• Publikační typ
• abstrakty MeSH

BACKGROUND: There is limited information on the mode of arrhythmia initiation in idiopathic ventricular fibrillation (IVF). A non-pause-dependent mechanism has been suggested to be the rule. OBJECTIVES: The aim of this study was to assess the mode and characteristics of initiation of polymorphic ventricular tachycardia (PVT) in patients with short or long-coupled PVT/IVF included in THESIS (THerapy Efficacy in Short or long-coupled idiopathic ventricular fibrillation: an International Survey), a multicenter study involving 287 IVF patients treated with drugs or radiofrequency ablation. METHODS: We reviewed the initiation of 410 episodes of ≥1 PVT triplet in 180 patients (58.3% females; age 39.6 ± 13.6 years) with IVF. The incidence of pause-dependency arrhythmia initiation (prolongation by >20 ms of the preceding cycle length) was assessed. RESULTS: Most arrhythmias (n = 295; 72%) occurred during baseline supraventricular rhythm without ambient premature ventricular complexes (PVCs), whereas 106 (25.9%) occurred during baseline rhythm including PVCs. Nine (2.2%) arrhythmias occurred during atrial/ventricular pacing and were excluded from further analysis. Mode of PVT initiation was pause-dependent in 45 (15.6%) and 64 (60.4%) of instances in the first and second settings, respectively, for a total of 109 of 401 (27.2%). More than one type of pause-dependent and/or non-pause-dependent initiation (mean: 2.6) occurred in 94.4% of patients with ≥4 events. Coupling intervals of initiating PVCs were <350 ms, 350-500 ms, and >500 ms in 76.6%, 20.72%, and 2.7% of arrhythmia initiations, respectively. CONCLUSIONS: Pause-dependent initiation occurred in more than a quarter of arrhythmic episodes in IVF patients. PVCs having long (between 350 and 500 ms) and very long (>500 ms) coupling intervals were observed at the initiation of nearly a quarter of PVT episodes.

• MeSH
• dospělí MeSH
• elektrokardiografie MeSH
• fibrilace komor * epidemiologie   MeSH
• katetrizační ablace MeSH
• komorová tachykardie patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Zástava srdeční a dechové funkce je velmi závažným problémem ústícím v úhyn pacienta. Můžeme se s ní setkat v rámci kolapsu pacienta souvisejícím s probíhajícím onemocněním nebo jako s komplikací při sedaci nebo anestezii pacienta. řešení zástavy vyžaduje rychlé zhodnocení životních funkcí zvířete s okamžitým zahájením kardiopulmonální resuscitace, a to zejména nepřímou srdeční masáží a asistovaným dýcháním. Zvládnutí postupu při kardiopulmonální resuscitaci (CPR) včetně tréninku veterinárních sester a veterinárních lékařů dané ambulance/kliniky, technické vybavení pracoviště a připravenost léčiv výrazně zvyšuje šance pacienta na přežití. Velmi důležité je předoperační vyšetření zvířete, které minimalizuje vznik neočekávaných komplikací v průběhu sedace nebo anestezie. Včasným rozpoznáním komplikací při anestezii (apnoe se srdeční akcí) a bezprostředním řešením problému lze v mnoha případech pacienta zachránit. Cílem článku je seznámit veterinární lékaře s postupem při resuscitaci drobných savců s přihlédnutím k specifické anatomii a fyziologii.

Cardiopulmonary arrest (CPA) is a life-threatening problem which quickly leads to the patient‘s death. CPA is a result of acute or chronic disease, or is associated with anaesthetic complication. Therapy of the CPA consists of quick life function evaluation and immediate initiation of cardiopulmonary resuscitation (CPR), especially chest compression and artificial ventilation. The chance of successful CPR is strongly dependent on training of professionals (veterinary doctors and nurses), technical equipment and drug preparedness and availability. Preoperative clinical examination is in small mammals particularly important, as it minimizes possible risks during sedation or anaesthesia. The earlier id the anaesthetic complication recognized (apnoeic pause), the quicker is CPR started and the better is prognosis. The aim of the article is to describe CPR in small mammals and its specific anatomy and physiology.

• MeSH
• domácí zvířata MeSH
• fretky MeSH
• kardiopulmonální resuscitace * metody   MeSH
• králíci MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH

N6-Methyladenosine (m6A) is the predominant internal RNA modification in eukaryotic messenger RNAs (mRNAs) and plays a crucial role in mRNA stability. Here, using human cells, we reveal that m6A sites in the coding sequence (CDS) trigger CDS-m6A decay (CMD), a pathway that is distinct from previously reported m6A-dependent degradation mechanisms. Importantly, CDS m6A sites act considerably faster and more efficiently than those in the 3' untranslated region, which to date have been considered the main effectors. Mechanistically, CMD depends on translation, whereby m6A deposition in the CDS triggers ribosome pausing and transcript destabilization. The subsequent decay involves the translocation of the CMD target transcripts to processing bodies (P-bodies) and recruitment of the m6A reader protein YT521-B homology domain family protein 2 (YTHDF2). Our findings highlight CMD as a previously unknown pathway, which is particularly important for controlling the expression of developmental regulators and retrogenes.

• MeSH
• 3' nepřekládaná oblast MeSH
• adenosin * analogy a deriváty   metabolismus   genetika   MeSH
• HEK293 buňky MeSH
• HeLa buňky MeSH
• lidé MeSH
• messenger RNA * genetika   metabolismus   MeSH
• otevřené čtecí rámce * MeSH
• proteiny vázající RNA * genetika   metabolismus   MeSH
• proteosyntéza * MeSH
• ribozomy metabolismus   genetika   MeSH
• stabilita RNA * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The 6C RNA family is a class of small RNAs highly conserved in Actinobacteria, including the genera Mycobacterium, Streptomyces and Corynebacterium whose physiological function has not yet been elucidated. We found that strong transcription of the cgb_03605 gene, which encodes 6C RNA in C. glutamicum, was driven by the SigA- and SigB-dependent promoter Pcgb_03605. 6C RNA was detected at high level during exponential growth phase (180 to 240 molcules per cell) which even increased at the entry of the stationary phase. 6C RNA level did not decrease within 240 min after transcription had been stopped with rifampicin, which suggests high 6C RNA stability. The expression of cgb_03605 further increased approximately twofold in the presence of DNA-damaging mitomycin C (MMC) and nearly threefold in the absence of LexA. Deletion of the 6C RNA gene cgb_03605 resulted in a higher sensitivity of C. glutamicum toward MMC and UV radiation. These results indicate that 6C RNA is involved in the DNA damage response. Both 6C RNA level-dependent pausing of cell growth and branched cell morphology in response to MMC suggest that 6C RNA may also be involved in a control of cell division.

• MeSH
• bakteriální RNA genetika   MeSH
• Corynebacterium glutamicum genetika   růst a vývoj   metabolismus   MeSH
• genetická transkripce MeSH
• malá nekódující RNA chemie   genetika   MeSH
• promotorové oblasti (genetika) MeSH
• regulace genové exprese u bakterií MeSH
• sekvence nukleotidů MeSH
• sigma faktor metabolismus   MeSH
• SOS odpověď (genetika) genetika   MeSH
• stabilita RNA MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Pervasive transcription is a widespread phenomenon leading to the production of a plethora of non-coding RNAs (ncRNAs) without apparent function. Pervasive transcription poses a threat to proper gene expression that needs to be controlled. In yeast, the highly conserved helicase Sen1 restricts pervasive transcription by inducing termination of non-coding transcription. However, the mechanisms underlying the specific function of Sen1 at ncRNAs are poorly understood. Here, we identify a motif in an intrinsically disordered region of Sen1 that mimics the phosphorylated carboxy-terminal domain (CTD) of RNA polymerase II, and structurally characterize its recognition by the CTD-interacting domain of Nrd1, an RNA-binding protein that binds specific sequences in ncRNAs. In addition, we show that Sen1-dependent termination strictly requires CTD recognition by the N-terminal domain of Sen1. We provide evidence that the Sen1-CTD interaction does not promote initial Sen1 recruitment, but rather enhances Sen1 capacity to induce the release of paused RNAPII from the DNA. Our results shed light on the network of protein-protein interactions that control termination of non-coding transcription by Sen1.

• MeSH
• DNA-helikasy chemie   metabolismus   MeSH
• fungální RNA metabolismus   MeSH
• konformace proteinů MeSH
• molekulární modely MeSH
• nekódující RNA metabolismus   MeSH
• proteinové domény MeSH
• proteiny vázající RNA chemie   metabolismus   MeSH
• regulace genové exprese u hub MeSH
• RNA-helikasy chemie   metabolismus   MeSH
• RNA-polymerasa II chemie   MeSH
• Saccharomyces cerevisiae - proteiny chemie   metabolismus   MeSH
• Saccharomyces cerevisiae genetika   metabolismus   MeSH
• terminace genetické transkripce MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

PURPOSE: Cystic fibrosis (CF) is a progressive disease which causes a continuous decline in lung capacity with age. Our study aimed to investigate the age-dependent deterioration in lung function and the effects of treatment with Fenretinide formulation (LAU-7b) in Cftr knockout (KO) mice. METHODS: Non-invasive whole-body plethysmography (WBP) was done to measure the baseline lung functions of KO and wild-type (WT) mice at the ages of 2 and 4 months. Mice were then treated for 21 days with PBS or 10 mg/kg/day LAU-7b initiated at 4 and 7 months. Standard airway resistance measurements, haematoxylin and eosin staining, and analysis of lipids, and markers of oxidation were performed. RESULTS: The 4- and 7-month-old KO mice had significantly higher lung enhanced pause (Penh) and resistance values than age-matched WT mice and 2-month-old KO mice. Likewise, analysis of ceramides showed that PBS-treated mice had higher levels of long-chain ceramides (LCCs; C14-C18) and lower levels of very-long-chain ceramides (VLCCs; C24-C26) compared to LAU-7b-treated mice. Cftr KO mice displayed markedly greater inflammatory cell infiltration and epithelial hyperplasia at the ages of 2, 4, and 7 months compared to WT. LAU-7b treatment significantly diminished this cellular infiltration and epithelial hyperplasia compared to PBS-treated mice. CONCLUSION: Our results demonstrate a progressive age-dependent decline in lung function in Cftr KO mice. Treatment with LAU-7b corrects the lipid imbalance observed in the aging KO and WT mice and, more importantly, inhibits the age-dependent deterioration in lung physiology and histopathology.

• MeSH
• ceramidy metabolismus   MeSH
• cystická fibróza metabolismus   patofyziologie   MeSH
• mastné kyseliny metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myši knockoutované MeSH
• myši MeSH
• pletysmografie MeSH
• plíce patofyziologie   MeSH
• progrese nemoci MeSH
• rezistence dýchacích cest fyziologie   MeSH
• stárnutí * MeSH
• věkové faktory MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Gene expression is a fundamental process that enables cells to produce specific proteins in a timely and spatially dependent manner. In eukaryotic cells, the complex organization of the cell body requires precise control of protein synthesis and localization. Certain mRNAs encode proteins with an N-terminal signal sequences that direct the translation apparatus toward a specific organelle. Here, we focus on the mechanisms governing the translation of mRNAs, which encode proteins with an endoplasmic reticulum (ER) signal in human cells. The binding of a signal-recognition particle (SRP) to the translation machinery halts protein synthesis until the mRNA-ribosome complex reaches the ER membrane. The commonly accepted model suggests that mRNA that encodes a protein that contains an ER signal peptide continuously repeats the cycle of SRP binding followed by association and dissociation with the ER. In contrast to the current view, we show that the long mRNAs remain on the ER while being translated. On the other hand, due to low ribosome occupancy, the short mRNAs continue the cycle, always facing a translation pause. Ultimately, this leads to a significant drop in the translation efficiency of small, ER-targeted proteins. The proposed mechanism advances our understanding of selective protein synthesis in eukaryotic cells and provides new avenues to enhance protein production in biotechnological settings.

• Publikační typ
• časopisecké články MeSH

• MeSH
• filozofie MeSH
• lingvistika MeSH

• Konspekt
• Věda. Všeobecnosti. Základy vědy a kultury. Vědecká práce
• NLK Obory
• lingvistika, lékařská terminologie
• humanitní vědy a umění

• MeSH
• biologie buňky MeSH
• molekulární biologie MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• biologie
• cytologie, klinická cytologie