A higher-order entity formed by the flexible assembly of RAP1 with TRF2

Essonne committee of the Ligue contre le cancer M18756 M22897 Foundation ARC pour la Recherche sur le Cancer SFI20121205503International audienceTelomere integrity is essential to maintain genome stability, and telomeric dysfunctions are associated with cancer and aging pathologies. In human, the shelterin complex binds TTAGGG DNA repeats and provides capping to chromosome ends. Within shel-terin, RAP1 is recruited through its interaction with TRF2, and TRF2 is required for telomere protection through a network of nucleic acid and protein interactions. RAP1 is one of the most conserved shelterin proteins although one unresolved question is how its interaction may influence TRF2 properties and regulate its capacity to bind multiple proteins. Through a combination of biochemical, biophysical and structural approaches, we unveiled a unique mode of assembly between RAP1 and TRF2. The complete interaction scheme between the full-length proteins involves a complex biphasic interaction of RAP1 that directly affects the binding properties of the assembly. These results reveal how a non-DNA binding protein can influence the properties of a DNA-binding partner by mutual conformational adjustments

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Estimation of Heat Released from Fire Based on Combustible Load in Inner Mongolian Grasslands

The grasslands of Inner Mongolia are prone to wildfires, which can endanger the grassland ecosystem, as well as people’s lives and property. The amount of heat released by grassland fires must be determined for the quantitative evaluation of grassland fires. On the basis of a field survey of combustible load and an indoor heat release experiment, together with the acquisition of NDVI and fire area data, this study evaluated the amount of combustible load, plant heat release, potential heat release, and fire-caused heat release in Inner Mongolia grasslands. The following results were obtained: (1) The models for determining Inner Mongolia’s combustible load (Y) per unit area throughout the growing and nongrowing seasons were Yi = 412.74NDVIi1.5917 and Yj = −7.21tj + Y10 (i represents May–October of the growing season; j represents November–April of the following year). In the northern temperate zones, grasslands and meadows showed a decline in combustible load per unit area. The interannual combustible load variance increased between 2001 and 2016; (2) the per square meter average heat release of Stipa capillata, Cleistogenes squarrosa, Carex doniana, Leymus chinensis, and other plants was 0.51, 0.18, 0.17, 0.3, and 1.42 MJ/g, respectively. Unit weights were released at 2.13, 1.77, 2.06, 1.9, and 3.99 MJ/m2; (3) from 2001 to 2016, Inner Mongolia’s grassland fires predominantly occurred in northern temperate grasslands and meadows. Over the 16 year period, the total heat emission was 1.01 × 1012 MJ, with variable decreasing trends noted in spring and fall. The main practical objectives of this paper were to provide basic data for fire spread modeling and suggest more scientific and effective fire management methods for the future

Spatial-Temporal Characteristics and Driving Forces of Aboveground Biomass in Desert Steppes of Inner Mongolia, China in the Past 20 Years

The desert steppe serves as a transitional zone between grasslands and deserts, and long-term monitoring of aboveground biomass (AGB) in the desert steppe is essential for understanding grassland changes. While AGB observation techniques based on multisource remote-sensing data and machine-learning algorithms have been widely applied, research on monitoring methods specifically for the desert steppe remains limited. In this study, we focused on the desert steppe of Inner Mongolia, China, as the study area and used field sampling data, MODIS data, MODIS-based vegetation indices (VI), and environmental factors (topography, climate, and soil) to compare the performance of four commonly used machine-learning algorithms: multiple linear regression (MLR), partial least-squares regression (PLS), random forest (RF), and support vector machine (SVM) in AGB estimation. Based on the optimal model, the spatial–temporal characteristics of AGB from 2000 to 2020 were calculated, and the driving forces of climate change and human activities on AGB changes were quantitatively analyzed using the random forest algorithm. The results are as follows: (1) RF demonstrated outstanding performance in terms of prediction accuracy and model robustness, making it suitable for AGB estimation in the desert steppe of Inner Mongolia; (2) VI contributed the most to the model, and no significant difference was found between soil-adjusted VIs and traditional VIs. Elevation, slope, precipitation, and temperature all had positive effects on the model; (3) from 2000 to 2020, the multiyear average AGB in the study area was 58.34 g/m2, exhibiting a gradually increasing distribution pattern from the inner region to the outer region (from north to south); (4) from 2000 to 2020, the proportions of grassland with AGB slightly and significantly increasing trend in the study area were 87.08% and 5.13%, respectively, while the proportions of grassland with AGB slightly and significantly decreasing trend were 7.76% and 0.05%, respectively; and (5) over the past 20 years, climate change, particularly precipitation, has been the primary driving force behind AGB changes of the study area. This research holds reference value for improving desert steppe monitoring capabilities and the rational planning of grassland resources

