Abstract
Most human genes generate multiple transcript isoforms. The differential expression of these isoforms can help specify cell types. Diverse transcript isoforms arise from the use of ...alternative transcription start sites, polyadenylation sites and splice sites; however, the relative contribution of these processes to isoform diversity in normal human physiology is unclear. To address this question, we investigated cell type-dependent differences in exon usage of over 18 000 protein-coding genes in 23 cell types from 798 samples of the Genotype-Tissue Expression Project. We found that about half of the expressed genes displayed tissue-dependent transcript isoforms. Alternative transcription start and termination sites, rather than alternative splicing, accounted for the majority of tissue-dependent exon usage. We confirmed the widespread tissue-dependent use of alternative transcription start sites in a second, independent dataset, Cap Analysis of Gene Expression data from the FANTOM consortium. Moreover, our results indicate that most tissue-dependent splicing involves untranslated exons and therefore may not increase proteome complexity. Thus, alternative transcription start and termination sites are the principal drivers of transcript isoform diversity across tissues, and may underlie the majority of cell type specific proteomes and functions.
RNA-seq is a powerful tool for the study of alternative splicing and other forms of alternative isoform expression. Understanding the regulation of these processes requires sensitive and specific ...detection of differential isoform abundance in comparisons between conditions, cell types, or tissues. We present DEXSeq, a statistical method to test for differential exon usage in RNA-seq data. DEXSeq uses generalized linear models and offers reliable control of false discoveries by taking biological variation into account. DEXSeq detects with high sensitivity genes, and in many cases exons, that are subject to differential exon usage. We demonstrate the versatility of DEXSeq by applying it to several data sets. The method facilitates the study of regulation and function of alternative exon usage on a genome-wide scale. An implementation of DEXSeq is available as an R/Bioconductor package.
Despite the dramatic development in digital manufacturing technologies in the recent years, 3D printing of earth materials, such as cob, still presents several challenges to the market-available 3D ...printing systems. This paper describes the development process of a 3D printing system for cob that fits the contemporary requirements of digital construction. The study first described the methodology of producing a revised cob recipe for the purpose of 3D printing. Then, the study conducted thorough investigations into the properties of three types of extrusion systems using both electromechanical and pneumatic methods, leading eventually to the development of a new bespoke dual-ram extruder. The study then explored systematically the relationship between the new 3DP system and the rheological properties of cob, followed by an exploration to the new geometric opportunities the new system offers. The study findings show that the new extrusion system improves greatly the 3DP process of cob in terms of extrusion rate, continuity, consistency, and mobility. The findings are expected to bring 3D printed cob construction closer to full-scale applications. On a broader scale the study contributes to the disciplines of architectural design and construction by providing a framework capable of bridging the knowledge gap between vernacular modes of building production and contemporary digital practice.
•Development of a bespoke dual-ram cob extrusion system•Improved cob mix and printing parameters for additive manufacturing•The new extrusion system increases the efficiency of 3D printing of Cob.•Cob can be printed with complex geometries using more than three axes of movement.•Robotic 3D printing of cob shows potentials for sustainable automated construction.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Acute hepatopancreatic necrosis disease (AHPND) has extended rapidly, causing alarming shrimp mortalities. Initially, the only known causative agent was Vibrio parahaemolyticus carrying a plasmid ...coding for the mortal toxins Pir
. Recently, it has been found that the plasmid and hence the disease, could be transferred among members of the Harveyi clade. The current study performs a genomic characterization of an isolate capable of developing AHPND in shrimp. Mortality studies and molecular and histopathological analyses showed the infection capacity of the strain. Multilocus sequence analysis placed the bacteria as a member of the Orientalis clade, well known for containing commensal and even probiotic bacteria used in the shrimp industry. Further whole genome comparative analyses, including Vibrio species from the Orientalis clade, and phylogenomic metrics (TETRA, ANI and DDH) showed that the isolate belongs to a previously unidentified species, now named Vibrio punensis sp. nov. strain BA55. Our findings show that the gene transfer capacity of Vibrio species goes beyond the clade classification, demonstrating a new pathogenic capacity to a previously known commensal clade. The presence of these genes in a different Vibrio clade may contribute to the knowledge of the Vibrio pathogenesis and has major implications for the spread of emerging diseases.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The study of viral communities has revealed the enormous diversity and impact these biological entities have on various ecosystems. These observations have sparked widespread interest in developing ...computational strategies that support the comprehensive characterisation of viral communities based on sequencing data. Here we introduce VIRify, a new computational pipeline designed to provide a user-friendly and accurate functional and taxonomic characterisation of viral communities. VIRify identifies viral contigs and prophages from metagenomic assemblies and annotates them using a collection of viral profile hidden Markov models (HMMs). These include our manually-curated profile HMMs, which serve as specific taxonomic markers for a wide range of prokaryotic and eukaryotic viral taxa and are thus used to reliably classify viral contigs. We tested VIRify on assemblies from two microbial mock communities, a large metagenomics study, and a collection of publicly available viral genomic sequences from the human gut. The results showed that VIRify could identify sequences from both prokaryotic and eukaryotic viruses, and provided taxonomic classifications from the genus to the family rank with an average accuracy of 86.6%. In addition, VIRify allowed the detection and taxonomic classification of a range of prokaryotic and eukaryotic viruses present in 243 marine metagenomic assemblies. Finally, the use of VIRify led to a large expansion in the number of taxonomically classified human gut viral sequences and the improvement of outdated and shallow taxonomic classifications. Overall, we demonstrate that VIRify is a novel and powerful resource that offers an enhanced capability to detect a broad range of viral contigs and taxonomically classify them.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A series of expanded‐ring NHC gold complexes of the formula (NaphtDHD−Ar)Au−X (NaphtDHD=4,5‐dihydro‐1H‐naphtho1,8‐ef1,3diazocin‐3(2H)‐ylidene; Ar: Mes=2,4,6‐trimethylphenyl, ...Dipp=2,6‐diisopropylphenyl or Xyl=2,6‐dimethylphenyl; X=Cl, NCCH3, NTf2) have been synthesized, including the first gold(I) triflimidate complex (5) stabilized by an eight‐membered NHC ligand. The new organogold compounds have been characterized by mass spectrometry, IR spectroscopy, and 1H and 13C NMR spectroscopy. The structural geometries of 3 b–c and 5 have been unequivocally established by crystallographic analysis revealing broad N‐C‐N angles (>121°) and high buried volume values (46–54%). The first catalytic studies were carried out on the cycloisomerization of 1,6‐enynes, obtaining full conversions (0.5 mol% catalyst loading) and excellent endo/exo selectivity (up to 99:1), and on the gold‐catalyzed phenol synthesis. Lastly, the (NaphtDHD‐Dipp)Au+ NTf2− species was subjected to a kinetic experiment in the cyclization of a N‐propargyl carboxamide to evaluate the efficiency of the pre‐formed catalyst (5) and the in situ activated gold complex (3 b+AgNTf2).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Nine‐ and ten‐membered N‐heterocyclic carbene (NHC) ligands have been developed and for the first time their gold(I) complexes were synthesized. The protonated NHC pro‐ligands 2 a–h were prepared by ...the reaction of readily available N,N′‐diarylformamidines with bis‐electrophilic building blocks, followed by anion exchange. In situ deprotonation of the tetrafluoroborates 2 a–h with tBuOK in the presence of AuCl(SMe2) provided fast access to NHC‐gold(I) complexes 3–10. These new NHC‐gold(I) complexes show very good catalytic activity in a cycloisomerization reaction (0.1 mol % catalyst loading, up to 100 % conversion) and their solid‐state structures reveal high steric hindrance around the metal atom (%Vbur up to 53.0) which is caused by their expanded‐ring architecture.
Meet the new members of the golden family: A new series of N‐heterocyclic carbene ligands bearing a rigid expanded‐ring backbone, supply unique stability to the gold(I) complex, and provide a high steric hindrance towards the metal center, which results in an excellent catalytic activity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The microbiota in broiler chicken intestines affects the animals' health, metabolism, and immunity both positively and negatively. Accordingly, it has a significant impact on animal productivity. ...Phages, host-specific parasites of bacterial cells, are a promising antimicrobial alternative that selectively target pathogens without disturbing the microbiota. The purpose of this study is to further characterize the commensal microbial community at production scale in broiler chickens treated with a Salmonella phage treatment. We evaluated the cecal microbiota of broilers reared in a commercial farming system where a phage cocktail against Salmonella, SalmoFree was supplied to animals. To do so, two field trials were conducted, incorporating three doses of phages in the broilers' drinking water. Our results showed that the core microbiome (taxa that were present in more than 50% of samples) contained species that are key to microbiota adaptation in the last stage of the production cycle. Among these, there are some important degraders of complex polysaccharides and producers of short chain fatty acids (SCFA) such as Eisenbergiella and Lachnoclostridium. The phage cocktail did not affect the normal development of the microbiota's structure. The addition of the phage cocktail resulted in a significant reduction in Campylobacter and an increase in Butyricimonas, Helicobacter and Rikenellaceae, which are common inhabitants in chicken gut with known negative and positive effects on their health and metabolism. Altogether, we consider that these results contribute valuable information to the implementation of large-scale phage therapy technologies.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Summary
A comprehensive review of thermodynamic cycles for the simultaneous production of power and cooling is presented. The study not only actualizes the bibliographic reviews previously realized ...by other authors regarding cycles such as Kalina, Goswami, or modifications of them. This review additionally includes an overview of hybrid cycles and other novel cycles reported in the literature. The hybrid cycles included in the study are systems integrated by two or three conventional cycles, mainly composed of Brayton, Rankine, and ORC for power generation; and compression, absorption, and ejector cycles for cooling production. The other novel cycles mentioned are thermodynamic cycles, which considerably differ from all the others. By using internal rectification, the Goswami cycle increased its efficiency by about 5%; however, by adding diverse components, as a condenser and a subcooler, the efficiency was significantly improved due to the considerable increase of the cooling production. Organic Rankine cycles integrating absorption refrigeration cycles are, in general, the most efficient hybrid cycles, reaching thermal efficiencies close to 40% for the simultaneous production of power and cooling. If a third output was provided, as heating or water distillation, the energy efficiencies were as high as 90%. The main problem with these systems is that, in general, they are too complex and costly because of the considerable number of components. The highest exergy destruction values are reported in solar collectors when used, followed by boilers or generators, and absorbers. The lower production costs were reported with systems integrating a Brayton cycle, an organic Rankine cycle, and an ejector‐cooling cycle. The disadvantage of these systems is that they need high operating temperatures.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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