Through recurrent bouts synchronous with the hair cycle, quiescent melanocyte stem cells (McSCs) become activated to generate proliferative progeny that differentiate into pigment-producing ...melanocytes. The signaling factors orchestrating these events remain incompletely understood. Here, we use single-cell RNA sequencing with comparative gene expression analysis to elucidate the transcriptional dynamics of McSCs through quiescence, activation, and melanocyte maturation. Unearthing converging signs of increased WNT and BMP signaling along this progression, we endeavored to understand how these pathways are integrated. Employing conditional lineage-specific genetic ablation studies in mice, we found that loss of BMP signaling in the lineage leads to hair graying due to a block in melanocyte maturation. We show that interestingly, BMP signaling functions downstream from activated McSCs and maintains WNT effector, transcription factor LEF1. Employing pseudotime analysis, genetics, and chromatin landscaping, we show that following WNT-mediated activation of McSCs, BMP and WNT pathways collaborate to trigger the commitment of proliferative progeny by fueling LEF1- and MITF-dependent differentiation. Our findings shed light upon the signaling interplay and timing of cues that orchestrate melanocyte lineage progression in the hair follicle and underscore a key role for BMP signaling in driving complete differentiation.
Summary
A systematic approach is used to design and tailor sensing materials for targeted analytes and specific applications. An example is used to demonstrate how potential sensing materials can be ...designed based on the chemical nature of both the target analyte and the sensing material, and thus predominant sensing mechanisms by which the two interact. The example analyte is a small, polar molecule able to hydrogen bond; therefore, a sensing material that targets the analyte should have polymer chains that pack tightly together, be polar, and be able to hydrogen bond. Any metal oxide dopants should be able to coordinate to both the target analyte and the polymer. Polyaniline and poly (o‐anisidine), along with nickel oxide and zinc oxide, are chosen as potential sensing materials and subsequently evaluated based on their ability to sorb the analyte in question.
Herbicide use on boreal transmission line rights-of-way has been relatively limited compared to more temperate regions and therefore challenges exist in estimating and communicating the associated ...risks. Herbicides directly enter the ecosystem through deposition on vegetation and soils and can be a vector of contamination to browsing herbivores. Triclopyr drift and foliage concentrations were quantified following basal bark (Garlon RTU) and low-volume foliar (Garlon XRT) field treatments to aspen (Populus tremuloides) saplings and willow (Salix bebbiana) shrubs, respectively. Greater drift concentrations localized at the stem base were observed following basal bark treatments. Conversely, concentrations in foliage following the low-volume foliar treatment (DT50 = 5.7 days and DT90 = 34.6 days) were much higher than following basal bark treatment, which also required two days to translocate into the leaves. However, dissipation was rapid from both application methods and triclopyr in foliage was less than 20 μg g−1 a year following application. A risk assessment revealed an acceptable level of risk for acute toxicity to wildlife browsing on contaminated leaves from the residues detected in this study; however, an unacceptable level of risk for chronic toxicity to long-term browsing moose. Site-specific data regarding browsing behaviour on herbicide treated rights-of-ways and species-specific reference values are needed to improve confidence in the tier-two risk assessment. Basal bark application is ideal when stem density is lower and toxic effects for herbivores is of concern and low-volume foliar applications are best suited in areas with higher stem density when off-target herbicide deposition is less acceptable.
Display omitted
•Higher herbicide concentrations localized at stem base following basal bark treatment.•Herbicide residue in foliage lower with basal bark than low-volume foliar treatment.•Herbicide residues from targeted treatments were below levels of ecological concern.•Browsing behaviour needed to more effectively estimate chronic effects for wildlife.•Suitable targeted treatment depends on stem density and acceptable risk to wildlife.
Background
The identification of extrauterine disease is critical to the management of patients with high‐risk endometrial cancer. The purpose of the current study was to determine the accuracy of ...preoperative positron emission tomography (PET)/computed tomography (CT) in the detection of extrauterine disease.
Methods
Women with high‐risk endometrial cancer were enrolled prospectively and underwent preoperative PET/CT followed by surgery, including sentinel lymph node biopsy and lymphadenectomy. Primary tumor factors on PET/CT were correlated with lymph node pathology. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for the detection of lymphadenopathy and peritoneal disease by PET/CT.
Results
A total of 112 patients were enrolled and underwent PET/CT between April 2013 and May 2016, 108 of whom were evaluable. On PET/CT, 21 patients (19.4%) were found to have extrauterine disease, 18 (17%) had positive lymph nodes, and 8 (7%) had peritoneal disease. A total of 108 patients underwent surgery, 103 of whom (95%) underwent lymphadenectomy. The sensitivity of PET/CT to detect positive lymph nodes was 45.8%, with a specificity of 91.1%, positive predictive value of 61.1%, and negative predictive value of 84.7%. The false‐negative rate was 54.2%. There was no difference in primary tumor characteristics on imaging noted between patients with positive and negative lymph nodes. The sensitivity of PET/CT to detect peritoneal disease was 37.5%, with a specificity of 97.8%, positive predictive value of 75%, and negative predictive value of 90.0%. The false‐negative rate was 62.5%.
Conclusions
Preoperative PET/CT did not reliably predict the presence of extrauterine disease in women with high‐risk endometrial cancer. Given the high false‐negative rates, PET/CT should not be used in the preoperative treatment planning of these patients.
Preoperative positron emission tomography (PET)/computed tomography (CT) does not reliably predict extrauterine disease in women with high‐risk endometrial cancer. PET/CT should not be used in the preoperative treatment planning in patients with high‐risk endometrial cancer.
A sentinel lymph node biopsy is widely accepted as the standard of care for surgical staging in low-grade endometrial cancer, but its value in high-grade endometrial cancer remains controversial. The ...aim of this systematic review and meta-analysis was to evaluate the performance characteristics of sentinel lymph node biopsy in patients with endometrial cancer with high-grade histology (registered in the International Prospective Register of Systematic Reviews with identifying number CRD42020160280).
We systematically searched the MEDLINE, Epub Ahead of Print, MEDLINE In-Process & Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Embase databases all through the OvidSP platform. The search was performed between January 1, 2000, and January 26, 2021. ClinicalTrials.gov was searched to identify ongoing registered clinical trials.
We included prospective cohort studies in which sentinel lymph node biopsy were evaluated in clinical stage I patients with high-grade endometrial cancer (grade 3 endometrioid, serous, clear cell, carcinosarcoma, mixed, undifferentiated or dedifferentiated, and high-grade not otherwise specified) with a cervical injection of indocyanine green for sentinel lymph node detection and at least a bilateral pelvic lymphadenectomy as a reference standard. If the data were not reported specifically for patients with high-grade histology, the authors were contacted for aggregate data.
We pooled the detection rates and measures of diagnostic accuracy using a generalized linear mixed-effects model with a logit and assessed the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 tool.
We identified 16 eligible studies of which the authors for 9 of the studies provided data on 429 patients with high-grade endometrial cancer specifically. The study-level median age was 66 years (range, 44–82.5 years) and the study-level median body mass index was 28.6 kg/m2 (range, 19.4–43.7 kg/m2). The pooled detection rates were 91% per patient (95% confidence interval, 85%–95%; I2=59%) and 64% bilaterally (95% confidence interval, 53%–73%; I2=69%). The overall node positivity rate was 26% (95% confidence interval, 19%–34%; I2=44%). Of the 87 patients with positive node results, a sentinel lymph node biopsy correctly identified 80, yielding a pooled sensitivity of 92% per patient (95% confidence interval, 84%–96%; I2=0%), a false negative rate of 8% (95% confidence interval, 4%–16%; I2=0%), and a negative predictive value of 97% (95% confidence interval, 95%–99%; I2=0%).
Sentinel lymph node biopsy accurately detect lymph node metastases in patients with high-grade endometrial cancer with a false negative rate comparable with that observed in low-grade endometrial cancer, melanoma, vulvar cancer, and breast cancer. These findings suggest that sentinel lymph node biopsy can replace complete lymphadenectomies as the standard of care for surgical staging in patients with high-grade endometrial cancer.
