A single Streptomyces symbiont makes multiple antifungals to support the fungus farming ant Acromyrmex octospinosus

Attine ants are dependent on a cultivated fungus for food and use antibiotics produced by symbiotic Actinobacteria as weedkillers in their fungus gardens. Actinobacterial species belonging to the genera Pseudonocardia, Streptomyces and Amycolatopsis have been isolated from attine ant nests and shown to confer protection against a range of microfungal weeds. In previous work on the higher attine Acromyrmex octospinosus we isolated a Streptomyces strain that produces candicidin, consistent with another report that attine ants use Streptomyces-produced candicidin in their fungiculture. Here we report the genome analysis of this Streptomyces strain and identify multiple antibiotic biosynthetic pathways. We demonstrate, using gene disruptions and mass spectrometry, that this single strain has the capacity to make candicidin and multiple antimycin compounds. Although antimycins have been known for > 60 years we report the sequence of the biosynthetic gene cluster for the first time. Crucially, disrupting the candicidin and antimycin gene clusters in the same strain had no effect on bioactivity against a co-evolved nest pathogen called Escovopsis that has been identified in similar to 30% of attine ant nests. Since the Streptomyces strain has strong bioactivity against Escovopsis we conclude that it must make additional antifungal(s) to inhibit Escovopsis. However, candicidin and antimycins likely offer protection against other microfungal weeds that infect the attine fungal gardens. Thus, we propose that the selection of this biosynthetically prolific strain from the natural environment provides A. octospinosus with broad spectrum activity against Escovopsis and other microfungal weeds.Publisher PDFPeer reviewe

FUTURE PARTICIPATION IN THE CONSERVATION RESERVE PROGRAM IN NORTH DAKOTA

The purpose of this study was to gauge the impact of agriculture and energy policies on conservation practices through a survey of conservation reserve program (CRP) contract holders in a selected Prairie Pothole Region of North Dakota-Burleigh, Kidder, and Stutsman Counties. The survey results showed that 48% of respondents are considering returning CRP acres to annual crop production once the contract expires. The largest influence on post-CRP land use was the market prices for production of annual crops. Respondents also identified lack of knowledge of conservation programs as a large hurdle to participation. This may indicate a need for improved communication from program information sources such as the Farm Service Agency and the Natural Resource Conservation Service, from where most contract holders get their information. These findings also provide interesting insight into the motivation and decision-making process surrounding conservation programs, in particular continued participation in the CRP. By understanding the main motivation and considerations for conservation participation (market prices, cost-sharing opportunities, and expected cost of production), federal conservation programs will be able to maximize conservation efforts, which will benefit landowners and resources alike

First-order melting of a weak spin-orbit Mott insulator into a correlated metal

The electronic phase diagram of the weak spin-orbit Mott insulator (Sr(1-x)Lax)3Ir2O7 is determined via an exhaustive experimental study. Upon doping electrons via La substitution, an immediate collapse in resistivity occurs along with a narrow regime of nanoscale phase separation comprised of antiferromagnetic, insulating regions and paramagnetic, metallic puddles persisting until x~0.04. Continued electron doping results in an abrupt, first-order phase boundary where the Neel state is suppressed and a homogenous, correlated, metallic state appears with an enhanced spin susceptibility and local moments. As the metallic state is stabilized, a weak structural distortion develops and suggests a competing instability with the parent spin-orbit Mott state.Comment: 5 pages, 4 figure

Using remote substituents to control solution structure and anion binding in lanthanide complexes.

A study of the anion-binding properties of three structurally related lanthanide complexes, which all contain chemically identical anion-binding motifs, has revealed dramatic differences in their anion affinity. These arise as a consequence of changes in the substitution pattern on the periphery of the molecule, at a substantial distance from the binding pocket. Herein, we explore these remote substituent effects and explain the observed behaviour through discussion of the way in which remote substituents can influence and control the global structure of a molecule through their demands upon conformational space. Peripheral modifications to a binuclear lanthanide motif derived from α,α′-bis(DO3 Ayl)-m-xylene are shown to result in dramatic changes to the binding constant for isophthalate. In this system, the parent compound displays considerable conformational flexibility, yet can be assumed to bind to isophthalate through a well-defined conformer. Addition of steric bulk remote from the binding site restricts conformational mobility, giving rise to an increase in binding constant on entropic grounds as long as the ideal binding conformation is not excluded from the available range of conformers

