Macrophages and neutrophils from humans and mice kill larval Strongyloides stercoralis during innate immunity

The parasitic nematode Strongyloides stercoralis (Ss) infects 30-100 million people worldwide, yet little is known about the immune response in humans. Previous studies on innate immunity to Ss in mice have demonstrated a role for eosinophils, neutrophils (PMN) and complement activation in the protective immune response

Application of spatio-temporal data in site-specific maize yield prediction with machine learning methods

In order to meet the requirements of sustainability and to determine yield drivers and limiting factors, it is now more likely that traditional yield modelling will be carried out using artificial intelligence (AI). The aim of this study was to predict maize yields using AI that uses spatio-temporal training data. The paper has advanced a new method of maize yield prediction, which is based on spatio-temporal data mining. To find the best solution, various models were used: counter-propagation artificial neural networks (CP-ANNs), XY-fused Querynetworks (XY-Fs), supervised Kohonen networks (SKNs), neural networks with Rectangular Linear Activations (ReLU), extreme gradient boosting (XGBoost), support-vector machine (SVM), and different subsets of the independent variables in five vegetation periods. Input variables for modelling included: soil parameters (pH, P2O5, K2O, Zn, clay content, ECa, draught force, Cone index), micro-relief averages, and meteorological parameters for the 63 treatment units in a 15.3 ha research field. The best performing method (XGBoost) reached 92.1% and 95.3% accuracy on the training and the test sets. Additionally, a novel method was introduced to treat individual units in a lattice system. The lattice-based smoothing performed an additional increase in Area under the curve (AUC) to 97.5% over the individual predictions of the XGBoost model. The models were developed using 48 different subsets of variables to determine which variables consistently contributed to prediction accuracy. By comparing the resulting models, it was shown that the best regression model was Extreme Gradient Boosting Trees, with 92.1% accuracy (on the training set). In addition, the method calculates the influence of the spatial distribution of site-specific soil fertility on maize grain yields. This paper provides a new method of spatio-temporal data analyses, taking the most important influencing factors on maize yields into account

IL-4(-/-) mice with lethal Mesocestoides corti infections--reduced Th2 cytokines and alternatively activated macrophages.

Protection against Mesocestoides corti, a cestode that invades vital organs, is dependent on the production of IL-4, as IL-4(-/-) mice were found to have higher parasite burdens when compared with wild-type mice. The goal of this study was to investigate the role of IL-4 in immunity to M. corti, focusing on the immunological profile and on potential mediators of pathology. IL-4(-/-) mice infected with M. corti showed 100% mortality by 32 days, whereas wild-type mice survived for approximately 1 year. Parasite burdens were significantly increased in the liver, peritoneal, and thoracic cavities of IL-4(-/-) mice, associated with impaired recruitment of inflammatory cells and a reduction in monocytes and macrophages. IL-5 production by splenocytes and expression in liver tissue was decreased in infected IL-4(-/-) mice compared with wild-type mice. In contrast, IL-4(-/-) mice produced increased amounts of IFNgamma and TNFalpha. Alternatively activated macrophages were a major feature of liver granulomas in wild-type mice evidenced by Arginase I expression, while livers from infected IL-4(-/-) mice showed impaired alternative macrophage activation without increased classical macrophage activation. Thus, lethality during M. corti infection of IL-4(-/-) mice is associated with decreased Th2 cytokines, increased Th1 cytokines and impairment of alternatively activated macrophages

Extracellular traps are associated with human and mouse neutrophil and macrophage mediated killing of larval Strongyloides stercoralis.

Neutrophils are multifaceted cells that are often the immune system\u27s first line of defense. Human and murine cells release extracellular DNA traps (ETs) in response to several pathogens and diseases. Neutrophil extracellular trap (NET) formation is crucial to trapping and killing extracellular pathogens. Aside from neutrophils, macrophages and eosinophils also release ETs. We hypothesized that ETs serve as a mechanism of ensnaring the large and highly motile helminth parasite Strongyloides stercoralis thereby providing a static target for the immune response. We demonstrated that S. stercoralis larvae trigger the release of ETs by human neutrophils and macrophages. Analysis of NETs revealed that NETs trapped but did not kill larvae. Induction of NETs was essential for larval killing by human but not murine neutrophils and macrophages in vitro. In mice, extracellular traps were induced following infection with S. stercoralis larvae and were present in the microenvironment of worms being killed in vivo. These findings demonstrate that NETs ensnare the parasite facilitating larval killing by cells of the immune system

DNA methylation clock DNAmFitAge shows regular exercise is associated with slower aging and systemic adaptation

DNAmPhenoAge, DNAmGrimAge, and the newly developed DNAmFitAge are DNA methylation (DNAm)-based biomarkers that reflect the individual aging process. Here, we examine the relationship between physical fitness and DNAm-based biomarkers in adults aged 33–88 with a wide range of physical fitness (including athletes with long-term training history). Higher levels of VO 2 max ( ρ = 0.2, p = 6.4E − 4, r = 0.19, p = 1.2E − 3), Jumpmax ( p = 0.11, p = 5.5E − 2, r = 0.13, p = 2.8E − 2), Gripmax ( ρ = 0.17, p = 3.5E − 3, r = 0.16, p = 5.6E − 3), and HDL levels ( ρ = 0.18, p = 1.95E − 3, r = 0.19, p = 1.1E − 3) are associated with better verbal short-term memory. In addition, verbal short-term memory is associated with decelerated aging assessed with the new DNAm biomarker FitAgeAcceleration ( ρ : − 0.18, p = 0.0017). DNAmFitAge can distinguish high-fitness individuals from low/medium-fitness individuals better than existing DNAm biomarkers and estimates a younger biological age in the high-fit males and females (1.5 and 2.0 years younger, respectively). Our research shows that regular physical exercise contributes to observable physiological and methylation differences which are beneficial to the aging process. DNAmFitAge has now emerged as a new biological marker of quality of life

Social rearing environment influences dog behavioral development

Early life experiences are known to influence behavior later in life. In dogs, environmental influences of early home rearing could be exploited to improve the chances of developing adult behavior most suited to the adult environment. For working dog organizations, such as Guide Dogs, suitable adult behavior is important to ensure that dogs can fulfill their role as guides for people with visual impairment. Here, we test the hypothesis that dogs' home rearing environment will influence behavioral development. To investigate this hypothesis, carers of potential guide dogs (puppy walkers) completed a questionnaire, termed the Puppy Walker Questionnaire (PWQ), about the dog's behavior at 5, 8, and 12 months of age. An additional 11 questions were answered about the home environment at the last assessment. Because no questionnaire existed which measured behavior most relevant to Guide Dogs, questions from an existing questionnaire (Canine Behaviour and Research Questionnaire) were combined with additional questions. Thus, a subsidiary aim of the study was to test the reliability of the PWQ for measuring behavioral development of potential guide dogs. The PWQ, scored on a 100-mm visual analogue scale, grouped into 5 new scales: trainability, distractibility, general anxiety, body sensitivity, and stair anxiety, with 4 Canine Behaviour and Research Questionnaire scales: excitability, separation-related behavior, attachment and attention seeking, and energy level. For each reliable scale, multivariate linear regression identified significant predictors from the home environmental questions. The results suggest that home rearing environment is indeed important for behavioral development: 9 of 11 environmental variables were significant predictors of behavioral scores. Those environmental variables that appeared most important were social in nature. Dogs were scored as higher in energy level, excitability, and distractibility if they had been raised in a home with children, lower on energy level and distractibility the more experience of puppy walking their carer had, and lower on separation-related behavior the more they had been able to play with other dogs. These findings have implications for matching between dogs' early and later home environments. Follow-up of dogs in this study could help to elucidate effects on guiding suitability and matching between dog and guide dog owner

Regulatory T Cell Expansion in HTLV-1 and Strongyloidiasis Co-infection Is Associated with Reduced IL-5 Responses to Strongyloides stercoralis Antigen

