Genome-based discovery of polyketide-derived secondary metabolism pathways in the barley pathogen <i>Ramularia collo-cygni</i>

Ramularia collo-cygni causes Ramularia leaf spot (RLS) disease of barley. The fungus develops asymptomatically within its host until late in the growing season, when necrotic lesions become visible on upper leaves. Fungal secondary metabolites (SM) have been proposed as important factors in RLS lesion formation but the biosynthetic pathways involved remain largely unknown. Mining the R. collo-cygni genome revealed the presence of 10 polyketide synthases (PKS), 10 nonribosomal peptide synthetases (NRPS), and 3 hybrid PKS-NRPS (HPS) identified within clusters of genes with predicted functions associated with secondary metabolism. SM core genes along with their predicted transcriptional regulators exhibited transcriptional coexpression during infection of barley plants. Moreover, their expression peaked during early stages of host colonization and preceded or overlapped with the appearance of disease symptoms, suggesting that SM may manipulate the host to promote colonization or protect R. collo-cygni from competing organisms. Accordingly, R. collo-cygni inhibited the growth of several fungi in vitro, indicating that it synthesized and excreted antifungal agents. Taken together, these findings demonstrate that the R. collo-cygni genome contains the genetic architecture to synthesize a wide range of SM and suggests that coexpression of PKS and HPS is associated with competitive colonization of the host and early symptom development. [Formula: see text] Copyright © 2018 The Author(s). This is an open access article distributed under the CC BY 4.0 International license . </jats:p

The contributions of biodiversity to the sustainable intensification of food production:Thematic Study to support the State of the World’s Biodiversity for Food and Agriculture

Biodiversity supports sustainable food production, although recognition of its roles has been relatively neglected in the sustainable intensification literature. In the current study, the roles of biodiversity in sustainable food production are considered, assessing how these roles can be measured, the current state of knowledge and opportunities for intervention. The trajectory of global food production, and the challenges and opportunities this presents for the roles of biodiversity in production, are also considered, as well as how biodiversitybased interventions fit within wider considerations for sustainable food systems. The positive interactions between a diverse array of organisms, including annual crops, animal pollinators, trees, micro-organisms, livestock and aquatic animals, support food production globally. To support these interactions, a range of interventions related to access to materials and practices are required. For annual crops, major interventions include breeding crops for more positive crop–crop interactions, and the integration of a wider range of crops into production systems. For animal pollinators, major interventions include the introduction of pollinator populations into production landscapes and the protection and improvement of pollinator habitat. For trees, a major required intervention is the greater integration of perennial legumes into farmland. For micro-organisms, the implementation of agronomic practices that support beneficial crop-microbe interactions is crucial. For livestock production, breed and crop feedstock diversification are essential, and the implementation of improved methods for manure incorporation into cropland. Finally, in the case of aquatic production, it is essential to support the wider adoption of multi-trophic production systems and to diversify crop- and animal-based feed resources. These and other interventions, and the research needs around them, are discussed. Looking to the future, understanding the drivers behind trends in food systems is essential for determining the options for biodiversity in supporting sustainable food production. The increased dominance of a narrow selection of foods globally indicates that efforts to more sustainably produce these foods are crucial. From a biodiversity perspective, this means placing a strong emphasis on breeding for resource use efficiency and adaptation to climate change. It also means challenging the dominance of these foods through focusing on productivity improvements for other crop, livestock and aquaculture species, so that they can compete successfully and find space within production systems. New biodiversity-based models that support food production need not only to be productive but to be profitable. Thus, as well as describing appropriate production system management practices that enhance production and support the environment, the labour, knowledge, time required to operationalize, and other costs of new production approaches, must be considered and minimized. To support the future roles of biodiversity in sustainable food production, we recommend that particular attention be given to the longitudinal analysis of food sectors to determine how the diversity of foods consumed from these sectors has changed over time. Analysis is already available for crops, but related research is needed for livestock and aquaculture sectors. This analysis will then support more optimal cross-sectoral interactions, in terms of the contributions each sector provides to supplying the different components of human diets. Additional meta-analyses and synthetic reviews of case studies are required as an evidence base for biodiversity-based food production system interventions, but future studies should pay more attention to articulating the potential biases in case study compilation (the problem of ‘cherry picking’ positive examples) and the measures that have been taken to minimize such effects

Differential Effect of TLR2 and TLR4 on the Immune Response after Immunization with a Vaccine against Neisseria meningitidis or Bordetella pertussis

Neisseria meningitidis and Bordetella pertussis are Gram-negative bacterial pathogens that can cause serious diseases in humans. N. meningitidis outer membrane vesicle (OMV) vaccines and whole cell pertussis vaccines have been successfully used in humans to control infections with these pathogens. The mechanisms behind their effectiveness are poorly defined. Here we investigated the role of Toll-like receptor (TLR) 2 and TLR4 in the induction of immune responses in mice after immunization with these vaccines. Innate and adaptive immune responses were compared between wild type mice and mice deficient in TLR2, TLR4, or TRIF. TRIF-deficient and TLR4-deficient mice showed impaired immunity after immunization. In contrast, immune responses were not lower in TLR2−/− mice but tended even to be higher after immunization. Together our data demonstrate that TLR4 activation contributes to the immunogenicity of the N. meningitidis OMV vaccine and the whole cell pertussis vaccine, but that TLR2 activation is not required

Systems microscopy approaches to understand cancer cell migration and metastasis

Cell migration is essential in a number of processes, including wound healing, angiogenesis and cancer metastasis. Especially, invasion of cancer cells in the surrounding tissue is a crucial step that requires increased cell motility. Cell migration is a well-orchestrated process that involves the continuous formation and disassembly of matrix adhesions. Those structural anchor points interact with the extra-cellular matrix and also participate in adhesion-dependent signalling. Although these processes are essential for cancer metastasis, little is known about the molecular mechanisms that regulate adhesion dynamics during tumour cell migration. In this review, we provide an overview of recent advanced imaging strategies together with quantitative image analysis that can be implemented to understand the dynamics of matrix adhesions and its molecular components in relation to tumour cell migration. This dynamic cell imaging together with multiparametric image analysis will help in understanding the molecular mechanisms that define cancer cell migration

A Temporal Gate for Viral Enhancers to Co-opt Toll-Like-Receptor Transcriptional Activation Pathways upon Acute Infection

Viral engagement with macrophages activates Toll-Like-Receptors (TLRs) and viruses must contend with the ensuing inflammatory responses to successfully complete their replication cycle. To date, known counter-strategies involve the use of viral-encoded proteins that often employ mimicry mechanisms to block or redirect the host response to benefit the virus. Whether viral regulatory DNA sequences provide an opportunistic strategy by which viral enhancer elements functionally mimic innate immune enhancers is unknown. Here we find that host innate immune genes and the prototypical viral enhancer of cytomegalovirus (CMV) have comparable expression kinetics, and positively respond to common TLR agonists. In macrophages but not fibroblasts we show that activation of NFκB at immediate-early times of infection is independent of virion-associated protein, M45. We find upon virus infection or transfection of viral genomic DNA the TLR-agonist treatment results in significant enhancement of the virus transcription-replication cycle. In macrophage time-course infection experiments we demonstrate that TLR-agonist stimulation of the viral enhancer and replication cycle is strictly delimited by a temporal gate with a determined half-maximal time for enhancer-activation of 6 h; after which TLR-activation blocks the viral transcription-replication cycle. By performing a systematic siRNA screen of 149 innate immune regulatory factors we identify not only anticipated anti-viral and pro-viral contributions but also new factors involved in the CMV transcription-replication cycle. We identify a central convergent NFκB-SP1-RXR-IRF axis downstream of TLR-signalling. Activation of the RXR component potentiated direct and indirect TLR-induced activation of CMV transcription-replication cycle; whereas chromatin binding experiments using wild-type and enhancer-deletion virus revealed IRF3 and 5 as new pro-viral host transcription factor interactions with the CMV enhancer in macrophages. In a series of pharmacologic, siRNA and genetic loss-of-function experiments we determined that signalling mediated by the TLR-adaptor protein MyD88 plays a vital role for governing the inflammatory activation of the CMV enhancer in macrophages. Downstream TLR-regulated transcription factor binding motif disruption for NFκB, AP1 and CREB/ATF in the CMV enhancer demonstrated the requirement of these inflammatory signal-regulated elements in driving viral gene expression and growth in cells as well as in primary infection of neonatal mice. Thus, this study shows that the prototypical CMV enhancer, in a restricted time-gated manner, co-opts through DNA regulatory mimicry elements, innate-immune transcription factors to drive viral expression and replication in the face of on-going pro-inflammatory antiviral responses in vitro and in vivo and; suggests an unexpected role for inflammation in promoting acute infection and has important future implications for regulating latency