Optimizing Phylogenetic Supertrees Using Answer Set Programming

The supertree construction problem is about combining several phylogenetic trees with possibly conflicting information into a single tree that has all the leaves of the source trees as its leaves and the relationships between the leaves are as consistent with the source trees as possible. This leads to an optimization problem that is computationally challenging and typically heuristic methods, such as matrix representation with parsimony (MRP), are used. In this paper we consider the use of answer set programming to solve the supertree construction problem in terms of two alternative encodings. The first is based on an existing encoding of trees using substructures known as quartets, while the other novel encoding captures the relationships present in trees through direct projections. We use these encodings to compute a genus-level supertree for the family of cats (Felidae). Furthermore, we compare our results to recent supertrees obtained by the MRP method.Comment: To appear in Theory and Practice of Logic Programming (TPLP), Proceedings of ICLP 201

Cultural, worldview and language awareness in highschool worldview textbooks

Suomalaisten koulujen kulttuuri-, katsomus- ja kielikentät moninaistuvat vauhdilla, ja kulttuuri-, katsomus- ja kielitietoisuuden (kukaki-tietoisuus) tutkimus on lisääntynyt peruskoulujen kontekstissa nopeasti. Tässä maisterintutkielmassa tutkin sitä, miten lukiokoulutuksen kontekstissa katsomusaineiden oppikirjat ilmentävät kukaki-tietoisuutta ja miten ne ohjaavat kukaki-tietoiseen opetukseen ja oppimiseen. Tutkimuksen teoreettisen katsauksen pohjalta olen luonut kukaki-tietoisuudesta kolme synteesikehikkoa, joita peilaan oppikirja-analyysistä nouseviin empiirisiin havaintoihin. Tutkimuksen metodi on siis teoriaohjaava sisällönanalyysi. Tutkimuksen lähdeaineisto koostuu viidestä lukiokoulutuksen katsomusaineiden oppikirjasta: kolmesta evankelisluterilaisen uskonnon ja kahdesta elämänkatsomustiedon oppikirjasta. Tutkimustulokset osoittavat, että kulttuuri-, katsomus- ja kielitietoisuuteen ohjaavat ja niihin liittyvien tietojen ja taitojen oppimista haittaavat tekijät ilmenevät oppikirjoissa neljän yhtenevän pääteeman kautta. Nämä neljä teemaa ovat (1) käsitteiden määrittely, (2) monikulttuurinen osaaminen ja katsomuslukutaito, (3) oppikirjan oletettu lukija ja (4) esitystavat ja representaatiot. Tämä tutkimus valottaa laajasti ja syväluotaavasti tutkittujen katsomusaineiden oppikirjojen vahvuuksia ja kehityksen kohteita kukaki-tietoisuuden saralla. Tutkimuksen yhtenä vahvuutena onkin sen anti oppikirjojen kehitystyölle. Tämän tutkimuksen tuloksista ei voi kuitenkaan tehdä päätelmiä oppikirjoja käyttävien lukioiden tai opettajien opetuksen kukaki-tietoisuudesta. Jatkotutkimukselle onkin tarvetta ja tärkeää olisi tutkia esimerkiksi lukion opettajien ja opiskelijoiden näkemyksiä oppikirjojen koetusta kukaki-tietoisuudesta

Enterovirus-associated changes in blood transcriptomic profiles of children with genetic susceptibility to type 1 diabetes

Aims/hypothesis Enterovirus infections have been associated with the development of type 1 diabetes in multiple studies, but little is known about enterovirus-induced responses in children at risk for developing type 1 diabetes. Our aim was to use genome-wide transcriptomics data to characterise enterovirus-associated changes in whole-blood samples from children with genetic susceptibility to type 1 diabetes. Methods Longitudinal whole-blood samples (356 samples in total) collected from 28 pairs of children at increased risk for developing type 1 diabetes were screened for the presence of enterovirus RNA. Seven of these samples were detected as enterovirus-positive, each of them collected from a different child, and transcriptomics data from these children were analysed to understand the individual-level responses associated with enterovirus infections. Transcript clusters with peaking or dropping expression at the time of enterovirus positivity were selected as the enterovirus-associated signals. Results Strong signs of activation of an interferon response were detected in four children at enterovirus positivity, while transcriptomic changes in the other three children indicated activation of adaptive immune responses. Additionally, a large proportion of the enterovirus-associated changes were specific to individuals. An enterovirus-induced signature was built using 339 genes peaking at enterovirus positivity in four of the children, and 77 of these genes were also upregulated in human peripheral blood mononuclear cells infected in vitro with different enteroviruses. These genes separated the four enterovirus-positive samples clearly from the remaining 352 blood samples analysed. Conclusions/interpretation We have, for the first time, identified enterovirus-associated transcriptomic profiles in whole-blood samples from children with genetic susceptibility to type 1 diabetes. Our results provide a starting point for understanding the individual responses to enterovirus infections in blood and their potential connection to the development of type 1 diabetes.Peer reviewe

Enterovirus-associated changes in blood transcriptomic profiles of children with genetic susceptibility to type 1 diabetes

Aims/hypothesis Enterovirus infections have been associated with the development of type 1 diabetes in multiple studies, but little is known about enterovirus-induced responses in children at risk for developing type 1 diabetes. Our aim was to use genome-wide transcriptomics data to characterise enterovirus-associated changes in whole-blood samples from children with genetic susceptibility to type 1 diabetes. Methods Longitudinal whole-blood samples (356 samples in total) collected from 28 pairs of children at increased risk for developing type 1 diabetes were screened for the presence of enterovirus RNA. Seven of these samples were detected as enterovirus-positive, each of them collected from a different child, and transcriptomics data from these children were analysed to understand the individual-level responses associated with enterovirus infections. Transcript clusters with peaking or dropping expression at the time of enterovirus positivity were selected as the enterovirus-associated signals. Results Strong signs of activation of an interferon response were detected in four children at enterovirus positivity, while transcriptomic changes in the other three children indicated activation of adaptive immune responses. Additionally, a large proportion of the enterovirus-associated changes were specific to individuals. An enterovirus-induced signature was built using 339 genes peaking at enterovirus positivity in four of the children, and 77 of these genes were also upregulated in human peripheral blood mononuclear cells infected in vitro with different enteroviruses. These genes separated the four enterovirus-positive samples clearly from the remaining 352 blood samples analysed. Conclusions/interpretation We have, for the first time, identified enterovirus-associated transcriptomic profiles in whole-blood samples from children with genetic susceptibility to type 1 diabetes. Our results provide a starting point for understanding the individual responses to enterovirus infections in blood and their potential connection to the development of type 1 diabetes.Peer reviewe

A Placebo-controlled double-blinded test of the biodiversity hypothesis of immune-mediated diseases : Environmental microbial diversity elicits changes in cytokines and increase in T regulatory cells in young children

Background: According to the biodiversity hypothesis of immune-mediated diseases, lack of microbiological di-versity in the everyday living environment is a core reason for dysregulation of immune tolerance and - even-tually - the epidemic of immune-mediated diseases in western urban populations. Despite years of intense research, the hypothesis was never tested in a double-blinded and placebo-controlled intervention trial.Objective: We aimed to perform the first placebo-controlled double-blinded test that investigates the effect of biodiversity on immune tolerance. Methods: In the intervention group, children aged 3-5 years were exposed to playground sand enriched with microbially diverse soil, or in the placebo group, visually similar, but microbially poor sand colored with peat (13 participants per treatment group). Children played twice a day for 20 min in the sandbox for 14 days. Sand, skin and gut bacterial, and blood samples were taken at baseline and after 14 days. Bacterial changes were followed for 28 days. Sand, skin and gut metagenome was determined by high throughput sequencing of bacterial 16 S rRNA gene. Cytokines were measured from plasma and the frequency of blood regulatory T cells was defined as a percentage of total CD3 +CD4 + T cells. Results: Bacterial richness (P < 0.001) and diversity (P < 0.05) were higher in the intervention than placebo sand. Skin bacterial community, including Gammaproteobacteria, shifted only in the intervention treatment to resemble the bacterial community in the enriched sand (P < 0.01). Mean change in plasma interleukin-10 (IL-10) concentration and IL-10 to IL-17A ratio supported immunoregulation in the intervention treatment compared to the placebo treatment (P = 0.02). IL-10 levels (P = 0.001) and IL-10 to IL-17A ratio (P = 0.02) were associated with Gammaproteobacterial community on the skin. The change in Treg frequencies was associated with the relative abundance of skin Thermoactinomycetaceae 1 (P = 0.002) and unclassified Alphaproteobacteria (P < 0.001). After 28 days, skin bacterial community still differed in the intervention treatment compared to baseline (P < 0.02). Conclusions: This is the first double-blinded placebo-controlled study to show that daily exposure to microbial biodiversity is associated with immune modulation in humans. The findings support the biodiversity hypothesis of immune-mediated diseases. We conclude that environmental microbiota may contribute to child health, and that adding microbiological diversity to everyday living environment may support immunoregulation.Peer reviewe

Effect of inactivated nature-derived microbial composition on mouse immune system

Introduction: The hygiene hypothesis suggests that decrease in early life infections due to increased societal-level hygiene standards subjects one to allergic and autoimmune diseases. In this report, we have studied the effect of sterilized forest soil and plant-based material on mouse immune system and gut microbiome. Methods: Inbred C57Bl/6 mice maintained in normal sterile environment were subjected to autoclaved forest soil-derived powder in their bedding for 1 h a day for 3 weeks. Immune response was measured by immune cell flow cytometry, serum cytokine enzyme-linked immunoassay (ELISA) and quantitative polymerase chain reaction (qPCR) analysis. Furthermore, the mouse gut microbiome was analyzed by sequencing. Results: When compared to control mice, mice treated with soil-derived powder had decreased level of pro-inflammatory cytokines namely interleukin (IL)-17F and IL-21 in the serum. Furthermore, splenocytes from mice treated with soil-derived powder expressed less IL-1b, IL-5, IL-6, IL-13, and tumor necrosis factor (TNF) upon cell activation. Gut microbiome appeared to be stabilized by the treatment. Conclusions: These results provide insights on the effect of biodiversity on murine immune system in sterile environment. Subjecting mice to soil-based plant and microbe structures appears to elicit immune response that could be beneficial, for example, in type 2 inflammation-related diseases, that is, allergic diseases.Peer reviewe

Skin, gut, and sand metagenomic data on placebo-controlled sandbox biodiversity intervention study

The metagenomic data presented in this article are related to the published research of "A Placebo-controlled doubleblinded test of the biodiversity hypothesis of immunemediated diseases: Environmental microbial diversity elicits changes in cytokines and increase in T regulatory cells in young children"This database contains 16S ribosomal RNA (rRNA) metagenomics of sandbox sand and skin and gut microbiota of children in the intervention and placebo daycares. In inter-vention daycares, children aged 3-5 years were exposed to playground sand enriched with microbially diverse soil. In placebo daycares, children were exposed to visually similar as in intervention daycares, but microbially poor sand col-ored with peat. Sand, skin and gut metagenomics were an-alyzed at baseline and after 14 and 28 days of interven-tion by high throughput sequencing of bacterial 16S rRNA gene on the Illumina MiSeq platform. This dataset shows how skin bacterial community composition, including classes Gammaproteobacteria and Bacilli, changed, and how the rel-ative abundance of over 30 bacterial genera shifted on the skin of children in the intervention treatment, while no shifts occurred in the placebo group.(c) 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Peer reviewe

A Placebo-controlled double-blinded test of the biodiversity hypothesis of immune-mediated diseases : Environmental microbial diversity elicits changes in cytokines and increase in T regulatory cells in young children

