87 research outputs found
Exploring genetic associations with ceRNA regulation in the human genome
No full textabstract: Competing endogenous RNAs (ceRNAs) are RNA molecules that sequester shared microRNAs (miRNAs) thereby affecting the expression of other targets of the miRNAs. Whether genetic variants in ceRNA can affect its biological function and disease development is still an open question. Here we identified a large number of genetic variants that are associated with ceRNA's function using Geuvaids RNA-seq data for 462 individuals from the 1000 Genomes Project. We call these loci competing endogenous RNA expression quantitative trait loci or ‘cerQTL’, and found that a large number of them were unexplored in conventional eQTL mapping. We identified many cerQTLs that have undergone recent positive selection in different human populations, and showed that single nucleotide polymorphisms in gene 3΄UTRs at the miRNA seed binding regions can simultaneously regulate gene expression changes in both cis and trans by the ceRNA mechanism. We also discovered that cerQTLs are significantly enriched in traits/diseases associated variants reported from genome-wide association studies in the miRNA binding sites, suggesting that disease susceptibilities could be attributed to ceRNA regulation. Further in vitro functional experiments demonstrated that a cerQTL rs11540855 can regulate ceRNA function. These results provide a comprehensive catalog of functional non-coding regulatory variants that may be responsible for ceRNA crosstalk at the post-transcriptional level.The final version of this article, as published in Nucleic Acids Research, can be viewed online at: https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkx33
Financial analysis of Pivovar Cerna Hora, a. s.
No full textThis bachelor thesis deals with a financial analysis of the company "Pivovar Cerna Hora, a. s." for the period 2011 - 2014. Its goal is to use the appropriate tools to evaluate the overall financial situation of the company. The work is divided into two parts. The methodological part describes the structure and relevance of selected financial indicators and methods. These are applied in practical part which contains the calculated values alongside their interpretations. It includes horizontal and vertical analysis of financial statements, ratio analysis and selected bankruptcy and credibility models. Finally, SWOT analysis focuses on non-financial indicators
Role of the long non-coding RNA PVT1 in the dysregulation of the ceRNA-ceRNA network in human breast cancer
No full textRecent findings have identified competing endogenous RNAs (ceRNAs) as the drivers in many disease conditions, including cancers. The ceRNAs indirectly regulate each other by reducing the amount of microRNAs (miRNAs) available to target messenger RNAs (mRNAs). The ceRNA interactions mediated by miRNAs are modulated by a titration mechanism, i.e. large changes in the ceRNA expression levels either overcome, or relieve, the miRNA repression on competing RNAs; similarly, a very large miRNA overexpression may abolish competition. The ceRNAs are also called miRNA decoys or miRNA sponges and encompass different RNAs competing with each other to attract miRNAs for interactions: mRNA, long non-coding RNAs (lncRNAs), pseudogenes, or circular RNAs. Recently, we developed a computational method for identifying ceRNA-ceRNA interactions in breast invasive carcinoma. We were interested in unveiling which lncRNAs could exert the ceRNA activity. We found a drastic rewiring in the cross-talks between ceRNAs from the physiological to the pathological condition. The main actor of this dysregulated lncRNA-associated ceRNA network was the lncRNA PVT1, which revealed a net biding preference towards the miR-200 family members in normal breast tissues. Despite its up-regulation in breast cancer tissues, mimicked by the miR-200 family members, PVT1 stops working as ceRNA in the cancerous state. The specific conditions required for a ceRNA landscape to occur are still far from being determined. Here, we emphasized the importance of the relative concentration of the ceRNAs, and their related miRNAs. In particular, we focused on the withdrawal in breast cancer tissues of the PVT1 ceRNA activity and performed a gene expression and sequence analysis of its multiple isoforms. We found that the PVT1 isoform harbouring the binding site for a representative miRNA of the miR-200 family shows a drastic decrease in its relative concentration with respect to the miRNA abundance in breast cancer tissues, providing a plausibility argument to the breakdown of the sponge program orchestrated by the oncogene PVT1. © 2017 Conte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
A network-based matrix factorization framework for ceRNA co-modules recognition of cancer genomic data
