Reconciling transport models across scales: the role of volume exclusion

Diffusive transport is a universal phenomenon, throughout both biological and physical sciences, and models of diffusion are routinely used to interrogate diffusion-driven processes. However, most models neglect to take into account the role of volume exclusion, which can significantly alter diffusive transport, particularly within biological systems where the diffusing particles might occupy a significant fraction of the available space. In this work we use a random walk approach to provide a means to reconcile models that incorporate crowding effects on different spatial scales. Our work demonstrates that coarse-grained models incorporating simplified descriptions of excluded volume can be used in many circumstances, but that care must be taken in pushing the coarse-graining process too far

Comparing consistency of stress and anxiety-related behaviors across time in zebrafish (Danio rerio)

Animals are frequently faced with stressors in their environment that they must overcome to survive and reproduce. Across vertebrates, two distinct stress coping styles or ‘personalities’ have been observed known as proactive (bold) and reactive (shy). Animal personalities may be advantageous by limiting individual variation and balancing different trade-offs in unpredictable environments. When identifying animal personalities, behavioral phenotypes must be consistent and repeatable across contexts and time. Here we use selectively bred lines of shy and bold zebrafish, previously shown to have consistent divergent fear- and anxiety-related behaviors across contexts, to test the repeatability and consistency of these behaviors across time exploring a novel environment. We find that each strain displays significantly different amounts of stationary time in the open field test. Overall the zebrafish personalities were highly repeatable across a 5 week period. Selectively bred individuals were more consistent than a wild caught strain with shy being more consistent than bold. We also examined the effects of sex on these behaviors. Contrary to prior studies, there were no significant differences in freezing time between sexes, though males and females were relatively consistent with females slightly higher. These results show the usefulness of our selectively-bred lines for animal personality research and specifically stress and anxiety-like behaviors. Differences in repeatability or consistency between coping styles may reflect the degree of selection being placed on individuals or the specific behavior

Contextual fear learning and memory differ between stress coping styles in zebrafish

Animals frequently overcome stressors and the ability to learn and recall these salient experiences is essential to an individual’s survival. As part of an animal’s stress coping style, behavioral and physiological responses to stressors are often consistent across contexts and time. However, we are only beginning to understand how cognitive traits can be biased by different coping styles. Here we investigate learning and memory differences in zebrafish (Danio rerio) displaying proactive and reactive stress coping styles. We assessed learning rate and memory duration using an associative fear conditioning paradigm that trained zebrafish to associate a context with exposure to a natural olfactory alarm cue. Our results show that both proactive and reactive zebrafish learn and remember this fearful association. However, we note significant interaction effects between stress coping style and cognition. Zebrafish with the reactive stress coping style acquired the fear memory at a significantly faster rate than proactive fish. While both stress coping styles showed equal memory recall one day postconditioning, reactive zebrafish showed significantly stronger recall of the conditioned context relative to proactive fish four days post-conditioning. Through understanding how stress coping strategies promote biases in processing salient information, we gain insight into mechanisms that can constrain adaptive behavioral responses

Antagonism of GABA-B but not GABA-A receptors in the VTA prevents stress- and intra-VTA CRF-induced reinstatement of extinguished cocaine seeking in rats

Stress-induced reinstatement of cocaine seeking requires corticotropin releasing factor (CRF) actions in the ventral tegmental area (VTA). However the mechanisms through which CRF regulates VTA function to promote cocaine use are not fully understood. Here we examined the role of GABAergic neurotransmission in the VTA mediated by GABA-A or GABA-B receptors in the reinstatement of extinguished cocaine seeking by a stressor, uncontrollable intermittent footshock, or bilateral intra-VTA administration of CRF. Rats underwent repeated daily cocaine self-administration (1.0 mg/kg/ing; 14 × 6 h/day) and extinction and were tested for reinstatement in response to footshock (0.5 mA, 0.5” duration, average every 40 s; range 10–70 s) or intra-VTA CRF delivery (500 ng/side) following intra-VTA pretreatment with the GABA-A antagonist, bicuculline, the GABA-B antagonist, 2-hydroxysaclofen or vehicle. Intra-VTA bicuculline (1, 10 or 20 ng/side) failed to block footshock- or CRF-induced cocaine seeking at either dose tested. By contrast, 2-hydroxysaclofen (0.2 or 2 μg/side) prevented reinstatement by both footshock and intra-VTA CRF at a concentration that failed to attenuate food-reinforced lever pressing (45 mg sucrose-sweetened pellets; FR4 schedule) in a separate group of rats. These data suggest that GABA-B receptor-dependent CRF actions in the VTA mediate stress-induced cocaine seeking and that GABA-B receptor antagonists may have utility for the management of stress-induced relapse in cocaine addicts

