Raman Scattering Errors in Stimulated-Raman-Induced Logic Gates in

^{133}Ba^{+} is illuminated by a laser that is far detuned from optical transitions, and the resulting spontaneous Raman scattering rate is measured. The observed scattering rate is lower than previous theoretical estimates. The majority of the discrepancy is explained by a more accurate treatment of the scattered photon density of states. This work establishes that, contrary to previous models, there is no fundamental atomic physics limit to laser-driven quantum gates from laser-induced spontaneous Raman scattering.

Evaluation of 5-(Trifluoromethyl)-1,2,4-oxadiazole-Based Class IIa HDAC Inhibitors for Huntington's Disease.

Using an iterative structure-activity relationship driven approach, we identified a CNS-penetrant 5-(trifluoromethyl)-1,2,4-oxadiazole (TFMO, 12) with a pharmacokinetic profile suitable for probing class IIa histone deacetylase (HDAC) inhibition in vivo. Given the lack of understanding of endogenous class IIa HDAC substrates, we developed a surrogate readout to measure compound effects in vivo, by exploiting the >100-fold selectivity compound 12 exhibits over class I/IIb HDACs. We achieved adequate brain exposure with compound 12 in mice to estimate a class I/IIb deacetylation EC50, using class I substrate H4K12 acetylation and global acetylation levels as a pharmacodynamic readout. We observed excellent correlation between the compound 12 in vivo pharmacodynamic response and in vitro class I/IIb cellular activity. Applying the same relationship to class IIa HDAC inhibition, we estimated the compound 12 dose required to inhibit class IIa HDAC activity, for use in preclinical models of Huntington's disease.

Insights into piezophily from genetic studies on the deep-sea bacterium, Photobacterium profundum SS9.

The deep-sea bacterium, Photobacterium profundum SS9, has been adopted as a model organism to understand the molecular basis of cold-adapted high-pressure-loving (piezophilic) growth. Despite growing optimally at 28 MPa (15 degrees C), P. profundum SS9 can grow over a wide range of pressures and temperatures. The ability to grow at atmospheric pressure has enabled a limited set of genetic tools to be developed, which has provided genetic insights into the mechanism of piezophilic growth in P. profundum SS9. This review focuses on how genetic studies have uncovered the importance of processes affecting the DNA and the bacterial cell envelope in the piezophilic growth of P. profundum SS9. In addition, a method was developed to assess quantitative piezophilic colony growth of P. profundum SS9 on solid agar. Future studies, using this methodology, could provide novel insights into the molecular basis of piezophilic, surface-attached growth.

Importance of proteins controlling initiation of DNA replication in the growth of the high-pressure-loving bacterium Photobacterium profundum SS9.

The molecular mechanism(s) by which deep-sea bacteria grow optimally under high hydrostatic pressure at low temperatures is poorly understood. To gain further insight into the mechanism(s), a previous study screened transposon mutant libraries of the deep-sea bacterium Photobacterium profundum SS9 and identified mutants which exhibited alterations in growth at high pressure relative to that of the parent strain. Two of these mutants, FL23 (PBPRA3229::mini-Tn10) and FL28 (PBPRA1039::mini-Tn10), were found to have high-pressure sensitivity and enhanced-growth phenotypes, respectively. The PBPRA3229 and PBPRA1039 genes encode proteins which are highly similar to Escherichia coli DiaA, a positive regulator, and SeqA, a negative regulator, respectively, of the initiation of DNA replication. In this study, we investigated the hypothesis that PBPRA3229 and PBPRA1039 encode DiaA and SeqA homologs, respectively. Consistent with this, we determined that the plasmid-carried PBPRA3229 and PBPRA1039 genes restored synchrony to the initiation of DNA replication in E. coli mutants lacking DiaA and SeqA, respectively. Additionally, PBPRA3229 restored the cold sensitivity phenotype of an E. coli dnaA(Cs) diaA double mutant whereas PBPRA1039 suppressed the cold sensitivity phenotype of an E. coli dnaA(Cs) single mutant. Taken together, these findings show that the genes disrupted in FL23 and FL28 encode DiaA and SeqA homologs, respectively. Consequently, our findings add support to a model whereby high pressure affects the initiation of DNA replication in P. profundum SS9 and either the presence of a positive regulator (DiaA) or the removal of a negative regulator (SeqA) promotes growth under these conditions.