Changes in transcriptional orientation are associated with increases in evolutionary rates of enterobacterial genes

<p>Abstract</p> <p>Background</p> <p>Changes in transcriptional orientation (“CTOs”) occur frequently in prokaryotic genomes. Such changes usually result from genomic inversions, which may cause a conflict between the directions of replication and transcription and an increase in mutation rate. However, CTOs do not always lead to the replication-transcription confrontation. Furthermore, CTOs may cause deleterious disruptions of operon structure and/or gene regulations. The currently existing CTOs may indicate relaxation of selection pressure. Therefore, it is of interest to investigate whether CTOs have an independent effect on the evolutionary rates of the affected genes, and whether these genes are subject to any type of selection pressure in prokaryotes.</p> <p>Methods</p> <p>Three closely related enterbacteria, <it>Escherichia coli</it>, <it>Klebsiella pneumoniae</it> and <it>Salmonella enterica serovar Typhimurium</it>, were selected for comparisons of synonymous (<it>dS</it>) and nonsynonymous (<it>dN</it>) substitution rate between the genes that have experienced changes in transcriptional orientation (changed-orientation genes, “COGs”) and those that do not (same-orientation genes, “SOGs”). The <it>dN</it>/<it>dS</it> ratio was also derived to evaluate the selection pressure on the analyzed genes. Confounding factors in the estimation of evolutionary rates, such as gene essentiality, gene expression level, replication-transcription confrontation, and decreased <it>dS</it> at gene terminals were controlled in the COG-SOG comparisons.</p> <p>Results</p> <p>We demonstrate that COGs have significantly higher <it>dN</it> and <it>dS</it> than SOGs when a series of confounding factors are controlled. However, the <it>dN</it>/<it>dS</it> ratios are similar between the two gene groups, suggesting that the increase in <it>dS</it> can sufficiently explain the increase in <it>dN</it> in COGs. Therefore, the increases in evolutionary rates in COGs may be mainly mutation-driven.</p> <p>Conclusions</p> <p>Here we show that CTOs can increase the evolutionary rates of the affected genes. This effect is independent of the replication-transcription confrontation, which is suggested to be the major cause of inversion-associated evolutionary rate increases. The real cause of such evolutionary rate increases remains unclear but is worth further explorations.</p

POWER: PhylOgenetic WEb Repeater—an integrated and user-optimized framework for biomolecular phylogenetic analysis

POWER, the PhylOgenetic WEb Repeater, is a web-based service designed to perform user-friendly pipeline phylogenetic analysis. POWER uses an open-source LAMP structure and infers genetic distances and phylogenetic relationships using well-established algorithms (ClustalW and PHYLIP). POWER incorporates a novel tree builder based on the GD library to generate a high-quality tree topology according to the calculated result. POWER accepts either raw sequences in FASTA format or user-uploaded alignment output files. Through a user-friendly web interface, users can sketch a tree effortlessly in multiple steps. After a tree has been generated, users can freely set and modify parameters, select tree building algorithms, refine sequence alignments or edit the tree topology. All the information related to input sequences and the processing history is logged and downloadable for the user's reference. Furthermore, iterative tree construction can be performed by adding sequences to, or removing them from, a previously submitted job. POWER is accessible at

Phosphorous Diffuser Diverged Blue Laser Diode for Indoor Lighting and Communication.

An advanced light-fidelity (Li-Fi) system based on the blue Gallium nitride (GaN) laser diode (LD) with a compact white-light phosphorous diffuser is demonstrated for fusing the indoor white-lighting and visible light communication (VLC). The phosphorous diffuser adhered blue GaN LD broadens luminescent spectrum and diverges beam spot to provide ample functionality including the completeness of Li-Fi feature and the quality of white-lighting. The phosphorous diffuser diverged white-light spot covers a radiant angle up to 120(o) with CIE coordinates of (0.34, 0.37). On the other hand, the degradation on throughput frequency response of the blue LD is mainly attributed to the self-feedback caused by the reflection from the phosphor-air interface. It represents the current state-of-the-art performance on carrying 5.2-Gbit/s orthogonal frequency-division multiplexed 16-quadrature-amplitude modulation (16-QAM OFDM) data with a bit error rate (BER) of 3.1 × 10(-3) over a 60-cm free-space link. This work aims to explore the plausibility of the phosphorous diffuser diverged blue GaN LD for future hybrid white-lighting and VLC systems

