Describing Genomic and Epigenomic Traits Underpinning Emerging Fungal Pathogens.

An unprecedented number of pathogenic fungi are emerging and causing disease in animals and plants, putting the resilience of wild and managed ecosystems in jeopardy. While the past decades have seen an increase in the number of pathogenic fungi, they have also seen the birth of new big data technologies and analytical approaches to tackle these emerging pathogens. We review how the linked fields of genomics and epigenomics are transforming our ability to address the challenge of emerging fungal pathogens. We explore the methodologies and bioinformatic toolkits that currently exist to rapidly analyze the genomes of unknown fungi, then discuss how these data can be used to address key questions that shed light on their epidemiology. We show how genomic approaches are leading a revolution into our understanding of emerging fungal diseases and speculate on future approaches that will transform our ability to tackle this increasingly important class of emerging pathogens

Mathematizing Darwin

Ernst Mayr called the first part of the evolutionary synthesis the ‘Fisherian synthesis’ on account of the dominant role played by R.A. Fisher in forging a mathematical theory of natural selection together with J.B.S. Haldane and Sewall Wright in the decade 1922–1932. It is here argued that Fisher’s contribution relied on a close reading of Darwin’s work to a much greater extent than did the contributions of Haldane and Wright, that it was synthetic in contrast to their analytic approach and that it was greatly influenced by his friendship with the Darwin family, particularly with Charles’s son Leonard

On the multiple ecological roles of water in river networks

The distribution and movement of water can influence the state and dynamics of terrestrial and aquatic ecosystems through a diversity of mechanisms. These mechanisms can be organized into three general categories wherein water acts as (1) a resource or habitat for biota, (2) a vector for connectivity and exchange of energy, materials, and organisms, and (3) as an agent of geomorphic change and disturbance. These latter two roles are highlighted in current models, which emphasize hydrologic connectivity and geomorphic change as determinants of the spatial and temporal distributions of species and processes in river systems. Water availability, on the other hand, has received less attention as a driver of ecological pattern, despite the prevalence of intermittent streams, and strong potential for environmental change to alter the spatial extent of drying in many regions. Here we summarize long-term research from a Sonoran Desert watershed to illustrate how spatial patterns of ecosystem structure and functioning reflect shifts in the relative importance of different 'roles of water' across scales of drainage size. These roles are distributed and interact hierarchically in the landscape, and for the bulk of the drainage network it is the duration of water availability that represents the primary determinant of ecological processes. Only for the largest catchments, with the most permanent flow regimes, do flood-associated disturbances and hydrologic exchange emerge as important drivers of local dynamics. While desert basins represent an extreme case, the diversity of mechanisms by which the availability and flow of water influence ecosystem structure and functioning are general. Predicting how river ecosystems may respond to future environmental pressures will require clear understanding of how changes in the spatial extent and relative overlap of these different roles of water shape ecological patterns. © 2013 Sponseller et al

PETMiner - A visual analysis tool for petrophysical properties of core sample data

The aim of the PETMiner software is to reduce the time and monetary cost of analysing petrophysical data that is obtained from reservoir sample cores. Analysis of these data requires tacit knowledge to fill ‘gaps’ so that predictions can be made for incomplete data. Through discussions with 30 industry and academic specialists, we identified three analysis use cases that exemplified the limitations of current petrophysics analysis tools. We used those use cases to develop nine core requirements for PETMiner, which is innovative because of its ability to display detailed images of the samples as data points, directly plot multiple sample properties and derived measures for comparison, and substantially reduce interaction cost. An 11-month evaluation demonstrated benefits across all three use cases by allowing a consultant to: (1) generate more accurate reservoir flow models, (2) discover a previously unknown relationship between one easy-to-measure property and another that is costly, and (3) make a 100-fold reduction in the time required to produce plots for a report

Associating GWAS Information with the Notch Signaling Pathway Using Transcription Profiling

Genome-wide association studies (GWAS) have identified SNPs associated with breast cancer. However, they offer limited insights about the biological mechanisms by which SNPs confer risk. We investigated the association of GWAS information with a major oncogenic pathway in breast cancer, the Notch signaling pathway. We first identified 385 SNPs and 150 genes associated with risk for breast cancer by mining data from 41 GWAS. We then investigated their expression, along with 32 genes involved in the Notch signaling pathway using two publicly available gene expression data sets from the Caucasian (42 cases and 143 controls) and Asian (43 cases and 43 controls) populations. Pathway prediction and network modeling confirmed that Notch receptors and genes involved in the Notch signaling pathway interact with genes containing SNPs associated with risk for breast cancer. Additionally, we identified other SNP-associated biological pathways relevant to breast cancer, including the P53, apoptosis and MAP kinase pathways

Asymmetric interlimb transfer of concurrent adaptation to opposing dynamic forces

Interlimb transfer of a novel dynamic force has been well documented. It has also been shown that unimanual adaptation to opposing novel environments is possible if they are associated with different workspaces. The main aim of this study was to test if adaptation to opposing velocity dependent viscous forces with one arm could improve the initial performance of the other arm. The study also examined whether this interlimb transfer occurred across an extrinsic, spatial, coordinative system or an intrinsic, joint based, coordinative system. Subjects initially adapted to opposing viscous forces separated by target location. Our measure of performance was the correlation between the speed profiles of each movement within a force condition and an ‘average’ trajectory within null force conditions. Adaptation to the opposing forces was seen during initial acquisition with a significantly improved coefficient in epoch eight compared to epoch one. We then tested interlimb transfer from the dominant to non-dominant arm (D → ND) and vice-versa (ND → D) across either an extrinsic or intrinsic coordinative system. Interlimb transfer was only seen from the dominant to the non-dominant limb across an intrinsic coordinative system. These results support previous studies involving adaptation to a single dynamic force but also indicate that interlimb transfer of multiple opposing states is possible. This suggests that the information available at the level of representation allowing interlimb transfer can be more intricate than a general movement goal or a single perceived directional error

Microelectrode array recordings from the ventral roots in chronically implanted cats

ventral spinal roots contain the axons of spinal motoneurons and provide the only location in the peripheral nervous system where recorded neural activity can be assured to be motor rather than sensory. This study demonstrates recordings of single unit activity from these ventral root axons using floating microelectrode arrays (FMAs). Ventral root recordings were characterized by examining single unit yield and signal-to-noise ratios (SNR) with 32-channel FMAs implanted chronically in the L6 and L7 spinal roots of nine cats. Single unit recordings were performed for implant periods of up to 12 weeks. Motor units were identified based on active discharge during locomotion and inactivity under anesthesia. Motor unit yield and SNR were calculated for each electrode, and results were grouped by electrode site size, which were varied systematically between 25 and 160μm to determine effects on signal quality. The unit yields and SNR did not differ significantly across this wide range of electrode sizes. Both SNR and yield decayed over time, but electrodes were able to record spikes with SNR >2 up to 12 weeks post-implant. These results demonstrate that it is feasible to record single unit activity from multiple isolated motor units with penetrating microelectrode arrays implanted chronically in the ventral spinal roots. This approach could be useful for creating a spinal nerve interface for advanced neural prostheses, and results of this study will be used to improve design of microelectrodes for chronic neural recording in the ventral spinal roots. © 2014 Debnath, Bauman, Fisher, Weber and Gaunt

Molecular genotyping of placental site and epithelioid trophoblastic tumours; female predominance

OBJECTIVE: To investigate a large series of placental site trophoblastic tumours (PSTT) and epithelioid trophoblastic tumours (ETT) and determine the relationship between their development and the type and sex of both the immediately antecedent and causative pregnancies. METHODS: The antecedent pregnancy was determined from patient records in 92 cases with a confirmed diagnosis of PSTT, ETT or mixed PSTT/ETT. In a subset of 57 cases, type and sex of the causative pregnancy was established by molecular genotyping of patient and tumour tissue microdissected from formalin-fixed, paraffin-embedded blocks. RESULTS: The antecedent pregnancy was a normal live birth in 59 (64%) cases, a hydatidiform mole in 19 (21%) and other pregnancy loss in 14 (15%). Where the sex was recorded, 36 (78%) of 46 antecedent normal pregnancies were female, a significantly greater proportion than expected (p<0.0001). Genotyping of 57 cases found 15 (26%) to derive from hydatidiform moles while 42 (74%) arose in non-molar pregnancies. Where the causative pregnancy was non-molar, 38 (91%) tumours arose in female conceptions, significantly greater than expected (p <0.0001). Analysis of short tandem repeats on the X chromosome in three tumours with an XY chromosomal constitution confirmed that the X chromosome was maternal in origin. CONCLUSIONS: PSTT and ETT predominantly arise in female pregnancies but can develop in male pregnancies. A male derived X chromosome is not required for the development of these tumours. While these tumours are predominantly female it is not because most originate in complete hydatidiform moles

Using false discovery rates to benchmark SNP-callers in next-generation sequencing projects

This is the final version of the article. Available from Nature Publishing Group via the DOI in this record.Sequence alignments form the basis for many comparative and population genomic studies. Alignment tools provide a range of accuracies dependent on the divergence between the sequences and the alignment methods. Despite widespread use, there is no standard method for assessing the accuracy of a dataset and alignment strategy after resequencing. We present a framework and tool for determining the overall accuracies of an input read dataset, alignment and SNP-calling method providing an isolate in that dataset has a corresponding, or closely related reference sequence available. In addition to this tool for comparing False Discovery Rates (FDR), we include a method for determining homozygous and heterozygous positions from an alignment using binomial probabilities for an expected error rate. We benchmark this method against other SNP callers using our FDR method with three fungal genomes, finding that it was able achieve a high level of accuracy. These tools are available at http://cfdr.sourceforge.net/.R.A.F. was funded by the Natural Environment Research Council (NERC). D.A.H. and M.C.F. were supported by the Wellcome Trust. No additional external funding received for this study

Causality and the Interpretation of Epidemiologic Evidence

There is an ongoing debate regarding how and when an agent’s or determinant’s impact can be interpreted as causation with respect to some target disease. The so-called criteria of causation, originating from the seminal work of Sir Austin Bradford Hill and Mervyn Susser, are often schematically applied disregarding the fact that they were meant neither as criteria nor as a checklist for attributing to a hazard the potential of disease causation. Furthermore, there is a tendency to misinterpret the lack of evidence for causation as evidence for lack of a causal relation. There are no criteria in the strict sense for the assessment of evidence concerning an agent’s or determinant’s propensity to cause a disease, nor are there criteria to dismiss the notion of causation. Rather, there is a discursive process of conjecture and refutation. In this commentary, I propose a dialogue approach for the assessment of an agent or determinant. Starting from epidemiologic evidence, four issues need to be addressed: temporal relation, association, environmental equivalence, and population equivalence. If there are no valid counterarguments, a factor is attributed the potential of disease causation. More often than not, there will be insufficient evidence from epidemiologic studies. In these cases, other evidence can be used instead that increases or decreases confidence in a factor being causally related to a disease. Even though every verdict of causation is provisional, action must not be postponed until better evidence is available if our present knowledge appears to demand immediate measures for health protection