Sub-lethal fungicide concentrations both reduce and stimulate the growth rate of non-target soil fungi from a natural grassland

Conventional agriculture has relied extensively on the use of fungicides to prevent or control crop diseases. However, some fungicides, particularly broad-spectrum fungicides, not only eliminate target pathogens but also non-target and beneficial soil microbes. This scenario is not only limited to agricultural soil, but this may also potentially occur when neighboring environments are contaminated by fungicides through spray drift. Although concentrations may be sub-lethal, the chemicals may accumulate in the soil when used continuously resulting in more toxic effects. In this study, the effect on the colony extension rate of 31 filamentous soil saprobic fungi, initially isolated from a protected grassland ecosystem, were analyzed under fungicide treatment. These isolates were considered naive (no deliberate exposure), hence presumed to have not developed resistance. Two currently used fungicides with different modes of action were added to Potato Dextrose Agar at varying concentrations. Results showed a wide range of tolerance and sensitivity to isopyrazam and prothioconazole. Fungi belonging to the phylum Basidiomycota were most negatively affected by both fungicides. Phylum Mucoromycota were the most tolerant to prothioconazole while isolates belonging to phylum Ascomycota differed in their responses to both fungicides. Negative effects on the growth rate were more pronounced at higher concentrations except for a few isolates that were inhibited at 1 mg·L−1. A slightly positive effect was also observed in three of the isolates under fungicide treatment. Lastly, the negative impact of fungicides was not associated with the growth strategy of the fungi, whether fast growing or slow growing, rather it is isolate-specific and phylogenetically conserved. The results of this study demonstrate that co-occurring fungi differ in their sensitivity to fungicides even without prior exposure. This difference in sensitivity among co-occurring fungi may result in shifts in community composition of the soil fungal community to the detriment of the more sensitive isolates

Limited role of fungal diversity in maintaining soil processes in grassland soil under concurrent fungicide stress

Background Fungicides are an effective tool for protecting crops and maintaining a steady food supply. However, as pathogens continue to evolve, it is crucial to prolong the effectiveness of fungicides by delaying resistance development. A key strategy to achieving this is to combine or rotate fungicides with different modes of action. As fungicides lack specificity, they inevitably affect both pathogenic and non-pathogenic fungi when surrounding environments are unintentionally contaminated. Our study aims to investigate the effects of recommended application methods to prevent resistance development, specifically repeated-single fungicide, simultaneous mixture, and sequential applications on non-target soil fungi, and the subsequent impacts on important soil processes. We used fungicides with different modes of action on soil microcosms inoculated with fungi at varying levels of diversity (3, 5, and 8 species) isolated from a protected grassland. Results We found that repeated treatments of individual isopyrazam and prothioconazole differentially inhibited fungal activity. Although mixture applications are considered more protectant against crop pathogen resistance than repeated application, our study revealed stronger negative effects of simultaneous application on saprobic fungi and consequently on soil processes. However, contrary to expectations, higher fungal diversity did not translate to improved soil function under these conditions. Conclusions The simultaneous application of fungicides with different modes of action (MoA) has more pronounced non-target effects on soil compared to the individual or sequential application of fungicides. These non-target effects extend beyond the intended control of pathogenic fungi, impacting saprobic and beneficial soil microbes and the critical processes they drive. When fungicides are applied concurrently, microbial activities in the soil are significantly altered, even in soils with high microbial diversity. Our study emphasizes the importance of carefully considering the unintended consequences of fungicide use in agriculture. As we strive for a secure food supply, it is crucial to investigate the broader environmental impacts of these chemical interventions, including their effects on non-pathogenic fungi and overall soil health

Neuroprotective and Neurorestorative Properties of Copolymer-1: Its Immunomodulating Effects on Ischemic Stroke

Stroke is a pathology of great relevance worldwide as it currently occupies the second motif of death and the third reason of disability. Although exits some therapies that are used successfully in the clinic, a very high percentage of patients do not have the opportunity to benefit from them; therefore, it is imperative to propose other alternatives that may favor more patients. In this chapter, we briefly review the inflammatory response induced by stroke and also its deleterious and protective effects. We will describe the characteristics of copolymer-1 and the effects that this compound has shown in models of cerebral ischemia

