ALBERT

Description: Background The significant advances in microarray and proteomics analyses have resulted in an exponential increase in potential new targets and have promised to shed light on the identification of disease markers and cellular pathways. We aim to collect and decipher the HCC-related genes at the systems level. Results Here, we build an integrative platform, the E ncyclopedia of H epatocellular C arcinoma genes O nline, dubbed EHCO http://ehco.iis.sinica.edu.tw, to systematically collect, organize and compare the pileup of unsorted HCC-related studies by using natural language processing and softbots. Among the eight gene set collections, ranging across PubMed, SAGE, microarray, and proteomics data, there are 2,906 genes in total; however, more than 77% genes are only included once, suggesting that tremendous efforts need to be exerted to characterize the relationship between HCC and these genes. Of these HCC inventories, protein binding represents the largest proportion (~25%) from Gene Ontology analysis. In fact, many differentially expressed gene sets in EHCO could form interaction networks (e.g. HBV-associated HCC network) by using available human protein-protein interaction datasets. To further highlight the potential new targets in the inferred network from EHCO, we combine comparative genomics and interactomics approaches to analyze 120 evolutionary conserved and overexpressed genes in HCC. 47 out of 120 queries can form a highly interactive network with 18 queries serving as hubs. Conclusion This architectural map may represent the first step toward the attempt to decipher the hepatocarcinogenesis at the systems level. Targeting hubs and/or disruption of the network formation might reveal novel strategy for HCC treatment.

Description: Chemokine (C-C motif) ligand 3 (CCL3), also known as macrophage inflammatory protein-1alpha, is a cytokine involved in inflammation and activation of polymorphonuclear leukocytes. CCL3 has been detected in infiltrating cells and tumor cells. Chondrosarcoma is a highly malignant tumor that causes distant metastasis. However, the effect of CCL3 on human chondrosarcoma metastasis is still unknown. Here, we found that CCL3 increased cellular migration and expression of matrix metalloproteinase (MMP)-2 in human chondrosarcoma cells. Pre-treatment of cells with the MMP-2 inhibitor or transfection with MMP-2 specific siRNA abolished CCL3-induced cell migration. CCL3 has been reported to exert its effects through activation of its specific receptor, CC chemokine receptor 5 (CCR5). The CCR5 and AMP-activated protein kinase (AMPK) inhibitor or siRNA also attenuated CCL3-upregulated cell motility and MMP-2 expression. CCL3-induced expression of MMP-2 and migration were also inhibited by specific inhibitors, and inactive mutants of AMPK, p38 mitogen activated protein kinase (p38 or p38-MAPK), and nuclear factor kappaB (NF-kappaB) cascades. On the other hand, CCL3 treatment demonstrably activated AMPK, p38, and NF-kappaB signaling pathways. Furthermore, the expression levels of CCL3, CCR5, and MMP-2 were correlated in human chondrosarcoma specimens. Taken together, our results indicate that CCL3 enhances the migratory ability of human chondrosarcoma cells by increasing MMP-2 expression via the CCR5, AMPK, p38, and NF-kappaB pathways.

Description: Background: Protein phosphorylation regulated by plant hormone is involved in the coordination of fundamental plant development. Brassinosteroids (BRs), a group of phytohormones, regulated phosphorylation dynamics remains to be delineated in plants. In this study, we performed a mass spectrometry (MS)-based phosphoproteomics to conduct a global and dynamic phosphoproteome profiling across five time points of BR treatment in the period between 5 min and 12 h. MS coupling with phosphopeptide enrichment techniques has become the powerful tool for profiling protein phosphorylation. However, MS-based methods tend to have data consistency and coverage issues. To address these issues, bioinformatics approaches were used to complement the non-detected proteins and recover the dynamics of phosphorylation events. Results: A total of 1104 unique phosphorylated peptides from 739 unique phosphoproteins were identified. The time-dependent gene ontology (GO) analysis shows the transition of biological processes from signaling transduction to morphogenesis and stress response. The protein-protein interaction analysis found that most of identified phosphoproteins have strongly connections with known BR signaling components. The analysis by using Motif-X was performed to identify 15 enriched motifs, 11 of which correspond to 6 known kinase families. To uncover the dynamic activities of kinases, the enriched motifs were combined with phosphorylation profiles and revealed that the substrates of casein kinase 2 and mitogen-activated protein kinase were significantly phosphorylated and dephosphorylated at initial time of BR treatment, respectively. The time-dependent kinase-substrate interaction networks were constructed and showed many substrates are the downstream of other signals, such as auxin and ABA signaling. While comparing BR responsive phosphoproteome and gene expression data, we found most of phosphorylation changes were not led by gene expression changes. Our results suggested many downstream proteins of BR signaling are induced by phosphorylation via various kinases, not through transcriptional regulation. Conclusions: Through a large-scale dynamic profile of phosphoproteome coupled with bioinformatics, a complicated kinase-centered network related to BR-regulated growth was deciphered. The phosphoproteins and phosphosites identified in our study provide a useful dataset for revealing signaling networks of BR regulation, and also expanded our knowledge of protein phosphorylation modification in plants as well as further deal to solve the plant growth problems.

