Biology subjects

Wilson, S.

Publications and source records attributed to Wilson, S..

46 records · Page 3Linked to original sources

bioRxiv2020

Extent of similarity between agricultural and natural land covers shapes how biodiversity responds to agricultural expansion at landscape scales

The impact of agriculture on biodiversity depends on the extent and types of agriculture and the degree to which agricultural land contrasts with the natural ecosystem. Most research on the latter comes from studies on the influence of different agricultural types within a single ecosystem with far less study on how the natural ecosystem context shapes the response of biodiversity to agricultural production. We used citizen science data from agricultural areas in Canadas Eastern Hardwood-Boreal (forest ecosystem, n=108 landscapes) and Prairie Pothole (prairie ecosystem, n=99) regions to examine how ecosystem context shapes the response of avian species diversity, functional diversity and abundance to the amount of arable crop and pastoral agriculture at landscape scales. Avian surveys were conducted along 8km transects of Breeding Bird Survey routes with land cover assembled within a 20km2 landscape around each transect. The amount of agriculture at which species diversity peaked differed between the forest (15%) and prairie (51%) ecosystems, indicating that fewer species tolerated the expansion of agriculture in the former. In both ecosystems, functional diversity initially increased with agriculture and peaked at higher amounts (forest: 42%, prairie: 77%) than species diversity suggesting that functional redundancy was lost first as agriculture increased. Species turnover with increasing agriculture was primarily among functional groups in forest where a shift from a low to a high agriculture landscape led to a decline in the percent of the community represented by Neotropical migrants, insectivores, upper foliage gleaners and bark foragers, and an increase in the percent of the community represented by short-distance migrants, granivores, omnivores and ground gleaners. There were few distinct shifts in the percent of the community represented by different functional groups in the prairie ecosystem. Total abundance was the least sensitive measure examined in both ecosystems and indicated that species losses with agriculture are likely followed by numerical compensation from agriculture tolerant species. Our results highlight the importance of ecosystem context for understanding how biodiversity is affected by agricultural production with declines in diversity occurring at lower agricultural extents in ecosystems with lower similarity between natural and agricultural land covers. These findings allow for more specific conservation recommendations including managing for species intolerant to agriculture in prairie ecosystems and limiting the expansion of high contrast agriculture and the loss of semi-natural habitat, such as hedge rows, in historically forested ecosystems.

ecology↗

bioRxiv2019

Transcriptome of the parasitic flatworm Schistosoma mansoni during intra-mammalian development

Schistosomes are parasitic blood flukes that survive for many years within the mammalian host vasculature. How the parasites establish a chronic infection in the hostile bloodstream environment, whilst evading the host immune response is poorly understood. The parasite develops morphologically and grows as it migrates to its preferred vascular niche, avoiding or repairing damage from the host immune system. In this study, we investigated temporal changes in gene expression during the intra-mammalian development of Schistosoma mansoni. RNA-seq data were analysed from parasites developing in the lung through to egg-laying mature adult worms, providing a comprehensive picture of in vivo intra-mammalian development. Remarkably, genes involved in signalling pathways, developmental control, and adaptation to oxidative stress were up-regulated in the lung stage. The data also suggested a potential role in immune evasion for a previously uncharacterised gene. This study not only provides a large and comprehensive data resource for the research community, but also reveals new directions for further characterising host-parasite interactions that could ultimately lead to new control strategies for this neglected tropical disease pathogen.\n\nAuthor SummaryThe life cycle of the parasitic flatworm Schistosoma mansoni is split between snail and mammalian (often human) hosts. An infection can last for more than 10 years, during which time the parasite physically interacts with its mammalian host as it moves through the bloodstream, travelling through the lungs and liver, to eventually establish a chronic infection in the blood vessels around the host gut. Throughout this complex journey, the parasite develops from a relatively simple larval form into a more complex, sexually reproducing adult. To understand the molecular basis of parasite interactions with the host during this complex journey we have produced genome-wide expression data from developing parasites. The parasites were collected from experimentally-infected mice over its developmental time-course from the poorly studied lung stage, to the fully mature egg-laying adult worm. The data highlight many genes involved in processes known to be associated with key stages of the infection. In addition, the gene expression data provide a unique view of interactions between the parasite and the immune system in the lung, including novel players in host-parasite interactions. A detailed understanding of these processes may provide new opportunities to design intervention strategies, particularly those focussed on the early stages of the infection that are not targeted by current chemotherapy.

microbiology↗

bioRxiv2019

A library of cell-surface and secreted proteins from Schistosoma mansoni identifies early serological markers of infection

Schistosomiasis is a major global health problem caused by blood-dwelling parasitic worms and is currently treated by the mass administration of the drug praziquantel. Appropriate drug treatment strategies are informed by diagnostics that establish the prevalence and intensity of infection, which, in regions of low transmission should be highly sensitive. To identify sensitive new serological markers of Schistosoma mansoni infections, we have compiled a recombinant protein library of 115 parasite cell surface and secreted proteins expressed in mammalian cells. The vast majority of them were shown to be immunoreactive and to contain heat-labile conformational epitopes when tested against pooled human sera from endemic regions. After probing the library against a time series of sera samples from experimental infections in mice, we identified several markers of infection, the majority of which belong to the saposin-domain-containing and cathepsin families of proteins. These new markers will be a valuable tool to detect ongoing and previous S. mansoni infections, including in regions of low transmission. We envisage that this new recombinant protein resource will be used in a wide range of cellular and molecular assays to further our understanding of Schistosoma biology.

immunology↗

bioRxiv2018

Bioprinted pluripotent stem cell-derived kidney organoids provide opportunities for high content screening.