Examining the Angular Effects of UAV-LS on Vegetation Metrics Using a Framework for Mediating Effects

Discrete point cloud data from unmanned aerial vehicle laser scanning (UAV-LS) can provide information on the three-dimensional structure of a forest, the leaf area index (LAI) at the landscape or sample plot scales, the distribution of the vertical forest structure at a fine resolution, and other information. The retrieved parameters, however, may be affected in a non-negligible way by the inclusion of scan angle information. In this study, we introduced a relational model that encompasses the angular effect, predicted the mechanism of this effect, and extracted the vegetation structure indices that the angular effect might influence. Second, we quantified the direct and indirect effects, particularly the magnitude of the angular effect in broadleaf forests, and used mediated effects to investigate the components and processes that influence the angular effect. The findings demonstrate that some of the differences between the LAIe extracted by UAV-LS and the Decagon LAIe considering the angular effect of UAV-LS can be explained by adjusting physical LiDAR parameters (aerial height, laser divergence fraction, and scanning angle) and vertical forest structure variables. Along continuous and closed forest vertical gradients, the indirect angle impact is negative for the upper canopy and positive for the understory. Three-dimensional vegetation measurements were created using multiangle LiDAR data. In conclusion, this article (1) addresses the angular effect in UAV-LS; and (2) discusses how the angular effect affects 3D vegetation parameters such as LAIe, demonstrates the nonlinear trend of the angular effect, and demonstrates how multiangle LiDAR data can be used to obtain 3D vegetation parameters. This study serves as a reference for reducing the uncertainty in simulations of the angular effect and vegetation light transmission, in addition to the uncertainty in analyses of the vegetation characteristics determined by UAV-LS (e.g., the uncertainty of LAIe)

The Variations of Land Surface Phenology in Northeast China and Its Responses to Climate Change from 1982 to 2013

Northeast China is located at high northern latitudes and is a typical region of relatively high sensitivity to global climate change. Studies of the land surface phenology in Northeast China and its response to climate change are important for understanding global climate change. In this study, the land surface phenology parameters were calculated using the third generation dataset from the Global Inventory Modeling and Mapping Studies (GIMMS 3g) that was collected from 1982 to 2013 were estimated to analyze the variations of the land surface phenology in Northeast China at different scales and to discuss the internal relationships between phenology and climate change. We examined the phonological changes of all ecoregions. The average start of the growing season (SOS) did not exhibit a significant trend throughout the study area; however, the end of the growing season (EOS) was significantly delayed by 4.1 days or 0.13 days/year (p < 0.05) over the past 32 years. The SOS for the Hulunbuir Plain, Greater Khingan Mountains and Lesser Khingan Mountains was earlier, and the SOS for the Sanjing, Songnen and Liaohe Plains was later. In addition, the EOS of the Greater Khingan Mountains, Lesser Khingan Mountains and Changbai Mountains was later than the EOS of the Liaohe Plain. The spring temperature had the greatest impact on the SOS. Precipitation had an insignificant impact on forest SOS and a relatively large impact on grassland SOS. The EOS was affected by both temperature and precipitation. Furthermore, although temperature had a lag effect on the EOS, no significant lag effect was observed for the SOS

A higher-order entity formed by the flexible assembly of RAP1 with TRF2.

Telomere integrity is essential to maintain genome stability, and telomeric dysfunctions are associated with cancer and aging pathologies. In human, the shelterin complex binds TTAGGG DNA repeats and provides capping to chromosome ends. Within shelterin, RAP1 is recruited through its interaction with TRF2, and TRF2 is required for telomere protection through a network of nucleic acid and protein interactions. RAP1 is one of the most conserved shelterin proteins although one unresolved question is how its interaction may influence TRF2 properties and regulate its capacity to bind multiple proteins. Through a combination of biochemical, biophysical and structural approaches, we unveiled a unique mode of assembly between RAP1 and TRF2. The complete interaction scheme between the full-length proteins involves a complex biphasic interaction of RAP1 that directly affects the binding properties of the assembly. These results reveal how a non-DNA binding protein can influence the properties of a DNA-binding partner by mutual conformational adjustments