Ionizing radiation is a potent carcinogen, inducing cancer through DNA damage. The signatures of mutations arising in human tissues following in vivo exposure to ionizing radiation have not been ...documented. Here, we searched for signatures of ionizing radiation in 12 radiation-associated second malignancies of different tumour types. Two signatures of somatic mutation characterize ionizing radiation exposure irrespective of tumour type. Compared with 319 radiation-naive tumours, radiation-associated tumours carry a median extra 201 deletions genome-wide, sized 1-100 base pairs often with microhomology at the junction. Unlike deletions of radiation-naive tumours, these show no variation in density across the genome or correlation with sequence context, replication timing or chromatin structure. Furthermore, we observe a significant increase in balanced inversions in radiation-associated tumours. Both small deletions and inversions generate driver mutations. Thus, ionizing radiation generates distinctive mutational signatures that explain its carcinogenic potential.
Constructing activity budgets for marine animals when they are at sea and cannot be directly observed is challenging, but recent advances in bio-logging technology offer solutions to this problem. ...Accelerometers can potentially identify a wide range of behaviours for animals based on unique patterns of acceleration. However, when analysing data derived from accelerometers, there are many statistical techniques available which when applied to different data sets produce different classification accuracies. We investigated a selection of supervised machine learning methods for interpreting behavioural data from captive otariids (fur seals and sea lions). We conducted controlled experiments with 12 seals, where their behaviours were filmed while they were wearing 3-axis accelerometers. From video we identified 26 behaviours that could be grouped into one of four categories (foraging, resting, travelling and grooming) representing key behaviour states for wild seals. We used data from 10 seals to train four predictive classification models: stochastic gradient boosting (GBM), random forests, support vector machine using four different kernels and a baseline model: penalised logistic regression. We then took the best parameters from each model and cross-validated the results on the two seals unseen so far. We also investigated the influence of feature statistics (describing some characteristic of the seal), testing the models both with and without these. Cross-validation accuracies were lower than training accuracy, but the SVM with a polynomial kernel was still able to classify seal behaviour with high accuracy (>70%). Adding feature statistics improved accuracies across all models tested. Most categories of behaviour -resting, grooming and feeding-were all predicted with reasonable accuracy (52-81%) by the SVM while travelling was poorly categorised (31-41%). These results show that model selection is important when classifying behaviour and that by using animal characteristics we can strengthen the overall accuracy.
An epigenetic clock for human skeletal muscle Voisin, Sarah; Harvey, Nicholas R.; Haupt, Larisa M. ...
Journal of cachexia, sarcopenia and muscle,
August 2020, Letnik:
11, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Background
Ageing is associated with DNA methylation changes in all human tissues, and epigenetic markers can estimate chronological age based on DNA methylation patterns across tissues. However, the ...construction of the original pan‐tissue epigenetic clock did not include skeletal muscle samples and hence exhibited a strong deviation between DNA methylation and chronological age in this tissue.
Methods
To address this, we developed a more accurate, muscle‐specific epigenetic clock based on the genome‐wide DNA methylation data of 682 skeletal muscle samples from 12 independent datasets (18–89 years old, 22% women, 99% Caucasian), all generated with Illumina HumanMethylation (HM) arrays (HM27, HM450, or HMEPIC). We also took advantage of the large number of samples to conduct an epigenome‐wide association study of age‐associated DNA methylation patterns in skeletal muscle.
Results
The newly developed clock uses 200 cytosine‐phosphate–guanine dinucleotides to estimate chronological age in skeletal muscle, 16 of which are in common with the 353 cytosine‐phosphate–guanine dinucleotides of the pan‐tissue clock. The muscle clock outperformed the pan‐tissue clock, with a median error of only 4.6 years across datasets (vs. 13.1 years for the pan‐tissue clock, P < 0.0001) and an average correlation of ρ = 0.62 between actual and predicted age across datasets (vs. ρ = 0.51 for the pan‐tissue clock). Lastly, we identified 180 differentially methylated regions with age in skeletal muscle at a false discovery rate < 0.005. However, gene set enrichment analysis did not reveal any enrichment for gene ontologies.
Conclusions
We have developed a muscle‐specific epigenetic clock that predicts age with better accuracy than the pan‐tissue clock. We implemented the muscle clock in an r package called Muscle Epigenetic Age Test available on Bioconductor to estimate epigenetic age in skeletal muscle samples. This clock may prove valuable in assessing the impact of environmental factors, such as exercise and diet, on muscle‐specific biological ageing processes.
