Increased chromatin accessibility facilitates intron retention in specific cell differentiation states

Dynamic intron retention (IR) in vertebrate cells is of widespread biological importance. Aberrant IR is associated with numerous human diseases including several cancers. Despite consistent reports demonstrating that intrinsic sequence features can help introns evade splicing, conflicting findings about cell type or condition-specific IR regulation by trans-regulatory and epigenetic mechanisms demand an unbiased and systematic analysis of IR in a controlled experimental setting. We integrated matched mRNA sequencing (RNA-seq), whole-genome bisulfite sequencing (WGBS), nucleosome occupancy methylome sequencing (NOMe-Seq), and chromatin immunoprecipitation sequencing (ChIP-seq) data from primary human myeloid and lymphoid cells. Using these multi-omics data and machine learning we trained two complementary models to determine the role of epigenetic factors in the regulation of IR in cells of the innate immune system. We show that increased chromatin accessibility, as revealed by nucleosome-free regions, contributes substantially to the retention of introns in a cell-specific manner. We also confirm that intrinsic characteristics of introns are key for them to evade splicing. This study suggests an important role of chromatin architecture in IR regulation. With an increasing appreciation that pathogenic alterations are linked to RNA processing, our findings may provide useful insights for the development of novel therapeutic approaches that target aberrant splicing

Research on the structuring of water clusters in Chlorella vulgaris water suspension

Many bioactive compounds of natural origin have beneficial effects on human health and are used to treat different diseases. Chlorella is a genus of green algae with a high potential for producing biologically active substances. Exposure to extreme conditions can enhance its antioxidant activity and the production of concrete metabolites. C. vulgaris is cultivated in plantations. It is accessible in pharmacies and drugstores. The Health Act of 2005 in Bulgaria allows the therapeutic and prophylactic use of herbs, both independently by patients and as prescribed by a doctor. This study performed comparative spectral analyses of C. vulgaris using a 1% suspension of C. vulgaris in deionized water (v/v) by the methods of Non-equilibrium energy spectrum (NES) and Differential non-equilibrium energy spectrum (DNES). The research was performed in order to make indirect studies of the biological effects of C. vulgaris, which are connected with calcium conductivity and anti-inflammatory and anti-tumor effects. The effects of structuring of water clusters by C. vulgaris were examined. The data from spectral analyses, connected with a peak at (E =-0.1312 eV)(?=9.45 ?m) (?=1058 cm-1), revealed anti-inflammatory effects. The anti-oxidant and anti-tumor effects of C. vulgaris were shown at (E=-0.1387 eV)(?=8.95 ?m)(?=1117 cm-1). The results showed effects of improvement of calcium conductivity and anti-inflammatory, antioxidant and antitumor effects of C. vulgaris on human health

Widespread Aberrant Alternative Splicing despite Molecular Remission in Chronic Myeloid Leukaemia Patients

Vast transcriptomics and epigenomics changes are characteristic of human cancers, including leukaemia. At remission, we assume that these changes normalise so that omics-profiles resemble those of healthy individuals. However, an in-depth transcriptomic and epigenomic analysis of cancer remission has not been undertaken. A striking exemplar of targeted remission induction occurs in chronic myeloid leukaemia (CML) following tyrosine kinase inhibitor (TKI) therapy. Using RNA sequencing and whole-genome bisulfite sequencing, we profiled samples from chronic-phase CML patients at diagnosis and remission and compared these to healthy donors. Remarkably, our analyses revealed that abnormal splicing distinguishes remission samples from normal controls. This phenomenon is independent of the TKI drug used and in striking contrast to the normalisation of gene expression and DNA methylation patterns. Most remarkable are the high intron retention (IR) levels that even exceed those observed in the diagnosis samples. Increased IR affects cell cycle regulators at diagnosis and splicing regulators at remission. We show that aberrant splicing in CML is associated with reduced expression of specific splicing factors, histone modifications and reduced DNA methylation. Our results provide novel insights into the changing transcriptomic and epigenomic landscapes of CML patients during remission. The conceptually unanticipated observation of widespread aberrant alternative splicing after remission induction warrants further exploration. These results have broad implications for studying CML relapse and treating minimal residual disease

Children’s and adolescents’ rising animal-source food intakes in 1990–2018 were impacted by age, region, parental education and urbanicity

