The challenges of long-term invasive mammal management: lessons from the UK

We consider the motivations, strategies, and costs involved in invasive mammal management undertaken in the UK. Widespread established invasive mammals require long-term management to limit damage or spread, but ongoing management is costly and complex. Long-term management is most effective where it is applied at a landscape scale, but this requires overarching co-ordination between multiple stakeholders. Five challenges for successful long-term management of invasive mammal species are identified as follows: defining landscape-scale strategies, management co-ordination, stakeholder and community engagement, sustainable funding, and evidence requirements. We make recommendations on the supportive infrastructure needed for effective landscape-scale management of invasive mammals to fulfil long-term conservation aims, as follows. 1. There is a need for evidence-based Invasive Species Action Plans to provide strategy for the long-term ongoing management of prioritised species at appropriate scales. 2. Where possible, multispecies approaches to invasive species management should be adopted. 3. Trusted leadership should be identified to take ownership of Action Plans and provide an overarching co-ordination to bring individuals, organisations, and funders together. 4. Support for a centralised hub for training, data, and knowledge flows will greatly improve scientific outcomes through a searchable evidence base, and via best practice and knowledge sharing.     

Synthesis and cathepsin D inhibition of peptide-hydroxyethyl amine isosteres with cyclic tertiary amines

Summary  Cathepsin D, a lysosomal aspartic protease, has been suggested to play a role in the metastatic potential of several types of cancer. A high activated cathepsin D level in breast tumor tissue has been associated with an increased incidence of relapse and metastasis. High levels of active cathepsin D have also been found in colon cancer, prostate cancer, uterine cancer and ovarian cancer. Hydroxyethyl isosteres with cyclic tertiary amine have proven to be clinically useful as inhibitors of aspartyl proteases similar to cathepsin D in activity, such as the HIV-1 aspartyl protease. The design and the synthesis of (hydroxyethyl)amine isostere inhibitors with cyclic tertiary amines is described. The IC₅₀ and K_i(app) values for the six cathepsin D inhibitors and pepstatin are reported. Compounds7b,3(S)-[Acetyl-L-valyl-L-phenylalanylamino]-4-phenyl-1-N-piperidine-2(S)-butanol, and7c, 3(S)-[Acetyl-L-leucyl-L-phenylalanylamino]-4-phenyl-1-N-piperidine-2(S)-butanol, showed the most potent inhibition of cathepsin D hydrolysis of hemoglobin with IC₅₀ values of 3.5 nM and 4.5 nM, respectively.     

The Mycorrhizal Fungus, Sebacina vermifera, Enhances Seed Germination and Biomass Production in Switchgrass (Panicum virgatum L)

Seed dormancy and slow seedling establishment are two major concerns in switchgrass (Panicum virgatum L.) production, often resulting in a poor stand with reduced productivity. Studies were conducted to investigate the stability of artificial associations between switchgrass and the ectomycorrhizal fungus, Sebacina vermifera, and to evaluate the potential benefits of this novel association in seed germination and biomass production. All six strains of S. vermifera tested had a high frequency of colonization on switchgrass roots of a synthetic cultivar NF/GA-993. The positive effects of the associations were reflected in plant height, root length, and biomass production. Inoculated plants produced as much as 75%, 113%, and 18% more shoot biomass than un-inoculated control plants in the first, second, and third harvest, respectively, with no consequent reduction in root biomass. Further, culture filtrates from some strains of S. vermifera increased seed germination in the switchgrass cultivar Kanlow by 52% over the control (p?<?0.05). This study illustrates the great potential of microbial associations to increase biomass production and productivity of switchgrass.     

B7-H3 drives immunosuppression and Co-targeting with CD47 is a new therapeutic strategy in β-catenin activated melanomas

In melanoma, immune cell infiltration into the tumor is associated with better patient outcomes and response to immunotherapy. T-cell non-inflamed tumors (cold tumors) are associated with tumor cell-intrinsic Wnt/β-catenin activation, and are typically resistant to anti-PD-1 alone or in combination with anti-CTLA-4 therapy. Reversal of the ‘cold tumor’ phenotype and identifying new effective immunotherapies are challenges. We sought to investigate the role of a newer immunotherapy agent, B7-H3, in this setting. RNA sequencing was used to identify co-targeting strategies upon B7-H3 inhibition in a well-defined preclinical melanoma model driven by β-catenin. We found that immune checkpoint molecule B7-H3 confers a suppressive tumor microenvironment by modulating antiviral signals and innate immunity. B7-H3 inhibition led to an inflamed microenvironment, up-regulation of CD47/SIRPa signaling, and together with blockade of the macrophage checkpoint CD47 resulted in additive antitumor responses. We found that the antitumor effects of the B7-H3/CD47 antibody combination were dependent on cytokine signaling pathways (CCR5/CCL5 and IL4).     

Single nucleotide polymorphism discovery in barley using autoSNPdb

Molecular markers are used to provide the link between genotype and phenotype, for the production of molecular genetic maps and to assess genetic diversity within and between related species. Single nucleotide polymorphisms (SNPs) are the most abundant molecular genetic marker. SNPs can be identified in silico , but care must be taken to ensure that the identified SNPs reflect true genetic variation and are not a result of errors associated with DNA sequencing. The SNP detection method autoSNP has been developed to identify SNPs from sequence data for any species. Confidence in the predicted SNPs is based on sequence redundancy, and haplotype co-segregation scores are calculated for a further independent measure of confidence. We have extended the autoSNP method to produce autoSNPdb, which integrates SNP and gene annotation information with a graphical viewer. We have applied this software to public barley expressed sequences, and the resulting database is available over the Internet. SNPs can be viewed and searched by sequence, functional annotation or predicted synteny with a reference genome, in this case rice. The correlation between SNPs and barley cultivar, expressed tissue type and development stage has been collated for ease of exploration. An average of one SNP per 240 bp was identified, with SNPs more prevalent in the 5' regions and simple sequence repeat (SSR) flanking sequences. Overall, autoSNPdb can provide a wealth of genetic polymorphism information for any species for which sequence data are available.