RANK signaling in osteoclast precursors results in a more permissive epigenetic landscape and sexually divergent patterns of gene expression.

Background: Sex is an important risk factor in the development of osteoporosis and other bone loss disorders, with women often demonstrating greater susceptibility than men. While variation in sex steroids, such as estradiol, accounts for much of the risk, there are likely additional non-endocrine factors at transcriptional and epigenetic levels that result in a higher rate of bone loss in women. Identification of these factors could improve risk assessment and therapies to preserve and improve bone health. Methods: Osteoclast precursors were isolated male and female C57Bl/6 mice and cultured with either MCSF alone or MCSF and RANKL. Following the culture period RNA was isolated for RNA sequencing and DNA was isolated for tagmentation and ATAC sequencing. RNA-Seq and ATAC-seq were evaluated via pathway analysis to identify sex- and RANKL-differential transcription and chromatin accessibility. Results: Osteoclasts demonstrated significant alterations in gene expression compared to macrophages with both shared and differential pathways between the sexes. Transcriptional pathways differentially regulated between male and female cells were associated with immunological functions with evidence of greater sensitivity in male macrophages and female osteoclasts. ATAC-Seq revealed a large increase in chromatin accessibility following RANKL treatment with few alterations attributable to sex. Comparison of RNA-Seq and ATAC-seq data revealed few common pathways suggesting that many of the transcriptional changes of osteoclastogenesis occur independently of chromatin remodeling.

Suppression resource decisions are the dominant influence on containment of Australian forest and grass fires.

Fire agencies aim to contain wildfires before they impact on life, property and infrastructure and to reduce the risk of damage to the environment. Despite the large cost of suppression, there are few data on the success of suppression efforts under varying weather, fuel and resource scenarios. We examined over 2200 forest and 4600 grass fires in New South Wales, Australia to determine the dominant influences on the containment of wildfires. A random forest modelling approach was used to analyse the effect of a range of human and environmental factors. The number of suppression resources per area of fire were the dominant influence on the containment of both forest and grass fires. As fire weather conditions worsened the probability of containment decreased across all fires and as fuel loads and slope increased the probability of containment decreased for forest fires. Environmental controls limit the effectiveness of wildfire management. However, results suggest investment in suppression resources and strategic fuel management will increase the probability of containment.

Some Wildfire Ignition Causes Pose More Risk of Destroying Houses than Others.

Many houses are at risk of being destroyed by wildfires. While previous studies have improved our understanding of how, when and why houses are destroyed by wildfires, little attention has been given to how these fires started. We compiled a dataset of wildfires that destroyed houses in New South Wales and Victoria and, by comparing against wildfires where no houses were destroyed, investigated the relationship between the distribution of ignition causes for wildfires that did and did not destroy houses. Powerlines, lightning and deliberate ignitions are the main causes of wildfires that destroyed houses. Powerlines were 6 times more common in the wildfires that destroyed houses data than in the wildfires where no houses were destroyed data and lightning was 2 times more common. For deliberate- and powerline-caused wildfires, temperature, wind speed, and forest fire danger index were all significantly higher and relative humidity significantly lower (P < 0.05) on the day of ignition for wildfires that destroyed houses compared with wildfires where no houses were destroyed. For all powerline-caused wildfires the first house destroyed always occurred on the day of ignition. In contrast, the first house destroyed was after the day of ignition for 78% of lightning-caused wildfires. Lightning-caused wildfires that destroyed houses were significantly larger (P < 0.001) in area than human-caused wildfires that destroyed houses. Our results suggest that targeting fire prevention strategies around ignition causes, such as improving powerline safety and targeted arson reduction programmes, and reducing fire spread may decrease the number of wildfires that destroy houses.