562 research outputs found
Exploring the adoption of precision agricultural technologies: a cross regional study of EU farmers
Precision agricultural technologies (PATs) allow more detailed management of in-field variability. Policy and advisory communities have championed PATs as a route to preserving natural capital whilst increasing productivity from agricultural land. A range of PATs are currently available for the agricultural producer but uptake varies by the type of technology and region. Whereas most studies on uptake have focused on US or Australia we empirically examine uptake of machine guidance (MG) and variable rate nitrogen technologies (VRNT) within European farming systems. Using primary information from 971 arable crop growers across five countries: Belgium, Germany, Greece, the Netherlands and the UK, a multilevel random intercept regression estimated a) the differences between adoption and non-adoption and b) the differences between VRNT and MG adoption. We find, aside from size and income differences, which reflect the economic cost barrier to adoption, an attitudinal difference, in terms of optimism towards the technology's economic return leading to more probability of uptake. Moreover innovative and information seeking behaviour also proved significant when upgrading from machine guidance to variable rate technologies. Subsidy and taxation were considered positive drivers of uptake within the community. However, results suggest that more indirect interventions, such as informational support to counteract industry bias, and demonstration to prove the viability of economic return may be effective at meeting land manager and policy expectations towards PATs
Evolution and spread of Venezuelan equine encephalitis complex alphavirus in the Americas.
Venezuelan equine encephalitis (VEE) complex alphaviruses are important re-emerging arboviruses that cause life-threatening disease in equids during epizootics as well as spillover human infections. We conducted a comprehensive analysis of VEE complex alphaviruses by sequencing the genomes of 94 strains and performing phylogenetic analyses of 130 isolates using complete open reading frames for the nonstructural and structural polyproteins. Our analyses confirmed purifying selection as a major mechanism influencing the evolution of these viruses as well as a confounding factor in molecular clock dating of ancestors. Times to most recent common ancestors (tMRCAs) could be robustly estimated only for the more recently diverged subtypes; the tMRCA of the ID/IAB/IC/II and IE clades of VEE virus (VEEV) were estimated at ca. 149–973 years ago. Evolution of the IE subtype has been characterized by a significant evolutionary shift from the rest of the VEEV complex, with an increase in structural protein substitutions that are unique to this group, possibly reflecting adaptation to its unique enzootic mosquito vector Culex (Melanoconion) taeniopus. Our inferred tree topologies suggest that VEEV is maintained primarily in situ, with only occasional spread to neighboring countries, probably reflecting the limited mobility of rodent hosts and mosquito vectors
Network model of immune responses reveals key effectors to single and co-infection dynamics by a respiratory bacterium and a gastrointestinal helminth
Co-infections alter the host immune response but how the systemic and local processes at the site of infection interact is still unclear. The majority of studies on co-infections concentrate on one of the infecting species, an immune function or group of cells and often focus on the initial phase of the infection. Here, we used a combination of experiments and mathematical modelling to investigate the network of immune responses against single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminth Trichostrongylus retortaeformis. Our goal was to identify representative mediators and functions that could capture the essence of the host immune response as a whole, and to assess how their relative contribution dynamically changed over time and between single and co-infected individuals. Network-based discrete dynamic models of single infections were built using current knowledge of bacterial and helminth immunology; the two single infection models were combined into a co-infection model that was then verified by our empirical findings. Simulations showed that a T helper cell mediated antibody and neutrophil response led to phagocytosis and clearance of B. bronchiseptica from the lungs. This was consistent in single and co-infection with no significant delay induced by the helminth. In contrast, T. retortaeformis intensity decreased faster when co-infected with the bacterium. Simulations suggested that the robust recruitment of neutrophils in the co-infection, added to the activation of IgG and eosinophil driven reduction of larvae, which also played an important role in single infection, contributed to this fast clearance. Perturbation analysis of the models, through the knockout of individual nodes (immune cells), identified the cells critical to parasite persistence and clearance both in single and co-infections. Our integrated approach captured the within-host immuno-dynamics of bacteria-helminth infection and identified key components that can be crucial for explaining individual variability between single and co-infections in natural populations
Influencing incentives for precision agricultural technologies within European arable farming systems
Molecular Interactions of Prodiginines with the BH3 Domain of Anti-Apoptotic Bcl-2 Family Members
Prodigiosin and obatoclax, members of the prodiginines family, are small molecules with anti-cancer properties that are
currently under preclinical and clinical trials. The molecular target(s) of these agents, however, is an open question.
