scholarly journals Reducing 14-3-3ζ expression influences adipocyte maturity and impairs function

2020 ◽  
Author(s):  
Abel K. Oppong ◽  
Kadidia Diallo ◽  
Isabelle Robillard Frayne ◽  
Christine Des Rosiers ◽  
Gareth E. Lim
Keyword(s):  
Binding Sites ◽  
De Novo ◽  
Hormone Sensitive Lipase ◽  
Lipolytic Enzyme ◽  
Molecular Scaffolds ◽  
Mature Adipocyte ◽  
Metabolic Functions ◽  
Negative Effect ◽  
Subsequent Activation ◽  
The Impact

AbstractOne of the primary metabolic functions of a mature adipocyte is to supply energy via lipolysis, or the catabolism of stored lipids. Hormone-sensitive lipase (HSL) is a critical lipolytic enzyme, and its phosphorylation and subsequent activation by PKA generates phospho-binding sites for 14-3-3 proteins, a ubiquitously expressed family of molecular scaffolds. While we previously identified essential roles of the 14-3-3ζ isoform in murine adipogenesis, the presence of 14-3-3 protein binding sites on HSL suggests that 14-3-3ζ could also influence mature adipocyte processes like lipolysis. Herein, we demonstrate that 14-3-3ζ is necessary for lipolysis in male mice and fully differentiated 3T3-L1 adipocytes, as depletion of 14-3-3ζ significantly impaired glycerol and FFA release. Unexpectedly, this was not due to impairments in signaling events underlying lipolysis; instead, reducing 14-3-3ζ expression was found to significantly impact adipocyte maturity, as observed by reduced abundance of PPARγ2 protein and expression of mature adipocytes genes and those associated with de novo triglyceride synthesis and lipolysis. The impact of 14-3-3ζ depletion on adipocyte maturity was further examined with untargeted lipidomics, which revealed that reductions in 14-3-3ζ abundance promoted the acquisition of a lipidomic signature that resembled undifferentiated, pre-adipocytes. Collectively, these findings reveal a novel aspect of 14-3-3ζ in adipocytes, as reducing 14-3-3ζ was found to have a negative effect on adipocyte maturity and adipocyte-specific processes like lipolysis.

scholarly journals Reducing 14-3-3ζ expression influences adipocyte maturity and impairs function

2020 ◽  
Vol 319 (1) ◽  
pp. E117-E132
Author(s):  
Abel K. Oppong ◽  
Kadidia Diallo ◽  
Isabelle Robillard Frayne ◽  
Christine Des Rosiers ◽  
Gareth E. Lim
Keyword(s):  
Binding Sites ◽  
De Novo ◽  
Hormone Sensitive Lipase ◽  
Peroxisome Proliferator ◽  
Mature Adipocyte ◽  
Peroxisome Proliferator Activated Receptor ◽  
Triacylglycerol Lipase ◽  
Metabolic Functions ◽  
Negative Effect ◽  
The Impact

One of the primary metabolic functions of a mature adipocyte is to supply energy via lipolysis, or the catabolism of stored lipids. Adipose triacylglycerol lipase (ATGL) and hormone-sensitive lipase (HSL) are critical lipolytic enzymes, and their phosphorylation generates phospho-binding sites for 14-3-3 proteins, a ubiquitously expressed family of molecular scaffolds. Although we previously identified essential roles of the 14-3-3ζ isoform in murine adipogenesis, the presence of 14-3-3 protein binding sites on ATGL and HSL suggests that 14-3-3ζ could also influence mature adipocyte processes like lipolysis. Here we demonstrate that 14-3-3ζ is necessary for lipolysis in male mice and fully differentiated 3T3-L1 adipocytes, as depletion of 14-3-3ζ significantly impaired glycerol and free fatty acid (FFA) release. Unexpectedly, reducing 14-3-3ζ expression was found to significantly impact adipocyte maturity, as observed by reduced abundance of peroxisome proliferator-activated receptor (PPAR)γ2 protein and expression of mature adipocyte genes and those associated with de novo triglyceride synthesis and lipolysis. The impact of 14-3-3ζ depletion on adipocyte maturity was further examined with untargeted lipidomics, which revealed that reductions in 14-3-3ζ abundance promoted the acquisition of a lipidomic signature that resembled undifferentiated preadipocytes. Collectively, these findings reveal a novel aspect of 14-3-3ζ in adipocytes, as reducing 14-3-3ζ was found to have a negative effect on adipocyte maturity and adipocyte-specific processes like lipolysis.

