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

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 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

scholarly journals The Estrogen-Occupied Estrogen Receptor Functions as a Negative Regulator to Inhibit Cell Proliferation Induced by Insulin/IGF-1: A Cell Context-Specific Antimitogenic Action of Estradiol on Rat Lactotrophs in Culture

Endocrinology ◽  
2002 ◽  
Vol 143 (7) ◽  
pp. 2750-2758 ◽  
Author(s):  
Kengo Kawashima ◽  
Koji Yamakawa ◽  
Wakaba Takahashi ◽  
Soichi Takizawa ◽  
Ping Yin ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Proliferative Activity ◽  
Cell Number ◽  
Negative Regulator ◽  
Simultaneous Treatment ◽  
Wide Range ◽  
Dependent Inhibition ◽  
Context Specific ◽  
Basal Proliferation

Abstract Estrogens stimulate cell proliferation in typical estrogen-responsive tissues including the anterior pituitary gland. Here we report that 17-β estradiol (E2) has estrogen receptor-mediated mitogenic and antimitogenic actions on rat lactotrophs in primary culture, depending on the cell context. E2 did not affect basal proliferation at 2 d after treatment, but it increased it at 4 d. Insulin markedly increased proliferative activity, which was inhibited by simultaneous treatment with E2, even after only 2 d of treatment. This antimitogenic action on insulin-induced proliferation was also observed with other estrogens but not with nonestrogenic steroids. Treatment with antiestrogens in combination with E2 antagonized both the mitogenic and antimitogenic actions of E2. Antiestrogen treatment alone inhibited basal proliferation, and it mimicked the inhibitory action of E2 on insulin-induced proliferation with less potency. In parallel with cell proliferation, an insulin-induced increase in the cell number of cyclin D1-immunoreactive lactotrophs was inhibited by E2 treatment. Although the antimitogenic action of E2 was seen with a wide range of doses of insulin or IGF-1, proliferation was stimulated rather than inhibited by E2 when cells were treated with serum or forskolin/isobutylmethylxanthine instead of insulin, indicating a mitogen-specific, but not proliferative activity-dependent, inhibition by E2. The results of estrogen-occupied estrogen receptors as negative regulators of proliferation suggest a novel interaction between estrogen and growth factors in the regulation of proliferation in estrogen-responsive cells.

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 The miRNA Pull Out Assay as a Method to Validate the miR-28-5p Targets Identified in Other Tumor Contexts in Prostate Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Milena Rizzo ◽  
Gabriele Berti ◽  
Francesco Russo ◽  
Monica Evangelista ◽  
Marco Pellegrini ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Tumor Suppressor ◽  
Protein Level ◽  
Mirna Targets ◽  
Pull Out ◽  
General Terms ◽  
Specific Tumor ◽  
Context Specific ◽  
Tumor Types

miR-28-5p is an intragenic miRNA which is underexpressed in several tumor types showing a tumor suppressor (TS) activity. Routinely, the known miR-28-5p targets are validated in specific tumor contexts but it is unclear whether these targets are also being regulated in other tumor types. To this end, we adopted the miRNA pull out assay to capture the miR-28-5p targets in DU-145 prostate cancer (PCa) cells. Firstly, we demonstrated that miR-28-5p acts as a TS-miRNA in PCa, affecting cell proliferation, survival, and apoptosis. Secondly, we evaluated the enrichment of the 10 validated miR-28-5p targets in the pull out sample. We showed that E2F6, TEX-261, MAPK1, MPL, N4BP1, and RAP1B but not BAG1, OTUB1, MAD2L1, and p21 were significantly enriched, suggesting that not all the miR-28-5p targets are regulated by this miRNA in PCa. We then verified whether the miR-28-5p-interacting targets were regulated by this miRNA. We selected E2F6, the most enriched target in the pull out sample, and demonstrated that miR-28-5p downregulated E2F6 at the protein level suggesting that our approach was effective. In general terms, these findings support the miRNA pull out assay as a useful method to identify context-specific miRNA targets.

scholarly journals Loss of lrrk2 impairs dopamine catabolism, cell proliferation, and neuronal regeneration in the zebrafish brain

2017 ◽  
Author(s):  
Stefano Suzzi ◽  
Reiner Ahrendt ◽  
Stefan Hans ◽  
Svetlana A. Semenova ◽  
Saygın Bilican ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Brain Injury ◽  
Neuronal Regeneration ◽  
Loss Of Function ◽  
Larval Brain ◽  
Stab Injury ◽  
Zebrafish Brain ◽  
Specific Effects ◽  
The Brain

AbstractLRRK2 mutations are a major cause of Parkinson’s disease. Pathogenicity of LRRK2 loss-of-function is controversial, as knockout in rodents reportedly induces no brain-specific effects and knockdown studies in zebrafish are conflicting. Here we show that CRISPR/Cas9-engineered deletion of the ~60-kbp-long zebrafish lrrk2 locus elicits a pleomorphic, albeit transient brain phenotype in maternal-zygotic mutants (mzLrrk2). Intriguingly, 11-month-old mzLrrk2 adults display increased dopamine and serotonin catabolism. Additionally, we find decreased mitosis in the larval brain and reduced stab injury-induced neuronal regeneration in the adult telencephalon. Finally, hypokinesia associates with loss of lrrk2 in larvae. Our results demonstrate that lrrk2 knockout has an early neurodevelopmental effect, and leads to perturbed dopamine and serotonin catabolism in a LRRK2 knockout. We propose mzLrrk2 zebrafish as a valuable tool to study LRRK2 loss-of-function in vivo, and provide a link between LRRK2 and the control of basal cell proliferation in the brain that may become potentially critical upon challenges like brain injury.

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.

Modulation of Calcium Signaling in Glioblastoma Multiforme: A Therapeutic Promise for Natural Products

2020 ◽  
Vol 20 (18) ◽  
pp. 1879-1899
Author(s):  
Amir R. Afshari ◽  
Hamid Mollazadeh ◽  
Mohammad Soukhtanloo ◽  
Azar Hosseini ◽  
Elmira Mohtashami ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Natural Products ◽  
Glioblastoma Multiforme ◽  
Calcium Signaling ◽  
Signaling Pathways ◽  
Potential Treatment ◽  
Treatment Target ◽  
Drug Candidates ◽  
Therapeutic Modalities ◽  
Context Specific

Glioblastoma multiforme (GBM) continues as one of the most lethal cerebral cancers despite standard therapeutic modalities, such as maximum surgical resection and chemoradiation. The minimal effectiveness of existing therapies necessitates the development of additional drug candidates that could improve the prognosis of GBM patients. Accumulating evidence suggests that calcium (Ca2+) is involved in the processes of cell proliferation, metastasis, angiogenesis, migration, and invasiveness. Therefore, Ca2+ could serve as a crucial regulator of tumorigenesis and a potential treatment target in GBM. In this context, specific natural products are known to modulate Ca2+ signaling pathways implicated in tumor growth, apoptosis, angiogenesis, and development of GBM. Here, the focus is on the function of Ca2+ as a therapeutic target in GBM and reviewing certain natural products that affect the signaling pathways of Ca2+.

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
Sign in / Sign up

Export Citation Format

Share Document