994 resultados para PRE-MESSENGER-RNAS


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AIM: Heart disease is recognized as a consequence of dysregulation of cardiac gene regulatory networks. Previously, unappreciated components of such networks are the long non-coding RNAs (lncRNAs). Their roles in the heart remain to be elucidated. Thus, this study aimed to systematically characterize the cardiac long non-coding transcriptome post-myocardial infarction and to elucidate their potential roles in cardiac homoeostasis. METHODS AND RESULTS: We annotated the mouse transcriptome after myocardial infarction via RNA sequencing and ab initio transcript reconstruction, and integrated genome-wide approaches to associate specific lncRNAs with developmental processes and physiological parameters. Expression of specific lncRNAs strongly correlated with defined parameters of cardiac dimensions and function. Using chromatin maps to infer lncRNA function, we identified many with potential roles in cardiogenesis and pathological remodelling. The vast majority was associated with active cardiac-specific enhancers. Importantly, oligonucleotide-mediated knockdown implicated novel lncRNAs in controlling expression of key regulatory proteins involved in cardiogenesis. Finally, we identified hundreds of human orthologues and demonstrate that particular candidates were differentially modulated in human heart disease. CONCLUSION: These findings reveal hundreds of novel heart-specific lncRNAs with unique regulatory and functional characteristics relevant to maladaptive remodelling, cardiac function and possibly cardiac regeneration. This new class of molecules represents potential therapeutic targets for cardiac disease. Furthermore, their exquisite correlation with cardiac physiology renders them attractive candidate biomarkers to be used in the clinic.

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BACKGROUND: The pre-conditioning of tumor vessels by low-dose photodynamic therapy (L-PDT) was shown to enhance the distribution of chemotherapy in different tumor types. However, how light dose affects drug distribution and tumor response is unknown. Here we determined the effect of L-PDT fluence on vascular transport in human mesothelioma xenografts. The best L-PDT conditions regarding drug transport were then combined with Lipoplatin(®) to determine tumor response. in vivo. Lasers Surg. Med. 47:323-330, 2015. © 2015 Wiley Periodicals, Inc. METHODS: Nude mice bearing dorsal skinfold chambers were implanted with H-Meso1 cells. Tumors were treated by Visudyne(®) -mediated photodynamic therapy with 100 mW/cm(2) fluence rate and a variable fluence (5, 10, 30, and 50 J/cm(2) ). FITC-Dextran (FITC-D) distribution was assessed in real time in tumor and normal tissues. Tumor response was then determined with best L-PDT conditions combined to Lipoplatin(®) and compared to controls in luciferase expressing H-Meso1 tumors by size and whole body bioluminescence assessment (n = 7/group). RESULTS: Tumor uptake of FITC-D following L-PDT was significantly enhanced by 10-fold in the 10 J/cm(2) but not in the 5, 30, and 50 J/cm(2) groups compared to controls. Normal surrounding tissue uptake of FITC-D following L-PDT was significantly enhanced in the 30 J/cm(2) and 50 J/cm(2) groups compared to controls. Altogether, the FITC-D tumor to normal tissue ratio was significantly higher in the 10 J/cm(2) group compared others. Tumor growth was significantly delayed in animals treated by 10 J/cm2-L-PDT combined to Lipoplatin(®) compared to controls. CONCLUSIONS: Fluence of L-PDT is critical for the optimal distribution and effect of subsequently administered chemotherapy. These findings have an importance for the clinical translation of the vascular L-PDT concept in the clinics. Lasers Surg. Med. 47:323-330, 2015.

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Se realiza una revisión bibliográfica con el objetivo de conocer los protocolos actuales de rehabilitación tras la reconstrucción quirúrgica del ligamento cruzado anterior de la rodilla. Se efectúa una búsqueda de los estudios clínicos experimentales actuales que evalúan los procedimientos y protocolos de fisioterapia utilizados durante la rehabilitación del LCA. La búsqueda se realiza en las bases de datos: Medline, PEDro y Science Direct, entre diciembre de 2013 y enero de 2014. Se incluyen los publicados a partir del 2010, desarrollados en humanos con ruptura parcial o total del ligamento y redactados en español o inglés. Se analizan los 21 estudios que cumplen con los criterios de inclusión y exclusión estipulados y se valora el proceso metodológico empleado, la presencia de sesgos y limitaciones, la aplicabilidad de los resultados y la descripción precisa de los protocolos. Se concluye afirmando que no existe unanimidad en los protocolos y procedimientos de fisioterapia y que éstos no ofrecen diferencias destacables si se comparan con los diseñados 20 años atrás. Por lo que se propone y elaborar un protocolo de rehabilitación propio teniendo en cuenta la información obtenida y usando como referencia las guías clínicas más empleadas en la práctica clínica.