scholarly journals PKC and ERK mediate GH-stimulated lipolysis

2013 ◽  
Vol 51 (2) ◽  
pp. 213-224 ◽  
Author(s):  
Heather E Bergan ◽  
Jeffrey D Kittilson ◽  
Mark A Sheridan
Keyword(s):  
Molecular Mechanisms ◽  
De Novo ◽  
Hormone Sensitive Lipase ◽  
Akt Pathway ◽  
Lipolytic Enzyme ◽  
Erk Pathway ◽  
Physiological Processes ◽  
Kinase C ◽  
Hormone Sensitive ◽  
Growth Promoting

GH regulates several physiological processes in vertebrates, including the promotion of growth, an anabolic process, and the mobilization of stored lipids, a catabolic process. In this study, we used hepatocytes isolated from rainbow trout (Oncorhynchus mykiss) as a model to examine the mechanism of GH action on lipolysis. GH stimulated lipolysis as measured by increased glycerol release in both a time- and a concentration-related manner. The promotion of lipolysis was accompanied by GH-stimulated phosphorylation of the lipolytic enzyme hormone-sensitive lipase (HSL). GH-stimulated lipolysis was also manifested by an increased expression of the two HSL-encoding mRNAs, HSL1 and HSL2. The signaling pathways that underlie GH-stimulated lipolysis were also studied. GH resulted in the activation of phospholipase C (PLC)/protein kinase C (PKC) and the MEK/ERK pathway, whereas JAK–STAT and the PI3K–Akt pathway were deactivated. The blockade of PLC/PKC and the MEK/ERK pathway inhibited GH-stimulated lipolysis and GH-stimulated phosphorylation of HSL as well as GH-stimulated HSL mRNA expression, whereas the blockade of JAK–STAT or the PI3K–Akt pathway had no effect on the activation of lipolysis or the expression of HSL stimulated by GH. These results indicate that GH promotes lipolysis by activating HSL and by enhancing the de novo expression of HSL mRNAs via the activation of PKC and ERK. These findings also suggest molecular mechanisms for activating the lipid catabolic actions of GH while simultaneously deactivating anabolic processes such as antilipolysis and the growth-promoting actions of GH.

scholarly journals A novel k-mer set memory (KSM) motif representation improves regulatory variant prediction

2017 ◽  
Author(s):  
Yuchun Guo ◽  
Kevin Tian ◽  
Haoyang Zeng ◽  
Xiaoyun Guo ◽  
David Kenneth Gifford
Keyword(s):  
Binding Sites ◽  
Regulatory Networks ◽  
Motif Discovery ◽  
De Novo ◽  
Binding Motif ◽  
Large Set ◽  
Public Resource ◽  
Regulatory Variant ◽  
The Impact

ABSTRACTThe representation and discovery of transcription factor (TF) sequence binding specificities is critical for understanding gene regulatory networks and interpreting the impact of disease-associated non-coding genetic variants. We present a novel TF binding motif representation, the K-mer Set Memory (KSM), which consists of a set of aligned k-mers that are over-represented at TF binding sites, and a new method called KMAC for de novo discovery of KSMs. We find that KSMs more accurately predict in vivo binding sites than position weight matrix models (PWMs) and other more complex motif models across a large set of ChIP-seq experiments. KMAC also identifies correct motifs in more experiments than four state-of-the-art motif discovery methods. In addition, KSM derived features outperform both PWM and deep learning model derived sequence features in predicting differential regulatory activities of expression quantitative trait loci (eQTL) alleles. Finally, we have applied KMAC to 1488 ENCODE TF ChIP-seq datasets and created a public resource of KSM and PWM motifs. We expect that the KSM representation and KMAC method will be valuable in characterizing TF binding specificities and in interpreting the effects of non-coding genetic variations.

