The Experts below are selected from a list of 145197 Experts worldwide ranked by ideXlab platform
Marcel Karperien - One of the best experts on this subject based on the ideXlab platform.
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systemic and Local Regulation of the growth plate
Endocrine Reviews, 2003Co-Authors: B C J Van Der Eerden, Marcel KarperienAbstract:The growth plate is the final target organ for longitudinal growth and results from chondrocyte proliferation and differentiation. During the first year of life, longitudinal growth rates are high, followed by a decade of modest longitudinal growth. The age at onset of puberty and the growth rate during the pubertal growth spurt (which occurs under the influence of estrogens and GH) contribute to sex difference in final height between boys and girls. At the end of puberty, growth plates fuse, thereby ceasing longitudinal growth. It has been recognized that receptors for many hormones such as estrogen, GH, and glucocorticoids are present in or on growth plate chondrocytes, suggesting that these hormones may influence processes in the growth plate directly. Moreover, many growth factors, i.e., IGF-I, Indian hedgehog, PTHrP, fibroblast growth factors, bone morphogenetic proteins, and vascular endothelial growth factor, are now considered as crucial regulators of chondrocyte proliferation and differentiation. In this review, we present an update on the present perception of growth plate function and the Regulation of chondrocyte proliferation and differentiation by systemic and Local regulators of which most are now related to human growth disorders.
Sensen Chen - One of the best experts on this subject based on the ideXlab platform.
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evaluating the effect of coal mine safety supervision system policy in china s coal mining industry a two phase analysis
Resources Policy, 2015Co-Authors: Sensen Chen, Ying FanAbstract:The construction of a vertical-management system of coal mine safety supervision since 2000 is an important measure to improve coal mine safety in China. This paper examines its effect on coal mine production safety by combining the structural break test, by which the establishment of the supervision system is divided into two phases (2000–2009 and 2010–2013), with an unbiased grey Markov model. This paper then proposes a staged evaluation framework through considering the respective characteristics of sample data and model applicability. The results show that the models are suitable for forecasting the death rate per million tons (DRPMT) of coal due to their desirable characteristics. Coal mine safety has significantly improved since 2000 with the constant decline of DRPMT due to the gradual construction of supervision institutions, which produced increasingly positive institutional effect (2.3373 persons/million tons) in the first phase. However, the benefit from institution construction was close to zero (0.0667 persons per million tons per year) in the second phase due to a supervision-institution construction standstill. By analyzing the current problems, this paper suggests continuing to improve the current supervision system for coal mine safety through further adjusting respective functions of "State Supervision" and Local Regulation departments; namely, reducing the Regulation functions in the "State Supervision", improving its supervising ability for Local Regulation departments and playing a leading role in coal mine accident investigation.
David Y Chiang - One of the best experts on this subject based on the ideXlab platform.
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impaired Local Regulation of ryanodine receptor type 2 by protein phosphatase 1 promotes atrial fibrillation
Cardiovascular Research, 2014Co-Authors: David Y Chiang, Na Li, Qiongling Wang, Katherina M Alsina, Ann P Quick, Julia O Reynolds, Guoliang Wang, Darlene G Skapura, Niels Voigt, Dobromir DobrevAbstract:Aims Altered Ca2+ handling in atrial fibrillation (AF) has been associated with dysregulated protein phosphatase 1 (PP1) and subcellular heterogeneities in protein phosphorylation, but the underlying mechanisms remain unclear. This is due to a lack of investigation into the Local , rather than global, Regulation of PP1 on different subcellular targets such as ryanodine receptor type 2 (RyR2), especially in AF. Methods and results We tested the hypothesis that impaired Local Regulation of PP1 causes RyR2 hyperphosphorylation thereby promoting AF susceptibility. To specifically disrupt PP1's Local Regulation of RyR2, we used the spinophilin knockout (Sp−/−) mice ( Mus musculus ) since PP1 is targeted to RyR2 via spinophilin. Without spinophilin, the interaction between PP1 and RyR2 was reduced by 64%, while RyR2 phosphorylation was increased by 43% at serine (S)2814 but unchanged at S2808. Lipid bilayer experiments revealed that single RyR2 channels isolated from Sp−/− hearts had an increased open probability. Likewise, Ca2+ spark frequency normalized to sarcoplasmic reticulum Ca2+ content was also enhanced in Sp−/− atrial myocytes, but normalized by Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitors KN-93 and AIP and also by genetic inhibition of RyR2 S2814 phosphorylation. Finally, Sp−/− mice exhibited increased atrial ectopy and susceptibility to pacing-induced AF, both of which were also prevented by the RyR2 S2814A mutation. Conclusion PP1 regulates RyR2 Locally by counteracting CaMKII phosphorylation of RyR2. Decreased Local PP1 Regulation of RyR2 contributes to RyR2 hyperactivity and promotes AF susceptibility. This represents a novel mechanism for subcellular modulation of calcium channels and may represent a potential drug target of AF.
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impaired Local Regulation of ryanodine receptor type 2 by protein phosphatase 1 promotes atrial fibrillation
European Heart Journal, 2013Co-Authors: David Y Chiang, Na Li, Qiongling Wang, Ann P Quick, Guoliang Wang, Darlene G Skapura, Xander H T WehrensAbstract:Purpose: Atrial fibrillation (AF) is the most common cardiac arrhythmia with a growing prevalence yet current pharmaceutical treatments are ineffective. Previous studies suggest that protein phosphatase 1 (PP1) is dysregulated globally in AF patients but its Local Regulation on key Ca2+-handling proteins such as ryanodine receptor type-2 (RyR2) is not known. In this study we hypothesize that decreased PP1 Regulation of RyR2 promotes AF through increasing Ca2+/calmodulin-dependent protein kinase II (CaMKII) phosphorylation of RyR2. Methods: To study the Local Regulation of RyR2 by PP1, we used spinophilin knockout mice (KO), since PP1 targets RyR2 via spinophilin. The interaction between RyR2 and PP1 was measured using co-immunoprecipitation while RyR2 phosphorylation level was quantified using Western blot. RyR2 activity was determined by measuring 1) single RyR2 channel activity in a lipid bilayer system and 2) Ca2+ sparks frequency in atrial myocytes loaded with Fluo4-AM. Baseline cardiac characteristics were determined using echocardiography and histological staining while AF inducibility was assessed by intracardiac electrophysiology study. Results: The interaction of PP1 with RyR2 was reduced by 55% in the KO hearts compared to WT (P<0.001). RyR2 phosphorylation at Serine 2814 was increased by 43% in the KO atria (P<0.05 vs. WT) while unchanged at Serine 2808. Single RyR2 channels isolated from KO hearts had a higher open probability (0.10±0.02) compared to that from WT (0.02±0.01; P<0.01). Ca2+ spark frequency normalized to sarcoplasmic reticulum (SR) Ca2+ content was increased in atrial myocytes isolated from KO mice (1.72±0.26 a.u.) compared to WT (0.77±0.20 a.u.; P<0.05). Furthermore, this increase was rescued by CaMKII-inhibitor KN93 but not by protein kinase A (PKA) inhibitor H89. End diastolic diameter of hearts from KO mice was 10% smaller than that from WT (P<0.01) but both the heart weight to body weight ratio and ejection fraction were unchanged. Also, there was no difference in fibrosis between KO and WT heart based on histological sections stained with Masson's trichome. However, when subjected to intracardiac electrical stimulation, KO mice had a higher incidence of pacing-induced AF (100%) compared to WT (33%; P<0.01). Conclusions: PP1 regulates RyR2 by counteracting CaMKII but not PKA phosphorylation of RyR2. Spinophilin deficiency leads to decreased PP1 Regulation of RyR2 which may promote AF. This Regulation may represent a novel therapeutic target for treating AF.
Jesse M Engreitz - One of the best experts on this subject based on the ideXlab platform.
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Local Regulation of gene expression by lncrna promoters transcription and splicing
Nature, 2016Co-Authors: Jesse M Engreitz, Jenna E Haines, Elizabeth M Perez, Glen Munson, Jenny Chen, Michael Kane, Patrick Mcdonel, Mitchell GuttmanAbstract:Mammalian genomes are pervasively transcribed to produce thousands of long non-coding RNAs (lncRNAs). A few of these lncRNAs have been shown to recruit regulatory complexes through RNA-protein interactions to influence the expression of nearby genes, and it has been suggested that many other lncRNAs can also act as Local regulators. Such Local functions could explain the observation that lncRNA expression is often correlated with the expression of nearby genes. However, these correlations have been challenging to dissect and could alternatively result from processes that are not mediated by the lncRNA transcripts themselves. For example, some gene promoters have been proposed to have dual functions as enhancers, and the process of transcription itself may contribute to gene Regulation by recruiting activating factors or remodelling nucleosomes. Here we use genetic manipulation in mouse cell lines to dissect 12 genomic loci that produce lncRNAs and find that 5 of these loci influence the expression of a neighbouring gene in cis. Notably, none of these effects requires the specific lncRNA transcripts themselves and instead involves general processes associated with their production, including enhancer-like activity of gene promoters, the process of transcription, and the splicing of the transcript. Furthermore, such effects are not limited to lncRNA loci: we find that four out of six protein-coding loci also influence the expression of a neighbour. These results demonstrate that cross-talk among neighbouring genes is a prevalent phenomenon that can involve multiple mechanisms and cis-regulatory signals, including a role for RNA splice sites. These mechanisms may explain the function and evolution of some genomic loci that produce lncRNAs and broadly contribute to the Regulation of both coding and non-coding genes.
Ying Fan - One of the best experts on this subject based on the ideXlab platform.
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evaluating the effect of coal mine safety supervision system policy in china s coal mining industry a two phase analysis
Resources Policy, 2015Co-Authors: Sensen Chen, Ying FanAbstract:The construction of a vertical-management system of coal mine safety supervision since 2000 is an important measure to improve coal mine safety in China. This paper examines its effect on coal mine production safety by combining the structural break test, by which the establishment of the supervision system is divided into two phases (2000–2009 and 2010–2013), with an unbiased grey Markov model. This paper then proposes a staged evaluation framework through considering the respective characteristics of sample data and model applicability. The results show that the models are suitable for forecasting the death rate per million tons (DRPMT) of coal due to their desirable characteristics. Coal mine safety has significantly improved since 2000 with the constant decline of DRPMT due to the gradual construction of supervision institutions, which produced increasingly positive institutional effect (2.3373 persons/million tons) in the first phase. However, the benefit from institution construction was close to zero (0.0667 persons per million tons per year) in the second phase due to a supervision-institution construction standstill. By analyzing the current problems, this paper suggests continuing to improve the current supervision system for coal mine safety through further adjusting respective functions of "State Supervision" and Local Regulation departments; namely, reducing the Regulation functions in the "State Supervision", improving its supervising ability for Local Regulation departments and playing a leading role in coal mine accident investigation.