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BACKGROUND: Frailty is detected by weight loss, weakness, slow walking velocity, reduced physical activity or poor endurance/exhaustion. Handwriting has not been examined in the context of frailty, despite its functional importance. OBJECTIVE: Our goal was to examine quantitative handwriting measures in people meeting 0, 1, and 2 or more (2+) frailty criteria. We also examined if handwriting parameters were associated with gait performance, weakness, poor endurance/exhaustion and cognitive impairment. METHODS: From the population-based Lc65+, 72 subjects meeting 2+ frailty criteria with complete handwriting samples were identified. Gender-matched controls meeting 1 criterion or no criteria were identified. Cognitive impairment was defined by a Mini-Mental State Examination score of 25 or less or the lowest 20th percentile of Trail Making Test Part B. Handwriting was recorded using a writing tablet and measures of velocity, pauses, and pressure were extracted. RESULTS: Subjects with 2+ criteria were older, had more health problems and need for assistance but had higher education. No handwriting parameter differed between frailty groups (age and education adjusted). Writing velocity was not significantly slower among participants from the slowest 20th percentile of gait velocity but writing pressure was significantly lower among those from the lowest 20th percentile of grip strength. Poor endurance/exhaustion was not associated with handwriting measures. Low cognitive performance was related to longer pauses. CONCLUSIONS: Handwriting parameters might be associated with specific aspects of the frailty phenotype, but not reliably with global definitions of frailty at its earliest stages among subjects able to perform handwriting tests.

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The question of Pilot Project creation, due to support pre-development stage of software product elaboration, nowadays might be used as an approach, which allows improving the whole scheme of information technology project running. This subject is not new, but till now no model has been presented, which gives deep description of this important stage on the early phase of project. This Master's Thesis represents the research's results and findings concerning the pre-development study from the Software Engineering point of view. The aspects of feasibility study, pilot prototype developments are analyzed in this paper. As the result, the technique of Pilot Project is formulated and scheme has been presented. The experimental part is focused on particular area Pilot Project scheme's implementation- Internationally Distributed Software projects. The specific characteristic, aspects, obstacles, advantages and disadvantages are considered on the example of cross border region of Russia and Finland. The real case of Pilot Project technique implementation is given.

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OBJECTIVE: This pilot experimental study tested the feasibility and intended effect of an educational intervention for parents to help them assist their adolescent child with chronic illness (CI) in becoming autonomous. METHODS: A two-phase pre-post pilot intervention study targeting parents of adolescents with CI was conducted. Parents were allocated to group 1 and 2 and received the four-module intervention consecutively. Intended effect was measured through online questionnaires for parents and adolescents before, at 2 months after, and at 4-6 months after the intervention. Feasibility was assessed through an evaluation questionnaire for parents. RESULTS: The most useful considered modules concerned the future of the adolescent and parents and social life. The most valued aspect was to exchange with other parents going through similar problems and receiving a new outlook on their relationship with their child. For parents, improvement trends appeared for shared management, parent protection, and self-efficacy, and worsening trends appeared for coping skills, parental perception of child vulnerability, and parental stress. For adolescents, improvement trends appeared for self-efficacy and parental bonding and worsening trends appeared for shared management and coping skills. CONCLUSION: Parents could benefit from peer-to-peer support and education as they support the needed autonomy development of their child. Future studies should test an online platform for parents to find peer support at all times and places.