The Transnational Women's Rights Movement and the World Economy

2020 ◽  
Vol 6 (2) ◽  
pp. 145-173 ◽  
Author(s):  
Heidi E. Rademacher
Keyword(s):  
Women's Rights ◽  
Small Body ◽  
World System ◽  
World Society ◽  
Women’S Rights ◽  
Social Movement Organizations ◽  
Global Movement ◽  
Negative Effect ◽  
Society Perspective ◽  
The Impact

Promoting the ratification of the Convention on the Elimination of All Forms of Discrimination against Women (CEDAW) was a key objective of the transnational women's movement of the 1980s and 1990s. Yet, few studies examine what factors contribute to ratification. The small body of literature on this topic comes from a world-society perspective, which suggests that CEDAW represented a global shift toward women's rights and that ratification increased as international NGOs proliferated. However, this framing fails to consider whether diffusion varies in a stratified world-system. I combine world-society and world-systems approaches, adding to the literature by examining the impact of women's and human rights transnational social movement organizations on CEDAW ratification at varied world-system positions. The findings illustrate the complex strengths and limitations of a global movement, with such organizations having a negative effect on ratification among core nations, a positive effect in the semiperiphery, and no effect among periphery nations. This suggests that the impact of mobilization was neither a universal application of global scripts nor simply representative of the broad domination of core nations, but a complex and diverse result of civil society actors embedded in a politically stratified world.

The Impact of Competitive Quasi-Market on Service Delivery in Benue State University, Makurdi Nigeria

GIS Business ◽  
2019 ◽  
Vol 14 (4) ◽  
pp. 85-98
Author(s):  
Idoko Peter
Keyword(s):  
Service Delivery ◽  
A Priori ◽  
Least Square ◽  
Secondary Source ◽  
State University ◽  
Ordinary Least Square ◽  
Negative Effect ◽  
The Impact ◽  
The Relationship

This research the impact of competitive quasi market on service delivery in Benue State University, Makurdi Nigeria. Both primary and secondary source of data and information were used for the study and questionnaire was used to extract information from the purposively selected respondents. The population for this study is one hundred and seventy three (173) administrative staff of Benue State University selected at random. The statistical tools employed was the classical ordinary least square (OLS) and the probability value of the estimates was used to tests hypotheses of the study. The result of the study indicates that a positive relationship exist between Competitive quasi marketing in Benue State University, Makurdi Nigeria (CQM) and Transparency in the service delivery (TRSP) and the relationship is statistically significant (p<0.05). Competitive quasi marketing (CQM) has a negative effect on Observe Competence in Benue State University, Makurdi Nigeria (OBCP) and the relationship is not statistically significant (p>0.05). Competitive quasi marketing (CQM) has a positive effect on Innovation in Benue State University, Makurdi Nigeria (INVO) and the relationship is statistically significant (p<0.05) and in line with a priori expectation. This means that a unit increases in Competitive quasi marketing (CQM) will result to a corresponding increase in innovation in Benue State University, Makurdi Nigeria (INVO) by a margin of 22.5%. It was concluded that government monopoly in the provision of certain types of services has greatly affected the quality of service experience in the institution. It was recommended among others that the stakeholders in the market has to be transparent so that the system will be productive to serve the society effectively

Problems of Implementation of an Import Substitution Policy in the Oil Industry

2019 ◽  
pp. 50-57
Author(s):  
Yu. V. Vertakova ◽  
A. S. Evtyukhin
Keyword(s):  
Import Substitution ◽  
Oil Industry ◽  
Investment Climate ◽  
Scientific Publications ◽  
Stage Of Development ◽  
Current Economic Situation ◽  
Negative Effect ◽  
Substitution Policy ◽  
Investment Process ◽  
The Impact

