Modular and coordinated expression of immune system regulatory and signaling components in the developing and adult nervous system

During development, the nervous system (NS) is assembled and sculpted through a concerted series of neurodevelopmental events orchestrated by a complex genetic programme. While neural-specific gene expression plays a critical part in this process, in recent years, a number of immune-related signaling and regulatory components have also been shown to play key physiological roles in the developing and adult NS. While the involvement of individual immune-related signaling components in neural functions may reflect their ubiquitous character, it may also reflect a much wider, as yet undescribed, genetic network of immune–related molecules acting as an intrinsic component of the neural-specific regulatory machinery that ultimately shapes the NS. In order to gain insights into the scale and wider functional organization of immune-related genetic networks in the NS, we examined the large scale pattern of expression of these genes in the brain. Our results show a highly significant correlated expression and transcriptional clustering among immune-related genes in the developing and adult brain, and this correlation was the highest in the brain when compared to muscle, liver, kidney and endothelial cells. We experimentally tested the regulatory clustering of immune system (IS) genes by using microarray expression profiling in cultures of dissociated neurons stimulated with the pro-inflammatory cytokine TNF-alpha, and found a highly significant enrichment of immune system-related genes among the resulting differentially expressed genes. Our findings strongly suggest a coherent recruitment of entire immune-related genetic regulatory modules by the neural-specific genetic programme that shapes the NS

Constructing the eastern european other: The horsemeat scandal and the migrant other

The Horsemeat scandal in the UK in 2013 ignited a furore about consumer deception and the bodily transgression of consuming something so alien to the British psyche. The imagination of the horse as a noble and mythic figure in British history and sociological imagination was invoked to construct the consumption of horsemeat as a social taboo and an immoral proposition in the British media debates. This paper traces the horsemeat scandal and its media framing in the UK. Much of the aversion to horsemeat was intertextually bound with discourses of immigration, the expansion of the EU and the threat in tandem to the UK. Food as a social and cultural artefact laden with symbolic meaning and national pride became a platform to construct the ‘Other’ – in this case the Eastern European Other. The media debates on the horsemeat scandal interwove the opening up of the EU and particularly UK to the influx of Eastern European migration. The horsemeat controversy in implicating the Eastern Europeans for the contamination of the supply chain became a means to not just construct the ‘Other’ but also to entwine contemporary policy debates about immigration. This temporal framing of contemporary debates enables a nation to renew and contemporise its notions of ‘otherness’ while sustaining an historic social imaginary of itself

Building a transdisciplinary expert consensus on the cognitive drivers of performance under pressure: An international multi-panel Delphi study

IntroductionThe ability to perform optimally under pressure is critical across many occupations, including the military, first responders, and competitive sport. Despite recognition that such performance depends on a range of cognitive factors, how common these factors are across performance domains remains unclear. The current study sought to integrate existing knowledge in the performance field in the form of a transdisciplinary expert consensus on the cognitive mechanisms that underlie performance under pressure.MethodsInternational experts were recruited from four performance domains [(i) Defense; (ii) Competitive Sport; (iii) Civilian High-stakes; and (iv) Performance Neuroscience]. Experts rated constructs from the Research Domain Criteria (RDoC) framework (and several expert-suggested constructs) across successive rounds, until all constructs reached consensus for inclusion or were eliminated. Finally, included constructs were ranked for their relative importance.ResultsSixty-eight experts completed the first Delphi round, with 94% of experts retained by the end of the Delphi process. The following 10 constructs reached consensus across all four panels (in order of overall ranking): (1) Attention; (2) Cognitive Control—Performance Monitoring; (3) Arousal and Regulatory Systems—Arousal; (4) Cognitive Control—Goal Selection, Updating, Representation, and Maintenance; (5) Cognitive Control—Response Selection and Inhibition/Suppression; (6) Working memory—Flexible Updating; (7) Working memory—Active Maintenance; (8) Perception and Understanding of Self—Self-knowledge; (9) Working memory—Interference Control, and (10) Expert-suggested—Shifting.DiscussionOur results identify a set of transdisciplinary neuroscience-informed constructs, validated through expert consensus. This expert consensus is critical to standardizing cognitive assessment and informing mechanism-targeted interventions in the broader field of human performance optimization

Canonical BMP–Smad Signalling Promotes Neurite Growth in Rat Midbrain Dopaminergic Neurons

Ventral midbrain (VM) dopaminergic (DA) neurons project to the dorsal striatum via the nigrostriatal pathway to regulate voluntary movements, and their loss leads to the motor dysfunction seen in Parkinson’s disease (PD). Despite recent progress in the understanding of VM DA neurogenesis, the factors regulating nigrostriatal pathway development remain largely unknown. The bone morphogenetic protein (BMP) family regulates neurite growth in the developing nervous system and may contribute to nigrostriatal pathway development. Two related members of this family, BMP2 and growth differentiation factor (GDF)5, have neurotrophic effects, including promotion of neurite growth, on cultured VM DA neurons. However, the molecular mechanisms regulating their effects on DA neurons are unknown. By characterising the temporal expression profiles of endogenous BMP receptors (BMPRs) in the developing and adult rat VM and striatum, this study identified BMP2 and GDF5 as potential regulators of nigrostriatal pathway development. Furthermore, through the use of noggin, dorsomorphin and BMPR/Smad plasmids, this study demonstrated that GDF5- and BMP2-induced neurite outgrowth from cultured VM DA neurons is dependent on BMP type I receptor activation of the Smad 1/5/8 signalling pathway

The intracellular portion of GITR enhances NGF-promoted neurite growth through an inverse modulation of Erk and NF-κB signalling

NF-κB transcription factors play a key role in regulating the growth of neural processes in the developing PNS. Although several secreted proteins have been shown to activate NF-κB to inhibit the growth of developing sympathetic neurons, it is unknown how the endogenous level of NF-κB activity present in these neurons is restricted to allow neurite growth to occur during their normal development. Here we show that activation of the glucocorticoid-induced tumour necrosis factor receptor (GITR) inhibits NF-κB activation while promoting the activation of Erk in developing sympathetic neurons. Conversely, inhibition of GITR results in an increase in NF-κB dependent gene transcription and a decrease in Erk activation leading to a reduction in neurite growth. These findings show that GITR signalling can regulate the extent of sympathetic neurite growth through an inverse modulation of Erk and NF-κB signalling, which provides an optimal environment for NGF-promoted growth

Prenatal stress-induced alterations in major physiological systems correlate with gut microbiota composition in adulthood

Early-life adverse experiences, including prenatal stress (PNS), are associated with a higher prevalence of neurodevelopmental, cardiovascular and metabolic disorders in affected offspring. Here, in a rat model of chronic PNS, we investigate the impact of late gestational stress on physiological outcomes in adulthood. Sprague-Dawley pregnant dams were subjected to repeated restraint stress from embryonic day 14 to day 20, and their male offspring were assessed at 4 months of age. PNS induced an exaggeration of the hypothalamic–pituitary–adrenal (HPA) axis response to stress, as well as an elevation of blood pressure and impairment of cognitive function. Altered respiratory control was also observed, as demonstrated by increased variability in basal respiratory frequency and abnormal frequency responses to both hypoxic and hypercapnic challenges. PNS also affected gastrointestinal neurodevelopment and function, as measured by a decrease in the innervation density of distal colon and an increase in the colonic secretory response to catecholaminergic stimulation. Finally, PNS induced long lasting alterations in the intestinal microbiota composition. 16S rRNA gene 454 pyrosequencing revealed a strong trend towards decreased numbers of bacteria in the Lactobacillus genus, accompanied by elevated abundance of the Oscillibacter, Anaerotruncus and Peptococcus genera in PNS animals. Strikingly, relative abundance of distinct bacteria genera significantly correlated with certain respiratory parameters and the responsiveness of the HPA axis to stress. Together, these findings provide novel evidence that PNS induces long-term maladaptive alterations in the gastrointestinal and respiratory systems, accompanied by hyper-responsiveness to stress and alterations in the gut microbiota

Extinctions in ancient and modern seas

In the coming century, life in the ocean will be confronted with a suite of environmental conditions that have no analog in human history. Thus, there is an urgent need to determine which marine species will adapt and which will go extinct. Here, we review the growing literature on marine extinctions and extinction risk in the fossil, historical, and modern records to compare the patterns, drivers, and biological correlates of marine extinctions at different times in the past. Characterized by markedly different environmental states, some past periods share common features with predicted future scenarios. We highlight how the different records can be integrated to better understand and predict the impact of current and projected future environmental changes on extinction risk in the ocean

Initiation and Long-Term Instability of the East Antarctic Ice Sheet

Antarctica’s continental-scale ice sheets have evolved over the past 50 million years1,2,3,4. However, the dearth of ice-proximal geological records5,6,7,8 limits our understanding of past East Antarctic Ice Sheet (EAIS) behaviour and thus our ability to evaluate its response to ongoing environmental change. The EAIS is marine-terminating and grounded below sea level within the Aurora subglacial basin, indicating that this catchment, which drains ice to the Sabrina Coast, may be sensitive to climate perturbations9,10,11. Here we show, using marine geological and geophysical data from the continental shelf seaward of the Aurora subglacial basin, that marine-terminating glaciers existed at the Sabrina Coast by the early to middle Eocene epoch. This finding implies the existence of substantial ice volume in the Aurora subglacial basin before continental-scale ice sheets were established about 34 million years ago1,2,3,4. Subsequently, ice advanced across and retreated from the Sabrina Coast continental shelf at least 11 times during the Oligocene and Miocene epochs. Tunnel valleys12 associated with half of these glaciations indicate that a surface-meltwater-rich sub-polar glacial system existed under climate conditions similar to those anticipated with continued anthropogenic warming10,11. Cooling since the late Miocene13 resulted in an expanded polar EAIS and a limited glacial response to Pliocene warmth in the Aurora subglacial basin catchment14,15,16. Geological records from the Sabrina Coast shelf indicate that, in addition to ocean temperature, atmospheric temperature and surface-derived meltwater influenced East Antarctic ice mass balance under warmer-than-present climate conditions. Our results imply a dynamic EAIS response with continued anthropogenic warming and suggest that the EAIS contribution to future global sea-level projections10,11,15,17 may be under-estimated