Bridging the Gap: Multi-Omics Profiling of Brain Tissue in Alzheimer's Disease and Older Controls in Multi-Ethnic Populations.

INTRODUCTION: Multi-omics studies in Alzheimer's disease (AD) revealed many potential disease pathways and therapeutic targets. Despite their promise of precision medicine, these studies lacked African Americans (AA) and Latin Americans (LA), who are disproportionately affected by AD. METHODS: To bridge this gap, Accelerating Medicines Partnership in AD (AMP-AD) expanded brain multi-omics profiling to multi-ethnic donors. RESULTS: We generated multi-omics data and curated and harmonized phenotypic data from AA (n=306), LA (n=326), or AA and LA (n=4) brain donors plus Non-Hispanic White (n=252) and other (n=20) ethnic groups, to establish a foundational dataset enriched for AA and LA participants. This study describes the data available to the research community, including transcriptome from three brain regions, whole genome sequence, and proteome measures. DISCUSSION: Inclusion of traditionally underrepresented groups in multi-omics studies is essential to discover the full spectrum of precision medicine targets that will be pertinent to all populations affected with AD.

Using 3D-digital photogrammetry to examine scaling of the body axis in burrowing skinks.

Three-dimensional (3D) modeling techniques have been increasingly utilized across disciplines for the visualization and analysis of complex structures. We employ 3D-digital photogrammetry for understanding the scaling of the body axis of 12 species of scincid lizards in the genus Brachymeles. These skinks represent a diverse radiation which shows tremendous variation in body size and degree of axial elongation. Because of the complex nature of the body axis, 3D-methods are important for understanding how the body axis evolves. 3D-digital photogrammetry presents a flexible, inexpensive, and portable system for the reconstruction of biological forms. As body size increased among species, the cross-sectional area and circumference of the head and other portions of the body axis increased isometrically, which indicates that species of differing sizes possess proportionally similar head and body shapes. These results suggest that there are no substantial head and body shape changes with body size among the sampled species, but further comparative studies with larger sample sizes and functional studies of size and morphology effects on burrowing or above-ground locomotion are needed.

Intraspecific male combat behaviour predicts morphology of cervical vertebrae in ruminant mammals.

Cranial weapons of all shapes and sizes are common throughout the animal kingdom and are frequently accompanied by the evolution of additional traits that enhance the use of those weapons. Bovids (cattle, sheep, goats, antelope) and cervids (deer) within the mammal clade Ruminantia are particularly well known for their distinct and varied cranial appendages in the form of horns and antlers, which are used as weapons in intraspecific combat between males for access to mates. Combat in these species takes many forms, including head-on collisions (ramming); stabbing an opponent's head or body with horn tips (stabbing); rearing and clashing downwards with horns (fencing); or interlocking antlers or horns while vigorously pushing and twisting (wrestling). Some aspects of weapon and skull morphology have been linked to combat behaviours in bovid and cervid species, but the contribution of postcranial structures that support these weapons, such as the neck, has not been explored. To investigate the role of the neck in intraspecific combat, we quantified biomechanically relevant linear variables of the cervical vertebrae (C1-C7) from males and females of 55 ruminant species. We then used phylogenetic generalized least-squares regression to assess differences among species that display primarily ramming, stabbing, fencing and wrestling combat styles. In males, we found that wrestlers have longer vertebral centra and longer neural spines than rammers, stabbers or fencers, while rammers have shorter and wider centra and taller neural spine lever arms. These results suggest a supportive role for the cervical vertebrae in resisting forces generated by male-male combat in ruminant mammals and indicate that evolutionary forces influencing cranial weapons also play a role in shaping the supporting anatomical structures.

Head-turning morphologies: Evolution of shape diversity in the mammalian atlas-axis complex.

Mammals flex, extend, and rotate their spines as they perform behaviors critical for survival, such as foraging, consuming prey, locomoting, and interacting with conspecifics or predators. The atlas-axis complex is a mammalian innovation that allows precise head movements during these behaviors. Although morphological variation in other vertebral regions has been linked to ecological differences in mammals, less is known about morphological specialization in the cervical vertebrae, which are developmentally constrained in number but highly variable in size and shape. Here, we present the first phylogenetic comparative study of the atlas-axis complex across mammals. We used spherical harmonics to quantify 3D shape variation of the atlas and axis across a diverse sample of species, and performed phylogenetic analyses to investigate if vertebral shape is associated with body size, locomotion, and diet. We found that differences in atlas and axis shape are partly explained by phylogeny, and that mammalian subclades differ in morphological disparity. Atlas and axis shape diversity is associated with differences in body size and locomotion; large terrestrial mammals have craniocaudally elongated vertebrae, whereas smaller mammals and aquatic mammals have more compressed vertebrae. These results provide a foundation for investigating functional hypotheses underlying the evolution of neck morphologies across mammals.

Assessing Soft-Tissue Shrinkage Estimates in Museum Specimens Imaged With Diffusible Iodine-Based Contrast-Enhanced Computed Tomography (diceCT).

The increased accessibility of soft-tissue data through diffusible iodine-based contrast-enhanced computed tomography (diceCT) enables comparative biologists to increase the taxonomic breadth of their studies with museum specimens. However, it is still unclear how soft-tissue measurements from preserved specimens reflect values from freshly collected specimens and whether diceCT preparation may affect these measurements. Here, we document and evaluate the accuracy of diceCT in museum specimens based on the soft-tissue reconstructions of brains and eyes of five bats. Based on proxies, both brains and eyes were roughly 60% of the estimated original sizes when first imaged. However, these structures did not further shrink significantly over a 4-week staining interval, and 1 week in 2.5% iodine-based solution yielded sufficient contrast for differentiating among soft-tissues. Compared to six "fresh" bat specimens imaged shortly after field collection (not fixed in ethanol), the museum specimens had significantly lower relative volumes of the eyes and brains. Variation in field preparation techniques and conditions, and long-term storage in ethanol may be the primary causes of shrinkage in museum specimens rather than diceCT staining methodology. Identifying reliable tissue-specific correction factors to adjust for the shrinkage now documented in museum specimens requires future work with larger samples.

A large carnivorous mammal from the Late Cretaceous and the North American origin of marsupials.

Marsupial mammal relatives (stem metatherians) from the Mesozoic Era (252-66 million years ago) are mostly known from isolated teeth and fragmentary jaws. Here we report on the first near-complete skull remains of a North American Late Cretaceous metatherian, the stagodontid Didelphodon vorax. Our phylogenetic analysis indicates that marsupials or their closest relatives evolved in North America, as part of a Late Cretaceous diversification of metatherians, and later dispersed to South America. In addition to being the largest known Mesozoic therian mammal (node-based clade of eutherians and metatherians), Didelphodon vorax has a high estimated bite force and other craniomandibular and dental features that suggest it is the earliest known therian to invade a durophagous predator-scavenger niche. Our results broaden the scope of the ecomorphological diversification of Mesozoic mammals to include therian lineages that, in this case, were linked to the origin and evolution of marsupials.