The crystal structure of the catalytic domain of a eukaryotic guanylate cyclase

<p>Abstract</p> <p>Background</p> <p>Soluble guanylate cyclases generate cyclic GMP when bound to nitric oxide, thereby linking nitric oxide levels to the control of processes such as vascular homeostasis and neurotransmission. The guanylate cyclase catalytic module, for which no structure has been determined at present, is a class III nucleotide cyclase domain that is also found in mammalian membrane-bound guanylate and adenylate cyclases.</p> <p>Results</p> <p>We have determined the crystal structure of the catalytic domain of a soluble guanylate cyclase from the green algae <it>Chlamydomonas reinhardtii </it>at 2.55 Å resolution, and show that it is a dimeric molecule.</p> <p>Conclusion</p> <p>Comparison of the structure of the guanylate cyclase domain with the known structures of adenylate cyclases confirms the close similarity in architecture between these two enzymes, as expected from their sequence similarity. The comparison also suggests that the crystallized guanylate cyclase is in an inactive conformation, and the structure provides indications as to how activation might occur. We demonstrate that the two active sites in the dimer exhibit positive cooperativity, with a Hill coefficient of ~1.5. Positive cooperativity has also been observed in the homodimeric mammalian membrane-bound guanylate cyclases. The structure described here provides a reliable model for functional analysis of mammalian guanylate cyclases, which are closely related in sequence.</p

A microchip optomechanical accelerometer

The monitoring of accelerations is essential for a variety of applications ranging from inertial navigation to consumer electronics. The basic operation principle of an accelerometer is to measure the displacement of a flexibly mounted test mass; sensitive displacement measurement can be realized using capacitive, piezo-electric, tunnel-current, or optical methods. While optical readout provides superior displacement resolution and resilience to electromagnetic interference, current optical accelerometers either do not allow for chip-scale integration or require bulky test masses. Here we demonstrate an optomechanical accelerometer that employs ultra-sensitive all-optical displacement read-out using a planar photonic crystal cavity monolithically integrated with a nano-tethered test mass of high mechanical Q-factor. This device architecture allows for full on-chip integration and achieves a broadband acceleration resolution of 10 \mu g/rt-Hz, a bandwidth greater than 20 kHz, and a dynamic range of 50 dB with sub-milliwatt optical power requirements. Moreover, the nano-gram test masses used here allow for optomechanical back-action in the form of cooling or the optical spring effect, setting the stage for a new class of motional sensors.Comment: 16 pages, 9 figure

Discriminative and reinforcing effects of brotizolam in rhesus monkeys

The reinforcing and discriminative stimulus effects of brotizolam, a benzodiazepine-hypnotic, were evaluated in rhesus monkeys. In one experiment, separate groups of monkeys ( N =3/group) were trained to discriminate pentobarbital (10 mg/kg, IG) or d -amphetamine (0.56–1.0 mg/kg, IG) from saline, in a discrete-trials avoidance/escape paradigm. Pentobarbital (5.6–10 mg/kg), diazepam (1.0–1.7 mg/kg), and brotizolam (0.3–1.7 mg/kg) resulted in 100% drug-lever responding in all three pentobarbital-trained monkeys. In d -amphetamine-trained monkeys brotizolam administration resulted only in saline-lever responding. In another experiment, monkeys were surgically prepared with indwelling intravenous catheters and lever pressing resulted in an injection of 0.1 mg/kg/injection sodium methohexital under a fixed-ratio 10 (FR 10) schedule. Pentobarbital (0.01–0.3 mg/kg/injection) and diazepam (0.003–0.10 mg/kg/injection) maintained responding above saline control levels when substituted for methohexital. Brotizolam (0.001–0.01 mg/kg/injection) resulted in more injections received compared to saline, but fewer injections compared to pentobarbital or diazepam. Thus, results from the present experiment suggest that brotizolam would have pentobarbital-like subjective effects. However, the abuse liability of brotizolam may be lower than that for diazepam.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46334/1/213_2005_Article_BF02244198.pd

A chip-scale integrated cavity-electro-optomechanics platform

We present an integrated optomechanical and electromechanical nanocavity, in which a common mechanical degree of freedom is coupled to an ultrahigh-Q photonic crystal defect cavity and an electrical circuit. The sys- tem allows for wide-range, fast electrical tuning of the optical nanocavity resonances, and for electrical control of optical radiation pressure back-action effects such as mechanical amplification (phonon lasing), cooling, and stiffening. These sort of integrated devices offer a new means to efficiently interconvert weak microwave and optical signals, and are expected to pave the way for a new class of micro-sensors utilizing optomechanical back-action for thermal noise reduction and low-noise optical read-out.Comment: 11 pages, 7 figure

Genomic approaches to understanding population divergence and speciation in birds

© 2016 American Ornithologists\u27 Union. The widespread application of high-throughput sequencing in studying evolutionary processes and patterns of diversification has led to many important discoveries. However, the barriers to utilizing these technologies and interpreting the resulting data can be daunting for first-time users. We provide an overview and a brief primer of relevant methods (e.g., whole-genome sequencing, reduced-representation sequencing, sequence-capture methods, and RNA sequencing), as well as important steps in the analysis pipelines (e.g., loci clustering, variant calling, whole-genome and transcriptome assembly). We also review a number of applications in which researchers have used these technologies to address questions related to avian systems. We highlight how genomic tools are advancing research by discussing their contributions to 3 important facets of avian evolutionary history. We focus on (1) general inferences about biogeography and biogeographic history, (2) patterns of gene flow and isolation upon secondary contact and hybridization, and (3) quantifying levels of genomic divergence between closely related taxa. We find that in many cases, high-throughput sequencing data confirms previous work from traditional molecular markers, although there are examples in which genome-wide genetic markers provide a different biological interpretation. We also discuss how these new data allow researchers to address entirely novel questions, and conclude by outlining a number of intellectual and methodological challenges as the genomics era moves forward