Longevity of an immunocontraceptive vaccine effect on fecundity in rats

Increases in human-wildlife conflicts alongside cultural shifts against lethal control methods are driving the need for alternative wildlife management tools such as fertility control. Contraceptive formulations suitable for oral delivery would permit broader remote application in wildlife species. This study evaluated the contraceptive effect and immune response to two novel injectable immunocontraceptive formulations targeting the Gonadotropin Releasing Hormone (GnRH): MAF-IMX294 and MAF-IMX294P conjugates, both identified as having potential as oral contraceptives. The study also explored whether in multiparous species immunocontraceptives may either totally prevent reproduction or also affect litter size. Female rats, chosen as a model species, were given three doses of either MAF-IMX294 or MAFIMX294P to compare anti-GnRH immune response and reproductive output up to 310 days posttreatment. Both formulations induced anti-GnRH antibody titres in 100% of rats and significantly impaired fertility compared to control animals. Following treatment with MAF-IMX294 and MAF-IMX294P 0 of 9 and 1 of 10 females respectively produced litters following the first mating challenge 45 days posttreatment, compared to 9 of 9 control animals. Across the whole 310 day study period 7 of 9 females from the MAF-IMX294 group and 10 of 10 females in the MAF-IMX294P group became fertile, producing at least one litter throughout six mating challenges. No significant differences were found between the two formulations in antibody titre response or duration of contraceptive effect, with an average time to first pregnancy of 166 days for MAFIMX294 and 177 days for MAF-IMX294P for all females that became fertile. Following treatment with MAF-IMX294 and MAF-IMX294P the first litter produced post-infertility in treated females was significantly smaller than in control animals. This indicates treatment with immunocontraceptives may induce an overall suppression of fecundity extending past an initial infertility effect. This increases the potential long-term impact of these immunocontraceptives in multiparous species such as commensal rodents

Epidemiological and health economic implications of symptom propagation in respiratory pathogens : a mathematical modelling investigation

Background: Respiratory pathogens inflict a substantial burden on public health and the economy. Although the severity of symptoms caused by these pathogens can vary from asymptomatic to fatal, the factors that determine symptom severity are not fully understood. Correlations in symptoms between infector-infectee pairs, for which evidence is accumulating, can generate large-scale clusters of severe infections that could be devastating to those most at risk, whilst also conceivably leading to chains of mild or asymptomatic infections that generate widespread immunity with minimal cost to public health. Although this effect could be harnessed to amplify the impact of interventions that reduce symptom severity, the mechanistic representation of symptom propagation within mathematical and health economic modelling of respiratory diseases is understudied. Methods and findings: We propose a novel framework for incorporating different levels of symptom propagation into models of infectious disease transmission via a single parameter, α. Varying α tunes the model from having no symptom propagation (α = 0, as typically assumed) to one where symptoms always propagate (α = 1). For parameters corresponding to three respiratory pathogens—seasonal influenza, pandemic influenza and SARS-CoV-2—we explored how symptom propagation impacted the relative epidemiological and health-economic performance of three interventions, conceptualised as vaccines with different actions: symptom-attenuating (labelled SA), infection-blocking (IB) and infection-blocking admitting only mild breakthrough infections (IB_MB). In the absence of interventions, with fixed underlying epidemiological parameters, stronger symptom propagation increased the proportion of cases that were severe. For SA and IB_MB, interventions were more effective at reducing prevalence (all infections and severe cases) for higher strengths of symptom propagation. For IB, symptom propagation had no impact on effectiveness, and for seasonal influenza this intervention type was more effective than SA at reducing severe infections for all strengths of symptom propagation. For pandemic influenza and SARS-CoV-2, at low intervention uptake, SA was more effective than IB for all levels of symptom propagation; for high uptake, SA only became more effective under strong symptom propagation. Health economic assessments found that, for SA-type interventions, the amount one could spend on control whilst maintaining a cost-effective intervention (termed threshold unit intervention cost) was very sensitive to the strength of symptom propagation. Conclusions: Overall, the preferred intervention type depended on the combination of the strength of symptom propagation and uptake. Given the importance of determining robust public health responses, we highlight the need to gather further data on symptom propagation, with our modelling framework acting as a template for future analysis

Microglia - mediated immunity partly contributes to the genetic association between Alzheimer's disease and hippocampal volume

Genome-wide association studies (GWAS) suggest that Alzheimer’s disease (AD) is partly explained by a burden of risk alleles (single nucleotide polymorphisms; SNPs) with relatively small effects. However, the mechanisms by which these loci cumulatively confer susceptibility remain largely unknown. Accumulating evidence suggests an association between increased AD risk allele burden (measured via a polygenic risk profile score; AD-RPS) with reduced hippocampal volume (HV) across a number of independent cohorts. These lines of research suggest that the reduced HV may be a causal mechanism of risk in the development of late-onset Alzheimer’s disease (AD). However, as RPS assesses broad, cumulative genetic risk, little is known about the biological processes which may explain this observation. Here, we leverage GWAS data from i) 17,008 late onset AD cases & 37,154 controls and ii) hippocampal volume (N = 12,147; N = 9707) to explore putative pathways that may explain this association. We first demonstrate an association between whole genome AD-RPS and HV (PT < 0.5, Z = −2.07, P = 0.038), confirming previous associations. Second, we restrict our analysis to SNPs within AD genes within a microglia mediated immunity network (NGENES = 56). A microglia AD-RPS was further associated with HV (PT < 0.01; Z = −2.152, P = 0.031). Last, using a competitive, permutation based approach, we show that the common variation within this candidate gene-set is associated with HV, controlling for SNP set-size (P = 0.024). Together, the observations suggest that the relationship between AD and HV is partially explained by genes within an AD-linked microglia mediated immunity network

Gold amides as anticancer drugs: synthesis and activity studies

Modular gold amide chemotherapeutics: Access to modern chemotherapeutics with robust and flexible synthetic routes that are amenable to extensive customisation is a key requirement in drug synthesis and discovery. A class of chiral gold amide complexes featuring amino acid derived ligands is reported herein. They all exhibit in vitro cytotoxicity against two slow growing breast cancer cell lines with limited toxicity towards normal epithelial cells