Predicting population responses to environmental change from individual-level mechanisms: towards a standardized mechanistic approach

Animal populations will mediate the response of global biodiversity to environmental changes. Population models are thus important tools for both understanding and predicting animal responses to uncertain future conditions. Most approaches, however, are correlative and ignore the individual-level mechanisms that give rise to population dynamics. Here, we assess several existing population modelling approaches, and find limitations to both ‘correlative’ and ‘mechanistic’ models. We advocate the need for a standardised mechanistic approach for linking individual mechanisms (physiology, behaviour and evolution) to population dynamics in spatially explicit landscapes. Such an approach is potentially more flexible and informative than current population models. Key to realising this goal, however, is overcoming current data limitations, the development and testing of eco-evolutionary theory to represent interactions between individual mechanisms, and standardised multidimensional environmental change scenarios which incorporate multiple stressors. Such progress is essential in supporting environmental decisions in uncertain future conditions

Demonstration of the use of environmental DNA for the non-invasive genotyping of a bivalve mollusk, the European flat oyster (Ostrea edulis)

Funding: European Marine Biological Research Infrastructure Cluster (EMBRIC) project funded by the European Union’s Horizon 2020 research and innovation program under grant agreement No 654008. UK Natural Environmental Research Council (grant number NE/L002531/1) (LH).Accurate SNP (single nucleotide polymorphism) genotype information is critical for a wide range of selective breeding applications in aquaculture, including parentage assignment, marker-assisted, and genomic selection. However, the sampling of tissue for genetic analysis can be invasive for juvenile animals or taxa where sampling tissue is difficult or may cause mortality (e.g. bivalve mollusks). Here, we demonstrate a novel, non-invasive technique for sampling DNA based on the collection of environmental DNA using European Flat Oysters (Ostrea edulis) as an example. The live animals are placed in individual containers until sufficient genetic material is released into the seawater which is then recovered by filtration. We compared the results of tissue and eDNA derived SNP genotype calls using a PCR based genotyping platform. We found that 100% accurate genotype calls from eDNA are possible, but depend on appropriate filtration and the dilution of the sample throughout the workflow. We also developed an additional low-cost DNA extraction technique which provided >99% correct SNP genotype calls in comparison to tissue. It was concluded that eDNA sampling can be used in hatchery and selective breeding programs applicable to any aquatic organism for which direct tissue sampling may result in animal welfare concerns or mortality.Publisher PDFPeer reviewe

Distance tuneable integral membrane protein containing floating bilayers via in situ directed self-assembly

Model membranes allow for structural and biophysical studies on membrane biochemistry at the molecular level, albeit on systems of reduced complexity which can limit biological accuracy. Floating supported bilayers offer a means of producing planar lipid membrane models not adhered to a surface, which allows for improved accuracy compared to other model membranes. Here we communicate the incorporation of an integral membrane protein complex, the multidomain β-barrel assembly machinery (Bam), into our recently developed in situ self-assembled floating supported bilayers. Using neutron reflectometry and quartz crystal microbalance measurements we show this sample system can be fabricated using a two-step self-assembly process. We then demonstrate the complexity of the model membrane and tuneability of the membrane-to-surface distance using changes in the salt concentration of the bulk solution. Results demonstrate an easily fabricated, biologically accurate and tuneable membrane assay system which can be utilized for studies on integral membrane proteins within their native lipid matrix

Multi-Sensor PHD: Construction and Implementation by Space Partitioning

International audienceThe Probability Hypothesis Density (PHD) is a well-known method for single-sensor multi-target tracking problems in a Bayesian framework, but the extension to the multi-sensor case seems to remain a challenge. In this paper, an extension of Mahler's work to the multi-sensor case provides an expression of the true PHD multi-sensor data update equation. Then, based on the configuration of the sensors' fields of view (FOVs), a joint partitioning of both the sensors and the state space provides an equivalent yet more practical expression of the data update equation, allowing a more effective implementation in specific FOV configurations

An open-format enteroid culture system for interrogation of interactions between Toxoplasma gondii and the intestinal epithelium.

When transmitted through the oral route, Toxoplasma gondii first interacts with its host at the small intestinal epithelium. This interaction is crucial to controlling initial invasion and replication, as well as shaping the quality of the systemic immune response. It is therefore an attractive target for the design of novel vaccines and adjuvants. However, due to a lack of tractable infection models, we understand surprisingly little about the molecular pathways that govern this interaction. The in vitro culture of small intestinal epithelium as 3D enteroids shows great promise for modeling the epithelial response to infection. However, the enclosed luminal space makes the application of infectious agents to the apical epithelial surface challenging. Here, we have developed three novel enteroid-based techniques for modeling T. gondii infection. In particular, we have adapted enteroid culture protocols to generate collagen-supported epithelial sheets with an exposed apical surface. These cultures retain epithelial polarization, and the presence of fully differentiated epithelial cell populations. They are susceptible to infection with, and support replication of, T. gondii. Using quantitative label-free mass spectrometry, we show that T. gondii infection of the enteroid epithelium is associated with up-regulation of proteins associated with cholesterol metabolism, extracellular exosomes, intermicrovillar adhesion, and cell junctions. Inhibition of host cholesterol and isoprenoid biosynthesis with Atorvastatin resulted in a reduction in parasite load only at higher doses, indicating that de novo synthesis may support, but is not required for, parasite replication. These novel models therefore offer tractable tools for investigating how interactions between T. gondii and the host intestinal epithelium influence the course of infection

Piperazinyl quinolines as chemosensitizers to increase fluconazole susceptibility of Candida albicans clinical isolates

The effectiveness of the potent antifungal drug fluconazole is being compromised by the rise of drug-resistant fungal pathogens. While inhibition of Hsp90 or calcineurin can reverse drug resistance in Candida, such inhibitors also impair the homologous human host protein and fungal-selective chemosensitizers remain rare. The MLPCN library was screened to identify compounds that selectively reverse fluconazole resistance in a Candida albicans clinical isolate, while having no antifungal activity when administered as a single agent. A piperazinyl quinoline was identified as a new small-molecule probe (ML189) satisfying these criteria.National Institutes of Health (U.S.) (1 R03 MH086456-01

Inhibition of Pannexin 1 Reduces the Tumorigenic Properties of Human Melanoma Cells

Pannexin 1 (PANX1) is a channel-forming glycoprotein expressed in many tissues including the skin. PANX1 channels allow the passage of ions and molecules up to 1 kDa, including ATP and other metabolites. In this study, we show that PANX1 is highly expressed in human melanoma tumors at all stages of disease progression, as well as in patient-derived cells and established melanoma cell lines. Reducing PANX1 protein levels using shRNA or inhibiting channel function with the channel blockers, carbenoxolone (CBX) and probenecid (PBN), significantly decreased cell growth and migration, and increased melanin production in A375-P and A375-MA2 cell lines. Further, treatment of A375-MA2 tumors in chicken embryo xenografts with CBX or PBN significantly reduced melanoma tumor weight and invasiveness. Blocking PANX1 channels with PBN reduced ATP release in A375-P cells, suggesting a potential role for PANX1 in purinergic signaling of melanoma cells. In addition, cell-surface biotinylation assays indicate that there is an intracellular pool of PANX1 in melanoma cells. PANX1 likely modulates signaling through the Wnt/beta-catenin pathway, because beta-catenin levels were significantly decreased upon PANX1 silencing. Collectively, our findings identify a role for PANX1 in controlling growth and tumorigenic properties of melanoma cells contributing to signaling pathways that modulate melanoma progression

Unacylated-Ghrelin Impairs Hippocampal Neurogenesis and Memory in Mice and Is Altered in Parkinson’s Dementia in Humans

Blood-borne factors regulate adult hippocampal neurogenesis and cognition in mammals. We report that elevating circulating unacylated-ghrelin (UAG), using both pharmacological and genetic methods, reduced hippocampal neurogenesis and plasticity in mice. Spatial memory impairments observed in ghrelin-O-acyl transferase-null (GOAT/) mice that lack acyl-ghrelin (AG) but have high levels of UAG were rescued by acyl-ghrelin. Acyl-ghrelin-mediated neurogenesis in vitro was dependent on non-cell-autonomous BDNF signaling that was inhibited by UAG. These findings suggest that post-translational acylation of ghrelin is important to neurogenesis and memory in mice. To determine relevance in humans, we analyzed circulating AG:UAG in Parkinson disease (PD) patients diagnosed with dementia (PDD), cognitively intact PD patients, and controls. Notably, plasma AG:UAG was only reduced in PDD. Hippocampal ghrelin-receptor expression remained unchanged; however, GOAT+ cell number was reduced in PDD. We identify UAG as a regulator of hippocampal-dependent plasticity and spatial memory and AG:UAG as a putative circulating diagnostic biomarker of dementia

An octameric PqiC toroid stabilises the outer-membrane interaction of the PqiABC transport system

The E. coli Paraquat Inducible (Pqi) Pathway is a putative Gram-negative phospholipid transport system. The pathway comprises three components: an integral inner membrane protein (PqiA), a periplasmic spanning MCE family protein (PqiB) and an outer membrane lipoprotein (PqiC). Interactions between all complex components, including stoichiometry, remain uncharacterised; nevertheless, once assembled into their quaternary complex, the trio of Pqi proteins are anticipated to provide a continuous channel between the inner and outer membranes of diderms. Here, we present X-ray structures of both the native and a truncated, soluble construct of the PqiC lipoprotein, providing insight into its biological assembly, and utilise neutron reflectometry to characterise the nature of the PqiB-PqiC-membrane interaction. Finally, we employ phenotypic complementation assays to probe specific PqiC residues, which imply the interaction between PqiB and PqiC is less intimate than previously anticipated.</p

Evolutionary inference across eukaryotes identifies universal features shaping organelle gene retention

Mitochondria and plastids power complex life. Why some genes and not others are retained in their organelle DNA (oDNA) genomes remains a debated question. Here, we attempt to identify the properties of genes and associated underlying mechanisms that determine oDNA retention. We harness over 15k oDNA sequences and over 300 whole genome sequences across eukaryotes with tools from structural biology, bioinformatics, machine learning, and Bayesian model selection. Previously hypothesized features, including the hydrophobicity of a protein product, and less well-known features, including binding energy centrality within a protein complex, predict oDNA retention across eukaryotes, with additional influences of nucleic acid and amino acid biochemistry. Notably, the same features predict retention in both organelles, and retention models learned from one organelle type quantitatively predict retention in the other, supporting the universality of these features—which also distinguish gene profiles in more recent, independent endosymbiotic relationships. A record of this paper’s transparent peer review process is included in the supplemental information