The use of environmental DNA (eDNA) surveys to monitor terrestrial species has been relatively limited, with successful implementations still confined to sampling DNA from natural or artificial water ...bodies and soil. Sampling water for eDNA depends on proximity to or availability of water, whereas eDNA from soil is limited in its spatial scale due to the large quantities necessary for processing and difficulty in doing so. These challenges limit the widespread use of eDNA in several systems, such as surveying forests for invasive insects. We developed two new eDNA aggregation approaches that overcome the challenges of above‐ground terrestrial sampling and eliminate the dependency on creating or utilizing pre‐existing water bodies to conduct eDNA sampling. The first, “spray aggregation,” uses spray action to remove eDNA from surface substrates and was developed for shrubs and other understorey vegetation, while the second, “tree rolling,” uses physical transfer via a roller to remove eDNA from the surface of tree trunks and large branches. We tested these approaches by surveying for spotted lanternfly, Lycorma delicatula, a recent invasive pest of northeastern USA that is considered a significant ecological and economic threat to forests and agriculture. We found that our terrestrial eDNA surveys matched visual surveys, but also detected L. delicatula presence ahead of visual surveys, indicating increased sensitivity of terrestrial eDNA surveys over currently used methodology. The terrestrial eDNA approaches we describe can be adapted for use in surveying a variety of forest insects and represent a novel strategy for surveying terrestrial biodiversity.
Imprime PGG (Imprime), an intravenously-administered, soluble β-glucan, has shown compelling efficacy in multiple phase 2 clinical trials with tumor targeting or anti-angiogenic antibodies. ...Mechanistically, Imprime acts as pathogen-associated molecular pattern (PAMP) directly activating innate immune effector cells, triggering a coordinated anti-cancer immune response. Herein, using whole blood from healthy human subjects, we show that Imprime-induced anti-cancer functionality is dependent on immune complex formation with naturally-occurring, anti-β glucan antibodies (ABA). The formation of Imprime-ABA complexes activates complement, primarily via the classical complement pathway, and is opsonized by iC3b. Immune complex binding depends upon Complement Receptor 3 and Fcg Receptor IIa, eliciting phenotypic activation of, and enhanced chemokine production by, neutrophils and monocytes, enabling these effector cells to kill antibody-opsonized tumor cells via the generation of reactive oxygen species and antibody-dependent cellular phagocytosis. Importantly, these innate immune cell changes were not evident in subjects with low ABA levels but could be rescued with exogenous ABA supplementation. Together, these data indicate that pre-existing ABA are essential for Imprime-mediated anti-cancer immune activation and suggest that pre-treatment ABA levels may provide a plausible patient selection biomarker to delineate patients most likely to benefit from Imprime-based therapy.
Reptiles are increasingly of conservation concern due to their susceptibility to habitat loss, emerging disease, and harvest in the wildlife trade. However, reptile populations are often difficult to ...monitor given the frequency of crypsis in their life history. This difficulty has left uncertain the conservation status of many species and the efficacy of conservation actions unknown. Environmental DNA (eDNA) surveys consistently elevate the detection rate of species they are designed to monitor, and while their use is promising for terrestrial reptile conservation, successes in developing such surveys have been sparse. We tested the degree to which inclusion of surface and soil eDNA sampling into conventional artificial‐cover methods elevates the detection probability of a small, cryptic terrestrial lizard, Scincella lateralis. The eDNA sampling of cover object surfaces with paint rollers elevated per sample detection probabilities for this species 4–16 times compared with visual surveys alone. We readily detected S. lateralis eDNA under cover objects up to 2 weeks after the last visual detection, and at some cover objects where no S. lateralis were visually observed in prior months. With sufficient sampling intensity, eDNA testing of soil under cover objects produced comparable per sample detection probabilities as roller surface methods. Our results suggest that combining eDNA and cover object methods can considerably increase the detection power of reptile monitoring programs, allowing more accurate estimates of population size, detection of temporal and spatial changes in habitat use, and tracking success of restoration efforts. Further research into the deposition and decay rates of reptile eDNA under cover objects, as well as tailored protocols for different species and habitats, is needed to bring the technique into widespread use.
