Morphological integration of the hominoid postcranium.

Previous research has suggested that magnitudes of integration may be distinct in the postcranium of hominoids when compared to other primate species. To test this hypothesis, we estimated and compared magnitudes of integration of eight postcranial bones from three-dimensional surface scans for 57 Hylobates lar, 58 Gorilla gorilla, 60 Pan troglodytes, 60 Homo sapiens, 60 Chlorocebus pygerythrus, and 60 Macaca fascicularis. We tested the hypotheses that 1) magnitudes of integration would be distinct in the postcranium of hominoids compared to cercopithecoids, with the explicit prediction that magnitudes of integration would be lower in hominoids than in cercopithecoids, and 2) girdle elements (scapula, os coxa) would have lower magnitudes of integration across all taxa. Integration was quantified using the integration coefficient of variation from interlandmark distances reflecting anatomical and developmental modules defined according to a priori criteria. A resampling protocol was employed to generate distributions of integration values that were then compared statistically using Mann-Whitney U tests with Bonferroni adjustment. Support for hypothesis 1 was mixed: with the exception of Gorilla, hominoid taxa were less integrated than the cercopithecoids for all anatomical modules. However, Homo, Gorilla, and, to a lesser extent, Pan showed higher integration than Hylobates and the cercopithecoids for homologous limb elements, with magnitudes of integration for both modules being lowest for Hylobates. These results generally support the hypothesis of distinct patterns of magnitudes of integration in the hominoid postcranium. The high integration of Gorilla may be explained by the effects of overall body size. The results supported the predictions of the second hypothesis. Regardless of taxon, the os coxa and scapula were generally the least integrated skeletal elements, while the femur and radius were the most integrated. The lower integration of the girdle elements suggests that the geometric complexities of particular elements may significantly influence study outcomes.

The relative efficacy of the cranium and os coxa for taxonomic assessment in macaques.

OBJECTIVES: The cranium is generally considered more reliable than the postcranium for assessing primate taxonomy, although recent research suggests that pelvic shape may be equally reliable. However, little research has focused on intrageneric taxonomic discrimination. Here, we test the relative taxonomic efficacy of the cranium and os coxa for differentiating two macaque species, with and without considering sexual dimorphism. MATERIALS AND METHODS: Geometric morphometric analyses were performed on cranial and os coxa landmarks for 119 adult Macaca fascicularis, M. mulatta, and Chlorocebus pygerythrus. Among-group shape variation was examined using canonical variates analyses. Cross-validated discriminant function analysis provided rates of correct group classification. Additionally, average morphological distances were compared with neutral genetic distances. RESULTS: Macaque species were clearly differentiated, both cranially and pelvically, when sex was not considered. Males were more often correctly classified based on the os coxa, while female classification rates were high for both morphologies. Female crania and male os coxa were differentiated approximately the same as genetic distance, while male crania were more similar (convergent), and female os coxa were more divergent than expected based on genetic distance. DISCUSSION: The hypothesis that cranial and os coxal shape can be used to discriminate among macaque species was supported. The cranium was better at differentiating females, while the os coxa was better at differentiating male macaques. Hence, there is no a priori reason for preferring the cranium when assessing intragenetic taxonomic relationships, but the effects of high levels of sexual dimorphism must be corrected for to accurately assess taxonomic signatures.

Morphological integration of anatomical, developmental, and functional postcranial modules in the crab-eating macaque (Macaca fascicularis).

