Christopher G. Mayne

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Multiple sclerosis (MS) is an incurable autoimmune neurodegenerative disease. Environmental factors may be key to MS prevention and treatment. MS prevalence and severity decrease with increasing sunlight exposure and vitamin D(3) supplies, supporting our hypothesis that the sunlight-dependent hormone, 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2) D(3) ),(More)
Because of their central importance in gene regulation and mediating the actions of many hormones, the nuclear receptors (NRs) have long been recognized as very important biological and pharmaceutical targets. Of all the surfaces available on a given NR, the singular site for regulation of receptor activity has almost invariably been the ligand-binding(More)
Somatic mutations in the estrogen receptor alpha (ERα) gene (ESR1), especially Y537S and D538G, have been linked to acquired resistance to endocrine therapies. Cell-based studies demonstrated that these mutants confer ERα constitutive activity and antiestrogen resistance and suggest that ligand-binding domain dysfunction leads to endocrine therapy(More)
Adaptive Multilevel Splitting (AMS) is a replica-based rare event sampling method that has been used successfully in high-dimensional stochastic simulations to identify trajectories across a high potential barrier separating one metastable state from another, and to estimate the probability of observing such a trajectory. An attractive feature of AMS is(More)
The inability to rapidly generate accurate and robust parameters for novel chemical matter continues to severely limit the application of molecular dynamics simulations to many biological systems of interest, especially in fields such as drug discovery. Although the release of generalized versions of common classical force fields, for example, General Amber(More)
Multiple sclerosis (MS) is a neurodegenerative disease resulting from an autoimmune attack on the axon-myelin unit. A female MS bias becomes evident after puberty and female incidence has tripled in the last half-century, implicating a female sex hormone interacting with a modifiable environmental factor. These aspects of MS suggest that many female MS(More)
The progesterone receptor (PR) is estrogen regulated, and PR levels in breast tumors can be used to predict the success of endocrine therapies targeting the estrogen receptor (ER). Tanaproget is a nonsteroidal progestin agonist with very high PR binding affinity and excellent in vivo potency. When appropriately radiolabeled, it might be used to image(More)
Systemic lupus erythematosis is an autoimmune disease of unknown etiology. Lupus pathology is thought to reflect autoantibody-mediated damage due to a failure of B lymphocyte tolerance. Since excessive B cell-activating factor belonging to the TNF family (BAFF) expression correlates with human and murine lupus, and BAFF signals B cell survival through(More)
The mucosal immune system mediates contact between the host and the trillions of microbes that symbiotically colonize the gastrointestinal tract. Failure to tolerate the antigens within this "extended self" can result in inflammatory bowel disease (IBD). Within the adaptive immune system, the most significant cells modulating this interaction are Foxp3(More)
Systemic lupus erythematosus pathology reflects autoantibody-mediated damage due to a failure of B-lymphocyte tolerance. We previously reported that B-lymphopenic A/WySnJ mice develop a lupus-like syndrome and linked this syndrome to the B-cell maturation defect-1 (Bcmd-1) mutant allele of the B-cell-activating factor belonging to the TNF family-receptor(More)