Retrospective model-based inference guides model-free credit assignment

An extensive reinforcement learning literature shows that organisms assign credit efficiently, even under conditions of state uncertainty. However, little is known about credit-assignment when state uncertainty is subsequently resolved. Here, we address this problem within the framework of an interaction between model-free (MF) and model-based (MB) control systems. We present and support experimentally a theory of MB retrospective-inference. Within this framework, a MB system resolves uncertainty that prevailed when actions were taken thus guiding an MF credit-assignment. Using a task in which there was initial uncertainty about the lotteries that were chosen, we found that when participants’ momentary uncertainty about which lottery had generated an outcome was resolved by provision of subsequent information, participants preferentially assigned credit within a MF system to the lottery they retrospectively inferred was responsible for this outcome. These findings extend our knowledge about the range of MB functions and the scope of system interactions

Molecular architecture of potassium chloride co-transporter KCC2

KCC2 is a neuron specific K+-Cl− co-transporter that controls neuronal chloride homeostasis, and is critically involved in many neurological diseases including brain trauma, epilepsies, autism and schizophrenia. Despite significant accumulating data on the biology and electrophysiological properties of KCC2, structure-function relationships remain poorly understood. Here we used calixarene detergent to solubilize and purify wild-type non-aggregated and homogenous KCC2. Specific binding of inhibitor compound VU0463271 was demonstrated using surface plasmon resonance (SPR). Mass spectrometry revealed glycosylations and phosphorylations as expected from functional KCC2. We show by electron microscopy (EM) that KCC2 exists as monomers and dimers in solution. Monomers are organized into “head” and “core” domains connected by a flexible “linker”. Dimers are asymmetrical and display a bent “S-shape” architecture made of four distinct domains and a flexible dimerization interface. Chemical crosslinking in reducing conditions shows that disulfide bridges are involved in KCC2 dimerization. Moreover, we show that adding a tag to the C-terminus is detrimental to KCC2 function. We postulate that the conserved KCC2 C-ter may be at the interface of dimerization. Taken together, our findings highlight the flexible multi-domain structure of KCC2 with variable anchoring points at the dimerization interface and an important C-ter extremity providing the first in-depth functional architecture of KCC2

Plant-RRBS, a bisulfite and next-generation sequencing-based methylome profiling method enriching for coverage of cytosine positions

Background: Cytosine methylation in plant genomes is important for the regulation of gene transcription and transposon activity. Genome-wide methylomes are studied upon mutation of the DNA methyltransferases, adaptation to environmental stresses or during development. However, from basic biology to breeding programs, there is a need to monitor multiple samples to determine transgenerational methylation inheritance or differential cytosine methylation. Methylome data obtained by sodium hydrogen sulfite (bisulfite)-conversion and next-generation sequencing (NGS) provide genome- wide information on cytosine methylation. However, a profiling method that detects cytosine methylation state dispersed over the genome would allow high-throughput analysis of multiple plant samples with distinct epigenetic signatures. We use specific restriction endonucleases to enrich for cytosine coverage in a bisulfite and NGS-based profiling method, which was compared to whole-genome bisulfite sequencing of the same plant material. Methods: We established an effective methylome profiling method in plants, termed plant-reduced representation bisulfite sequencing (plant-RRBS), using optimized double restriction endonuclease digestion, fragment end repair, adapter ligation, followed by bisulfite conversion, PCR amplification and NGS. We report a performant laboratory protocol and a straightforward bioinformatics data analysis pipeline for plant-RRBS, applicable for any reference-sequenced plant species. Results: As a proof of concept, methylome profiling was performed using an Oryza sativa ssp. indica pure breeding line and a derived epigenetically altered line (epiline). Plant-RRBS detects methylation levels at tens of millions of cytosine positions deduced from bisulfite conversion in multiple samples. To evaluate the method, the coverage of cytosine positions, the intra-line similarity and the differential cytosine methylation levels between the pure breeding line and the epiline were determined. Plant-RRBS reproducibly covers commonly up to one fourth of the cytosine positions in the rice genome when using MspI-DpnII within a group of five biological replicates of a line. The method predominantly detects cytosine methylation in putative promoter regions and not-annotated regions in rice. Conclusions: Plant-RRBS offers high-throughput and broad, genome- dispersed methylation detection by effective read number generation obtained from reproducibly covered genome fractions using optimized endonuclease combinations, facilitating comparative analyses of multi-sample studies for cytosine methylation and transgenerational stability in experimental material and plant breeding populations

The Molecular Clockwork of the Fire Ant Solenopsis invicta

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication

Hyeropic shift after LASIK induced Diffuse lamellar keratitis

BACKGROUND: Diffuse lamellar keratitis (DLK) is a relatively new syndrome that is increasingly being reported after LASIK. We have observed that a hyperopic shift may be associated with the occurrence of this diffuse lamellar keratitis. CASE PRESENTATION: A 26 year old man developed bilateral diffuse lamellar keratitis (DLK) following myopic LASIK. The residual refractive error was +0.5D OD and +0.25D OS at the end of the first week. The sterile infiltrates resolved over a period of 4–6 weeks on topical steroid therapy. A progressive hyperopic shift was noted in the right eye with an error +4.25Dsph/+0.25Dcyl 20 at the final follow up 6 months post surgery. CONCLUSION: Diffuse lamellar keratitis after LASIK may be associated with a significant hyperopic shift

Do adults with high functioning autism or Asperger Syndrome differ in empathy and emotion recognition?

