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Immunologic self-tolerance involves signals from co-inhibitory receptors. Several T cell co-inhibitors, including PD-1, are expressed upon activation, whereas CD5 and BTLA are expressed constitutively. The relationship between constitutively expressed co-inhibitors and when they are needed is unknown. Deletion of Btla demonstrated BTLA regulates CD5 expression. Loss of BTLA signals, but not signalling by its ligand, HVEM, leads to increased CD5 expression. Higher CD5 expression set during thymic selection is associated with increased self-recognition, suggesting that BTLA might be needed early to establish self-tolerance. We found that BTLA and PD-1 were needed post-thymic selection in recent thymic emigrants (RTE). RTE lacking BTLA caused a CD4 T cell and MHC class II dependent multi-organ autoimmune disease. Together, our findings identify a negative regulatory pathway between two constitutively expressed co-inhibitors, calibrating their expression. Expression of constitutive and induced co-inhibitory receptors is needed early to establish tolerance in the periphery for RTE.

Denne studien undersøkjer barnehagelærarars forteljingar om språkarbeid med fleirspråklege barn i barnehagen. Målet med studien var å få innsikt i barnehagelærars oppfatningar som dei byggjer praksisen med fleirspråklege barn i barnehagen på. Fire fokusgruppeintervju med totalt 20 barnehagelærarar blei gjennomførte. Den narrative analysen identifiserte fire sentrale tolkingsrepertoar for barnehagelæraranes oppfatningar av fleirspråkleg praksis: det ressursprega, det kompensatoriske, det monospråklege og det profesjonelle avmaktsrepertoaret. Tolkingsrepertoara kom til syne i alle fire intervjua, og dette tyder på eit mønster i oppfatningane. Tolkingsrepertoara var ikkje gjensidig utelukkande, til dømes kunne barnehagelærar både gi uttrykk for å oppfatte fleirspråklegheit som ressurs og samtidig kjenne avmakt i si eiga rolle. Likeins blei norskspråkleg utvikling trekt fram som målsetting for barnehagens språkarbeid samtidig som deltakarane fortalde om spontane transspråkingsaktivitetar. Dette tyder på ein variert og kompleks språkpraksis bygd på både formell og erfaringsbasert kompetanse og personlege oppfatningar. Funna gir innblikk i korleis barnehagelærarar forstår sin eigen og barnas posisjon i ein fleirspråkleg barnehagekontekst og har implikasjonar for utvikling av ein ressursbasert fleirspråkleg pedagogisk praksis. ENGLISH ABSTRACT Resource and Deficiency: Teachers’ Views on Complex Multilingual Practices in Early Childhood Education and Care This study explores teachers’ experiences of multilingual practices in early childhood education and care (ECEC). The purpose was to gain insight into the underlying assumptions that shape ECEC teachers’ multilingual practices. Data were collected through four focus group interviews with 20 teachers. The analysis of the ECEC teachers’ narratives identified four emerging interpretative repertoires: resource-based, compensatory, monolingual, and feelings of professional powerlessness. All four interpretative repertoires appeared in all the interviews, which suggests a pattern of views. The interpretative repertoires were not mutually exclusive. One participant could, for instance, explicitly view multilingualism as a resource while simultaneously expressing feelings of powerlessness regarding how to practice multilingual didactics. Similarly, monolingual Norwegian development was identified as the objective of planned activities while teachers described spontaneous translingual activities. These findings indicate varied and complex linguistic practices built on formal and experience-based competencies and personal beliefs and provide insight into ECEC teachers’ understandings of their own and the children’s positions within a complex multilingual ECEC context. The results have implications for further research- based development of multilingual practices.