Human strongyloidiasis varies from a mild, controlled infection to a severe frequently fatal disseminated infection depending on the hosts. Patients infected with the retrovirus HTLV-1 have more frequent and more severe forms of strongyloidiasis. It is not clear how human strongyloidiasis is controlled by the immune system and how HTLV-1 infection affects this control. We hypothesize that HTLV-1 leads to dissemination of Strongyloides stercoralis by augmenting regulatory T cell numbers, which in turn down regulate the immune response to the parasite. In our study, patients with HTLV-1 and Strongyloides co-infection had higher parasite burdens than patients with only strongyloidiasis. Eosinophils play an essential role in control of strongyloidiasis in animal models, and eosinophil counts were decreased in the HTLV-1 and Strongyloides stercoralis co-infected subjects compared to patients with only strongyloidiasis. The proportion of T cells with a regulatory cell phenotype was increased in HTLV-1 positive subjects co-infected with strongyloidiasis compared to patients with only strongyloidiasis. IL-5 is a key host molecule in stimulating eosinophil production and activation, and Strongyloides stercoralis antigen-specific IL-5 responses were reduced in strongyloidiasis/HTLV-1 co-infected patients. Reduced IL-5 responses and eosinophil counts were inversely correlated to the number of regulatory T cells. These findings suggest a role for regulatory T cells in susceptibility to Strongyloides hyperinfection

Mapping of Genes Involved in Glutathione, Carbohydrate and COR14b Cold Induced Protein Accumulation during Cold Hardening in Wheat

Using some of the chromosome substitution lines developed from the crosses of the donor Cheyenne to Chinese Spring we showed that the accumulation of water soluble carbohydrates during different stages of hardening was time dependent. Moreover there was a significant correlation between the rate of carbohydrate accumulation and the frost tolerance. The expression and regulation of a wheat gene homologous to the barley cold regulated cor14b gene was compared in frost sensitive and frost tolerant wheat genotypes at different temperatures. Studies made with chromosome substitution lines showed that the threshold induction temperature polymorphism of the cor14b wheat homologous gene was controlled by loci located on chromosome 5A of wheat, while cor14b gene was mapped, in Triticum monococcum, onto the long arm of chromosome 2Am. Our study on the effect of cold hardening on glutathione (GSH) metabolism showed that chromosome 5A of wheat has an influence on the GSH accumulation and on the ratio of reduced and oxidised glutathione as part of a complex regulatory function during cold hardening. In addition, the level of increase in GSH content during hardening may indicate the degree of the frost tolerance of wheat

Microarray-Based Analysis of Differential Gene Expression between Infective and Noninfective Larvae of Strongyloides stercoralis

Strongyloides stercoralis is a soil-transmitted helminth that affects an estimated 30–100 million people worldwide. Chronically infected persons who are exposed to corticosteroids can develop disseminated disease, which carries a high mortality (87–100%) if untreated. Despite this, little is known about the fundamental biology of this parasite, including the features that enable infection. We developed the first DNA microarray for this parasite and used it to compare infective third-stage larvae (L3i) with non-infective first stage larvae (L1). Using this method, we identified 935 differentially expressed genes. Functional characterization of these genes revealed L3i biased expression of heat shock proteins and genes with products that have previously been shown to be immunoreactive in infected humans. Genes putatively involved in transcription were found to have L1 biased expression. Potential chemotherapeutic and vaccine targets such as far-1, ucr 2.1 and hsp-90 were identified for further study

Intestinal strongyloidiasis and hyperinfection syndrome

In spite of recent advances with experiments on animal models, strongyloidiasis, an infection caused by the nematode parasite Strongyloides stercoralis, has still been an elusive disease. Though endemic in some developing countries, strongyloidiasis still poses a threat to the developed world. Due to the peculiar but characteristic features of autoinfection, hyperinfection syndrome involving only pulmonary and gastrointestinal systems, and disseminated infection with involvement of other organs, strongyloidiasis needs special attention by the physician, especially one serving patients in areas endemic for strongyloidiasis. Strongyloidiasis can occur without any symptoms, or as a potentially fatal hyperinfection or disseminated infection. Th(2 )cell-mediated immunity, humoral immunity and mucosal immunity have been shown to have protective effects against this parasitic infection especially in animal models. Any factors that suppress these mechanisms (such as intercurrent immune suppression or glucocorticoid therapy) could potentially trigger hyperinfection or disseminated infection which could be fatal. Even with the recent advances in laboratory tests, strongyloidiasis is still difficult to diagnose. But once diagnosed, the disease can be treated effectively with antihelminthic drugs like Ivermectin. This review article summarizes a case of strongyloidiasis and various aspects of strongyloidiasis, with emphasis on epidemiology, life cycle of Strongyloides stercoralis, clinical manifestations of the disease, corticosteroids and strongyloidiasis, diagnostic aspects of the disease, various host defense pathways against strongyloidiasis, and available treatment options