A 3-local identification of the alternating group of degree 8, the McLaughlin simple group and their automorphism groups

In this article we give 3-local characterizations of the alternating and symmetric groups of degree 8 and use these characterizations to recognize the sporadic simple group discovered by McLaughlin from its 3-local subgroups

The diarrhetic shellfish-poisoning toxin, okadaic acid, provokes gastropathy, dysbiosis and susceptibility to bacterial infection in a non-rodent bioassay, Galleria mellonella

Diarrhetic shellfish-poisoning (DSP) toxins such as okadaic acid and dinophysistoxins harm the human gastrointestinal tract, and therefore, their levels are regulated to an upper limit of 160 μg per kg tissue to protect consumers. Rodents are used routinely for risk assessment and studies concerning mechanisms of toxicity, but there is a general move toward reducing and replacing vertebrates for these bioassays. We have adopted insect larvae of the wax moth Galleria mellonella as a surrogate toxicology model. We treated larvae with environmentally relevant doses of okadaic acid (80–400 μg/kg) via intrahaemocoelic injection or gavage to determine marine toxin-related health decline: (1) whether pre-exposure to a sub-lethal dose of toxin (80 μg/kg) enhances susceptibility to bacterial infection, or (2) alters tissue pathology and bacterial community (microbiome) composition of the midgut. A sub-lethal dose of okadaic acid (80 μg/kg) followed 24 h later by bacterial inoculation (2 × 105 Escherichia coli) reduced larval survival levels to 47%, when compared to toxin (90%) or microbial challenge (73%) alone. Histological analysis of the midgut depicted varying levels of tissue disruption, including nuclear aberrations associated with cell death (karyorrhexis, pyknosis), loss of organ architecture, and gross epithelial displacement into the lumen. Moreover, okadaic acid presence in the midgut coincided with a shift in the resident bacterial population over time in that substantial reductions in diversity (Shannon) and richness (Chao-1) indices were observed at 240 μg toxin per kg. Okadaic acid-induced deterioration of the insect alimentary canal resembles those changes reported for rodent bioassays

mRNA display for the in vitro evolution of artificial proteins and enzymes

Artificial proteins and enzymes have the potential to aid in the production of pharmaceuticals and to facilitate basic biomedical research. Two methods currently exist for the development of artificial proteins: rational design and de novo selection. Rational design requires detailed knowledge of enzyme catalysis in order to design an enzyme active site in silico, and then introduce this active site into a protein. However, gaps in the understanding of protein folding and structure-function relationships make this approach challenging and far from routine. In contrast, laboratory evolution approaches to isolate artificial proteins and enzymes from libraries of variants are well established. In vitro selection techniques are powerful tools for the exploration of large areas of sequence space (up to 1013 unique sequences) in the search for functional proteins and enzymes. mRNA display selection methods have only recently been developed, and the application of this technique for the engineering of de novo enzymes has not been fully explored. This thesis describes the establishment of an mRNA display platform for the selection and evolution of novel proteins and enzymes from large, high-diversity libraries. The synthesis of novel selection substrates are described that will facilitate the application of mRNA display to the selection of Diels-Alderase enzymes. A novel application of mRNA display is described for the solution-phase selection of protein-ligand pairs using interaction-dependent reverse transcription. Further development of this research could increase the throughput of ligand discovery to complement the pace at which new macromolecular targets of interest are being discovered. The ability to generate tailor-made enzymes that catalyse novel reactions is of considerable interest. The applications of mRNA display selection described in this thesis will help to extend the range of enzyme catalysis, and to elucidate basic mechanisms of biocatalysis and protein evolution. Moreover, such ‘designer enzymes’ hold promise for a huge range of applications including, but not limited to, the synthesis of chemicals, pharmaceuticals, and production of renewable fuels

Polarisable force fields: what do they add in biomolecular simulations?

The quality of biomolecular simulations critically depends on the accuracy of the force field used to calculate the potential energy of the molecular configurations. Currently, most simulations employ non-polarisable force fields, which describe electrostatic interactions as the sum of Coulombic interactions between fixed atomic charges. Polarisation of these charge distributions is incorporated only in a mean-field manner. In the past decade, extensive efforts have been devoted to developing simple, efficient, and yet generally applicable polarisable force fields for biomolecular simulations. In this review, we summarise the latest developments in accounting for key biomolecular interactions with polarisable force fields and applications to address challenging biological questions. In the end, we provide an outlook for future development in polarisable force fields

Polarisable force fields:what do they add in biomolecular simulations?

The quality of biomolecular simulations critically depends on the accuracy of the force field used to calculate the potential energy of the molecular configurations. Currently, most simulations employ non-polarisable force fields, which describe electrostatic interactions as the sum of Coulombic interactions between fixed atomic charges. Polarization of these charge distributions is incorporated only in a mean-field manner. In the past decade, extensive efforts have been devoted to developing simple, efficient, and yet generally applicable polarisable force fields for biomolecular simulations. In this review, we summarise the latest developments in accounting for key biomolecular interactions with polarisable force fields and applications to address challenging biological questions. In the end, we provide an outlook for future development in polarisable force fields.Comment: 25 pages, 3 figure

Hematodinium sp. infection does not drive collateral disease contraction in a crustacean host

Host, pathogen, and environment are determinants of the disease triangle, the latter being a key driver of disease outcomes and persistence within a community. The dinoflagellate genus Hematodinium is detrimental to crustaceans globally – considered to suppress the innate defences of hosts, making them more susceptible to co-infections. Evidence supporting immune suppression is largely anecdotal and sourced from diffuse accounts of compromised decapods. We used a population of shore crabs (Carcinus maenas), where Hematodinium sp. is endemic, to determine the extent of collateral infections across two distinct environments (open-water, semi-closed dock). Using a multi-resource approach (PCR, histology, haematology, population genetics, eDNA), we identified 162 Hematodinium-positive crabs and size/sex-matched these to 162 Hematodinium-free crabs out of 1191 analysed. Crabs were interrogated for known additional disease-causing agents; haplosporidians, microsporidians, mikrocytids, Vibrio spp., fungi, Sacculina, trematodes, and haemolymph bacterial loads. We found no significant differences in occurrence, severity, or composition of collateral infections between Hematodinium-positive and Hematodinium-free crabs at either site, but crucially, we recorded site-restricted blends of pathogens. We found no gross signs of host cell immune reactivity towards Hematodinium in the presence or absence of other pathogens. We contend Hematodinium sp. is not the proximal driver of co-infections in shore crabs, which suggests an evolutionary drive towards latency in this environmentally plastic host