Persistent activation of transducin by bleached rhodopsin in salamander rods.

The hydrolysis-resistant GTP analogue GTP-gamma-S was introduced into rods isolated from the retina of the salamander Ambystoma tigrinum to study the origin of the persistent excitation induced by intense bleaching illumination. Dialysis of a dark-adapted rod with a whole-cell patch pipette containing 2 mM GTP-gamma-S resulted in a gradual decrease in circulating current. If the rod was first bleached and its sensitivity allowed to stabilize for at least 30 min, then dialysis with GTP-gamma-S produced a much faster current decay. The circulating current could be restored by superfusion with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, suggesting that the decay in current originated from persistent excitation of the phosphodiesterase by transducin bound to GTP-gamma-S. We conclude that the persistent excitation which follows bleaching is likely to involve the GTP-binding protein transducin, which mediates the normal photoresponse. This observation suggests that a form of rhodopsin which persists long after bleaching can activate transducin much as does photoisomerized rhodopsin, although with considerably lower gain

Equivalence of background and bleaching desensitization in isolated rod photoreceptors of the larval tiger salamander.

Psychophysical experiments have shown an equivalence between sensitivity reduction by background light and by bleaches for the human scotopic system. We have compared the effects of backgrounds and bleaches on the light-sensitive membrane-current responses of isolated rod photoreceptors from the salamander Ambystoma tigrinum. The quantum catch loss was factored out from the desensitization due to bleaching to give the fraction of "extra" desensitization due to adaptation. For backgrounds, desensitization is well described by the Weber/Fechner equation. The extra desensitization after bleaches can also be described by the Weber/Fechner equation, if an "equivalent" background produced by bleaching is made linearly proportional to the fraction of pigment bleached. A background which produces an extra desensitization of a factor of two is equivalent to a fractional bleach of approximately 6%. Equivalent background and bleaching desensitizations were associated with similar reductions in circulating current. There is a linear relation between log flash sensitivity and decrease in circulating current. Equivalent background and bleaching desensitizations were associated with similar increases in cGMP phosphodiesterase and guanylate cyclase activity. These were inferred from membrane current changes after steps into lithium or IBMX solutions. There were also similar reductions in the integration times of dim flash responses for equivalent desensitizations produced by backgrounds and bleaches. These results suggest that the equivalence between background and bleaching found psychophysically may arise at the very earliest stages of visual processing and that these two processes of desensitization have similar underlying mechanisms

Bleached pigment activates transduction in salamander cones.

We have used suction electrode recording together with rapid steps into 0.5 mM IBMX solution to investigate changes in guanylyl cyclase velocity produced by pigment bleaching in isolated cones of the salamander Ambystoma tigrinum. Both backgrounds and bleaches accelerate the time course of current increase during steps into IBMX. We interpret this as evidence that the velocity of the guanylyl cyclase is increased in background light or after bleaching. Our results indicate that cyclase velocity increases nearly linearly with increasing percent pigment bleached but nonlinearly (and may saturate) with increasing back-ground intensity. In cones (as previously demonstrated for rods), light-activated pigment and bleached pigment appear to have somewhat different effects on the transduction cascade. The effect of bleaching on cyclase rate is maintained for at least 15-20 min after the light is removed, much longer than is required after a bleach for circulating current and sensitivity to stabilize in an isolated cone. The effect on the cyclase rate can be completely reversed by treatment with liposomes containing 11-cis retinal. The effects of bleaching can also be partially reversed by beta-ionone, an analogue of the chromophore 11-cis-retinal which does not form a covalent attachment to opsin. Perfusion of a bleached cone with beta-ionone produces a rapid increase in circulating current and sensitivity, which rapidly reverses when the beta-ionone is removed. Perfusion with beta-ionone also causes a partial reversal of the bleach-induced acceleration of cyclase velocity. We conclude that bleaching produces an "equivalent background" excitation of the transduction cascade in cones, perhaps by a mechanism similar to that in rods

Neural regions associated with gain-loss frequency and average reward in older and younger adults

Research on the biological basis of reinforcement-learning has focused on how brain regions track expected value based on average reward. However, recent work suggests that humans are more attuned to reward frequency. Furthermore, older adults are less likely to use expected values to guide choice than younger adults. This raises the question of whether brain regions assumed to be sensitive to average reward, like the medial and lateral PFC, also track reward frequency, and whether there are age-based differences. Older (60-81 years) and younger (18-30 years) adults performed the Soochow Gambling task, which separates reward frequency from average reward, while undergoing fMRI. Overall, participants preferred options that provided negative net payoffs, but frequent gains. Older adults improved less over time, were more reactive to recent negative outcomes, and showed greater frequency-related activation in several regions, including DLPFC. We also found broader recruitment of prefrontal and parietal regions associated with frequency value and reward prediction errors in older adults, which may indicate compensation. The results suggest greater reliance on average reward for younger adults than older adults

Inorganic carbon physiology underpins macroalgal responses to elevated CO2

Beneficial effects of CO2 on photosynthetic organisms will be a key driver of ecosystem change under ocean acidification. Predicting the responses of macroalgal species to ocean acidification is complex, but we demonstrate that the response of assemblages to elevated CO2 are correlated with inorganic carbon physiology. We assessed abundance patterns and a proxy for CO2:HCO3- use (\u3b413C values) of macroalgae along a gradient of CO2 at a volcanic seep, and examined how shifts in species abundance at other Mediterranean seeps are related to macroalgal inorganic carbon physiology. Five macroalgal species capable of using both HCO3- and CO2 had greater CO2 use as concentrations increased. These species (and one unable to use HCO3-) increased in abundance with elevated CO2 whereas obligate calcifying species, and non-calcareous macroalgae whose CO2 use did not increase consistently with concentration, declined in abundance. Physiological groupings provide a mechanistic understanding that will aid us in determining which species will benefit from ocean acidification and why

