Sub-Second Dopamine Detection in Human Striatum

Fast-scan cyclic voltammetry at carbon fiber microelectrodes allows rapid (sub-second) measurements of dopamine release in behaving animals. Herein, we report the modification of existing technology and demonstrate the feasibility of making sub-second measurements of dopamine release in the caudate nucleus of a human subject during brain surgery. First, we describe the modification of our electrodes that allow for measurements to be made in a human brain. Next, we demonstrate in vitro and in vivo, that our modified electrodes can measure stimulated dopamine release in a rat brain equivalently to previously determined rodent electrodes. Finally, we demonstrate acute measurements of dopamine release in the caudate of a human patient during DBS electrode implantation surgery. The data generated are highly amenable for future work investigating the relationship between dopamine levels and important decision variables in human decision-making tasks

Mineral analysis of complete dog and cat foods in the UK and compliance with European guidelines

Mineral content of complete pet food is regulated to ensure health of the companion animal population. Analysis of adherence to these regulatory guidelines has not been conducted. Here, mineral composition of complete wet (n = 97) and dry (n = 80) canine and feline pet food sold in the UK was measured to assess compliance with EU guidelines. A majority of foods complied with ≥8 of 11 guidelines (99% and 83% for dry and wet food, respectively), but many failed to provide nutritional minimum (e.g. Cu, 20% of wet food) or exceeded nutritional maximum (e.g. Se, 76% of wet food). Only 6% (6/97) of wet and 38% (30/80) of dry food were fully compliant. Some foods (20–30% of all analysed) had mineral imbalance, such as not having the recommended ratio of Ca:P (between 1:1 to 2:1). Foods with high fish content had high levels of undesirable metal elements such as arsenic. This study highlights broad non-compliance of a range of popular pet foods sold in the UK with EU guidelines (94% and 61% of wet and dry foods, respectively). If fed exclusively and over an extended period, a number of these pet foods could impact the general health of companion animals

Rhesus macaques as a tractable physiological model of human ageing

This is the author accepted manuscript. The final version is available from the Royal Society via the DOI in this recordResearch in the basic biology of ageing is increasingly identifying mechanisms and modifiers of ageing in short-lived organisms such as worms and mice. The ultimate goal of such work is to improve human health, particularly in the growing segment of the population surviving into old age. Thus far, few interventions have robustly transcended species boundaries in the laboratory, suggesting that changes in approach are needed to avoid costly failures in translational human research. In this review, we discuss both well-established and alternative model organisms for ageing research and outline how research in nonhuman primates is sorely needed, first, to translate findings from shorter-lived organisms to humans, and second, to understand key aspects of ageing that are unique to primate biology. We focus on rhesus macaques as a particularly promising model organism for ageing research due to their social and physiological similarity to humans as well as the existence of key resources that have been developed for this species. As a case study, we compare gene regulatory signatures of ageing in the peripheral immune system between humans and rhesus macaques from a free-ranging study population in Cayo Santiago. We show that both mRNA expression and DNA methylation signatures of immune ageing are broadly shared between macaques and humans, indicating strong conservation of the trajectory of ageing in the immune system. We conclude with a review of key issues in the biology of ageing for which macaques and other nonhuman primates may uniquely contribute valuable insights, including the effects of social gradients on health and ageing. We anticipate that continuing research in rhesus macaques and other nonhuman primates will play a critical role in conjunction with model organism and human biodemographic research in ultimately improving translational outcomes and extending health and longevity in our ageing population.National Institutes of Health (NIH

Assessing the Quality of Care for Pneumonia in Integrated Community Case Management: A Cross-Sectional Mixed Methods Study

Background Pneumonia is the leading infectious cause of mortality in children under five worldwide. Community-level interventions, such as integrated community case management, have great potential to reduce the burden of pneumonia, as well as other diseases, especially in remote populations. However, there are still questions as to whether community health workers (CHW) are able to accurately assess symptoms of pneumonia and prescribe appropriate treatment. This research addresses limitations of previous studies using innovative methodology to assess the accuracy of respiratory rate measurement by CHWs and provides new evidence on the quality of care given for children with symptoms of pneumonia. It is one of few that assesses CHW performance in their usual setting, with independent re-examination by experts, following a considerable period of time post-training of CHWs. Methods In this cross-sectional mixed methods study, 1,497 CHW consultations, conducted by 90 CHWs in two districts of Luapula province, Zambia, were directly observed, with measurement of respiratory rate for children with suspected pneumonia recorded by video. Using the video footage, a retrospective reference standard assessment of respiratory rate was conducted by experts. Counts taken by CHWs were compared against the reference standard and appropriateness of the treatment prescribed by CHWs was assessed. To supplement observational findings, three focus group discussions and nine in depth interviews with CHWs were conducted. Results and Conclusion The findings support existing literature that CHWs are capable of measuring respiratory rates and providing appropriate treatment, with 81% and 78% agreement, respectively, between CHWs and experts. Accuracy in diagnosis could be strengthened through further training and the development of improved diagnostic tools appropriate for resource-poor settings

