Century-scale paleoclimatic reconstruction from Moon Lake, a closed-basin lake in the northern Great Plains

Estimates of past lake-water salinity from fossil diatom assemblages were used to infer past climatic conditions at Moon Lake, a climatically sensitive site in the northern Great Plains. A good correspondence between diatom-inferred salinity and historical records of mean annual precipitation minus evapotranspiration (P - ET) strongly suggests that the sedimentary record from Moon Lake can be used to reconstruct past climatic conditions. Century-scale analysis of the Holocene diatom record indicates four major hydrological periods: an early Holocene transition from an open freshwater system to a closed saline system by 7300 B.P., which corresponds with a transition from spruce forest to deciduous parkland to prairie and indicates a major shift from wet to dry climate; a mid-Holocene period of high salinity from 7300 to 4700 B.P., indicating low effective moisture (P - ET); a transitional period of high salinity from 4700 to 2200 B.P., characterized by poor diatom preservation; and a late Holocene period of variable lower salinity during the past 2,200 yr, indicating fluctuations in effective moisture

Moon Lake 11,000 Year Diatom-inferred Salinity Data

Estimates of past lake-water salinity from fossil diatom assemblages were used to infer past climatic conditions at Moon Lake, a climatically sensitive site in the northern Great Plains. A good correspondence between diatom-inferred salinity and historical records of mean annual precipitation minus evapotranspiration (P-ET) strongly suggests that the sedimentary record from Moon Lake can be used to reconstruct past climatic conditions. Century-scale analysis of the Holocene diatom record indicates four major hydrological periods: an early Holocene transition from an open freshwater system to a closed saline system by 7300 BP, which corresponds with a transition from spruce forest to deciduous parkland to prairie and indicates a major shift from wet to dry climate; a mid-Holocene period of high salinity from 7300 to 4700 BP, indicating low effective moisture (P-ET); a transitional period of high salinity 4700 to 2200 BP, characterized by poor diatom preservation; and a late Holocene period of variable lower salinity during the past 2,200 years, indicating fluctuations in effective moisture

Moon Lake 11,000 Year Diatom-inferred Salinity Data

Estimates of past lake-water salinity from fossil diatom assemblages were used to infer past climatic conditions at Moon Lake, a climatically sensitive site in the northern Great Plains. A good correspondence between diatom-inferred salinity and historical records of mean annual precipitation minus evapotranspiration (P-ET) strongly suggests that the sedimentary record from Moon Lake can be used to reconstruct past climatic conditions. Century-scale analysis of the Holocene diatom record indicates four major hydrological periods: an early Holocene transition from an open freshwater system to a closed saline system by 7300 BP, which corresponds with a transition from spruce forest to deciduous parkland to prairie and indicates a major shift from wet to dry climate; a mid-Holocene period of high salinity from 7300 to 4700 BP, indicating low effective moisture (P-ET); a transitional period of high salinity 4700 to 2200 BP, characterized by poor diatom preservation; and a late Holocene period of variable lower salinity during the past 2,200 years, indicating fluctuations in effective moisture

Dry Climate Disconnected the Laurentian Great Lakes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94725/1/eost16649.pd

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 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

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

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

FAM5C Contributes to Aggressive Periodontitis

Aggressive periodontitis is characterized by a rapid and severe periodontal destruction in young systemically healthy subjects. A greater prevalence is reported in Africans and African descendent groups than in Caucasians and Hispanics. We first fine mapped the interval 1q24.2 to 1q31.3 suggested as containing an aggressive periodontitis locus. Three hundred and eighty-nine subjects from 55 pedigrees were studied. Saliva samples were collected from all subjects, and DNA was extracted. Twenty-one single nucleotide polymorphisms were selected and analyzed by standard polymerase chain reaction using TaqMan chemistry. Non-parametric linkage and transmission distortion analyses were performed. Although linkage results were negative, statistically significant association between two markers, rs1935881 and rs1342913, in the FAM5C gene and aggressive periodontitis (p = 0.03) was found. Haplotype analysis showed an association between aggressive periodontitis and the haplotype A-G (rs1935881-rs1342913; p = 0.009). Sequence analysis of FAM5C coding regions did not disclose any mutations, but two variants in conserved intronic regions of FAM5C, rs57694932 and rs10494634, were found. However, these two variants are not associated with aggressive periodontitis. Secondly, we investigated the pattern of FAM5C expression in aggressive periodontitis lesions and its possible correlations with inflammatory/immunological factors and pathogens commonly associated with periodontal diseases. FAM5C mRNA expression was significantly higher in diseased versus healthy sites, and was found to be correlated to the IL-1β, IL-17A, IL-4 and RANKL mRNA levels. No correlations were found between FAM5C levels and the presence and load of red complex periodontopathogens or Aggregatibacter actinomycetemcomitans. This study provides evidence that FAM5C contributes to aggressive periodontitis

Exploitation and destabilization of a warm, freshwater ecosystem through engineered hydrological change

Exploitation of freshwater resources is having catastrophic effects on the ecological dynamics, stability, and quality of those water resources on a global scale, especially in arid and semiarid regions. Lake Kinneret, Israel (the Biblical Sea of Galilee), the only major natural freshwater lake in the Middle East, has been transformed functionally into a reservoir over the course of ∼70 years of hydrological alterations aimed mostly at producing electrical power and increasing domestic and agricultural water supply. Historical changes in lake chemistry and biology were reconstructed using analysis of sedimentary nutrient content, stable and radioisotope composition, biochemical and morphological fossils from algae, remains of aquatic invertebrates, and chemical indices of past light regimes. Together, these paleolimnological analyses of the lake's bottom sediments revealed that this transformation has been accompanied by acceleration in the rate of eutrophication, as indicated by increased accumulation rates of phosphorus, nitrogen, organic matter, phytoplankton and bacterial pigments, and remains of phytoplankton and zooplankton. Substantial increases in these indices of eutrophication coincide with periods of increased water‐level fluctuations and drainage of a major upstream wetland in the early to middle 20th century and suggest that management of the lake for increased water supply has degraded water quality to the point that ecosystem stability and sustainability are threatened. Such destabilization may be a model for eutrophication of freshwater lakes in other arid regions of the world in which management emphasizes water quantity over quality.Peer reviewedZoolog