AAV-mediated ERdj5 overexpression protects against P23H rhodopsin toxicity

Rhodopsin misfolding caused by the P23H mutation is a major cause of autosomal dominant retinitis pigmentosa (adRP), to date there are no effective treatments for adRP. The BiP co-chaperone and reductase ERdj5 (DNAJC10) is part of the ER quality control machinery and previous studies have shown that overexpression of ERdj5 in vitro enhanced the degradation of P23H rhodopsin; whereas knockdown of ERdj5 increased P23H rhodopsin ER retention and aggregation. Here, we investigated the role of ERdj5 in photoreceptor homeostasis in vivo by using an Erdj5 knock-out mouse crossed with the P23H knock-in mouse, and by adeno associated viral (AAV) vector-mediated gene augmentation of ERdj5 in P23H-3 rats. Electroretinogram (ERG) and optical coherence tomography (OCT) of Erdj5−/− and P23H+/−:Erdj5−/− mice showed no effect of ERdj5 ablation on retinal function or photoreceptor survival. Rhodopsin levels and localisation were similar to those of control animals at a range of time points. By contrast, when AAV2/8-ERdj5-HA was subretinally injected into P23H-3 rats, analysis of the full field ERG suggested that overexpression of ERdj5 reduced visual function loss 10 weeks post-injection. This correlated with a significant preservation of photoreceptor cells at 4 and 10 weeks post-injection. Assessment of the outer nuclear layer (ONL) morphology showed preserved ONL thickness and reduced rhodopsin retention in the ONL in the injected superior retina. Overall, these data suggest that manipulation of the ER quality control and ERAD factors to promote mutant protein degradation could be beneficial for the treatment of adRP caused by mutant rhodopsin

Melanopsin as a Sleep Modulator: Circadian Gating of the Direct Effects of Light on Sleep and Altered Sleep Homeostasis in Opn4−/− Mice

Analyses in mice deficient for the blue-light-sensitive photopigment melanopsin show that direct effects of light on behavior and EEG depend on the time of day. The data further suggest an unexpected role for melanopsin in sleep homeostasis

Determinants of change in subtropical tree diameter growth with ontogenetic stage

We evaluated the degree to which relative growth rate (RGR) of saplings and large trees is related to seven functional traits that describe physiological behavior and soil environmental factors related to topography and fertility for 57 subtropical tree species in Dinghushan, China. The mean values of functional traits and soil environmental factors for each species that were related to RGR varied with ontogenetic stage. Sapling RGR showed greater relationships with functional traits than large-tree RGR, whereas large-tree RGR was more associated with soil environment than was sapling RGR. The strongest single predictors of RGR were wood density for saplings and slope aspect for large trees. The stepwise regression model for large trees accounted for a larger proportion of variability (R 2 = 0.95) in RGR than the model for saplings (R 2 = 0.55). Functional diversity analysis revealed that the process of habitat filtering likely contributes to the substantial changes in regulation of RGR as communities transition from saplings to large trees. © 2014 Springer-Verlag Berlin Heidelberg

Computational Models of Classical Conditioning guest editors’ introduction

In the present special issue, the performance of current computational models of classical conditioning was evaluated under three requirements: (1) Models were to be tested against a list of previously agreed-upon phenomena; (2) the parameters were fixed across simulations; and (3) the simulations used to test the models had to be made available. These requirements resulted in three major products: (a) a list of fundamental classical-conditioning results for which there is a consensus about their reliability; (b) the necessary information to evaluate each of the models on the basis of its ordinal successes in accounting for the experimental data; and (c) a repository of computational models ready to generate simulations. We believe that the contents of this issue represent the 2012 state of the art in computational modeling of classical conditioning and provide a way to find promising avenues for future model development

