Defensive properties of pyrrolizidine alkaloids against microorganisms

The understanding of the selection factors that drive chemical diversification of secondary metabolites of constitutive defence systems in plants, such as pyrrolizidine alkaloids (PAs), is still incomplete. Historically, plants always have been confronted with microorganisms. Long before herbivores existed on this planet, plants had to cope with microbial pathogens. Therefore, plant pathogenic microorganisms may have played an important role in the early evolution of the secondary metabolite diversity. In this review, we discuss the impact that plant-produced PAs have on plant-associated microorganisms. The objective of the review is to present the current knowledge on PAs with respect to anti-microbial activities, adaptation and detoxification by microorganisms, pathogenic fungi, root protection and PA induction. Many in vitro experiments showed effects of PAs on microorganisms. These results point to the potential of microorganisms to be important for the evolution of PAs. However, only a few in vivo studies have been published and support the results of the in vitro studies. In conclusion, the topics pointed out in this review need further exploration by carrying out ecological experiments and field studies

PIRCHE-II Is Related to Graft Failure after Kidney Transplantation

Individual HLA mismatches may differentially impact graft survival after kidney transplantation. Therefore, there is a need for a reliable tool to define permissible HLA mismatches in kidney transplantation. We previously demonstrated that donor-derived Predicted Indirectly ReCognizable HLA Epitopes presented by recipient HLA class II (PIRCHE-II) play a role in de novo donor-specific HLA antibodies formation after kidney transplantation. In the present Dutch multi-center study, we evaluated the possible association between PIRCHE-II and kidney graft failure in 2,918 donor–recipient couples that were transplanted between 1995 and 2005. For these donors–recipients couples, PIRCHE-II numbers were related to graft survival in univariate and multivariable analyses. Adjusted for confounders, the natural logarithm of PIRCHE-II was associated with a higher risk for graft failure [hazard ratio (HR): 1.13, 95% CI: 1.04–1.23, p = 0.003]. When analyzing a subgroup of patients who had their first transplantation, the HR of graft failure for ln(PIRCHE-II) was higher compared with the overall cohort (HR: 1.22, 95% CI: 1.10–1.34, p < 0.001). PIRCHE-II demonstrated both early and late effects on graft failure in this subgroup. These data suggest that the PIRCHE-II may impact graft survival after kidney transplantation. Inclusion of PIRCHE-II in donor-selection criteria may eventually lead to an improved kidney graft survival

Eigenvalue asymptotics for weighted Laplace equations on rough Riemannian manifolds with boundary

Our topological setting is a smooth compact manifold of dimension two or higher with smooth boundary. Although this underlying topological structure is smooth, the Riemannian metric tensor is only assumed to be bounded and measurable. This is known as a rough Riemannian manifold. For a large class of boundary conditions we demonstrate a Weyl law for the asymptotics of the eigenvalues of the Laplacian associated to a rough metric. Moreover, we obtain eigenvalue asymptotics for weighted Laplace equations associated to a rough metric. Of particular novelty is that the weight function is not assumed to be of fixed sign, and thus the eigenvalues may be both positive and negative. Key ingredients in the proofs were demonstrated by Birman and Solomjak nearly fifty years ago in their seminal work on eigenvalue asymptotics. In addition to determining the eigenvalue asymptotics in the rough Riemannian manifold setting for weighted Laplace equations, we also wish to promote their achievements which may have further applications to modern problems

T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation

CD4(+) T-helper cells play an important role in alloimmune reactions following transplantation by stimulating humoral as well as cellular responses, which might lead to failure of the allograft. CD4(+) memory T-helper cells from a previous immunizing event can potentially be reactivated by exposure to HLA mismatches that share T-cell epitopes with the initial immunizing HLA. Consequently, reactivity of CD4(+) memory T-helper cells toward T-cell epitopes that are shared between immunizing HLA and donor HLA could increase the risk of alloimmunity following transplantation, thus affecting transplant outcome. In this study, the amount of T-cell epitopes shared between immunizing and donor HLA was used as a surrogate marker to evaluate the effect of donor-reactive CD4(+) memory T-helper cells on the 10-year risk of death-censored kidney graft failure in 190 donor/recipient combinations using the PIRCHE-II algorithm. The T-cell epitopes of the initial theoretical immunizing HLA and the donor HLA were estimated and the number of shared PIRCHE-II epitopes was calculated. We show that the natural logarithm-transformed PIRCHE-II overlap score, or Shared T-cell EPitopes (STEP) score, significantly associates with the 10-year risk of death-censored kidney graft failure, suggesting that the presence of pre-transplant donor-reactive CD4(+) memory T-helper cells might be a strong indicator for the risk of graft failure following kidney transplantation

