity_(B). These results highlight the comparability of behavioral coding and personality ratings and suggest that some aspects of personality structure were present in the common ancestor of Old World monkeys. (PsycINFO Database Record (c) 2008 APA, all rights reserved).

• MeSH
• biologická evoluce MeSH
• Cercopithecidae psychologie   MeSH
• chování zvířat MeSH
• druhová specificita MeSH
• lidé MeSH
• osobnost MeSH
• pohybová aktivita MeSH
• sociální chování MeSH
• sociální dominance MeSH
• sociální prostředí MeSH
• testování osobnosti MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH
• srovnávací studie MeSH

BACKGROUND: Activation of the type I interferon (IFN) response program is described for several autoimmune diseases, including systemic lupus erythematosus (SLE), multiple sclerosis (MS), myositis (IIM) and rheumatoid arthritis (RA). While IFNα contributes to SLE pathology, IFNβ therapy is often beneficial in MS, implying different immunoregulatory roles for these IFNs. This study was aimed to investigate potential diversification of IFNα-and IFNβ-mediated response programs in autoimmune diseases. METHODS: Peripheral blood gene expression of 23 prototypical type I IFN response genes (IRGs) was determined in 54 healthy controls (HCs), 69 SLE (47 test, 22 validation), 149 IFNβ-treated MS (71 test, 78 validation), 160 untreated MS, 78 IIM and 76 RA patients. Patients with a type I IFN signature were selected for analysis. RESULTS: We identified IFNα- and IFNβ-specific response programs (GC-A and GC-B, respectively) in SLE and IFNβ-treated MS patients. Concordantly, the GC-A/GC-B log-ratio was positive for all SLE patients and negative for virtually all IFNβ-treated MS patients, which was confirmed in additional cohorts. Applying this information to other autoimmune diseases, IIM patients displayed positive GC-A/GC-B log-ratios, indicating predominant IFNα activity. The GC-A/GC-B log-ratio in RA was lower and approached zero in part of the patients, implying relative importance of both clusters. Remarkably, GC-A/GC-B log-ratios appeared most heterogeneous in untreated MS; half of the patients displayed GC-A dominance, whereas others showed GC-B dominance or log-ratios near zero. CONCLUSIONS: Our findings show diversification of the type I IFN response in autoimmune diseases, suggesting different pathogenic roles of the type I IFNs.

• MeSH
• autoimunitní nemoci krev   farmakoterapie   imunologie   MeSH
• dospělí MeSH
• interferon alfa terapeutické užití   MeSH
• interferon beta terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• roztroušená skleróza krev   farmakoterapie   imunologie   MeSH
• senioři MeSH
• systémový lupus erythematodes krev   farmakoterapie   imunologie   MeSH
• výsledek terapie 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

Invazivní meningokoková onemocnění (IMO) jsou celosvětově významnou příčinou morbidity i mortality především u malých dětí. V řadě vyspělých zemí včetně celé Evropy i České republiky dominuje séroskupina B, proti které ještě donedávna nebyla k dispozici žádná plošně použitelná vakcína. V roce 2013 byla v Evropě registrována 4komponentní proteinová vakcína proti meningokoku B (4CMenB; Bexsero) a v USA jsou již dnes vakcíny k dispozici dvě. Jejich zavádění do národních imunizačních programů je velmi pomalé. Celosvětově bylo zatím distribuováno přes 1 milion dávek vakcíny v 19 zemích světa (1).

Invasive meningococcal disease causes significant morbidity and mortality globally, especially in small children. In many devoloped countries, whole Europe and the Czech Republic included, serogroup B dominates, against which no generally usable vaccine had been available until recently. 4-component meningococcal B protein vaccine (4CMenB; Bexsero) was licensed in Europe in 2013 and in the USA there already are two meningococcal B vaccines available. But their introduction into national immunisation schedules is very slow. Globally more than 1 million doses have been distributed in 19 countries (1).

• Klíčová slova
• národní imunizační program,
• MeSH
• analýza nákladů a výnosů MeSH
• kojenec MeSH
• lidé MeSH
• meningokokové infekce * epidemiologie   prevence a kontrola   MeSH
• meningokokové vakcíny * ekonomika   terapeutické užití   MeSH
• mladiství MeSH
• Neisseria meningitidis séroskupiny B MeSH
• očkovací programy * ekonomika   MeSH
• vakcinace ekonomika   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• přehledy MeSH
• Geografické názvy
• Česká republika MeSH
• Německo MeSH
• Spojené království MeSH
• Spojené státy americké MeSH