No full text\ua9 The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]. With the development of high-throughput technologies, the accumulation of large amounts of multidimensional genomic data provides an excellent opportunity to study the multilevel biological regulatory relationships in cancer. Based on the hypothesis of competitive endogenous ribonucleic acid (RNA) (ceRNA) network, lncRNAs can eliminate the inhibition of microRNAs (miRNAs) on their target genes by binding to intracellular miRNA sites so as to improve the expression level of these target genes. However, previous studies on cancer expression mechanism are mostly based on individual or two-dimensional data, and lack of integration and analysis of various RNA-seq data, making it difficult to verify the complex biological relationships involved. To explore RNA expression patterns and potential molecular mechanisms of cancer, a network-regularized sparse orthogonal-regularized joint non-negative matrix factorization (NSOJNMF) algorithm is proposed, which combines the interaction relations among RNA-seq data in the way of network regularization and effectively prevents multicollinearity through sparse constraints and orthogonal regularization constraints to generate good modular sparse solutions. NSOJNMF algorithm is performed on the datasets of liver cancer and colon cancer, then ceRNA co-modules of them are recognized. The enrichment analysis of these modules shows that >90% of them are closely related to the occurrence and development of cancer. In addition, the ceRNA networks constructed by the ceRNA co-modules not only accurately mine the known correlations of the three RNA molecules but also further discover their potential biological associations, which may contribute to the exploration of the competitive relationships among multiple RNAs and the molecular mechanisms affecting tumor development
INTERRELATIONSHIPS BETWEEN MACULAR CAROTENOIDS, RETINAL MORPHOMETRY, AND COGNITIVE FUNCTION IN PERSONS WITH MULTIPLE SCLEROSIS
No full textBackground: Multiple sclerosis (MS) is a neurodegenerative, autoimmune disease that affects oligodendrocyte-producing myelin cells and leads to cognitive, visual, affective, and motor problems, as well as fatigue, bowel dysfunction, among other symptoms. Although MS etiopathology is incompletely understood, it is known to be influenced by hereditary and environmental factors which can drastically affect the course of the disease. Amongst environmental factors, nutrition has gained significant attention. In 2015, The National Multiple Sclerosis Society published a report detailing that among various alternative approaches, diet was of the highest interest within the MS community, in part due to the limited dietary therapies as well as the poor efficacy of pharmacological approaches. Due to the health-promoting benefits that consumption of fruits and vegetables confer, their dietary components have gained substantial attention. Recently, lutein and zeaxanthin, dietary xanthophylls, have been shown to be associated with cognitive health. Although xanthophylls are not recognized to be essential, their lack of endogenous de novo synthesis necessitates regular dietary consumption to derive benefits. Macular xanthophylls are dietary carotenoids that comprise the macular pigment, serving as blue light filters and countering photooxidative damage. The robust antioxidant effects of carotenoids could support nerve health and protect against cognitive decline. However, macular xanthophyll status and its implications for markers of neuroaxonal degeneration, such as retinal morphometry, have not been examined among persons with MS. Specifically, the research presented herein aimed to explore the implications of macular and serum xanthophyll status for markers of retinal morphometry, and the associations between macular xanthophyll accumulation, retinal morphometry, and cognitive function in adults 18-64 years old with MS, with (MS-ON) and without ON (MS), and healthy controls (HC).
Methods: Adults 18-64 years (HC, n=42; MS, n=40-42) participated in a cross-sectional study. Macular pigment optical density (MPOD) was measured via heterochromatic flicker photometry using a macular densitometer. Retinal morphometry was measured via optical coherence tomography (OCT). Serum carotenoids were quantified using high-performance liquid chromatography. Dietary carotenoids were assessed using 7-day dietary records. Cognitive function was assessed using an Eriksen Flanker task for attentional control with event-related potentials (ERPs). One-way analysis of variance was conducted to determine group effects on macular, serum, and dietary carotenoids. Partial correlations examined the relationships between MPOD, OCT metrics, dietary variables, and serum carotenoids (with a false discovery rate [FDR] correction implemented for exploratory analyses with serum and dietary variables). Independent sample t-test/Mann-Whitney U-test was conducted to assess between-group differences, and Spearman’s Rank correlations were used to examine the relationships between MPOD and retinal morphometry with covariates and cognitive variables of interest. Linear regressions were used to explore the relationship between retinal and cognitive measures.
Results: Persons with MS-ON had lower MPOD and thickness and volume in OCT than HCs (i.e., optic disc retinal nerve fiber layer [odRNFL], macular retinal nerve fiber layer [mRNFL], total macular volume [TMV]). MS had significantly lower odRNFL thickness than HCs, and lower serum lutein than MS-ON subjects. Among MS, MPOD was positively correlated with odRNFL thickness and TMV, whereas odRNFL was negatively correlated with serum lutein and zeaxanthin. Between-group differences were observed in all cognitive outcomes showing lower attentional performance in persons with MS. After covariate adjustment, linear regressions showed that MPOD significantly predicted variance for incongruent P3 peak latency and odRNFL significantly predicted variance for congruent reaction time and congruent P3 peak latency. Interestingly, the interaction term between MPOD and odRNFL significantly predicted variance in all but one metric (congruent P3 peak latency).
Conclusion: These findings provide initial evidence that persons with MS-ON have poorer xanthophyll status in the macula and serum. Further, MPOD was positively associated with beneficial anatomical features in the MS group. These results suggest that MPOD might be protective of AVP structural integrity. Additionally, higher carotenoid accumulation in the macula and higher retinal and optic nerve thickness were associated with greater attentional control, using both behavioral and neuroelectric indices, among people with MS.Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2023-05-01The student, Jonathan Cerna, accepted the attached license on 2021-04-22 at 11:21.The student, Jonathan Cerna, submitted this Thesis for approval on 2021-04-22 at 11:36.This Thesis was approved for publication on 2021-04-27 at 18:20.DSpace SAF Submission Ingestion Package generated from Vireo submission #16502 on 2021-09-16 at 17:04:51Made available in DSpace on 2021-09-17T02:34:45Z (GMT). No. of bitstreams: 3
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Previous issue date: 2021-04-27Embargo set by: Seth Robbins for item 118573
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Construction of competing endogenous RNA networks from paired RNA-seq data sets by pointwise mutual information
No full text© 2019 The Author(s). Background: A long noncoding RNA (lncRNA) can act as a competing endogenous RNA (ceRNA) to compete with an mRNA for binding to the same miRNA. Such an interplay between the lncRNA, miRNA, and mRNA is called a ceRNA crosstalk. As an miRNA may have multiple lncRNA targets and multiple mRNA targets, connecting all the ceRNA crosstalks mediated by the same miRNA forms a ceRNA network. Methods have been developed to construct ceRNA networks in the literature. However, these methods have limits because they have not explored the expression characteristics of total RNAs. Results: We proposed a novel method for constructing ceRNA networks and applied it to a paired RNA-seq data set. The first step of the method takes a competition regulation mechanism to derive candidate ceRNA crosstalks. Second, the method combines a competition rule and pointwise mutual information to compute a competition score for each candidate ceRNA crosstalk. Then, ceRNA crosstalks which have significant competition scores are selected to construct the ceRNA network. The key idea, pointwise mutual information, is ideally suitable for measuring the complex point-to-point relationships embedded in the ceRNA networks. Conclusion: Computational experiments and results demonstrate that the ceRNA networks can capture important regulatory mechanism of breast cancer, and have also revealed new insights into the treatment of breast cancer. The proposed method can be directly applied to other RNA-seq data sets for deeper disease understanding
"Och gamla som lever som om vi vore unga" : En studie om äldre utlandsföddas upplevelse av ålderdomen
No full textSyftet med denna studie har varit att på ett explorativt sätt undersöka hur äldre utlandsfödda upplever sitt åldrande i Sverige, samt att med hjälp av intervjuer och tidigare forskning öka förståelsen för de specifika villkoren som åldrandet i Sverige innebär för denna grupp. Studiens empiriska material bestod av kvalitativa intervjuer i form av en fokusgrupp med sex respondenter mellan 60 till 84 år och en individuell intervju med en respondent som var 89 år. Samtliga respondenter var kvinnor. Studiens teoretiska referensram består bland annat av Blumers tre antaganden om grunden till symbolisk interaktionism och Bergs teoretiska förståelse om språkets vikt för jagets utveckling samt av Baumans teori om det individualiserade samhället tillsammans med Becks teori om att individen själv skapar sina förutsättningar för sin levnadsbana. Bergs karaktärsdrag för identitetsskapandet har använts som ett teoretiskt verktyg för studiens analys. Resultaten i denna studie visar att de äldre utlandsfödda är en utsatt grupp på grund av bristande i svenska språket. Resultaten visar också på att genom att ta till sig vissa delar av det svenska individualiserade samhällstänket och behålla sin ursprungskultur såsom