The effects of continuous prenatal exposure to ionizing radiation on germ cell survival and follicular development in the bovine

It is known that the germ cell of the prepuberal mammal is sensitive to acute doses of radiation; but only limited information is available on the effects of continuous irradiation. Gravid cows were continuously irradiated with either 8 or 15R of γ-rays for each of 10 days during select intervals of gestation. Fetuses absorbed approximately one-third of the air dose. Ovaries of prenatally irradiated heifers, aged 15 to 18 months, were removed at slaughter, serially sectioned, and prepared for microscopic analysis. Testes excised from newborn bull calves were prepared for microscopic analysis as well. Numbers of primary, growing, and vesicular follicles were determined from ovarian cross-sections, and primitive spermatogonia (gonocytes) were enumerated in seminiferous tubule cross-sections. Reductions (18 to 21% of control) in number of primary follicles were observed only in heifers irradiated between 60 and 110 days of Gestation (P \u3c 0.01). During this period the germ-cell population is comprised mainly of mitotically active oogonia, and it is, therefore, likely that this cell type is most susceptible to continuous irradiation. The process of follicular development, as reflected by counts of growing and vesicular follicles, was unimpeded (P \u3c 0.01). Number of gonocytes was significantly reduced (10 to 40% of control) in bull calves that were irradiated between 60 and 270 days (P \u3c 0.01); a developmental period that corresponds with the shift of the gonocyte from a mitotically active to a mitotically inactive state. The oocyte of the primordial follicle and the mitotically active gonocyte were relatively resistant to continuous irradiation. Gonocyte losses in the male were probably insufficient to materially affect sperm production, but the reproductive capacity of females irradiated between 60 and 110 days of gestation would likely be reduced

Ponderosa pine forest reconstruction: Comparisons with historical data

Dendroecological forest reconstruction techniques are used to estimate presettlement structure of northern Arizona ponderosa pine forests. To test the accuracy of these techniques, we remeasured 10 of the oldest forest plots in Arizona, a subset of 51 historical plots established throughout the region from 1909 to 1913, and compared reconstruction outputs to historical data collected. Results of this analysis revealed several distinct sources of error: (1) After about 90 years, 94 percent of the recorded trees were relocated and remeasured, but approximately three trees/ha were missing in the field due to obliteration by fire or decay; (2) sizes of trees living in 1909 were overestimated by an average of 11.9 percent; (3) snag and log decomposition models tended to underestimate time since tree death by an undetermined amount; and (4) historical sizes of cut trees were difficult to estimate due to uncertainties concerning harvest dates. The aggregate effect of these errors was to overestimate the number of trees occurring in 1909-1913. Sensitivity analysis applied to decomposition equations showed variations in reconstructed sizes of snags and logs by +/- 7 percent and stand density estimates by 7 percent. Results suggest that these reconstruction techniques are robust but tend to overestimate tree size and forest density

Pinyon-juniper fire regime: Natural range of variability

In this study, we used a variety of methods to quantify and describe historical patterns of fire and forest structure in two pinyon-juniper ecosystems of the Southwest. Sites were located on the Kaibab National Forest in Arizona, south of Grand Canyon National Park (Tusayan), and on the Carson National Forest in New Mexico, north of Espanola (Canjilon). Methodological approaches included analysis of fire scars, contemporary forest structure, fire evidence, modern fire records, and forest reconstruction. GIS surface maps, constructed using inverse distance weighted interpolation, were used to assess spatial patterns of fire and forest structure. Results indicated distinct fire histories and recent forest changes at the two sites. At Tusayan, surface fires burned historically at frequencies of 7.2-7.4 years (Weibull median probability) in canyons and draws dominated by ponderosa pine. On uplands dominated by pinyon-juniper communities, longer point fire intervals suggested fires occurred at a mean frequency of 41.6 years. Point intervals stratified by species indicated longer return periods for Utah juniper than pinyon or ponderosa pine. Fire evidence in the form of charred tree structures was ubiquitous at the site and there was no clear relationship between stand age and fire evidence. Live, old trees (300 yr) were prevalent and averaged 26 trees per hectare (TPH). Stands were all ages up to 400 yr and patch sizes were generally small (30 ha). Reconstructions showed a moderate overall increase (39(percent)) in stand density since the late 19th century. Ponderosa pine increases were responsible for the majority of recent structural changes although pinyon density also had apparently increased. We found no evidence of extensive stand replacing fire over the last 400 years at Tusayan and concluded that the historical pattern has been one of frequent surface fires in ponderosa pine communities and small severe fires on pinyon-juniper uplands. At Canjilon, fire scar analysis showed longer mean fire intervals (81.1 yr), suggesting that infrequent crown fires or severe surface fires were an important component of the historical regime. Like Tusayan, charred structures were found across the Canjilon site, although they appeared to be more abundant at lower elevations where stands ages were younger. Few live old trees (300 yr) were found at the site (4.2 TPH). The site dominated by stands in the 200-250-yr and 250-300-yr age classes. Mean patch sizes for stands of these age classes were 24 and 79 ha, respectively. Reconstructions showed relatively greater increases in tree density (61(percent)) with Rocky Mountain juniper and pinyon pine both showing positive changes since the late 19th century. Evidence of stand replacing fire was seen along the eastern edge of the study site and young trees appeared to be encroaching into previously open areas, particularly around big sagebrush meadows. Woodland treatments that may parallel historical patterns of fire and forest structure at these sites include targeted tree thinning and/or use of prescribed fire to create canopy openings of various sizes

The Fire and Tree Mortality Database, for Empirical Modeling of Individual Tree Mortality After Fire

Wildland fires have a multitude of ecological effects in forests, woodlands, and savannas across the globe. A major focus of past research has been on tree mortality from fire, as trees provide a vast range of biological services. We assembled a database of individual-tree records from prescribed fires and wildfires in the United States. The Fire and Tree Mortality (FTM) database includes records from 164,293 individual trees with records of fire injury (crown scorch, bole char, etc.), tree diameter, and either mortality or top-kill up to ten years post-fire. Data span 142 species and 62 genera, from 409 fires occurring from 1981-2016. Additional variables such as insect attack are included when available. The FTM database can be used to evaluate individual fire-caused mortality models for pre-fire planning and post-fire decision support, to develop improved models, and to explore general patterns of individual fire-induced tree death. The database can also be used to identify knowledge gaps that could be addressed in future research

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH -Mutant Molecular Profiles

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance