The modification of gene expression profile, a first step in adaptation to exercise, leads to changes in the level of molecules associated with skeletal muscle activity and energy metabolism—such as ...myokines—as well as those involved in their transcriptional regulation, like microRNA. This study aimed to investigate the influence of strenuous exercise on circulating microRNAs and their possible association with myokine response. Pre-competition and post-competition plasma samples were collected from 14 male athletes participating in a vertical run (+1,000 m gain, 3,600 m length). Circulating total (t-miRNA) and extracellular vesicle-associated (EV-miRNA) miRNAs were extracted from the pooled plasma. Nanoparticle tracking analysis was performed to investigate pre- and post-competition EV concentration and size distribution. A panel of 179 miRNAs was assayed by qPCR and analyzed by Exiqon GenEx v6 normalized on the global mean. t-miRNA and EV-miRNAs whose level was ≥5-fold up- or down-regulated were validated for each single subject. Target prediction on MirWalk v3.0, Gene-Ontology, and pathway enrichment analysis on Panther v17.0 were performed to define the potential biological role of the identified miRNAs. A panel of 14 myokines was assayed in each sample by a multiplex immunoassay. In whole plasma, five miRNAs were upregulated and two were downregulated; in the EV fraction, five miRNAs were upregulated and three were downregulated. Nanoparticle tracking analysis revealed a similar EV size distribution in pre- and post-competition samples and a decreased concentration in post-competition samples related to pre-competition samples. Gene-Ontology and pathway enrichment analysis revealed that the identified t-miRNAs and EV-miRNAs were potentially involved in metabolism regulation in response to exercise. Correlation between fold-change of the post-competition relative to pre-competition plasma level of both t-miRNAs and EV-miRNAs and myokines further confirmed these results. This study provides an example of a systemic response to acute endurance exercise, in which circulating miRNAs play a pivotal role.
Bone is the most frequent site of metastasis of the most common cancers in men and women. Bone metastasis incidence has been steadily increasing over the years, mainly because of higher life ...expectancy in oncologic patients. Although bone metastases are sometimes asymptomatic, their consequences are most often devastating, impairing both life quality and expectancy, due to the occurrence of the skeletal-related events, including bone fractures, hypercalcemia and spinal cord compression. Up to 75% of patients endure crippling cancer-induced bone pain (CIBP), against which we have very few weapons. This review's purpose is to discuss the molecular and cellular mechanisms that lead to CIBP, including how cancer cells convert the bone "virtuous cycle" into a cancer-fuelling "vicious cycle", and how this leads to the release of molecular mediators of pain, including protons, neurotrophins, interleukins, chemokines and ATP. Preclinical tests and assays to evaluate CIBP, including the incapacitance tester (in vivo), and neuron/glial activation in the dorsal root ganglia/spinal cord (ex vivo) will also be presented. Furthermore, current therapeutic options for CIBP are quite limited and nonspecific and they will also be discussed, along with up-and-coming options that may render CIBP easier to treat and let patients forget they are patients.
Old conifer forests in the Pacific Northwest have a wide range of microhabitats induced by canopy structure and substrate characteristics. We used the Wind River Canopy Crane to sample lichens and ...bryophytes throughout the spectrum of habitats available to epiphytes. Of the 111 species found in 72 sample units, 97 were lichens and 14 were bryophytes. Epiphyte communities showed marked variation with respect to height in the canopy, bark vs. wood, degree of sheltering, and stem diameter. Of these factors, height in the canopy was most strongly related to epiphyte communities. Furthermore, the top two meters of the tallest trees hosted a diverse assemblage of both rare species (Tholurna dissimilis) and weedy, nitrophilous species (Candelaria concolor, Hypogymnia tubulosa, Parmelia sulcata), presumably induced by birds delivering lichen propagules and nutrients. Ten species were more frequent on bare wood than bark, including Ophioparma rubricosa, Letharia vulpina, Placynthiella spp., Ptychographa xylographoides, Trapeliopsis flexuosa, and Xylographa parallela. Species richness was highly variable, even within habitats. The only factor found related to species richness was height in the canopy, the middle and upper layers each having about twice the species per sample unit as lower in the canopy.
We examined biotic soil crust cover and composition at nine shrub-steppe sites in central and eastern Oregon, U.S.A. One pair of livestock-grazed and excluded transects was established at each site. ...Data were collected on the cover of biotic soil crust and vascular plant species, soil surface pH and electrical conductivity, and other environmental variables. Using gradient analysis, we found that differences in community composition among sites were most strongly related to soil pH, electrical conductivity (EC), and Calcareous Index Value (CIV; a scale representing the relative calcium carbonate content of soils). Other important variables included precipitation, elevation, aspect, and temperature. We found total crust cover to be highest at sites with lower pH, EC, and CIV. Dominant species differed markedly between the more calcareous sites with higher pH, and the less calcareous, lower pH sites. Livestock exclusion was not an important gradient in the ordination of these data, being overshadowed by the strong soil chemistry and climate gradients. However, overall community composition of soil crust species was different between grazed and long-ungrazed sites (p = 0.02, Blocked Multi-Response Permutation Procedure). Comparison of grazed and long-ungrazed sites revealed lower cover of biotic crusts, nitrogen-fixing lichens, crust-dominated soil surface roughness, and lower species richness in the grazed transects. There was more bare ground in the grazed transects, on average (p ≤ 0.02 for all, two-tailed paired t-tests). Our results suggested that total bunchgrass cover was higher within exclosures, but conclusive evidence was lacking (p = 0.1, two-tailed paired t-test). Vascular plant composition, cover, richness, shrub cover, electrical conductivity, and pH were not different between the grazed and livestock-excluded transects. Thus, livestock-related reductions in cover and richness of biotic soil crusts were apparent while significant impacts to vascular plants were not obvious. We conclude that 1) biotic soil crusts are sensitive indicators of disturbance and 2) there are strong compositional differences in shrub steppe crust communities of Oregon, which are correlated with regional soil and climate gradients.
We studied lichen and bryophyte soil crust communities in a large public grazing allotment within a sagebrush steppe ecosystem in which the biotic soil crusts are largely intact. The allotment had ...been rested from grazing for 12 years, but experienced an extensive series of wildfires. In the 350, 4 × 0.5 m plots, stratified by topographic position, we found 60 species or species groups that can be distinguished in the field with a hand lens, averaging 11.5 species groups per plot. Lichen and bryophyte soil crust communities differed among topographic positions. Draws were the most disturbed, apparently from water erosion in a narrow channel and mass wasting from the steepened sides. Presumably because of this disturbance, draws had the lowest average species richness of all the topographic strata we examined. Biotic crust species richness and cover were inversely related to cover of the invasive annual, cheatgrass (Bromus tectorum), and positively related to cover of native bunchgrasses. Integrity of the biotic crust was more strongly related to cheatgrass than to fire. In general, we observed good recovery of crusts following fire, but only in those areas dominated by perennial bunchgrasses. We interpret the resilience of the biotic crust, in this case, to the low abundance of cheatgrass, low amounts of soil disturbance and high moss cover. These fires have not resulted in an explosion of the cheatgrass population, perhaps because of the historically low levels of livestock grazing.
Introduction
Communities change over time due to disturbances, variations in climate, and species invasions. Biological soil crust communities are important because they contribute to erosion control ...and nutrient cycling. Crust types may respond differently to changes in environmental conditions: single-celled organisms and bryophytes quickly recover after a disturbance, while lichens are slow growing and dominate favorable sites. Community change in crusts has seldom been assessed using repeated measures. For this study, we hypothesized that changes in crust composition were related to disturbance, topographic position, and invasive vegetation.
Methods
We monitored permanent plots in the Columbia Basin in 1999 and 2010 and compared changes in crust composition, cover, richness, and turnover with predictor variables of herbivore exclosure, elevation, heat load index, time since fire, presence of an invasive grass, and change in cover of the invasive grass.
Results
Bryophytes were cosmopolitan with high cover. Dominant lichens did not change dramatically. Indicator taxa differed by monitoring year. Bryophyte and total crust cover declined, and there was lower turnover outside of herbivore exclosures. Lichen cover did not change significantly. Plots that burned recently had high turnover. Increase in taxon richness was correlated with presence of an invasive grass in 1999. Change in cover of the invasive grass was positively related to proportional loss and negatively related to gain.
Conclusions
Composition and turnover metrics differed significantly over 11 years, though cover was more stable between years. This study can be a baseline for assessing change in crust composition due to anthropogenic influences.
Old conifer forests in the Pacific Northwest have a wide range of microhabitats induced by canopy structure and substrate characteristics. We used the Wind River Canopy Crane to sample lichens and ...bryophytes throughout the spectrum of habitats available to epiphytes. Of the 111 species found in 72 sample units, 97 were lichens and 14 were bryophytes. Epiphyte communities showed marked variation with respect to height in the canopy, bark vs. wood, degree of sheltering, and stem diameter. Of these factors, height in the canopy was most strongly related to epiphyte communities. Furthermore, the top two meters of the tallest trees hosted a diverse assemblage of both rare species (Tholurna dissimilis) and weedy, nitrophilous species (Candelaria concolor, Hypogymnia tubulosa, Parmelia sulcata), presumably induced by birds delivering lichen propagules and nutrients. Ten species were more frequent on bare wood than bark, including Ophioparma rubricosa, Letharia vulpina Placynthiella spp., Ptychographa xylographoides, Trapeliopsis flexuosa, and Xylographa parallela. Species richness was highly variable, even within habitats. The only factor found related to species richness was height in the canopy, the middle and upper layers each having about twice the species per sample unit as lower in the canopy.
Thesis (M.S.)--Oregon State University, 2001.
Typescript (photocopy). Includes bibliographical references (leaves 62-74). Also available via the World Wide Web.
Mutations in cell-free circulating DNA (cfDNA) have been studied for tracking disease relapse in colorectal cancer (CRC). This approach requires personalised assay design due to the lack of ...universally mutated genes. In contrast, early methylation alterations are restricted to defined genomic loci allowing comprehensive assay design for population studies. Our objective was to identify cancer-specific methylated biomarkers which could be measured longitudinally in cfDNA (liquid biopsy) to monitor therapeutic outcome in patients with metastatic CRC (mCRC).
Genome-wide methylation microarrays of CRC cell lines (n=149) identified five cancer-specific methylated loci (
,
,
,
). Digital PCR assays were employed to measure methylation of these genes in tumour tissue DNA (n=82) and cfDNA from patients with mCRC (n=182). Plasma longitudinal assessment was performed in a patient subset treated with chemotherapy or targeted therapy.
Methylation in at least one marker was detected in all tumour tissue samples and in 156 mCRC patient cfDNA samples (85.7%). Plasma marker prevalence was 71.4% for
, 68.5% for
, 69.7% for
, 69.1% for
and 65.1% for
. Dynamics of methylation markers was not affected by treatment type and correlated with objective tumour response and progression-free survival.
This five-gene methylation panel can be used to circumvent the absence of patient-specific mutations for monitoring tumour burden dynamics in liquid biopsy under different therapeutic regimens. This method might be proposed for assessing pharmacodynamics in clinical trials or when conventional imaging has limitations.
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