scholarly journals High Glycolytic Activity Enhances Stem Cell Reprogramming of Fahd1-KO Mouse Embryonic Fibroblasts

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2040
Author(s):  
Ahmad Salti ◽  
Solmaz Etemad ◽  
Marta Suarez Cubero ◽  
Eva Albertini ◽  
Beata Kovacs-Szalka ◽  
...  
Keyword(s):  
Mitochondrial Biogenesis ◽  
Cellular Reprogramming ◽  
Negative Regulator ◽  
Strong Increase ◽  
Marker Genes ◽  
Embryonic Fibroblasts ◽  
Glycolytic Activity ◽  
Mitochondrial Functions ◽  
Insight Into

Mitochondria play a key role in metabolic transitions involved in the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs), but the underlying molecular mechanisms remain largely unexplored. To obtain new insight into the mechanisms of cellular reprogramming, we studied the role of FAH domain-containing protein 1 (FAHD1) in the reprogramming of murine embryonic fibroblasts (MEFs) into iPSCs and their subsequent differentiation into neuronal cells. MEFs from wild type (WT) and Fahd1-knock-out (KO) mice were reprogrammed into iPSCs and characterized for alterations in metabolic parameters and the expression of marker genes indicating mitochondrial biogenesis. Fahd1-KO MEFs showed a higher reprogramming efficiency accompanied by a significant increase in glycolytic activity as compared to WT. We also observed a strong increase of mitochondrial DNA copy number and expression of biogenesis marker genes in Fahd1-KO iPSCs relative to WT. Neuronal differentiation of iPSCs was accompanied by increased expression of mitochondrial biogenesis genes in both WT and Fahd1-KO neurons with higher expression in Fahd1-KO neurons. Together these observations establish a role of FAHD1 as a potential negative regulator of reprogramming and add additional insight into mechanisms by which FAHD1 modulates mitochondrial functions.

scholarly journals Detecting Emotions through Electrodermal Activity in Learning Contexts: A Systematic Review

Sensors ◽  
2021 ◽  
Vol 21 (23) ◽  
pp. 7869
Author(s):  
Anne Horvers ◽  
Natasha Tombeng ◽  
Tibor Bosse ◽  
Ard W. Lazonder ◽  
Inge Molenaar
Keyword(s):  
Systematic Review ◽  
Learning Outcomes ◽  
Educational Research ◽  
Electrodermal Activity ◽  
Physiological Arousal ◽  
Strong Increase ◽  
Guidelines And Standards ◽  
Methodological Aspects ◽  
Insight Into

There is a strong increase in the use of devices that measure physiological arousal through electrodermal activity (EDA). Although there is a long tradition of studying emotions during learning, researchers have only recently started to use EDA to measure emotions in the context of education and learning. This systematic review aimed to provide insight into how EDA is currently used in these settings. The review aimed to investigate the methodological aspects of EDA measures in educational research and synthesize existing empirical evidence on the relation of physiological arousal, as measured by EDA, with learning outcomes and learning processes. The methodological results pointed to considerable variation in the usage of EDA in educational research and indicated that few implicit standards exist. Results regarding learning revealed inconsistent associations between physiological arousal and learning outcomes, which seem mainly due to underlying methodological differences. Furthermore, EDA frequently fluctuated during different stages of the learning process. Compared to this unimodal approach, multimodal designs provide the potential to better understand these fluctuations at critical moments. Overall, this review signals a clear need for explicit guidelines and standards for EDA processing in educational research in order to build a more profound understanding of the role of physiological arousal during learning.

scholarly journals MacroH2A histone variants modulate enhancer activity to repress oncogenic programs and cellular reprogramming

2021 ◽  
Author(s):  
Alexandre Gaspar-Maia ◽  
Wazim Mohammed Ismail ◽  
Amelia Mazzone ◽  
Jagneet Kaur ◽  
Stephanie Safgren ◽  
...  
Keyword(s):  
Regulatory Elements ◽  
Histone Variants ◽  
Cellular Reprogramming ◽  
Negative Regulator ◽  
Cellular Heterogeneity ◽  
Enhancer Activity ◽  
Active Enhancer ◽  
A Cell ◽  
Cell Type Specific

Abstract Considerable efforts have been made to characterize active enhancer elements, which can be annotated by accessible chromatin and H3 lysine 27 acetylation (H3K27ac). However, apart from poised enhancers that are observed in early stages of development and putative silencers, the functional significance of cis-regulatory elements lacking H3K27ac is poorly understood. Here we show that macroH2A histone variants mark a subset of enhancers in normal and cancer cells, which we coined ‘macroH2A-Bound Enhancers’, that negatively modulate enhancer activity. We find macroH2A variants enriched at enhancer elements that are devoid of H3K27ac in a cell type-specific manner, indicating a role for macroH2A at inactive enhancers to maintain cell identity. In following, reactivation of macro-bound enhancers is associated with oncogenic programs in breast cancer and its repressive role is correlated with the activity of macroH2A2 as a negative regulator of BRD4 chromatin occupancy. Finally, through single cell epigenomic profiling, we show that the loss of macroH2A2 leads to increased cellular heterogeneity that may help to explain the role of macroH2A variants in defining oncogenic transcriptional dependencies.