Complete Genome Viral Phylogenies Suggests the Concerted Evolution of Regulatory Cores and Accessory Satellites

We consider the concerted evolution of viral genomes in four families of DNA viruses. Given the high rate of horizontal gene transfer among viruses and their hosts, it is an open question as to how representative particular genes are of the evolutionary history of the complete genome. To address the concerted evolution of viral genes, we compared genomic evolution across four distinct, extant viral families. For all four viral families we constructed DNA-dependent DNA polymerase-based (DdDp) phylogenies and in addition, whole genome sequence, as quantitative descriptions of inter-genome relationships. We found that the history of the polymerase gene was highly predictive of the history of the genome as a whole, which we explain in terms of repeated, co-divergence events of the core DdDp gene accompanied by a number of satellite, accessory genetic loci. We also found that the rate of gene gain in baculovirus and poxviruses proceeds significantly more quickly than the rate of gene loss and that there is convergent acquisition of satellite functions promoting contextual adaptation when distinct viral families infect related hosts. The congruence of the genome and polymerase trees suggests that a large set of viral genes, including polymerase, derive from a phylogenetically conserved core of genes of host origin, secondarily reinforced by gene acquisition from common hosts or co-infecting viruses within the host. A single viral genome can be thought of as a mutualistic network, with the core genes acting as an effective host and the satellite genes as effective symbionts. Larger virus genomes show a greater departure from linkage equilibrium between core and satellites functions

Super-Resolution Dynamic Imaging of Dendritic Spines Using a Low-Affinity Photoconvertible Actin Probe

The actin cytoskeleton of dendritic spines plays a key role in morphological aspects of synaptic plasticity. The detailed analysis of the spine structure and dynamics in live neurons, however, has been hampered by the diffraction-limited resolution of conventional fluorescence microscopy. The advent of nanoscopic imaging techniques thus holds great promise for the study of these processes. We implemented a strategy for the visualization of morphological changes of dendritic spines over tens of minutes at a lateral resolution of 25 to 65 nm. We have generated a low-affinity photoconvertible probe, capable of reversibly binding to actin and thus allowing long-term photoactivated localization microscopy of the spine cytoskeleton. Using this approach, we resolve structural parameters of spines and record their long-term dynamics at a temporal resolution below one minute. Furthermore, we have determined changes in the spine morphology in response to pharmacologically induced synaptic activity and quantified the actin redistribution underlying these changes. By combining PALM imaging with quantum dot tracking, we could also simultaneously visualize the cytoskeleton and the spine membrane, allowing us to record complementary information on the morphological changes of the spines at super-resolution

An Imperfect Dopaminergic Error Signal Can Drive Temporal-Difference Learning

An open problem in the field of computational neuroscience is how to link synaptic plasticity to system-level learning. A promising framework in this context is temporal-difference (TD) learning. Experimental evidence that supports the hypothesis that the mammalian brain performs temporal-difference learning includes the resemblance of the phasic activity of the midbrain dopaminergic neurons to the TD error and the discovery that cortico-striatal synaptic plasticity is modulated by dopamine. However, as the phasic dopaminergic signal does not reproduce all the properties of the theoretical TD error, it is unclear whether it is capable of driving behavior adaptation in complex tasks. Here, we present a spiking temporal-difference learning model based on the actor-critic architecture. The model dynamically generates a dopaminergic signal with realistic firing rates and exploits this signal to modulate the plasticity of synapses as a third factor. The predictions of our proposed plasticity dynamics are in good agreement with experimental results with respect to dopamine, pre- and post-synaptic activity. An analytical mapping from the parameters of our proposed plasticity dynamics to those of the classical discrete-time TD algorithm reveals that the biological constraints of the dopaminergic signal entail a modified TD algorithm with self-adapting learning parameters and an adapting offset. We show that the neuronal network is able to learn a task with sparse positive rewards as fast as the corresponding classical discrete-time TD algorithm. However, the performance of the neuronal network is impaired with respect to the traditional algorithm on a task with both positive and negative rewards and breaks down entirely on a task with purely negative rewards. Our model demonstrates that the asymmetry of a realistic dopaminergic signal enables TD learning when learning is driven by positive rewards but not when driven by negative rewards

