A Period of Controlled Elevation of IOP (CEI) Produces the Specific Gene Expression Responses and Focal Injury Pattern of Experimental Rat Glaucoma

PURPOSE: We determine if several hours of controlled elevation of IOP (CEI) will produce the optic nerve head (ONH) gene expression changes and optic nerve (ON) damage pattern associated with early experimental glaucoma in rats. METHODS: The anterior chambers of anesthetized rats were cannulated and connected to a reservoir to elevate IOP. Physiologic parameters were monitored. Following CEI at various recovery times, ON cross-sections were graded for axonal injury. Anterior ONHs were collected at 0 hours to 10 days following CEI and RNA extracted for quantitative PCR measurement of selected messages. The functional impact of CEI was assessed by electroretinography (ERG). RESULTS: During CEI, mean arterial pressure (99 ± 6 mm Hg) and other physiologic parameters remained stable. An 8-hour CEI at 60 mm Hg produced significant focal axonal degeneration 10 days after exposure, with superior lesions in 83% of ON. Message analysis in CEI ONH demonstrated expression responses previously identified in minimally injured ONH following chronic IOP elevation, as well as their sequential patterns. Anesthesia with cannulation at 20 mm Hg did not alter these message levels. Electroretinographic A- and B-waves, following a significant reduction at 2 days after CEI, were fully recovered at 2 weeks, while peak scotopic threshold response (pSTR) remained mildly but significantly depressed. CONCLUSIONS: A single CEI reproduces ONH message changes and patterns of ON injury previously observed with chronic IOP elevation. Controlled elevation of IOP can allow detailed determination of ONH cellular and functional responses to an injurious IOP insult and provide a platform for developing future therapeutic interventions

Magnetic vortex oscillator driven by dc spin-polarized current

Transfer of angular momentum from a spin-polarized current to a ferromagnet provides an efficient means to control the dynamics of nanomagnets. A peculiar consequence of this spin-torque, the ability to induce persistent oscillations of a nanomagnet by applying a dc current, has previously been reported only for spatially uniform nanomagnets. Here we demonstrate that a quintessentially nonuniform magnetic structure, a magnetic vortex, isolated within a nanoscale spin valve structure, can be excited into persistent microwave-frequency oscillations by a spin-polarized dc current. Comparison to micromagnetic simulations leads to identification of the oscillations with a precession of the vortex core. The oscillations, which can be obtained in essentially zero magnetic field, exhibit linewidths that can be narrower than 300 kHz, making these highly compact spin-torque vortex oscillator devices potential candidates for microwave signal-processing applications, and a powerful new tool for fundamental studies of vortex dynamics in magnetic nanostructures.Comment: 14 pages, 4 figure

Cellulose acetate phthalate, a common pharmaceutical excipient, inactivates HIV-1 and blocks the coreceptor binding site on the virus envelope glycoprotein gp120

BACKGROUND: Cellulose acetate phthalate (CAP), a pharmaceutical excipient used for enteric film coating of capsules and tablets, was shown to inhibit infection by the human immunodeficiency virus type 1 (HIV-1) and several herpesviruses. CAP formulations inactivated HIV-1, herpesvirus types 1 (HSV-1) and 2 (HSV-2) and the major nonviral sexually transmitted disease (STD) pathogens and were effective in animal models for vaginal infection by HSV-2 and simian immunodeficiency virus. METHODS: Enzyme-linked immunoassays and flow cytometry were used to demonstrate CAP binding to HIV-1 and to define the binding site on the virus envelope. RESULTS: 1) CAP binds to HIV-1 virus particles and to the envelope glycoprotein gp120; 2) this leads to blockade of the gp120 V3 loop and other gp120 sites resulting in diminished reactivity with HIV-1 coreceptors CXCR4 and CCR5; 3) CAP binding to HIV-1 virions impairs their infectivity; 4) these findings apply to both HIV-1 IIIB, an X4 virus, and HIV-1 BaL, an R5 virus. CONCLUSIONS: These results provide support for consideration of CAP as a topical microbicide of choice for prevention of STDs, including HIV-1 infection

Sexual selection and mating system in Zorotypus gurneyi Choe (Insecta : Zoraptera)

Social behavior of a species in the little-known insect order Zoraptera is described for the first time. Zorotypus gurneyi Choe (Insecta: Zoraptera) is a wing-dimorphic species that lives colonially under the bark of rotting logs in central Panama. Males are larger than females in total body size and fight each other to gain access to females. Highly linear and stable dominance hierarchies exist among males. Higher-ranking males show such agonistic behavior as jerking, chasing, head-butting, hindleg-kicking, and grappling, whereas subordinates often try to avoid contacts. Higher-ranking males, the dominant males in particular, are well recognized by others and relatively free of injuries. Although the dominant males are often the largest, the correlation between body size and dominance rank is not always significant. The mating system of Z. gurneyi is an example of female defense polygyny in which the dominant males obtain the majority of matings (75% on average). Mating success among Z. gurneyi males is much more variable than that of some lekking species.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46900/1/265_2004_Article_BF00164179.pd

Sexual selection and mating system in Zorotypus gurneyi Choe (Insecta: Zoraptera)

Body size is clearly an important factor influencing the outcome of agonistic contests, but is often weakly correlated with dominance ranks in Zorotypus gurneyi Choe (Insecta: Zoraptera). The study of the development and dynamics of dominance relations using artificially constructed colonies show that age, or tenure within the colony, is the prime determinant of dominance among males. Dominance hierarchies become relatively stable within 2 or 3 days and males that emerge later normally begin at the bottom of the hierarchy regardless of size. Males interact much more frequently when they are simultaneously introduced to each other than when they are allowed to emerge at different times. In the latter case, males that emerge late appear to recognize relative dominance of older males and avoid direct contests. Considering the high correlation between dominance rank and mating success, there is a strong selective advantage to males that emerge earlier and such pressure of sexual selection may be responsible for the difference in life history strategies between Z. gurneyi and its sympatric congener, Z. barberi Gurney, in central Panama.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46901/1/265_2004_Article_BF00183473.pd

Identifying Ligand Binding Conformations of the β2-Adrenergic Receptor by Using Its Agonists as Computational Probes

Recently available G-protein coupled receptor (GPCR) structures and biophysical studies suggest that the difference between the effects of various agonists and antagonists cannot be explained by single structures alone, but rather that the conformational ensembles of the proteins need to be considered. Here we use an elastic network model-guided molecular dynamics simulation protocol to generate an ensemble of conformers of a prototypical GPCR, β2-adrenergic receptor (β2AR). The resulting conformers are clustered into groups based on the conformations of the ligand binding site, and distinct conformers from each group are assessed for their binding to known agonists of β2AR. We show that the select ligands bind preferentially to different predicted conformers of β2AR, and identify a role of β2AR extracellular region as an allosteric binding site for larger drugs such as salmeterol. Thus, drugs and ligands can be used as "computational probes" to systematically identify protein conformers with likely biological significance. © 2012 Isin et al

Electrical switching of vortex core in a magnetic disk

A magnetic vortex is a curling magnetic structure realized in a ferromagnetic disk, which is a promising candidate of a memory cell for future nonvolatile data storage devices. Thus, understanding of the stability and dynamical behaviour of the magnetic vortex is a major requirement for developing magnetic data storage technology. Since the experimental proof of the existence of a nanometre-scale core with out-of-plane magnetisation in the magnetic vortex, the dynamics of a vortex has been investigated intensively. However, the way to electrically control the core magnetisation, which is a key for constructing a vortex core memory, has been lacking. Here, we demonstrate the electrical switching of the core magnetisation by utilizing the current-driven resonant dynamics of the vortex; the core switching is triggered by a strong dynamic field which is produced locally by a rotational core motion at a high speed of several hundred m/s. Efficient switching of the vortex core without magnetic field application is achieved thanks to resonance. This opens up the potentiality of a simple magnetic disk as a building block for spintronic devices like a memory cell where the bit data is stored as the direction of the nanometre-scale core magnetisation.Comment: 20 pages, 4 figures. Supplementary discussion included. Accepted for publication in Nature Material