scholarly journals Context-Specific Effects of TGF-β/SMAD3 in Cancer Are Modulated by the Epigenome

Cell Reports ◽  
2015 ◽  
Vol 13 (11) ◽  
pp. 2480-2490 ◽  
Author(s):  
Ana Tufegdzic Vidakovic ◽  
Oscar M. Rueda ◽  
Stephin J. Vervoort ◽  
Ankita Sati Batra ◽  
Mae Akilina Goldgraben ◽  
...  
Keyword(s):  
Specific Effects ◽  
Context Specific

ERP Evidence for Implicit Priming of Top–Down Control of Attention

2016 ◽  
Vol 28 (5) ◽  
pp. 763-772 ◽  
Author(s):  
Chris Blais ◽  
Emily Hubbard ◽  
George R. Mangun
Keyword(s):  
Associative Learning ◽  
Stroop Effect ◽  
Congruency Effect ◽  
Simon Task ◽  
Electrical Signal ◽  
Lower Visual Field ◽  
Specific Effects ◽  
High Conflict ◽  
Contemporary Work ◽  
Context Specific

Proportion congruency effects are the observation that the magnitude of the Stroop effect increases as the proportion of congruent trials in a block increases. Contemporary work shows that proportion effects can be specific to a particular context. For example, in a Simon task in which items appearing above fixation are mostly congruent and items appearing below fixation are mostly incongruent, the Simon effect is larger for the items appearing at the top. There is disagreement as to whether these context-specific effects result from simple associative learning or, instead, a type of conflict-mediated associative learning. Here, we address this question in an ERP study using a Simon task in which the proportion congruency effect was context-specific, manipulating the proportion of congruent trials based on location (upper vs. lower visual field). We found significant behavioral proportion congruency effects that varied with the specific contexts. In addition, we observed that the N2 response of the ERPs to the stimuli was larger in amplitude for the high congruent (high conflict) versus low congruent (low conflict) conditions/contexts. Because the N2 is known to be greater in amplitude also for trials where conflict is high and is believed to be an electrical signal related to conflict detection in the medial frontal cortex, this supports the idea that conflict-mediated associative learning is involved in the proportion congruency effect.

scholarly journals Context-specific Effects of Fibulin-5 (DANCE/EVEC) on Cell Proliferation, Motility, and Invasion

2002 ◽  
Vol 277 (30) ◽  
pp. 27367-27377 ◽  
Author(s):  
William P. Schiemann ◽  
Gerard C. Blobe ◽  
Dario E. Kalume ◽  
Akhilesh Pandey ◽  
Harvey F. Lodish
Keyword(s):  
Cell Proliferation ◽  
Specific Effects ◽  
Context Specific

scholarly journals Context-specific effects of facial dominance and trustworthiness on hypothetical leadership decisions

PLoS ONE ◽  
2019 ◽  
Vol 14 (7) ◽  
pp. e0214261
Author(s):  
Hannah S. Ferguson ◽  
Anya Owen ◽  
Amanda C. Hahn ◽  
Jaimie Torrance ◽  
Lisa M. DeBruine ◽  
...  
Keyword(s):  
Specific Effects ◽  
Context Specific ◽  
Leadership Decisions

FLT3-ITD Has Developmental Context Specific Effects on Hematopoiesis and Myeloid Leukemogenesis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 843-843
Author(s):  
Jeffrey A. Magee ◽  
Shaina Porter ◽  
Andrew Cluster
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Clonal Evolution ◽  
Myeloid Differentiation ◽  
Cell Physiology ◽  
Gene Products ◽  
Self Renewal ◽  
Developmental Context ◽  
Specific Effects ◽  
Context Specific

