Peroxisome biogenesis disorders (PBDs) are multisystemic autosomal recessive disorders resulting from mutations in PEX genes required for normal peroxisome assembly and metabolic activities. Here, we evaluated the potential effectiveness of aminoglycoside G418 (geneticin) and PTC124 (ataluren) nonsense suppression therapies for the treatment of PBD patients with disease-causing nonsense mutations. PBD patient skin fibroblasts producing stable PEX2 or PEX12 nonsense transcripts and Chinese hamster ovary (CHO) cells with a Pex2 nonsense allele all showed dramatic improvements in peroxisomal very long chain fatty acid catabolism and plasmalogen biosynthesis in response to G418 treatments. Cell imaging assays provided complementary confirmatory evidence of improved peroxisome assembly in G418-treated patient fibroblasts. In contrast, we observed no appreciable rescue of peroxisome lipid metabolism or assembly for any patient fibroblast or CHO cell culture treated with various doses of PTC124. Additionally, PTC124 did not show measurable nonsense suppression in immunoblot assays that directly evaluated the read-through of PEX7 nonsense alleles found in PBD patients with rhizomelic chondrodysplasia punctata type 1 (RCDP1). Overall, our results support the continued development of safe and effective nonsense suppressor therapies that could benefit a significant subset of individuals with PBDs. Furthermore, we suggest that the described cell culture assay systems could be useful for evaluating and screening for novel nonsense suppressor therapies.
Music and language are universal human abilities with many apparent similarities relating to their acoustics, structure, and frequent use in social situations. We might therefore expect them to be understood and processed similarly, and indeed an emerging body of research suggests that this is the case. But the focus has historically been on the individual, looking at the passive listener or the isolated speaker or performer, even though social interaction is the primary site of use for both domains. Nonetheless, an important goal of emerging research is to compare music and language in terms of acoustics and structure, social interaction, and functional origins to develop parallel accounts across the two domains. Indeed, a central aim of both of evolutionary musicology and language evolution research is to understand the adaptive significance or functional origin of human music and language. An influential proposal to emerge in recent years has been referred to as the social bonding hypothesis. Here, within a comparative approach to animal communication systems, I review empirical studies in support of the social bonding hypothesis in humans, non-human primates, songbirds, and various other mammals. In support of this hypothesis, I review six research fields: (i) the functional origins of music; (ii) the functional origins of language; (iii) mechanisms of social synchrony for human social bonding; (iv) language and social bonding in humans; (v) music and social bonding in humans; and (vi) pitch, tone and emotional expression in human speech and music. I conclude that the comparative study of complex vocalizations and behaviors in various extant species can provide important insights into the adaptive function(s) of these traits in these species, as well as offer evidence-based speculations for the existence of “musilanguage” in our primate ancestors, and thus inform our understanding of the biology and evolution of human music and language.
Social density processes impact the activity and order of collective behaviours in a variety of biological systems. Much effort has been devoted to understanding how density of people affects collective human motion in the context of pedestrian flows. However, there is a distinct lack of empirical data investigating the effects of social density on human behaviour in cooperative contexts. Here, we examine the functioning and performance of human teams in a central-place foraging arena using high-resolution GPS data. We show that team functioning (level of coordination) is greatest at intermediate social densities, but contrary to our expectations, increased coordination at intermediate densities did not translate into improved collective foraging performance, and foraging accuracy was equivalent across our density treatments. We suggest that this is likely a consequence of foragers relying upon visual channels (local information) to achieve coordination but relying upon auditory channels (global information) to maximise foraging returns. These findings provide new insights for the development of more sophisticated models of human collective behaviour that consider different networks for communication (e.g. visual and vocal) that have the potential to operate simultaneously in cooperative contexts.
Language may be one of most important attributes which separates humans from other animal species. It has been suggested by some commentators that the primary biological function of human language is to deceive and selfishly manipulate social competitors. However, despite the existence of a large body of relevant theoretical and empirical literature in favor of the social bonding hypothesis for language function, the ostensible evidence and arguments for the deception hypothesis have not been fully discussed. The following review analyses the evidence and theoretical arguments from human social behavior, comparative animal behavior, and developmental psychology and suggests that deception shows clear signs of a derived function for language. Furthermore, in addition to being used relatively infrequently across most human and non-human animal contexts, deception appears to be utilized just as often for prosocial and social bonding functions, as it is for antisocial purposes. Future studies should focus on theoretical and experimental investigations which explore interactions between deceptive and honest language use in the context of social bonding.
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