Combining experimental and computational techniques we find that prodigiosin binds to the BH3 domain in some BCL-2
protein families, which play an important role in the apoptotic programmed cell death. In particular, our results indicate
a large affinity of prodigiosin for MCL-1, an anti-apoptotic member of the BCL-2 family. In melanoma cells, we demonstrate
that prodigiosin activates the mitochondrial apoptotic pathway by disrupting MCL-1/BAK complexes. Computer simulations
with the PELE software allow the description of the induced fit process, obtaining a detailed atomic view of the molecular
interactions. These results provide new data to understand the mechanism of action of these molecules, and assist in the
development of more specific inhibitors of anti-apoptotic BCL-2 proteins.Spanish government and the European Union (FIS-PI10/00338) and from the ERC-2009-Adg
25027-PELE European project
Shape - but Not Size - Codivergence between Male and Female Copulatory Structures in Onthophagus Beetles
Genitalia are among the fastest evolving morphological traits in arthropods. Among the many hypotheses aimed at explaining this observation, some explicitly or implicitly predict concomitant male and female changes of genital traits that interact during copulation (i.e., lock and key, sexual conflict, cryptic female choice and pleiotropy). Testing these hypotheses requires insights into whether male and female copulatory structures that physically interact during mating also affect each other's evolution and patterns of diversification. Here we compare and contrast size and shape evolution of male and female structures that are known to interact tightly during copulation using two model systems: (a) the sister species O. taurus (1 native, 3 recently established populations) and O. illyricus, and (b) the species-complex O. fracticornis-similis-opacicollis. Partial Least Squares analyses indicated very little to no correlation between size and shape of copulatory structures, both in males and females. Accordingly, comparing shape and size diversification patterns of genitalia within each sex showed that the two components diversify readily - though largely independently of each other - within and between species. Similarly, comparing patterns of divergence across sexes showed that relative sizes of male and female copulatory organs diversify largely independent of each other. However, performing this analysis for genital shape revealed a signature of parallel divergence. Our results therefore suggest that male and female copulatory structures that are linked mechanically during copulation may diverge in concert with respect to their shapes. Furthermore, our results suggest that genital divergence in general, and co-divergence of male and female genital shape in particular, can evolve over an extraordinarily short time frame. Results are discussed in the framework of the hypotheses that assume or predict concomitant evolutionary changes in male and female copulatory organs
Regulated Expression of CCL21 in the Prostate Tumor Microenvironment Inhibits Tumor Growth and Metastasis in an Orthotopic Model of Prostate Cancer
Currently there are no curative therapies available for patients with metastatic prostate cancer. Thus, novel therapies are needed to treat this patient population. Immunotherapy represents one promising approach for the elimination of occult metastatic tumors. However, the prostate tumor microenvironment (TME) represents a hostile environment capable of suppressing anti-tumor immunity and effector cell function. In view of this immunosuppressive activity, we engineered murine prostate cancer cells with regulated expression (tet-on) of CCL21. Prostate tumor cells implanted orthotopically produced primary prostate tumors with predictable metastatic disease in draining lymph nodes and distant organs. Expression of CCL21 in the prostate TME enhanced survival, inhibited tumor growth and decreased the frequency of local (draining lymph node) and distant metastasis. Therefore, these studies provide a strong rationale for further evaluation of CCL21 in tumor immunity and its use in cancer immunotherapy
Influence of omega-6 PUFA arachidonic acid and bone marrow adipocytes on metastatic spread from prostate cancer
Small molecule anionophores promote transmembrane anion permeation matching CFTR activity
Anion selective ionophores, anionophores, are small molecules capable of facilitating the
transmembrane transport of anions. Inspired in the structure of natural product prodigiosin, four
novel anionophores 1a-d, including a 1,2,3-triazole group, were prepared. These compounds proved
highly efficient anion exchangers in model phospholipid liposomes. The changes in the hydrogen bond
cleft modified the anion transport selectivity exhibited by these compounds compared to prodigiosin
and suppressed the characteristic high toxicity of the natural product. Their activity as anionophores
in living cells was studied and chloride efflux and iodine influx from living cells mediated by these
derivatives was demonstrated. These compounds were shown to permeabilize cellular membranes
to halides with efficiencies close to the natural anion channel CFTR at doses that do not compromise
cellular viability. Remarkably, optimal transport efficiency was measured in the presence of pH
gradients mimicking those found in the airway epithelia of Cystic Fibrosis patients. These results
support the viability of developing small molecule anionophores as anion channel protein surrogates
with potential applications in the treatment of conditions such as Cystic Fibrosis derived from the
malfunction of natural anion transport mechanisms.European Union’s Horizon 2020 research and innovation programme under grant agreement No. 667079, La Marató de TV3 Foundation (20132730), ConsejerÃa de Educación de la Junta de Castilla y León (Projects BU340U13 and BU092U16
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