Evolution of Interferon-Based Therapy for Chronic Hepatitis C

Since 1986, interferon-alfa (IFN-α) monotherapy has been administered for patients with chronic hepatitis C (CHC). However, sustained response rate is only about 8% to 9%. Subsequent introduction of ribavirin in combination with IFN-α was a major breakthrough in the treatment of CHC. Sustained virological responses (SVRs) rate is about 30% in hepatitis C virus genotype 1 (HCV-1) patients, and is about 65% in HCV-2 or -3 patients. After 2000, pegylated interferon (PegIFN) much improved the rates of SVR. Presently, PegIFN-α-ribavirin combination therapy has been current standard of care for patients infected with HCV. In patients with HCV-1, treatment for 48 weeks is optimal, but 24 weeks of treatment is sufficient in HCV-2 or -3 infected patients. Clinical factors have been identified as predictors for the efficacy of the IFN-based therapy. The baseline factor most strongly predictive of an SVR is the presence of HCV-2 or -3 infections. Rapid virological response (RVR) is the single best predictor of an SVR to PegIFN-ribavirin therapy. If patients can't achieve a RVR but achieve a complete early virological response (cEVR), treatment with current standard of care can provide more than 90% SVR rate. HCV-1 patients who do not achieve an EVR should discontinue the therapy. Recent advances of protease inhibitor may contribute the development of a novel triple combination therapy

Genome-wide survey and expression analysis of the bHLH-PAS genes in the amphioxus Branchiostoma floridae reveal both conserved and diverged expression patterns between cephalochordates and vertebrates

BACKGROUND: The bHLH-PAS transcription factors are found in both protostomes and deuterostomes. They are involved in many developmental and physiological processes, including regional differentiation of the central nervous system, tube-formation, hypoxia signaling, aromatic hydrocarbon sensing, and circadian rhythm regulation. To understand the evolution of these genes in chordates, we analyzed the bHLH-PAS genes of the basal chordate amphioxus (Branchiostoma floridae). RESULTS: From the amphioxus draft genome database, we identified ten bHLH-PAS genes, nine of which could be assigned to known orthologous families. The tenth bHLH-PAS gene could not be assigned confidently to any known bHLH family; however, phylogenetic analysis clustered this gene with arthropod Met family genes and two spiralian bHLH-PAS-containing sequences, suggesting that they may share the same ancestry. We examined temporal and spatial expression patterns of these bHLH-PAS genes in developing amphioxus embryos. We found that BfArnt, BfNcoa, BfSim, and BfHifα were expressed in the central nervous system in patterns similar to those of their vertebrate homologs, suggesting that their functions may be conserved. By contrast, the amphioxus BfAhr and BfNpas4 had expression patterns distinct from those in vertebrates. These results imply that there were changes in gene regulation after the divergence of cephalochordates and vertebrates. CONCLUSIONS: We have identified ten bHLH-PAS genes from the amphioxus genome and determined the embryonic expression profiles for these genes. In addition to the nine currently recognized bHLH-PAS families, our survey suggests that the BfbHLHPAS-orphan gene along with arthropod Met genes and the newly identified spiralian bHLH-PAS-containing sequences represent an ancient group of genes that were lost in the vertebrate lineage. In a comparison with the expression patterns of the vertebrate bHLH-PAS paralogs, which are the result of whole-genome duplication, we found that although several members seem to retain conserved expression patterns during chordate evolution, many duplicated paralogs may have undergone subfunctionalization and neofunctionalization in the vertebrate lineage. In addition, our survey of amphioxus bHLH-PAS gene models from genome browser with experimentally verified cDNA sequences calls into question the accuracy of the current in silico gene annotation of the B. floridae genome

DEA-based integrated relationship of returns to scale – an application to road maintenance in Taiwan

An Integrated Relationship of Returns to Scale (IRRS) associated with multiple-stage Data Envelopment Analysis (DEA) is proposed for identifying the returns to scale (RTS) among decision-making units (DMUs) appropriately and accurately. The validity and feasibility of the proposed method is tested by using 31 case studies on highway maintenance and construction offices based on the data provided by the Directorate General of Highways (Taiwan). The results show that the multi-stage DEA method with IRRS is more useful than the traditional single-stage DEA for evaluating the status of RTS for each DMU. Among the 31 units evaluated, 14 units are categorized as having increasing returns to scale, 4 have decreasing returns to scale, and no unit has constant returns to scale; the returns for the remaining 13 units cannot be determined

Promoter-sharing by different genes in human genome – CPNE1 and RBM12 gene pair as an example

<p>Abstract</p> <p>Background</p> <p>Regulation of gene expression plays important role in cellular functions. Co-regulation of different genes may indicate functional connection or even physical interaction between gene products. Thus analysis on genomic structures that may affect gene expression regulation could shed light on the functions of genes.</p> <p>Results</p> <p>In a whole genome analysis of alternative splicing events, we found that two distinct genes, <it>copine I </it>(<it>CPNE1</it>) and <it>RNA binding motif protein 12 </it>(<it>RBM12</it>), share the most 5' exons and therefore the promoter region in human. Further analysis identified many gene pairs in human genome that share the same promoters and 5' exons but have totally different coding sequences. Analysis of genomic and expressed sequences, either cDNAs or expressed sequence tags (ESTs) for <it>CPNE1 </it>and <it>RBM12</it>, confirmed the conservation of this phenomenon during evolutionary courses. The co-expression of the two genes initiated from the same promoter is confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) in different tissues in both human and mouse. High degrees of sequence conservation among multiple species in the 5'UTR region common to <it>CPNE1 </it>and <it>RBM12 </it>were also identified.</p> <p>Conclusion</p> <p>Promoter and 5'UTR sharing between <it>CPNE1 </it>and <it>RBM12 </it>is observed in human, mouse and zebrafish. Conservation of this genomic structure in evolutionary courses indicates potential functional interaction between the two genes. More than 20 other gene pairs in human genome were found to have the similar genomic structure in a genome-wide analysis, and it may represent a unique pattern of genomic arrangement that may affect expression regulation of the corresponding genes.</p

Alcohol Use, Abuse, and Dependency in Shanghai

The use of alcohol for social and ceremonial occasions was recorded in Chinese history as early as 1760 B.C. during the Yin Dynasty (Ci-Hai Encyclopedia, 1979:936). The cultural tradition of ancient China placed alcoholic beverages at the center of social occasions, which presumably was the origin of the adage: Without wine, there is no li (or etiquette). Thus, the use of alcoholic beverages has always been accompanied by the concept of propriety and the discharging of one\u27s role obligations m social functions, rather than that of personal indulgence