Small unmanned aircraft systems (UAS) may be useful for conducting high-precision, low-disturbance waterbird surveys, but limited data exist on their effectiveness. We evaluated the capacity of a ...small UAS to census a large (>6,000 nests) coastal Common tern (Sterna hirundo) colony of which ground surveys are particularly disruptive and time-consuming. We compared aerial photographic tern counts to ground nest counts in 45 plots (5-m radius) throughout the colony at three intervals over a nine-day period in order to identify sources of variation and establish a coefficient to estimate nest numbers from UAS surveys. We also compared a full colony ground count to full counts from two UAS surveys conducted the following day. Finally, we compared colony disturbance levels over the course of UAS flights to matched control periods. Linear regressions between aerial and ground counts in plots had very strong correlations in all three comparison periods (R2 = 0.972-0.989, P < 0.001) and regression coefficients ranged from 0.928-0.977 terns/nest. Full colony aerial counts were 93.6% and 94.0%, respectively, of the ground count. Varying visibility of terns with ground cover, weather conditions and image quality, and changing nest attendance rates throughout incubation were likely sources of variation in aerial detection rates. Optimally timed UAS surveys of Common tern colonies following our method should yield population estimates in the 93-96% range of ground counts. Although the terns were initially disturbed by the UAS flying overhead, they rapidly habituated to it. Overall, we found no evidence of sustained disturbance to the colony by the UAS. We encourage colonial waterbird researchers and managers to consider taking advantage of this burgeoning technology.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The taxonomy of the order Piroplasmida, which includes a number of clinically and economically relevant organisms, is a hotly debated topic amongst parasitologists. Three genera (Babesia, Theileria, ...and Cytauxzoon) are recognized based on parasite life cycle characteristics, but molecular phylogenetic analyses of 18S sequences have suggested the presence of five or more distinct Piroplasmida lineages. Despite these important advancements, a few studies have been unable to define the taxonomic relationships of some organisms (e.g. C. felis and T. equi) with respect to other Piroplasmida. Additional evidence from mitochondrial genome sequences and synteny should aid in the inference of Piroplasmida phylogeny and resolution of taxonomic uncertainties. In this study, we have amplified, sequenced, and annotated seven previously uncharacterized mitochondrial genomes (Babesia canis, Babesia vogeli, Babesia rossi, Babesia sp. Coco, Babesia conradae, Babesia microti-like sp., and Cytauxzoon felis) and identified additional ribosomal fragments in ten previously characterized mitochondrial genomes. Phylogenetic analysis of concatenated mitochondrial and 18S sequences as well as cox1 amino acid sequence identified five distinct Piroplasmida groups, each of which possesses a unique mitochondrial genome structure. Specifically, our results confirm the existence of four previously identified clades (B. microti group, Babesia sensu stricto, Theileria equi, and a Babesia sensu latu group that includes B. conradae) while supporting the integration of Theileria and Cytauxzoon species into a single fifth taxon. Although known biological characteristics of Piroplasmida corroborate the proposed phylogeny, more investigation into parasite life cycles is warranted to further understand the evolution of the Piroplasmida. Our results provide an evolutionary framework for comparative biology of these important animal and human pathogens and help focus renewed efforts toward understanding the phylogenetic relationships within the group.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Different thresholds of Wnt signalling are thought to drive stem cell maintenance, regeneration, differentiation and cancer. However, the principle that oncogenic Wnt signalling could be specifically ...targeted remains controversial. Here we examine the requirement of BCL9/9l, constituents of the Wnt-enhanceosome, for intestinal transformation following loss of the tumour suppressor APC. Although required for Lgr5+ intestinal stem cells and regeneration, Bcl9/9l deletion has no impact upon normal intestinal homeostasis. Loss of BCL9/9l suppressed many features of acute APC loss and subsequent Wnt pathway deregulation in vivo. This resulted in a level of Wnt pathway activation that favoured tumour initiation in the proximal small intestine (SI) and blocked tumour growth in the colon. Furthermore, Bcl9/9l deletion completely abrogated β-catenin driven intestinal and hepatocellular transformation. We speculate these results support the just-right hypothesis of Wnt-driven tumour formation. Importantly, loss of BCL9/9l is particularly effective at blocking colonic tumourigenesis and mutations that most resemble those that occur in human cancer.
