Translational control is crucial in the regulation of gene expression and deregulation of translation is associated with a wide range of cancers and human diseases. Ribosome profiling is a technique that provides genome wide information of mRNA in translation based on deep sequencing of ribosome protected mRNA fragments (RPF). RPFdb is a comprehensive resource for hosting, analyzing and visualizing RPF data, available at www.rpfdb.org or http://sysbio.sysu.edu.cn/rpfdb/index.html. The current version of database contains 777 samples from 82 studies in 8 species, processed and reanalyzed by a unified pipeline. There are two ways to query the database: by keywords of studies or by genes. The outputs are presented in three levels. (i) Study level: including meta information of studies and reprocessed data for gene expression of translated mRNAs; (ii) Sample level: including global perspective of translated mRNA and a list of the most translated mRNA of each sample from a study; (iii) Gene level: including normalized sequence counts of translated mRNA on different genomic location of a gene from multiple samples and studies. To explore rich information provided by RPF, RPFdb also provides a genome browser to query and visualize context-specific translated mRNA. Overall our database provides a simple way to search, analyze, compare, visualize and download RPF data sets.

The prevalence of renal fibrosis is higher in older than in younger individuals. Through paracrine activity, bone marrow mesenchymal stem cell-derived microvesicles (BM-MSC-MVs) influence the process of renal fibrosis. Differences in microRNA (miRNA) expression of BM-MSC-MVs that correlate with the age of the subjects and the correlation between miRNA expression and the process of renal fibrosis have not been established. The present study aimed to analyze differences in miRNA expression of BM-MSC-MVs between young or older rats and its influence on tumor growth factor-beta 1 (TGF-β1)-mediated epithelial-mesenchymal transition (EMT) of HK2 cells to explore the causes of renal fibrosis in aged tissues.

To identify the immediate economic impact of maternal death on rural Chinese households.

Grapefruit seed extract (GSE), which has powerful anti-fungal activity, can induce apoptosis in S. cerevisiae. The yeast cells underwent apoptosis as determined by testing for apoptotic markers of DNA cleavage and typical chromatin condensation by Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling (TUNEL) and 4,6'-diaminidino-2-phenylindole (DAPI) staining and electron microscopy. The changes of ΔΨmt (mitochondrial transmembrane potential) and ROS (reactive oxygen species) indicated that the mitochondria took part in the apoptotic process. Changes in this process detected by metabonomics and proteomics revealed that the yeast cells tenaciously resisted adversity. Proteins related to redox, cellular structure, membrane, energy and DNA repair were significantly increased. In this study, the relative changes in the levels of proteins and metabolites showed the tenacious resistance of yeast cells. However, GSE induced apoptosis in the yeast cells by destruction of the mitochondrial 60 S ribosomal protein, L14-A, and prevented the conversion of pantothenic acid to coenzyme A (CoA). The relationship between the proteins and metabolites was analyzed by orthogonal projections to latent structures (OPLS). We found that the changes of the metabolites and the protein changes had relevant consistency.

Intradialytic hypotension (IDH) is a global public health problem. A rising number of IDH sufferers resort to Chinese patent medicine, Shengmai Injection (SMI) in China. The objectives of present study are to assess the effectiveness and safety of SMI as an adjunct therapy for IDH. A systematic search of 6 medical databases was performed up to December 2011. Randomized trials involving SMI adjuvant therapy versus conventional therapy were identified. RevMan 5.0 was used for data analysis. Ten randomized clinical trials with 437 participants were identified. Methodological quality was considered inadequate in all trials. Compared with conventional therapy, SMI adjunct therapy showed significant effects in improving the clinic effective rate (P < 0.01), decreasing the incidence of IDH episode (P < 0.01), decreasing the frequency of nursing interventions (P < 0.01), and increasing diastolic blood pressure (P < 0.01). There was no statistical significance in the improvement of mean arterial pressure (P = 0.22) and systolic blood pressure (P = 0.08) between two groups. Four studies had mentioned adverse events, but no serious adverse effects were reported in any of the included trials. In conclusion, SMI adjunct therapy appears to be potentially effective in treatment of IDH and is generally safe. However, further rigorous designed trials are needed.

N(ε)-carboxymethyl-lysine (CML) is a major advanced glycation end-product (AGEs) widely found in foods. The aim of our study was to evaluate how exogenous CML-peptide is dynamically absorbed from the gastrointestinal tract and eliminated by renal tubular secretion using microPET imaging.

