The small and large intestine contain transcriptionally related mesenchymal stromal cell subsets that derive from embryonic Gli1+ mesothelial cells

Intestinal fibroblasts (FB) play essential roles in intestinal homeostasis. Here we show that the small and large intestinal lamina propria (LP) contain similar FB subsets that locate in specific anatomical niches and express distinct arrays of epithelial support genes. However, there were tissue specific differences in the transcriptional profile of intestinal FB subsets in the two sites. All adult intestinal LP mesenchymal stromal cells (MSC), including FB, smooth muscle cells (SMC) and pericytes derive from Gli1-expressing embryonic precursors which we identify as mesothelial cells. Trajectory analysis suggested that adult SMC and FB derive from distinct embryonic intermediates, and that adult FB subsets develop in a linear trajectory from CD81+ FB. Finally, we show that colonic subepithelial PDGFRαhi FB comprise several functionally and anatomically distinct populations that originate from an Fgfr2-expressing FB intermediate. Collectively our results provide novel insights into MSC diversity, location, function and ontogeny, with implications for our understanding of intestinal development, homeostasis and disease.

The small and large intestine contain transcriptionally related mesenchymal stromal cell subsets that derive from embryonic Gli1+ mesothelial cells

Intestinal fibroblasts (FB) play essential roles in intestinal homeostasis. Here we show that the small and large intestinal lamina propria (LP) contain similar FB subsets that locate in specific anatomical niches and express distinct arrays of epithelial support genes. However, there were tissue specific differences in the transcriptional profile of intestinal FB subsets in the two sites. All adult intestinal LP mesenchymal stromal cells (MSC), including FB, smooth muscle cells (SMC) and pericytes derive from Gli1-expressing embryonic precursors which we identify as mesothelial cells. Trajectory analysis suggested that adult SMC and FB derive from distinct embryonic intermediates, and that adult FB subsets develop in a linear trajectory from CD81+ FB. Finally, we show that colonic subepithelial PDGFRαhi FB comprise several functionally and anatomically distinct populations that originate from an Fgfr2-expressing FB intermediate. Collectively our results provide novel insights into MSC diversity, location, function and ontogeny, with implications for our understanding of intestinal development, homeostasis and disease.

A comparison of methyl and gaseous elemental mercury in the urban atmosphere

This study was carried out to compare the levels of mercury species, i.e., elemental mercury (Hg°) and methyl mercury (MeHg), in indoor and outdoor air in urban areas in Canada. Offices, laboratories for undergraduate studies, and laboratories for research, in a public building located in the downtown core of the city of Toronto, were selected. Hg° was measured using an automated mercury vapour analyzer. MeHg in the air was collected using a carbotrap, and the trapped MeHg was thermally desorbed and analyzed using a CVAFS. The results showed that both indoor MeHg and Hg° levels were related to location function and air circulation. Outdoor MeHg levels were significantly elevated, ranging between 21 and 41% of total mercury (THg) levels, compared to those reported from previous studies. Outdoor Hg° fluctuations were not found to be significantly related to temperature or sunlight exposure, and outdoor MeHg levels were connected to soil and vegetation abundance. Average indoor Hg° levels were found to be between 1.4 and 15 times higher than outdoor levels, whereas MeHg indoor levels were not consistently higher than outdoor levels. Although the mercury concentrations in the indoor environment are still lower than the safety standard for Hg° and organic mercury, they are comparable to those observed near point sources. Thus, indoor air can be a source of mercury to the atmosphere.

A comparison of methyl and gaseous elemental mercury in the urban atmosphere

This study was carried out to compare the levels of mercury species, i.e., elemental mercury (Hg°) and methyl mercury (MeHg), in indoor and outdoor air in urban areas in Canada. Offices, laboratories for undergraduate studies, and laboratories for research, in a public building located in the downtown core of the city of Toronto, were selected. Hg° was measured using an automated mercury vapour analyzer. MeHg in the air was collected using a carbotrap, and the trapped MeHg was thermally desorbed and analyzed using a CVAFS. The results showed that both indoor MeHg and Hg° levels were related to location function and air circulation. Outdoor MeHg levels were significantly elevated, ranging between 21 and 41% of total mercury (THg) levels, compared to those reported from previous studies. Outdoor Hg° fluctuations were not found to be significantly related to temperature or sunlight exposure, and outdoor MeHg levels were connected to soil and vegetation abundance. Average indoor Hg° levels were found to be between 1.4 and 15 times higher than outdoor levels, whereas MeHg indoor levels were not consistently higher than outdoor levels. Although the mercury concentrations in the indoor environment are still lower than the safety standard for Hg° and organic mercury, they are comparable to those observed near point sources. Thus, indoor air can be a source of mercury to the atmosphere.

RDmap: A Map for Exploring Rare Diseases

Background: The complexity of the phenotypic characteristics and molecular bases of many rare human genetic diseases make the diagnosis of such diseases a challenge for clinicians. A map for visualizing, locating and navigating rare diseases based on similarity will help clinicians and researchers understand and easily explore these diseases. Methods: By defining the quantitative distance among phenotypes and pathogenic genes based on corresponding ontology systems, the distance matrix of rare diseases included in Orphanet was calculated and mapped into Euclidean space. Enhanced by clustering classes and disease information, a rare disease map was developed based on ECharts. Results: The rare disease map called RDmap was published at http://rdmap.nbscn.org. The phenotype-based map comprises 3,287 rare diseases and the gene-based map comprises 3,789 rare genetic diseases and they were bridged by 1,718 overlapping diseases. RDmap works similar to the widely used Google map and supports zooming and panning. The phenotype similarity base disease location function performed better than traditional keyword search in an in-silico evaluation and 20 published cases of rare diseases also demonstrated that RDmap can be used by clinicians to improve diagnosis. Conclusion: RDmap is the first user-interactive map-style rare disease knowledgebase. It will help clinicians and researchers explore the increasing complicated rare genetic diseases.

Prioritizing transcriptomic and epigenomic experiments by using an optimization strategy that leverages imputed data

Motivation Successful science often involves not only performing experiments well, but also choosing well among many possible experiments. In a hypothesis generation setting, choosing an experiment well means choosing an experiment whose results are interesting or novel. In this work, we formalize this selection procedure in the context of genomics and epigenomics data generation. Specifically, we consider the task faced by a scientific consortium such as the National Institutes of Health ENCODE Consortium, whose goal is to characterize all of the functional elements in the human genome. Given a list of possible cell types or tissue types (“biosamples”) and a list of possible high throughput sequencing assays, where at least one experiment has been performed in each biosample and for each assay, we ask “Which experiments should ENCODE perform next?” Results We demonstrate how to represent this task as a submodular optimization problem, where the goal is to choose a panel of experiments that maximize the facility location function. A key aspect of our approach is that we use imputed data, rather than experimental data, to directly answer the posed question. We find that, across several evaluations, our method chooses a panel of experiments that span a diversity of biochemical activity. Finally, we propose two modifications the facility location function, including a novel submodular-supermodular function, that allow incorporation of domain knowledge or constraints into the optimization procedure. Availability and Implementation Our method is available as a Python package at https://github.com/jmschrei/kiwano and can be installed using the command pip install kiwano. The source code used here and the similarity matrix can be found at http://doi.org/10.5281/zenodo.3708538. Supplementary information Supplementary data are available at Bioinformatics online.

SETTLER EDUCATION

This paper begins with a critical exploration, from the location of a settler, of how land acknowledgements and practices of self-location function in child and youth care teaching and learning. I critically examine settler practices of acknowledgement, self-location, appropriation, consciousness-raising, and allyship. I use the concepts of settler ethics and responsibilities to underline the importance of accountability in child and youth care pedagogy. I argue that settlers have a responsibility to take action within the challenging ethical landscape of teaching and learning within the settler colonial context. My overall aim is to contribute to the critical and decolonizing literature in child and youth care from the location of a settler educator and child and youth care practitioner.

Etymologie ludowe w toponimach na pograniczu polsko-ruskim

Toponyms are interesting linguistic material. They contain knowledge about the environment of our existence - its formation, wealth, history, and even about spatial or social relations. The purpose of this article was to obtain and analyse naming material (names and their folk etymologies) from seventeen villages located within three rural communes on both sides of the San River. The analysis was based on comparison of folk and scientific etymologies. This allowed to answer the questions of how current residents of the former ethnic borderland understand foreign names in their localities, what kind of conceptualisation of the world emerges from folk etymologies, and whether the river San as a natural obstacle significantly influenced the linguistic concepts of its right and left-bank residents. The analysis of toponyms indicates that in rural communities of the studied area, proper names were often motivated by historical, settlement and topographic specifics. Therefore, simple motivation dominates here: creators most often referred to physical properties such as shape and appearance. From other aspects, location, function and local residents were often considered. The relatively high percentage of names with foreign phonetic influences, largely incomprehensible to their contemporary users, stems from the turbulent history of this area and the overlapping Ruthenic, Slovak and other influences. No statistically important differences in conceptualisation of the world between the residents of the east and west sides of the river were detected.