Colitis is characterized by an exacerbated intestinal immune response, but the genetic and other mechanisms regulating immune activation remain incompletely understood. In order to identify new pathways leading to colitis, we sought to identify genes with increased expression in the colons of patients that also are near loci identified by genome wide association studies (GWAS) associated with IBD risk. One such SNP, rs9557195 was of particular interest because it is within an intron of G-protein-coupled receptor (GPR) 183, known to be important for lymphocyte migration. Furthermore, this SNP is in close proximity to the gene encoding another G-protein coupled receptor, GPR18. Analyzing publicly available datasets, we found transcripts of GPR183 and GPR18 to be increased in colon biopsies from ulcerative colitis and Crohn’s disease patients, and GPR183 was even more increased in patients resistant to TNF treatment. Expression of both genes also was increased in mouse models of colitis. Therefore, our aim was to understand if increased expression of these GPRs in the intestine is related to disease severity in colitis models. Here we investigated the role of these receptors in the T cell transfer model and the dextran sulfate sodium model. In the T cell transfer model, GPR183 expression on donor T cells, as well as on other cell types in the Rag-/- recipients, was not essential for severe colitis induction. Furthermore, deficiency in Rag-/- mice for the enzyme that synthesizes a cholesterol metabolite that is a major ligand for GPR183 also did not affect disease. Similarly, lack of GPR18 expression in T cells or other cell types did not affect colitis pathogenesis in the T cell transfer or in the dextran sulfate sodium model. Therefore, despite increased expression of transcripts for these genes in the intestine during inflammation in humans and mice, they are not required for disease severity in mouse models of colitis induced by chemical injury or T cell cytokines, perhaps due to redundancy in mechanisms important for homing and survival of lymphocytes to the inflamed intestine.

The B and T lymphocyte attenuator (BTLA) is an Ig super family member that binds to the herpes virus entry mediator (HVEM), a TNF receptor super family (TNFRSF) member. Engagement of BTLA by HVEM triggers inhibitory signals, although recent evidence indicates that BTLA also may act as an activating ligand for HVEM. In this study, we reveal a novel role for the BTLA-HVEM pathway in promoting the survival of activated CD8(+) T cells in the response to an oral microbial infection. Our data show that both BTLA- and HVEM-deficient mice infected with Listeria monocytogenes had significantly reduced numbers of primary effector and memory CD8(+) T cells, despite normal proliferation and expansion compared to controls. In addition, blockade of the BTLA-HVEM interaction early in the response led to significantly reduced numbers of antigen-specific CD8(+) T cells. HVEM expression on the CD8(+) T cells as well as BTLA expression on a cell type other than CD8(+) T lymphocytes, was required. Collectively, our data demonstrate that the function of the BTLA-HVEM pathway is not limited to inhibitory signaling in T lymphocytes, and instead, that BTLA can provide crucial, HVEM-dependent signals that promote survival of antigen activated CD8(+) T cell during bacterial infection.

Male and female birds have different roles in reproduction and, thereby in their reproductive investment, which in turn may increase negative effects of poorer breeding conditions caused by e.g., climate change or ecosystem regime shifts. By using a 33-year time series of resightings of Atlantic puffins Fratercula arctica individually colour-ringed as breeders in previous years, we showed that the difference in colony attendance of male and female birds depended on the environmental conditions for raising young, proxied by the average duration of the chick period and size of the herring Clupea harengus fed to the chicks in the colony each year. The longer the chick period, the more was the sex ratio of adults sitting visibly in the colony biased in favour of males. An increase in herring size, indicating better feeding conditions for raising chicks, led to more observations of both sexes. Additionally, we found that birds were observed less with age and females more so than males. We discuss the results in relation to general life-history theory on sexual differences in trade-offs between individual investment in breeding and own survival. Our results suggest that females are increasingly more willing than males to invest in provisioning for the chick the more and longer the chick needs such care., Competing Interests: None declared., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Actuarial senescence, the decline of survival with age, is well documented in the wild. Rates of senescence vary widely between taxa, to some extent also between sexes, with the fastest life histories showing the highest rates of senescence. Few studies have investigated differences in senescence among populations of the same species, although such variation is expected from population-level differences in environmental conditions, leading to differences in vital rates and thus life histories. We predict that, within species, populations differing in productivity (suggesting different paces of life) should experience different rates of senescence, but with little or no sexual difference in senescence within populations of monogamous, monomorphic species where the sexes share breeding duties. We compared rates of actuarial senescence among three contrasting populations of the Atlantic puffin Fratercula arctica. The dataset comprised 31 years (1990-2020) of parallel capture-mark-recapture data from three breeding colonies, Isle of May (North Sea), Røst (Norwegian Sea) and Hornøya (Barents Sea), showing contrasting productivities (i.e. annual breeding success) and population trends. We used time elapsed since first capture as a proxy for bird age, and productivity and the winter North Atlantic Oscillation Index (wNAO) as proxies for the environmental conditions experienced by the populations within and outside the breeding season, respectively. In accordance with our predictions, we found that senescence rates differed among the study populations, with no evidence for sexual differences. There was no evidence for an effect of wNAO, but the population with the lowest productivity, Røst, showed the lowest rate of senescence. As a consequence, the negative effect of senescence on the population growth rate (λ) was up to 3-5 times smaller on Røst (Δλ = -0.009) than on the two other colonies. Our findings suggest that environmentally induced differences in senescence rates among populations of a species should be accounted for when predicting effects of climate variation and change on species persistence. There is thus a need for more detailed information on how both actuarial and reproductive senescence influence vital rates of populations of the same species, calling for large-scale comparative studies., (© 2023 The Authors. Journal of Animal Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Society.)

