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McDermott, Jason E.

Publications and source records attributed to McDermott, Jason E..

23 records · Page 2

Night shift schedule causes circadian dysregulation of DNA repair genes and elevated DNA damage in humans

Circadian disruption has been identified as a risk factor for health disorders such as obesity, cardiovascular disease, and cancer. Although epidemiological studies suggest an increased risk of various cancers associated with circadian misalignment due to night shift work, the underlying mechanisms have yet to be elucidated. Here, we sought to investigate the potential mechanistic role that circadian disruption of cancer hallmark pathway genes may play in the increased cancer risk in shift workers. In a controlled laboratory study, we investigated the circadian transcriptome of cancer hallmark pathway genes and associated biological pathways in circulating leukocytes obtained from healthy young adults during a 24‐hour constant routine protocol following 3 days of simulated day shift or night shift. The simulated night shift schedule significantly altered the normal circadian rhythmicity of genes involved in cancer hallmark pathways. A DNA repair pathway showed significant enrichment of rhythmic genes following the simulated day shift schedule, but not following the simulated night shift schedule. In functional assessments, we demonstrated that there was an increased sensitivity to both endogenous and exogenous sources of DNA damage after exposure to simulated night shift. Our results suggest that circadian dysregulation of DNA repair may increase DNA damage and potentiate elevated cancer risk in night shift workers.

circadian misalignment↗

Integrated Proteomic and Glycoproteomic Characterization of Human High-Grade Serous Ovarian Carcinoma

Many gene products exhibit great structural heterogeneity because of an array of modifications. These modifications are not directly encoded in the genomic template but often affect the functionality of proteins. Protein glycosylation plays a vital role in proper protein functions. However, the analysis of glycoproteins has been challenging compared with other protein modifications, such as phosphorylation. Here, we perform an integrated proteomic and glycoproteomic analysis of 83 prospectively collected high-grade serous ovarian carcinoma (HGSC) and 23 non-tumor tissues. Integration of the expression data from global proteomics and glycoproteomics reveals tumor-specific glycosylation, uncovers different glycosylation associated with three tumor clusters, and identifies glycosylation enzymes that were correlated with the altered glycosylation. In addition to providing a valuable resource, these results provide insights into the potentialroles of glycosylation in the pathogenesis of HGSC, with the possibility of distinguishing pathological outcomes of ovarian tumors from non-tumors, as well as classifying tumor clusters.

Hu, Yingwei↗

Terabase Metagenome Sequencing of Grassland Soil Microbiomes

ABSTRACT To enable an in-depth survey of the metabolic potential of complex soil microbiomes, we performed ultra-deep metagenome sequencing, collecting >1 Tb of sequence data from three grassland soils representing different precipitation regimes.

59 BASIC BIOLOGICAL SCIENCES↗

Ten Simple Rules to becoming a principal investigator

The biggest choke point in an academic career is going from postdoc to principal investigator (PI), moving from doing someone else’s research to getting other people to do yours. It is not an easy transition, draws on few of the skills you learn at the bench and the odds are clearly not ever in your favour. So calling this article ten simple rules is obviously a simplification: it is more accurate to call them ten tricky steps. In this article, we use Principal Investigator to mean anyone who runs their own research group, using funding that they have been awarded to answer their own questions. PI encompasses a number of different job titles depending on where the research is performed – fellow, lecturer, associate professor, senior scientist. The acid test is whether you can describe the people working for you as the X group, where X is your surname. The normal route from undergraduate to lab head involves a PhD, one or most postdoc positions and then PI. Given the diversity of ways to be a PI, the final step up from postdoc takes a number of forms – in the UK this tends to be either an individual fellowship or a lecturer position, in the US it generally starts with an independent position with associated funding – either as a startup package or funded grant. The aim of this article is to identify some of the broader skills (rules 1-4) and behaviours (rules 5-10) that can help with becoming a PI. They are meant as advice, not instruction. As you will see, most of them are soft/ leadership skills, which can as easily be applied to the world outside academia as within it.

99 GENERAL AND MISCELLANEOUS↗