A unified framework for analysis of individual-based models in ecology and beyond

Individual-based models, 'IBMs', describe naturally the dynamics of interacting organisms or social or financial agents. They are considered too complex for mathematical analysis, but computer simulations of them cannot give the general insights required. Here, we resolve this problem with a general mathematical framework for IBMs containing interactions of an unlimited level of complexity, and derive equations that reliably approximate the effects of space and stochasticity. We provide software, specified in an accessible and intuitive graphical way, so any researcher can obtain analytical and simulation results for any particular IBM without algebraic manipulation. We illustrate the framework with examples from movement ecology, conservation biology, and evolutionary ecology. This framework will provide unprecedented insights into a hitherto intractable panoply of complex models across many scientific fields.Peer reviewe

Phytotoxin produced by the netted scab pathogen, Streptomyces turgidiscabies strain 65, isolated in Sweden

Streptomyces spp. are a highly diverse group of bacteria most of which are soil-inhabiting saprophytes. A few are plant pathogens that produce a family of phytotoxins called thaxtomins and cause significant economic losses, e.g., by reducing the marketability of potato tubers (Solanum tuberosum). In northern Europe, S. scabies, S. turgidiscabies and S. europaeiscabiei are the most common plant pathogenic species. In this study, a Streptomyces strain isolated from a netted scab lesion on a tuber of potato cv. Bintje in northern Sweden was identified as S. turgidiscabies but was found to differ in the genomic region carrying genes required for thaxtomin biosynthesis. Our results showed that the strain did not produce thaxtomin but rather phytotoxin fridamycin E, which is an anthraquinone novel to plant pathogenic Streptomyces spp. Fridamycin E was shown to reduce or inhibit sprouting of potato microtubers in vitro. While fridamycin E is known to have antibiotic activity against Gram-positive bacteria, the inhibitory activity of fridamycin E on plant growth is a novel finding.Peer reviewe

Exposure to environmental contaminants is associated with altered hepatic lipid metabolism in non-alcoholic fatty liver disease

Background & aims: Recent experimental models and epidemiological studies suggest that specific environmental contaminants (ECs) contribute to the initiation and pathology of nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanisms linking EC exposure with NAFLD remain poorly understood and there is no data on their impact on the human liver metabolome. Herein, we hypothesized that exposure to ECs, particularly perfluorinated alkyl substances (PFAS), impacts liver metabolism, specifically bile acid metabolism. Methods: In a well-characterized human NAFLD cohort of 105 individuals, we investigated the effects of EC exposure on liver metabolism. We characterized the liver (via biopsy) and circulating metabolomes using 4 mass spectrometry-based analytical platforms, and measured PFAS and other ECs in serum. We subsequently compared these results with an exposure study in a PPARa-humanized mouse model. Results: PFAS exposure appears associated with perturbation of key hepatic metabolic pathways previously found altered in NAFLD, particularly those related to bile acid and lipid metabolism. We identified stronger associations between the liver metabolome, chemical exposure and NAFLD-associated clinical variables (liver fat content, HOMA-IR), in females than males. Specifically, we observed PFAS-associated upregulation of bile acids, triacylglycerols and ceramides, and association between chemical exposure and dysregulated glucose metabolism in females. The murine exposure study further corroborated our findings, vis-a-vis a sex-specific association between PFAS exposure and NAFLD-associated lipid changes. Conclusions: Females may be more sensitive to the harmful impacts of PFAS. Lipid-related changes subsequent to PFAS exposure may be secondary to the interplay between PFAS and bile acid metabolism. Lay summary: There is increasing evidence that specific environmental contaminants, such as perfluorinated alkyl substances (PFAS), contribute to the progression of non-alcoholic fatty liver disease (NAFLD). However, it is poorly understood how these chemicals impact human liver metabolism. Here we show that human exposure to PFAS impacts metabolic processes associated with NAFLD, and that the effect is different in females and males. (C) 2021 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.Peer reviewe

Stat5 Synergizes with T Cell Receptor/Antigen Stimulation in the Development of Lymphoblastic Lymphoma

Signal transducer and activator of transcription (STAT) proteins are latent transcription factors that mediate a wide range of actions induced by cytokines, interferons, and growth factors. We now report the development of thymic T cell lymphoblastic lymphomas in transgenic mice in which Stat5a or Stat5b is overexpressed within the lymphoid compartment. The rate of lymphoma induction was markedly enhanced by immunization or by the introduction of TCR transgenes. Remarkably, the Stat5 transgene potently induced development of CD8+ T cells, even in mice expressing a class II–restricted TCR transgene, with resulting CD8+ T cell lymphomas. These data demonstrate the oncogenic potential of dysregulated expression of a STAT protein that is not constitutively activated, and that TCR stimulation can contribute to this process

Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function

Interleukin (IL)-21 is the most recently recognized of the cytokines that share the common cytokine receptor γ chain (γc), which is mutated in humans with X-linked severe combined immunodeficiency. We now report that IL-21 synergistically acts with IL-15 to potently promote the proliferation of both memory (CD44high) and naive (CD44low) phenotype CD8+ T cells and augment interferon-γ production in vitro. IL-21 also cooperated, albeit more weakly, with IL-7, but not with IL-2. Correspondingly, the expansion and cytotoxicity of CD8+ T cells were impaired in IL-21R−/− mice. Moreover, in vivo administration of IL-21 in combination with IL-15 boosted antigen-specific CD8+ T cell numbers and resulted in a cooperative effect on tumor regression, with apparent cures of large, established B16 melanomas. Thus, our studies reveal that IL-21 potently regulates CD8+ T cell expansion and effector function, primarily in a synergistic context with IL-15

Octupole correlations in the structure of O2 bands in the N=88 nuclei150Sm Gd

Knowledge of the exact microscopic structure of the 01 + ground state and first excited 02 + state in 150Sm is required to understand the branching of double β decay to these states from 150Nd. The detailed spectroscopy of 150Sm and 152Gd has been studied using (α,xn) reactions and the γ -ray arrays AFRODITE and JUROGAM II. Consistently strong E1 transitions are observed between the excited Kπ = 02 + bands and the lowest negative parity bands in both nuclei. These results are discussed in terms of the possible permanent octupole deformation in the first excited Kπ = 02 + band and also in terms of the “tidal wave” model of Frauendorf.Web of Scienc

A stage-structured model to predict the effect of temperature and salinity on glass eel Anguilla anguilla pigmentation development

The pigmentation development process of glass eels Anguilla anguilla from stage V-B to VIA3 was modelled by gamma cumulative functions. These functions varied with respect to the factors temperature and salinity whose effects were adjusted by beta functions. Temperature was shown to accelerate pigmentation, while salinity acted as a secondary factor slowing down the pigmentation. The model fits the development of 15 samples kept at various temperatures and salinities in the Vilaine River, as well as samples monitored at other dates and places in Europe. It allows the prediction of the duration of estuarine residency for glass eels, in winter and spring, in the Atlantic estuaries

Exposure to environmental contaminants is associated with altered hepatic lipid metabolism in non-alcoholic fatty liver disease

Background & aimsRecent experimental models and epidemiological studies suggest that specific environmental contaminants (ECs) contribute to the initiation and pathology of NAFLD. However, the underlying mechanisms linking EC exposure with NAFLD remain poorly understood and there is no data on their impact on the human liver metabolome. Herein, we hypothesized that exposure to ECs, particularly perfluorinated alkyl substances (PFAS), impacts liver metabolism, specifically bile acid metabolism.MethodsIn a well-characterized human NAFLD cohort of 105 individuals, we investigated the effects of EC exposure on liver metabolism. We characterized the liver (via biopsy) and circulating metabolomes using four mass spectrometry-based analytical platforms, and measured PFAS and other ECs in serum. We subsequently compared these results with an exposure study in a PPARα-humanized mouse model.ResultsPFAS exposure appears associated with perturbation of key hepatic metabolic pathways previously found altered in NAFLD, particularly as regards bile acid and lipid metabolism. We identified stronger associations between the liver metabolome, chemical exposure and NAFLD-associated clinical variables (liver fat content, HOMA-IR), in female subjects versus males. Specifically, we observed PFAS-associated up-regulation of bile acids, triacylglycerols and ceramides, and association between chemical exposure and dysregulated glucose metabolism in females. The murine exposure study further corroborated our findings, vis-à-vis a sex-specific association between PFAS exposure and NAFLD-associated lipid changes.ConclusionsFemales may be more sensitive to the harmful impacts of PFAS. Lipid-related changes subsequent to PFAS exposure may be secondary to the interplay between PFAS and bile acid metabolism.</p