Intrauterine growth restriction (IUGR) predisposes to obesity and adipose dysfunction. We previously demonstrated IUGR-induced increased visceral adipose deposition and dysregulated expression of peroxisome proliferator activated receptor- γ 2 (PPAR γ 2) in male adolescent rats, prior to the onset of obesity. In other studies, activation of PPAR γ increases subcutaneous adiponectin expression and normalizes visceral adipose deposition. We hypothesized that maternal supplementation with docosahexaenoic acid (DHA), a PPAR γ agonist, would normalize IUGR adipose deposition in association with increased PPAR γ , adiponectin, and adiponectin receptor expression in subcutaneous adipose. To test these hypotheses, we used a well-characterized model of uteroplacental-insufficiency-(UPI-) induced IUGR in the rat with maternal DHA supplementation. Our primary findings were that maternal DHA supplementation during rat pregnancy and lactation (1) normalizes IUGR-induced changes in adipose deposition and visceral PPAR γ expression in male rats and (2) increases serum adiponectin, as well as adipose expression of adiponectin and adiponectin receptors in former IUGR rats. Our novel findings suggest that maternal DHA supplementation may normalize adipose dysfunction and promote adiponectin-induced improvements in metabolic function in IUGR.

Campylobacter jejuni is an important food-borne and zoonotic pathogen with a worldwide distribution. Humans and chickens are hosts of this pathogen. At present, there is no ideal vaccine for controlling human campylobacteriosis or the carriage of C. jejuni by chickens. Bacterial in vivo-induced antigens are useful as potential vaccine candidates and biomarkers of virulence.

Xanthophylls, oxygenated derivatives of carotenes, play critical roles in photosynthetic apparatus of cyanobacteria, algae, and higher plants. Although the xanthophylls biosynthetic pathway of algae is largely unknown, it is of particular interest because they have a very complicated evolutionary history. Carotenoid hydroxylase (CHY) is an important protein that plays essential roles in xanthophylls biosynthesis. With the availability of 18 sequenced algal genomes, we performed a comprehensive comparative analysis of chy genes and explored their distribution, structure, evolution, origins, and expression.

Whether differentiation of induced pluripotent stem cells (iPSCs) in ischemic myocardium enhances their immunogenicity, thereby increasing their chance for rejection, is unclear. Here, we dynamically demonstrated the immunogenicity and rejection of iPSCs in ischemic myocardium using bioluminescent imaging (BLI). Murine iPSCs were transduced with a tri-fusion (TF) reporter gene consisting of firefly luciferase-red fluorescent protein-truncated thymidine kinase (fluc-mrfp-tTK). Ascorbic acid (Vc) were used to induce iPSCs to differentiate into cardiomyocytes (CM). iPSCs and iPS-CMs were intramyocardially injected into immunocompetent or immunosuppressed allogenic murine with myocardial infarction. BLI was performed to track transplanted cells. Immune cell infiltration was evaluated by immunohistochemistry. Syngeneic iPSCs were also injected and evaluated. The results demonstrated that undifferentiated iPSCs survived and proliferated in allogenic immunocompetent recipients early post-transplantation, accompanying with mild immune cell infiltration. With in vivo differentiation, a progressive immune cell infiltration could be detected. While transplantation of allogenic iPSC-CMs were observed an acute rejection from receipts. In immune-suppressed recipients, the proliferation of iPSCs could be maintained and intramyocardial teratomas were formed. Transplantation of syngeneic iPSCs and iPSC-CMs were also observed progressive immune cell infiltration. This study demonstrated that iPSC immunogenicity increases with in vivo differentiation, which will increase their chance for rejection in iPSC-based therapy.

Protein domains are subunits that can fold and evolve independently. Identification of domain boundary locations is often the first step in protein folding and function annotations. Most of the current methods deduce domain boundaries by sequence-based analysis, which has low accuracy. There is no efficient method for predicting discontinuous domains that consist of segments from separated sequence regions. As template-based methods are most efficient for protein 3D structure modeling, combining multiple threading alignment information should increase the accuracy and reliability of computational domain predictions.

Galactomannans are hemicellulosic polysaccharides composed of a (1 → 4)-linked β-D-mannan backbone substituted with single-unit (1 → 6)-α-linked D-galactosyl residues. Developing fenugreek (Trigonella foenum-graecum) seeds are known to accumulate large quantities of galactomannans in the endosperm, and were thus used here as a model system to better understand galactomannan biosynthesis and its regulation. We first verified the specific deposition of galactomannans in developing endosperms and determined that active accumulation occurred from 25 to 38 days post anthesis (DPA) under our growth conditions. We then examined the expression levels during seed development of ManS and GMGT, two genes encoding backbone and side chain synthetic enzymes. Based on transcript accumulation dynamics for ManS and GMGT, cDNA libraries were constructed using RNA isolated from endosperms at four ages corresponding to before, at the beginning of, and during active galactomannan deposition. DNA from these libraries was sequenced using the 454 sequencing technology to yield a total of 1.5 million expressed sequence tags (ESTs). Through analysis of the EST profiling data, we identified genes known to be involved in galactomannan biosynthesis, as well as new genes that may be involved in this process, and proposed a model for the flow of carbon from sucrose to galactomannans. Measurement of in vitro ManS and GMGT activities and analysis of sugar phosphate and nucleotide sugar levels in the endosperms of developing fenugreek seeds provided data consistent with this model. In vitro enzymatic assays also revealed that the ManS enzyme from fenugreek endosperm preferentially used GDP-mannose as the substrate for the backbone synthesis.

Susceptibility to ankylosing spondylitis (AS) is largely genetically determined. JARID1A, JMY and PTGER4 have recently been found to be associated with AS in patients of western European descent. We aim to examine the influence of JARID1A, JMY, and PTGER4 polymorphisms on the susceptibility to and the severity of ankylosing spondylitis in Chinese ethnic majority Han population. This work can lead the clinical doctors to intervene earlier. Blood samples were drawn from 396 AS patients and 404 unrelated healthy controls. Both the AS patients and the controls are Han Chinese. The AS patients are classified based on the severity of the disease. Thirteen tag single nucleotide polymorphisms (tagSNPs) in JARID1A, JMY and PTGER4 are selected and genotyped. Frequencies of different genotypes and alleles are analyzed among the different severity AS patients and the controls. The rs2284336 SNP in JARID1A, the rs16876619 and rs16876657 SNPs in JMY are associated with susceptibility of AS. The rs11062357 SNP in JARID1A, the rs2607142 SNP in JMY and rs10440635 in PTGER4 are related to severity of AS. Haplotype analyses indicate PTGER4 is related to susceptibility to AS; JARID1A and JMY are related to severity of AS.

Etk is a non-receptor tyrosine kinase, which provides a strong survival signal in human prostate cancer cells. Src, another tyrosine kinase that cross-activates with Etk, has been shown to play an important role in prostate cancer metastasis. Herein, we discovered a new class of Etk inhibitors. Within those inhibitors, CTA095 was identified as a potent Etk and Src dual inhibitor. CTA095 was found to induce autophagy as well as apoptosis in human prostate cancer cells. In addition, CTA095 inhibited HUVEC cell tube formation and "wound healing" of human prostate cancer cells, implying its role in inhibition of angiogenesis and metastasis of human prostate cancer. More interestingly, CTA095 could overcome Src inhibitor resistance in prostate cancer cells. It induces apoptosis in Src inhibitor resistant prostate cancer cells, likely through a mechanism of down regulation of Myc and BCL2. This finding indicates that simultaneously targeting Etk and Src could be a promising approach to overcome drug resistance in prostate cancer.

Melanocortin 4 receptor (MC4R) has an important role in the regulation of energy homeostasis in both mammals and fish. In this study, MC4R was characterized in S. prenanti (Schizothorax prenanti) and designated as SpMC4R. SpMC4R cDNA is composed of 1004 nucleotides with a 978 nucleotide open reading frame encoding a protein of 326 amino acids. The SpMC4R contained predicted regions that were structural features of MCR subtypes of vertebrates. In addition, phylogenetic analyses suggested that S. prenanti MC4R was closely related to fish MC4Rs. The SpMC4R mRNA was detected in embryos at developmental stages. Further, its mRNA was detectable in unfertilized eggs. Using real-time RT-PCR, MC4R is widely expressed, with highest levels of expression in brain and ovary. An experiment was conducted to determine the expression profile of MC4R during short-term and long-term fasting of the brain. The expression level of MC4R in unfed fish was significantly increased at 6, 9 and 24h post-fasting (hpf) and 14days fasting than in fed fish, this suggests that MC4R is conserved peptide that might be involved in the regulation of food intake and other physiological function in S. prenanti.

In the present study, we downregulated FANCF expression by small interfering RNA (siRNA) in OVCAR ovarian cancer cells to address the effects of decreased FANCF expression on the function of the Fanconi anemia (FA)/breast cancer susceptibility gene (BRCA) pathway. Furthermore, we investigated whether this method increases the sensitivity of OVCAR3 cells to adriamycin (ADM) and the possible mechanism(s). We found that silencing of FANCF inactivated the FA/BRCA pathway by decreasing the monoubiquitination and focus formation of FANCD2 and reduced the function of the FA/BRCA pathway, resulting in the inhibition of cell proliferation, increased cell apoptosis and DNA damage in OVCAR3 cells. Moreover, we observed that silencing of FANCF enhanced the antiproliferative effect of ADM in OVCAR3 cells and increased ADM intracellular accumulation consequently sensitizing OVCAR3 cells to ADM. Furthermore, silencing of FANCF increased cell apoptosis of OVCAR3 cells which was caused by decreased mitochondrial membrane potential (MMP)-induced DNA damage, activated Jun N-terminal kinase (JNK), increased release of cytochrome c, increased expression of cleaved caspase-3 and poly(ADP-ribose) polymerase (PARP) dependent on JNK activation following treatment of ADM. Collectively, we confirm that silencing of FANCF sensitizes OVCAR3 ovarian cancer cells to ADM, suggesting that FANCF may serve as a potential target for therapeutic strategies in the treatment of ovarian cancer.

Scalp acupuncture (SA) is a commonly used therapeutic approach for stroke throughout China and elsewhere in the world. The objective of this study was to assess clinical efficacy and safety of SA for acute ischemic stroke. A systematical literature search of 6 databases was conducted to identify randomized controlled trials (RCTs) of SA for acute ischemic stroke compared with western conventional medicines (WCMs). All statistical analyses were performed by the Rev Man Version 5.0. Eight studies with 538 participants were included in the studies. The studies were deemed to have an unclear risk of bias based on the Cochrane Back Review Group. Compared with the WCM, 6 RCTs showed significant effects of SA for improving neurological deficit scores (P < 0.01); 4 RCTs showed significant effects of SA for favoring the clinical effective rate (P < 0.01) However, the adverse events have not been documented. In conclusion, SA appears to be able to improve neurological deficit score and the clinical effective rate when compared with WCM, though the beneficial effect from SA is possibly overvalued because of generally low methodology of the included trials. No evidence is available for adverse effects. Rigorous well-designed clinical trials are needed.

The neural cell adhesion molecule L1 plays important roles in neuronal migration and survival, neuritogenesis and synaptogenesis. L1 has also been found in tumors of different origins, with levels of L1 expression correlating positively with the metastatic potential of tumors. To select antibodies targeting the varied functions of L1, we screened the Tomlinson library of recombinant human antibody fragments to identify antibodies binding to recombinant human L1 protein comprising the entire extracellular domain of human L1. We obtained four L1 binding single-chain variable fragment antibodies (scFvs), named I4, I6, I13, and I27 and showed by enzyme-linked immunosorbent assay (ELISA) that scFvs I4 and I6 have high affinity to the immunoglobulin-like (Ig) domains 1-4 of L1, while scFvs I13 and I27 bind strongly to the fibronectin type III homologous (Fn) domains 1-3 of L1. Application of scFvs I4 and I6 to human SK-N-SH neuroblastoma cells reduced proliferation and transmigration of these cells. Treatment of SK-N-SH cells with scFvs I13 and I27 enhanced cell proliferation and migration, neurite outgrowth, and protected against the toxic effects of H(2)O(2) by increasing the ratio of Bcl-2/Bax. In addition, scFvs I4 and I6 inhibited and scFvs I13 and I27 promoted phosphorylation of src and Erk. Our findings indicate that scFvs reacting with the immunoglobulin-like domains 1-4 inhibit L1 functions, whereas scFvs interacting with the fibronectin type III domains 1-3 trigger L1 functions of cultured neuroblastoma cells.

Salinity is one of the most common abiotic stresses in agriculture production. Salt tolerance of rice (Oryza sativa) is an important trait controlled by various genes. The mechanism of rice salt tolerance, currently with limited understanding, is of great interest to molecular breeding in improving grain yield. In this study, a gene regulatory network of rice salt tolerance is constructed using a systems biology approach with a number of novel computational methods. We developed an improved volcano plot method in conjunction with a new machine-learning method for gene selection based on gene expression data and applied the method to choose genes related to salt tolerance in rice. The results were then assessed by quantitative trait loci (QTL), co-expression and regulatory binding motif analysis. The selected genes were constructed into a number of network modules based on predicted protein interactions including modules of phosphorylation activity, ubiquity activity, and several proteinase activities such as peroxidase, aspartic proteinase, glucosyltransferase, and flavonol synthase. All of these discovered modules are related to the salt tolerance mechanism of signal transduction, ion pump, abscisic acid mediation, reactive oxygen species scavenging and ion sequestration. We also predicted the three-dimensional structures of some crucial proteins related to the salt tolerance QTL for understanding the roles of these proteins in the network. Our computational study sheds some new light on the mechanism of salt tolerance and provides a systems biology pipeline for studying plant traits in general.

Susceptibility to and severity of ankylosing spondylitis (AS) are largely genetically determined. PPARGC1B, RUNX3 and TBKBP1 have recently been found to be associated with AS in patients of western European descent. Our purpose is to examine the influence of PPARGC1B, RUNX3 and TBKBP1 polymorphisms on the susceptibility to and the severity of ankylosing spondylitis in Chinese ethnic majority Han population.