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In this article we seek to integrate theories of music origins and dance with hominin fossil anatomy and the paleoecological contexts of hominin evolution. Based on the association between rhythm in music, dance and locomotion, we propose that early bipedal hominins may have evolved neurobiological substrates different from other great apes due to the rhythmic aspects of bipedal walking and running. Combined with the emancipation of the hands resulting from erect posture, we propose that the neurobiological changes necessary for technological innovation, cultural practices and human musical abilities may have evolved, at least in incipient form, much earlier than previously thought. The consequent ability to synchronize movement and sound production may have also proved beneficial as early bipedal hominins ventured out of late Miocene and early Pliocene woodland and forested habitats and into more open habitats with increased predation risk. We also postulate that, along with bipedalism, paedomorphic morphogenesis of the skull at the base of the hominin clade was a necessary prerequisite for the evolution of vocal modulation and singing in later varieties of hominin. To date research into the evolution of music and dance has yet to be integrated with the fossil and paleoecological evidence of early hominin evolution. This paper seeks to fill this lacuna in the extant literature on human evolution. We also suggest that autocatalytic feedback loops evolving synergistically with hominin erect posture, skull and hand morphology, neurochemical processes and the self-domestication syndrome, have been operative from early hominins some 6 Ma to the present. We document this process by reference to primatological, ethnographic, neurochemical and archaeological data.

Abstract Background Necrotizing meningoencephalitis (NME, aka Pug dog encephalitis) is an inflammatory brain condition associated with advanced disease at initial presentation, rapid progression, and poor response to conventional immunomodulatory therapy. Hypothesis/Objectives That genetic risk for NME, defined by a common germline DNA haplotype located on chromosome 12, is associated with altered blood cytokine concentrations and leukocyte subsets in asymptomatic Pugs. Animals Forty Pug dogs asymptomatic for NME from a hospital sample. Methods Prospective observational cohort study, including germline genome‐wide genotyping, plasma cytokine determination by multiplexed profiling, and leukocyte subset characterization by flow cytometric analysis. Results Seven (18%) dogs were high risk, 10 (25%) medium risk, and 23 (58%) low risk for NME, giving a risk haplotype frequency of 30%. High and medium risk Pugs had significantly lower proportion of CD4+ T cells (median 22% [range, 7.3%‐38%] vs 29% [range, 16%‐41%], P = .03) and higher plasma IL‐10 concentrations than low‐risk Pugs (median 14.11 pg/mL [range, 9.66‐344.19 pg/mL] vs 12.21 pg/mL [range, 2.59‐18.53 pg/mL], P = .001). No other variables were significantly associated with the NME haplotype‐based risk. Conclusions and Clinical Importance These data suggest an immunological underpinning to NME and a biologic rationale for future clinical trials that investigate novel diagnostic, preventative, and therapeutic strategies for this disease.

Abstract Background Resources within the Undiagnosed Diseases Network (UDN), such as genome sequencing (GS) and model organisms aid in diagnosis and identification of new disease genes, but are currently difficult to access by clinical providers. While these resources do contribute to diagnoses in many cases, they are not always necessary to reach diagnostic resolution. The UDN experience has been that participants can also receive diagnoses through the thoughtful and customized application of approaches and resources that are readily available in clinical settings. Methods The UDN Genetic Counseling and Testing Working Group collected case vignettes that illustrated how clinically available methods resulted in diagnoses. The case vignettes were classified into three themes; phenotypic considerations, selection of genetic testing, and evaluating exome/GS variants and data. Results We present 12 participants that illustrate how clinical practices such as phenotype‐driven genomic investigations, consideration of variable expressivity, selecting the relevant tissue of interest for testing, utilizing updated testing platforms, and recognition of alternate transcript nomenclature resulted in diagnoses. Conclusion These examples demonstrate that when a diagnosis is elusive, an iterative patient‐specific approach utilizing assessment options available to clinical providers may solve a portion of cases. However, this does require increased provider time commitment, a particular challenge in the current practice of genomics.