Description: Background: Complete or partial trisomy 10q involves a duplication of 10q, or the long arm of chromosome 10. Distal 10q trisomy is a well-recognized and defined but rare genetic syndrome in which duplication of distal segments of 10q results in a pattern of malformations. Although abnormal chromosome phenotypes are commonly detected by visualization of chromosomes by traditional cytogenetic techniques, this approach is marginal in both diagnostic sensitivity and potential for biological interpretation, thus making implementation of advanced techniques and analysis methods an important consideration in a health service.Case presentationThe present study describes the case of a Taiwanese boy from healthy parents with mental, growth, and psychomotor retardations. Additional clinical features included facial dysmorphism, microcephaly, brain atrophy, camptodactyly, and—as the first reported case—bilateral renal atrophy with chronic kidney disease stage 2 and the presence of a renal cyst in one kidney. A novel 21.8 Mb copy number variation region in chromosome region 10q23.1–10q25.1 was verified by array-comparative genomic hybridization in combination with quantitative real-time polymerase chain reaction. Subsequently, 200 protein-coding genes were identified in this copy number variation region and analyzed for their biological meaning using the database for annotation, visualization and integrated discovery. Conclusion: According to the result of gene functional enrichment analysis using database for annotation, visualization and integrated discovery, the Wnt signaling pathway is the most pertinent to the gene content in the copy number variation region. A change in the expression levels of some Wnt signaling pathway components and of NFKB2 and PTEN genes due to a gain in their gene copy number may be associated with the patient’s clinical outcomes including brain atrophy, bilateral renal atrophy with chronic kidney disease stage 2, a renal cyst in one kidney, and growth retardation.

Description: Background: An emerging Hi-C protocol has the ability to probe three-dimensional (3D) architecture and capture chromatin interactions in a genome-wide scale. It provides informative results to address how chromatin organization changes contribute to disease/tumor occurrence and progression in response to stimulation of environmental chemicals or hormones. Results: In this study, using MCF7 cells as a model system, we found estrogen stimulation significantly impact chromatin interactions, leading to alteration of gene regulation and the associated histone modification states. Many chromosomal interaction regions at different levels of interaction frequency were identified. In particular, the top 10 hot regions with the highest interaction frequency are enriched with breast cancer specific genes. Furthermore, four types of E2-mediated strong differential (gain- or loss-) chromosomal (intra- or inter-) interactions were classified, in which the number of gain-chromosomal interactions is less than the number of loss-chromosomal interactions upon E2 stimulation. Finally, by integrating with eight histone modification marks, DNA methylation, regulatory elements regions, ERalpha and Pol-II binding activities, associations between epigenetic patterns and high chromosomal interaction frequency were revealed in E2-mediated gene regulation. Conclusions: The work provides insight into the effect of chromatin interaction on E2/ERalpha regulated downstream genes in breast cancer cells.

Description: Background: Long-term alendronate therapy may lead to atypical femoral fractures in a very few patients. However, the management protocol to optimize fracture healing remains undetermined. The purpose of this study was to describe the time to union of atypical femoral fractures after surgical nailing in patients on long-term alendronate therapy, with continuation of alendronate or discontinuation of alendronate, and administration of bone-forming agents.FindingsFrom January 2004 to December 2011, the records of patients at our institution on long-term alendronate therapy for more than 36 months and sustaining atypical femoral fractures that had undergone surgical nailing, with continuation of alendronate or discontinuation of alendronate and administration of bone-forming agents were reviewed.During the 8-year study period, we treated 10 atypical femoral fractures with surgical nailing in 7 consecutive osteopenic or osteoporotic patients on long-term alendronate therapy for more than 36 months. There were no post-operative complications or needs for revision surgery. All fractures achieved union during follow-up. Mean union time was 23.5 months (range, 18--31 months) for 6 fractures with continuation of alendronate after surgery, and 4.5 months (range, 4--5 months) for 4 fractures with discontinuation of alendronate and administration of bone-forming agents after surgery. Conclusions: Discontinuation of alendronate and administration of bone-forming agents after surgical nailing may promote union of atypical femoral fractures in patients on long-term alendronate therapy.

Description: Author(s): Wen-Che Tsai, Yen-Ting Chen, Chia-Hsien Lin, Wei-Ting Hsu, Yung-Sheng Hsu, Li-Chyong Chen, Kuei-Hsien Chen, and Wen-Hao Chang The optical properties of single InGaN/GaN heterostructure nanowires (NWs) with a mean diameter down to 18 nm are investigated. Sharp emission lines originating from the recombination of localized excitons in the InGaN disk layer can be resolved. Excitation-dependent energy shifts, together with spe... [Phys. Rev. B 88, 155323] Published Mon Oct 28, 2013

Description: Computational drug design approaches are important for shortening the time and reducing the cost for drug discovery and development. Among these methods, molecular docking and quantitative structure activity r...

Description: Author(s): Guoqing Chang, Bahadur Singh, Su-Yang Xu, Guang Bian, Shin-Ming Huang, Chuang-Han Hsu, Ilya Belopolski, Nasser Alidoust, Daniel S. Sanchez, Hao Zheng, Hong Lu, Xiao Zhang, Yi Bian, Tay-Rong Chang, Horng-Tay Jeng, Arun Bansil, Han Hsu, Shuang Jia, Titus Neupert, Hsin Lin, and M. Zahid Hasan Weyl semimetals are novel topological conductors that host Weyl fermions as emergent quasiparticles. In this Rapid Communication, we propose a new type of Weyl semimetal state that breaks both time-reversal symmetry and inversion symmetry in the R AlGe ( R = rare − earth ) family. Compared to previous pred... [Phys. Rev. B 97, 041104(R)] Published Tue Jan 09, 2018