Mus musculus deficient for secretory antibodies show delayed growth with an altered urinary metabolome

© 2019 The Author(s). Background: The polymeric immunoglobulin receptor (pIgR) maintains the integrity of epithelial barriers by transporting polymeric antibodies and antigens through the epithelial mucosa into the lumen. In this study, we examined the role of pIgR in maintaining gut barrier integrity, which is important for the normal development in mice. Methods: Cohorts of pIgR -/- mice and their wildtype controls were housed under Specific Pathogen Free (SPF) conditions and monitored for weight gain as an indicator of development over time. The general physiology of the gastrointestinal tract was analysed using immunohistochemistry in young (8-12 weeks of age) and aged mice (up to 18 months of age), and the observed immunopathology in pIgR -/- mice was further characterised using flow cytometry. Urinary metabolites were analysed using gas chromatography-mass spectrometry (GC-MS), which revealed changes in metabolites that correlated with age-related increase in gut permeability in pIgR -/- mice. Results: We observed that pIgR -/- mice exhibited delayed growth, and this phenomenon is associated with low-grade gut inflammation that increased with ageing. The gross intraepithelial lymphocytic (IEL) infiltration characteristic of pIgR -/- mice was redefined as CD8α+αβ+ T cells, the majority of which expressed high levels of CD103 and CD69 consistent with tissue resident memory T cells (TRM). Comparison of the urinary metabolome between pIgR -/- and wild-type mice revealed key changes in urinary biomarkers fucose, glycine and Vitamin B5, suggestive of altered mucosal permeability. A significant increase in gut permeability was confirmed by analysing the site-specific uptake of sugar probes in different parts of the intestine. Conclusion: Our data show that loss of the secretory antibody system in mice results in enhanced accumulation of inflammatory IELs in the gut, which likely reflects ongoing inflammation in reaction to gut microbiota or food antigens, leading to delayed growth in pIgR -/- mice. We demonstrate that this leads to the presence of a unique urinary metabolome profile, which may provide a biomarker for altered gut permeability

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Title What can Hierarchies do for Data Streams

For additional information, see the DB TECH REPORTS homepage: 〈www.cs.aau.dk/DBTR〉. Any software made available via DB TECH REPORTS is provided “as is ” and without any express or implied warranties, including, without limitation, the implied warranty of merchantability and fitness for a particular purpose. The DB TECH REPORTS icon is made from two letters in an early version of the Rune alphabet, which was used by the Vikings, among others. Runes have angular shapes and lack horizontal lines because the primary storage medium was wood, although they may also be found on jewelry, tools, and weapons. Runes were perceived as having magic, hidden powers. The first letter in the logo is “Dagaz, ” the rune for day or daylight and the phonetic equivalent of “d. ” Its meanings include happiness, activity, and satisfaction. The second letter is “Berkano, ” which is associated with the birch tree. Its divinatory meanings include health, new beginnings, growth, plenty, and clearance. It is associated with Idun, goddess of Spring, and with fertility. It is the phonetic equivalent of “b.” Much effort has been put into building data streams management systems for querying data streams. Here, data streams have been viewed as a flow of low-level data items, e.g., sensor readings or IP packet data. Stream query languages have mostly been SQL-based, with the STREAM and TelegraphCQ languages as examples. However, there has been little work on supporting OLAP-like queries that provide multi-dimensional and summarized views of stream data. In this paper, we introduce a multidimensional stream query language and its formal semantics. Our approach enables powerful OLAP queries against data streams with dimension hierarchies, thus turning low-level data streams into informative high-level aggregates. A comparison with STREAM shows that our approach is more flexible and powerful for high-level OLAP queries, as well as far more compact and concise.

Title Algebra-Based Optimization of XML-Extended OLAP Queries

For additional information, see the DB TECH REPORTS homepage: 〈www.cs.aau.dk/DBTR〉. Any software made available via DB TECH REPORTS is provided “as is ” and without any express or implied warranties, including, without limitation, the implied warranty of merchantability and fitness for a particular purpose. The DB TECH REPORTS icon is made from two letters in an early version of the Rune alphabet, which was used by the Vikings, among others. Runes have angular shapes and lack horizontal lines because the primary storage medium was wood, although they may also be found on jewelry, tools, and weapons. Runes were perceived as having magic, hidden powers. The first letter in the logo is “Dagaz, ” the rune for day or daylight and the phonetic equivalent of “d. ” Its meanings include happiness, activity, and satisfaction. The second letter is “Berkano, ” which is associated with the birch tree. Its divinatory meanings include health, new beginnings, growth, plenty, and clearance. It is associated with Idun, goddess of Spring, and with fertility. It is the phonetic equivalent of “b.” In today’s OLAP systems, integrating fast changing data, e.g., stock quotes, physically into a cube is complex and time-consuming. The widespread use of XML makes it very possible that this data i