Review of insect pathogen risks for the black soldier fly (Hermetia illucens) and guidelines for reliable production

Black soldier fly [BSF; Hermetia illucens L. (Diptera: Stratiomyidae)] larvae are very effective in transforming low-grade food waste into valuable high-end proteins and fat, in intensive production facilities. The production output of this species is growing quickly, but upscaling brings risks to the health status of the reared insects. Until now, not a single major case of disease outbreak caused by a pathogen in a BSF production unit has been reported. This contrasts with data on other species of mass-produced insects, which have experienced various disease outbreaks, indicating that BSFs are comparatively resistant to insect diseases. Further, there are no records of natural infections caused by entomopathogens in BSF. In this review, the known entomopathogens of Diptera, especially BSF, and their potential risks for causing disease in these insects are summarized

Testing for coeliac disease rarely leads to a diagnosis: a population-based study

Background Coeliac disease (CD) has an estimated prevalence of ∼1% in Europe with a significant gap between undiagnosed and diagnosed CD. Active case finding may help to bridge this gap yet the diagnostic yield of such active case finding in general practice by serological testing is unknown. Objective The aim of this study was to determine (1) the frequency of diagnosed CD in the general population, and (2) to investigate the yield of active case finding by general practitioners. Methods Electronic medical records of 207.200 patients registered in 49 general practices in The Netherlands in 2016 were analysed. An extensive search strategy, based on International Classification of Primary Care codes, free text and diagnostic test codes was performed to search CD- or gluten-related contacts. Results The incidence of CD diagnosis in general practice in 2016 was 0.01%. The prevalence of diagnosed CD reported in the general practice in the Netherlands was 0.19%, and considerably higher than previously reported in the general population. During the one year course of the study 0.95% of the population had a gluten-related contact with their GP; most of them (72%) were prompted by gastrointestinal complaints. Serological testing was performed in 66% (n = 1296) of these patients and positive in only 1.6% (n = 21). Conclusion The number of diagnosed CD patients in the Netherlands is substantially higher than previously reported. This suggests that the gap between diagnosed and undiagnosed patients is lower than generally assumed. This may explain that despite a high frequency of gluten-related consultations in general practice the diagnostic yield of case finding by serological testing is low.Key points The diagnostic approach of GPs regarding CD and the diagnostic yield is largely unknown Case finding in a primary health care practice has a low yield of 1.6% CD testing was mostly prompted by consultation for gastrointestinal symptoms There is a heterogeneity in types of serological test performed in primary car

Perceived stress, family impact, and changes in physical and social daily life activities of children with chronic somatic conditions during the COVID-19 pandemic

Background: The COVID-19 pandemic has inevitably affected children and their families. This study examines the impact of the COVID-19 measures in children with chronic somatic conditions (CSC) and their parents and compares them with a Dutch general population sample. Methods: We included a sample of children with CSC (0–18 years, n = 326) and compared them with children (8–18 years, n = 1,287) from the Dutch general population. Perceived stress, coping, social interaction with friends and family, physical activity, eating behavior, family support, parenting perception, and financial situation were assessed once with the self-reported and parent-reported COVID-19 child check questionnaire, between November 2020 and May 2021. Comparisons between the two samples were made by using t-tests and chi square tests. Results: The proportion of children who reported being less physically active and having less social interaction with friends since the COVID-19 pandemic was higher in children with CSC than in children from the general population. Children with CSC and their parents experienced less stress than children and parents from the general population. Moreover, parents of children with CSC aged 0–7 years and parents of children aged 8–18 years from the general population experienced less support and more financial deterioration than parents of children with CSC aged 8–18 years. In the parents from the general population only, this deteriorated financial situation was associated with more stress, worse family interaction and parenting perception, and less received support. Conclusions: The impact of COVID-19 on children with CSC and their parents differed from those in the general population. Addressing the collateral damage of COVID-19 measures in children and their families may give direction to policy and potentially prevent lifelong impact