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McGowan, M.

Publications and source records attributed to McGowan, M..

4 recordsLinked to original sources

Photostimulus intensity, rather than colour or polarization, is the key driver for stable fly visual attraction in laboratory bioassays

Foraging hematophagous flies such as the stable fly, Stomoxys calcitrans, are shown or expected to sense multiple characteristics of visual host cues. These include relative intensity, spectral composition, and the angle and degree of polarization. Here, we investigated the role of each of these visual cue characteristics on stable fly attraction. In laboratory two-choice bioassays, we offered groups of female or male stable flies a choice between paired photostimuli that differed in their visual characteristics, recording the flies' landing responses on stimuli as the response criterion. Bioassay flies preferentially selected lower-intensity visual stimuli even when paired stimuli markedly differed in spectral composition and polarization characteristics (a high degree of horizontal or vertical polarization). When paired stimuli had identical relative intensity, flies failed to discriminate between the stimulus that presented ultraviolet, blue, green, and red wavebands and a corresponding paired stimulus lacking one of these wavebands. Our results support the hypothesis that foraging stable flies may respond to colour and polarization characteristics of visual stimuli as modulations of perceived intensity. Acquired knowledge on the mechanisms that underlie stable fly visual attraction may inform the design of vision-based traps so that they become optimally attractive to stable flies and other biting flies.

animal behavior and cognition↗

A complete human pancreatic cancer genome

Cancer genome sequencing is essential for understanding tumor evolution and advancing precision medicine.1 However, reference gaps and germline variants obscure detection of small and large somatic variants and methylation in repetitive regions.1-3 It is common for tumor cells to gain or lose chromosome arms due to somatic structural changes that occur inside highly repetitive satellite DNA sequences in the centromeres.4 To identify the full spectrum of somatic variants, including complex rearrangements, we construct and curate near-complete, haplotype-resolved assemblies of the most recent common ancestor of an early-passage broadly-consented hypodiploid pancreatic cancer cell line and matched normal tissues. The tumor assembly completely recapitulates all 35 tumor chromosomes observed with karyotyping, with multiple translocation-induced hybrid chromosomes. The hybrid chromosomes contain putative functional dicentric and fused centromeres, nested foldback inversions causing 14 breakpoints with a haplotype switch in a single event, and centromeric satellite tandem duplications up to 136 kbp. Direct comparison of tumor and normal assembly haplotypes uncovers >7,000 variants altering >1 Mbp of sequence in repetitive regions that have been hidden by reference gaps and germline variants. 44 % of somatic small variants change representation because they alter germline variants on GRCh38, impacting mutational signatures and kataegis/omikli clusters. Most somatic LINE insertions originate from two hypomethylated non-reference germline LINE insertions, highlighting their impact on insertion mutation burden. These assemblies demonstrate that centromeric, acrocentric, and telomeric regions conventionally excluded from analysis harbor extensive somatic and epigenetic changes. Resolving complete tumor genomes enables a deeper understanding of cancer structural plasticity and the endpoints of breakage-fusion-bridge cycles. These assembled, curated paired normal-tumor benchmarks will serve as a critical foundation for developing future algorithms to characterize the most intractable regions of cancer genomes.

genomics↗

Conservation of C4BP-binding Sequence Patterns in Streptococcus pyogenes M and Enn Proteins

Antigenically sequence variable M proteins of the major bacterial pathogen Streptococcus pyogenes (Strep A) are responsible for recruiting human C4b-binding protein (C4BP) to the bacterial surface, which enables Strep A to evade destruction by the immune system. The most sequence divergent portion of M proteins, the hypervariable region (HVR), is responsible for binding C4BP. Structural evidence points to the conservation of two C4BP-binding sequence patterns (M2 and M22) in the HVR of numerous M proteins, with this conservation applicable to vaccine immunogen design. These two patterns, however, only partially explain C4BP-binding by Strep A. Here, we identified several M proteins that lack these patterns but still bind C4BP, and determined the structures of two, M68 and M87 HVRs, in complex with a C4BP fragment. Mutagenesis of these M proteins led to identification of amino acids that are crucial for C4BP-binding, enabling formulation of new C4BP-binding patterns. Mutagenesis was also carried out on M2 and M22 proteins to refine or generate experimentally grounded C4BP-binding patterns. The M22 pattern was the most populated among M proteins, followed by the M87 and M2 patterns, while the M68 pattern was rare. These patterns, except for M68, were also evident in numerous M-like Enn proteins. Binding of C4BP via these patterns to Enn proteins was verified. We conclude that C4BP-binding patterns occur frequently in Strep A strains of differing M types, being present in their M or Enn proteins, or frequently both, providing further impetus for their use as vaccine immunogens.

microbiology↗

The role of Staphylococcus agnetis and Staphylococcus hyicus in the pathogenesis of buffalo fly skin lesions in cattle

Buffalo flies (Haematobia irritans exigua) are hematophagous ectoparasites of cattle causing production and welfare impacts in northern Australian herds. Skin lesions associated with buffalo fly infestation and Stephanofilaria nematode infection are manifested as focal dermatitis or ulcerated areas most commonly on the medial canthus of the eye, along the lateral and ventral neck and on the abdomen of cattle. For closely related horn flies (Haematobia irritans irritans), Staphylococcus aureus have been suggested as a contributing factor in the development of lesions. To investigate the potential role of bacterial infection in the pathogenesis of buffalo fly lesions, swabs were taken from lesions and normal skin, and bacteria were also isolated from surface washings of buffalo flies and surface-sterilised homogenized flies. Bacterial identification was conducted by MALDI-TOF, strain typing by rep-PCR and DNA sequencing to determine species similarity and virulence factors. Of 49 bacterial isolates collected from lesions, 37 were identified as Staphylococcus agnetis and 12 as Staphylococcus hyicus, whereas from normal skin four isolates were S. hyicus and one was Staphylococcus sciuri. Of the Staphylococcus isolates isolated from buffalo flies, five were identified as S. agnetis and three as S. hyicus. Fifty percent of the buffalo fly isolates had rep-PCR genotypic patterns identical to the lesion isolates. Genome sequencing of 16 S. agnetis and four S. hyicus isolates revealed closely similar virulence factor profiles, with all isolates possessing exfoliative toxin A and C genes. The findings from this study suggest the involvement of S. agnetis and S. hyicus in buffalo fly lesion pathogenesis. This should be taken into account in the development of effective treatment and control strategies for lesions.

microbiology↗