Integrated monitoring of mola mola behaviour in space and time

Over the last decade, ocean sunfish movements have been monitored worldwide using various satellite tracking methods. This study reports the near-real time monitoring of finescale (< 10 m) behaviour of sunfish. The study was conducted in southern Portugal in May 2014 and involved satellite tags and underwater and surface robotic vehicles to measure both the movements and the contextual environment of the fish. A total of four individuals were tracked using custom-made GPS satellite tags providing geolocation estimates of fine-scale resolution. These accurate positions further informed sunfish areas of restricted search (ARS), which were directly correlated to steep thermal frontal zones. Simultaneously, and for two different occasions, an Autonomous Underwater Vehicle (AUV) videorecorded the path of the tracked fish and detected buoyant particles in the water column. Importantly, the densities of these particles were also directly correlated to steep thermal gradients. Thus, both sunfish foraging behaviour (ARS) and possibly prey densities, were found to be influenced by analogous environmental conditions. In addition, the dynamic structure of the water transited by the tracked individuals was described by a Lagrangian modelling approach. The model informed the distribution of zooplankton in the region, both horizontally and in the water column, and the resultant simulated densities positively correlated with sunfish ARS behaviour estimator (r(s) = 0.184, p < 0.001). The model also revealed that tracked fish opportunistically displace with respect to subsurface current flow. Thus, we show how physical forcing and current structure provide a rationale for a predator's finescale behaviour observed over a two weeks in May 2014

Wound dressings for a proteolytic-rich environment

Wound dressings have experienced continuous and significant changes over the years based on the knowledge of the biochemical events associated with chronic wounds. The development goes from natural materials used to just cover and conceal the wound to interactive materials that can facilitate the healing process, addressing specific issues in non-healing wounds. These new types of dressings often relate with the proteolytic wound environment and the bacteria load to enhance the healing. Recently, the wound dressing research is focusing on the replacement of synthetic polymers by natural protein materials to delivery bioactive agents to the wounds. This article provides an overview on the novel protein-based wound dressings such as silk fibroin keratin and elastin. The improved properties of these dressings, like the release of antibiotics and growth factors, are discussed. The different types of wounds and the effective parameters of healing process will be reviewed

A collaboratively-derived science-policy research agenda

The need for policy makers to understand science and for scientists to understand policy processes is widely recognised. However, the science-policy relationship is sometimes difficult and occasionally dysfunctional; it is also increasingly visible, because it must deal with contentious issues, or itself becomes a matter of public controversy, or both. We suggest that identifying key unanswered questions on the relationship between science and policy will catalyse and focus research in this field. To identify these questions, a collaborative procedure was employed with 52 participants selected to cover a wide range of experience in both science and policy, including people from government, non-governmental organisations, academia and industry. These participants consulted with colleagues and submitted 239 questions. An initial round of voting was followed by a workshop in which 40 of the most important questions were identified by further discussion and voting. The resulting list includes questions about the effectiveness of science-based decision-making structures; the nature and legitimacy of expertise; the consequences of changes such as increasing transparency; choices among different sources of evidence; the implications of new means of characterising and representing uncertainties; and ways in which policy and political processes affect what counts as authoritative evidence. We expect this exercise to identify important theoretical questions and to help improve the mutual understanding and effectiveness of those working at the interface of science and policy

Nitrogen stable isotopes indicate differences in nitrogen cycling between two contrasting Jamaican montane forests

Background and aims The aim of this study is to enhance our knowledge of nitrogen (N) cycling and N acquisition in tropical montane forests through analysis of stable N isotopes (δ15N). Methods Leaves from eight common tree species, leaf litter, soils from three depths and roots were sampled from two contrasting montane forest types in Jamaica (mull ridge and mor ridge) and were analysed for δ15N. Results All foliar δ15N values were negative and varied among the tree species but were significantly more negative in the mor ridge forest (by about 2 ‰). δ15N of soils and roots were also more negative in mor ridge forests by about 3 ‰. Foliar δ15N values were closer to that of soil ammonium than soil nitrate suggesting that trees in these forests may have a preference for ammonium; this may explain the high losses of nitrate from similar tropical montane forests. There was no correlation between the rankings of foliar δ15N in the two forest types suggesting a changing uptake ratio of different N forms between forest types. Conclusions These results indicate that N is found at low concentrations in this ecosystem and that there is a tighter N cycle in the mor ridge forest, confirmed by reduced nitrogen availability and lower rates of nitrification. Overall, soil or root δ15N values are more useful in assessing ecosystem N cycling patterns as different tree species showed differences in foliar δ15N between the two forest types