The autonomous transcription of integrated retroviruses strongly depends on genetic and epigenetic effects of the chromatin at the site of integration. These effects are mostly suppressive and proviral activity can be finally silenced by mechanisms, such as DNA methylation and histone modifications. To address the role of the integration site at the whole-genome-scale, we performed clonal analysis of provirus silencing with an avian leucosis/sarcoma virus-based reporter vector and correlated the transcriptional silencing with the epigenomic landscape of respective integrations. We demonstrate efficient provirus silencing in human HCT116 cell line, which is strongly but not absolutely dependent on the de novo DNA methyltransferase activity, particularly of Dnmt3b. Proviruses integrated close to the transcription start sites of active genes into the regions enriched in H3K4 trimethylation display long-term stability of expression and are resistant to the transcriptional silencing after over-expression of Dnmt3a or Dnmt3b. In contrast, proviruses in the intergenic regions tend to spontaneous transcriptional silencing even in Dnmt3a(-/-) Dnmt3b(-/-) cells. The silencing of proviruses within genes is accompanied with DNA methylation of long terminal repeats, whereas silencing in intergenic regions is DNA methylation-independent. These findings indicate that the epigenomic features of integration sites are crucial for their permissivity to the proviral expression.

• MeSH
• Alpharetrovirus genetika   MeSH
• DNA-(cytosin-5-)methyltransferasa genetika   metabolismus   MeSH
• epigeneze genetická MeSH
• genetická transkripce MeSH
• integrace viru MeSH
• lidé MeSH
• metylace DNA MeSH
• nádorové buněčné linie MeSH
• proviry genetika   MeSH
• umlčování genů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Text usiluje o předložení souvislostí, které determinují proces společenské integrace osob se zdravotním znevýhodněním. Integrace je čtenáři předkládána jako dynamický proces, na jehož vývoji se podílí tři základní složky. Jde o složku sociální, psychologickou a biologickou, které jsou podrobněji popsány v ucelených statích. Autorka usiluje o předložení souvislostí, které působí na úspěšnost celého procesu vrůstání jedince s handicapem do majority společnosti. V části, která seznamuje čtenáře se společenskými hledisky, jsou předloženy základní myšlenkové modely, jež lze zaznamenat v postojích majority vůči dané minoritě Druhá ucelená část věnovaná psychologickým hlediskům usiluje o vhled do specifik psychologie handicapu. Tato část je uzavřena konstatováním neexistence specifického osobnostního typu osob s handicapem. Biologická podmíněnost zdůrazňuje především důležitost typu handicapu, jeho rozsah a dobu vzniku pro následný vývoj jedince, a to především v oblasti poznávacích procesů, dovedností a schopností. Proces společenské integrace je zde chápán jako cesta k dosažení optimální kvality života jedince se zdravotním postižením.

The article attempts to summarize facts determining the process of the social integration of persons with health handicaps. The integration is presented to the reader as a dynamic process with three principal components participating in its development. These are the social psychological and biological components, which are detailed in comprehensive works. The author tries to offer associated facts affecting the success of the whole process of the incorporation of a handicapped individual into the majority society. In the part making the reader familiar with social standpoints, principal conceptual models are presented, which can be observed in attitudes of the majority to the given minority. The second part aimed at psychological standpoints tries to provide an insight into specific features of the handicap psychology. This part is concluded by expressing the non-existence of a specific personality type of handicapped people. Biological conditioning particularly emphasizes the importance of the handicap type, of its extent and time of its origination for the subsequent development of the individual, particularly in the field of cognitive processes, skill and capability. The process of the social integration is considered as a way to achieving an optimum life quality of an individual with a health handicap.

• MeSH
• adaptace psychologická MeSH
• lidé MeSH
• postižení psychologie   rehabilitace   MeSH
• předsudek MeSH
• sociální přizpůsobení MeSH
• žaloby wrongful life MeSH
• Check Tag
• lidé MeSH

• MeSH
• katecholaminy fyziologie   MeSH
• koronární nemoc etiologie   MeSH
• sympatický nervový systém MeSH

The important role of humans in the development of current ecosystems was recognized decades ago; however, the integration of history and ecology in order to inform conservation has been difficult. We identified four issues that hinder historical ecological research and considered possible solutions. First, differences in concepts and methods between the fields of ecology and history are thought to be large. However, most differences stem from miscommunication between ecologists and historians and are less substantial than is usually assumed. Cooperation can be achieved by focusing on the features ecology and history have in common and through understanding and acceptance of differing points of view. Second, historical ecological research is often hampered by differences in spatial and temporal scales between ecology and history. We argue that historical ecological research can only be conducted at extents for which sources in both disciplines have comparable resolutions. Researchers must begin by clearly defining the relevant scales for the given purpose. Third, periods for which quantitative historical sources are not easily accessible (before AD 1800) have been neglected in historical ecological research. Because data from periods before 1800 are as relevant to the current state of ecosystems as more recent data, we suggest that historical ecologists actively seek out data from before 1800 and apply analytic methods commonly used in ecology to these data. Fourth, humans are not usually considered an intrinsic ecological factor in current ecological research. In our view, human societies should be acknowledged as integral parts of ecosystems and societal processes should be recognized as driving forces of ecosystem change.

• MeSH
• ekologie MeSH
• zachování přírodních zdrojů MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Photosynthetic microalgae have been in the spotlight of biotechnological production (biofuels, lipids, etc), however, current barriers in mass cultivation of microalgae are limiting its successful industrialization. Therefore, a mathematical model integrating both the biological and hydrodynamical parts of the cultivation process may improve our understanding of relevant phenomena, leading to further optimization of the microalgae cultivation. RESULTS: We introduce a unified multidisciplinary simulation tool for microalgae culture systems, particularly the photobioreactors. Our approach describes changes of cell growth determined by dynamics of heterogeneous environmental conditions such as irradiation and mixing of the culture. Presented framework consists of (i) a simplified model of microalgae growth in a culture system (the advection-diffusion-reaction system within a phenomenological model of photosynthesis and photoinhibition), (ii) the fluid dynamics (Navier-Stokes equations), and (iii) the irradiance field description (Beer-Lambert law). To validate the method, a simple case study leading to hydrodynamically induced fluctuating light conditions was chosen. The integration of computational fluid dynamics (ANSYS Fluent) revealed the inner property of the system, the flashing light enhancement phenomenon, known from experiments. CONCLUSION: Our physically accurate model of microalgae culture naturally exhibits features of real system, can be applied to any geometry of microalgae mass cultivation and thus is suitable for biotechnological applications.

• MeSH
• biologické modely MeSH
• fotosyntéza * MeSH
• hydrodynamika * MeSH
• kultivační techniky * MeSH
• mikrořasy růst a vývoj   fyziologie   účinky záření   MeSH
• počítačová simulace MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Retroviruses and retrovirus-derived vectors integrate nonrandomly into the genomes of host cells with specific preferences for transcribed genes, gene-rich regions, and CpG islands. However, the genomic features that influence the transcriptional activities of integrated retroviruses or retroviral vectors are poorly understood. We report here the cloning and characterization of avian sarcoma virus integration sites from chicken tumors. Growing progressively, dependent on high and stable expression of the transduced v-src oncogene, these tumors represent clonal expansions of cells bearing transcriptionally active replication-defective proviruses. Therefore, integration sites in our study distinguished genomic loci favorable for the expression of integrated retroviruses and gene transfer vectors. Analysis of integration sites from avian sarcoma virus-induced tumors showed strikingly nonrandom distribution, with proviruses found prevalently within or close to transcription units, particularly in genes broadly expressed in multiple tissues but not in tissue-specifically expressed genes. We infer that proviruses integrated in these genomic areas efficiently avoid transcriptional silencing and remain active for a long time during the growth of tumors. Defining the differences between unselected retroviral integration sites and sites selected for long-terminal-repeat-driven gene expression is relevant for retrovirus-mediated gene transfer and has ramifications for gene therapy.

• MeSH
• chromozomy virologie   MeSH
• exprese genu MeSH
• genetická terapie metody   MeSH
• genetické vektory MeSH
• integrace viru MeSH
• kur domácí MeSH
• proviry genetika   fyziologie   MeSH
• ptačí sarkom virologie   MeSH
• viry ptačího sarkomu genetika   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Predicting and quantifying phenotypic consequences of genetic variants in rare disorders is a major challenge, particularly pertinent for 'actionable' genes such as thyroid hormone transporter MCT8 (encoded by the X-linked SLC16A2 gene), where loss-of-function (LoF) variants cause a rare neurodevelopmental and (treatable) metabolic disorder in males. The combination of deep phenotyping data with functional and computational tests and with outcomes in population cohorts, enabled us to: (i) identify the genetic aetiology of divergent clinical phenotypes of MCT8 deficiency with genotype-phenotype relationships present across survival and 24 out of 32 disease features; (ii) demonstrate a mild phenocopy in ~400,000 individuals with common genetic variants in MCT8; (iii) assess therapeutic effectiveness, which did not differ among LoF-categories; (iv) advance structural insights in normal and mutated MCT8 by delineating seven critical functional domains; (v) create a pathogenicity-severity MCT8 variant classifier that accurately predicted pathogenicity (AUC:0.91) and severity (AUC:0.86) for 8151 variants. Our information-dense mapping provides a generalizable approach to advance multiple dimensions of rare genetic disorders.

• MeSH
• deep learning * MeSH
• dítě MeSH
• dospělí MeSH
• fenotyp * MeSH
• genetická variace MeSH
• genetické asociační studie MeSH
• genomika metody   MeSH
• hormony štítné žlázy metabolismus   genetika   MeSH
• lidé MeSH
• mentální retardace vázaná na chromozom X genetika   metabolismus   MeSH
• mladiství MeSH
• mutace ztráty funkce MeSH
• předškolní dítě MeSH
• přenašeče monokarboxylových kyselin * genetika   metabolismus   MeSH
• stupeň závažnosti nemoci MeSH
• svalová atrofie genetika   metabolismus   patologie   MeSH
• svalová hypotonie genetika   metabolismus   MeSH
• symportéry * genetika   metabolismus   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• chorobopisy - počítačové systémy MeSH
• management znalostí MeSH
• metody pro podporu rozhodování MeSH
• péče o pacienta MeSH
• počítačové zpracování obrazu MeSH
• počítačové zpracování signálu MeSH
• řízení zdravotnictví MeSH
• studium lékařství MeSH
• zdravotnické informační systémy MeSH
• Publikační typ
• sborníky MeSH

• Konspekt
• Lékařské vědy. Lékařství
• NLK Obory
• lékařská informatika
• NLK Publikační typ
• ročenky

In gait stability analysis, patients suffering from dysfunction problems are impacted by shifts in their dynamic balance. Monitoring the patients' progress is important for allowing physicians and patients to observe the rehabilitation process accurately. In this study, we designed a new methodology for classifying gait disorders to quantify patients' progress. The dataset in this study includes 84 measurements of 37 patients based on a physician's opinion. In this study, the system, which includes a Kinect camera to observe and store the frames of patients walking down a hallway, a key-point detector to detect the skeletal key points, and an encoder transformer classifier network integrated with generator-discriminator networks (ET-GD), is designed to evaluate the classification of gait dysfunction. The detector extracts the skeletal key points of patients. After feature engineering, the selected high-level features are fed into the proposed neural network to analyse patient movement and perform the final evaluation of gait dysfunction. The proposed network is inspired by the 1D encoder transformer, which is integrated with two main networks: a network for classification and a network to generate fake output data similar to the input data. Furthermore, we used a discriminator structure to distinguish between the actual data (input) and fake data (generated data). Due to the multi-structural networks in the proposed method, multi-loss functions need to be optimised; this increases the accuracy of the encoder transformer classifier.

• MeSH
• analýza chůze MeSH
• chůze (způsob) * MeSH
• chůze MeSH
• lidé MeSH
• neuronové sítě MeSH
• pohybové poruchy * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Individual groups of retroviruses and retroviral vectors differ in their integration site preference and interaction with the host genome. Hence, immediately after infection genome-wide distribution of integrated proviruses is non-random. During long-term in vitro or persistent in vivo infection, the genomic position and chromatin environment of the provirus affects its transcriptional activity. Thus, a selection of long-term stably expressed proviruses and elimination of proviruses, which have been gradually silenced by epigenetic mechanisms, helps in the identification of genomic compartments permissive for proviral transcription. We compare here the extent and time course of provirus silencing in single cell clones of the K562 human myeloid lymphoblastoma cell line that have been infected with retroviral reporter vectors derived from avian sarcoma/leukosis virus (ASLV), human immunodeficiency virus type 1 (HIV) and murine leukaemia virus (MLV). While MLV proviruses remain transcriptionally active, ASLV proviruses are prone to rapid silencing. The HIV provirus displays gradual silencing only after an extended time period in culture. The analysis of integration sites of long-term stably expressed proviruses shows a strong bias for some genomic features-especially integration close to the transcription start sites of active transcription units. Furthermore, complex analysis of histone modifications enriched at the site of integration points to the accumulation of proviruses of all three groups in gene regulatory segments, particularly close to the enhancer loci. We conclude that the proximity to active regulatory chromatin segments correlates with stable provirus expression in various retroviral species.

• MeSH
• aktivace transkripce * MeSH
• Alpharetrovirus genetika   MeSH
• buněčné linie MeSH
• chromatin genetika   MeSH
• epigeneze genetická MeSH
• genetické vektory genetika   MeSH
• genový targeting MeSH
• HIV-1 genetika   MeSH
• integrace viru MeSH
• lidé MeSH
• myši MeSH
• plazmidy genetika   MeSH
• počátek transkripce MeSH
• proviry genetika   MeSH
• regulace exprese virových genů MeSH
• regulační oblasti nukleových kyselin * MeSH
• stabilita RNA MeSH
• umlčování genů MeSH
• virus myší leukemie genetika   MeSH
• zesilovače transkripce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH