955 research outputs found
Expressing dual concern in criticism for wrongdoing: The persuasive power of criticizing with care
To call attention to and motivate action on ethical issues in business or society, messengers often criticize groups for wrongdoing and ask these groups to change their behavior. When criticizing target groups, messengers frequently identify and express concern about harm caused to a victim group, and in the process address a target group by criticizing them for causing this harm and imploring them to change. However, we find that when messengers criticize a target group for causing harm to a victim group in this way—expressing singular concern for the victim group—members of the target group infer, often incorrectly, that the messenger views the target group as less moral and unworthy of concern. This inferred lack of moral concern reduces criticism acceptance and prompts backlash from the target group. To address this problem, we introduce dual concern messaging—messages that simultaneously communicate that a target group causes harm to a victim group and express concern for the target group. A series of several experiments demonstrate that dual concern messages reduce inferences that a critical messenger lacks moral concern for the criticized target group, increase the persuasiveness of the criticism among members of the target group, and reduce backlash from consumers against a corporate messenger. When pursuing justice for victims of a target group, dual concern messages that communicate concern for the victim group
as well as the target group are more effective in fostering openness toward criticism, rather than defensiveness, in a target group, thus setting the stage for change
Lack of Assortative Mating for Tail, Body Size, or Condition in the Elaborate Monomorphic Turquoise-Browed Motmot (\u3cem\u3eEumomota superciliosa\u3c/em\u3e)
Elaborate male and female plumage can be maintained by mutual sexual selection and function as a mate-choice or status signal in both sexes. Both male and female Turquoise-browed Motmot (Eumomota superciliosa) have long tails that terminate in widened blue-and-black rackets that appear to hang, unattached, below the body of the bird. I tested whether mutual sexual selection maintains the Turquoise-browed Motmot’s elaborate tail plumage by testing the prediction that mating occurs in an assortative manner for tail plumage. I also tested whether assortative mating occurs for body size, a potential measure of dominance, and for phenotypic condition, a measure of individual quality. Assortative mating was measured (1) within all pairs in the study population, (2) within newly formed pairs, and (3) within experimentally induced pairs that formed after removal of females from stable pairs. Assortative mating was not found for tail plumage, body size, or phenotypic condition in any of these samples. Therefore, there was no support for the “mutual sexual selection” hypothesis. I discuss the hypothesis that the tail is sexually selected in males only, and that natural selection accounts for the evolutionary maintenance of the elaborate female tail.
La existencia de plumaje elaborado en los machos y las hembras puede ser mantenida por selecci´on sexual mutua, y funcionar como una se˜nal para la selecci´on de parejas o del estatus de los individuos en ambos sexos. Tanto los machos como las hembras de la especie Eumomota superciliosa tienen colas largas que terminan en unas raquetas ensanchadas de color azul y negro, que parecen colgar debajo del cuerpo de las aves. En este estudio prob´e si el plumaje elaborado de la cola de esta especie es mantenido mediante selecci´on sexual mutua, evaluando la predicci´on de que el apareamiento es asociativo con respecto al plumaje de la cola. Tambi´en prob´e si existe apareamiento asociativo con respecto al tama˜no (una medida potencial de la dominancia) y con respecto a la condici´on fenot´ıpica (una medida de la calidad de los individuos). El apareamiento asociativo fue medido para todas las parejas de la poblaci´on de estudio, para parejas formadas recientemente y para parejas cuya formaci´on fue inducida experimentalmente mediante la remoci´on de las hembras de parejas estables. No se encontr´o apareamiento asociativo con respecto al plumaje de la cola, al tama˜no corporal, ni a la condici´on fenot´ıpica en ninguna de estas muestras. Por lo tanto, no existi´o respaldo para la hip´otesis de selecci´on sexual mutua. Discuto la hip´otesis que plantea que la cola es objeto de selecci´on sexual s´olo en los machos, y que la selecci´on natural permite explicar el mantenimiento evolutivo de la cola elaborada en las hembras
Non-Invasive Detection of a Small Number of Bioluminescent Cancer Cells In Vivo