Background: According to the biodiversity hypothesis of immune-mediated diseases, lack of microbiological di-versity in the everyday living environment is a core reason for dysregulation of immune tolerance and - even-tually - the epidemic of immune-mediated diseases in western urban populations. Despite years of intense research, the hypothesis was never tested in a double-blinded and placebo-controlled intervention trial.Objective: We aimed to perform the first placebo-controlled double-blinded test that investigates the effect of biodiversity on immune tolerance. Methods: In the intervention group, children aged 3-5 years were exposed to playground sand enriched with microbially diverse soil, or in the placebo group, visually similar, but microbially poor sand colored with peat (13 participants per treatment group). Children played twice a day for 20 min in the sandbox for 14 days. Sand, skin and gut bacterial, and blood samples were taken at baseline and after 14 days. Bacterial changes were followed for 28 days. Sand, skin and gut metagenome was determined by high throughput sequencing of bacterial 16 S rRNA gene. Cytokines were measured from plasma and the frequency of blood regulatory T cells was defined as a percentage of total CD3 +CD4 + T cells. Results: Bacterial richness (P < 0.001) and diversity (P < 0.05) were higher in the intervention than placebo sand. Skin bacterial community, including Gammaproteobacteria, shifted only in the intervention treatment to resemble the bacterial community in the enriched sand (P < 0.01). Mean change in plasma interleukin-10 (IL-10) concentration and IL-10 to IL-17A ratio supported immunoregulation in the intervention treatment compared to the placebo treatment (P = 0.02). IL-10 levels (P = 0.001) and IL-10 to IL-17A ratio (P = 0.02) were associated with Gammaproteobacterial community on the skin. The change in Treg frequencies was associated with the relative abundance of skin Thermoactinomycetaceae 1 (P = 0.002) and unclassified Alphaproteobacteria (P < 0.001). After 28 days, skin bacterial community still differed in the intervention treatment compared to baseline (P < 0.02). Conclusions: This is the first double-blinded placebo-controlled study to show that daily exposure to microbial biodiversity is associated with immune modulation in humans. The findings support the biodiversity hypothesis of immune-mediated diseases. We conclude that environmental microbiota may contribute to child health, and that adding microbiological diversity to everyday living environment may support immunoregulation.Peer reviewe

Biodiversity intervention enhances immune regulation and health-associated commensal microbiota among daycare children

As the incidence of immune-mediated diseases has increased rapidly in developed societies, there is an unmet need for novel prophylactic practices to fight against these maladies. This study is the first human intervention trial in which urban environmental biodiversity was manipulated to examine its effects on the commensal microbiome and immunoregulation in children. We analyzed changes in the skin and gut microbiota and blood immune markers of children during a 28-day biodiversity intervention. Children in standard urban and nature-oriented daycare centers were analyzed for comparison. The intervention diversified both the environmental and skin Gammaproteobacterial communities, which, in turn, were associated with increases in plasma TGF-beta 1 levels and the proportion of regulatory T cells. The plasma IL-10:IL-17A ratio increased among intervention children during the trial. Our findings suggest that biodiversity intervention enhances immunoregulatory pathways and provide an incentive for future prophylactic approaches to reduce the risk of immune-mediated diseases in urban societies.Peer reviewe

Skin exposure to soil microbiota elicits changes in cell-mediated immunity to pneumococcal vaccine

A resilient immune system is characterized by its capacity to respond appropriately to challenges, such as infections, and it is crucial in vaccine response. Here we report a paired randomized intervention-control trial in which we evaluated the effect of microbially rich soil on immune resilience and pneumococcal vaccine response. Twenty-five age and sex matched pairs of volunteers were randomized to intervention and control groups. The intervention group rubbed hands three times a day in microbially rich soil until participants received a pneumococcal vaccine on day 14. Vaccine response, skin and gut bacteriome and blood cytokine levels were analyzed on days 0, 14 and 35. Peripheral blood mononuclear cells (PBMCs) were stimulated with vaccine components and autoclaved soil for cytokine production. Commensal bacterial community shifted only in the intervention group during the 14-day intervention period. When PBMCs collected on day 14 before the vaccination were stimulated with the vaccine components, IFN-y production increased in the intervention but not in the control group. On day 35, vaccination induced a robust antibody response in both groups. In parallel, gut bacterial community was associated with TGF-β plasma levels and TGF-β decrease in plasma was lower in the intervention group. The results indicate that exposure to microbially rich soil can modulate the cell-mediated immunity to components in pneumococcal vaccine