The present study examined whether adults with high functioning autism (HFA) showed greater difficulties in (i) their self-reported ability to empathise with others and/or (ii) their ability to read mental states in others’ eyes than adults with Asperger syndrome (AS). The Empathy Quotient (EQ) and ‘Reading the Mind in the Eyes’ Test (Eyes Test) were compared in 43 adults with AS and 43 adults with HFA. No significant difference was observed on EQ score between groups, while adults with AS performed significantly better on the Eyes Test than those with HFA. This suggests that adults with HFA may need more support, particularly in mentalizing and complex emotion recognition, and raises questions about the existence of subgroups within autism spectrum conditions

Influence of Efforts of Employer and Employee on Return-to-Work Process and Outcomes

Background Research on disability and RTW outcome has led to significant advances in understanding these outcomes, however, limited studies focus on measuring the RTW process. After a prolonged period of sickness absence, the assessment of the RTW process by investigating RTW Effort Sufficiency (RTW-ES) is essential. However, little is known about factors influencing RTW-ES. Also, the correspondence in factors determining RTW-ES and RTW is unknown. The purpose of this study was to investigate 1) the strength and relevance of factors related to RTW-ES and RTW (no/partial RTW), and 2) the comparability of factors associated with RTW-ES and with RTW. Methods During 4 months, all assessments of RTW-ES and RTW (no/partial RTW) among employees applying for disability benefits after 2 years of sickness absence, performed by labor experts at 3 Dutch Social Insurance Institute locations, were investigated by means of a questionnaire. Results Questionnaires concerning 415 cases were available. Using multiple logistic regression analysis, the only factor related to RTW-ES is a good employer-employee relationship. Factors related to RTW (no/partial RTW) were found to be high education, no previous periods of complete disability and a good employer-employee relationship. Conclusions Different factors are relevant to RTW-ES and RTW, but the employer-employee relationship is relevant for both. Considering the importance of the assessment of RTW-ES after a prolonged period of sickness absence among employees who are not fully disabled, this knowledge is essential for the assessment of RTW-ES and the RTW process itself

The Red Sea, Coastal Landscapes, and Hominin Dispersals

This chapter provides a critical assessment of environment, landscape and resources in the Red Sea region over the past five million years in relation to archaeological evidence of hominin settlement, and of current hypotheses about the role of the region as a pathway or obstacle to population dispersals between Africa and Asia and the possible significance of coastal colonization. The discussion assesses the impact of factors such as topography and the distribution of resources on land and on the seacoast, taking account of geographical variation and changes in geology, sea levels and palaeoclimate. The merits of northern and southern routes of movement at either end of the Red Sea are compared. All the evidence indicates that there has been no land connection at the southern end since the beginning of the Pliocene period, but that short sea crossings would have been possible at lowest sea-level stands with little or no technical aids. More important than the possibilities of crossing the southern channel is the nature of the resources available in the adjacent coastal zones. There were many climatic episodes wetter than today, and during these periods water draining from the Arabian escarpment provided productive conditions for large mammals and human populations in coastal regions and eastwards into the desert. During drier episodes the coastal region would have provided important refugia both in upland areas and on the emerged shelves exposed by lowered sea level, especially in the southern sector and on both sides of the Red Sea. Marine resources may have offered an added advantage in coastal areas, but evidence for their exploitation is very limited, and their role has been over-exaggerated in hypotheses of coastal colonization

Subjective face recognition difficulties, aberrant sensibility, sleeping disturbances and aberrant eating habits in families with Asperger syndrome

BACKGROUND: The present study was undertaken in order to determine whether a set of clinical features, which are not included in the DSM-IV or ICD-10 for Asperger Syndrome (AS), are associated with AS in particular or whether they are merely a familial trait that is not related to the diagnosis. METHODS: Ten large families, a total of 138 persons, of whom 58 individuals fulfilled the diagnostic criteria for AS and another 56 did not to fulfill these criteria, were studied using a structured interview focusing on the possible presence of face recognition difficulties, aberrant sensibility and eating habits and sleeping disturbances. RESULTS: The prevalence for face recognition difficulties was 46.6% in individuals with AS compared with 10.7% in the control group. The corresponding figures for subjectively reported presence of aberrant sensibilities were 91.4% and 46.6%, for sleeping disturbances 48.3% and 23.2% and for aberrant eating habits 60.3% and 14.3%, respectively. CONCLUSION: An aberrant processing of sensory information appears to be a common feature in AS. The impact of these and other clinical features that are not incorporated in the ICD-10 and DSM-IV on our understanding of AS may hitherto have been underestimated. These associated clinical traits may well be reflected by the behavioural characteristics of these individuals