Viral CpG Deficiency Provides No Evidence That Dogs Were Intermediate Hosts for SARS-CoV-2.

Due to the scope and impact of the COVID-19 pandemic there exists a strong desire to understand where the SARS-CoV-2 virus came from and how it jumped species boundaries to humans. Molecular evolutionary analyses can trace viral origins by establishing relatedness and divergence times of viruses and identifying past selective pressures. However, we must uphold rigorous standards of inference and interpretation on this topic because of the ramifications of being wrong. Here, we dispute the conclusions of Xia (2020. Extreme genomic CpG deficiency in SARS-CoV-2 and evasion of host antiviral defense. Mol Biol Evol. doi:10.1093/molbev/masa095) that dogs are a likely intermediate host of a SARS-CoV-2 ancestor. We highlight major flaws in Xia's inference process and his analysis of CpG deficiencies, and conclude that there is no direct evidence for the role of dogs as intermediate hosts. Bats and pangolins currently have the greatest support as ancestral hosts of SARS-CoV-2, with the strong caveat that sampling of wildlife species for coronaviruses has been limited

Variation at the Calpain 3 gene is associated with meat tenderness in zebu and composite breeds of cattle

<p>Abstract</p> <p>Background</p> <p>Quantitative Trait Loci (QTL) affecting meat tenderness have been reported on Bovine chromosome 10. Here we examine variation at the Calpain 3 (<it>CAPN3</it>) gene in cattle, a gene located within the confidence interval of the QTL, and which is a positional candidate gene based on the biochemical activity of the protein.</p> <p>Results</p> <p>We identified single nucleotide polymorphisms (SNP) in the genomic sequence of the <it>CAPN3 </it>gene and tested three of these in a sample of 2189 cattle. Of the three SNP genotyped, the <it>CAPN3:c.1538+225G>T </it>had the largest significant additive effect, with an allele substitution effect in the Brahman of <it>α </it>= -0.144 kg, SE = 0.060, <it>P </it>= 0.016, and the polymorphism explained 1.7% of the residual phenotypic variance in that sample of the breed. Significant haplotype substitution effects were found for all three breeds, the Brahman, the Belmont Red, and the Santa Gertrudis. For the common haplotype, the haplotype substitution effect in the Brahman was <it>α </it>= 0.169 kg, SE = 0.056, <it>P </it>= 0.003. The effect of this gene was compared to Calpastatin in the same sample. The SNP show negligible frequencies in taurine breeds and low to moderate minor allele frequencies in zebu or composite animals.</p> <p>Conclusion</p> <p>These associations confirm the location of a QTL for meat tenderness in this region of bovine chromosome 10. SNP in or near this gene may be responsible for part of the overall difference between taurine and zebu breeds in meat tenderness, and the greater variability in meat tenderness found in zebu and composite breeds. The evidence provided so far suggests that none of these tested SNP are causative mutations.</p

Neuroimaging and Responsibility Assessments

Could neuroimaging evidence help us to assess the degree of a person’s responsibility for a crime which we know that they committed? This essay defends an affirmative answer to this question. A range of standard objections to this high-tech approach to assessing people’s responsibility is considered and then set aside, but I also bring to light and then reject a novel objection—an objection which is only encountered when functional (rather than structural) neuroimaging is used to assess people’s responsibility

Molecular Adaptations for Sensing and Securing Prey and Insight into Amniote Genome Diversity from the Garter Snake Genome

Colubridae represents the most phenotypically diverse and speciose family of snakes, yet no well-assembled and annotated genome exists for this lineage. Here, we report and analyze the genome of the garter snake, Thamnophis sirtalis, a colubrid snake that is an important model species for research in evolutionary biology, physiology, genomics, behavior, and the evolution of toxin resistance. Using the garter snake genome, we show how snakes have evolved numerous adaptations for sensing and securing prey, and identify features of snake genome structure that provide insight into the evolution of amniote genomes. Analyses of the garter snake and other squamate reptile genomes highlight shifts in repeat element abundance and expansion within snakes, uncover evidence of genes under positive selection, and provide revised neutral substitution rate estimates for squamates. Our identification of Z and W sex chromosome-specific scaffolds provides evidence for multiple origins of sex chromosome systems in snakes and demonstrates the value of this genome for studying sex chromosome evolution. Analysis of gene duplication and loss in visual and olfactory gene families supports a dim-light ancestral condition in snakes and indicates that olfactory receptor repertoires underwent an expansion early in snake evolution. Additionally, we provide some of the first links between secreted venom proteins, the genes that encode them, and their evolutionary origins in a rear-fanged colubrid snake, together with new genomic insight into the coevolutionary arms race between garter snakes and highly toxic newt prey that led to toxin resistance in garter snakes

ASSESSING TARGET SPECIFICITY OF THE SMALL MOLECULE INHIBITOR MARIMASTAT TO SNAKE VENOM TOXINS: A NOVEL APPLICATION OF THERMAL PROTEOME PROFILING

New treatments that circumvent the pitfalls of traditional antivenom therapies are critical to address the problem of snakebite globally. Numerous snake venom toxin inhibitors have shown promising cross-species neutralization of medically significant venom toxins in vivo and in vitro. The development of high-throughput approaches for the screening of such inhibitors could accelerate their identification, testing, and implementation, and thus holds exciting potential for improving the treatments and outcomes of snakebite envenomation worldwide. Energetics-based proteomic approaches, including Thermal Proteome Profiling (TPP) and Proteome Integral Solubility Alteration (PISA) assays, represent “deep proteomics” methods for high throughput, proteome-wide identification of drug targets and ligands. In the following study, we apply TPP and PISA methods to characterize the interactions between venom toxin proteoforms in Crotalus atrox (Western Diamondback Rattlesnake) and the snake venom metalloprotease (SVMP) inhibitor marimastat. We investigate its venom proteome-wide effects and characterize its interactions with specific SVMP proteoforms, as well as its potential targeting of non-SVMP venom toxin families. We also compare the performance of PISA thermal window and soluble supernatant with insoluble precipitate using two inhibitor concentrations, providing the first demonstration of the utility of a sensitive high-throughput PISA-based approach to assess the direct targets of small molecule inhibitors for snake venom

Global aspects of double geometry

We consider the concept of a generalised manifold in the O(d,d) setting, i.e., in double geometry. The conjecture by Hohm and Zwiebach for the form of finite generalised diffeomorphisms is shown to hold. Transition functions on overlaps are defined. Triple overlaps are trivial concerning their action on coordinates, but non-trivial on fields, including the generalised metric. A generalised manifold is an ordinary manifold, but the generalised metric on the manifold carries a gerbe structure. We show how the abelian behaviour of the gerbe is embedded in the non-abelian T-duality group. We also comment on possibilities and difficulties in the U-duality setting.Comment: 20 pp. v3: refs. added, discussion added on limitations of formalis

ATF2 COMMISSIONING

ATF2 is a final-focus test beam line that aims to focus the low-emittance beam from the ATF damping ring to a beam size of about 37 nm, and at the same time to demonstrate nm beam stability, using numerous advanced beam diagnostics and feedback tools. The construction has been finished at the end of 2008 and the beam commissioning of ATF2 has started in December of 2008. ATF2 is constructed and commissioned by ATF international collaborations with strong US, Asian and European participation