Cell culture medium (CCM) formulations are chemically defined to reduce lot-to-lot variability and complexity of the medium while still providing all essential nutrients supporting cell growth and productivity of various cell lines. However, raw material impurities may still introduce variations and inconsistencies to final CCM formulations. In one of our previous studies (Weiss et al. Biotechnol Prog. 2021;37(4):e3148), we have demonstrated the impact of iron raw material impurity on Chinese hamster ovary (CHO) cell performance and critical quality attributes (CQAs) of recombinant proteins within the Cellvento® 4CHO CCM platform by identifying manganese impurity as the main root cause for improved cell performance and altered glycosylation profiles. This study sought to investigate the impact of iron raw material impurities within another medium platform, namely EX-CELL® Advanced CHO Fed-Batch-Medium. As opposed to previously published results, in this platform, copper instead of manganese impurity present within the used ferric ammonium citrate (FAC) iron source was responsible for an improved cell performance of a CHOZN® cell line and a slight difference in CQAs of the produced recombinant protein. The use of tightly controlled raw material specifications or the use of low impurity iron sources is therefore crucial to minimize the impact of impurities on cell performance in any CCM platform and thereby guarantee consistent and reproducible cell culture processes., (© 2022 Merck KGaA. Biotechnology Progress published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

In (st)age-structured populations, the long-run population growth rate is negatively affected by temporal variation in vital rates. In most cases, natural selection should minimize temporal variation in the vital rates to which the long-run population growth is most sensitive, resulting in demographic buffering. By reviewing empirical studies on demographic buffering in wild populations, we found overall support for this hypothesis. However, we also identified issues when testing for demographic buffering. In particular, solving scaling problems for decomposing, measuring, and comparing stochastic variation in vital rates and accounting for density dependence are required in future tests of demographic buffering. In the current context of climate change, demographic buffering may mitigate the negative impact of environmental variation and help populations to persist in an increasingly variable environment., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Meaningful comparison of variation in quantitative trait requires controlling for both the dimension of the varying entity and the dimension of the factor generating variation. Although the coefficient of variation (CV; standard deviation divided by the mean) is often used to measure and compare variation of quantitative traits, it only accounts for the dimension of the former, and its use for comparing variation may sometimes be inappropriate. Here, we discuss the use of the CV to compare measures of evolvability and phenotypic plasticity, two variational properties of quantitative traits. Using a dimensional analysis, we show that contrary to evolvability, phenotypic plasticity cannot be meaningfully compared across traits and environments by mean-scaling trait variation. We further emphasize the need of remaining cognizant of the dimensions of the traits and the relationship between mean and standard deviation when comparing CVs, even when the scales on which traits are expressed allow meaningful calculation of the CV., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Evolution Letters published by Wiley Periodicals LLC on behalf of Society for the Study of Evolution (SSE) and European Society for Evolutionary Biology (ESEB).)