The emerging role of circular RNAs in cardiovascular diseases

Journal of Physiology and Biochemistry - Cardiovascular disease (CVD) is one of the vital causes of morbidity and mortality, and the number of deaths from CVD has increased worldwide. Circular RNAs...     

A model of the ACE2 structure and function as a SARS-CoV receptor

The angiotensin-converting enzyme 2 (ACE2) is an important regulator of the renin-angiotensin system and was very recently identified as a functional receptor for the SARS virus. The ACE2 sequence is similar (sequence identities 43% and 35%, and similarities 61% and 55%, respectively) to those of the testis-specific form of ACE (tACE) and the Drosophila homolog of ACE (AnCE). The high level of sequence similarity allowed us to build a robust homology model of the ACE2 structure with a root-mean-square deviation from the aligned crystal structures of tACE and AnCE less than 0.5A. A prominent feature of the model is a deep channel on the top of the molecule that contains the catalytic site. Negatively charged ridges surrounding the channel may provide a possible binding site for the positively charged receptor-binding domain (RBD) of the S-glycoprotein, which we recently identified [Biochem. Biophys. Res. Commun. 312 (2003) 1159]. Several distinct patches of hydrophobic residues at the ACE2 surface were noted at close proximity to the charged ridges that could contribute to binding. These results suggest a possible binding region for the SARS-CoV S-glycoprotein on ACE2 and could help in the design of experiments to further elucidate the structure and function of ACE2.     

A Genome-wide RNAi Screen Reveals a Trio-Regulated Rho GTPase Circuitry Transducing Mitogenic Signals Initiated by G Protein-Coupled Receptors

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Highlights? Human cancers harbor frequent mutations in Gq-linked GPCRs and Gα_q subunits ? A genome-wide RNAi screen revealed that Trio is essential for activating AP-1 via Gα_q ? A network of Trio-regulated Rho GTPases and MAPKs links Gq to the nucleus ? A hard-wired Gq-Trio signaling axis promotes the growth of many human malignancies     

Elements in Lung Tissues of Patients from a High Lung Cancer Incidence Area of China

The concentrations of trace elements are closely related to tumor genesis, progression, and therapy. In order to establish the extent to which trace elements apply to lung cancer, 15 trace elements were determined in 60 lung tissue samples from residents of Xuanwei and Fuyuan, two counties with extremely high lung cancer incidences in Yunnan province, China. The results indicated that the levels of V, Fe, Zn, Cd, Ni, Cu, Se, and Pb in the lung cancer tissues were significantly different from those in benign tissues. Among the eight elements, the levels of V, Fe, Zn, and Cd in the lung cancer tissues were lower than those in the benign tissues, while those of Ni, Cu, Se, and Pb were higher. Multiple conditional logistic regression showed that among the 15 elements, Cu, Pb (β > 0, OR > 1), and Zn (β < 0, OR < 1) were closely related to the lung cancer. Cu and Pb were classified as risk factors for local lung cancer and Zn was identified as a protective factor. The results obtained will provide dietary suggestions in terms of how to reduce lung cancer risks by appropriately balancing the intakes of certain trace elements especially for individuals who are from those two counties.     

CpG_MPs: identification of CpG methylation patterns of genomic regions from high-throughput bisulfite sequencing data

High-throughput bisulfite sequencing is widely used to measure cytosine methylation at single-base resolution in eukaryotes. It permits systems-level analysis of genomic methylation patterns associated with gene expression and chromatin structure. However, methods for large-scale identification of methylation patterns from bisulfite sequencing are lacking. We developed a comprehensive tool, CpG_MPs, for identification and analysis of the methylation patterns of genomic regions from bisulfite sequencing data. CpG_MPs first normalizes bisulfite sequencing reads into methylation level of CpGs. Then it identifies unmethylated and methylated regions using the methylation status of neighboring CpGs by hotspot extension algorithm without knowledge of pre-defined regions. Furthermore, the conservatively and differentially methylated regions across paired or multiple samples (cells or tissues) are identified by combining a combinatorial algorithm with Shannon entropy. CpG_MPs identified large amounts of genomic regions with different methylation patterns across five human bisulfite sequencing data during cellular differentiation. Different sequence features and significantly cell-specific methylation patterns were observed. These potentially functional regions form candidate regions for functional analysis of DNA methylation during cellular differentiation. CpG_MPs is the first user-friendly tool for identifying methylation patterns of genomic regions from bisulfite sequencing data, permitting further investigation of the biological functions of genome-scale methylation patterns.     

Dietary High Vanadium Causes Oxidative Damage-Induced Renal and Hepatic Toxicity in Broilers

The purpose of this study was to investigate the renal and hepatic oxidative damage and toxicity caused by dietary high vanadium in broilers. A total of 420 one-day-old avian broilers were divided into six groups and fed on a corn–soybean basal diet as control diet (vanadium 0.073 mg/kg), and five high vanadium diets (vanadium 5 mg/kg, high vanadium group I; 15 mg/kg, high vanadium group II; 30 mg/kg, high vanadium group III; 45 mg/kg, high vanadium group IV; and 60 mg/kg, high vanadium group V) throughout the experimental period of 42 days. The results showed that the renal and hepatic superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, ability to inhibit hydroxy radical, and malondialdehyde (MDA), glutathione, and vanadium contents were not significantly changed in high vanadium group I and II when compared with those of the control groups. However, the SOD and GSH-Px activities, ability to inhibit hydroxy radical, and GSH content were significantly decreased, and the MDA and vanadium contents were markedly increased in high vanadium groups III, IV, and V. At the same time, the lesions were also observed in the kidney and liver of high vanadium groups III, IV, and V. The renal tubular epithelial cells showed granular degeneration and vacuolar degeneration, and hepatocytes showed granular degeneration, vacuolar degeneration, and fatty degeneration. It was concluded that dietary vanadium in the range of 30–60 mg/kg could cause oxidative damage and vanadium accumulation, which induced renal and hepatic toxicity and lesions. The renal and hepatic function was finally impaired in boilers.     

Evaluation of swollenin from <Emphasis Type="Italic">Trichoderma pseudokoningii</Emphasis> as a potential synergistic factor in the enzymatic hydrolysis of cellulose with low cellulase loadings

Swollenin is a novel plant expansin-like protein that has been proposed to have a cellulose disruption activity. In this study, the recombinant swollenin (SWO2) from Trichoderma pseudokoningii S38 was successfully produced and purified in Aspergillus niger with a final yield of up to 10 mg of purified protein from 1 l of fermentation supernatant. The recombinant protein was found to exhibit very low level of endoglucanase activity and caused a slight increase in the crystallinity when treating cellulose. Simultaneous incubation of SWO2 with low-dose cellulases resulted in a significant synergistic activity in cellulose hydrolysis. Specifically, an even greater increase in the synergistic activity was obtained when cellulose was pretreated with swollenin followed by cellulase hydrolysis. Our results, therefore, provide a novel approach for the potential application of swollenin in the efficient saccharification of cellulosic materials.