Improved insulin sensitivity after weight loss and exercise training is mediated by a reduction in plasma fatty acid mobilization, not enhanced oxidative capacity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65588/1/jphysiol.2009.175489.pd

Computing and data processing

The applications of computers and data processing to astronomy are discussed. Among the topics covered are the emerging national information infrastructure, workstations and supercomputers, supertelescopes, digital astronomy, astrophysics in a numerical laboratory, community software, archiving of ground-based observations, dynamical simulations of complex systems, plasma astrophysics, and the remote control of fourth dimension supercomputers

Multimodal Spontaneous Emotion Corpus for Human Behavior Analysis

Emotion is expressed in multiple modalities, yet most research has considered at most one or two. This stems in part from the lack of large, diverse, well-annotated, multimodal databases with which to develop and test algorithms. We present a well-annotated, multimodal, multidimensional spontaneous emotion corpus of 140 participants. Emotion inductions were highly varied. Data were acquired from a variety of sensors of the face that included high-resolution 3D dynamic imaging, high-resolution 2D video, and thermal (infrared) sensing, and contact physiological sensors that included electrical conductivity of the skin, respiration, blood pressure, and heart rate. Facial expression was annotated for both the occurrence and intensity of facial action units from 2D video by experts in the Facial Action Coding System (FACS). The corpus further includes derived features from 3D, 2D, and IR (infrared) sensors and baseline results for facial expression and action unit detection. The entire corpus will be made available to the research community

Plasma ferritin concentration is positively associated with in vivo fatty acid mobilization and insulin resistance in obese women

High rates of fatty acid (FA) mobilization from adipose tissue are associated with insulin resistance (IR) in obesity. In vitro evidence suggests that iron stimulates lipolysis in adipocytes, but whether iron is related to in vivo FA mobilization is unknown. We hypothesized that plasma ferritin concentration ([ferritin]), a marker of body iron stores, would be positively associated with FA mobilization. We measured [ferritin], the rate of appearance of FA in the systemic circulation (FA Ra; stable isotope dilution), key adipose tissue lipolytic proteins and IR (hyperinsulinaemicâ euglycaemic clamp) in 20 obese, premenopausal women. [Ferritin] was correlated with FA Ra (r = 0.65; P = 0.002) and IR (r = 0.57; P = 0.008); these relationships remained significant after controlling for body mass index and plasma [Câ reactive protein] (a marker of systemic inflammation) in multiple regression analyses. We then stratified subjects into tertiles based on [ferritin] to compare subjects with â Highâ ferritinâ versus â Lowâ ferritinâ . Plasma [hepcidin] was more than fivefold greater (P < 0.05) in the Highâ ferritin versus Lowâ ferritin group, but there was no difference in plasma [Câ reactive protein] between groups, indicating that the large difference in plasma [ferritin] reflects a difference in iron stores, not systemic inflammation. We found that FA Ra, adipose protein abundance of hormoneâ sensitive lipase and adipose triglyceride lipase, and IR were significantly greater in subjects with Highâ ferritin versus Lowâ ferritin (all P < 0.05). These data provide the first evidence linking iron and in vivo FA mobilization and suggest that elevated iron stores might contribute to IR in obesity by increasing systemic FA availability.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146491/1/eph12367_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146491/2/eph12367.pd

Skeletal muscle ferritin abundance is tightly related to plasma ferritin concentration in adults with obesity

Obesity is associated with complex perturbations to whole- body and tissue iron homeostasis. Recent evidence suggests a potentially important influence of iron storage in skeletal muscle on whole- body iron homeostasis, but this association is not clearly resolved. The primary aim of this study was to assess the relationship between whole- body and skeletal muscle iron stores by measuring the abundance of the key iron storage (ferritin) and import (transferrin receptor) proteins in skeletal muscle, as well as markers of whole- body iron homeostasis in men (n = 19) and women (n = 43) with obesity. Plasma ferritin concentration (a marker of whole- body iron stores) was highly correlated with muscle ferritin abundance (r = 0.77, P = 2 à  10- 13) and negatively associated with muscle transferrin receptor abundance (r = - 0.76, P = 1 à  10- 12). These relationships persisted when accounting for sex, age, BMI and plasma C- reactive protein concentration. In parallel with higher whole- body iron stores in our male versus female participants, men had 2.2- fold higher muscle ferritin abundance (P = 1 à  10- 4) compared with women. In accordance with lower muscle iron storage, women had 2.7- fold higher transferrin receptor abundance (P = 7 à  10- 10) compared with men. We conclude that muscle iron storage and import proteins are tightly and independently related to plasma ferritin concentration in adults with obesity, suggesting that skeletal muscle may be an underappreciated iron store.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163407/2/eph12853_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163407/1/eph12853.pd

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

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

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