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Suojakaasupakkaaminen (MAP) on yleistynyt viime aikoina, koska sen avulla voidaan säilöä tuoreita tai vähän käsiteltyjä elintarvikkeita pidempään. Suurin syy hyllyiän pidentymiseen on hiilidioksidin aiheuttama mikrobien kasvun hidastuminen. Toisaalta huolena on patogeenisten mikrobien lisääntyminen anaerobisissa olosuhteissa. Pidempi säilyvyys voidaan saavuttaa myös käyttämällä vähemmän lisä- ja säilöntäaineita. Samalla suojakaasupakkaaminen kuitenkin vähentää myös pilaantuneiden tuotteiden määrää. Eniten suojakaasua käytetään lihan pakkaamisessa. Suojakaasupakkaamisessa elintarvikepakkaukseen syötetään normaalista huoneilmasta poikkeava kaasuseos. Pääasiassa kaasuseos koostuu hiilidioksidista, hapesta ja typestä. Lisäksi voidaan käyttää pieniä määriä hiilimonoksidia, argonia ja rikkidioksidia. Kaasuseoksen koostumus määräytyy elintarvikkeiden ominaisuuksien ja vaatimusten perusteella. Halutun kaasukoostumuksen tulee säilyä pakkauksessa muutamasta päivästä muutamaan kuukauteen riippuen elintarvikkeesta. Siksi tärkein pakkaukselta vaadittava ominaisuus on riittävä kaasutiiveys ja erityisesti hapenläpäisevyys. Koska suurin osa suojakaasupakkauksista on tällä hetkellä muovisia, tutkittiin kokeellisessa osiossa kartonkipakkausten tiiveysominaisuuksia. Kokeet tehtiin vertailemalla erilaisten vuoka- ja kansimateriaalien vaikutusta pakkausten tiiveyteen. Vuokien onnistuminen oli suurin yksittäinen tuloksiin vaikuttanut tekijä. Epäonnistuneen vuoan vaikutukset näkyivät myös saumauksessa, koska saumaustyökalun ja vuoan piti sopia yhteen. Lisäksi näkymättömät mikroreiät hankaloittivat todellisten vuotokohtien paikallistamista. Vuototestausten perusteella materiaaleille löydettiin kuitenkin viitteelliset optimiparametrit. Tärkein saumauksessa vaikuttanut tekijä oli sopivan saumauslämpötilan valinta. Prässättyjen vuokien laatu oli epätasainen. Siksi erityisesti rinnakkaisten kansitus- ja hapenläpäisymittausten väliset erot olivat merkitseviä. Lisäksi prässäys laski materiaalien hapenläpäisyominaisuuksia. Yksittäisten vuokien tiiveysominaisuudet täyttivät kuitenkin kaupallisille kaasupakkauksille asetetut vaatimukset. Vesihöyrynläpäisevyydessä materiaalin vesihöyrynläpäisy oli merkittävämpää kuin vesihöyryn kulkeutuminen vuotokohtien tai epäonnistuneiden saumojen kautta.

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A large part of the mammalian genome is transcribed into noncoding RNAs. Long noncoding RNAs (lncRNAs) have emerged as critical epigenetic regulators of gene expression. Distinct molecular mechanisms allow lncRNAs either to activate or to repress gene expression, thereby participating in the regulation of cellular and tissue function. LncRNAs, therefore, have important roles in healthy and diseased hearts, and might be targets for therapeutic intervention. In this Review, we summarize the current knowledge of the roles of lncRNAs in cardiac development and ageing. After describing the definition and classification of lncRNAs, we present an overview of the mechanisms by which lncRNAs regulate gene expression. We discuss the multiple roles of lncRNAs in the heart, and focus on the regulation of embryonic stem cell differentiation, cardiac cell fate and development, and cardiac ageing. We emphasize the importance of chromatin remodelling in this regulation. Finally, we discuss the therapeutic and biomarker potential of lncRNAs.

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The key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (lncRNAs) during cardiac differentiation and morphogenesis. Enhancer expression correlates with the emergence of active enhancer chromatin states, the initiation of RNA polymerase II at enhancer loci and expression of target genes. Orthologous human sequences are also transcribed in fetal human hearts and cardiac progenitor cells. Through a systematic bioinformatic analysis, we identified and characterized, for the first time, a catalog of lncRNAs that are expressed during embryonic stem cell differentiation into cardiomyocytes and associated with active cardiac enhancer sequences. RNA-sequencing demonstrates that many of these transcripts are polyadenylated, multi-exonic long noncoding RNAs. Moreover, knockdown of two enhancer-associated lncRNAs resulted in the specific downregulation of their predicted target genes. Interestingly, the reactivation of the fetal gene program, a hallmark of the stress response in the adult heart, is accompanied by increased expression of fetal cardiac enhancer transcripts. Altogether, these findings demonstrate that the activity of cardiac enhancers and expression of their target genes are associated with the production of enhancer-derived lncRNAs.