Parasite spill-back from domestic hosts may induce an Allee effect in wildlife hosts

The exchange of native pathogens between wild and domesticated animals can lead to novel disease dynamics. A simple model reveals that the spill-back of native parasites\ud from domestic to wild hosts may cause a demographic Allee effect. Because parasite spill-over and spill-back decouples the abundance of parasite infectious stages from the abundance of the wild host population, parasitism and mortality of the wild host population increases non-linearly as host abundance decreases. Analogous to the effects of satiation of generalist predators, parasite spill-back can produce an unstable equilibrium in the abundance of the host population above which the host population persists and below which it is at risk of extirpation. These effects are likely to be most pronounced in systems where the parasite has a high efficiency of transmission from domestic to wild host populations due to prolonged sympatry, disease vectors, or proximity of domesticated populations to wildlife migratory corridors

The power of forecasts to advance ecological theory

Ecological forecasting provides a powerful set of methods for predicting short- and long-term change in living systems. Forecasts are now widely produced, enabling proactive management for many applied ecological problems. However, despite numerous calls for an increased emphasis on prediction in ecology, the potential for forecasting to accelerate ecological theory development remains underrealized. Here, we provide a conceptual framework describing how ecological forecasts can energize and advance ecological theory. We emphasize the many opportunities for future progress in this area through increased forecast development, comparison and synthesis. Our framework describes how a forecasting approach can shed new light on existing ecological theories while also allowing researchers to address novel questions. Through rigorous and repeated testing of hypotheses, forecasting can help to refine theories and understand their generality across systems. Meanwhile, synthesizing across forecasts allows for the development of novel theory about the relative predictability of ecological variables across forecast horizons and scales. We envision a future where forecasting is integrated as part of the toolset used in fundamental ecology. By outlining the relevance of forecasting methods to ecological theory, we aim to decrease barriers to entry and broaden the community of researchers using forecasting for fundamental ecological insight

Efficient pedigree recording for fast population genetics simulation

In this paper we describe how to efficiently record the entire genetic history of a population in forwards-time, individual-based population genetics simulations with arbitrary breeding models, population structure and demography. This approach dramatically reduces the computational burden of tracking individual genomes by allowing us to simulate only those loci that may affect reproduction (those having non-neutral variants). The genetic history of the population is recorded as a succinct tree sequence as introduced in the software package msprime, on which neutral mutations can be quickly placed afterwards. Recording the results of each breeding event requires storage that grows linearly with time, but there is a great deal of redundancy in this information. We solve this storage problem by providing an algorithm to quickly 'simplify' a tree sequence by removing this irrelevant history for a given set of genomes. By periodically simplifying the history with respect to the extant population, we show that the total storage space required is modest and overall large efficiency gains can be made over classical forward-time simulations. We implement a general-purpose framework for recording and simplifying genealogical data, which can be used to make simulations of any population model more efficient. We modify two popular forwards-time simulation frameworks to use this new approach and observe efficiency gains in large, whole-genome simulations of one to two orders of magnitude. In addition to speed, our method for recording pedigrees has several advantages: (1) All marginal genealogies of the simulated individuals are recorded, rather than just genotypes. (2) A population of N individuals with M polymorphic sites can be stored in O(N log N + M) space, making it feasible to store a simulation's entire final generation as well as its history. (3) A simulation can easily be initialized with a more efficient coalescent simulation of deep history. The software for recording and processing tree sequences is named tskit

The mechanisms of phenology: the patterns and processes of phenological shifts

Species across a wide range of taxa and habitats are shifting phenological events in response to climate change. While advances are common, shifts vary in magnitude and direction within and among species, and the basis for this variation is relatively unknown. We examine previously suggested patterns of variation in phenological shifts in order to understand the cue–response mechanisms that underlie phenological change. Here, we review what is known about the mechanistic basis for nine factors proposed to predict phenological change (latitude, elevation, habitat type, trophic level, migratory strategy, ecological specialization, species’ seasonality, thermoregulatory mode, and generation time). We find that many studies either do not identify a specific underlying mechanism or do not evaluate alternative mechanistic hypotheses, limiting the ability of scientists to predict future responses to global change with accuracy. We present a conceptual framework that emphasizes a critical distinction between environmental (cue-driven) and organismal (response-driven) mechanisms causing variation in phenological shifts and discuss how this distinction can reduce confusion in the field and improve predictions of future phenological change

Toxoplasma gondii migration within and infection of human retina.

Toxoplasmic retinochoroiditis is a common blinding retinal infection caused by the parasite, Toxoplasma gondii. Basic processes relating to establishment of infection in the human eye by T. gondii tachyzoites have not been investigated. To evaluate the ability of tachyzoites to navigate the human retina, we developed an ex vivo assay, in which a suspension containing 1.5 × 10(7) parasites replaced vitreous in a posterior eyecup. After 8 hours, the retina was formalin-fixed and paraffin-embedded, and sections were immunostained to identify tachyzoites. To determine the preference of tachyzoites for human retinal neuronal versus glial populations, we infected dissociated retinal cultures, subsequently characterized by neuron-specific enolase or glial fibrillary acidic protein expression, and retinal cell lines, with YFP-expressing tachyzoites. In migration assays, retinas contained 110-250 live tachyzoites; 64.5-95.2% (mean  =79.6%) were localized to the nerve fiber layer, but some were detected in the outer retina. Epifluorescence imaging of dissociated retinal cultures 24 hours after infection indicated preferential infection of glia. This observation was confirmed in growth assays, with significantly higher (p ≤ 0.005) numbers of tachyzoites measured in glial verus neuronal cell lines. Our translational studies indicate that, after entering retina, tachyzoites may navigate multiple tissue layers. Tachyzoites preferentially infect glial cells, which exist throughout the retina. These properties may contribute to the success of T. gondii as a human pathogen

Selective Transcription Factor Blockade Reduces Human Retinal Endothelial Cell Expression of Intercellular Adhesion Molecule-1 and Leukocyte Binding

The interaction between leukocytes and cytokine-activated retinal endothelium is an initiating step in non-infectious uveitis involving the posterior eye, mediated by cell adhesion molecules. However, because cell adhesion molecules are required for immune surveillance, therapeutic interventions would ideally be employed indirectly. Using 28 primary human retinal endothelial cell isolates, this study sought to identify transcription factor targets for reducing levels of the key retinal endothelial cell adhesion molecule, intercellular adhesion molecule (ICAM)-1, and limiting leukocyte binding to the retinal endothelium. Five candidate transcription factors—C2CD4B, EGR3, FOSB, IRF1, and JUNB—were identified by differential expression analysis of a transcriptome generated from IL-1β- or TNF-α-stimulated human retinal endothelial cells, interpreted in the context of the published literature. Further filtering involved molecular studies: of the five candidates, C2CD4B and IRF1 consistently demonstrated extended induction in IL-1β- or TNF-α-activated retinal endothelial cells and demonstrated a significant decrease in both ICAM-1 transcript and ICAM-1 membrane-bound protein expression by cytokine-activated retinal endothelial cells following treatment with small interfering RNA. RNA interference of C2CD4B or IRF1 significantly reduced leukocyte binding in a majority of human retinal endothelial cell isolates stimulated by IL-1β or TNF-α. Our observations suggest that the transcription factors C2CD4B and IRF1 may be potential drug targets for limiting leukocyte–retinal endothelial cell interactions in non-infectious uveitis involving the posterior eye

<i>T. gondii</i> tachyzoites infect human retinal glial cells in preference to neurons.

<p>(A). Immediately prior to infection, dissociated human retinal cultures presented a layer of glial cells with neurons positioned above. Original magnification: 100X. (B and C). Expression of (B) neuron specific enolase (NSE) (red), as detected by rabbit polyclonal anti-human NSE antibody and Alexa Fluor 594-conjugated donkey anti-rabbit immunoglobulin (Ig)G antibody and (C) glial fibrillary acidic protein (GFAP) (red), as detected by sheep polyclonal anti-human GFAP antibody and Alexa Fluor 594-conjugated donkey anti-sheep IgG antibody. <i>T. gondii</i> tachyzoites express YFP (green). Original magnification: 630X. Negative control cultures showed no positive staining. (D). Graph showing percentage growth of tachyzoites in Y79 human retinoblastoma cells and MIO-M1 human Müller glial cells, plus positive control human foreskin fibroblasts (FF), over a 24-hour period. n = 7–8 wells/condition. Columns  =  mean. Error bars  =  standard error of mean. Representative of two independent experiments.</p