HMGA2 promotes adipogenesis by activating C/EBPβ-mediated expression of PPARγ

AbstractAdipogenesis is orchestrated by a highly ordered network of transcription factors including peroxisome-proliferator activated receptor-gamma (PPARγ) and CCAAT-enhancer binding protein (C/EBP) family proteins. High mobility group protein AT-hook 2 (HMGA2), an architectural transcription factor, has been reported to play an essential role in preadipocyte proliferation, and its overexpression has been implicated in obesity in mice and humans. However, the direct role of HMGA2 in regulating the gene expression program during adipogenesis is not known. Here, we demonstrate that HMGA2 is required for C/EBPβ-mediated expression of PPARγ, and thus promotes adipogenic differentiation. We observed a transient but marked increase of Hmga2 transcript at an early phase of differentiation of mouse 3T3-L1 preadipocytes. Importantly, Hmga2 knockdown greatly impaired adipocyte formation, while its overexpression promoted the formation of mature adipocytes. We found that HMGA2 colocalized with C/EBPβ in the nucleus and was required for the recruitment of C/EBPβ to its binding element at the Pparγ2 promoter. Accordingly, HMGA2 and C/EBPβ cooperatively enhanced the Pparγ2 promoter activity. Our results indicate that HMGA2 is an essential constituent of the adipogenic transcription factor network, and thus its function may be affected during the course of obesity

Genome-wide and expression analysis of protein phosphatase 2C in rice and Arabidopsis

<p>Abstract</p> <p>Background</p> <p>The protein phosphatase 2Cs (PP2Cs) from various organisms have been implicated to act as negative modulators of protein kinase pathways involved in diverse environmental stress responses and developmental processes. A genome-wide overview of the PP2C gene family in plants is not yet available.</p> <p>Results</p> <p>A comprehensive computational analysis identified 80 and 78 PP2C genes in <it>Arabidopsis thaliana </it>(AtPP2Cs) and <it>Oryza sativa </it>(OsPP2Cs), respectively, which denotes the PP2C gene family as one of the largest families identified in plants. Phylogenic analysis divided PP2Cs in Arabidopsis and rice into 13 and 11 subfamilies, respectively, which are supported by the analyses of gene structures and protein motifs. Comparative analysis between the PP2C genes in Arabidopsis and rice identified common and lineage-specific subfamilies and potential 'gene birth-and-death' events. Gene duplication analysis reveals that whole genome and chromosomal segment duplications mainly contributed to the expansion of both OsPP2Cs and AtPP2Cs, but tandem or local duplication occurred less frequently in Arabidopsis than rice. Some protein motifs are widespread among the PP2C proteins, whereas some other motifs are specific to only one or two subfamilies. Expression pattern analysis suggests that 1) most PP2C genes play functional roles in multiple tissues in both species, 2) the induced expression of most genes in subfamily A by diverse stimuli indicates their primary role in stress tolerance, especially ABA response, and 3) the expression pattern of subfamily D members suggests that they may constitute positive regulators in ABA-mediated signaling pathways. The analyses of putative upstream regulatory elements by two approaches further support the functions of subfamily A in ABA signaling, and provide insights into the shared and different transcriptional regulation machineries in dicots and monocots.</p> <p>Conclusion</p> <p>This comparative genome-wide overview of the PP2C family in Arabidopsis and rice provides insights into the functions and regulatory mechanisms, as well as the evolution and divergence of the PP2C genes in dicots and monocots. Bioinformatics analyses suggest that plant PP2C proteins from different subfamilies participate in distinct signaling pathways. Our results have established a solid foundation for future studies on the functional divergence in different PP2C subfamilies.</p

Curcumin Attenuates Angiogenesis in Liver Fibrosis and Inhibits Angiogenic Properties of Hepatic Stellate Cells

Sinusoidal pathological angiogenesis is a novel therapeutic target for liver fibrosis. We demonstrated that curcumin ameliorated fibrotic injury and sinusoidal angiogenesis in rat liver with fibrosis caused by carbon tetrachloride. Curcumin reduced the expression of angiogenic markers in fibrotic liver. Experiments in vitro showed that the viability and vascularization of rat liver sinusoidal endothelial cells (LSECs) were not impaired by curcumin. Further investigations showed that curcumin inhibited VEGF expression in hepatic stellate cells (HSCs) by disrupting PDGF-βR/ERK and mTOR pathways. HSC motility and vascularization were also suppressed by curcumin via blocking PDGF-βR/FAK/RhoA cascade. Gain- or loss-of-function analyses revealed that activation of PPARγ was required for curcumin to inhibit angiogenic properties of HSCs. We concluded that curcumin attenuated sinusoidal angiogenesis in liver fibrosis possibly by targeting HSCs via a PPARγ activation-dependent mechanism. PPARγ could be a target molecule for reducing pathological angiogenesis during liver fibrosis

Internal and contextual factors, knowledge processes and performance: From the Chinese provider's perspective

This is the post-print version of the final paper published in Expert Systems with Applications. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2011 Elsevier B.V.This paper explores the influences of two internal factors, i.e. supplier team’s IT-based skills and communication with client’s team, and two contextual factors, i.e. supplier team’s understanding of client’s culture and collaboration with client’s team, on knowledge processes and performance in global sourcing of IT services from the Chinese provider’s perspective. Knowledge processes are characterized by knowledge sharing, knowledge-based coordination and expertise management, and performance is measured by product success and personal satisfaction. Data have been collected in 13 companies in Xi’an Software Park, with 26 in-depth, semi-structured interviews held with top and middle managers, and 200 structured questionnaires distributed to knowledge workers who are involved in global sourcing projects. The results indicate that supplier team’s IT-based skills, communication with client’s team, cultural understanding of client’s culture and collaboration with client’s team are positively associated with knowledge process and performance. Also, knowledge sharing, knowledge-based coordination and expertise management are found to be crucial for those influential factors to function positively and contribute to the performance. The findings of this study suggest that the effects of key factors on knowledge processes and performance in global sourcing of IT services appear to transcend the social and cultural differences; however, contextual factors seem to have more significant influences on knowledge processes and performance in global sourcing of IT services.National Natural Science Foundation of Chin

Características litogeoquímicas y petrográficas en los bordes norte y sur del segmento Lima - Batolito de la Costa, comparada con el sureste de China - [Boletín D 35]

En el presente trabajo, se muestran los resultados obtenidos en el marco del convenio específico entre el Instituto Geológico Minero y Metalúrgico (INGEMMET) y el Servicio Geológico de China (CGS: China Geological Survey), entre los años 2017 y 2018. El área de estudio corresponde principalmente al Segmento Lima. En los cuerpos plutónicos del segmento Lima (128 a 33 Ma), se pueden observar con claridad las variaciones litológicas laterales asociadas a la diferenciación magmática directa, varían de dioritas a monzogranitos. Esto indica un desarrollo continuo en los ensambles magmáticos o super unidades. Las estructuras internas de los cuerpos intrusivos más característicos se pueden observar en cuerpos de monzogranitos de las super unidades Puscao, Tiabaya y Pativilca, donde se puede observar zonas de enclaves máficos: dispersos, a manera de capas (seudo estratificado) y diques sin magmáticos, estructuras asociadas principalmente a mezcla de magma. Para comprender la distribución temporal y espacial de la población de cristales de las rocas plutónicas del Batolito de la Costa, en el segmento Lima, se generó una base de datos composicional con las principales características petrográficas de cada roca, con ella, se generaron diagramas binarios MINEA (Minerales Esenciales y Accesorios). Donde se pudo observar, que las mayores concentraciones de feldespato potásico (K) están asociadas a rocas de la super unidades Linga, Tiabaya y Santa Rosa, asociados al magmatismo de 83.6 a 72.1 Ma. Por la gran extensión del área de trabajo, afinidad litológica y rango de edad antes definida (61-90 Ma), la Super Unidad Santa Rosa fue agrupada con otras super unidades (La Mina, San Jerónimo, Puscao) y definida como Superemsamble Santa Rosa, esto para el presente trabajo. En el análisis geoquímico, los diagramas de elementos trazas y elementos de tierras raras muestras una evolución de magmas mantélicos a muy diferenciados. Los magmas mantélicos están asociados a rocas de la Super Unidad Patap y los magmas diferenciados están asociados al Superensamble Santa Rosa y Super Unidad Catahuasi. Las mayores anomalías de HFSE, como Th y U, muestran las rocas del Superensamble Santa Rosa y Super Unidad Linga. Esto quiere decir que son rocas diferenciadas y de gran energía. Las rocas de este segmento muestran anomalías negativas de Nb y Ta, típicas de magmatismo de arco andino. A medida que el magma evoluciona, se observa un dominio de anfíboles y granate en los elementos de tierras raras pesadas evidenciada por la anomalía negativa mostrada en Y e Yb. Este último se puede asociar a ocurrencias de Cu-Mo y Mo, debido a que el Mo está controlado por la anomalía de Y en el fundido. Durante el año 2018, se obtuvieron 59 nuevas edades isotópicas U-Pb, estas se realizaron sobre zircones en rocas ígneas, principalmente en rocas plutónicas. Los estudios isotópicos fueron realizados por el Servicio Geológico de China del Centro de Nanjing

Dissection of QTL effects for root traits using a chromosome arm-specific mapping population in bread wheat

A high-resolution chromosome arm-specific mapping population was used in an attempt to locate/detect gene(s)/QTL for different root traits on the short arm of rye chromosome 1 (1RS) in bread wheat. This population consisted of induced homoeologous recombinants of 1RS with 1BS, each originating from a different crossover event and distinct from all other recombinants in the proportions of rye and wheat chromatin present. It provides a simple and powerful approach to detect even small QTL effects using fewer progeny. A promising empirical Bayes method was applied to estimate additive and epistatic effects for all possible marker pairs simultaneously in a single model. This method has an advantage for QTL analysis in minimizing the error variance and detecting interaction effects between loci with no main effect. A total of 15 QTL effects, 6 additive and 9 epistatic, were detected for different traits of root length and root weight in 1RS wheat. Epistatic interactions were further partitioned into inter-genomic (wheat and rye alleles) and intra-genomic (rye–rye or wheat–wheat alleles) interactions affecting various root traits. Four common regions were identified involving all the QTL for root traits. Two regions carried QTL for almost all the root traits and were responsible for all the epistatic interactions. Evidence for inter-genomic interactions is provided. Comparison of mean values supported the QTL detection

The transcriptional landscape of Shh medulloblastoma

© The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demonstrate the previously unappreciated importance of non-coding RNA transcripts. We identify alterations within the cAMP dependent pathway (GNAS, PRKAR1A) which converge on GLI2 activity and show that 18% of tumors have a genetic event that directly targets the abundance and/or stability of MYCN. Furthermore, we discover an extensive network of fusions in focally amplified regions encompassing GLI2, and several loss-of-function fusions in tumor suppressor genes PTCH1, SUFU and NCOR1. Molecular convergence on a subset of genes by nucleotide variants, copy number aberrations, and gene fusions highlight the key roles of specific pathways in the pathogenesis of Sonic hedgehog medulloblastoma and open up opportunities for therapeutic intervention.info:eu-repo/semantics/publishedVersio