scholarly journals Root-derived trans-zeatin cytokinin protects Arabidopsis plants against photoperiod stress

2020 ◽  
Author(s):  
Manuel Frank ◽  
Anne Cortleven ◽  
Ondrej Novak ◽  
Thomas Schmülling
Keyword(s):  
Cell Death ◽  
Response Regulator ◽  
Light Period ◽  
Negative Regulator ◽  
Marker Genes ◽  
Signaling Proteins ◽  
Negative Consequences ◽  
Regulatory Circuit ◽  
Cytokinin Synthesis

ABSTRACTRecently, a novel type of abiotic stress caused by a prolongation of the light period - coined photoperiod stress - has been described in Arabidopsis. During the night after the prolongation of the light period, stress and cell death marker genes are induced. The next day, strongly stressed plants display a reduced photosynthetic efficiency and leaf cells eventually enter programmed cell death. The phytohormone cytokinin (CK) acts as a negative regulator of this photoperiod stress syndrome. In this study, we show that Arabidopsis wild-type plants increase the CK concentration in response to photoperiod stress. Analysis of cytokinin synthesis and transport mutants revealed that root-derived trans-zeatin (tZ)-type CKs protect against photoperiod stress. The CK signaling proteins ARABIDOPSIS HISTIDINE PHOSPHOTRANSFER PROTEIN 2 (AHP2), AHP3 and AHP5 and transcription factors ARABIDOPSIS RESPONSE REGULATOR 2 (ARR2), ARR10 and ARR12 are required for the protective activity of CK. Analysis of higher order B-type arr mutants suggested that a complex regulatory circuit exists in which the loss of ARR10 or ARR12 can rescue the arr2 phenotype. Together the results revealed the role of root-derived CK acting in the shoot through the two-component signaling system to protect from the negative consequences of strong photoperiod stress.

A comprehensive overview of PPM1A: From structure to disease

2021 ◽  
pp. 153537022110618
Author(s):  
Mao Li ◽  
Xingfeng Xu ◽  
Yan Su ◽  
Xiaoyun Shao ◽  
Yali Zhou ◽  
...  
Keyword(s):  
Negative Regulator ◽  
Comprehensive Overview ◽  
Physiological Processes ◽  
Stress Response Pathway ◽  
Family Protein ◽  
Wide Range ◽  
Proliferation And Apoptosis ◽  
Insight Into ◽  
Phosphate Groups

PPM1A (magnesium-dependent phosphatase 1 A, also known as PP2Cα) is a member of the Ser/Thr protein phosphatase family. Protein phosphatases catalyze the removal of phosphate groups from proteins via hydrolysis, thus opposing the role of protein kinases. The PP2C family is generally considered a negative regulator in the eukaryotic stress response pathway. PPM1A can bind and dephosphorylate various proteins and is therefore involved in the regulation of a wide range of physiological processes. It plays a crucial role in transcriptional regulation, cell proliferation, and apoptosis and has been suggested to be closely related to the occurrence and development of cancers of the lung, bladder, and breast, amongst others. Moreover, it is closely related to certain autoimmune diseases and neurodegenerative diseases. In this review, we provide an insight into currently available knowledge of PPM1A, including its structure, biological function, involvement in signaling pathways, and association with diseases. Lastly, we discuss whether PPM1A could be targeted for therapy of certain human conditions.

scholarly journals A novel role of Zebrafish TMEM33 in negative regulation of interferon production by two distinct mechanisms

2021 ◽  
Vol 17 (2) ◽  
pp. e1009317
Author(s):  
Long-Feng Lu ◽  
Can Zhang ◽  
Zhuo-Cong Li ◽  
Xiao-Yu Zhou ◽  
Jing-Yu Jiang ◽  
...  
Keyword(s):  
Transmembrane Domain ◽  
Transmembrane Protein ◽  
Mrna Level ◽  
Negative Regulator ◽  
Functional Domain ◽  
Mitochondrial Antiviral Signaling ◽  
Viral Components ◽  
Insight Into ◽  
Zebrafish Liver

The transmembrane protein 33 (TMEM33) was originally identified as an endoplasmic reticulum (ER) protein that influences the tubular structure of the ER and modulates intracellular calcium homeostasis. However, the role of TMEM33 in antiviral immunity in vertebrates has not been elucidated. In this article, we demonstrate that zebrafish TMEM33 is a negative regulator of virus-triggered interferon (IFN) induction via two mechanisms: mitochondrial antiviral signaling protein (MAVS) ubiquitination and a decrease in the kinase activity of TANK binding kinase 1 (TBK1). Upon stimulation with viral components, tmem33 was remarkably upregulated in the zebrafish liver cell line. The IFNφ1 promoter (IFNφ1pro) activity and mRNA level induced by retinoic acid-inducible gene (RIG)-I-like receptors (RLRs) were significantly inhibited by TMEM33. Knockdown of TMEM33 increased host ifn transcription. Subsequently, we found that TMEM33 was colocalized in the ER and interacted with the RLR cascades, whereas MAVS was degraded by TMEM33 during the K48-linked ubiquitination. On the other hand, TMEM33 reduced the phosphorylation of mediator of IFN regulatory factor 3 (IRF3) activation (MITA)/IRF3 by acting as a decoy substrate of TBK1, which was also phosphorylated. A functional domain assay revealed that the N-terminal transmembrane domain 1 (TM1) and TM2 regions of TMEM33 were necessary for IFN suppression. Finally, TMEM33 significantly attenuated the host cellular antiviral capacity by blocking the IFN response. Taken together, our findings provide insight into the different mechanisms employed by TMEM33 in cellular IFN-mediated antiviral process.