Abstract Much progress has been made toward identifying the mutations that cause human acute myeloid leukemia (AML), and these studies have shown that pediatric and adult AML are often caused by different mutations. Genetic differences between pediatric and adult AML may underlie differences in outcomes and necessitate different treatment strategies, yet we have few insights into why these differences occur. One possibility is that the mechanisms that regulate normal hematopoiesis change with age, and mutations therefore have age-specific phenotypes in pre-leukemic progenitors. To fully understand how AML evolves in children and adults, and how targeting individual pathways might impact cell physiology at different ages, it is important to understand how somatic mutations interface with the normal, temporally dynamic programs that regulate hematopoiesis. The FLT3-Internal Tandem Duplication (FLT3-ITD) mutation is common in adult AML but rare in early childhood AML (30-40% of adult AML, 5-10% of AML in children <10 years old, <1% of infant AML). FLT3-ITD mutations occur late in the clonal evolution of AML cells, and they are thought to drive cell proliferation and survival. In mice, FLT3-ITD has been shown to deplete adult hematopoietic stem cells (HSCs) by promoting myeloid differentiation. This may explain why the mutation occurs late in clonal evolution - HSCs must first acquire mutations that enhance self-renewal - but it also raises the question of why infant HSCs, which have an inherently higher self-renewal capacity, do not give rise to FLT3-ITD positive AML more often than is observed. We used FLT3-ITD knock-in mice to test whether FLT3-ITD has developmental context specific effects on hematopoiesis. In adult mice, FLT3-ITD depleted the HSC pool and expanded multipotent progenitor (MPP) and myeloid progenitor populations consistent with prior studies. In fetal mice, FLT3-ITD had no effect on HSC or MPP numbers, HSC function (as determined by limit dilution transplants) or myelopoiesis. FLT3-ITD did not affect hematopoiesis until shortly after birth. These temporal differences were evident even in the presence of cooperating Runx1 mutations. To understand why fetal and adult progenitors responded differently to FLT3-ITD, we characterized signal transduction and gene expression in fetal, neonatal and adult progenitors. We found that STAT5 was activated by FLT3-ITD at all stages of development, but MAPK was activated only in post-natal progenitors concordant with the onset of HSC and myeloid phenotypes. To our surprise, conditional Stat5a/b deletion exacerbated the HSC depletion and myeloid expansion phenotypes of adult FLT3-ITD mice rather than rescuing them. This suggests that STAT5 helps to maintain adult, FLT3-ITD mutant progenitors in an undifferentiated state even as other effectors promote myeloid differentiation. We next used microarrays to test whether FLT3-ITD has age-specific effects on gene expression in HSCs and MPPs, and to identify normal temporal changes in gene expression that may modulate the FLT3-ITD phenotypes. These studies made several key points: 1) In wild type HSCs, most fetal-specific genes were inactivated and most adult-specific genes were activated between birth and P14. This transition was earlier than prior studies have suggested, and it correlated with the age at which FLT3-ITD induced HSC depletion and myeloid expansion. 2) FLT3-ITD did not alter gene expression until after birth, coincident with onset of the HSC depletion and myeloid expansion phenotypes. 3) FLT3-ITD target genes were more differentially expressed in MPPs than in HSCs, consistent with recent data suggesting that MPPs are a cell of origin for FLT3-ITD driven AML. 4) Most, but not all, FLT3-ITD target genes were STAT5 dependent. Our analyses have identified novel, adult-specific candidate effectors of FLT3-ITD. Moreover, our findings raise the question of whether fetal genetic programs can suppress FLT3-ITD driven leukemogenesis, and we have begun to address this question with gain of function models. AML cells may exhibit "context addiction" (i.e.a sustained requirement for normal adult gene products and a toxic response to fetal gene products), that could be exploited therapeutically. Disclosures No relevant conflicts of interest to declare.

scholarly journals DNA methylation mutants in Physcomitrella patens elucidate individual roles of CG and non-CG methylation in genome regulation

2020 ◽  
Vol 117 (52) ◽  
pp. 33700-33710
Author(s):  
Katherine Domb ◽  
Aviva Katz ◽  
Keith D. Harris ◽  
Rafael Yaari ◽  
Efrat Kaisler ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Physcomitrella Patens ◽  
Plant Genome ◽  
Specific Effects ◽  
Genome Regulation ◽  
Expression Of Genes ◽  
The Individual ◽  
Context Specific ◽  
Study Context ◽  
Or Genes

Cytosine (DNA) methylation in plants regulates the expression of genes and transposons. While methylation in plant genomes occurs at CG, CHG, and CHH sequence contexts, the comparative roles of the individual methylation contexts remain elusive. Here, we present Physcomitrella patens as the second plant system, besides Arabidopsis thaliana, with viable mutants with an essentially complete loss of methylation in the CG and non-CG contexts. In contrast to A. thaliana, P. patens has more robust CHH methylation, similar CG and CHG methylation levels, and minimal cross-talk between CG and non-CG methylation, making it possible to study context-specific effects independently. Our data found CHH methylation to act in redundancy with symmetric methylation in silencing transposons and to regulate the expression of CG/CHG-depleted transposons. Specific elimination of CG methylation did not dysregulate transposons or genes. In contrast, exclusive removal of non-CG methylation massively up-regulated transposons and genes. In addition, comparing two exclusively but equally CG- or CHG-methylated genomes, we show that CHG methylation acts as a greater transcriptional regulator than CG methylation. These results disentangle the transcriptional roles of CG and non-CG, as well as symmetric and asymmetric methylation in a plant genome, and point to the crucial role of non-CG methylation in genome regulation.

scholarly journals Multi-tissue Multi-omics Nutrigenomics Indicates Context-specific Effects of DHA on Rat Brain

2020 ◽  
Author(s):  
Guanglin Zhang ◽  
Qingying Meng ◽  
Montgomery Blencowe ◽  
Agrawal Rahul ◽  
Fernando Gomez-Pinilla ◽  
...  
Keyword(s):  
Serum Triglyceride ◽  
Chow Group ◽  
Chow Diet ◽  
Immune Functions ◽  
Specific Effects ◽  
High Fructose ◽  
Metabolic Conditions ◽  
Nutritional Effects ◽  
Context Specific ◽  
The Brain

AbstractScopeWe explored the influence of DHA on cardiometabolic and cognitive phenotypes, and multiomic alterations in the brain under two metabolic conditions to understand context-specific nutritional effects.Methods and ResultsRats were randomly assigned to a DHA-rich or a control chow diet while drinking water or high fructose solution, followed by profiling of metabolic and cognitive phenotypes and the transcriptome and DNA methylome of the hypothalamus and hippocampus. DHA reduced serum triglyceride and improved insulin resistance and memory exclusively in the fructose-consuming rats. In hippocampus, DHA affected genes related to synapse functions in the chow group but immune functions in the fructose group; in hypothalamus, DHA altered immune pathways in the chow group but metabolic pathways in the fructose group. Network modeling revealed context-specific regulators of DHA effects, including Klf4 and Dusp1 for chow condition and Lum, Fn1, and Col1a1 for fructose condition in hippocampus, as well as Cyr61, JunB, Ier2, and Pitx2 under chow condition and Hcar1, Cdh1, and Osr1 under fructose condition in hypothalamus.ConclusionDHA exhibits differential influence on epigenetic loci, genes, pathways, and metabolic and cognitive phenotypes under different dietary contexts, supporting population stratification in DHA studies to achieve precision nutrition.

scholarly journals The Effects of Gender Signals and Performance in Online Product Reviews

2022 ◽  
Vol 4 ◽  
Author(s):  
Sandipan Sikdar ◽  
Rachneet Sachdeva ◽  
Johannes Wachs ◽  
Florian Lemmerich ◽  
Markus Strohmaier
Keyword(s):  
General Trend ◽  
Product Reviews ◽  
Product Categories ◽  
Learning Classifier ◽  
Specific Effects ◽  
Review Helpfulness ◽  
Social Media Platforms ◽  
And Performance ◽  
Context Specific ◽  
Gender Specific

This work quantifies the effects of signaling gender through gender specific user names, on the success of reviews written on the popular amazon.com shopping platform. Highly rated reviews play an important role in e-commerce since they are prominently displayed next to products. Differences in reviews, perceived—consciously or unconsciously—with respect to gender signals, can lead to crucial biases in determining what content and perspectives are represented among top reviews. To investigate this, we extract signals of author gender from user names to select reviews where the author’s likely gender can be inferred. Using reviews authored by these gender-signaling authors, we train a deep learning classifier to quantify the gendered writing style (i.e., gendered performance) of reviews written by authors who do not send clear gender signals via their user name. We contrast the effects of gender signaling and performance on the review helpfulness ratings using matching experiments. This is aimed at understanding if an advantage is to be gained by (not) signaling one’s gender when posting reviews. While we find no general trend that gendered signals or performances influence overall review success, we find strong context-specific effects. For example, reviews in product categories such as Electronics or Computers are perceived as less helpful when authors signal that they are likely woman, but are received as more helpful in categories such as Beauty or Clothing. In addition to these interesting findings, we believe this general chain of tools could be deployed across various social media platforms.

scholarly journals SAT-033 Studying Cell-Context Specific Effects on the Function of the AT1R in iPSCs and Their Differentiated Derivatives

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Kyla Bourque ◽  
Dominic Devost ◽  
Darlaine Pétrin ◽  
Terence Hébert
Keyword(s):  
Specific Effects ◽  
Context Specific

scholarly journals Context-Dependent Roles of Claudins in Tumorigenesis

2021 ◽  
Vol 11 ◽  
Author(s):  
Jian Li
Keyword(s):  
Tumor Suppressors ◽  
Tumor Biology ◽  
Tumor Development ◽  
Tumor Promoters ◽  
Biological Functions ◽  
Tissue Integrity ◽  
Diagnosis And Prognosis ◽  
Specific Effects ◽  
Organ Type ◽  
Context Specific

The barrier and fence functions of the claudin protein family are fundamental to tissue integrity and human health. Increasing evidence has linked claudins to signal transduction and tumorigenesis. The expression of claudins is frequently dysregulated in the context of neoplastic transformation. Studies have uncovered that claudins engage in nearly all aspects of tumor biology and steps of tumor development, suggesting their promise as targets for treatment or biomarkers for diagnosis and prognosis. However, claudins can be either tumor promoters or tumor suppressors depending on the context, which emphasizes the importance of taking various factors, including organ type, environmental context and genetic confounders, into account when studying the biological functions and targeting of claudins in cancer. This review discusses the complicated roles and intrinsic and extrinsic determinants of the context-specific effects of claudins in cancer.

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