Characterizing Conformational Changes Along the Dimerization Helix of the Global Regulator, FNR, Using Fluorescence Spectroscopy

The FNR protein is a transcription factor that allows Escherichia coli to undergo anaerobic cellular respiration. It is known to positively regulate the expression ofseveral genes required for anaerobic respiration as well as negatively regulate genes responsible for aerobic respiration. Consequently, FNR is active under anaerobic conditions and inactive under aerobic conditions. Although the tertiary structure ofFNR is unknown, previous studies have indicated that FNR is inactive in the monomeric state and active in the dimeric state. Thus, it is believed that in anaerobic conditions, FNR undergoes a confonnational change from the monomeric to dimeric state. The mechanism involved in going from the monomeric to dimeric state is not completely understood, but it is thought to be triggered by the acquisition ofa [4Fe-4S]2+ cluster in the N-tenninal region ofFNR. The acquisition ofthe cluster causes a confonnational change to be transmitted through the allosteric domain to the dimerization helix resulting in the active dimeric species. Infonnation regarding the environment of amino acid residues in the dimerization helix in both the active and inactive fonns of FNR could be helpful in eliciting a better understanding ofthe dimerization mechanism. Such environmental conditions can be detennined by the fluorescent properties ofthe amino acid, tryptophan. Surface exposed tryptophan residues are expected to have a longer Amax than those buried in the hydrophobic core. In order to gain insight into the environment ofthe amino acids on the dimerization helix we have created tryptophan mutants (LWI46, MW147, MW157, KW163, and KW164) that either lay on or near the helix. The mutants KW163 and KW164 all lie on the periphery ofthe helix while LW146, MW147 and MW157 lie on the helix. Ofthe five mutants, KW163 retained anaerobic activity most similar to that of the wild type indicating that its structure is similar to the wild type protein with the exception ofthe single amino acid substitution. By comparing the fluorescence ofthe active and inactive forms of KW163, we hope to gain a better understanding ofthe dimerization mechanism ofFNR

Aripiprazole in the acute and maintenance phase of bipolar I disorder

Bipolar affective disorder is a disabling illness with substantial morbidity and many management challenges. Traditional mood stabilizers such as lithium, valproate, and carbamazepine are often inadequate in controlling symptoms both during the acute and maintenance phase of treatment. Aripiprazole is a second-generation antipsychotic with a unique mechanism of action. Evidence suggests that it is effective in acute manic and mixed states. There are limited data to suggest its efficacy as a maintenance agent. Future studies will be needed to better define the role of aripiprazole relative to other traditional pharmacologic agents

Contrasting Computational Models of Mate Preference Integration Across 45 Countries.

Humans express a wide array of ideal mate preferences. Around the world, people desire romantic partners who are intelligent, healthy, kind, physically attractive, wealthy, and more. In order for these ideal preferences to guide the choice of actual romantic partners, human mating psychology must possess a means to integrate information across these many preference dimensions into summaries of the overall mate value of their potential mates. Here we explore the computational design of this mate preference integration process using a large sample of n = 14,487 people from 45 countries around the world. We combine this large cross-cultural sample with agent-based models to compare eight hypothesized models of human mating markets. Across cultures, people higher in mate value appear to experience greater power of choice on the mating market in that they set higher ideal standards, better fulfill their preferences in choice, and pair with higher mate value partners. Furthermore, we find that this cross-culturally universal pattern of mate choice is most consistent with a Euclidean model of mate preference integration

Assortative mating and the evolution of desirability covariation

Mate choice lies dose to differential reproduction, the engine of evolution. Patterns of mate choice consequently have power to direct the course of evolution. Here we provide evidence suggesting one pattern of human mate choice-the tendency for mates to be similar in overall desirability-caused the evolution of a structure of correlations that we call the d factor. We use agent-based models to demonstrate that assortative mating causes the evolution of a positive manifold of desirability, d, such that an individual who is desirable as a mate along any one dimension tends to be desirable across all other dimensions. Further, we use a large cross-cultural sample with n = 14,478 from 45 countries around the world to show that this d-factor emerges in human samples, is a cross-cultural universal, and is patterned in a way consistent with an evolutionary history of assortative mating. Our results suggest that assortative mating can explain the evolution of a broad structure of human trait covariation