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We describe the first endocast reconstruction of a hyaenodont mammal based on X‐ray microtomography. The endocast belongs to the type material of the European hyaenodont Proviverra typica. We performed phylogenetic analysis to contextualize the evolution of endocranial size and complexity in Hyaenodonta. We added several European hyaenodonts and modified several codings of the most recent character–taxon matrix established to question the relationships within Hyaenodonta. Including these new species in a phylogenetic analysis reveals a new clade: Hyaenodontoidea. Comparisons with several previously described endocasts show that there was an increase in complexity in the convolutions of the encephalon within Hyaenodontidae history. Moreover, the analysis of the encephalization quotient reveals that the endocranium of the Hyaenodonta is not smaller than those of fossil Carnivora or some extant Carnivora. Therefore, the extinction of Hyaenodonta may not be linked to the relative size of hyaenodont brains.
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Inflammatory bowel disease (IBD) in dogs is associated with clinical signs of intestinal dysfunction, as well as abnormal lymphocytic and myeloid cell infiltrates in the small and/or large intestine. Thus, in many respects IBD in dogs resembles IBD in humans. However, the factors that trigger intestinal inflammation in dogs with IBD are not well understood and have been variously attributed to immune responses against dietary antigens or intestinal antigens. Previous studies in humans with IBD have documented increased production of IgG and IgA antibodies specific to intestinal bacteria, and this abnormal immune response has been linked to disease pathogenesis. Therefore, we investigated the humoral immune response against gut bacteria in dogs with IBD, using flow cytometry to quantitate IgG and IgA binding. Studies were also done to investigate the source of these antibodies (locally produced versus systemic production) and whether greater antibody binding to bacteria is associated with increased inflammatory responses. We found that dogs with IBD had significantly higher percentages and overall amounts of IgG bound to their intestinal bacteria compared to healthy dogs. Similarly, significantly higher percentages of bacteria were IgA+ bacteria were also found in dogs with IBD. Serum antibody recognition of gut bacteria was not different between healthy dogs and dogs with IBD, suggesting that anti-bacterial antibodies were primarily produced locally in the gut rather than systemically. Importantly, bacteria in the Actinobacteria phylum and in particular the genus Collinsella had significantly greater levels of antibody binding in dogs with IBD. Based on these findings, we concluded that antibody binding to commensal gut bacteria was significantly increased in dogs with IBD, that particular phyla were preferential targets for gut antibodies, and that anti-bacterial antibody responses may play an important role in regulating gut inflammation.
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Resolving the phylogenetic relationships of closely related species using a small set of loci is challenging as sufficient information may not be captured from a limited sample of the genome. Relying on few loci can also be problematic when conflict between gene-trees arises from incomplete lineage sorting and/or ongoing hybridization, problems especially likely in recently diverged lineages. Here, we developed a method using limited genomic resources that allows identification of many low copy candidate loci from across the nuclear and chloroplast genomes, design probes for target capture and sequence the captured loci. To validate our method we present data from Eucalyptus and Melaleuca, two large and phylogenetically problematic genera within the Myrtaceae family. With one annotated genome, one transcriptome and two whole-genome shotgun sequences of one Eucalyptus and four Melaleuca species, respectively, we identified 212 loci representing 263 kbp for targeted sequence capture and sequencing. Of these, 209 were successfully tested from 47 samples across five related genera of Myrtaceae. The average percentage of reads mapped back to the reference was 57.6% with coverage of more than 20 reads per position across 83.5% of the data. The methods developed here should be applicable across a large range of taxa across all kingdoms. The core methods are very flexible, providing a platform for various genomic resource availabilities and are useful from shallow to deep phylogenies.
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Variable, glutamine-encoding, CAA interruptions indicate that a property of the uninterrupted HTT CAG repeat sequence, distinct from the length of huntingtin’s polyglutamine segment, dictates the rate at which Huntington’s disease (HD) develops. The timing of onset shows no significant association with HTT cis-eQTLs but is influenced, sometimes in a sex-specific manner, by polymorphic variation at multiple DNA maintenance genes, suggesting that the special onset-determining property of the uninterrupted CAG repeat is a propensity for length instability that leads to its somatic expansion. Additional naturally occurring genetic modifier loci, defined by GWAS, may influence HD pathogenesis through other mechanisms. These findings have profound implications for the pathogenesis of HD and other repeat diseases and question the fundamental premise that polyglutamine length determines the rate of pathogenesis in the “polyglutamine disorders.”
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Urine is increasingly being considered as a source of biomarker development in Duchenne Muscular Dystrophy (DMD), a severe, life-limiting disorder that affects approximately 1 in 4500 boys. In this study, we considered the mdx mice—a murine model of DMD—to discover biomarkers of disease, as well as pharmacodynamic biomarkers responsive to prednisolone, a corticosteroid commonly used to treat DMD. Longitudinal urine samples were analyzed from male age-matched mdx and wild-type mice randomized to prednisolone or vehicle control via liquid chromatography tandem mass spectrometry. A large number of metabolites (869 out of 6,334) were found to be significantly different between mdx and wild-type mice at baseline (Bonferroni-adjusted p-value < 0.05), thus being associated with disease status. These included a metabolite with m/z = 357 and creatine, which were also reported in a previous human study looking at serum. Novel observations in this study included peaks identified as biliverdin and hypusine. These four metabolites were significantly higher at baseline in the urine of mdx mice compared to wild-type, and significantly changed their levels over time after baseline. Creatine and biliverdin levels were also different between treated and control groups, but for creatine this may have been driven by an imbalance at baseline. In conclusion, our study reports a number of biomarkers, both known and novel, which may be related to either the mechanisms of muscle injury in DMD or prednisolone treatment.