Quantifying bioirrigation using ecological parameters: a stochastic approach†

Irrigation by benthic macrofauna has a major influence on the biogeochemistry and microbial community structure of sediments. Existing quantitative models of bioirrigation rely primarily on chemical, rather than ecological, information and the depth-dependence of bioirrigation intensity is either imposed or constrained through a data fitting procedure. In this study, stochastic simulations of 3D burrow networks are used to calculate mean densities, volumes and wall surface areas of burrows, as well as their variabilities, as a function of sediment depth. Burrow networks of the following model organisms are considered: the polychaete worms Nereis diversicolor and Schizocardium sp., the shrimp Callianassa subterranea, the echiuran worm Maxmuelleria lankesteri, the fiddler crabs Uca minax, U. pugnax and U. pugilator, and the mud crabs Sesarma reticulatum and Eurytium limosum. Consortia of these model organisms are then used to predict burrow networks in a shallow water carbonate sediment at Dry Tortugas, FL, and in two intertidal saltmarsh sites at Sapelo Island, GA. Solute-specific nonlocal bioirrigation coefficients are calculated from the depth-dependent burrow surface areas and the radial diffusive length scale around the burrows. Bioirrigation coefficients for sulfate obtained from network simulations, with the diffusive length scales constrained by sulfate reduction rate profiles, agree with independent estimates of bioirrigation coefficients based on pore water chemistry. Bioirrigation coefficients for O(2 )derived from the stochastic model, with the diffusion length scales constrained by O(2 )microprofiles measured at the sediment/water interface, are larger than irrigation coefficients based on vertical pore water chemical profiles. This reflects, in part, the rapid attenuation with depth of the O(2 )concentration within the burrows, which reduces the driving force for chemical transfer across the burrow walls. Correction for the depletion of O(2 )in the burrows results in closer agreement between stochastically-derived and chemically-derived irrigation coefficient profiles

Adolescent Engagement in Dangerous Behaviors Is Associated with Increased White Matter Maturity of Frontal Cortex

Background: Myelination of white matter in the brain continues throughout adolescence and early adulthood. This cortical immaturity has been suggested as a potential cause of dangerous and impulsive behaviors in adolescence. Methodology/Principal Findings: We tested this hypothesis in a group of healthy adolescents, age 12–18 (N = 91), who underwent diffusion tensor imaging (DTI) to delineate cortical white matter tracts. As a measure of real-world risk taking, participants completed the Adolescent Risk Questionnaire (ARQ) which measures engagement in dangerous activities. After adjusting for age-related changes in both DTI and ARQ, engagement in dangerous behaviors was found to be positively correlated with fractional anisotropy and negatively correlated with transverse diffusivity in frontal white matter tracts, indicative of increased myelination and/or density of fibers (ages 14–18, N = 60). Conclusions/Significance: The direction of correlation suggests that rather than having immature cortices, adolescents who engage in dangerous activities have frontal white matter tracts that are more adult in form than their more conservative peers

Invasive Plants and Enemy Release: Evolution of Trait Means and Trait Correlations in Ulex europaeus

Several hypotheses that attempt to explain invasive processes are based on the fact that plants have been introduced without their natural enemies. Among them, the EICA (Evolution of Increased Competitive Ability) hypothesis is the most influential. It states that, due to enemy release, exotic plants evolve a shift in resource allocation from defence to reproduction or growth. In the native range of the invasive species Ulex europaeus, traits involved in reproduction and growth have been shown to be highly variable and genetically correlated. Thus, in order to explore the joint evolution of life history traits and susceptibility to seed predation in this species, we investigated changes in both trait means and trait correlations. To do so, we compared plants from native and invaded regions grown in a common garden. According to the expectations of the EICA hypothesis, we observed an increase in seedling height. However, there was little change in other trait means. By contrast, correlations exhibited a clear pattern: the correlations between life history traits and infestation rate by seed predators were always weaker in the invaded range than in the native range. In U. europaeus, the role of enemy release in shaping life history traits thus appeared to imply trait correlations rather than trait means. In the invaded regions studied, the correlations involving infestation rates and key life history traits such as flowering phenology, growth and pod density were reduced, enabling more independent evolution of these key traits and potentially facilitating local adaptation to a wide range of environments. These results led us to hypothesise that a relaxation of genetic correlations may be implied in the expansion of invasive species