Hip structure and locomotion in ambulatory and cursorial carnivores reinvestigated [abstract]

Understanding how the femoral head articulates with the acetabulum of the pelvis should allow one to infer the pattern of hip mobility in living and fossil species. In 1977, Jenkins and Camazine analyzed cineradiographic films of carnivores (cat, dog, raccoon) during locomotion. They hypothesized that raccoons, which climb trees as well as walk terrestrially, would have hip joints adapted for greater abduction, where as the nearly strictly terrestrial dogs would have more adducted hips, and cats would be intermediate. Inferences made in this study have been used extensively to infer locomotor behavior and evolution in primates, although they were not tested thoroughly due to methodological limitations at the time. We tested the hypothesis that ambulatory carnivores (raccoons; Procyonidae) would have shallower acetabulae, lower greater trochanters, higher femoral neck-shaft angle and higher position of the fovea capitis than terrestrial ones (dogs; Canidae), and that cats (Felidae) would be intermediate

The Genomic Substrate for Adaptive Radiation: Copy Number Variation across 12 Tribes of African Cichlid Species

© 2019 Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution 2019. This work is written by US Government employees and is in the public domain in the US. The initial sequencing of five cichlid genomes revealed an accumulation of genetic variation, including extensive copy number variation in cichlid lineages particularly those that have undergone dramatic evolutionary radiation. Gene duplication has the potential to generate substantial molecular substrate for the origin of evolutionary novelty. We use array-based comparative heterologous genomic hybridization to identify copy number variation events (CNVEs) for 168 samples representing 53 cichlid species including the 5 species for which full genome sequence is available. We identify an average of 50-100 CNVEs per individual. For those species represented by multiple samples, we identify 150-200 total CNVEs suggesting a substantial amount of intraspecific variation. For these species, only ∼10% of the detected CNVEs are fixed. Hierarchical clustering of species according to CNVE data recapitulates phylogenetic relationships fairly well at both the tribe and radiation level. Although CNVEs are detected on all linkage groups, they tend to cluster in "hotspots" and are likely to contain and be flanked by transposable elements. Furthermore, we show that CNVEs impact functional categories of genes with potential roles in adaptive phenotypes that could reasonably promote divergence and speciation in the cichlid clade. These data contribute to a more complete understanding of the molecular basis for adaptive natural selection, speciation, and evolutionary radiation

Answering Dreyfus's Challenge: Toward a Theory of Concepts without Intellectualism

John McDowell’s debates about concepts with Robert Brandom and Hubert Dreyfus over the past two decades reveal key commitments each philosopher makes. McDowell is committed to giving concepts a role in our embodied coping, extending rational form to human experience. Brandom is committed to defining concepts in a way that helps make rationality distinct. And Dreyfus is committed to explaining how rational understanding develops out of lesser abilities we share with human infants and other animals (I call this “Dreyfus’s challenge”). These commitments appear irreconcilable. I argue to the contrary that they are, in principle, reconcilable, provided we give up their shared “rationalist” commitment to the idea that the rational use of language is necessary for having concepts. First, I exploit Brandom and McDowell’s debate to motivate abandoning the rationalist commitment. Next, I exploit Dreyfus and McDowell’s debate to establish the need for a broader notion of concepts to answer Dreyfus’s challenge. I turn to Elizabeth Camp’s broader notion of concepts as spontaneously, systematically recombinable representations, and establish that it lacks resources for distinguishing human rationality. To resolve that weakness, I integrate Camp’s notion of concepts with John Haugeland’s theory of objectivity, which does make rationality distinct. Finally, drawing my integration of Camp and Haugeland, I propose a way to answer Dreyfus’s challenge, which I call “relaxed holism.” The core of relaxed holism is a cumulative, developmental sequence of three related cognitive abilities: representation, concepts, and metacognition. I argue that relaxed holism also reconciles both McDowell’s commitment to giving normatively governed concepts a role in embodied coping, and Brandom’s commitment to defining concepts in a way that helps make rationality distinct

