D2 dopamine receptor activation of potassium channels in identified rat lactotrophs: whole-cell and single-channel recording

Dopamine (DA) is the major physiological regulator of prolactin secretion from the anterior pituitary, exerting a tonic inhibitory control that is mediated by D2 DA receptors. D2 receptors in both the anterior pituitary and CNS are thought to produce some of their inhibitory effects via a coupling to potassium (K+) channels to increase K+ conductance. Utilizing the reverse hemolytic plaque assay and patch-clamp techniques, we characterize the actions of DA on membrane potential and associated DA-activated whole-cell current, as well as the single K+ channels that underlie the response in primary rat lactotrophs. We demonstrate that DA (5 nM to 1 microM) or D2- selective agonists (RU24213 and quinpirole) evoke a hyperpolarization of membrane potential that was blocked by D2 antagonists and associated with an increased K+ conductance. Whole-cell current responses to ramp voltage commands revealed a DA-activated current whose reversal potential was near the calculated Nernst potential for K+, varied as a function of K+ concentration, exhibited some inward rectification, and was Ca2+ independent. The current was insensitive to tetraethylammonium (TEA; 10 mM), partially blocked by 4-aminopyridine (4-AP; 5 mM), and almost completely inhibited by quinine (100 microM). Cell-attached recordings in the presence of DA or a D2 agonist revealed the opening of a K+ channel that was not present in the absence of DA or when a D2 receptor antagonist was included with DA. Analysis of the single- channel current showed the current-voltage relationship to be linear at negative patch potentials and yielded a unitary conductance of 40.2 pS in the presence of 150 mM KCl. The channels were not blocked by TEA (10 mM), were slightly suppressed by 4-AP (5 mM), and were almost completely inhibited by quinine (100 microM). These experiments establish that in primary rat lactotrophs, DA acts at D2 receptors to activate the opening of single K+ channels, which results in an increase in K+ conductance and associated membrane hyperpolarization. This is the first characterization of single DA-activated K+ channels in an endocrine cell

Incorporating real time velocity map image reconstruction into closed-loop coherent control

We report techniques developed to utilize three-dimensional momentum information as feedback in adaptive femtosecond control of molecular dynamics. Velocity map imaging is used to obtain the three-dimensional momentum map of the dissociating ions following interaction with a shaped intense ultrafast laser pulse. In order to recover robust feedback information, however, the two-dimensional momentum projection from the detector must be inverted to reconstruct the full three-dimensional momentum of the photofragments. These methods are typically slow or require manual inputs and are therefore accomplished offline after the images have been obtained. Using an algorithm based upon an “onion-peeling” (also known as “back projection”) method, we are able to invert 1040 × 1054 pixel images in under 1 s. This rapid inversion allows the full photofragment momentum to be used as feedback in a closed-loop adaptive control scheme, in which a genetic algorithm tailors an ultrafast laser pulse to optimize a specific outcome. Examples of three-dimensional velocity map image based control applied to strong-field dissociation of CO and O2 are presented

Single nucleotide polymorphisms at the TRAF1/C5 locus are associated with rheumatoid arthritis in a Han Chinese population

<p>Abstract</p> <p>Background</p> <p>Genetic variants in <it>TRAF1C5 </it>and <it>PTPN22 </it>genes have been shown to be significantly associated with arthritis rheumatoid in Caucasian populations. This study investigated the association between single nucleotide polymorphisms (SNPs) in <it>TRAF1/C5 </it>and <it>PTPN22 </it>genes and rheumatoid arthritis (RA) in a Han Chinese population. We genotyped SNPs rs3761847 and rs7021206 at the <it>TRAF1/C5 </it>locus and rs2476601 SNP in the <it>PTPN22 </it>gene in a Han Chinese cohort composed of 576 patients with RA and 689 controls. The concentrations of anti-cyclic citrullinated peptide antibodies (CCP) and rheumatoid factor (RF) were determined for all affected patients. The difference between the cases and the controls was compared using <it>χ</it>²analysis.</p> <p>Results</p> <p>Significant differences in SNPs rs3761847 and rs7021206 at <it>TRAF1/C5 </it>were observed between the case and control groups in this cohort; the allelic p-value was 0.0018 with an odds ratio of 1.28 for rs3761847 and 0.005 with an odds ratio of 1.27 for rs7021206. This significant association between rs3761847 and RA was independent of the concentrations of anti-CCP and RF. No polymorphism of rs2476601 was observed in this cohort.</p> <p>Conclusions</p> <p>We first demonstrated that genetic variants at the <it>TRAF1/C5 </it>locus are significantly associated with RA in Han Chinese, suggesting that <it>TRAF1/C5 </it>may play a role in the development of RA in this population, which expands the pathogenesis role of <it>TRAF1/C5 </it>in a different ethnicity.</p

Unworking Milton: Steps to a Georgics of the Mind

Traditionally read as a poem about laboring subjects who gain power through abstract and abstracting forms of bodily discipline, John Milton’s Paradise Lost (1667, 1674) more compellingly foregrounds the erotics of the Garden as a space where humans and nonhumans intra-act materially and sexually. Following Christopher Hill, who long ago pointed to not one but two revolutions in the history of seventeenth-century English radicalism—the first, ‘the one which succeeded[,] . . . the protestant ethic’; and the second, ‘the revolution which never happened,’ which sought ‘communal property, a far wider democracy[,] and rejected the protestant ethic’—I show how Milton’s Paradise Lost gives substance to ‘the revolution which never happened’ by imagining a commons, indeed a communism, in which human beings are not at the center of things, but rather constitute one part of the greater ecology of mind within Milton’s poem. In the space created by this ecological reimagining, plants assume a new agency. I call this reimagining ‘ecology to come.

Plant-made vaccines in support of the Millennium Development Goals

Vaccines are one of the most successful public health achievements of the last century. Systematic immunisation programs have reduced the burden of infectious diseases on a global scale. However, there are limitations to the current technology, which often requires costly infrastructure and long lead times for production. Furthermore, the requirement to keep vaccines within the cold-chain throughout manufacture, transport and storage is often impractical and prohibitively expensive in developing countries—the very regions where vaccines are most needed. In contrast, plant-made vaccines (PMVs) can be produced at a lower cost using basic greenhouse agricultural methods, and do not need to be kept within such narrow temperature ranges. This increases the feasibility of developing countries producing vaccines locally at a small-scale to target the specific needs of the region. Additionally, the ability of plant-production technologies to rapidly produce large quantities of strain-specific vaccine demonstrates their potential use in combating pandemics. PMVs are a proven technology that has the potential to play an important role in increasing global health, both in the context of the 2015 Millennium Development Goals and beyond

The role of complement in ocular pathology

Functionally active complement system and complement regulatory proteins are present in the normal human and rodent eye. Complement activation and its regulation by ocular complement regulatory proteins contribute to the pathology of various ocular diseases including keratitis, uveitis and age-related macular degeneration. Furthermore, a strong relationship between age-related macular degeneration and polymorphism in the genes of certain complement components/complement regulatory proteins is now well established. Recombinant forms of the naturally occurring complement regulatory proteins have been exploited in the animal models for treatment of these ocular diseases. It is hoped that in the future recombinant complement regulatory proteins will be used as novel therapeutic agents in the clinic for the treatment of keratitis, uveitis, and age-related macular degeneration