CHOPCHOP: a CRISPR/Cas9 and TALEN web tool for genome editing

Major advances in genome editing have recently been made possible with the development of the TALEN and CRISPR/Cas9 methods. The speed and ease of implementing these technologies has led to an explosion of mutant and transgenic organisms. A rate-limiting step in efficiently applying TALEN and CRISPR/Cas9 methods is the selection and design of targeting constructs. We have developed an online tool, CHOPCHOP (https://chopchop.rc.fas.harvard.edu), to expedite the design process. CHOPCHOP accepts a wide range of inputs (gene identifiers, genomic regions or pasted sequences) and provides an array of advanced options for target selection. It uses efficient sequence alignment algorithms to minimize search times, and rigorously predicts off-target binding of single-guide RNAs (sgRNAs) and TALENs. Each query produces an interactive visualization of the gene with candidate target sites displayed at their genomic positions and color-coded according to quality scores. In addition, for each possible target site, restriction sites and primer candidates are visualized, facilitating a streamlined pipeline of mutant generation and validation. The ease-of-use and speed of CHOPCHOP make it a valuable tool for genome engineering

Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum.

Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is a common and clinically distinct form of familial spastic paraplegia that is linked to the SPG11 locus on chromosome 15 in most affected families. We analyzed 12 ARHSP-TCC families, refined the SPG11 candidate interval and identified ten mutations in a previously unidentified gene expressed ubiquitously in the nervous system but most prominently in the cerebellum, cerebral cortex, hippocampus and pineal gland. The mutations were either nonsense or insertions and deletions leading to a frameshift, suggesting a loss-of-function mechanism. The identification of the function of the gene will provide insight into the mechanisms leading to the degeneration of the corticospinal tract and other brain structures in this frequent form of ARHSP

Towards establishing a fungal economics spectrum in soil saprobic fungi

Trait-based frameworks are promising tools to understand the functional consequences of community shifts in response to environmental change. The applicability of these tools to soil microbes is limited by a lack of functional trait data and a focus on categorical traits. To address this gap for an important group of soil microorganisms, we identify trade-offs underlying a fungal economics spectrum based on a large trait collection in 28 saprobic fungal isolates, derived from a common grassland soil and grown in culture plates. In this dataset, ecologically relevant trait variation is best captured by a three-dimensional fungal economics space. The primary explanatory axis represents a dense-fast continuum, resembling dominant life-history trade-offs in other taxa. A second significant axis reflects mycelial flexibility, and a third one carbon acquisition traits. All three axes correlate with traits involved in soil carbon cycling. Since stress tolerance and fundamental niche gradients are primarily related to the dense-fast continuum, traits of the 2nd (carbon-use efficiency) and especially the 3rd (decomposition) orthogonal axes are independent of tested environmental stressors. These findings suggest a fungal economics space which can now be tested at broader scales

Design processes and multi-regulation of biomimetic building skins: A comparative analysis

Biomimetics is an opportunity for the development of energy efficient building systems. Several biomimetic building skins (Bio-BS) have been built over the past decade, however few addressed multi-regulation although the biological systems they are inspired by have multi-functional properties. Recent studies have suggested that despite numerous tools and methods described in the literature for the development of biomimetic systems, their use for designing Bio-BS is scarce. To assess the main challenges of biomimetic design processes and their influence on the final design, this paper presents a comparative analysis of several existing Bio-BS. The analyses were carried out with univariable and multivariate descriptive tools in order to highlight the main trends, similarities and differences between the projects. The authors evaluated the design process of thirty existing Bio-BS, including a focus on the steps related to the understanding of the biological models. Data was collected throughout interviews. The univariate analysis revealed that very little Bio-BS followed a biomimetic design framework (5%). None of the Bio-BS was as multi-functional as their biological model(s) of inspiration. A further conclusion drawn that Bio-BS are mostly inspired by single biological organisms (82%), which mostly belong to the kingdom of animals (53%) and plants (37%). The multivariate analysis outlined that the Bio-BS were distributed into two main groups: (1) academic projects which present a strong correlation with the inputs in biology in their design processes and resulted in radical innovation; (2) public building projects which used conventional design and construction methods for incremental innovation by improving existing building systems. These projects did not involve biologists neither a thorough understanding of biological models during their design process. Since some biomimetic tools are available and Bio-BS have shown limitations in terms of multifunctionality, there is a need to promote the use of multidisciplinary tools in the design process of Bio-BS, and address the needs of the designers to enhance the application of multi-regulation capabilities for improved performances

Psychometric properties of the measure of achieved capabilities in homeless services