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Speciation genomic studies aim to interpret patterns of genome-wide variation in light of the processes that give rise to new species. However, interpreting the genomic ‘landscape’ of speciation is difficult, because many evolutionary processes can impact levels of variation. Facilitated by the first chromosome-level assembly for the group, we use whole-genome sequencing and simulations to shed light on the processes that have shaped the genomic landscape during a radiation of monkeyflowers. After inferring the phylogenetic relationships among the nine taxa in this radiation, we show that highly similar diversity (π) and differentiation (FST) landscapes have emerged across the group. Variation in these landscapes was strongly predicted by the local density of functional elements and the recombination rate, suggesting that the landscapes have been shaped by widespread natural selection. Using the varying divergence times between pairs of taxa, we show that the correlations between FST and genome features arose almost immediately after a population split and have become stronger over time. Simulations of genomic landscape evolution suggest that background selection (i.e., selection against deleterious mutations) alone is too subtle to generate the observed patterns, but scenarios that involve positive selection and genetic incompatibilities are plausible alternative explanations. Finally, tests for introgression among these taxa reveal widespread evidence of heterogeneous selection against gene flow during this radiation. Combined with previous evidence for adaptation in this system, we conclude that the correlation in FST among these taxa informs us about the processes contributing to adaptation and speciation during a rapid radiation.
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Although mothers influence the traits of their offspring in many ways beyond the transmission of genes, it remains unclear how important such “maternal effects” are to phenotypic differences among individuals. Synthesizing estimates derived from detailed pedigrees, we evaluated the amount of phenotypic variation determined by maternal effects in animal populations. Maternal effects account for half as much phenotypic variation within populations as do additive genetic effects. Maternal effects most greatly affect morphology and phenology but, surprisingly, are not stronger in species with prolonged maternal care than in species without. While maternal effects influence juvenile traits more than adult traits on average, they do not decline across ontogeny for behavior or physiology, and they do not weaken across the life cycle in species without maternal care. These findings underscore maternal effects as an important source of phenotypic variation and emphasize their potential to affect many ecological and evolutionary processes.
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Sensitivity of plant species to individual arbuscular mycorrhizal (AM) fungal species is of primary importance to understanding the role of AM fungal diversity and composition in plant ecology. Currently, we do not have a predictive framework for understanding which plant species are sensitive to different AM fungal species. In two greenhouse studies, we tested for differences in plant sensitivity to different AM fungal species and mycorrhizal responsiveness across 17 grassland plant species of North America that varied in successional stage, native status, and plant family by growing plants with different AM fungal treatments including eight single AM fungal isolates, diverse mixtures of AM fungi, and non-inoculated controls. We found that late successional grassland plant species were highly responsive to AM fungi and exhibited stronger sensitivity in their response to individual AM fungal taxa compared to non-native or early successional native grassland plant species. We confirmed these results using a meta-analysis that included 13 experiments, 37 plant species, and 40 fungal isolates (from nine publications and two greenhouse experiments presented herein). Mycorrhizal responsiveness and sensitivity of response (i.e., variation in plant biomass response to different AM fungal taxa) did not differ by the source of fungal inocula (i.e., local or not local) or plant family. Sensitivity of plant response to AM fungal species was consistently correlated with the average mycorrhizal response of that plant species. This study identifies that AM fungal identity is more important to the growth of late successional plant species than early successional or non-native plant species, thereby predicting that AM fungal composition will be more important to plant community dynamics in late successional communities than in early successional or invaded plant communities.
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Graphics are becoming increasingly important for scientists to effectively communicate their findings to broad audiences, but most researchers lack expertise in visual media. We suggest collaboration between scientists and graphic designers as a way forward and discuss the results of a pilot project to test this type of collaboration.
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PLEASE NOTE, THESE DATA WERE ALSO ANALYZED FOR A SUBSEQUENT PUBLICATION in eLife. PLEASE SEE https://doi.org/10.7554/eLife.43226 FOR MORE INFORMATION. Recordings from Pacinian corpuscles in the 1960s showed that touch elicits symmetric activation followed by rapid adaptation. Sinusoidal stimulation resulted in frequency doubling within a sensitive frequency band, suggesting that these receptors function as frequency-tuned vibration sensors. At the time, the surrounding lamellar capsule was proposed to generate these response dynamics by acting as a mechanical filter. However, similar response dynamics have since been seen in many other mechanoreceptors, leading to controversy over the specificity of this hypothesis. Using a combination of in vivo electrophysiology, feedback-controlled mechanical stimulation, and simulation, we resolve this controversy in favor of a systems-level mechanical filter that is independent of specific anatomical features or specific mechanoelectrical transduction channels.
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