Combinación del ADN Ambiental Superficial y del Suelo con Objetos de Cubierta Artificiales para Mejorar la Detección por Censos de los Reptiles Terrestres
Resumen
El interés por la conservación de los reptiles es cada vez mayor debido a su susceptibilidad ante la pérdida del hábitat, enfermedades emergentes y la captura para el mercado de fauna. Sin embargo, las poblaciones de reptiles son difíciles de monitorear por lo frecuente que es la cripsis en sus historias de vida. Esta dificultad deja incierto el estado de conservación de muchas especies y desconocida la eficacia de las acciones de conservación. Los censos de ADN ambiental (DNAa) elevan sistemáticamente la tasa de detección de las especies que monitorean, y aunque su uso es prometedor para la conservación de los reptiles terrestres, han sido escasos los éxitos en el desarrollo de dichos censos. Analizamos el grado al que la inclusión del muestreo de DNAa superficial y del suelo a los métodos convencionales de cobertura artificial eleva la probabilidad de detección de una pequeña lagartija terrestre críptica: Scincella lateralis. El muestreo de DNAa de las superficies con cobertura de objetos con rodillos de pintura elevó las probabilidades de detección por muestra para esta especie 4–16 veces más que los censos visuales. Detectamos fácilmente el DNAa de S. lateralis bajo los objetos de cubierta hasta dos semanas después de la última detección visual y en algunos objetos de cubierta en donde no se había observado en los meses previos a S. lateralis. Con suficiente intensidad de muestreo, el análisis de DNAa del suelo bajo objetos de cubierta produjo probabilidades de detección por muestra comparables como métodos de rodillo superficial. Nuestros resultados sugieren que la combinación del DNAa y los métodos de objetos de cobertura puede incrementar considerablemente el poder de detección de los programas de monitoreo de reptiles, lo que permite estimaciones más precisas del tamaño poblacional, detección de los cambios espaciales y temporales en el uso de hábitat y el éxito de rastreo de los esfuerzos de restauración. Además, se necesita la investigación sobre las tasas de depósito y descomposición del DNAa de reptiles bajo objetos de cubierta, así como los protocolos hechos para diferentes especies y hábitats, para que la técnica entre al uso difundido.
The detection of somatic mutations from cancer genome sequences is key to understanding the genetic basis of disease progression, patient survival and response to therapy. Benchmarking is needed for ...tool assessment and improvement but is complicated by a lack of gold standards, by extensive resource requirements and by difficulties in sharing personal genomic information. To resolve these issues, we launched the ICGC-TCGA DREAM Somatic Mutation Calling Challenge, a crowdsourced benchmark of somatic mutation detection algorithms. Here we report the BAMSurgeon tool for simulating cancer genomes and the results of 248 analyses of three in silico tumors created with it. Different algorithms exhibit characteristic error profiles, and, intriguingly, false positives show a trinucleotide profile very similar to one found in human tumors. Although the three simulated tumors differ in sequence contamination (deviation from normal cell sequence) and in subclonality, an ensemble of pipelines outperforms the best individual pipeline in all cases. BAMSurgeon is available at https://github.com/adamewing/bamsurgeon/.
Fungus-growing ants depend on a fungal mutualist that can fall prey to fungal pathogens. This mutualist is cultivated by these ants in structures called fungus gardens. Ants exhibit weeding behaviors ...that keep their fungus gardens healthy by physically removing compromised pieces. However, how ants detect diseases of their fungus gardens is unknown. Here, we applied the logic of Koch's postulates using environmental fungal community gene sequencing, fungal isolation, and laboratory infection experiments to establish that
spp. can act as previously unrecognized pathogens of
fungus gardens. Our environmental data showed that
are the most abundant noncultivar fungi in wild
fungus gardens. We further determined that metabolites produced by
induce an ant weeding response that mirrors their response to live
. Combining ant behavioral experiments with bioactivity-guided fractionation and statistical prioritization of metabolites in
extracts demonstrated that
ants weed in response to peptaibols, a specific class of secondary metabolites known to be produced by
fungi. Similar assays conducted using purified peptaibols, including the two previously undescribed peptaibols trichokindins VIII and IX, suggested that weeding is likely induced by peptaibols as a class rather than by a single peptaibol metabolite. In addition to their presence in laboratory experiments, we detected peptaibols in wild fungus gardens. Our combination of environmental data and laboratory infection experiments strongly support that peptaibols act as chemical cues of
pathogenesis in
fungus gardens.
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide and its progressive form, steatohepatitis, will be the leading indication for liver transplant by 2020. ...While risk factors for steatohepatitis have been identified, little work has been performed to identify factors protective against NAFLD development.
This study sought to identify factors predictive of normal liver histology in a bariatric cohort.
Patients undergoing weight loss surgery with liver biopsies at the time of surgery were included. Patients with other causes of chronic liver disease were excluded.
One hundred fifty-nine patients were included. Forty-nine patients had normal liver histology and 110 patients had NAFLD. Several previously identified factors associated with normal liver histology were found. Black race was the strongest predictor of the absence of NAFLD with an odds ratio (OR) of 6.8, 95% confidence interval (CI) 2.4-18.9. Low HOMA-IR was also associated with normal histology (OR 1.4, 95% CI 1.03-1.9). In contrast, low HDL was associated with a decreased chance of normal histology (OR 0.38, 95% CI 0.05-0.83). Interestingly, a novel protective factor, the absence of obstructive sleep apnea (OSA) was strongly associated with normal histology (OR 5.6, 95% CI 2.0-16.1). In multivariate regression controlling for BMI, black race, absence of OSA, low HOMA-IR and low ALT independently predicted normal liver histology with an area under the ROC curve of 0.85.
Our study confirmed several factors associated with normal liver histology, including black race and identified a novel factor, absence of OSA. Further evaluation of these factors will allow for improved understanding of the pathogenesis of NAFLD.
Buprestids are an emerging threat to broadleaf forests across the world. Bronze birch borer (Agrilus anxius, BBB) poses a serious threat to European birch species if the insect were to be introduced. ...Due to their cryptic lifestyle feeding on the vascular tissue of their host plants, buprestids and other wood borers can be difficult to observe or detect. Early detection tools are vital to swiftly implement eradication measures and prevent the establishment of introduced species. In this study, we developed novel qPCR and LAMP assays for BBB and investigated the specificity and sensitivity for their use as early detection tools in European forests. Plant chemicals may limit these assays, so we conducted sensitivity testing with extracted foliage and plant vascular tissues to determine potential inhibition effects on DNA amplification. Both assays were specific to the target species when tested against the DNA of 17 other European Agrilus/buprestid species, two Scolytinae, and five Cerambycids (N = 24). Both assays varied in sensitivity with the qPCR assay amplifying at a concentration as low as 20 fg/μL, whereas the LAMP assay amplified as low as 3.2 pg/μL. Plant chemicals in DNA extracts from leaves did not impact the sensitivity of either assay, reaching similar detection levels. In contrast, vascular tissue reduced the sensitivity of the LAMP assay, amplifying as low as 0.04 ng/μL compared with 0.008 ng/μL in the control. These results demonstrate that both assays are highly specific and sensitive tools that can be used to detect frass and identify larvae as well as monitor the spread of A. anxius. qPCR resulted in more sensitive than LAMP overall. Thus, if results are needed quickly to make fast management decisions or as an initial screening of samples, the LAMP method is optimal. However, if fine detection is critical, then qPCR is preferential.
Bronze birch borer (Agrilus anxius) is a pest of European birch (Betula spp.) to prevent it from establishing in European forests, we designed LAMP and qPCR assays. Both assays are specific to bronze birch borer to a low limit of detection of DNA and were field‐validated with frass and larval samples.
Platform-specific error profiles necessitate confirmatory studies where predictions made on data generated using one technology are additionally verified by processing the same samples on an ...orthogonal technology. However, verifying all predictions can be costly and redundant, and testing a subset of findings is often used to estimate the true error profile.
To determine how to create subsets of predictions for validation that maximize accuracy of global error profile inference, we developed Valection, a software program that implements multiple strategies for the selection of verification candidates. We evaluated these selection strategies on one simulated and two experimental datasets.
Valection is implemented in multiple programming languages, available at: http://labs.oicr.on.ca/boutros-lab/software/valection.
Abstract
Though neuromorphic computers have typically targeted applications in machine learning and neuroscience (‘cognitive’ applications), they have many computational characteristics that are ...attractive for a wide variety of computational problems. In this work, we review the current state-of-the-art for non-cognitive applications on neuromorphic computers, including simple computational kernels for composition, graph algorithms, constrained optimization, and signal processing. We discuss the advantages of using neuromorphic computers for these different applications, as well as the challenges that still remain. The ultimate goal of this work is to bring awareness to this class of problems for neuromorphic systems to the broader community, particularly to encourage further work in this area and to make sure that these applications are considered in the design of future neuromorphic systems.
PDF