Background Purposeful participation in personally meaningful life tasks, enjoyment of positive reciprocal relationships, and opportunities to realize one’s potential are growth-related aspects of a meaningful life that should be considered important dimensions of recovery from homelessness. The extent to which homeless services support individuals to achieve the capabilities they need to become who they want to be and do what they want to do is, in turn, an important indicator of their efectiveness. In this study, we developed a measure of achieved capabilities (MACHS) for use in homeless services settings, and assessed its construct and concurrent validity. Methods We analysed data collected from homeless services users at two time points in eight European countries to assess the factor structure and psychometric properties of the new measure. Participants were adults engaged with either Housing First (n=245) or treatment as usual (n=320). Results Exploratory and confrmatory factor analyses yielded a four-factor structure of the capabilities measure: community integration, optimism, safety, and self-determination. We obtained evidence for construct validity through observed correlations between achieved capabilities and recovery, working alliance and satisfaction with services. Moreover, we obtained evidence of the measure’s concurrent validity from its positive association between HF and personal recovery, which was fully mediated by achieved capabilities. Conclusions Findings demonstrate that the MACHS is a valid and reliable measure that may be used to assess the extent to which homeless services support their clients to develop capabilities needed for growth-related recovery. Implications for practice and future research directions are discussed.info:eu-repo/semantics/publishedVersio

Psychometric properties of the measure of achieved capabilities in homeless services

Background Purposeful participation in personally meaningful life tasks, enjoyment of positive reciprocal relationships, and opportunities to realize one’s potential are growth-related aspects of a meaningful life that should be considered important dimensions of recovery from homelessness. The extent to which homeless services support individuals to achieve the capabilities they need to become who they want to be and do what they want to do is, in turn, an important indicator of their efectiveness. In this study, we developed a measure of achieved capabilities (MACHS) for use in homeless services settings, and assessed its construct and concurrent validity. Methods We analysed data collected from homeless services users at two time points in eight European countries to assess the factor structure and psychometric properties of the new measure. Participants were adults engaged with either Housing First (n=245) or treatment as usual (n=320). Results Exploratory and confrmatory factor analyses yielded a four-factor structure of the capabilities measure: community integration, optimism, safety, and self-determination. We obtained evidence for construct validity through observed correlations between achieved capabilities and recovery, working alliance and satisfaction with services. Moreover, we obtained evidence of the measure’s concurrent validity from its positive association between HF and personal recovery, which was fully mediated by achieved capabilities. Conclusions Findings demonstrate that the MACHS is a valid and reliable measure that may be used to assess the extent to which homeless services support their clients to develop capabilities needed for growth-related recovery. Implications for practice and future research directions are discussed.Horizon2020 of the European Commissioninfo:eu-repo/semantics/publishedVersio

Epigenetic Reprogramming Sensitizes CML Stem Cells to Combined EZH2 and Tyrosine Kinase Inhibition.

UNLABELLED: A major obstacle to curing chronic myeloid leukemia (CML) is residual disease maintained by tyrosine kinase inhibitor (TKI)-persistent leukemic stem cells (LSC). These are BCR-ABL1 kinase independent, refractory to apoptosis, and serve as a reservoir to drive relapse or TKI resistance. We demonstrate that Polycomb Repressive Complex 2 is misregulated in chronic phase CML LSCs. This is associated with extensive reprogramming of H3K27me3 targets in LSCs, thus sensitizing them to apoptosis upon treatment with an EZH2-specific inhibitor (EZH2i). EZH2i does not impair normal hematopoietic stem cell survival. Strikingly, treatment of primary CML cells with either EZH2i or TKI alone caused significant upregulation of H3K27me3 targets, and combined treatment further potentiated these effects and resulted in significant loss of LSCs compared to TKI alone, in vitro, and in long-term bone marrow murine xenografts. Our findings point to a promising epigenetic-based therapeutic strategy to more effectively target LSCs in patients with CML receiving TKIs. SIGNIFICANCE: In CML, TKI-persistent LSCs remain an obstacle to cure, and approaches to eradicate them remain a significant unmet clinical need. We demonstrate that EZH2 and H3K27me3 reprogramming is important for LSC survival, but renders LSCs sensitive to the combined effects of EZH2i and TKI. This represents a novel approach to more effectively target LSCs in patients receiving TKI treatment. Cancer Discov; 6(11); 1248-57. ©2016 AACR.See related article by Xie et al., p. 1237This article is highlighted in the In This Issue feature, p. 1197