Temporal coding
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Cardiac arrhythmias represent wide and heterogenic group of disturbances in the cardiac rhythm. Pathophysiology of individual arrhythmias is highly complex and dysfunction in ion channels/currents involved in generation or spreading of action potential is usually documented. Non-coding RNAs (ncRNAs) represent highly variable group of molecules regulating the heart expression program, including regulation of the expression of individual ion channels and intercellular connection proteins, e.g. connexins.Within this chapter, we will describe basic electrophysiological properties of the myocardium. We will focus on action potential generation and spreading in pacemaker and non-pacemaker cells, including description of individual ion channels (natrium, potassium and calcium) and their ncRNA-mediated regulation. Most of the studies have so far focused on microRNAs, thus, their regulatory function will be described into greater detail. Clinical consequences of altered ncRNA regulatory function will also be described together with potential future directions of the research in the field.
- Klíčová slova
- Arrhythmia, CACNA1C, Connexin 43, Ion channels, MicroRNA, Non-coding RNA,
- MeSH
- iontové kanály MeSH
- lidé MeSH
- mikro RNA MeSH
- nekódující RNA * MeSH
- srdce MeSH
- srdeční arytmie * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- iontové kanály MeSH
- mikro RNA MeSH
- nekódující RNA * MeSH
The majority of the human genome encodes RNAs that do not code for proteins. These non-coding RNAs (ncRNAs) affect normal expression of the genes, including oncogenes and tumour suppressive genes, which make them a new class of targets for drug development in cancer. Although microRNAs (miRNAs) are the most studied regulatory ncRNAs to date, and miRNA-targeted therapeutics have already reached clinical development, including the mimics of the tumour suppressive miRNAs miR-34 and miR-16, which reached phase I clinical trials for the treatment of liver cancer and mesothelioma, the importance of long non-coding RNAs (lncRNAs) is increasingly being recognised. Here, we describe obstacles and advances in the development of ncRNA therapeutics and provide the comprehensive overview of the ncRNA chemistry and delivery technologies. Furthermore, we summarise recent knowledge on the biological functions of miRNAs and their involvement in carcinogenesis, and discuss the strategies of their therapeutic manipulation in cancer. We review also the emerging insights into the role of lncRNAs and their potential as targets for novel treatment paradigms. Finally, we provide the up-to-date summary of clinical trials involving miRNAs and future directions in the development of ncRNA therapeutics.
- Klíčová slova
- cancer, delivery systems, long non-coding RNA, microRNA, non-coding RNA, therapy,
- MeSH
- cílená molekulární terapie metody trendy MeSH
- lidé MeSH
- mikro RNA genetika MeSH
- modely genetické MeSH
- nádory farmakoterapie genetika MeSH
- nekódující RNA genetika MeSH
- protinádorové látky terapeutické užití MeSH
- regulace genové exprese u nádorů účinky léků MeSH
- RNA dlouhá nekódující genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- mikro RNA MeSH
- nekódující RNA MeSH
- protinádorové látky MeSH
- RNA dlouhá nekódující MeSH
Osteoarthritis (OA) is a frequent musculoskeletal disorder affecting millions of people worldwide. Despite advances in understanding the pathogenesis of OA, prognostic biomarkers or effective targeted treatment are not currently available. Research on epigenetic factors has yielded some new insights as new technologies for their detection continue to emerge. In this context, non-coding RNAs, including microRNAs, long non-coding RNAs, circular RNAs, piwi-interacting RNAs, and small nucleolar RNAs, regulate intracellular signaling pathways and biological processes that have a crucial role in the development of several diseases. In this review, we present current knowledge on the role of epigenetic factors with a focus on non-coding RNAs in the development, prediction and treatment of OA. This article is categorized under: RNA in Disease and Development > RNA in Disease.
- Klíčová slova
- biomarker, epigenetic factors, non-coding RNA, osteoarthritis, targeted treatment,
- MeSH
- kruhová RNA MeSH
- lidé MeSH
- mikro RNA * genetika MeSH
- osteoartróza * genetika MeSH
- Piwi-interagující RNA MeSH
- RNA dlouhá nekódující * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- kruhová RNA MeSH
- mikro RNA * MeSH
- Piwi-interagující RNA MeSH
- RNA dlouhá nekódující * MeSH
Cells must change their properties in order to adapt to a constantly changing environment. Most of the cellular sensing and regulatory mechanisms described so far are based on proteins that serve as sensors, signal transducers, and effectors of signalling pathways, resulting in altered cell physiology. In recent years, however, remarkable examples of the critical role of non-coding RNAs in some of these regulatory pathways have been described in various organisms. In this review, we focus on all classes of non-coding RNAs that play regulatory roles during stress response, starvation, and ageing in different yeast species as well as in structured yeast populations. Such regulation can occur, for example, by modulating the amount and functional state of tRNAs, rRNAs, or snRNAs that are directly involved in the processes of translation and splicing. In addition, long non-coding RNAs and microRNA-like molecules are bona fide regulators of the expression of their target genes. Non-coding RNAs thus represent an additional level of cellular regulation that is gradually being uncovered.
- Klíčová slova
- RNA modifications, epitranscriptome, lncRNA, tRNA, yeast,
- MeSH
- mikro RNA * genetika MeSH
- RNA dlouhá nekódující * genetika MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- mikro RNA * MeSH
- RNA dlouhá nekódující * MeSH
Recent studies on the theoretical performance of latency and rate code in single neurons have revealed that the ultimate accuracy is affected in a nontrivial way by aspects such as the level of spontaneous activity of presynaptic neurons, amount of neuronal noise or the duration of the time window used to determine the firing rate. This study explores how the optimal decoding performance and the corresponding conditions change when the energy expenditure of a neuron in order to spike and maintain the resting membrane potential is accounted for. It is shown that a nonzero amount of spontaneous activity remains essential for both the latency and the rate coding. Moreover, the optimal level of spontaneous activity does not change so much with respect to the intensity of the applied stimulus. Furthermore, the efficiency of the temporal and the rate code converge to an identical finite value if the neuronal activity is observed for an unlimited period of time.
- Klíčová slova
- Fisher information, Metabolic cost, Rate coding, Temporal coding,
- MeSH
- časové faktory MeSH
- energetický metabolismus * MeSH
- lidé MeSH
- membránové potenciály MeSH
- modely neurologické * MeSH
- nervová síť cytologie fyziologie MeSH
- neuronové sítě * MeSH
- neurony fyziologie MeSH
- počítačová simulace MeSH
- výpočetní biologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Whole-genome sequencing analyses revealed that the majority of the human genome is transcribed and identified thousands of protein non-coding transcripts. Non-coding RNAs (ncRNAs) are divided into two main groups: small and long ncRNAs. This review is focused on the regulatory ncRNAs mainly on microRNAs and long ncRNAs. These ncRNAs regulate gene expression at the transcriptional and post-transcriptional levels. In this context, ncRNAs are involved in the regulation of most cellular processes and their deregulation has serious impacts on the phenotype. Hundreds of studies have implicated ncRNAs in the pathogenesis of many diseases ranging from metabolic disorders to diseases of organ systems as well as various types of cancers.Clinically, ncRNAs belong to a new generation of diagnostic and prognostic biomarkers with a great potential. Due to high tissue specificity and ability to regulate multiple genes often within one signaling pathway, ncRNAs represent attractive therapeutic targets. Increasing knowledge about a wide spectrum of ncRNA actions demonstrate a pivotal role of these transcripts in expression regulation. Many aspects of the ncRNA biology are still unclear and their understanding will provide us a new perspective on the complexity of the regulatory network.
- Klíčová slova
- gene expression regulation, miRNA lncRNA., non-coding RNA,
- MeSH
- lidé MeSH
- mikro RNA genetika fyziologie MeSH
- nekódující RNA genetika fyziologie MeSH
- regulace genové exprese genetika fyziologie MeSH
- RNA dlouhá nekódující genetika fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- mikro RNA MeSH
- nekódující RNA MeSH
- RNA dlouhá nekódující MeSH
The circulating human transcriptome, which includes both coding and non-coding RNA (ncRNA) molecules, represents a rich source of potential biomarkers for colorectal cancer (CRC) that has only recently been explored. In particular, the release of RNA-containing extracellular vesicles (EVs), in a multitude of different in vitro cell systems and in a variety of body fluids, has attracted wide interest. The role of RNA species in EVs is still not fully understood, but their capacity to act as a form of distant communication between cells and their higher abundance in association with cancer demonstrated their relevance. In this review, we report the evidence from both in vitro and human studies on microRNAs (miRNAs) and other ncRNA profiles analysed in EVs in relation to CRC as diagnostic, prognostic and predictive markers. The studies so far highlighted that, in exosomes, the most studied category of EVs, several miRNAs are able to accurately discriminate CRC cases from controls as well as to describe the progression of the disease and its prognosis. Most of the time, the in vitro findings support the miRNA profiles detected in human exosomes. The expression profiles measured in exosomes and other EVs differ and, interestingly, there is a variability of expression also among different subsets of exosomes according to their proteic profile. On the other hand, evidence is still limited for what concerns exosome miRNAs as early diagnostic and predictive markers of treatment. Several other ncRNAs that are carried by exosomes, mostly long ncRNAs and circular RNAs, seem also to be dysregulated in CRC. Besides various technical challenges, such as the standardisation of EVs isolation methods and the optimisation of methodologies to characterise the whole spectrum of RNA molecules in exosomes, further studies are needed in order to elucidate their relevance as CRC markers.
