A depauperate immune repertoire precedes evolution of sociality in bees

Background Sociality has many rewards, but can also be dangerous, as high population density and low genetic diversity, common in social insects, is ideal for parasite transmission. Despite this risk, honeybees and other sequenced social insects have far fewer canonical immune genes relative to solitary insects. Social protection from infection, including behavioral responses, may explain this depauperate immune repertoire. Here, based on full genome sequences, we describe the immune repertoire of two ecologically and commercially important bumblebee species that diverged approximately 18 million years ago, the North American Bombus impatiens and European Bombus terrestris. Results We find that the immune systems of these bumblebees, two species of honeybee, and a solitary leafcutting bee, are strikingly similar. Transcriptional assays confirm the expression of many of these genes in an immunological context and more strongly in young queens than males, affirming Bateman’s principle of greater investment in female immunity. We find evidence of positive selection in genes encoding antiviral responses, components of the Toll and JAK/STAT pathways, and serine protease inhibitors in both social and solitary bees. Finally, we detect many genes across pathways that differ in selection between bumblebees and honeybees, or between the social and solitary clades. Conclusions The similarity in immune complement across a gradient of sociality suggests that a reduced immune repertoire predates the evolution of sociality in bees. The differences in selection on immune genes likely reflect divergent pressures exerted by parasites across social contexts

Role of Reuniens Nucleus Projections to the Medial Prefrontal Cortex and to the Hippocampal Pyramidal CA1 Area in Associative Learning

We studied the interactions between short- and long-term plastic changes taking place during the acquisition of a classical eyeblink conditioning and following high-frequency stimulation (HFS) of the reuniens nucleus in behaving mice. Synaptic changes in strength were studied at the reuniens-medial prefrontal cortex (mPFC) and the reuniens-CA1 synapses. Input/output curves and a paired-pulse study enabled determining the functional capabilities of the two synapses and the optimal intensities to be applied at the reuniens nucleus during classical eyeblink conditioning and for HFS applied to the reuniens nucleus. Animals were conditioned using a trace paradigm, with a tone as conditioned stimulus (CS) and an electric shock to the trigeminal nerve as unconditioned stimulus (US). A single pulse was presented to the reuniens nucleus to evoke field EPSPs (fEPSPs) in mPFC and CA1 areas during the CS-US interval. No significant changes in synaptic strength were observed at the reuniens-mPFC and reuniens-CA1 synapses during the acquisition of eyelid conditioned responses (CRs). Two successive HFS sessions carried out during the first two conditioning days decreased the percentage of CRs, without evoking any long-term potentiation (LTP) at the recording sites. HFS of the reuniens nucleus also prevented the proper acquisition of an object discrimination task. A subsequent study revealed that HFS of the reuniens nucleus evoked a significant decrease of paired-pulse facilitation. In conclusion, reuniens nucleus projections to prefrontal and hippocampal circuits seem to participate in the acquisition of associative learning through a mechanism that does not required the development of LTP

Substitutional Reality System: A Novel Experimental Platform for Experiencing Alternative Reality

We have developed a novel experimental platform, referred to as a substitutional reality (SR) system, for studying the conviction of the perception of live reality and related metacognitive functions. The SR system was designed to manipulate people's reality by allowing them to experience live scenes (in which they were physically present) and recorded scenes (which were recorded and edited in advance) in an alternating manner without noticing a reality gap. All of the naïve participants (n = 21) successfully believed that they had experienced live scenes when recorded scenes had been presented. Additional psychophysical experiments suggest the depth of visual objects does not affect the perceptual discriminability between scenes, and the scene switch during head movement enhance substitutional performance. The SR system, with its reality manipulation, is a novel and affordable method for studying metacognitive functions and psychiatric disorders

IL-17RA Is Required for CCL2 Expression, Macrophage Recruitment, and Emphysema in Response to Cigarette Smoke

Chronic Obstructive Pulmonary Disease (COPD) is characterized by airspace enlargement and peribronchial lymphoid follicles; however, the immunological mechanisms leading to these pathologic changes remain undefined. Here we show that cigarette smoke is a selective adjuvant that augments in vitro and in vivo Th17, but not Th1, cell differentiation via the aryl hydrocarbon receptor. Smoke exposed IL-17RA−/− mice failed to induce CCL2 and MMP12 compared to WT mice. Remarkably, in contrast to WT mice, IL-17RA−/− mice failed to develop emphysema after 6 months of cigarette smoke exposure. Taken together, these data demonstrate that cigarette smoke is a potent Th17 adjuvant and that IL-17RA signaling is required for chemokine expression necessary for MMP12 induction and tissue emphysema

High Post-Capture Survival for Sharks, Rays and Chimaeras Discarded in the Main Shark Fishery of Australia?

Most sharks, rays and chimaeras (chondrichthyans) taken in commercial fisheries are discarded (i.e. returned to the ocean either dead or alive). Quantifying the post-capture survival (PCS) of discarded species is therefore essential for the improved management and conservation of this group. For all chondrichthyans taken in the main shark fishery of Australia, we quantified the immediate PCS of individuals reaching the deck of commercial shark gillnet fishing vessels and applied a risk-based method to semi-quantitatively determine delayed and total PCS. Estimates of immediate, delayed and total PCS were consistent, being very high for the most commonly discarded species (Port Jackson shark, Australian swellshark, and spikey dogfish) and low for the most important commercial species (gummy and school sharks). Increasing gillnet soak time or water temperature significantly decreased PCS. Chondrichthyans with bottom-dwelling habits had the highest PCS whereas those with pelagic habits had the lowest PCS. The risk-based approach can be easily implemented as a standard practice of on-board observing programs, providing a convenient first-step assessment of the PCS of all species taken in commercial fisheries

Surprised at All the Entropy: Hippocampal, Caudate and Midbrain Contributions to Learning from Prediction Errors

Influential concepts in neuroscientific research cast the brain a predictive machine that revises its predictions when they are violated by sensory input. This relates to the predictive coding account of perception, but also to learning. Learning from prediction errors has been suggested for take place in the hippocampal memory system as well as in the basal ganglia. The present fMRI study used an action-observation paradigm to investigate the contributions of the hippocampus, caudate nucleus and midbrain dopaminergic system to different types of learning: learning in the absence of prediction errors, learning from prediction errors, and responding to the accumulation of prediction errors in unpredictable stimulus configurations. We conducted analyses of the regions of interests' BOLD response towards these different types of learning, implementing a bootstrapping procedure to correct for false positives. We found both, caudate nucleus and the hippocampus to be activated by perceptual prediction errors. The hippocampal responses seemed to relate to the associative mismatch between a stored representation and current sensory input. Moreover, its response was significantly influenced by the average information, or Shannon entropy of the stimulus material. In accordance with earlier results, the habenula was activated by perceptual prediction errors. Lastly, we found that the substantia nigra was activated by the novelty of sensory input. In sum, we established that the midbrain dopaminergic system, the hippocampus, and the caudate nucleus were to different degrees significantly involved in the three different types of learning: acquisition of new information, learning from prediction errors and responding to unpredictable stimulus developments. We relate learning from perceptual prediction errors to the concept of predictive coding and related information theoretic accounts

Pathogenic Roles of CD14, Galectin-3, and OX40 during Experimental Cerebral Malaria in Mice

An in-depth knowledge of the host molecules and biological pathways that contribute towards the pathogenesis of cerebral malaria would help guide the development of novel prognostics and therapeutics. Genome-wide transcriptional profiling of the brain tissue during experimental cerebral malaria (ECM ) caused by Plasmodium berghei ANKA parasites in mice, a well established surrogate of human cerebral malaria, has been useful in predicting the functional classes of genes involved and pathways altered during the course of disease. To further understand the contribution of individual genes to the pathogenesis of ECM, we examined the biological relevance of three molecules – CD14, galectin-3, and OX40 that were previously shown to be overexpressed during ECM. We find that CD14 plays a predominant role in the induction of ECM and regulation of parasite density; deletion of the CD14 gene not only prevented the onset of disease in a majority of susceptible mice (only 21% of CD14-deficient compared to 80% of wildtype mice developed ECM, p<0.0004) but also had an ameliorating effect on parasitemia (a 2 fold reduction during the cerebral phase). Furthermore, deletion of the galectin-3 gene in susceptible C57BL/6 mice resulted in partial protection from ECM (47% of galectin-3-deficient versus 93% of wildtype mice developed ECM, p<0.0073). Subsequent adherence assays suggest that galectin-3 induced pathogenesis of ECM is not mediated by the recognition and binding of galectin-3 to P. berghei ANKA parasites. A previous study of ECM has demonstrated that brain infiltrating T cells are strongly activated and are CD44+CD62L− differentiated memory T cells [1]. We find that OX40, a marker of both T cell activation and memory, is selectively upregulated in the brain during ECM and its distribution among CD4+ and CD8+ T cells accumulated in the brain vasculature is approximately equal