att träffa likasinnade och spansktalande så har de äldre anpassat sig till att få ut det bästa av Sverige och sin ursprungskultur. Titel: ”Och gamla som lever som om vi vore unga” – En studie om äldre utlandsföddas upplevelse av ålderdomen Författare: Ella Cerna Gonzalez Antal ord: 11 259 Nyckelord: Äldre, utlandsfödda, äldreforskning, ålderdom, åldrande, språk, identitetThe purpose of this study has been to research in an explorative way how senior citizens who were born in other countries experience their ageing in Sweden. The study's empirical material consisted of qualitative interviews in the form of a focus group with six respondents between the age of 60 and 84 years old and one individual interview with a respondent who was 89 years. All respondents were women. The study's theoretical frame of reference consists, among other things, of Blumer's three assumptions about the basis of symbolic interactionism and Berg's theoretical understanding of the importance of language for the development of self, and of Bauman's theory of individualized society. Another is Beck's theory about the individual himself that creates the conditions for their own life path. Berg's character traits for identity creation have been used as a theoretical tool for the study's analysis. The results of this study show that the elderly born in other countries are a vulnerable group due to a lack of Swedish language. The results also show that by adopting certain parts of the Swedish individualized society and retaining its original culture such as meeting like-minded and Hispanic speakers, the elderly have adapted to getting the best out of Sweden and their native culture. Title: "And old people who live as if we were young" - A study about elderly born in other countries experience of old age Author: Ella Cerna Gonzalez Number of words: 11,259 Keywords: Elderly, born in other countries, gerontology, old age, aging, language, identit
"Och gamla som lever som om vi vore unga" : En studie om äldre utlandsföddas upplevelse av ålderdomen
No full textSyftet med denna studie har varit att på ett explorativt sätt undersöka hur äldre utlandsfödda upplever sitt åldrande i Sverige, samt att med hjälp av intervjuer och tidigare forskning öka förståelsen för de specifika villkoren som åldrandet i Sverige innebär för denna grupp. Studiens empiriska material bestod av kvalitativa intervjuer i form av en fokusgrupp med sex respondenter mellan 60 till 84 år och en individuell intervju med en respondent som var 89 år. Samtliga respondenter var kvinnor. Studiens teoretiska referensram består bland annat av Blumers tre antaganden om grunden till symbolisk interaktionism och Bergs teoretiska förståelse om språkets vikt för jagets utveckling samt av Baumans teori om det individualiserade samhället tillsammans med Becks teori om att individen själv skapar sina förutsättningar för sin levnadsbana. Bergs karaktärsdrag för identitetsskapandet har använts som ett teoretiskt verktyg för studiens analys. Resultaten i denna studie visar att de äldre utlandsfödda är en utsatt grupp på grund av bristande i svenska språket. Resultaten visar också på att genom att ta till sig vissa delar av det svenska individualiserade samhällstänket och behålla sin ursprungskultur såsom att träffa likasinnade och spansktalande så har de äldre anpassat sig till att få ut det bästa av Sverige och sin ursprungskultur. Titel: ”Och gamla som lever som om vi vore unga” – En studie om äldre utlandsföddas upplevelse av ålderdomen Författare: Ella Cerna Gonzalez Antal ord: 11 259 Nyckelord: Äldre, utlandsfödda, äldreforskning, ålderdom, åldrande, språk, identitetThe purpose of this study has been to research in an explorative way how senior citizens who were born in other countries experience their ageing in Sweden. The study's empirical material consisted of qualitative interviews in the form of a focus group with six respondents between the age of 60 and 84 years old and one individual interview with a respondent who was 89 years. All respondents were women. The study's theoretical frame of reference consists, among other things, of Blumer's three assumptions about the basis of symbolic interactionism and Berg's theoretical understanding of the importance of language for the development of self, and of Bauman's theory of individualized society. Another is Beck's theory about the individual himself that creates the conditions for their own life path. Berg's character traits for identity creation have been used as a theoretical tool for the study's analysis. The results of this study show that the elderly born in other countries are a vulnerable group due to a lack of Swedish language. The results also show that by adopting certain parts of the Swedish individualized society and retaining its original culture such as meeting like-minded and Hispanic speakers, the elderly have adapted to getting the best out of Sweden and their native culture. Title: "And old people who live as if we were young" - A study about elderly born in other countries experience of old age Author: Ella Cerna Gonzalez Number of words: 11,259 Keywords: Elderly, born in other countries, gerontology, old age, aging, language, identit
Evaluation of cyclic behavior of dense sands under multidirectional loading using centrifuge tests
No full textThe seismic performance of nuclear power plant (NPP) structures constructed on compacted, coarse-grained soil depends on the soil’s cyclic shear stress – shear strain – volumetric strain response. NPPs founded on a thick deposit of dense coarse-grained soil may experience nontrivial settlements due to small, but accumulated volumetric strains during an earthquake. Studies that have investigated the seismic response of granular are primarily limited to unidirectional loading. However, since seismic events are multidirectional in nature, design based on unidirectional studies may lead to underestimation of vertical strains, and nontrivial settlements that can impact structures. While correlations to estimate vertical strains from drained and undrained cyclic element tests are available, they do not all explicitly incorporate multidirectional shaking. Moreover, typical drainage conditions in the field may be partially drained while shaking-induced vertical strains accumulate. This work forms a unique database of dynamic centrifuge “case-histories” that provide insight into the shear and volumetric response of dense coarse-grained soils under unidirectional and bidirectional loading under partially drained conditions. Dynamic centrifuge tests were performed on thick (up to 20m) layers of saturated dense Ottawa sand (D = 95%) with models representing both free-field and a soil-structure (near field) system excited using unidirectional and bidirectional historical broadband motions.
Free-field centrifuge experiments highlight that shear response in each orthogonal direction is not affected by multidirectionality. Thus, site shear response can be estimated for use in one-dimensional non-linear site response analysis. In contrast, centrifuge tests illustrated that volumetric strains (v) and excess porewater pressures (evaluated in terms of excess porewater pressure ratio, ru) are affected by multidirectionality irrespective of density, with the ratios of bidirectional to unidirectional v and ru ranging from 1 to 4. Consequently, multidirectional factors relationships for v and ru are proposed as a function of FSliq. Furthermore, Energy-based intensity measures (Arias and Housner intensities) provided nearly unique estimates of excess PWP and (v) for both 1D and 2D motions, indicating that they capture multi-directionality effects, while vectored peak accelerations and velocities (PGA and PGV) yielded different relationships for 1D and 2D motions.
A semi-empirical hyperbolic (GQ/H), simplified model based on ground motion intensity parameters (e.g., Housner Intensity), and shear wave velocity (Vs) is proposed to estimate vertical strains in dense coarse-grained soils under free field conditions. Comparison of GQ/H model predictions and estimates based on undrained cyclic shear tests indicated that the latter consistently overpredicts the measured settlements in the dense sand profiles. In contrast, the approach based on drained cyclic shear tests reasonably agrees with both measured settlements and GQ/H-v model. Further comparison of recorded near field settlements from centrifuge test data indicate that the (GQ/H) simplified free model underestimates settlements beneath the structures tested here.
Lastly, a semi-empirical near field model to estimate vertical strains beneath structures is proposed. This model also includes ground motion intensity measures to account for duration (e.g., Housner intensity) in conjunction with a rocking stiffness parameter (originally proposed by Gazetas 1991) derived from shear wave velocity Vs. The vertical strain model requires estimates of Housner Intensity by means of nonlinear site response analysis. The proposed vertical strain models reasonably capture free field and near field settlements on dense sands recorded in dynamic centrifuge tests.
The aforementioned two semi-empirical models are used in conjunction to estimate settlements of structures founded primarily on dense sands during shaking.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2020-05-01The student, Alfonso Cerna Diaz, accepted the attached license on 2018-04-17 at 14:57.The student, Alfonso Cerna Diaz, submitted this Dissertation for approval on 2018-04-17 at 15:02.This Dissertation was approved for publication on 2018-04-20 at 08:15.DSpace SAF Submission Ingestion Package generated from Vireo submission #12217 on 2018-08-31 at 17:27:46Made available in DSpace on 2018-09-04T20:47:11Z (GMT). No. of bitstreams: 2
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Previous issue date: 2018-04-20Embargo set by: Seth Robbins for item 107391
Lift date: 2020-09-04T20:47:38Z
Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemEmbargo set by: Seth Robbins for item 107391
Lift date: 2020-09-04T20:50:11Z
Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemLimited Restriction Lifted for Item 107391 on 2020-09-05T09:15:20Z
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