Mitochondria-Localized Glutamic Acid-Rich Protein (MGARP) Gene Transcription Is Regulated by Sp1

Background: Mitochondria-localized glutamic acid-rich protein (MGARP) is a novel mitochondrial transmembrane protein expressed mainly in steroidogenic tissues and in the visual system. Previous studies showed that MGARP functions in hormone biosynthesis and its expression is modulated by the HPG axis. Methodology/principal findings: By bioinformatics, we identified two characteristic GC-rich motifs that are located proximal to the transcription start site (TSS) of MGARP, and each contains two Specificity protein 1 (Sp1) binding elements. We then determined that the −3 kb proximal MGARP promoter is activated in a Sp1-dependent manner using reporter assays and knockdown of Sp1 led to decreased expression of endogenous MGARP messages. We also demonstrated that one of the two GC-rich motifs, GC-Box1, harbors prominent promoter activity mediated by Sp1, and that it requires both GC boxes for full transcriptional activation. These findings suggest a dominant role for these GC boxes and Sp1 in activating the MGARP promoter through a synergistic mechanism. Consistently, the results of an Electrophoretic Mobility Gel Shift Assay (EMSA) and Chromatin Immunoprecipitation (ChIP) confirmed that Sp1 specifically interacts with the GC-rich region. We further found that estrogen receptor α (ERα), a known Sp1 co-activator, could potentiate GC-boxes containing MGARP promoter activity and this effect is mediated by Sp1. Knockdown of Sp1 significantly diminished the MGARP promoter transactivation and the expression of endogenous MGARP mediated by both Sp1 and ERα. Conclusions/significance: The present study identified a proximal core sequence in the MGARP promoter that is composed of two enriched Sp1 binding motifs and established Sp1 as one major MGARP transactivator whose functions are synergistic with ERα, providing a novel understanding of the mechanisms of MGARP gene transcriptional regulation

Prediction of peptide drift time in ion mobility mass spectrometry from sequence-based features

BACKGROUND: Ion mobility-mass spectrometry (IMMS), an analytical technique which combines the features of ion mobility spectrometry (IMS) and mass spectrometry (MS), can rapidly separates ions on a millisecond time-scale. IMMS becomes a powerful tool to analyzing complex mixtures, especially for the analysis of peptides in proteomics. The high-throughput nature of this technique provides a challenge for the identification of peptides in complex biological samples. As an important parameter, peptide drift time can be used for enhancing downstream data analysis in IMMS-based proteomics. RESULTS: In this paper, a model is presented based on least square support vectors regression (LS-SVR) method to predict peptide ion drift time in IMMS from the sequence-based features of peptide. Four descriptors were extracted from peptide sequence to represent peptide ions by a 34-component vector. The parameters of LS-SVR were selected by a grid searching strategy, and a 10-fold cross-validation approach was employed for the model training and testing. Our proposed method was tested on three datasets with different charge states. The high prediction performance achieve demonstrate the effectiveness and efficiency of the prediction model. CONCLUSIONS: Our proposed LS-SVR model can predict peptide drift time from sequence information in relative high prediction accuracy by a test on a dataset of 595 peptides. This work can enhance the confidence of protein identification by combining with current protein searching techniques

Franco Moretti’s Interdisciplinary Approach and its Influence on Foreign Literature Studies in China

Western literary theorist Franco Moretti’s researches are featured with interdisciplinarity. His approach began with the conceptual model of “world literature”, followed by the methodology of “distant reading”, and ended with the practice of “computational criticism”. This paper aims to explore the dynamic interaction between Darwin’s evolutionary theory and Wallerstein’s world-systems analysis, as well as the interplay between close reading and distant reading, and the dialogue between traditional criticism and computational criticism. With the popularization of the Internet, the revolution of information technology and the wave of globalization, the categorization of disciplines with distinct barriers can no longer meet the complexity of modernization, and the call for interdisciplinary integration is constantly heard. Nevertheless, interdisciplinary research is in urgent need of theoretical framework and practical guidance for reference. This paper seeks to contribute to the interdisciplinary study of foreign literature in China within the purview of “new liberal arts”

Structural characterization of an α-1, 6-linked galactomannan from natural Cordyceps 2 sinensis

An α-1, 6-linked galactomannan was isolated and purified from natural Cordyceps sinensis. The fine structure analysis of this polysaccharide was elucidated based on partial acid hydrolysis, monosaccharide composition, methylation and 1D/2D nuclear magnetic resonance (NMR) spectroscopy. Monosaccharide composition analysis revealed that this polysaccharide was mainly composed of galactose (68.65%), glucose (6.65%) and mannose (24.02%). However, after partial acid hydrolysis the percentages of galactose, glucose and mannose were changed to 3.96%, 13.82% and 82.22%, respectively. The molecular weight of this polysaccharide was 7207. Methylation and NMR analysis revealed that this galactomannan had a highly branched structure, mainly consisted of a mannan skeleton and galactofuranosyl chains. The structure of galactofuranosyl part was formed by alternating (1 → 5)-lined β-Galf and (1 → 6)-liked β-Galf or a single (1 → 6)-liked β-Galf, attaching to the O-2 and O-4 of the mannose chain, and terminated at β-T-Galf. The mannan core was revealed by analyzing the partial acid hydrolysate of the galactomannan and the structure was composed of (1 → 6)-linked α-Manp backbone, with substituted at C-2 by short chains of 2-substituted Manp or Galf branches

BMPRIA mediated signaling is essential for temporomandibular joint development in mice

The central importance of BMP signaling in the development and homeostasis of synovial joint of appendicular skeleton has been well documented, but its role in the development of temporomandibular joint (TMJ), also classified as a synovial joint, remains completely unknown. In this study, we investigated the function of BMPRIA mediated signaling in TMJ development in mice by transgenic loss-of- and gain-of-function approaches. We found that BMPRIA is expressed in the cranial neural crest (CNC)-derived developing condyle and glenoid fossa, major components of TMJ, as well as the interzone mesenchymal cells. Wnt1-Cre mediated tissue specific inactivation of BmprIa in CNC lineage led to defective TMJ development, including failure of articular disc separation from a hypoplastic condyle, persistence of interzone cells, and failed formation of a functional fibrocartilage layer on the articular surface of the glenoid fossa and condyle, which could be at least partially attributed to the down-regulation of Ihh in the developing condyle and inhibition of apoptosis in the interzone. On the other hand, augmented BMPRIA signaling by Wnt1-Cre driven expression of a constitutively active form of BmprIa (caBmprIa) inhibited osteogenesis of the glenoid fossa and converted the condylar primordium from secondary cartilage to primary cartilage associated with ectopic activation of Smad-dependent pathway but inhibition of JNK pathway, leading to TMJ agenesis. Our results present unambiguous evidence for an essential role of finely tuned BMPRIA mediated signaling in TMJ development

Simultaneous stabilization of Pb and improvement of soil strength using nZVI

This study demonstrates the feasibility of nanoscale Zero-Valent Iron (nZVI) for simultaneous stabilization of Pb and improvement of soil strength via batch experiments. The soil samples were prepared using slurry and pre-consolidation method at nZVI doses of 0.2%, 1%, 5%, and 10% (by dry weight). The physicochemical and geotechnical properties of Pb-contaminated soil treated by nZVI were analyzed. The results indicate that the contamination of Pb(II) resulted in a notable reduction in the undrained shear strength of soil from 16.85 kPa to 7.25 kPa. As expected, the Pb in exchangeable and carbonate-bound fractions decreased significantly with the increasing doses of nZVI. Meanwhile, the undrained shear strength of Pb-contaminated soil enhanced substantially as the increase of nZVI, from 25.83 kPa (0.2% nZVI treatment) to 69.33 kPa (10% nZVI treatment). An abundance of bubbles, generated from the oxidation of nZVI, was recorded. The mechanisms for simultaneous stabilization of Pb and soil improvement primarily include: 1) the precipitation and transformation of Pb-/Fe-hydrated oxides on the soil particles and their induced bounding effects; 2) the increased drainage capability of soil as the occupation of nZVI aggregates and bubbles in the macropores space and 3) the lower soil density derived from the increase in microbubbles retained in the soil. This study is provided to facilitate the application of nZVI in the redevelopment of contaminated soil