Ser-634 and Ser-636 of Kaposi’s Sarcoma-Associated Herpesvirus RTA are Involved in Transactivation and are Potential Cdk9 Phosphorylation Sites

The replication and transcription activator (RTA) of Kaposi’s sarcoma-associated herpesvirus (KSHV), K-RTA, is a lytic switch protein that moderates the reactivation process of KSHV latency. By mass spectrometric analysis of affinity purified K-RTA, we showed that Thr-513 or Thr-514 was the primary in vivo phosphorylation site. Thr-513 and Thr-514 are proximal to the nuclear localization signal (527KKRK530) and were previously hypothesized to be target sites of Ser/Thr kinase hKFC. However, substitutions of Thr with Ala at 513 and 514 had no effect on K-RTA subcellular localization or transactivation activity. By contrast, replacement of Ser with Ala at Ser-634 and Ser-636 located in a Ser/Pro-rich region of K-RTA, designated as S634A/S636A, produced a polypeptide with ∼10 kDa shorter in molecular weight and reduced transactivation in a luciferase reporter assay relative to the wild type. In contrast to prediction, the decrease in molecular weight was not due to lack of phosphorylation because the overall Ser and Thr phosphorylation state in K-RTA and S634A/S636A were similar, excluding that Ser-634 or Ser-636 motif served as docking sites for consecutive phosphorylation. Interestingly, S634A/S636A lost ∼30% immuno-reactivity to MPM2, an antibody specific to pSer/pThr-Pro motif, indicating that 634SPSP637 motif was in vivo phosphorylated. By in vitro kinase assay, we showed that K-RTA is a substrate of CDK9, a Pro-directed Ser/Thr kinase central to transcriptional regulation. Importantly, the capability of K-RTA in associating with endogenous CDK9 was reduced in S634A/S636A, which suggested that Ser-634 and Ser-636 may be involved in CDK9 recruitment. In agreement, S634A/S636A mutant exhibited ∼25% reduction in KSHV lytic cycle reactivation relative to that by the wild type K-RTA. Taken together, our data propose that Ser-634 and Ser-636 of K-RTA are phosphorylated by host transcriptional kinase CDK9 and such a process contributes to a full transcriptional potency of K-RTA

Effects of Salvianolic Acid B on Protein Expression in Human Umbilical Vein Endothelial Cells

Salvianolic acid B (Sal B), a pure water-soluble compound extracted from Radix Salviae miltiorrhizae, has been reported to possess potential cardioprotective efficacy. To identify proteins or pathways by which Sal B might exert its protective activities on the cardiovascular system, two-dimensional gel electrophoresis-based comparative proteomics was performed, and proteins altered in their expression level after Sal B treatment were identified by MALDI-TOF MS/MS. Human umbilical vein endothelial cells (HUVECs) were incubated at Sal B concentrations that can be reached in human plasma by pharmacological intervention. Results indicated that caldesmon, an actin-stabilizing protein, was downregulated in Sal B-exposed HUVECs. Proteins that showed increased expression levels upon Sal B treatment were vimentin, T-complex protein 1, protein disulfide isomerase, tropomyosin alpha, heat shock protein beta-1, UBX domain-containing protein 1, alpha enolase, and peroxiredoxin-2. Additionally, Sal B leads to increased phosphorylation of nucleophosmin in a dose-dependent manner and promotes proliferation of HUVECs. We found that Sal B exhibited a coordinated regulation of enzymes and proteins involved in cytoskeletal reorganization, oxidative stress, and cell growth. Our investigation would provide understanding to the endothelium protection information of Sal B

Fly-DPI: database of protein interactomes for D. melanogaster in the approach of systems biology

