Biology subjects

Wilson, S.

Publications and source records attributed to Wilson, S..

6 recordsLinked to original sources

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↗