Recent advances in the directed differentiation of human pluripotent stem cells to kidney brings with it the prospect of drug screening and disease modelling using patient-derived stem cell lines. Development of such an approach for high content screening will require substantial quality control and improvements in throughput. Here we demonstrate the use of the NovoGen MMX 3D bioprinter for the generation of highly reproducible kidney organoids from as few as 4,000 cells. Histological and immunohistochemical analyses confirmed the presence of renal epithelium, glomeruli, stroma and endothelium, while single cell RNAseq revealed equivalence to the cell clusters present within previously described organoids. The process is highly reproducible, rapid and transferable between cell lines, including genetically engineered reporter lines. We also demonstrate the capacity to bioprint organoids in a 96-well format and screen for response to doxorubicin toxicity as a proof of concept for high content compound screening.

cell biology↗

bioRxiv2018

Prioritize diversity or declining species? Trade-offs and synergies in spatial planning for the conservation of migratory birds

Stemming biodiversity loss requires strategic conservation guided by well-articulated and achievable targets, whether they be proactive (e.g., protect diverse places) or reactive (e.g., protect threatened species). Both types of targets can be effective, but there are trade-offs, especially for broadly-distributed ecosystems or taxa, such as migratory species, a group for which conservation has been challenged by limited knowledge of distributions throughout the annual cycle. We combined novel spatiotemporal distribution models with population trend data to first examine focal areas for the conservation of Neotropical migratory birds (n=112 species) during the non-breeding period in the Western Hemisphere based on a proactive approach (highest diversity) versus a reactive approach (strongest declines) to conservation. For the focal areas, we then assessed the extent of recent anthropogenic impact, protected area status and projected future changes in land cover using three shared socioeconomic pathways (Sustainability=SSP1, Business-as-usual=SSP2, Regional nationalism=SSP3). Spatial priorities were strikingly different when targeting areas of high species diversity, emphasizing southern Mexico and northern Central America, versus areas with more severe declines across species, emphasizing the Andean cordilleras of South America. Only a fraction of the non-breeding region (1.4%) met targets for diversity and decline, mostly in southern Central America. Current levels of protection were similar for the two targets. Areas prioritized to conserve high species diversity have experienced less recent anthropogenic impact than areas prioritized for decline but are predicted to experience more rapid land conversion to less suitable open, agricultural landscapes in the next three decades under both an SSP1 and SSP2 scenario. Only the SSP3 scenario projected similar conversion rates for the two targets. Our findings indicate how even within taxa, efficient conservation efforts will depend on the careful consideration of desired targets combined with reliable predictions about the locations and types of land cover change under alternative socioeconomic futures.

ecology↗

bioRxiv2018

Automated literature mining and hypothesis generation through a network of Medical Subject Headings

The scientific literature is vast, growing, and increasingly specialized, making it difficult to connect disparate observations across subfields. To address this problem, we sought to develop automated hypothesis generation by networking at scale the MeSH terms curated by the National Library of Medicine. The result is a Mesh Term Objective Reasoning (MeTeOR) approach that tallies associations among genes, drugs and diseases from PubMed and predicts new ones.\n\nComparisons to reference databases and algorithms show MeTeOR tends to be more reliable. We also show that many predictions based on the literature prior to 2014 were published subsequently. In a practical application, we validated experimentally a surprising new association found by MeTeOR between novel Epidermal Growth Factor Receptor (EGFR) associations and CDK2. We conclude that MeTeOR generates useful hypotheses from the literature (http://meteor.lichtargelab.org/).\n\nAUTHOR SUMMARYThe large size and exponential expansion of the scientific literature forms a bottleneck to accessing and understanding published findings. Manual curation and Natural Language Processing (NLP) aim to address this bottleneck by summarizing and disseminating the knowledge within articles as key relationships (e.g. TP53 relates to Cancer). However, these methods compromise on either coverage or accuracy, respectively. To mitigate this compromise, we proposed using manually-assigned keywords (MeSH terms) to extract relationships from the publications and demonstrated a comparable coverage but higher accuracy than current NLP methods. Furthermore, we combined the extracted knowledge with semi-supervised machine learning to create hypotheses to guide future work and discovered a direct interaction between two important cancer genes.

bioinformatics↗

bioRxiv2018

Cell Diameter in Bacillus subtilis is Determined by the Opposing Actions of Two Distinct Cell Wall Synthetic Systems

Rod shaped bacteria grow by adding material into their cell wall via the action of two spatially distinct enzymatic systems: The Rod system moves around the cell circumference, while the class A penicillin-binding proteins (aPBPs) are unorganized. To understand how the combined action of these two systems defines bacterial dimensions, we examined how each system affects the growth and width of Bacillus subtilis, as well as the mechanical anisotropy and orientation of material within their sacculi. We find that rod diameter is not determined by MreB, rather it depends on the balance between the systems: The Rod system reduces diameter, while aPBPs increase it. RodA/PBP2A can both thin or widen cells, depending on its levels relative to MreBCD. Increased Rod system activity correlates with an increased density of directional MreB filaments, and a greater fraction of directionally moving PBP2A molecules. This increased circumferential synthesis increases the amount of oriented material within the sacculi, increasing their mechanical anisotropy and reinforcing rod shape. Together, these experiments explain how the combined action of the two main cell wall synthetic systems build rods of different widths, a model that appears generalizable: Escherichia coli containing Rod system mutants show the same relationship between the density of directionally moving MreB filaments and cell width.

microbiology↗

bioRxiv2018

A network of epigenomic and transcriptional cooperation encompassing an epigenomic master regulator in cancer

Coordinated experiments focused on transcriptional responses and chromatin states are well-equipped to capture different epigenomic and transcriptomic levels governing the circuitry of a regulatory network. We propose a workflow for the genome-wide identification of epigenomic and transcriptional cooperation to elucidate transcriptional networks in cancer. Gene promoter annotation in combination with network analysis and sequence-resolution of enriched transcriptional motifs in epigenomic data reveals transcription factor families that act synergistically with epigenomic master regulators. A close teamwork of the transcriptional and epigenomic machinery was discovered. The network is tightly connected and includes the histone lysine demethylase KDM3A, basic helix-loop-helix factors MYC, HIF1A, and SREBF1, as well as differentiation factors AP1, MYOD1, SP1, MEIS1, ZEB1 and ELK1. In such a cooperation network, one component opens the chromatin, another one recognizes gene-specific DNA motifs, others scaffold between histones, cofactors, and the transcriptional complex. In cancer, due to the ability to team up with transcription factors, epigenetic factors concert mitogenic and metabolic gene networks, claiming the role of a cancer master regulators or epioncogenes.\n\nSpecific histone modification patterns are commonly associated with open or closed chromatin states, and are linked to distinct biological outcomes by transcriptional activation or repression. Disruption of patterns of histone modifications is associated with loss of proliferative control and cancer. There is tremendous therapeutic potential in understanding and targeting histone modification pathways. Thus, investigating cooperation of chromatin remodelers and the transcriptional machinery is not only important for elucidating fundamental mechanisms of chromatin regulation, but also necessary for the design of targeted therapeutics.

systems biology↗

bioRxiv2018

Optimizing conservation of migratory species over their full annual cycle in the Western Hemisphere

Limited knowledge of the distribution, abundance, and habitat associations of migratory species introduces uncertainty about the most effective conservation actions. We used Neotropical migratory birds as a model group to evaluate contrasting approaches to land prioritization to support [≥]30% of the global abundances of 117 species throughout the annual cycle in the Western hemisphere. Conservation targets were achieved in 43% less land area in plans based on annual vs. weekly optimizations. Plans agnostic to population structure required comparatively less land area to meet targets, but at the expense of representation. Less land area was also needed to meet conservation targets when human-dominated lands were included rather than excluded from solutions. Our results point to key trade-offs between efforts minimizing the opportunity costs of conservation vs. those ensuring spatiotemporal representation of populations, and demonstrate a novel approach to the conservation of migratory species based on leading-edge abundance models and linear programming to identify portfolios of priority landscapes and inform conservation planners.

ecology↗

bioRxiv2018

In Vivo Measurements of the Frequency-Dependent Impedance of the Spinal Cord

Improved knowledge of the electrode-tissue impedance will be useful in optimizing the clinical protocols and resulting efficacy of the existing and emerging approaches to spinal cord stimulation. Toward that end, the complex impedance (amplitude and phase) of in vivo ovine spinal cord tissue was measured at the electrode-pial subdural surface interface from 5 Hz to 1 MHz, and with the bi-polar electrodes oriented both parallel and perpendicular to the rostral-caudal axis of the spinal cord. At stimulation frequencies above 10 kHz, most of the impedance then becomes resistive in nature and the phase diference between the stimulation signal and the resulting current drops to {approx} 10{ring}, thus maximizing power transfer to the tissues. Also, at these higher frequencies, the current pulse maintains significantly greater fidelity to the shape of the stimulation signal applied across the electrodes. Lastly, there were lower impedances associated with parallel as opposed to perpendicular orientation of the electrodes, thus reflecting the effects of fiber orientation within the spinal cord. Impedance differences of this kind have not been reported with epidural stimulation because of the electrical shunting effects of the intervening layer of relatively high conductivity cerebrospinal fluid. These observations provide a quantitative basis for improved models of spinal cord stimulation and suggest certain advantages for direct intradural stimulation relative to the standard epidural approaches. (Some figures in this article are in colour only in the electronic version)

biophysics↗