Axially doped p–i–n InAs0.93Sb0.07 nanowire arrays have been grown on Si substrates and fabricated into photodetectors for shortwave infrared detection. The devices exhibit a leakage current density ...around 2 mA/cm2 and a 20% cutoff of 2.3 μm at 300 K. This record low leakage current density for InAsSb based devices demonstrates the suitability of nanowires for the integration of III–V semiconductors with silicon technology.
Attempts to understand farmer conservation behavior based on quantitative socio-demographic, attitude, and awareness variables have been largely inconclusive. In order to understand fully how farmers ...are making conservation decisions, 32 in-depth interviews were conducted in the Eagle Creek watershed in central Indiana. Coding for environmental attitudes and practice adoption revealed several dominant themes, representing multi-dimensional aspects of environmental attitudes. Farmers who were motivated by off-farm environmental benefits and those who identified responsibilities to others (stewardship) were most likely to adopt conservation practices. Those farmers who focused on the farm as business and were most concerned about profitability were less likely to adopt practices. The notion of environmental stewardship in particular was found to be much more complex than the way it is traditionally measured in quantitative studies. The interplay between on-farm and off-farm benefits to practice adoption is an issue that quantitative studies largely do not address. This study seeks to increase understanding of farmers’ environmental attitudes and the connections to conservation behavior.
The mechanisms through which wave action induces cliff erosion are not well quantified, which limits our ability to model future cliff erosion. Previous studies have investigated using seismic ...measurements of cliff‐top ground motion from wave impacts as a proxy for potential wave driven cliff erosion. However, most attention has focussed on averaged hourly statistics, rather than at the individual wave impact scale. Higher temporal resolution studies are needed to determine the extent to which frequent, low magnitude impacts transfer wave energy into cliff rock, compared to violent impacts that occur much less frequently. We carried out fieldwork in Taranaki, New Zealand on a cliff that is exposed to broken, breaking, and unbroken wave impacts at different tidal stages. Synchronized seismometer, wave gauge, and video data were collected to observe a range of wave impact types under different marine conditions. Approximately 7500 wave impacts were manually classified into eight groups according to the stage of wave transformation at impact using video data. Corresponding seismic signals were then analysed to compare ground motion and impact types. The greatest peaks in ground motion were associated with impact classes identifiable by the wave breaking just in front of, or onto the cliff face. Waves classed as broken and unbroken had a median displacement of 4.2 μm and 5.1 μm, respectively, whereas breaking wave impact classes had a median displacement value of 25.8 μm. Spectral analyses of impact types suggest that different impacts produce peaks in energy at different frequency bands, and the total energy transfer is higher for breaking wave impact classes. This research provides a first step in assessing the spectral signature of wave impacts at an individual wave scale, providing a new method to investigate wave–cliff interaction.
Individual wave impacts on a coastal cliff in Taranaki, New Zealand were categorized using video and the corresponding ground displacement measured by a seismometer were analysed. Results show that waves classified as breaking at impact generated highest ground displacement. Power spectral density (PSD) analyses shows differences in the magnitude of energy across different frequency bands for different impact types for this dataset, further work should focus on replicating these seismic signatures at other sites.
Echinoderms are characterized by a distinctive high-magnesium calcite endoskeleton as adults, but elements of this have been drastically reduced in some groups. Herein, we describe a new pentaradial ...echinoderm,
n. gen. n. sp., which provides, to our knowledge, the oldest evidence of secondary non-mineralization of the echinoderm skeleton. This material was collected from the Cambrian Kinzers Formation in York (Pennsylvania, USA) and is dated as
510 Ma. Detailed morphological observations demonstrate that the ambulacra (i.e. axial region) are composed of flooring and cover plates, but the rest of the body (i.e. extraxial region) is preserved as a dark film and lacks any evidence of skeletal plating. Moreover, X-ray fluorescence analysis reveals that the axial region is elevated in iron. Based on our morphological and chemical data and on taphonomic comparisons with other fossils from the Kinzers Formation, we infer that the axial region was originally calcified, while the extraxial region was non-mineralized. Phylogenetic analyses recover
as an edrioasteroid, indicating that this partial absence of skeleton resulted from a secondary reduction. We hypothesize that skeletal reduction resulted from lack of expression of the skeletogenic gene regulatory network in the extraxial body wall during development. Secondary reduction of the skeleton in
might have allowed for greater flexibility of the body wall.
