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“How do we create new artificial proteins? In this review, we present a range of experimental approaches based on combinatorial and directed evolution methods used to explore sequence space and recreate structured

or active proteins. These approaches can help to understand constraints of natural evolution and can lead to new useful proteins. Strategies such as binary patterning or modular assembly can efficiently speed structural and functional innovation. Many natural protein architectures are symmetric or repeated and presumably have emerged by coalescence of simpler fragments. This process can be experimentally reproduced; a range of artificial proteins obtained from idealized fragments has recently been described and some of these have already found direct applications.”
“The major substrate underlying amphetamine (AMPH)-induced locomotor activity selleck chemicals is associated this website with dopamine forebrain circuits. Brain regions associated with AMPH-induced locomotor activity express high levels of retinoid receptors. However, the role of these transcription factors in dopamine-mediated effects remains poorly understood. Two nuclear receptor families, the retinoic acid receptors (RAR) and the retinoid X receptors (RXR), transduce retinoic acid signal. RARs are specifically involved in retinoid signaling, whereas RXRs also participate in other signaling pathways

as partners for other nuclear receptors such as Nur77, an orphan member of the nuclear receptor family expresses in dopamine system.

To explore the role of retinoid receptors and Nur77 in AMPH-induced locomotor activity, we administered Pyruvate dehydrogenase lipoamide kinase isozyme 1 selective retinoid receptor drugs in combination with AMPH in adult wild-type and Nur77-deficient

mice. At a low dose, AMPH similarly increased ambulatory activity in wild-type and Nur77-deficient mice, while it did not alter non-ambulatory activity.

At a high dose, AMPH did not alter ambulatory activity anymore, while non-ambulatory activity strongly increased in wild-type mice. Nur77-deficient mice still displayed a higher ambulatory activity with no change in non-ambulatory activity. HX531, a synthetic RXR antagonist, blocks AMPH-induced ambulatory activity, whereas RAR drugs tested remained without effect. Interestingly, the effect of HX531 was abolished in Nur77-deficient mice, suggesting that this orphan nuclear receptor is essential for the action of the RXR drug.

This study shows that RXR and Nur77 participate in AMPH-induced locomotor activity and prompts for further investigations on the role of Nur77 and RXR in addiction and reward-related behaviors.”
“Semliki Forest virus (SFV) is a member of the Alphavirus genus, which produces its replicase proteins in the form of a nonstructural (ns) polyprotein precursor P1234. The maturation of the replicase occurs in a temporally controlled manner by protease activity of nsP2.