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Biology subjects

Stull, C.

Publications and source records attributed to Stull, C..

2 recordsLinked to original sources

Genetic architecture of trophic adaptations in cichlid fishes

Since Darwin, biologists have sought to understand the evolution and origins of phenotypic adaptations. The skull is particularly diverse due to intense natural selection such as feeding biomechanics. We investigate the genetic and molecular origins of trophic adaptation using Lake Malawi cichlids, which have undergone an exemplary evolutionary radiation. We analyze morphological differences in the lateral and ventral head among an insectivore that eats by suction feeding, an obligate biting herbivore, and their F2 hybrids. We identify variation in a series of morphologies including mandible width, mandible length, and buccal length that directly affect feeding kinematics and function. Using quantitative trait loci (QTL) mapping, we find that many genes of small effects influence these craniofacial adaptations. Intervals for some traits are enriched in genes related to potassium transport and sensory systems, the latter suggesting correlation between feeding structures and sensory adaptations for foraging. Craniofacial phenotypes largely map to distinct genetic intervals, and morphologies in the head do not correlate. Together, these suggest that craniofacial traits are mostly inherited as separate modules, which confers a high potential for the evolution of morphological diversity. Though these traits are not restricted by genetic pleiotropy, functional demands of feeding and sensory structures likely introduce constraints on variation. In all, we provide insights into the quantitative genetic basis of trophic adaptation, identify mechanisms that influence the direction of morphological evolution, and provide molecular inroads to craniofacial variation.

evolutionary biology↗

Transcriptional, epigenetic, and functional reprogramming of blood monocytes in non-human primates following chronic alcohol drinking

Chronic heavy drinking (CHD) of alcohol is a known risk factor for increased susceptibility to bacterial and viral infection as well as impaired wound healing. Evidence suggests that these defects are mediated by a dysregulated inflammatory response originating from myeloid cells, notably monocytes and macrophages, but the mechanisms remain poorly understood. Our ability to study CHD is impacted by the complexities of human drinking patterns and behavior as well as comorbidities and confounding risk factors for patients with alcohol use disorders. To overcome these challenges, we utilize a translational rhesus macaque model of voluntary ethanol self-administration that closely recapitulates human drinking patterns and chronicity. In this study, we examined the effects of CHD on blood monocytes and alveolar macrophages in control and CHD female macaques after 12 months of daily ethanol consumption. While monocytes from CHD female macaques generated a hyper-inflammatory response to ex vivo LPS stimulation, their response to E.Coli was dampened. In depth scRNA-Seq analysis of purified monocytes revealed significant shifts in classical monocyte subsets with accumulation of cells expressing markers of hypoxia (HIF1A) and inflammation (NFkB signaling pathway) in CHD macaques. The increased presence of monocyte subsets poised to generate a hyperinflammatory response was confirmed by the epigenetic analysis which revealed higher accessibility of promoter regions that regulate genes involved in cytokine signaling pathways. Finally, alveolar macrophages (AM) from the same animals produced higher levels of inflammatory mediators in response to LPS stimulation, but reduced ability to phagocytose bacteria. Collectively, data presented in this manuscript demonstrate that CHD primes monocytes and tissue-resident macrophages towards a more hyper-inflammatory immune response with compromised functional abilities, which could be used in diagnostic purposes or preventative measures for patients with alcohol use disorders.

immunology↗