New Constraints (and Motivations) for Abelian Gauge Bosons in the MeV-TeV Mass Range

We survey the phenomenological constraints on abelian gauge bosons having masses in the MeV to multi-GeV mass range (using precision electroweak measurements, neutrino-electron and neutrino-nucleon scattering, electron and muon anomalous magnetic moments, upsilon decay, beam dump experiments, atomic parity violation, low-energy neutron scattering and primordial nucleosynthesis). We compute their implications for the three parameters that in general describe the low-energy properties of such bosons: their mass and their two possible types of dimensionless couplings (direct couplings to ordinary fermions and kinetic mixing with Standard Model hypercharge). We argue that gauge bosons with very small couplings to ordinary fermions in this mass range are natural in string compactifications and are likely to be generic in theories for which the gravity scale is systematically smaller than the Planck mass - such as in extra-dimensional models - because of the necessity to suppress proton decay. Furthermore, because its couplings are weak, in the low-energy theory relevant to experiments at and below TeV scales the charge gauged by the new boson can appear to be broken, both by classical effects and by anomalies. In particular, if the new gauge charge appears to be anomalous, anomaly cancellation does not also require the introduction of new light fermions in the low-energy theory. Furthermore, the charge can appear to be conserved in the low-energy theory, despite the corresponding gauge boson having a mass. Our results reduce to those of other authors in the special cases where there is no kinetic mixing or there is no direct coupling to ordinary fermions, such as for recently proposed dark-matter scenarios.Comment: 49 pages + appendix, 21 figures. This is the final version which appears in JHE

Investigation of first ray mobility during gait by kinematic fluoroscopic imaging-a novel method

<p>Abstract</p> <p>Background</p> <p>It is often suggested that sagittal instability at the first tarso-metatarsal joint level is a primary factor for hallux valgus and that sagittal instability increases with the progression of the deformity. The assessment of the degree of vertical instability is usually made by clinical evaluation while any measurements mostly refer to a static assessment of medial ray mobility (i.e. the plantar/dorsal flexion in the sagittal plane). Testing methods currently available cannot attribute the degree of mobility to the corresponding anatomical joints making up the medial column of the foot. The aim of this study was to develop a technique which allows for a quantification of the in-vivo sagittal mobility of the joints of the medial foot column during the roll-over process under full weight bearing.</p> <p>Methods</p> <p>Mobility of first ray bones was investigated by dynamic distortion-free fluoroscopy (25 frames/s) of 14 healthy volunteers and 8 patients with manifested clinical instability of the first ray. A CAD-based evaluation method allowed the determination of mobility and relative displacements and rotations of the first ray bones within the sagittal plane during the stance phase of gait.</p> <p>Results</p> <p>Total flexion of the first ray was found to be 13.63 (SD 6.14) mm with the healthy volunteers and 13.06 (SD 8.01) mm with the patients (resolution: 0.245 mm/pixel). The dorsiflexion angle was 5.27 (SD 2.34) degrees in the healthy volunteers and increased to 5.56 (SD 3.37) degrees in the patients. Maximum rotations were found at the naviculo-cuneiform joints and least at the first tarso-metatarsal joint level in both groups.</p> <p>Conclusions</p> <p>Dynamic fluoroscopic assessment has been shown to be a valuable tool for characterisation of the kinematics of the joints of the medial foot column during gait.</p> <p>A significant difference in first ray flexion and angular rotation between the patients and healthy volunteers however could not be found.</p

Purification and Characterization of a Sperm Motility Inhibiting Factor from Caprine Epididymal Plasma

Several studies have been reported on the occurrence of sperm motility inhibiting factors in the male reproductive fluids of different mammalian species, but these proteins have not been adequately purified and characterized. A novel sperm motility inhibiting factor (MIF-II) has been purified from caprine epididymal plasma (EP) by Hydroxylapatite gel adsorption chromatography, DEAE-Cellulose ion-exchange chromatography and chromatofocusing. The MIF-II has been purified to apparent homogeneity and the molecular weight estimated by Sephacryl S-300 gel filtration is 160 kDa. MIF-II is a dimeric protein, made up of two subunits each having a molecular mass of 80 kDa as shown by SDS-PAGE. The isoelectric point of MIF-II is 5.1 as determined by chromatofocusing and isoelectric focusing. It is a heat labile protein and maximal active at the pH 6.9 to 7.5. The sperm motility inhibiting protein factor at 2 µg/ml (12.5 nM) level showed maximal motility-inhibiting activity. The observation that the epididymal plasma factor lowered the intracellular cAMP level of spermatozoa in a concentration-dependent manner suggests that it may block the motility of caprine cauda spermatozoa by interfering the cAMP dependent motility function. The results revealed that the purified protein factor has the potential of sperm motility inhibition and may serve as a vaginal contraceptive. The antibody raised against the MIF-II has the potential for enhancement of forward motility of cauda-spermatozoa. This antibody may thus be useful for solving some of the problems of male infertility due to low sperm motility