Reward learning and working memory: Effects of massed versus spaced training and post-learning delay period

Neuroscience research has illuminated the mechanisms supporting learning from reward feedback, demonstrating a critical role for the striatum and midbrain dopamine system. However, in humans, short-term working memory that is dependent on frontal and parietal cortices can also play an important role, particularly in commonly used paradigms in which learning is relatively condensed in time. Given the growing use of reward-based learning tasks in translational studies in computational psychiatry, it is important to understand the extent of the influence of working memory and also how core gradual learning mechanisms can be better isolated. In our experiments, we manipulated the spacing between repetitions along with a post-learning delay preceding a test phase. We found that learning was slower for stimuli repeated after a long delay (spaced-trained) compared to those repeated immediately (massed-trained), likely reflecting the remaining contribution of feedback learning mechanisms when working memory is not available. For massed learning, brief interruptions led to drops in subsequent performance, and individual differences in working memory capacity positively correlated with overall performance. Interestingly, when tested after a delay period but not immediately, relative preferences decayed in the massed condition and increased in the spaced condition. Our results provide additional support for a large role of working memory in reward-based learning in temporally condensed designs. We suggest that spacing training within or between sessions is a promising approach to better isolate and understand mechanisms supporting gradual reward-based learning, with particular importance for understanding potential learning dysfunctions in addiction and psychiatric disorders

Application of the Aquifer Impact Model to support decisions at a CO2 sequestration site

The National Risk Assessment Partnership (NRAP) has developed a suite of tools to assess and manage risk at CO sequestration sites. The NRAP tool suite includes the Aquifer Impact Model (AIM), which evaluates the potential for groundwater impacts from leaks of CO and brine through abandoned wellbores. There are two aquifer reduced-order models (ROMs) included with the AIM tool, a confined alluvium aquifer, and an unconfined carbonate aquifer. The models accept aquifer parameters as a range of variable inputs so they may have broad applicability. The generic aquifer models may be used at the early stages of site selection, when site-specific data is not available. Guidelines have been developed for determining when the generic ROMs might be applicable to a new site. This paper considers the application of the AIM to predicting the impact of CO or brine leakage were it to occur at the Illinois Basin Decatur Project (IBDP). Results of the model sensitivity analysis can help guide characterization efforts; the hydraulic parameters and leakage source term magnitude are more sensitive than clay fraction or cation exchange capacity. Sand permeability was the only hydraulic parameter measured at the IBDP site. More information on the other hydraulic parameters could reduce uncertainty in risk estimates. Some non-adjustable parameters are significantly different for the ROM than for the observations at the IBDP site. The generic ROMs could be made more useful to a wider range of sites if the initial conditions and no-impact threshold values were adjustable parameters. © 2017 Society of Chemical Industry and John Wiley & Sons, Ltd. 2 2

An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly

Erythropoetin-producing hepatoma (Eph) receptors are cell-surface protein tyrosine kinases mediating cell-cell communication. Upon activation, they form signaling clusters. We report crystal structures of the full ectodomain of human EphA2 (eEphA2) both alone and in complex with the receptor-binding domain of the ligand ephrinA5 (ephrinA5 RBD). Unliganded eEphA2 forms linear arrays of staggered parallel receptors involving two patches of residues conserved across A-class Ephs. eEphA2-ephrinA5 RBD forms a more elaborate assembly, whose interfaces include the same conserved regions on eEphA2, but rearranged to accommodate ephrinA5 RBD. Cell-surface expression of mutant EphA2s showed that these interfaces are critical for localization at cell-cell contacts and activation-dependent degradation. Our results suggest a 'nucleation' mechanism whereby a limited number of ligand-receptor interactions 'seed' an arrangement of receptors which can propagate into extended signaling arrays

Orbital interactions and chemical reactivity of metal particles and metal surfaces

A review is presented with 101 refs. on chem. bonding to metal surfaces and small metal particles demonstrating the power of symmetry concepts to predict changes in chem. bonding. Ab-initio calcns. of chemisorption to small particles, as well as semiempirical extended Hueckel calcns. applied to the study of the reactivity of metal slabs are reviewed. On small metal particles, classical notions of electron promotion and hybridization are found to apply. The surroundings of a metal atom (ligands in complexes, other metal atoms at surfaces), affect bonding and reactivity through the prehybridization they induce. A factor specific for large particles and surfaces is the required localization of electrons on the atoms involved in the metal surface bond. At the surface, the bond energy is found to relate to the grou8p orbital local d. of states at the Fermi level. The use of this concept is extensively discussed and illustrated for chemisorption of CO and dissocn. of NO on metal surfaces. A discussion is given of the current decompn. schemes of bond energies and related concepts (exchange (Pauli)-repulsion, polarization, charge transfer). The role of non-orthogonality of fragment orbitals and of kinetic and potential energy for Pauli repulsion and (orbital) polarization is analyzed. Numerous examples are discussed to demonstrate the impact of those concepts on chem. bonding theor

Protein disulphide isomerase-mediated grafting of cysteine-containing peptides onto over-bleached hair

The ability of Protein disulphide isomerase (PDI) to promote the grafting of two cysteine-containing peptides onto hair was investigated in order to develop an alternative treatment for over-bleached hair. The studied peptides were designed based on human keratin and human lung surfactant proteins and were linked to a fluorescent dye to facilitate visualisation of the grafting process and to assess hair penetration. The ability of the peptides to restore mechanical and thermal properties lost by repeated bleaching treatments was also studied. After eight bleaching treatments, hair samples displayed 42% less mechanical resistance, coupled with a decrease in α-helix denaturation enthalpies and temperatures. Hair surface damage following bleaching was visualized by scanning electron microscopy. Addition of PDI to the treatment formulations promoted peptide attachment to the hair via disulphide bonds, facilitating their penetration into the hair cortex, as observed by fluorescence microscopy. The proposed peptide treatment resulted in an increase in α-helix denaturation enthalpy in over-bleached hair, as well as an increase in both Young's modulus and tensile strength. Thus, mechanical and thermal properties were improved after the peptide treatment in the presence of PDI; suggesting that the formulations presented in this work are promising candidates for hair-care applications

Differences in Brain Function and Changes with Intervention in Children with Poor Spelling and Reading Abilities

Previous fMRI studies in English-speaking samples suggested that specific interventions may alter brain function in language-relevant networks in children with reading and spelling difficulties, but this research strongly focused on reading impaired individuals. Only few studies so far investigated characteristics of brain activation associated with poor spelling ability and whether a specific spelling intervention may also be associated with distinct changes in brain activity patterns. We here investigated such effects of a morpheme-based spelling intervention on brain function in 20 children with comparatively poor spelling and reading abilities using repeated fMRI. Relative to 10 matched controls, children with comparatively poor spelling and reading abilities showed increased activation in frontal medial and right hemispheric regions and decreased activation in left occipito-temporal regions prior to the intervention, during processing of a lexical decision task. After five weeks of intervention, spelling and reading comprehension significantly improved in the training group, along with increased activation in the left temporal, parahippocampal and hippocampal regions. Conversely, the waiting group showed increases in right posterior regions. Our findings could indicate an increased left temporal activation associated with the recollection of the new learnt morpheme-based strategy related to successful training

Individual Facial Coloration in Male Eulemur fulvus rufus: A Condition-dependent Ornament?

Researchers studying individual variation in conspicuous skin coloration in primates have suggested that color indicates male quality. Although primate fur color can also be flamboyant, the potential condition dependence and thus signaling function of fur remains poorly studied. We studied sources of variation in sexually dichromatic facial hair coloration in red-fronted lemurs (Eulemur fulvus rufus). We collected data on 13 adult males in Kirindy Forest, Madagascar, during two study periods in 2006 and 2007, to determine whether variation in facial hair coloration correlates with male age, rank, androgen status, and reproductive success. We quantified facial hair coloration via standardized digital photographs of each male, assessed androgen status using fecal hormone measurements, and obtained data on reproductive success through genetic paternity analyses. Male facial hair coloration showed high individual variation, and baseline coloration was related to individual androgen status but not to any other parameter tested. Color did not reflect rapid androgen changes during the mating season. However, pronounced long-term changes in androgen levels between years were accompanied by changes in facial hair coloration. Our data suggest that facial hair coloration in red-fronted lemur males is under proximate control of androgens and may provide some information about male quality, but it does not correlate with dominance rank or male reproductive success

