The Masquerade : March - Two Step

https://digitalcommons.library.umaine.edu/mmb-ps/2178/thumbnail.jp

Investigating the benefits of molecular profiling of advanced non-small cell lung cancer tumors to guide treatments.

In this study we utilized data on patient responses to guided treatments, and we evaluated their benefit for a non-small cell lung cancer cohort. The recommended therapies used were predicted using tumor molecular profiles that involved a range of biomarkers but primarily used immunohistochemistry markers. A dataset describing 91 lung non-small cell lung cancer patients was retrospectively split into two. The first group's drugs were consistent with a treatment plan whereby all drugs received agreed with their tumor's molecular profile. The second group each received one or more drug that was expected to lack benefit. We found that there was no significant difference in overall survival or mortality between the two groups. Patients whose treatments were predicted to be of benefit survived for an average of 402 days, compared to 382 days for those that did not (P = 0.7934). In the matched treatment group, 48% of patients were deceased by the time monitoring had finished compared to 53% in the unmatched group (P = 0.6094). The immunohistochemistry biomarker for the ERCC1 receptor was found to be a marker that could be used to predict future survival; ERCC1 loss was found to be predictive of poor survival

Shikimate pathway in apicomplexan parasites

No abstract available

Fast and Efficient Postsynthetic DNA Labeling in Cells by Means of Strain-Promoted Sydnone-Alkyne Cycloadditions

Fast and efficient: DNA strands, modified with the novel bioorthogonal reporters sydnones, undergo fast and efficient labeling with cyclooctynes and have the potential to become essential tools for imaging DNA and possibly RNA in cells. Sydnones are highly stable mesoionic 1,3-dipoles that react with cyclooctynes through strain-promoted sydnone-alkyne cycloaddition (SPSAC). Although sydnones have been shown to be valuable bioorthogonal chemical reporters for the labeling of proteins and complex glycans, nucleic acids have not yet been tagged by SPSAC. Evaluation of SPSAC kinetics with model substrates showed fast reactions with cyclooctyne probes (up to k=0.59 M$^{-1}$ s$^{-1}$), and two different sydnones were effectively incorporated into both 2’-deoxyuridines at position 5, and 7-deaza-2’-deoxyadenosines at position 7. These modified nucleosides were synthetically incorporated into single-stranded DNAs, which were successfully postsynthetically labeled with cyclooctyne probes both in vitro and in cells. These results show that sydnones are versatile bioorthogonal tags and have the premise to become essential tools for tracking DNA and potentially RNA in living cells

Size exclusion chromatography as a technique for the investigation of novel extracellular vesicles in cancer

Abstract: (1) Background: Cancer cells release extracellular vesicles that are a rich target for biomarker discovery and provide a promising mechanism for liquid biopsy. SEC is an increasingly popular technique which has been rediscovered for the purposes of EV isolation and purification from diverse biofluids. (2) Methods: A review was undertaken to identify all papers which described size exclusion as their primary EV isolation method in cancer research. (3) Results: 37 papers were identified and discussed which showcases the breadth of applications that EVs can be utilised, from proteomics, to RNA, and through to functionality. A range of different methods are highlighted, with Sepharose-based techniques predominating. (4) Conclusions: EVs isolated using SEC are able to identify cancer cells, highlight active pathways in tumourigenesis, clinically distinguish cohorts and remain functionally active for further experiments

New Thresholds and Strategies for Management of Bean Leaf Beetles in Iowa Soybean

The bean leaf beetle is an annual pest of soybean in midwestern states. Adult beetles feed on any aboveground plant part and are especially fond of soybean pods late in the growing season. Larvae, which are similar in appearance to com rootworm larvae, feed below the soil surface on soybean nodules, but their impact on yield or plant health is not known. In addition to the physical injury that bean leaf beetle adults cause to soybean plants, this insect also transmits bean pod mottle virus-a potentially yield-robbing plant disease that makes proper management of this insect even more critical. This report focuses on a new concept for managing second-generation bean leaf beetle adults, the performance of insecticides in controlling this pest, and the problems related to bean pod mottle virus and transmission by adult beetles

Wikipedia as an encyclopaedia of life

In his 2003 essay E O Wilson outlined his vision for an “encyclopaedia of life” comprising “an electronic page for each species of organism on Earth”, each page containing “the scientific name of the species, a pictorial or genomic presentation of the primary type specimen on which its name is based, and a summary of its diagnostic traits.” Although the “quiet revolution” in biodiversity informatics has generated numerous online resources, including some directly inspired by Wilson's essay (e.g., "http://ispecies.org":http://ispecies.org, "http://www.eol.org":http://www.eol.org), we are still some way from the goal of having available online all relevant information about a species, such as its taxonomy, evolutionary history, genomics, morphology, ecology, and behaviour. While the biodiversity community has been developing a plethora of databases, some with overlapping goals and duplicated content, Wikipedia has been slowly growing to the point where it now has over 100,000 pages on biological taxa. My goal in this essay is to explore the idea that, largely independent of the efforts of biodiversity informatics and well-funded international efforts, Wikipedia ("http://en.wikipedia.org/wiki/Main_Page":http://en.wikipedia.org/wiki/Main_Page) has emerged as potentially the best platform for fulfilling E O Wilson’s vision

TP53 regulates miRNA association with AGO2 to remodel the miRNA-mRNA interaction network

DNA damage activates TP53-regulated surveillance mechanisms that are crucial in suppressing tumorigenesis. TP53 orchestrates these responses directly by transcriptionally modulating genes, including microRNAs (miRNAs), and by regulating miRNA biogenesis through interacting with the DROSHA complex. However, whether the association between miRNAs and AGO2 is regulated following DNA damage is not yet known. Here, we show that, following DNA damage, TP53 interacts with AGO2 to induce or reduce AGO2's association of a subset of miRNAs, including multiple let-7 family members. Furthermore, we show that specific mutations in TP53 decrease rather than increase the association of let-7 family miRNAs, reducing their activity without preventing TP53 from interacting with AGO2. This is consistent with the oncogenic properties of these mutants. Using AGO2 RIP-seq and PAR-CLIP-seq, we show that the DNA damage–induced increase in binding of let-7 family members to the RISC complex is functional. We unambiguously determine the global miRNA–mRNA interaction networks involved in the DNA damage response, validating them through the identification of miRNA-target chimeras formed by endogenous ligation reactions. We find that the target complementary region of the let-7 seed tends to have highly fixed positions and more variable ones. Additionally, we observe that miRNAs, whose cellular abundance or differential association with AGO2 is regulated by TP53, are involved in an intricate network of regulatory feedback and feedforward circuits. TP53-mediated regulation of AGO2–miRNA interaction represents a new mechanism of miRNA regulation in carcinogenesis