Animal-source foods (ASF) provide nutrition for children and adolescents’ physical and cognitive development. Here, we use data from the Global Dietary Database and Bayesian hierarchical models to quantify global, regional and national ASF intakes between 1990 and 2018 by age group across 185 countries, representing 93% of the world’s child population. Mean ASF intake was 1.9 servings per day, representing 16% of children consuming at least three daily servings. Intake was similar between boys and girls, but higher among urban children with educated parents. Consumption varied by age from 0.6 at <1 year to 2.5 servings per day at 15–19 years. Between 1990 and 2018, mean ASF intake increased by 0.5 servings per week, with increases in all regions except sub-Saharan Africa. In 2018, total ASF consumption was highest in Russia, Brazil, Mexico and Turkey, and lowest in Uganda, India, Kenya and Bangladesh. These findings can inform policy to address malnutrition through targeted ASF consumption programmes.publishedVersio

Incident type 2 diabetes attributable to suboptimal diet in 184 countries

The global burden of diet-attributable type 2 diabetes (T2D) is not well established. This risk assessment model estimated T2D incidence among adults attributable to direct and body weight-mediated effects of 11 dietary factors in 184 countries in 1990 and 2018. In 2018, suboptimal intake of these dietary factors was estimated to be attributable to 14.1 million (95% uncertainty interval (UI), 13.8–14.4 million) incident T2D cases, representing 70.3% (68.8–71.8%) of new cases globally. Largest T2D burdens were attributable to insufficient whole-grain intake (26.1% (25.0–27.1%)), excess refined rice and wheat intake (24.6% (22.3–27.2%)) and excess processed meat intake (20.3% (18.3–23.5%)). Across regions, highest proportional burdens were in central and eastern Europe and central Asia (85.6% (83.4–87.7%)) and Latin America and the Caribbean (81.8% (80.1–83.4%)); and lowest proportional burdens were in South Asia (55.4% (52.1–60.7%)). Proportions of diet-attributable T2D were generally larger in men than in women and were inversely correlated with age. Diet-attributable T2D was generally larger among urban versus rural residents and higher versus lower educated individuals, except in high-income countries, central and eastern Europe and central Asia, where burdens were larger in rural residents and in lower educated individuals. Compared with 1990, global diet-attributable T2D increased by 2.6 absolute percentage points (8.6 million more cases) in 2018, with variation in these trends by world region and dietary factor. These findings inform nutritional priorities and clinical and public health planning to improve dietary quality and reduce T2D globally.publishedVersio

The great tit HapMap project: a continental‐scale analysis of genomic variation in a songbird

A major aim of evolutionary biology is to understand why patterns of genomic diversity vary within taxa and space. Large-scale genomic studies of widespread species are useful for studying how environment and demography shape patterns of genomic divergence. Here, we describe one of the most geographically comprehensive surveys of genomic variation in a wild vertebrate to date; the great tit (Parus major) HapMap project. We screened ca 500,000 SNP markers across 647 individuals from 29 populations, spanning ~30 degrees of latitude and 40 degrees of longitude – almost the entire geographical range of the European subspecies. Genome-wide variation was consistent with a recent colonisation across Europe from a South-East European refugium, with bottlenecks and reduced genetic diversity in island populations. Differentiation across the genome was highly heterogeneous, with clear ‘islands of differentiation’, even among populations with very low levels of genome-wide differentiation. Low local recombination rates were a strong predictor of high local genomic differentiation (FST), especially in island and peripheral mainland populations, suggesting that the interplay between genetic drift and recombination causes highly heterogeneous differentiation landscapes. We also detected genomic outlier regions that were confined to one or more peripheral great tit populations, probably as a result of recent directional selection at the species' range edges. Haplotype-based measures of selection were related to recombination rate, albeit less strongly, and highlighted population-specific sweeps that likely resulted from positive selection. Our study highlights how comprehensive screens of genomic variation in wild organisms can provide unique insights into spatio-temporal evolutionary dynamics

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr

Implementing shared micro-depots in the last-mile logistics in Finland

The purpose of this research-based bachelor’s thesis is to simplify the transition to shared micro-depots for start-up logistics companies in Finland, based on the understanding of the peculiarities of logistics in the Finnish market. While the aim is to create practical recommendations for those willing who want to switch to a new system. The implementation of the practice of introducing shared micro-depots is another step towards more sustainable and cleaner logistics. The objectives were formulated as a research question: How to make it easier for Finnish start-up logistics companies to switch to shared micro-depots in last-mile logistics? Research objects are last-mile logistics as a final step of the delivery process and micro-depots as a logistics facility. Transportation is a key component of logistics which is investigated in this paper. The companies of a foreign origin are investigated in this paper. Essential recommendations for the Finnish start-up companies which intend to adopt these experimental logistics technologies, are proposed within the framework of this work. This paper uses an empirical type of research, as new data is collected from various scientific literature sources and studies. The research methods of the thesis were a questionnaire and two structured qualitative interviews. Since the paper describes the trend of introducing shared micro-depots into the last-mile logistics, it can be argued that we also have a descriptive study in front of us. Primary research is conducted mainly in Helsinki Region. Target audience - Finnish start-up logistics companies, operating in the last-mile logistics. The results revealed that the initiative of a shared micro-depot’s introduction has not only the pitfalls, but a substantial list of benefits, such as provision of environment-friendly and cost-efficient services while implementing sustainable types of modes in the last-mile logistics delivery; growing IT development thrives in Finland, especially in Helsinki and Espoo where reaserch and development centers are located; more and more emerging opportunities and terms for route optimisation. I would like to express my gratitude to a director of operations at DSV and a head of CoDi (Collection & Distribution) at DB Schenker. I prepared a questionnaire for DSV and DB Schenker in advance, utilising a Webropol 3.0 tool in order to conduct company-focused interviews

Kooperationstheoretische Analyse der Ökumene zwischen der römisch-katholischen und orthodoxen Kirche

Die Ökumene zwischen der römisch-katholischen und orthodoxen Kirche (OK-RK Ökumene) eignet sich gut für eine Analyse aus betriebswirtschaftlich-organisatorischer Sicht, da sie wegen der derzeitigen theologischen Nähe am Wendepunkt zur Realisierung vermutet wird und somit die Frage der Organisation in Einheit ein zentrales Anliegen bei den Kirchen geworden ist. Da sich die Suche nach einem geeigneten Modell für die Einheit schwierig gestaltet, soll zuerst geklärt werden, ob eine Einheit möglich ist. So leiten sich die zwei forschungsleitenden Fragen der Dissertation ab: (1) Unter welchen Bedingungen (Kontext) kann eine Zusammenarbeit von OK und RK stattfinden? (2) Welche Formen kann diese Zusammenarbeit annehmen? Die Arbeit interpretiert die OK-RK Ökumene als Kooperation, und analysiert folglich die Ökumenechronik (ca. 20 Jahrhunderte, unterteilt in 29 Perioden) mit Hilfe des Kooperationsbezugsrahmens von Schrader (1993). Ad (1) werden mittels hierarchische Clusterung und Klassifikationsbäumen einerseits Kontextmuster erkannt, für die eine Kooperation unwahrscheinlich ist, und andererseits solche erkannt, für die das Auftreten von Unionen oder andere Kooperationsformen wahrscheinlich ist. Ad (2) wird der Kontingenzidee folgend die Zielform für die Ökumene konkretisiert, unter der Annahme eines im gleichen Cluster bleibenden Kontextes. Abschließend werden die in der Ökumeneliteratur diskutierten Einheitsmodelle bewertet, sowie Empfehlungen für die Gestaltung eines Ziel-Einheitsmodells ausgesprochen. Die Arbeit stellt die erste empirische Prüfung des Meta-Bezugsrahmens von Schrader dar. Seine Kontingenzhypothese konnte bestätigt werden, die Effizienzhypothese weder bestätigt, noch widerlegt werden. Es lassen sich drei Hypothesen für die Kooperationsforschung ableiten: (a) Die Existenz von Kooperationen ist höchst kontextsensibel. Sind "zu wenige" Kontextmerkmale vorhanden, entsteht keine Kooperation bzw. eine bestehende Kooperation erlischt. (b) Die Kooperationsformen differenzieren sich in Abhängigkeit vom Partnerfit. Während die anderen Kontextmerkmale (subsumiert unter "Umweltdruck") eine Notwendigkeit für das Zustandekommen von Kooperationen darstellen, muss Partnerfit nicht gegeben sein. Sein (teilweises) Fehlen (Misfit) führt aber zu spezifischen, "fast leeren" Kooperationsformen, d.h. zu Formen mit wenigen "wahren" Merkmalen. (c) Unter den Merkmalen des Partnerfits hat das Merkmal Interdependenz der Partner einen großen Einfluss auf die Entscheidung zur Kooperation