To investigate whether polymorphic forms of the human dopamine D4 receptor have different functional characteristics, we have stably expressed cDNAs of the D4 .2, D4 .4, and D4 .7 isoforms in several cell lines . Chinese hamster ovary CHO-K1 cell lines expressing D4 receptor variants displayed pharmacological profiles that were in close agreement with previous data from transiently expressed D4 receptors in COS-7 cells . Dopamine stimulation of the D4 receptors resulted in a concentration-dependent inhibition of the forskolin-stimulated cyclic AMP (cAMP) levels . The potency of dopamine to inhibit cAMP formation was about twofold reduced for D4 .7 (EC so of -37 nM) compared with the D4 .2 and D4 .4 variants (EC SO of -16 nM) . Antagonists block the dopamine-mediated inhibition of cAMP formation with a rank order of potency of emonapride > haloperidol = clozapine > raclopride . There was no obvious correlation between the efficacy of inhibition of forskolin-stimulated cAMP levels and the D4 subtypes . Dopamine could completely reverse prostaglandin E 2 -stimulated cAMP levels for all three D4 receptor variants . Deletion of the repeat sequence does not affect functional activity of the receptor . The data presented indicate that the polymorphic repeat sequence causes only small changes in the ability of the D4 receptor to block cAMP production in CHO cells . Key Words : Dopamine receptors-D4-Cyclic AMP-Variants .

Dopamine-modulated behaviors, including information processing and reward, are subject to behavioral plasticity. Disruption of these behaviors is thought to support drug addictions and psychoses. The plasticity of dopaminemediated behaviors, for example, habituation and sensitization, are not well understood at the molecular level. We show that in the nematode Caenorhabditis elegans, a D1-like dopamine receptor gene (dop-1) modulates the plasticity of mechanosensory behaviors in which dopamine had not been implicated previously. A mutant of dop-1 displayed faster habituation to nonlocalized mechanical stimulation. This phenotype was rescued by the introduction of a wild-type copy of the gene. The dop-1 gene is expressed in mechanosensory neurons, particularly the ALM and PLM neurons. Selective expression of the dop-1 gene in mechanosensory neurons using the mec-7 promoter rescues the mechanosensory deficit in dop-1 mutant animals. The tyrosine hydroxylase-deficient C. elegans mutant (cat-2) also displays these specific behavioral deficits. These observations provide genetic evidence that dopamine signaling modulates behavioral plasticity in C. elegans.

During translation termination, class II release factor RF3 binds to the ribosome to promote rapid dissociation of a class I release factor (RF) in a GTP-dependent manner. We present the crystal structure of E. coli RF3*GDP, which has a three-domain architecture strikingly similar to the structure of EF-Tu*GTP. Biochemical data on RF3 mutants show that a surface region involving domains II and III is important for distinct steps in the action cycle of RF3. Furthermore, we present a cryo-electron microscopy (cryo-EM) structure of the posttermination ribosome bound with RF3 in the GTP form. Our data show that RF3*GTP binding induces large conformational changes in the ribosome, which break the interactions of the class I RF with both the decoding center and the GTPase-associated center of the ribosome, apparently leading to the release of the class I RF.

Kinetics and cryo-electronmicroscopy data provide insights into GTPase ObgE’s role as a ribosome anti-association factor that is modulated by nutrient availability, coupling growth control to ribosome biosynthesis and protein translation.

Adverse cellular conditions often lead to nonproductive translational stalling and arrest of ribosomes on mRNAs. Here, we used fast kinetics and cryo-EM to characterize Escherichia coli HflX, a GTPase with unknown function. Our data reveal that HflX is a heat shock-induced ribosome-splitting factor capable of dissociating vacant as well as mRNA-associated ribosomes with deacylated tRNA in the peptidyl site. Structural data demonstrate that the N-terminal effector domain of HflX binds to the peptidyl transferase center in a strikingly similar manner as that of the class I release factors and induces dramatic conformational changes in central intersubunit bridges, thus promoting subunit dissociation. Accordingly, loss of HflX results in an increase in stalled ribosomes upon heat shock. These results suggest a primary role of HflX in rescuing translationally arrested ribosomes under stress conditions.

In this work, we have studied interactions of nucleobases and aromatic amino acids with graphene (G) and graphene oxide (GO) flakes by ab initio density functional theory (DFT). It is evident from the results that GO complexes are stabilized by hydrogen bonding interactions whereas G complexes are stabilized by π−π interactions, leading to enhanced binding energies for GO complexes compared to G complexes. Moreover, time-dependent DFT (TD-DFT) calculations for the optical properties reveal that the GO nanoflakes and GO−nucleobase composite absorb visible light in the range of 400−700 nm, which may be useful for light-emitting devices. The insights obtained from our study will be useful to understand the role of GO flakes as carriers in targeted drug delivery and biosensors.

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Background: Stop codon frequencies in 4684 bacterial genomes are analyzed. Results: With increasing genomic GC content, TAA% decreases, and TGA% increases reciprocally, but TAG% remains almost unchanged (ϳ20%). The TAG:TGA ratio matches well with the RF1:RF2 ratio. Conclusion: TAG is the minor stop codon, and expression of genes with TAG is correlated with the RF1 level. Significance: Our work establishes the correlation between stop codon frequency and RF1/RF2 abundance.