We investigated the therapeutic potential of JQ1, an inhibitor of the BET class of human bromodomain proteins, in B-cell acute lymphoblastic leukemia (B-ALL). We show that JQ1 potently reduces the ...viability of B-ALL cell lines with high-risk cytogenetics. Among the most sensitive were lines with rearrangements of CRLF2, which is overexpressed in ∼ 10% of B-ALL. CRLF2 heterodimerizes with the IL7 receptor (IL7R) and signals through JAK2, JAK1, and STAT5 to drive proliferation and suppress apoptosis. As previously observed, JQ1 induced the down-regulation of MYC transcription, the loss of BRD4 at the MYC promoter, and the reduced expression of c-Myc target genes. Strikingly, JQ1 also down-regulated IL7R transcription, depleted BRD4 from the IL7R promoter, and reduced JAK2 and STAT5 phosphorylation. Genome-wide expression profiling demonstrated a restricted effect of JQ1 on transcription, with MYC and IL7R being among the most down-regulated genes. Indeed, IL7R was the only cytokine receptor in CRLF2-rearranged B-ALL cells significantly down-regulated by JQ1 treatment. In mice xenografted with primary human CRLF2-rearranged B-ALL, JQ1 suppressed c-Myc expression and STAT5 phosphorylation and significantly prolonged survival. Thus, bromodomain inhibition is a promising therapeutic strategy for B-ALL as well as other conditions dependent on IL7R signaling.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We have established Meloidogyne hapla as a tractable model plant-parasitic nematode amenable to forward and reverse genetics, and we present a complete genome sequence. At 54 Mbp, M. hapla represents ...not only the smallest nematode genome yet completed, but also the smallest metazoan, and defines a platform to elucidate mechanisms of parasitism by what is the largest uncontrolled group of plant pathogens worldwide. The M. hapla genome encodes significantly fewer genes than does the free-living nematode Caenorhabditis elegans (most notably through a reduction of odorant receptors and other gene families), yet it has acquired horizontally from other kingdoms numerous genes suspected to be involved in adaptations to parasitism. In some cases, amplification and tandem duplication have occurred with genes suspected of being acquired horizontally and involved in parasitism of plants. Although M. hapla and C. elegans diverged >500 million years ago, many developmental and biochemical pathways, including those for dauer formation and RNAi, are conserved. Although overall genome organization is not conserved, there are areas of microsynteny that may suggest a primary biological function in nematodes for those genes in these areas. This sequence and map represent a wealth of biological information on both the nature of nematode parasitism of plants and its evolution.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
IMPORTANCE: There are currently no approved treatments for peanut allergy. OBJECTIVE: To assess the efficacy and adverse events of epicutaneous immunotherapy with a peanut patch among peanut-allergic ...children. DESIGN, SETTING, AND PARTICIPANTS: Phase 3, randomized, double-blind, placebo-controlled trial conducted at 31 sites in 5 countries between January 8, 2016, and August 18, 2017. Participants included peanut-allergic children (aged 4-11 years n = 356 without a history of a severe anaphylactic reaction) developing objective symptoms during a double-blind, placebo-controlled food challenge at an eliciting dose of 300 mg or less of peanut protein. INTERVENTIONS: Daily treatment with peanut patch containing either 250 μg of peanut protein (n = 238) or placebo (n = 118) for 12 months. MAIN OUTCOMES AND MEASURES: The primary outcome was the percentage difference in responders between the peanut patch and placebo patch based on eliciting dose (highest dose at which objective signs/symptoms of an immediate hypersensitivity reaction developed) determined by food challenges at baseline and month 12. Participants with baseline eliciting dose of 10 mg or less were responders if the posttreatment eliciting dose was 300 mg or more; participants with baseline eliciting dose greater than 10 to 300 mg were responders if the posttreatment eliciting dose was 1000 mg or more. A threshold of 15% or more on the lower bound of a 95% CI around responder rate difference was prespecified to determine a positive trial result. Adverse event evaluation included collection of treatment-emergent adverse events (TEAEs). RESULTS: Among 356 participants randomized (median age, 7 years; 61.2% male), 89.9% completed the trial; the mean treatment adherence was 98.5%. The responder rate was 35.3% with peanut-patch treatment vs 13.6% with placebo (difference, 21.7% 95% CI, 12.4%-29.8%; P < .001). The prespecified lower bound of the CI threshold was not met. TEAEs, primarily patch application site reactions, occurred in 95.4% and 89% of active and placebo groups, respectively. The all-causes rate of discontinuation was 10.5% in the peanut-patch group vs 9.3% in the placebo group. CONCLUSIONS AND RELEVANCE: Among peanut-allergic children aged 4 to 11 years, the percentage difference in responders at 12 months with the 250-μg peanut-patch therapy vs placebo was 21.7% and was statistically significant, but did not meet the prespecified lower bound of the confidence interval criterion for a positive trial result. The clinical relevance of not meeting this lower bound of the confidence interval with respect to the treatment of peanut-allergic children with epicutaneous immunotherapy remains to be determined. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02636699
Abstract
Advances in technological capabilities, operational simplicity and cost efficiency have promoted the rapid integration of unmanned aerial vehicles (UAVs) into ecological research, providing ...access to study taxa that are otherwise difficult to survey, such as bats. Many bat species are currently at risk, but accurately surveying populations is challenging for species that do not roost in large aggregations. Acoustic recorders attached to UAVs provide an opportunity to survey bats in challenging habitats. However, UAVs may alter bat behaviour, leading to avoidance of the UAV, reduced detection rates and inaccurate surveys. We evaluated the number of bat passes detected with and without the presence of a small, commercial UAV in open habitats. Only 22% of bat passes were recorded in the presence of the UAV (0.23 ± 0.09 passes/min) compared to control periods without the UAV (1.03 ± 0.17 passes/min), but the effect was smaller on the big brown bat/silver-haired bat (
Eptesicus fuscus
/
Lasionycteris noctivagans
) acoustic complex. Noise interference from the UAV also reduced on-board bat detection rates. We conclude that acoustic records attached to UAVs may inaccurately survey bat populations due to low and variable detection rates by such recorders.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Data from observational studies suggest that body mass index (BMI) is causally related to esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE). However, the relationships may ...be affected by bias and confounding.
We used data from the Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study: 999 patients with EAC, 2061 patients with BE, and 2169 population controls. We applied the two-stage control function instrumental variable method of the Mendelian randomization approach to estimate the unbiased, unconfounded effect of BMI on risk of EAC and BE. This was performed using a genetic risk score, derived from 29 genetic variants shown to be associated with BMI, as an instrument for lifetime BMI. A higher score indicates propensity to obesity. All tests were two-sided.
The genetic risk score was not associated with potential confounders, including gastroesophageal reflux symptoms and smoking. In the instrumental variable analyses (IV), EAC risk increased by 16% (IV-odds ratio OR = 1.16, 95% confidence interval CI = 1.01 to 1.33) and BE risk increased by 12% (IV-OR = 1.12, 95% CI = 1.00 to 1.25) per 1kg/m(2) increase in BMI. BMI was statistically significantly associated with EAC and BE in conventional epidemiologic analyses.
People with a high genetic propensity to obesity have higher risks of esophageal metaplasia and neoplasia than people with low genetic propensity. These analyses provide the strongest evidence to date that obesity is independently associated with BE and EAC, and is not due to confounding or bias inherent in conventional epidemiologic analyses.
Small off-the-shelf unmanned aircraft systems (UAS) could prove useful for surveying waterbirds. A low-end model was evaluated for surveying flocks of Canada Geese (Branta canadensis) and Snow Geese ...(Chen caerulescens) by comparing photographic counts from repeated flybys to repeated visual ground counts. Due to low contrast of Canada Geese with the ground, UAS counts based on confident detections only had a lower mean than ground counts for five out of six flocks (>30% lower for three flocks) and coefficients of variation (CV) ranging from 11–106%, compared to 1–6% for ground counts. Conversely, UAS counts of high-contrast Snow Geese were 60% higher on average and less variable (CV = 1–6%) than ground counts (CV = 11%). In some cases the aircraft likely detected birds that were not seen from the ground due to an obstructed view. Shortcomings of the UAS were mainly related to its unsophisticated imaging system compared to more expensive models. Otherwise, the UAS proved capable of being conveniently transported and deployed over flocks without causing them to flush. Further consideration should be given to off-the-shelf UAS for surveying waterbirds over small areas (<5-km radius) that are difficult to survey from the ground or as an option for performing low-disturbance surveys.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The growing field of aeroecology is limited by difficulties associated with sampling in the air column. Aerial insects are particularly hard to sample, despite being the main prey in the air column, ...with some recent studies attempting to use drones as a collection method. We conducted a study to determine the optimal drone settings for collecting insects above the canopy, where drones are seldom used. By attaching a net to the body of a small, commercial drone, we tested yield from different height, speed, and net settings in wetlands, as well as compared insect diversity across different habitat canopies. Height was the most important setting; grazing the canopy yielded significantly more insects than flying one meter above it. Speed, drone type, and net size did not influence the number of insects caught per trial. Wetland canopies had higher abundance, diversity, and species richness in its arthropod populations compared to forest canopies or lakes. Compared to the yield of Lindgren funnels-a traditional sampling method in entomology-drones captured higher diversity and abundance of insects in a fraction of the time. This study confirms that drones are an efficient and accurate way to collect canopy arthropods.
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