Transgenic technologies to induce sterility

The last few years have witnessed a considerable expansion in the number of tools available to perform molecular and genetic studies on the genome of Anopheles mosquitoes, the vectors of human malaria. As a consequence, knowledge of aspects of the biology of mosquitoes, such as immunity, reproduction and behaviour, that are relevant to their ability to transmit disease is rapidly increasing, and could be translated into concrete benefits for malaria control strategies. Amongst the most important scientific advances, the development of transgenic technologies for Anopheles mosquitoes provides a crucial opportunity to improve current vector control measures or design novel ones. In particular, the use of genetic modification of the mosquito genome could provide for a more effective deployment of the sterile insect technique (SIT) against vector populations in the field. Currently, SIT relies on the release of radiation sterilized males, which compete with wild males for mating with wild females. The induction of sterility in males through the genetic manipulation of the mosquito genome, already achieved in a number of other insect species, could eliminate the need for radiation and increase the efficiency of SIT-based strategies. This paper provides an overview of the mechanisms already in use for inducing sterility by transgenesis in Drosophila and other insects, and speculates on possible ways to apply similar approaches to Anopheles mosquitoes

Transgenic technologies to induce sterility

The last few years have witnessed a considerable expansion in the number of tools available to perform molecular and genetic studies on the genome of Anopheles mosquitoes, the vectors of human malaria. As a consequence, knowledge of aspects of the biology of mosquitoes, such as immunity, reproduction and behaviour, that are relevant to their ability to transmit disease is rapidly increasing, and could be translated into concrete benefits for malaria control strategies. Amongst the most important scientific advances, the development of transgenic technologies for Anopheles mosquitoes provides a crucial opportunity to improve current vector control measures or design novel ones. In particular, the use of genetic modification of the mosquito genome could provide for a more effective deployment of the sterile insect technique (SIT) against vector populations in the field. Currently, SIT relies on the release of radiation sterilized males, which compete with wild males for mating with wild females. The induction of sterility in males through the genetic manipulation of the mosquito genome, already achieved in a number of other insect species, could eliminate the need for radiation and increase the efficiency of SIT-based strategies. This paper provides an overview of the mechanisms already in use for inducing sterility by transgenesis in Drosophila and other insects, and speculates on possible ways to apply similar approaches to Anopheles mosquitoes

Y-Chromosome Variation in Hominids: Intraspecific Variation Is Limited to the Polygamous Chimpanzee

The original publication is available at www.plosone.orgBackground: We have previously demonstrated that the Y-specific ampliconic fertility genes DAZ (deleted in azoospermia) and CDY (chromodomain protein Y) varied with respect to copy number and position among chimpanzees (Pan troglodytes). In comparison, seven Y-chromosomal lineages of the bonobo (Pan paniscus), the chimpanzee’s closest living relative, showed no variation. We extend our earlier comparative investigation to include an analysis of the intraspecific variation of these genes in gorillas (Gorilla gorilla) and orangutans (Pongo pygmaeus), and examine the resulting patterns in the light of the species’ markedly different social and mating behaviors. Methodology/Principal Findings: Fluorescence in situ hybridization analysis (FISH) of DAZ and CDY in 12 Y-chromosomal lineages of western lowland gorilla (G. gorilla gorilla) and a single lineage of the eastern lowland gorilla (G. beringei graueri) showed no variation among lineages. Similar findings were noted for the 10 Y-chromosomal lineages examined in the Bornean orangutan (Pongo pygmaeus), and 11 Y-chromosomal lineages of the Sumatran orangutan (P. abelii). We validated the contrasting DAZ and CDY patterns using quantitative real-time polymerase chain reaction (qPCR) in chimpanzee and bonobo. Conclusion/Significance: High intraspecific variation in copy number and position of the DAZ and CDY genes is seen only in the chimpanzee. We hypothesize that this is best explained by sperm competition that results in the variant DAZ and CDY haplotypes detected in this species. In contrast, bonobos, gorillas and orangutans—species that are not subject to sperm competition—showed no intraspecific variation in DAZ and CDY suggesting that monoandry in gorillas, and preferential female mate choice in bonobos and orangutans, probably permitted the fixation of a single Y variant in each taxon. These data support the notion that the evolutionary history of a primate Y chromosome is not simply encrypted in its DNA sequences, but is also shaped by the social and behavioral circumstances under which the specific species has evolved.Funded by the Deutsche Forschungsgemeinschaft (SCHE 214/8)Publisher's versio