Decipher (Decipher Biosciences Inc) is a genomic classifier (GC) developed to estimate the risk of distant metastasis (DM) after radical prostatectomy (RP) in patients with prostate cancer.
To ...validate the GC in the context of a randomized phase 3 trial.
This ancillary study used RP specimens from the phase 3 placebo-controlled NRG/RTOG 9601 randomized clinical trial conducted from March 1998 to March 2003. The specimens were centrally reviewed, and RNA was extracted from the highest-grade tumor available in 2019 with a median follow-up of 13 years. Clinical-grade whole transcriptomes from samples passing quality control were assigned GC scores (scale, 0-1). A National Clinical Trials Network-approved prespecified statistical plan included the primary objective of validating the independent prognostic ability of GC for DM, with secondary end points of prostate cancer-specific mortality (PCSM) and overall survival (OS). Data were analyzed from September 2019 to December 2019.
Salvage radiotherapy (sRT) with or without 2 years of bicalutamide.
The preplanned primary end point of this study was the independent association of the GC with the development of DM.
In this ancillary study of specimens from a phase 3 randomized clinical trial, GC scores were generated from 486 of 760 randomized patients with a median follow-up of 13 years; samples from a total of 352 men (median interquartile range age, 64.5 (60-70) years; 314 White 89.2% participants) passed microarray quality control and comprised the final cohort for analysis. On multivariable analysis, the GC (continuous variable, per 0.1 unit) was independently associated with DM (hazard ratio HR, 1.17; 95% CI, 1.05-1.32; P = .006), PCSM (HR, 1.39; 95% CI, 1.20-1.63; P < .001), and OS (HR, 1.17; 95% CI, 1.06-1.29; P = .002) after adjusting for age, race/ethnicity, Gleason score, T stage, margin status, entry prostate-specific antigen, and treatment arm. Although the original planned analysis was not powered to detect a treatment effect interaction by GC score, the estimated absolute effect of bicalutamide on 12-year OS was less when comparing patients with lower vs higher GC scores (2.4% vs 8.9%), which was further demonstrated in men receiving early sRT at a prostate-specific antigen level lower than 0.7 ng/mL (-7.8% vs 4.6%).
This ancillary validation study of the Decipher GC in a randomized trial cohort demonstrated association of the GC with DM, PCSM, and OS independent of standard clinicopathologic variables. These results suggest that not all men with biochemically recurrent prostate cancer after surgery benefit equally from the addition of hormone therapy to sRT.
ClinicalTrials.gov identifier: NCT00002874.
Abstract
Background
Sleep disturbances are associated with risk of cognitive decline but it is not clear if treating disturbed sleep mitigates decline. We examined differences in cognitive ...trajectories before and after sleep treatment initiation.
Method
Data came from the 2006–2014 Health and Retirement Study (HRS). At each of 5 waves, participants were administered cognitive assessments and scores were summed. Participants also reported if, in prior 2 weeks, they had taken medications or used other treatments to improve sleep. Our sample (N = 3 957) included individuals who at HRS 2006 were 50 years and older, had no cognitive impairment, reported no sleep treatment, and indicated experiencing sleep disturbance. We identified differences between those receiving versus not receiving treatment in subsequent waves and, among those treated (n = 1 247), compared cognitive trajectories before and after treatment.
Results
At baseline, those reporting sleep treatment at subsequent waves were more likely to be younger, female, Caucasian, to have more health conditions, to have higher body mass index, and more depressive symptoms (all ps ≤ .015). Decline in cognitive performance was mitigated in periods after sleep treatment versus periods before (B = −0.20, 95% CI = −0.25, −0.15, p < .001 vs B = −0.26, 95% CI = −0.32, −0.20, p < .001), and this same trend was seen for self-initiated and doctor-recommended treatments. Trends were driven by those with higher baseline cognitive performance—those with lower performance saw cognitive declines following sleep treatment.
Conclusions
In middle-aged and older adults with sleep disturbance, starting sleep treatment may slow cognitive decline. Future research should assess types, combinations, and timing of treatments most effective in improving cognitive health in later life.
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