Repeated \u3cem\u3eN\u3c/em\u3e-Acetylcysteine Administration Alters Plasticity-Dependent Effects of Cocaine

Cocaine produces a persistent reduction in cystine–glutamate exchange via system xc− in the nucleus accumbens that may contribute to pathological glutamate signaling linked to addiction. System xc− influences glutamate neurotransmission by maintaining basal, extracellular glutamate in the nucleus accumbens, which, in turn, shapes synaptic activity by stimulating group II metabotropic glutamate autoreceptors. In the present study, we tested the hypothesis that a long-term reduction in system xc− activity is part of the plasticity produced by repeated cocaine that results in the establishment of compulsive drug seeking. To test this, the cysteine prodrug N-acetylcysteine was administered before daily cocaine to determine the impact of increased cystine–glutamate exchange on the development of plasticity-dependent cocaine seeking. Although N-acetylcysteine administered before cocaine did not alter the acute effects of cocaine on self-administration or locomotor activity, it prevented behaviors produced by repeated cocaine including escalation of drug intake, behavioral sensitization, and cocaine-primed reinstatement. Because sensitization or reinstatement was not evident even 2–3 weeks after the last injection of N-acetylcysteine, we examined whether N-acetylcysteine administered before daily cocaine also prevented the persistent reduction in system xc− activity produced by repeated cocaine. Interestingly, N-acetylcysteine pretreatment prevented cocaine-induced changes in [35S]cystine transport via system xc−, basal glutamate, and cocaine-evoked glutamate in the nucleus accumbens when assessed at least 3 weeks after the last N-acetylcysteine pretreatment. These findings indicate that N-acetylcysteine selectively alters plasticity-dependent behaviors and that normal system xc− activity prevents pathological changes in extracellular glutamate that may be necessary for compulsive drug seeking

Adjustable microchip ring trap for cold atoms and molecules

We describe the design and function of a circular magnetic waveguide produced from wires on a microchip for atom interferometry using deBroglie waves. The guide is a two-dimensional magnetic minimum for trapping weak-field seeking states of atoms or molecules with a magnetic dipole moment. The design consists of seven circular wires sharing a common radius. We describe the design, the time-dependent currents of the wires and show that it is possible to form a circular waveguide with adjustable height and gradient while minimizing perturbation resulting from leads or wire crossings. This maximal area geometry is suited for rotation sensing with atom interferometry via the Sagnac effect using either cold atoms, molecules and Bose-condensed systems

Functionalising the azobenzene motif delivers a light-responsive membrane-interactive compound with the potential for photodynamic therapy applications

When adorned with n-octyl chains azobenzene is able to disrupt a variety of calcein-loaded phospholipid liposomes. The levels of lysis observed are dependent both on the lipid headgroup and the conformation of the azobenzene compound. In all cases studied, it has been shown that the cis-conformer is more membrane-interactive than the trans-conformer, suggesting that this class of molecule could be optimised for photo-dynamic therapy applications against infectious pathogens

Fluxes and distribution of dissolved iron in the eastern (sub-) tropical North Atlantic Ocean

Aeolian dust transport from the Saharan/Sahel desert regions is considered the dominant external input of iron (Fe) to the surface waters of the eastern (sub-) tropical North Atlantic Ocean. To test this hypothesis, we investigated the sources of dissolved Fe (DFe) and quantified DFe fluxes to the surface ocean in this region. In winter 2008, surface water DFe concentrations varied between <0.1 nM and 0.37 nM, with an average of 0.13 ± 0.07 nM DFe (n = 194). A strong correlation between mixed layer averaged concentrations of dissolved aluminum (DAl), a proxy for dust input, and DFe indicated dust as a source of DFe to the surface ocean. The importance of Aeolian nutrient input was further confirmed by an increase of 0.1 nM DFe and 0.05 ?M phosphate during a repeat transect before and after a dust event. An exponential decrease of DFe with increasing distance from the African continent, suggested that continental shelf waters were a source of DFe to the northern part of our study area. Relatively high Fe:C ratios of up to 3 × 10?5 (C derived from apparent oxygen utilization (AOU)) indicated an external source of Fe to these African continental shelf waters. Below the wind mixed layer along 12°N, enhanced DFe concentrations (>1.5 nM) correlated positively with apparent oxygen utilization (AOU) and showed the importance of organic matter remineralization as an DFe source. As a consequence, vertical diffusive mixing formed an important Fe flux to the surface ocean in this region, even surpassing that of a major dust event