Biology subjects

Campbell, R. M.

Publications and source records attributed to Campbell, R. M..

3 recordsLinked to original sources

bioRxiv2021

Relationships between the hard and soft dimensions of the nose in Pan troglodytes and Homo sapiens reveal the nasal protrusions of Plio-Pleistocene hominids

By identifying similarity in bone and soft tissue covariation patterns in hominids, it is possible to produce facial approximation methods that are compatible with more than one species of primate. In this study, we conducted an interspecific comparison of the nasomaxillary region in chimpanzees and modern humans with the aim of producing a method for predicting the nasal protrusions of ancient Plio-Pleistocene hominids. We addressed this aim by first collecting and performing regression analyses of linear and angular measurements of nasal cavity length and inclination in modern humans (Homo sapiens; n = 72) and chimpanzees (Pan troglodytes; n = 19), and then by performing a set of out-of-group tests. The first test was performed on two subjects that belonged to the same genus as the training sample, i.e., Homo (n = 1) and Pan (n = 1), and the second test, which functioned as an interspecies compatibility test, was performed on Pan paniscus (n = 1), Gorilla gorilla (n = 3), Pongo pygmaeus (n = 1), Pongo abelli (n = 1), Symphalangus syndactylus (n = 3), and Papio hamadryas (n = 3). We identified statistically significant correlations in both humans and chimpanzees with slopes that displayed homogeneity of covariation. Joint prediction formulae were found to be compatible with humans and chimpanzees as well as all other African great apes, i.e., bonobos and gorillas. The main conclusion that can be drawn from this study is that regression models for approximating nasal projection are homogenous among humans and African apes and can thus be reasonably extended to ancestors leading to these clades.

paleontology↗

bioRxiv2021

Towards the restoration of ancient hominid craniofacial anatomy: Chimpanzee morphology reveals covariation between craniometrics and facial soft tissue thickness

In modern humans, facial soft tissue thicknesses have been shown to covary with craniometric dimensions. However, to date it has not been confirmed whether these relationships are shared with non-human apes. In this study, we analyze these relationships in chimpanzees (Pan troglodytes) with the aim of producing regression models for approximating facial soft tissue thicknesses in Plio-Pleistocene hominid individuals. Using CT scans of 19 subjects, 637 soft tissue, and 349 craniometric measurements, statistically significant multiple regression models were established for 26 points on the face and head. Examination of regression model validity resulted in minimal differences between observed and predicted soft tissue thickness values. Assessment of interspecies compatibility using a bonobo (Pan paniscus) and modern human (Homo sapiens) subject resulted in minimal differences for the bonobo but large differences for the modern human. These results clearly show that (1) soft tissue thicknesses covary with craniometric dimensions in P. troglodytes, (2) confirms that such covariation is uniformly present in both extant Homo and Pan species, and (3) suggests that chimp-derived regression models have interspecies compatibility with hominids who have similar craniometric dimensions to P. troglodytes. As the craniometric dimensions of early hominids, such as South African australopithecines, are more similar to P. troglodytes than those of H. sapiens, chimpanzee-derived regression models may be used for approximating their craniofacial anatomy. It is hoped that the results of the present study and the reference dataset for facial soft tissue thicknesses of chimpanzees it provides will encourage further research into this topic.

zoology↗

bioRxiv2020

A First-in-class, Highly Selective and Cell-active AllostericInhibitor of Protein Arginine Methyltransferase 6 (PRMT6)

PRMT6 catalyzes monomethylation and asymmetric dimethylation of arginine residues in various proteins, plays important roles in biological processes and is associated with multiple cancers. While there are several reported PRMT6 inhibitors, a highly selective PRMT6 inhibitor has not been reported to date. Furthermore, allosteric inhibitors of protein methyltransferases are rare. Here we report the discovery and characterization of a first-in-class, highly selective allosteric inhibitor of PRMT6, SGC6870. SGC6870 is a potent PRMT6 inhibitor (IC50 = 77 {+/-} 6 nM) with outstanding selectivity for PRMT6 over a broad panel of other methyltransferases and non-epigenetic targets. Notably, the crystal structure of the PRMT6-SGC6870 complex and kinetic studies revealed SGC6870 binds a unique, induced allosteric pocket. Additionally, SGC6870 engages PRMT6 and potently inhibits its methyltransferase activity in cells. Moreover, SGC6870s enantiomer, SGC6870N, is inactive against PRMT6 and can be utilized as a negative control. Collectively, SGC6870 is a well-characterized PRMT6 chemical probe and valuable tool for further investigating PRMT6 functions in health and disease.

biochemistry↗