44 research outputs found

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

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    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

    Long-term trends in survival of a declining population: the case of the little owl (Athene noctua) in the Netherlands

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    The little owl (Athene noctua) has declined significantly in many parts of Europe, including the Netherlands. To understand the demographic mechanisms underlying their decline, we analysed all available Dutch little owl ringing data. The data set spanned 35 years, and included more than 24,000 ringed owls, allowing detailed estimation of survival rates through multi-state capture–recapture modelling taking dispersal into account. We investigated geographical and temporal variation in age-specific survival rates and linked annual survival estimates to population growth rate in corresponding years, as well as to environmental covariates. The best model for estimating survival assumed time effects on both juvenile and adult survival rates, with average annual survival estimated at 0.258 (SE = 0.047) and 0.753 (SE = 0.019), respectively. Juvenile survival rates decreased with time whereas adult survival rates fluctuated regularly among years, low survival occurring about every 4 years. Years when the population declined were associated with low juvenile survival. More than 60% of the variation in juvenile survival was explained by the increase in road traffic intensity or in average temperature in spring, but these correlations rather reflect a gradual decrease in juvenile survival coinciding with long-term global change than direct causal effects. Surprisingly, vole dynamics did not explain the cyclic dynamics of adult survival rate. Instead, dry and cold years led to low adult survival rates. Low juvenile survival rates, that limit recruitment of first-year breeders, and the regular occurrence of years with poor adult survival, were the most important determinants of the population decline of the little owl

    Depression of Collateral Blood Flow Following Arterial Thrombosis

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    PESTICIDE ASSESSMENT OF FIELD CORN AND SOYBEANS: NORTHERN PLAINS STATES

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    This report summarizes the pesticide assessment for corn and soybeans in the Northern Plains. Without insecticides, corn rootworm larvae and other soil insects would cause substantial corn yield losses. The loss of seed treatments would result in yield losses to both corn and soybeans. Among the herbicides, the loss of thiocarbamates would cause the greatest corn yield losses, while either dinitroanilines or triazines would cause the greatest soybean yield losses. This report includes pest rankings, estimates of acreages treated with pesticides or other pest management practices, and estimates of pest losses with and without pesticide use for insects, diseases, nematodes, and weed

    Modeling vegetation community responses to sea-level rise on Barrier Island systems: A case study on the Cape Canaveral Barrier Island complex, Florida, USA

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    <div><p>Society needs information about how vegetation communities in coastal regions will be impacted by hydrologic changes associated with climate change, particularly sea level rise. Due to anthropogenic influences which have significantly decreased natural coastal vegetation communities, it is important for us to understand how remaining natural communities will respond to sea level rise. The Cape Canaveral Barrier Island complex (CCBIC) on the east central coast of Florida is within one of the most biologically diverse estuarine systems in North America and has the largest number of threatened and endangered species on federal property in the contiguous United States. The high level of biodiversity is susceptible to sea level rise. Our objective was to model how vegetation communities along a gradient ranging from hydric to upland xeric on CCBIC will respond to three sea level rise scenarios (0.2 m, 0.4 m, and 1.2 m). We used a probabilistic model of the current relationship between elevation and vegetation community to determine the impact sea level rise would have on these communities. Our model correctly predicted the current proportions of vegetation communities on CCBIC based on elevation. Under all sea level rise scenarios the model predicted decreases in mesic and xeric communities, with the greatest losses occurring in the most xeric communities. Increases in total area of salt marsh were predicted with a 0.2 and 0.4 m rise in sea level. With a 1.2 m rise in sea level approximately half of CCBIC’s land area was predicted to transition to open water. On the remaining land, the proportions of most of the vegetation communities were predicted to remain similar to that of current proportions, but there was a decrease in proportion of the most xeric community (oak scrub) and an increase in the most hydric community (salt marsh). Our approach provides a first approximation of the impacts of sea level rise on terrestrial vegetation communities, including important xeric upland communities, as a foundation for management decisions and future modeling.</p></div

    Differential mRNA expression of Ara-C-metabolizing enzymes explains Ara-C sensitivity in MLL gene-rearranged infant acute lymphoblastic leukemia

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    Infant acute lymphoblastic leukemia (ALL) is characterized by a high incidence of mixed lineage leukemia (MLL) gene rearrangements, a poor outcome, and resistance to chemotherapeutic drugs. One exception is cytosine arabinoside (Ara-C), to which infant ALL cells are highly sensitive. To investigate the mechanism underlying Ara-C sensitivity in infants with ALL, mRNA levels of Ara-C-metabolizing enzymes were measured in infants (n = 18) and older children (noninfants) with ALL (n = 24). In the present study, infant ALL cells were 3.3-fold more sensitive to Ara-C (P =.007) and accumulated 2.3-fold more Ara-CTP (P =.011) upon exposure to Ara-C, compared with older children with ALL. Real-time quantitative reverse trancriptase-polymerase chain reaction (RT-PCR) (TaqMan) revealed that infants express 2-fold less of the Ara-C phosphorylating enzyme deoxycytidine kinase (dCK) mRNA (P =.026) but 2.5-fold more mRNA of the equilibrative nucleoside transporter 1 (hENT1), responsible for Ara-C membrane transport (P =.001). The mRNA expression of pyrimidine nucleotidase I (PN-I), cytidine deaminase (CDA), and deoxycytidylate deaminase (dCMPD) did not differ significantly between both groups. hENT1 mRNA expression inversely correlated with in vitro resistance to Ara-C (r(s) = -0.58, P =.006). The same differences concerning dCK and hENT1 mRNA expression were observe
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