BACKGROUND: Proteins control and mediate many biological activities of cells by interacting with other protein partners. This work presents a statistical model to predict protein interaction networks of Drosophila melanogaster based on insight into domain interactions. RESULTS: Three high-throughput yeast two-hybrid experiments and the collection in FlyBase were used as our starting datasets. The co-occurrences of domains in these interactive events are converted into a probability score of domain-domain interaction. These scores are used to infer putative interaction among all available open reading frames (ORFs) of fruit fly. Additionally, the likelihood function is used to estimate all potential protein-protein interactions. All parameters are successfully iterated and MLE is obtained for each pair of domains. Additionally, the maximized likelihood reaches its converged criteria and maintains the probability stable. The hybrid model achieves a high specificity with a loss of sensitivity, suggesting that the model may possess major features of protein-protein interactions. Several putative interactions predicted by the proposed hybrid model are supported by literatures, while experimental data with a low probability score indicate an uncertain reliability and require further proof of interaction. Fly-DPI is the online database used to present this work. It is an integrated proteomics tool with comprehensive protein annotation information from major databases as well as an effective means of predicting protein-protein interactions. As a novel search strategy, the ping-pong search is a naïve path map between two chosen proteins based on pre-computed shortest paths. Adopting effective filtering strategies will facilitate researchers in depicting the bird's eye view of the network of interest. Fly-DPI can be accessed at . CONCLUSION: This work provides two reference systems, statistical and biological, to evaluate the reliability of protein interaction. First, the hybrid model statistically estimates both experimental and predicted protein interaction relationships. Second, the biological information for filtering and annotation itself is a strong indicator for the reliability of protein-protein interaction. The space-temporal or stage-specific expression patterns of genes are also critical for identifying proteins involved in a particular situation

Central obesity and atherogenic dyslipidemia in metabolic syndrome are associated with increased risk for colorectal adenoma in a Chinese population

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome (MetS) is composed of cardiovascular risk factors including insulin resistance, obesity, dyslipidemia, and hypertension. Most of the components of MetS have been linked to the development of neoplasm. The purpose of this study was to evaluate the relationship between individual components of MetS and colorectal adenoma.</p> <p>Methods</p> <p>The study subjects were recruited from a pool of 4872 individuals who underwent a health check-up examination during the period January 2006 to May 2008. Each participant fulfilled a structured questionnaire. MetS was defined based on the America Heart Association and National Heart Lung Blood Institute criteria. Subjects with history of colon cancer, colon polyps, colitis, or prior colonic surgery were excluded.</p> <p>Results</p> <p>A total of 4122 subjects were included for final analysis (2367 men and 1755 women; mean age, 49.6 ± 11.7 years). Of them, MetS was diagnosed in 708 men (29.9%) and in 367 women (20.9%). Among the patients with MetS, 34.6% had adenoma, 31.7% had hyperplastic polyps and 23.3% were polyp-free (p < 0.0001, Chi-square test). The adjusted OR for colorectal adenoma was significantly higher in the subjects with MetS (OR, 1.31, CI: 1.09-1.57). A stronger association between MetS and colorectal adenoma was found in men (OR:1.44, CI:1.16-1.80) than in women (OR:1.04, CI:0.74-1.46). The adjusted OR for adenoma increased as the number of MetS components increased (p for trend = 0.0001 ). When the individual components of MetS were analyzed separately, only central obesity (OR:1.36, CI:1.14-1.63), low HDL cholesterol levels (OR:1.30, CI:1.10-1.54) and high triglyceride levels (OR:1.26, CI:1.04-1.53) were independently associated with colorectal adenoma.</p> <p>Conclusions</p> <p>Of the components of MetS analyzed in this study, central obesity and dyslipidemia are independent risk factors for colorectal adenoma. With regard to the prevention of colorectal neoplasm, life-style modification such as weight reduction is worthwhile.</p

Biomechanical investigation of flexor digitorum tendons in trigger finger patients using sonography

Trigger finger (TF) has generally been ascribed to primary changes in the first annular (A1) pulley. Repeated friction between the A1 pulley and flexor digitorum tendons could result in swelling of soft tissues, and thus it has been speculated that TF affects tendons’ biomechanical behaviors. However, the pathology mechanism related to these behaviors remains unclear. The purposes of this study are to understand (1) the variations in the morphologies of the flexor digitorum profundus (FDP) and flexor digitorum superficialis (FDS) between normal fingers and TFs, (2) the differences in the biomechanical behaviors of the FDP and FDS between normal fingers and TFs in various finger flexion positions, and (3) the effect of various finger positions on the biomechanical behaviors of the FDP and FDS