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

Immunogenic salivary proteins of Triatoma infestans\textit {Triatoma infestans}

$\textit {Background:}$ Triatomines are vectors of $\textit {Trypanosoma cruzi}$, the etiological agent of Chagas disease in Latin America. The most effective vector, $\textit {Triatoma infestans}$, has been controlled successfully in much of Latin America using insecticide spraying. Though rarely undertaken, surveillance programs are necessary in order to identify new infestations and estimate the intensity of triatomine bug infestations in domestic and peridomestic habitats. Since hosts exposed to triatomines develop immune responses to salivary antigens, these responses can be evaluated for their usefulness as epidemiological markers to detect infestations of $\textit {T. infestans}$. $\textit {Methodology/Principal Findings:}$ $\textit {T. infestans}$ salivary proteins were separated by 2D-gel electrophoresis and tested for their immunogenicity by Western blotting using sera from chickens and guinea pigs experimentally exposed to $\textit {T. infestans}$. From five highly immunogenic protein spots, eight salivary proteins were identified by nano liquid chromatography-electrospray ionization-tandem mass spectrometry (nanoLC-ESI-MS/MS) and comparison to the protein sequences of the National Center for Biotechnology Information (NCBI) database and expressed sequence tags of a unidirectionally cloned salivary gland cDNA library from $\textit {T. infestans}$ combined with the NCBI yeast protein sub-database. The 14.6 kDa salivary protein [gi|149689094] was produced as recombinant protein (r$\it Ti$SP14.6) in a mammalian cell expression system and recognized by all animal sera. The specificity of rTiSP14.6 was confirmed by the lack of reactivity to anti-mosquito and anti-sand fly saliva antibodies. However, r$\it Ti$SP14.6 was recognized by sera from chickens exposed to four other triatomine species, $\textit {Triatoma brasiliensis, T. sordida, Rhodnius prolixus}$, and $\textit {Panstrongylus megistus}$ and by sera of chickens from an endemic area of $\textit {T. infestans}$ and Chagas disease in Bolivia. $\textit {Conclusions/Significance:}$ The recombinant r$\it Ti$SP14.6 is a suitable and promising epidemiological marker for detecting the presence of small numbers of different species of triatomines and could be developed for use as a new tool in surveillance programs, especially to corroborate vector elimination in Chagas disease vector control campaigns

Analyses of allele-specific gene expression in highly divergent mouse crosses identifies pervasive allelic imbalance

Complex human traits are influenced by variation in regulatory DNA through mechanisms that are not fully understood. Since regulatory elements are conserved between humans and mice, a thorough annotation of cis regulatory variants in mice could aid in this process. Here we provide a detailed portrait of mouse gene expression across multiple tissues in a three-way diallel. Greater than 80% of mouse genes have cis regulatory variation. These effects influence complex traits and usually extend to the human ortholog. Further, we estimate that at least one in every thousand SNPs creates a cis regulatory effect. We also observe two types of parent-of-origin effects, including classical imprinting and a novel, global allelic imbalance in favor of the paternal allele. We conclude that, as with humans, pervasive regulatory variation influences complex genetic traits in mice and provide a new resource toward understanding the genetic control of transcription in mammals

Nudges for Privacy and Security: Understanding and Assisting Users' Choices Online

Advancements in information technology often task users with complex and consequential privacy and security decisions. A growing body of research has investigated individuals' choices in the presence of privacy and information security tradeoffs, the decision-making hurdles affecting those choices, and ways to mitigate such hurdles. This article provides a multi-disciplinary assessment of the literature pertaining to privacy and security decision making. It focuses on research on assisting individuals' privacy and security choices with soft paternalistic interventions that nudge users toward more beneficial choices. The article discusses potential benefits of those interventions, highlights their shortcomings, and identifies key ethical, design, and research challenges.National Science Foundation [CNS-1012763, CNS-0627513, CNS-0905562]; Google; CMU CyLab from the Army Research Office [DAAD19-02-1-0389, W911NF-09-1-0273]; IWT SBO SPION Project; Nokia; France Telecom; CMU/Portugal Information and Communication Technologies InstituteThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]