OBJECTIVES: Integration and modularity reflect the coordinated action of past evolutionary processes and, in turn, constrain or facilitate phenotypic evolvability. Here, we analyze magnitudes of integration in the macaque postcranium to test whether 20 a priori defined modules are (1) more tightly integrated than random sets of postcranial traits, and (2) are differentiated based on mode of definition, with developmental modules expected to be more integrated than functional or anatomical modules. MATERIALS AND METHODS: The 3D morphometric data collected for eight limb and girdle bones for 60 macaques were collated into anatomical, developmental, and functional modules. A resampling technique was used to create random samples of integration values for each module for statistical comparison. RESULTS: Our results found that not all a priori defined modules were more strongly integrated than random samples of postcranial traits and that specific types of modules did not present consistent patterns of integration. Rather, girdle and joint modules were consistently less integrated than limb modules, and forelimb elements were less integrated than hindlimbs. DISCUSSION: The results suggest that morphometrically complex modules tend to be less integrated than simple limb bones, irrespective of the number of available traits. However, differences in integration of the fore- and hindlimb more likely reflects the multitude of locomotory, feeding, and social functions involved. It remains to be tested whether patterns of integration identified here are primate universals, and to what extent they vary depending on phylogenetic or functional factors.

An effect size for comparing the strength of morphological integration across studies.

Understanding how and why phenotypic traits covary is a major interest in evolutionary biology. Biologists have long sought to characterize the extent of morphological integration in organisms, but comparing levels of integration for a set of traits across taxa has been hampered by the lack of a reliable summary measure and testing procedure. Here, we propose a standardized effect size for this purpose, calculated from the relative eigenvalue variance, V r e l $V_{rel}$ . First, we evaluate several eigenvalue dispersion indices under various conditions, and show that only V r e l $V_{rel}$ remains stable across samples size and the number of variables. We then demonstrate that V r e l $V_{rel}$ accurately characterizes input patterns of covariation, so long as redundant dimensions are excluded from the calculations. However, we also show that the variance of the sampling distribution of V r e l $V_{rel}$ depends on input levels of trait covariation, making V r e l $V_{rel}$ unsuitable for direct comparisons. As a solution, we propose transforming V r e l $V_{rel}$ to a standardized effect size (Z-score) for representing the magnitude of integration for a set of traits. We also propose a two-sample test for comparing the strength of integration between taxa, and show that this test displays appropriate statistical properties. We provide software for implementing the procedure, and an empirical example illustrates its use.

R+ pramipexole as a mitochondrially focused neuroprotectant: initial early phase studies in ALS.

R+ pramipexole (PPX) is a lipophilic cation that concentrates into brain and mitochondria and efficiently scavenges reactive oxygen and nitrogen species (RONS). Under the auspices of a Physician-Sponsor IND, R+PPX was dosed to small numbers of ALS patients for tolerability and safety while efficacy measures were also collected. The purpose of this paper is to describe the outcomes of these initial clinical studies. In a futility design study, 30 patients with early SALS were evaluated monthly for ALSFRS-R scores and FVC measurements for three months during lead-in, followed by open-label dosing at 30 mg/day of R+PPX for the next six months. In the dose escalation study, 10 subjects with early ALS received daily doses of R+PPX from 10 mg t.i.d. to 100 mg t.i.d. over seven weeks. In the open-label extension analysis, subjects from the initial studies were treated with 30 mg/day for at least six months, then switched to 60 mg/day. R+PPX was tolerated well in all studies. In the futility study, slopes of decline in ALSFRS-R scores and neurophysiological index (NI) values yielded non-significant reductions during treatment. In the dose-escalation study, all subjects increased daily R+PPX intake safely to 100 mg t.i.d. Markers of ALS did not change (ALSFRS-R) or improved (FVC). Trough and peak plasma (PPX) increased linearly with dosing, and several subjects achieved plasma (PPX) >1 microM. In the open-label extension protocol, changing from 30 to 60 mg/day caused a non-significant 17% reduction in slope of decline of ALSFRS-R. It was concluded that R+PPX was tolerated well in long-term dosing at 30 and 60 mg/day. Encouraging but non-significant effects of R+PPX on ALS decline were observed. High doses of R+PPX were tolerated well and yielded neuroprotective plasma levels. These findings support longer-term testing of higher R+PPX doses as a potential disease-altering therapy for SALS.