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Traditional mutation assessment methods generally focus on predicting disruptive changes in protein-coding regions rather than non-coding regulatory regions like untranslated regions (UTRs) of mRNAs. The UTRs, however, are known to have many sequence and structural motifs that can regulate translational and transcriptional efficiency and stability of mRNAs through interaction with RNA-binding proteins and other non-coding RNAs like microRNAs (miRNAs). In a recent study, transcriptomes of tumor cells harboring mutant and wild-type KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) genes in patients with non-small cell lung cancer (NSCLC) have been sequenced to identify single nucleotide variations (SNVs). About 40% of the total SNVs (73,717) identified were mapped to UTRs, but omitted in the previous analysis. To meet this obvious demand for analysis of the UTRs, we designed a comprehensive pipeline to predict the effect of SNVs on two major regulatory elements, secondary structure and miRNA target sites. Out of 29,290 SNVs in 6462 genes, we predict 472 SNVs (in 408 genes) affecting local RNA secondary structure, 490 SNVs (in 447 genes) affecting miRNA target sites and 48 that do both. Together these disruptive SNVs were present in 803 different genes, out of which 188 (23.4%) were previously known to be cancer-associated. Notably, this ratio is significantly higher (one-sided Fisher's exact test p-value = 0.032) than the ratio (20.8%) of known cancer-associated genes (n = 1347) in our initial data set (n = 6462). Network analysis shows that the genes harboring disruptive SNVs were involved in molecular mechanisms of cancer, and the signaling pathways of LPS-stimulated MAPK, IL-6, iNOS, EIF2 and mTOR. In conclusion, we have found hundreds of SNVs which are highly disruptive with respect to changes in the secondary structure and miRNA target sites within UTRs. These changes hold the potential to alter the expression of known cancer genes or genes linked to cancer-associated pathways.

Amid a time of unprecedented social‐ecological change, professionals within and outside of the US wildlife conservation community have called for transformation of existing processes and structures to ensure that the benefits of wildlife conservation can be realized well into the future. Current momentum behind an initiative to help increase conservation relevancy among population segments that have historically been underserved by the conservation community is underway. Sustainable institutional change will not be realized, however, without attending to internal cultural change within the conservation community itself. Although elements of an ideal institution have been suggested, specific interventions related to institutional culture need deeper exploration. State fish and wildlife agencies—a primary organizational actor within the conservation community—play a central role in institutional transformation. Using a systems framework, this essay describes key leverage points for cultural change for which interventions could result in sustainable culture shifts. Five possible interventions are introduced to stimulate conversation among conservation practitioners seeking to initiate transformational change within their specific cultural contexts.

International audienceThis paper presents a development of a seismic sensor for the future Compact Linear Collider (CLIC). Sensor in which three different types of sub-nanometre displacement transducers have been integrated: a Fabry-Pérot interferometer, an optical encoder and a capacitive transducer. This sensor allows us to compare the resolution of all the transducers under the same conditions, thus enabling us to verify the most suitable transducer for a seismic sensor. The best resolution of 28.8 pm was achieved with the optical encoder. This in combination with ease of installation makes it an ideal candidate for a seismic senor for CLIC

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