1.An evolutionarily conserved role for the aryl hydrocarbon receptor in the regulation of movement.
Williams EG1, Mouchiroud L1, Frochaux M2, Pandey A3, Andreux PA1, Deplancke B2, Auwerx J1. PLoS Genet. 2014 Sep 25;10(9):e1004673. doi: 10.1371/journal.pgen.1004673. eCollection 2014.
The BXD genetic reference population is a recombinant inbred panel descended from crosses between the C57BL/6 (B6) and DBA/2 (D2) strains of mice, which segregate for about 5 million sequence variants. Recently, some of these variants have been established with effects on general metabolic phenotypes such as glucose response and bone strength. Here we phenotype 43 BXD strains and observe they have large variation (-5-fold) in their spontaneous activity during waking hours. QTL analyses indicate that -40% of this variance is attributable to a narrow locus containing the aryl hydrocarbon receptor (Ahr), a basic helix-loop-helix transcription factor with well-established roles in development and xenobiotic metabolism. Strains with the D2 allele of Ahr have reduced gene expression compared to those with the B6 allele, and have significantly higher spontaneous activity. This effect was also observed in B6 mice with a congenic D2 Ahr interval, and in B6 mice with a humanized AHR allele which, like the D2 allele, is expressed much less and has less enzymatic activity than the B6 allele.
2.A Proline-Tryptophan Turn in the Intrinsically Disordered Domain 2 of NS5A Protein Is Essential for Hepatitis C Virus RNA Replication.
Dujardin M1, Madan V2, Montserret R3, Ahuja P1, Huvent I1, Launay H1, Leroy A4, Bartenschlager R2, Penin F3, Lippens G1, Hanoulle X5. J Biol Chem. 2015 Jul 31;290(31):19104-20. doi: 10.1074/jbc.M115.644419. Epub 2015 Jun 17.
Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) and its interaction with the human chaperone cyclophilin A are both targets for highly potent and promising antiviral drugs that are in the late stages of clinical development. Despite its high interest in regards to the development of drugs to counteract the worldwide HCV burden, NS5A is still an enigmatic multifunctional protein poorly characterized at the molecular level. NS5A is required for HCV RNA replication and is involved in viral particle formation and regulation of host pathways. Thus far, no enzymatic activity or precise molecular function has been ascribed to NS5A that is composed of a highly structured domain 1 (D1), as well as two intrinsically disordered domains 2 (D2) and 3 (D3), representing half of the protein. Here, we identify a short structural motif in the disordered NS5A-D2 and report its NMR structure. We show that this structural motif, a minimal Pro(314)-Trp(316) turn, is essential for HCV RNA replication, and its disruption alters the subcellular distribution of NS5A.
3.Effects of ketamine exposure on dopamine concentrations and dopamine type 2 receptor mRNA expression in rat brain tissue.
Li B1, Liu ML2, Wu XP3, Jia J1, Cao J1, Wei ZW1, Wang YJ1. Int J Clin Exp Med. 2015 Jul 15;8(7):11181-7. eCollection 2015.
OBJECTIVE: To explore the effects of ketamine abuse on the concentration of dopamine (DA), a monoamine neurotransmitter, and the mRNA expression of dopamine type 2 (D2) receptors in brain tissue, we used male Wistar rats to model ketamine abuse through chronic intraperitoneal infusion of ketamine across different doses.