scholarly journals Drosophila Rab39 Attenuates Lysosomal Degradation

2021 ◽  
Vol 22 (19) ◽  
pp. 10635
Author(s):  
Zsolt Lakatos ◽  
Péter Benkő ◽  
Gábor Juhász ◽  
Péter Lőrincz
Keyword(s):  
De Novo ◽  
Fat Body ◽  
Small Gtpases ◽  
Negative Regulator ◽  
Valuable Insight ◽  
Biological Mechanisms ◽  
Lysosomal Degradation ◽  
The Common ◽  
Insight Into

Lysosomal degradation, the common destination of autophagy and endocytosis, is one of the most important elements of eukaryotic metabolism. The small GTPases Rab39A and B are potential new effectors of this pathway, as their malfunction is implicated in severe human diseases like cancer and neurodegeneration. In this study, the lysosomal regulatory role of the single Drosophila Rab39 ortholog was characterized, providing valuable insight into the potential cell biological mechanisms mediated by these proteins. Using a de novo CRISPR-generated rab39 mutant, we found no failure in the early steps of endocytosis and autophagy. On the contrary, we found that Rab39 mutant nephrocytes internalize and degrade endocytic cargo at a higher rate compared to control cells. In addition, Rab39 mutant fat body cells contain small yet functional autolysosomes without lysosomal fusion defect. Our data identify Drosophila Rab39 as a negative regulator of lysosomal clearance during both endocytosis and autophagy.

Plasminogen Activation In Vivo upon Intravenous Infusion of DDAVP

1992 ◽  
Vol 67 (01) ◽  
pp. 111-116 ◽  
Author(s):  
Marcel Levi ◽  
Jan Paul de Boer ◽  
Dorina Roem ◽  
Jan Wouter ten Cate ◽  
C Erik Hack
Keyword(s):  
Monoclonal Antibodies ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Fold Increase ◽  
Fibrinolytic System ◽  
Plasminogen Activation ◽  
Plasminogen Activator Activity ◽  
Insight Into

SummaryInfusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in plasma plasminogen activator activity. Whether this increase results in the generation of plasmin in vivo has never been established.A novel sensitive radioimmunoassay (RIA) for the measurement of the complex between plasmin and its main inhibitor α2 antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated α2-antiplasmin and monoclonal antibodies against plasmin. The assay was validated in healthy volunteers and in patients with an activated fibrinolytic system.Infusion of DDAVP in a randomized placebo controlled crossover study resulted in all volunteers in a 6.6-fold increase in PAP complex, which was maximal between 15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP complex decreased with an apparent half-life of disappearance of about 120 min. Infusion of DDAVP did not induce generation of thrombin, as measured by plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex.We conclude that the increase in plasminogen activator activity upon the infusion of DDAVP results in the in vivo generation of plasmin, in the absence of coagulation activation. Studying the DDAVP induced increase in PAP complex of patients with thromboembolic disease and a defective plasminogen activator response upon DDAVP may provide more insight into the role of the fibrinolytic system in the pathogenesis of thrombosis.

On Metaphysics and the Political: A Polemics of Reading Baudelaire in the 1930s

2019 ◽  
Vol 58 (2) ◽  
pp. 249-259
Author(s):  
Joseph Acquisto
Keyword(s):  
Twentieth Century ◽  
Political Crisis ◽  
The Political ◽  
Modern Poetry ◽  
Progressive Politics ◽  
The World ◽  
Relationship Of ◽  
The Relationship ◽  
Insight Into

This essay examines a polemic between two Baudelaire critics of the 1930s, Jean Cassou and Benjamin Fondane, which centered on the relationship of poetry to progressive politics and metaphysics. I argue that a return to Baudelaire's poetry can yield insight into what seems like an impasse in Cassou and Fondane. Baudelaire provides the possibility of realigning metaphysics and politics so that poetry has the potential to become the space in which we can begin to think the two of them together, as opposed to seeing them in unresolvable tension. Or rather, the tension that Baudelaire animates between the two allows us a new way of thinking about the role of esthetics in moments of political crisis. We can in some ways see Baudelaire as responding, avant la lettre, to two of his early twentieth-century readers who correctly perceived his work as the space that breathes a new urgency into the questions of how modern poetry relates to the world from which it springs and in which it intervenes.

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