- MeSH
- exozómy genetika metabolismus MeSH
- extracelulární vezikuly genetika metabolismus MeSH
- kolorektální nádory krev diagnóza genetika metabolismus MeSH
- lidé MeSH
- mikro RNA genetika metabolismus MeSH
- nádorové biomarkery genetika metabolismus MeSH
- nekódující RNA genetika metabolismus MeSH
- progrese nemoci MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- mikro RNA MeSH
- nádorové biomarkery MeSH
- nekódující RNA MeSH
Ixodes ricinus ticks are distributed across Europe and are a vector of tick-borne diseases. Although I. ricinus transcriptome studies have focused exclusively on protein coding genes, the last decade witnessed a strong increase in long non-coding RNA (lncRNA) research and characterization. Here, we report for the first time an exhaustive analysis of these non-coding molecules in I. ricinus based on 131 RNA-seq datasets from three different BioProjects. Using this data, we obtained a consensus set of lncRNAs and showed that lncRNA expression is stable among different studies. While the length distribution of lncRNAs from the individual data sets is biased toward short length values, implying the existence of technical artefacts, the consensus lncRNAs show a more homogeneous distribution emphasizing the importance to incorporate data from different sources to generate a solid reference set of lncRNAs. KEGG enrichment analysis of host miRNAs putatively targeting lncRNAs upregulated upon feeding showed that these miRNAs are involved in several relevant functions for the tick-host interaction. The possibility that at least some tick lncRNAs act as host miRNA sponges was further explored by identifying lncRNAs with many target regions for a given host miRNA or sets of host miRNAs that consistently target lncRNAs together. Overall, our findings suggest that lncRNAs that may act as sponges have diverse biological roles related to the tick-host interaction in different tissues.
- Klíčová slova
- Ixodes ricinus, RNA-sequencing, ectoparasite-host interactions, host immunity, lncRNA,
- MeSH
- klíště * genetika MeSH
- mikro RNA * genetika MeSH
- nemoci přenášené klíšťaty * MeSH
- RNA dlouhá nekódující * genetika MeSH
- výpočetní biologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- mikro RNA * MeSH
- RNA dlouhá nekódující * MeSH
Understanding the neural systems underpinning social cognition is a primary focus of contemporary social neuroscience. Using functional magnetic resonance imaging (fMRI), the present study asked if brain activity reflecting socio-cognitive processes differs between individuals according to their social behavior; namely, between a group of drivers with frequent traffic offenses and a group with none. Socio-cognitive processing was elicited by employing videos from a traffic awareness campaign, consisting of reckless and anti-social driving behavior ending in tragic consequences, and control videos with analogous driving themes but without such catastrophic endings. We investigated whether relative increases in brain function during the observation of these campaign stimuli compared with control videos differed between these two groups. To develop the results of our previous study we focused our analyses on superior temporal sulcus/gyrus (STS/STG). This revealed a bigger increase in brain activity within this region during the campaign stimuli in safe compared with dangerous drivers. Furthermore, by thematically coding drivers' verbal descriptions of the stimuli, we also demonstrate differences in STS reactivity according to drivers' scores on two indices of socio-cognitive processing: subjects' perceived consequences of actors' actions, and their affective evaluation of the clips. Our results demonstrate the influence of social behavior and socio-cognitive processing on STS reactivity to social stimuli, developing considerably our understanding of the role of this region in social cognition.
- Klíčová slova
- Antisocial behavior, Road safety campaign videos, STS, Social cognition, fMRI,
- MeSH
- dopravní nehody psychologie MeSH
- dospělí MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mapování mozku * MeSH
- mladý dospělý MeSH
- počítačové zpracování obrazu MeSH
- řízení motorových vozidel psychologie MeSH
- sociální chování * MeSH
- spánkový lalok patofyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The significance of long non-coding RNAs (lncRNAs) in the development and progression of human cancers has attracted increasing attention in recent years of investigations. Having versatile interactions and diverse functions, lncRNAs can act as oncogenes or tumor-suppressors to actively regulate cell proliferation, survival, stemness, drug resistance, invasion and metastasis. LINC00467, an oncogenic member of long intergenic non-coding RNAs, is upregulated in numerous malignancies and its high expression is often related to poor clinicopathological features. LINC00467 facilitates the progression of cancer via sponging tumor-suppressive microRNAs, inhibiting cell death cascade, modulating cell cycle controllers, and regulating signalling pathways including AKT, STAT3, NF-κB and Wnt/β-catenin. A growing number of studies have revealed that LINC00467 may serve as a novel prognostic biomarker and its inhibitory targeting has a valuable therapeutic potential to suppress the malignant phenotypes of cancer cells. In the present review, we discuss the importance of LINC00467 and provide a comprehensive collection of its functions and molecular mechanisms in a variety of cancer types.
- Klíčová slova
- Cancer, LINC00467, Oncogene, lncRNA, miRNA,
- MeSH
- beta-katenin genetika MeSH
- biologické markery MeSH
- karcinogeneze genetika MeSH
- lidé MeSH
- mikro RNA * genetika MeSH
- nádorové buněčné linie MeSH
- nádory * genetika MeSH
- NF-kappa B MeSH
- onkogeny genetika MeSH
- proliferace buněk genetika MeSH
- protoonkogenní proteiny c-akt genetika MeSH
- regulace genové exprese u nádorů MeSH
- RNA dlouhá nekódující * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- beta-katenin MeSH
- biologické markery MeSH
- mikro RNA * MeSH
- NF-kappa B MeSH
- protoonkogenní proteiny c-akt MeSH
- RNA dlouhá nekódující * MeSH