The presented study addresses the issues of implementation of an import substitution policy in the Russian oil industry. Support of domestic production is a key objective specified in the message of the President of the Russian Federation in 2019. In light of the current economic situation and considering the importance of the oil industry for the Russian economy, an import substitution policy could help achieve the objective set by the President.Aim. The study aims to identify the problems and ways of implementation of an import substitution policy in the Russian oil industry.Tasks. The authors analyze scientific publications on import substitution and the state of the Russian oil industry at the current stage of development; determine the directions and fundamental trends in the development of the oil industry; identify obstacles that hinder the implementation of an import substitution policy in the oil industry; describe conditions that facilitate the development of the  investment process in the oil industry; propose comprehensive methods and ways to intensify investments and optimize costs for enterprises in the oil industry.Methods. This study uses general scientific methods of cognition, comparative and statistical analysis to identify problems in the implementation of an import substitution policy in the oil industry.Results. Examination of the current state and development prospects of the oil industry allows the authors to identify obstacles to the development of import substitution. The study shows their impact on the potential of import substitution, which has a negative effect on the prospects of intensification of investment processes, and proposes comprehensive methods and mechanisms that could neutralize the impact of the identified obstacles, thus facilitating the formation of a positive investment climate. Conclusions. Investment climate is shown to have a decisive impact on the potential of import substitution in the Russian oil industry, and ways of overcoming negative trends in the development of the oil industry are proposed.

Others' participation rate influences an individual's charitable behavior: Others' similarity as a moderator

2017 ◽  
Vol 45 (10) ◽  
pp. 1607-1618 ◽  
Author(s):  
Seung Yun Lee ◽  
Sunho Jung ◽  
Sangdo Oh ◽  
Seong Hoon Park
Keyword(s):  
Undergraduate Students ◽  
Participation Rate ◽  
High Rate ◽  
Charitable Behavior ◽  
High Participation ◽  
Negative Effect ◽  
The Impact ◽  
And Diffusion ◽  
High Participation Rate ◽  
Diffusion Of Responsibility

We proposed that a moderator, others' similarity, would determine the impact of high participation rates of others on an individual's charitable behavior, and aimed to show that this moderator would work through the diffusion of responsibility motive. Participants (N = 152 undergraduate students) completed measures of charitable behavior and diffusion of responsibility, after being assigned to 1 of 2 conditions where a set percentage of other students (manipulated as either similar undergraduate students or dissimilar graduate students) were stated to have already donated to a charitable campaign (high contribution condition = 70% participation, low contribution condition = 30% participation). Our results showed that the high participation rate of others increased an individual's charitable behavior when the others in question were similar to that individual, but not when the others were dissimilar. In addition, the high rate of participation by others increased the diffusion of responsibility motive when the others in question were dissimilar to that individual, leading to a negative effect on that individual's charitable behavior.

AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations

Blood ◽  
2009 ◽  
Vol 114 (26) ◽  
pp. 5352-5361 ◽  
Author(s):  
Jih-Luh Tang ◽  
Hsin-An Hou ◽  
Chien-Yuan Chen ◽  
Chieh-Yu Liu ◽  
Wen-Chien Chou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Remission Rate ◽  
Adult Patients ◽  
Poor Prognostic Factor ◽  
The Impact ◽  
Runx1 Mutation ◽  
Acute Myeloid

AbstractSomatic mutation of the AML1/RUNX1(RUNX1) gene is seen in acute myeloid leukemia (AML) M0 subtype and in AML transformed from myelodysplastic syndrome, but the impact of this gene mutation on survival in AML patients remains unclear. In this study, we sought to determine the clinical implications of RUNX1 mutations in 470 adult patients with de novo non-M3 AML. Sixty-three distinct RUNX1 mutations were identified in 62 persons (13.2%); 32 were in N-terminal and 31, C-terminal. The RUNX1 mutation was closely associated with male sex, older age, lower lactic dehydrogenase value, French-American-British M0/M1 subtypes, and expression of HLA-DR and CD34, but inversely correlated with CD33, CD15, CD19, and CD56 expression. Furthermore, the mutation was positively associated with MLL/PTD but negatively associated with CEBPA and NPM1 mutations. AML patients with RUNX1 mutations had a significantly lower complete remission rate and shorter disease-free and overall survival than those without the mutation. Multivariate analysis demonstrated that RUNX1 mutation was an independent poor prognostic factor for overall survival. Sequential analysis in 133 patients revealed that none acquired novel RUNX1 mutations during clinical courses. Our findings provide evidence that RUNX1 mutations are associated with distinct biologic and clinical characteristics and poor prognosis in patients with de novo AML.

scholarly journals Effect of Competition and Climatic Conditions on the Growth of Beech in the Mixed Pine Beech Stand: Lithuanian Case Study

2020 ◽  
Vol 3 (1) ◽  
pp. 49
Author(s):  
Edgaras Linkevičius ◽  
Gerda Junevičiūtė
Keyword(s):  
Intraspecific Competition ◽  
Tree Species ◽  
Forest Growth ◽  
Competition Effect ◽  
Diameter Increment ◽  
Cart Analysis ◽  
Crown Width ◽  
Beech Stand ◽  
Negative Effect ◽  
The Impact

Climate change and warming will potentially have profound effects on forest growth and yield, especially for pure stands in the near future. Thus, increased attention has been paid to mixed stands, e.g., pine and beech mixtures. However, the interaction of tree species growing in mixtures still remains unknown. Thus, the aim of this study was to investigate the impact of the interspecific and intraspecific competition to diameter, height, and crown width of pine and beech trees growing in mixtures, as well as to evaluate the impact of climatic indicators to the beech radial diameter increment. The data was collected in 2017 at the mixed mature pine beech double layer stand, located in the western part of Lithuania. The sample plot of 1.2 hectare was established and tree species, diameter at the breast height, tree height, height-to-crown base, height-to-crown width, and position were measured for all 836 trees. Additionally, a representative sample of radial diameter increments were estimated only for the beech trees by taking out core discs at the height of 1 m when the stand was partially cut. Competition analysis was based on the distance-dependent competition index, which was further based on crown parameters. Climatic effect was evaluated using classification and regression tree (CART) analysis. We found almost no interspecific competition effect to diameter, height, or crown width for both tree species growing in the first layer. However, it had an effect on beeches growing in the second layer. The intraspecific competition effect was important for pine and beech trees, showing a negative effect for both of them. Our results show the possible coexistence of these tree species due to niche differentiation. An analysis of climatic indicators from 1991–2005 revealed that precipitation from February–May of the current vegetation year and mean temperatures from July to September expressed radial diameter increment effects for beech trees. Low temperatures during March and April, as well as high precipitation during January, had a negative effect on beech radial increments. From 2006–2016, the highest effect on radial diameter increments was the mean temperatures from July to September, as well as the precipitation in January of the current year. From 1991–2016, the highest effect on radial diameter increments was the temperature from July to September 1991–2016 and the precipitation in June 1991–2016. Generally, cool temperatures and higher precipitation in June had a positive effect on beech radial increments. Therefore, our results show a sensitivity to high temperatures and droughts during summer amid Lithuanian’s growth conditions.

scholarly journals The Impact of Urban Recreation Environment on Residents’ Happiness—Based on a Case Study in China

2021 ◽  
Vol 13 (10) ◽  
pp. 5549
Author(s):  
Lei Kang ◽  
Zhaoping Yang ◽  
Fang Han
Keyword(s):  
Low Income ◽  
Subjective Evaluation ◽  
Objective Evaluation ◽  
Income Group ◽  
High Income Group ◽  
Rapid Urbanization ◽  
Indirect Impact ◽  
Negative Effect ◽  
The Impact ◽  
Urban Recreation

Rapid urbanization promotes the expansion of urban tourism and recreation functions, but it also brings many problems, which affect residents’ happiness. Previous studies have emphasized the direct impact of urban recreation environment on happiness, and few have explored the indirect impact of urban recreation environment on happiness through subjective evaluation. Based on the survey data of nearly 10,000 permanent residents in 40 key tourism cities in China, this paper establishes a theoretical framework of the direct and indirect impact of urban recreation environment on happiness. The objective evaluation of natural recreation environment and sociocultural recreation environment has an important influence on happiness, but the influence of natural recreation environment is greater than that of sociocultural recreation environment. Individual subjective satisfaction with urban recreation environment mediates the relationship between urban objective environment and happiness. Urban parks have a positive effect on happiness, while tourist attractions have a negative effect. The influence of urban location on happiness is nonlinear. The high-income group is more sensitive to the recreation environment, while the low-income group is less sensitive to the recreation environment. These findings provide insights for further improving citizens’ quality of life and designing urban construction in developing countries under the conditions of rapid urbanization.

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