Early detection of tumors can significantly improve the outcome of tumor treatment. One of the most frequently asked questions in cancer imaging is how many cells can be detected non-invasively in a live animal. Although many factors limit such detection, increasing the light emission from cells is one of the most effective ways of overcoming these limitations. Here, we describe development and utilization of a lentiviral vector containing enhanced firefly luciferase (luc2) gene. The resulting single cell clones of the mouse mammary gland tumor (4T1-luc2) showed stable light emission in the range of 10,000 photons/sec/cell. In some cases individual 4T1-luc2 cells inserted under the skin of a nu/nu mouse could be detected non-invasively using a cooled CCD camera in some cases. In addition, we showed that only few cells are needed to develop tumors in these mice and tumor progression can be monitored right after the cells are implanted. Significantly higher luciferase activity in these cells allowed us to detect micrometastases in both, syngeneic Balb/c and nu/nu mice
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
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
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
Body mass index in early adulthood and colorectal cancer risk for carriers and non-carriers of germline mutations in DNA mismatch repair genes
BACKGROUND: Carriers of germline mutations in DNA mismatch repair (MMR) genes have a high risk of colorectal cancer (CRC), but the modifiers of this risk are not well established. We estimated an association between body mass index (BMI) in early adulthood and subsequent risk of CRC for carriers and, as a comparison, estimated the association for non-carriers. METHODS: A weighted Cox regression was used to analyse height and weight at 20 years reported by 1324 carriers of MMR gene mutations (500 MLH1, 648 MSH2, 117 MSH6 and 59 PMS2) and 1219 non-carriers from the Colon Cancer Family Registry. RESULTS: During 122,304 person-years of observation, we observed diagnoses of CRC for 659 carriers (50%) and 36 non-carriers (3%). For carriers, the risk of CRC increased by 30% for each 5 kg m(-2) increment in BMI in early adulthood (hazard ratio, HR: 1.30; 95% confidence interval, CI: 1.08-1.58; P=0.01), and increased by 64% for non-carriers (HR: 1.64; 95% CI: 1.02-2.64; P=0.04) after adjusting for sex, country, cigarette smoking and alcohol drinking (and the MMR gene that was mutated in carriers). The difference in HRs for carriers and non-carriers was not statistically significant (P=0.50). For MLH1 and PMS2 (MutLα heterodimer) mutation carriers combined, the corresponding increase was 36% (HR: 1.36; 95% CI: 1.05-1.76; P=0.02). For MSH2 and MSH6 (MutSα heterodimer) mutation carriers combined, the HR was 1.26 (95% CI: 0.96-1.65; P=0.09). There was no significant difference between the HRs for MutLα and MutSα heterodimer carriers (P=0.56). CONCLUSION: Body mass index in early adulthood is positively associated with risk of CRC for MMR gene mutation carriers and non-carriers
Body mass index in early adulthood and colorectal cancer risk for carriers and non-carriers of germline mutations in DNA mismatch repair genes
BACKGROUND: Carriers of germline mutations in DNA mismatch repair (MMR) genes have a high risk of colorectal cancer (CRC), but the modifiers of this risk are not well established. We estimated an association between body mass index (BMI) in early adulthood and subsequent risk of CRC for carriers and, as a comparison, estimated the association for non-carriers. METHODS: A weighted Cox regression was used to analyse height and weight at 20 years reported by 1324 carriers of MMR gene mutations (500 MLH1, 648 MSH2, 117 MSH6 and 59 PMS2) and 1219 non-carriers from the Colon Cancer Family Registry. RESULTS: During 122,304 person-years of observation, we observed diagnoses of CRC for 659 carriers (50%) and 36 non-carriers (3%). For carriers, the risk of CRC increased by 30% for each 5 kg m(-2) increment in BMI in early adulthood (hazard ratio, HR: 1.30; 95% confidence interval, CI: 1.08-1.58; P=0.01), and increased by 64% for non-carriers (HR: 1.64; 95% CI: 1.02-2.64; P=0.04) after adjusting for sex, country, cigarette smoking and alcohol drinking (and the MMR gene that was mutated in carriers). The difference in HRs for carriers and non-carriers was not statistically significant (P=0.50). For MLH1 and PMS2 (MutLα heterodimer) mutation carriers combined, the corresponding increase was 36% (HR: 1.36; 95% CI: 1.05-1.76; P=0.02). For MSH2 and MSH6 (MutSα heterodimer) mutation carriers combined, the HR was 1.26 (95% CI: 0.96-1.65; P=0.09). There was no significant difference between the HRs for MutLα and MutSα heterodimer carriers (P=0.56). CONCLUSION: Body mass index in early adulthood is positively associated with risk of CRC for MMR gene mutation carriers and non-carriers
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