Polymer multilayer tattooing for enhanced DNA vaccination

DNA vaccines have many potential benefits but have failed to generate robust immune responses in humans. Recently, methods such as in vivo electroporation have demonstrated improved performance, but an optimal strategy for safe, reproducible, and pain-free DNA vaccination remains elusive. Here we report an approach for rapid implantation of vaccine-loaded polymer films carrying DNA, immune-stimulatory RNA, and biodegradable polycations into the immune-cell-rich epidermis, using microneedles coated with releasable polyelectrolyte multilayers. Films transferred into the skin following brief microneedle application promoted local transfection and controlled the persistence of DNA and adjuvants in the skin from days to weeks, with kinetics determined by the film composition. These ‘multilayer tattoo’ DNA vaccines induced immune responses against a model HIV antigen comparable to electroporation in mice, enhanced memory T-cell generation, and elicited 140-fold higher gene expression in non-human primate skin than intradermal DNA injection, indicating the potential of this strategy for enhancing DNA vaccination.Howard Hughes Medical Institute (Investigator)Ragon Institute of MGH, MIT, and HarvardNational Institutes of Health (U.S.) (NIH AI095109)United States. Dept. of Defense. Institute for Soldier Nanotechnologies (contract W911NF-07-D-0004)United States. Dept. of Defense. Institute for Soldier Nanotechnologies (contract W911NF-07-0004

Estimating the effects of race and social vulnerability on hospital admission and mortality from COVID-19

OBJECTIVE: To estimate the risk of hospital admission and mortality from COVID-19 to patients and measure the association of race and area-level social vulnerability with those outcomes. MATERIALS AND METHODS: Using patient records collected at a multisite hospital system from April 2020 to October 2020, the risk of hospital admission and the risk of mortality were estimated for patients who tested positive for COVID-19 and were admitted to the hospital for COVID-19, respectively, using generalized estimating equations while controlling for patient race, patient area-level social vulnerability, and time course of the pandemic. RESULTS: Black individuals were 3.57 as likely (95% CI, 3.18-4.00) to be hospitalized than White people, and patients living in the most disadvantaged areas were 2.61 times as likely (95% CI, 2.26-3.02) to be hospitalized than those living in the least disadvantaged areas. While Black patients had lower raw mortality than White patients, mortality was similar after controlling for comorbidities and social vulnerability. DISCUSSION: Our findings point to potent correlates of race and socioeconomic status, including resource distribution, employment, and shared living spaces, that may be associated with inequitable burden of disease across patients of different races. CONCLUSIONS: Public health and policy interventions should address these social factors when responding to the next pandemic

The effectiveness of the controlled release of gentamicin from polyelectrolyte multilayers in the treatment of Staphylococcus aureus infection in a rabbit bone model

While the infection rate of orthopedic implants is low, the required treatment, which can involve six weeks of antibiotic therapy and two additional surgical operations, is life threatening and expensive, and thus motivates the development of a one-stage re-implantation procedure. Polyelectrolyte multilayers incorporating gentamicin were fabricated using the layer-by-layer deposition process for use as a device coating to address an existing bone infection in a direct implant exchange operation. The films eluted about 70% of their payload in vitro during the first three days and subsequently continued to release drug for more than four additional weeks, reaching a total average release of over 550 μg/cm[superscript 2]. The coatings were demonstrated to be bactericidal against Staphylococcus aureus, and degradation products were generally nontoxic towards MC3T3-E1 murine preosteoblasts. Film-coated titanium implants were compared to uncoated implants in an in vivo S. aureus bone infection model. After a direct exchange procedure, the antimicrobial-coated devices yielded bone homogenates with a significantly lower degree of infection than uncoated devices at both day four (p < 0.004) and day seven (p < 0.03). This study has demonstrated that a self-assembled ultrathin film coating is capable of effectively treating an experimental bone infection in vivo and lays the foundation for development of a multi-therapeutic film for optimized, synergistic treatment of pain, infection, and osteomyelitis.National Institutes of Health (U.S.) (National Institute on Aging Grant 5R01AG029601-03