Sulphur cinquefoil (Potentilla recta L.) is an invasive perennial forb threatening rangelands in western North America. To identify best management strategies to control P. recta, we examined ...targeted goat (Capra hircus L.) grazing conducted once (pre-flowering) versus twice (pre-flowering and flowering and seed set), aminopyralid application, and integrated targeted grazing and aminopyralid as management strategies. We also examined the interaction between treatments and seasonality (spring and summer) and explored the possibility of off-target effects to non-target species. Two intermountain rangelands in British Columbia, Canada, were treated, one with targeted grazing treatments only and one with targeted grazing and herbicide treatments. Targeted grazing treatments were implemented in 2019 and 2020, and aminopyralid was applied once in 2019 at a rate of 56 g ai ha−1. Potentilla recta aboveground biomass and number of seed heads declined following targeted grazing treatments at both field sites in 2019 and 2020 when compared with the control, with no differences between targeted grazing treatments. In May 2020, before the implementation of targeted grazing for the second year, a decrease in P. recta biomass was not measured in the targeted grazing treatments, but biomass was 87% to 99% less in the herbicide-only and targeted grazing plus herbicide treatments. In July 2020, declines in biomass and seed heads in the herbicide-only and targeted grazing plus herbicide treatments did not differ from grazing twice, and aminopyralid effects did not differ among the three herbicide treatments. Further research is required to examine legacy effects of targeted goat grazing and aminopyralid on P. recta, establish reapplication frequency of treatments, and determine whether integrating targeted goat grazing and aminopyralid is needed in the long term to manage P. recta. A long-term study is also needed to examine off-target effects from targeted goat grazing and aminopyralid and ways to mitigate these effects to promote healthy native rangeland plant communities.
Petroleum hydrocarbon (PHC) degradation slows significantly during the winter which substantially increases the time it takes to remediate soil in Arctic landfarms. The aim of this laboratory trial ...was to assess the potential of a meat and bonemeal (MBM) biochar to stimulate PHC degradation in contaminated soil collected from Iqaluit, Canada. Over 90 days, 3% (w/w) MBM biochar significantly increased F3- (equivalent nC16-C34) PHC degradation rate constants (k) in frozen soils when compared to the fertilizer (urea and monoammonium phosphate) control. Taking into consideration extensive variability within treatments and negative k values, this difference may not reflect significant remediation. Decreasing C17/Pr and C18/Ph ratios in the frozen soil suggest that this reduction is a result of microbial degradation rather than volatilization. Amendment type and application rate affected the immediate abiotic losses of F2 and F3-PHC in sterile soils, with the greatest losses occurring in compost-amended treatments in the first 24 h. In frozen soils, MBM biochar was found to increase liquid water content (θliquid) but not nutrient supply rates. Under frozen but not thawed conditions, genes for aromatic (C2,3O and nahAc) but not aliphatic (alkB) PHC degradation increased over time in both biochar-amended and control treatments but total viable PHC-degrading populations only increased in biochar-amended soils. Based on these results, it is possible that PHC degradation in biochar-amended soils is active and even enhanced under frozen conditions, but further investigation is required.
•Laboratory-scale PHC degradation was investigated under frozen and thawed conditions using biochar and compost amendments.•Under frozen conditions, F3-PHC degradation rate constants were higher in biochar-amended soils.•Liquid water content increased in frozen soils amended with biochar, but not nutrient supply rates.•Total PHC-degrading microbial populations were stimulated in frozen soils amended with biochar.•Biochar applications at 3% (w/w) have the potential to increase PHC remediation rates in frozen soils.
Summary
A sensor array containing five different sensing materials has been created that is able to distinguish between six different volatile organic compounds (VOCs) at an analyte concentration of ...5 ppm. While none of the sensing materials, poly (2,5‐dimethyl aniline) (P25DMA) and P25DMA doped with four different metal oxide nanoparticles (Al2O3, NiO, TiO2, and ZnO), were selective towards any single analyte on their own, through the use of a filtering algorithm, this partial selectivity was exploited. Principal component analysis (PCA) was used as that a filtering algorithm, which was able to separate the responses from the sensing materials and identify six different gas analytes (acetaldehyde, acetone, benzene, ethanol, formaldehyde, and methanol). Both unknown gas analytes and a gas mixture were evaluated to determine the effectiveness of this sensor array.
What differentiates successful from unsuccessful open source software projects? This paper develops and tests a model of the impacts of license restrictiveness and organizational sponsorship on two ...indicators of success: user interest in, and development activity on, open source software development projects. Using data gathered from Freshmeat.net and project home pages, the main conclusions derived from the analysis are that (1) license restrictiveness and organizational sponsorship interact to influence user perceptions of the likely utility of open source software in such a way that users are most attracted to projects that are sponsored by nonmarket organizations and that employ nonrestrictive licenses, and (2) licensing and sponsorship address complementary developer motivations such that the influence of licensing on development activity depends on what kind of organizational sponsor a project has. Theoretical and practical implications are discussed, and the paper outlines several avenues for future research.
PDF
