Genome-wide profiling of human cap-independent translation-enhancing elements.

We report an in vitro selection strategy to identify RNA sequences that mediate cap-independent initiation of translation. This method entails mRNA display of trillions of genomic fragments, selection for initiation of translation and high-throughput deep sequencing. We identified >12,000 translation-enhancing elements (TEEs) in the human genome, generated a high-resolution map of human TEE-bearing regions (TBRs), and validated the function of a subset of sequences in vitro and in cultured cells

The crowdfunding business model in Poland and sustainable development – value transfer

Cel – Celem badań jest wykazanie transferu wartości w modelu biznesowym przedsiębiorstw korzystających z crowdfundingu w Polsce w oparciu o ideę zrównoważonego rozwoju w prowadzeniu biznesu. Metoda badań – Przeprowadzono badanie ankietowe na grupie 121 przedsiębiorstw korzystających z crowdfundingu. Badanie to zostało przeprowadzone w oparciu o wartości Nortona i Kaplana. Wyniki badań ankietowych pozwoliły na opracowanie modelu przepływu wartości zgodnie z koncepcją E3 oraz ideą zrównoważonego rozwoju w prowadzeniu biznesu. Wnioski – Przeprowadzone analizy wykazały, że najważniejszą perspektywą wartości crowdfundingu jest perspektywa finansowa i procesowa, zaś biorąc pod uwagę model crowdfundingu w powiązaniu z koncepcją zrównoważonego rozwoju, najważniejsze są wymiary: ekonomiczny i społeczny. Oryginalność / wartość / implikacje / rekomendacje – Wartością dodaną badań jest poznanie modelu biznesowego crowdfundingu i tworzenie wartości w CF dla firmy stosującej model E3 z uwzględnieniem wartości ekonomicznych, społecznych i środowiskowych. Stworzono ponadto nowy model w oparciu o wyniki ankietowe, co wpisuje się w dyskurs naukowy i wypełnia lukę badawczą w tym obszarze. Ponadto model ten pozwala na analizę zarówno wartości oferowanej, jak i wartości uchwyconej – nie tylko dla firm, ale też każdego uczestnika zgodnie w ideą zrównoważonego rozwoju.Purpose – The purpose of the research was to present the transfer of value in the business model of companies using crowdfunding in Poland based on the idea of sustainability in doing business. Research method – A survey was conducted on a group of 121 enterprises using crowdfunding. It used the Norton-Kaplan value map and the value flow model in accordance with the E3 concept and the idea of sustainable development Results – The conducted analyses have shown that the most important perspective of the value of crowdfunding is the financial and procedural perspective, while taking into account the crowdfunding model in conjunction with the concept of sustainable development, the most important are the economic and social dimensions. Originality / value / implications / recommendations – The added value of research is learning about the crowdfunding business model and creating value in CF for a company using the E3 model, taking into account economic, social and environmental values. Moreover, a new model was created based on the survey results, which is in line with the scientific discourse and thus bridges the research gap in this area. In addition, this model allows for the analysis of both the value offered and the value captured, not only for companies, but for each participant in accordance with the idea of sustainable development.Badanie zostało sfinansowane z grantu NCN nr umowy 2017/25/B/HS4/02225.Aneta Ewa Waszkiewicz: [email protected] Kukurba: [email protected] Salwin: [email protected] Wójcik: [email protected] Ewa Waszkiewicz - Szkoła Główna Handlowa w WarszawieMaria Kukurba - Politechnika WarszawskaMariusz Salwin - Politechnika WarszawskaCezary Wójcik - Szkoła Główna Handlowa w WarszawieAdvances in Crowdfunding: Research and Practice, 2020, Shneor R., Zhao L., Flåten B.T. 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Effect of polyols and selected dental materials on the ability to create a cariogenic biofilm : on children caries-associated "Streptococcus Mutans" isolates

Secondary caries is a disease associated with the formation of biofilm on the border of the tooth and dental filling. Its development is strongly influenced by the dietary sweet foods and the type of dental material. The aim of the study was to assess the effect of sweeteners on the ability of clinical Streptococcus mutans strains to form biofilm on dental materials. Strains were isolated from plaque samples from 40 pediatric patients from the 3–6 ICADS II group. The ability to form biofilm was tested on composite and glass ionomer dental materials used for milk teeth filling in the presence of sucrose, xylitol, sorbitol, and erythritol. The bacterial film mass after 12, 24, 48, and 72 h and the number of bacterial colonies significantly decreased (p < 0.01) compared to the initial value for 5% erythritol and sorbitol on examined materials. A greater inhibitory effect was noted for glass ionomers compared to composites. Sucrose and xylitol supported biofilm formation, while erythritol had the best inhibitory effect. The use of fluoride-releasing glass ionomers exerted an effect synergistic to erythritol, i.e., inhibited plaque formation and the amount of cariogenic S. mutans. Selection of proper type of dental material together with replacing sucrose with polyols can significantly decrease risk of secondary caries development. Erithritol in combination with glass ionomer seems to be the most effective in secondary caries prevention

Differences in sweet taste perception and its association with the "Streptococcus mutans" cariogenic profile in preschool children with caries

The aim of the study was to verify the hypothesis about differences in sweet taste perception in the group of preschool children with and without caries, and to determine its relationship with cariogenic microbiota and the frequency of sweets consumption in children. The study group included of 63 children aged 2&ndash;6 years: 32 with caries and 31 without caries. The study consisted of collecting questionnaire data and assessment of dental status using the decayed, missing, filled in primary teeth index (dmft) and the International Caries Detection and Assessment System (ICDAS II). The evaluation of sweet taste perception was carried out using a specific method that simultaneously assessed the level of taste preferences and the sensitivity threshold for a given taste. The microbiological analysis consisted of the assessment of the quantitative and qualitative compositions of the oral microbiota of the examined children. The sweet taste perception of children with caries was characterized by a lower susceptibility to sucrose (the preferred sucrose solution concentration was &gt;4 g/L) compared to children without caries (in the range &le; 4 g/L, p = 0.0015, chi-square test). A similar relationship was also observed for frequent snacking between meals (p = 0.0038, chi-square test). The analysis of studied variables showed the existence of a strong positive correlation between the perception of sweet taste and the occurrence and intensity of the cariogenic process (p = 0.007 for dmft; and p = 0.012 for ICDAS II), as well as the frequency of consuming sweets (p &le; 0.001 for frequent and repeated consumption of sweets during the day, Spearman test) in children with caries. Additionally, children with an elevated sucrose taste threshold were more than 10-times more likely to develop S. mutans presence (OR = 10.21; 95% CI 3.11&ndash;33.44). The results of this study suggest the future use of taste preferences in children as a diagnostic tool for the early detection of increased susceptibility to caries through microbial dysbiosis towards specific species of microorganisms

Allelic Expression of Deleterious Protein-Coding Variants across Human Tissues

Personal exome and genome sequencing provides access to loss-of-function and rare deleterious alleles whose interpretation is expected to provide insight into individual disease burden. However, for each allele, accurate interpretation of its effect will depend on both its penetrance and the trait's expressivity. In this regard, an important factor that can modify the effect of a pathogenic coding allele is its level of expression; a factor which itself characteristically changes across tissues. To better inform the degree to which pathogenic alleles can be modified by expression level across multiple tissues, we have conducted exome, RNA and deep, targeted allele-specific expression (ASE) sequencing in ten tissues obtained from a single individual. By combining such data, we report the impact of rare and common loss-of-function variants on allelic expression exposing stronger allelic bias for rare stop-gain variants and informing the extent to which rare deleterious coding alleles are consistently expressed across tissues. This study demonstrates the potential importance of transcriptome data to the interpretation of pathogenic protein-coding variants

Profiling allele-specific gene expression in brains from individuals with autism spectrum disorder reveals preferential minor allele usage.

One fundamental but understudied mechanism of gene regulation in disease is allele-specific expression (ASE), the preferential expression of one allele. We leveraged RNA-sequencing data from human brain to assess ASE in autism spectrum disorder (ASD). When ASE is observed in ASD, the allele with lower population frequency (minor allele) is preferentially more highly expressed than the major allele, opposite to the canonical pattern. Importantly, genes showing ASE in ASD are enriched in those downregulated in ASD postmortem brains and in genes harboring de novo mutations in ASD. Two regions, 14q32 and 15q11, containing all known orphan C/D box small nucleolar RNAs (snoRNAs), are particularly enriched in shifts to higher minor allele expression. We demonstrate that this allele shifting enhances snoRNA-targeted splicing changes in ASD-related target genes in idiopathic ASD and 15q11-q13 duplication syndrome. Together, these results implicate allelic imbalance and dysregulation of orphan C/D box snoRNAs in ASD pathogenesis

HSRA: Hadoop-based spliced read aligner for RNA sequencing data

[Abstract] Nowadays, the analysis of transcriptome sequencing (RNA-seq) data has become the standard method for quantifying the levels of gene expression. In RNA-seq experiments, the mapping of short reads to a reference genome or transcriptome is considered a crucial step that remains as one of the most time-consuming. With the steady development of Next Generation Sequencing (NGS) technologies, unprecedented amounts of genomic data introduce significant challenges in terms of storage, processing and downstream analysis. As cost and throughput continue to improve, there is a growing need for new software solutions that minimize the impact of increasing data volume on RNA read alignment. In this work we introduce HSRA, a Big Data tool that takes advantage of the MapReduce programming model to extend the multithreading capabilities of a state-of-the-art spliced read aligner for RNA-seq data (HISAT2) to distributed memory systems such as multi-core clusters or cloud platforms. HSRA has been built upon the Hadoop MapReduce framework and supports both single- and paired-end reads from FASTQ/FASTA datasets, providing output alignments in SAM format. The design of HSRA has been carefully optimized to avoid the main limitations and major causes of inefficiency found in previous Big Data mapping tools, which cannot fully exploit the raw performance of the underlying aligner. On a 16-node multi-core cluster, HSRA is on average 2.3 times faster than previous Hadoop-based tools. Source code in Java as well as a user’s guide are publicly available for download at http://hsra.dec.udc.es.Ministerio de Economía, Industria y Competitividad; TIN2016-75845-PXunta de Galicia; ED431G/0

Genome, transcriptome and proteome: the rise of omics data and their integration in biomedical sciences

Advances in the technologies and informatics used to generate and process large biological data sets (omics data) are promoting a critical shift in the study of biomedical sciences. While genomics, transcriptomics and proteinomics, coupled with bioinformatics and biostatistics, are gaining momentum, they are still, for the most part, assessed individually with distinct approaches generating monothematic rather than integrated knowledge. As other areas of biomedical sciences, including metabolomics, epigenomics and pharmacogenomics, are moving towards the omics scale, we are witnessing the rise of inter-disciplinary data integration strategies to support a better understanding of biological systems and eventually the development of successful precision medicine. This review cuts across the boundaries between genomics, transcriptomics and proteomics, summarizing how omics data are generated, analysed and shared, and provides an overview of the current strengths and weaknesses of this global approach. This work intends to target students and researchers seeking knowledge outside of their field of expertise and fosters a leap from the reductionist to the global-integrative analytical approach in research

Population- and individual-specific regulatory variation in Sardinia

Genetic studies of complex traits have mainly identified associations with noncoding variants. To further determine the contribution of regulatory variation, we combined whole-genome and transcriptome data for 624 individuals from Sardinia to identify common and rare variants that influence gene expression and splicing. We identified 21,183 expression quantitative trait loci (eQTLs) and 6,768 splicing quantitative trait loci (sQTLs), including 619 new QTLs. We identified high-frequency QTLs and found evidence of selection near genes involved in malarial resistance and increased multiple sclerosis risk, reflecting the epidemiological history of Sardinia. Using family relationships, we identified 809 segregating expression outliers (median z score of 2.97), averaging 13.3 genes per individual. Outlier genes were enriched for proximal rare variants, providing a new approach to study large-effect regulatory variants and their relevance to traits. Our results provide insight into the effects of regulatory variants and their relationship to population history and individual genetic risk.M.P. is supported by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement 633964 (ImmunoAgeing). Z.Z. is supported by the National Science Foundation (NSF) GRFP (DGE- 114747) and by the Stanford Center for Computational, Evolutionary, and Human Genomics (CEHG). Z.Z., J.R.D., and G.T.H. also acknowledge support from the Stanford Genome Training Program (SGTP; NIH/NHGRI T32HG000044). J.R.D. is supported by the Stanford Graduate Fellowship. K.R.K. is supported by Department of Defense, Air Force Office of Scientific Research, National Defense Science and Engineering Graduate (NDSEQ) Fellowship 32 CFR 168a. S.J.S. is supported by the NIHR Cambridge Biomedical Research Centre. The SardiNIA project is supported in part by the intramural program of the National Institute on Aging through contract HHSN271201100005C to the Consiglio Nazionale delle Ricerche of Italy. The RNA sequencing was supported by the PB05 InterOmics MIUR Flagship grant; by the FaReBio2011 “Farmaci e Reti Biotecnologiche di Qualità” grant; and by Sardinian Autonomous Region (L.R. no. 7/2009) grant cRP3-154 to F. Cucca, who is also supported by the Italian Foundation for Multiple Sclerosis (FISM 2015/R/09) and by the Fondazione di Sardegna (ex Fondazione Banco di Sardegna, Prot. U1301.2015/AI.1157.BE Prat. 2015-1651). S.B.M. is supported by the US National Institutes of Health through R01HG008150, R01MH101814, U01HG007436, and U01HG009080. All of the authors would like to thank the CRS4 and the SCGPM for the computational infrastructure supporting this project