Rapid learning of predictive maps with STDP and theta phase precession

The predictive map hypothesis is a promising candidate principle for hippocampal function. A favoured formalisation of this hypothesis, called the successor representation, proposes that each place cell encodes the expected state occupancy of its target location in the near future. This predictive framework is supported by behavioural as well as electrophysiological evidence and has desirable consequences for both the generalisability and efficiency of reinforcement learning algorithms. However, it is unclear how the successor representation might be learnt in the brain. Error-driven temporal difference learning, commonly used to learn successor representations in artificial agents, is not known to be implemented in hippocampal networks. Instead, we demonstrate that spike-timing dependent plasticity (STDP), a form of Hebbian learning, acting on temporally compressed trajectories known as 'theta sweeps', is sufficient to rapidly learn a close approximation to the successor representation. The model is biologically plausible - it uses spiking neurons modulated by theta-band oscillations, diffuse and overlapping place cell-like state representations, and experimentally matched parameters. We show how this model maps onto known aspects of hippocampal circuitry and explains substantial variance in the temporal difference successor matrix, consequently giving rise to place cells that demonstrate experimentally observed successor representation-related phenomena including backwards expansion on a 1D track and elongation near walls in 2D. Finally, our model provides insight into the observed topographical ordering of place field sizes along the dorsal-ventral axis by showing this is necessary to prevent the detrimental mixing of larger place fields, which encode longer timescale successor representations, with more fine-grained predictions of spatial location

Thermoregulatory traits combine with range shifts to alter the future of montane ant assemblages

Predicting and understanding the biological response to future climate change is a pressing challenge for humanity. In the 21st century, many species will move into higher latitudes and higher elevations as the climate warms. In addition, the relative abundances of species within local assemblages are likely to change. Both effects have implications for how ecosystems function. Few biodiversity forecasts, however, take account of both shifting ranges and changing abundances. We provide a novel analysis predicting the potential changes to assemblage‐level relative abundances in the 21st century. We use an established relationship linking ant abundance and their colour and size traits to temperature and UV‐B to predict future abundance changes. We also predict future temperature driven range shifts and use these to alter the available species pool for our trait‐mediated abundance predictions. We do this across three continents under a low greenhouse gas emissions scenario (RCP2.6) and a business‐as‐usual scenario (RCP8.5). Under RCP2.6, predicted changes to ant assemblages by 2100 are moderate. On average, species richness will increase by 26%, while species composition and relative abundance structure will be 26% and 30% different, respectively, compared with modern assemblages. Under RCP8.5, however, highland assemblages face almost a tripling of species richness and compositional and relative abundance changes of 66% and 77%. Critically, we predict that future assemblages could be reorganized in terms of which species are common and which are rare: future highland assemblages will not simply comprise upslope shifts of modern lowland assemblages. These forecasts reveal the potential for radical change to montane ant assemblages by the end of the 21st century if temperature increases continue. Our results highlight the importance of incorporating trait–environment relationships into future biodiversity predictions. Looking forward, the major challenge is to understand how ecosystem processes will respond to compositional and relative abundance changes.Australian Research Council, Grant/Award Number: DP120100781; University of Pretoria; Leverhulme Trust; NERC; DST‐NRF CIB.http://wileyonlinelibrary.com/journal/gcb2020-06-01hj2019Zoology and Entomolog

A hierarchical kinetic theory of birth, death, and fission in age-structured interacting populations

We study mathematical models describing the evolution of stochastic age-structured populations. After reviewing existing approaches, we develop a complete kinetic framework for age-structured interacting populations undergoing birth, death and fission processes in spatially dependent environments. We define the full probability density for the population-size age chart and find results under specific conditions. Connections with more classical models are also explicitly derived. In particular, we show that factorial moments for non-interacting processes are described by a natural generalization of the McKendrick-von Foerster equation, which describes mean-field deterministic behavior. Our approach utilizes mixed-type, multidimensional probability distributions similar to those employed in the study of gas kinetics and with terms that satisfy BBGKY-like equation hierarchies

Habitat-Specific Population Growth of a Farmland Bird

BACKGROUND: To assess population persistence of species living in heterogeneous landscapes, the effects of habitat on reproduction and survival have to be investigated. METHODOLOGY/PRINCIPAL FINDINGS: We used a matrix population model to estimate habitat-specific population growth rates for a population of northern wheatears Oenanthe oenanthe breeding in farmland consisting of a mosaic of distinct habitat (land use) types. Based on extensive long-term data on reproduction and survival, habitats characterised by tall field layers (spring- and autumn-sown crop fields, ungrazed grasslands) displayed negative stochastic population growth rates (log lambda(s): -0.332, -0.429, -0.168, respectively), that were markedly lower than growth rates of habitats characterised by permanently short field layers (pastures grazed by cattle or horses, and farmyards, log lambda(s): -0.056, +0.081, -0.059). Although habitats differed with respect to reproductive performance, differences in habitat-specific population growth were largely due to differences in adult and first-year survival rates, as shown by a life table response experiment (LTRE). CONCLUSIONS/SIGNIFICANCE: Our results show that estimation of survival rates is important for realistic assessments of habitat quality. Results also indicate that grazed grasslands and farmyards may act as source habitats, whereas crop fields and ungrazed grasslands with tall field layers may act as sink habitats. We suggest that the strong decline of northern wheatears in Swedish farmland may be linked to the corresponding observed loss of high quality breeding habitat, i.e. grazed semi-natural grasslands

Integrins promote axonal regeneration after injury of the nervous system.

Integrins are cell surface receptors that form the link between extracellular matrix molecules of the cell environment and internal cell signalling and the cytoskeleton. They are involved in several processes, e.g. adhesion and migration during development and repair. This review focuses on the role of integrins in axonal regeneration. Integrins participate in spontaneous axonal regeneration in the peripheral nervous system through binding to various ligands that either inhibit or enhance their activation and signalling. Integrin biology is more complex in the central nervous system. Integrins receptors are transported into growing axons during development, but selective polarised transport of integrins limits the regenerative response in adult neurons. Manipulation of integrins and related molecules to control their activation state and localisation within axons is a promising route towards stimulating effective regeneration in the central nervous system

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Evaluation of Sub-National Population Projections: a Case Study for London and the Thames Valley

Sub-national population projections help allocate national funding to local areas for planning local services. For example, water utilities prepare plans to meet future water demand over long-term horizons. Future demand depends on projected populations and households and forecasts of per household and per capita domestic water consumption in supply zones. This paper reports on population projections prepared for a water utility, Thames Water, which supplies water to over nine million people in London and the Thames Valley. Thames Water required an evaluation of the accuracy of the delivered projections against alternatives and estimates of uncertainty. The paper reviews how such evaluations have been made by researchers. The factors leading to variation in sub-national projections are identified. The methods, assumptions and results for English sub-national areas, used in five sets of projections, are compared. There is a consensus across projections about the future fertility and mortality but varying views about the future impact of internal and international migration flows. However, the greatest differences were between projections using ethnic populations. and those using homogeneous populations. Areas with high populations of ethnic minorities were projected to grow faster when an ethnic-specific model was used. This result is important for assessing projections for countries housing diverse populations with different demographic profiles. Historic empirical prediction intervals are used to assess the uncertainty of the London and the Thames Valley projections. By 2101 the preferred projection suggests that the population of the Thames Water region will have grown by 85% within an 80% empirical prediction interval between 45 and 125%

Climate mediates the effects of disturbance on ant assemblage structure

Many studies have focused on the impacts of climate change on biological assemblages, yet little is known about howclimate interacts with other major anthropogenic influences on biodiversity, such as habitat disturbance. Using a unique global database of 1128 local ant assemblages, we examined whether climate mediates the effects of habitat disturbance on assemblage structure at a global scale. Species richness and evenness were associated positively with temperature, and negatively with disturbance. However, the interaction among temperature, precipitation and disturbance shaped species richness and evenness. The effectwas manifested through a failure of species richness to increase substantially with temperature in transformed habitats at low precipitation. At low precipitation levels, evenness increased with temperature in undisturbed sites, peaked at medium temperatures in disturbed sites and remained low in transformed sites. In warmer climates with lower rainfall, the effects of increasing disturbance on species richness and evenness were akin to decreases in temperature of up to 98C. Anthropogenic disturbance and ongoing climate change may interact in complicated ways to shape the structure of assemblages, with hot, arid environments likely to be at greatest risk. © 2015 The Author(s) Published by the Royal Society. All rights reserved

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice