Contemplating Mindfulness at Work: An Integrative Review

Mindfulness research activity is surging within organizational science. Emerging evidence across multiple fields suggests that mindfulness is fundamentally connected to many aspects of workplace functioning, but this knowledge base has not been systematically integrated to date. This review coalesces the burgeoning body of mindfulness scholarship into a framework to guide mainstream management research investigating a broad range of constructs. The framework identifies how mindfulness influences attention, with downstream effects on functional domains of cognition, emotion, behavior, and physiology. Ultimately, these domains impact key workplace outcomes, including performance, relationships, and well-being. Consideration of the evidence on mindfulness at work stimulates important questions and challenges key assumptions within management science, generating an agenda for future research

Inhibition of Chk1 Kills Tetraploid Tumor Cells through a p53-Dependent Pathway

Tetraploidy constitutes an adaptation to stress and an intermediate step between euploidy and aneuploidy in oncogenesis. Tetraploid cells are particularly resistant against genotoxic stress including radiotherapy and chemotherapy. Here, we designed a strategy to preferentially kill tetraploid tumor cells. Depletion of checkpoint kinase-1 (Chk1) by siRNAs, transfection with dominant-negative Chk1 mutants or pharmacological Chk1 inhibition killed tetraploid colon cancer cells yet had minor effects on their diploid counterparts. Chk1 inhibition abolished the spindle assembly checkpoint and caused premature and abnormal mitoses that led to p53 activation and cell death at a higher frequency in tetraploid than in diploid cells. Similarly, abolition of the spindle checkpoint by knockdown of Bub1, BubR1 or Mad2 induced p53-dependent apoptosis of tetraploid cells. Chk1 inhibition reversed the cisplatin resistance of tetraploid cells in vitro and in vivo, in xenografted human cancers. Chk1 inhibition activated p53-regulated transcripts including Puma/BBC3 in tetraploid but not in diploid tumor cells. Altogether, our results demonstrate that, in tetraploid tumor cells, the inhibition of Chk1 sequentially triggers aberrant mitosis, p53 activation and Puma/BBC3-dependent mitochondrial apoptosis

Gauging NOTCH1 Activation in Cancer Using Immunohistochemistry

Fixed, paraffin-embedded (FPE) tissues are a potentially rich resource for studying the role of NOTCH1 in cancer and other pathologies, but tests that reliably detect activated NOTCH1 (NICD1) in FPE samples have been lacking. Here, we bridge this gap by developing an immunohistochemical (IHC) stain that detects a neoepitope created by the proteolytic cleavage event that activates NOTCH1. Following validation using xenografted cancers and normal tissues with known patterns of NOTCH1 activation, we applied this test to tumors linked to dysregulated Notch signaling by mutational studies. As expected, frequent NICD1 staining was observed in T lymphoblastic leukemia/lymphoma, a tumor in which activating NOTCH1 mutations are common. However, when IHC was used to gauge NOTCH1 activation in other human cancers, several unexpected findings emerged. Among B cell tumors, NICD1 staining was much more frequent in chronic lymphocytic leukemia than would be predicted based on the frequency of NOTCH1 mutations, while mantle cell lymphoma and diffuse large B cell lymphoma showed no evidence of NOTCH1 activation. NICD1 was also detected in 38% of peripheral T cell lymphomas. Of interest, NICD1 staining in chronic lymphocytic leukemia cells and in angioimmunoblastic lymphoma was consistently more pronounced in lymph nodes than in surrounding soft tissues, implicating factors in the nodal microenvironment in NOTCH1 activation in these diseases. Among carcinomas, diffuse strong NICD1 staining was observed in 3.8% of cases of triple negative breast cancer (3 of 78 tumors), but was absent from 151 non-small cell lung carcinomas and 147 ovarian carcinomas. Frequent staining of normal endothelium was also observed; in line with this observation, strong NICD1 staining was also seen in 77% of angiosarcomas. These findings complement insights from genomic sequencing studies and suggest that IHC staining is a valuable experimental tool that may be useful in selection of patients for clinical trials

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

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

Global perspectives on observing ocean boundary current systems

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Todd, R. E., Chavez, F. P., Clayton, S., Cravatte, S., Goes, M., Greco, M., Ling, X., Sprintall, J., Zilberman, N., V., Archer, M., Aristegui, J., Balmaseda, M., Bane, J. M., Baringer, M. O., Barth, J. A., Beal, L. M., Brandt, P., Calil, P. H. R., Campos, E., Centurioni, L. R., Chidichimo, M. P., Cirano, M., Cronin, M. F., Curchitser, E. N., Davis, R. E., Dengler, M., deYoung, B., Dong, S., Escribano, R., Fassbender, A. J., Fawcett, S. E., Feng, M., Goni, G. J., Gray, A. R., Gutierrez, D., Hebert, D., Hummels, R., Ito, S., Krug, M., Lacan, F., Laurindo, L., Lazar, A., Lee, C. M., Lengaigne, M., Levine, N. M., Middleton, J., Montes, I., Muglia, M., Nagai, T., Palevsky, H., I., Palter, J. B., Phillips, H. E., Piola, A., Plueddemann, A. J., Qiu, B., Rodrigues, R. R., Roughan, M., Rudnick, D. L., Rykaczewski, R. R., Saraceno, M., Seim, H., Sen Gupta, A., Shannon, L., Sloyan, B. M., Sutton, A. J., Thompson, L., van der Plas, A. K., Volkov, D., Wilkin, J., Zhang, D., & Zhang, L. Global perspectives on observing ocean boundary current systems. Frontiers in Marine Science, 6, (2010); 423, doi: 10.3389/fmars.2019.00423.Ocean boundary current systems are key components of the climate system, are home to highly productive ecosystems, and have numerous societal impacts. Establishment of a global network of boundary current observing systems is a critical part of ongoing development of the Global Ocean Observing System. The characteristics of boundary current systems are reviewed, focusing on scientific and societal motivations for sustained observing. Techniques currently used to observe boundary current systems are reviewed, followed by a census of the current state of boundary current observing systems globally. The next steps in the development of boundary current observing systems are considered, leading to several specific recommendations.RT was supported by The Andrew W. Mellon Foundation Endowed Fund for Innovative Research at WHOI. FC was supported by the David and Lucile Packard Foundation. MGo was funded by NSF and NOAA/AOML. XL was funded by China’s National Key Research and Development Projects (2016YFA0601803), the National Natural Science Foundation of China (41490641, 41521091, and U1606402), and the Qingdao National Laboratory for Marine Science and Technology (2017ASKJ01). JS was supported by NOAA’s Global Ocean Monitoring and Observing Program (Award NA15OAR4320071). DZ was partially funded by the Joint Institute for the Study of the Atmosphere and Ocean (JISAO) under NOAA Cooperative Agreement NA15OAR4320063. BS was supported by IMOS and CSIRO’s Decadal Climate Forecasting Project. We gratefully acknowledge the wide range of funding sources from many nations that have enabled the observations and analyses reviewed here

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies