<Emphasis Type="Italic">In silico</Emphasis> Analysis of Synonymous Codon Usage Pattern of <Emphasis Type="Italic">Rhizobium etli</Emphasis> CFN 42

Understanding the extent and pattern of codon bias and the forces affecting codon usage are the key steps towards elucidating choice of codons at the level of individual genes. In the present study, codon usage pattern among 3,703 genes of nitrogen fixing bacterium, Rhizobium etli CFN 42 was analyzed. The study aims to identify the factors responsible for codon usage bias and highly expressed genes of this bacterium. Multivariate statistical analysis revealed a single major explanatory axis accounting for codon usage variation among the genes. Correlation analysis suggested that the axis has strong significant positive correlation with GC_3s i.e. GC content at the third codon position. A significant negative correlation between effective number of codons and GC_3s content was observed suggesting that the codon usage was affected by gene nucleotide composition. These findings suggested mutational role as the major factor in shaping codon usage bias among the genes. Further, correspondence analysis of Relative Synonymous Codon Usage revealed cluster of highly expressed genes. Notably, 26 codons were determined as the ‘optimal codons’ that were significantly more frequent among the highly expressed genes tested by χ² test (P < 0.01). Such results may add value to the efforts of developing bio-fertilizers based on symbiotic or non-symbiotic bacteria for improving soil fertility.     

A new rat model of portal hypertension induced by intraportal injection of microspheres

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From the Cover: Insulin stimulation of SREBP-1c processing in transgenic rat hepatocytes requires p70 S6-kinase

Insulin activates sterol regulatory element-binding protein-1c (SREBP-1c) in liver, thereby increasing fatty acid and triglyceride synthesis. We created a line of transgenic rats that produce epitope-tagged human SREBP-1c in liver under control of the constitutive apolipoprotein E promoter/enhancer. This system allows us to dissect the pathway by which insulin stimulates SREBP-1c processing without interference by the insulin-mediated increase in SREBP-1c mRNA. Rats are used because freshly isolated rat hepatocytes respond much more robustly to insulin than do mouse hepatocytes. The data reveal that insulin-mediated stimulation of SREBP-1c processing requires the mechanistic target of rapamycin complex 1 (mTORC1), which also is required for insulin-mediated SREBP-1c mRNA induction. However, in contrast to mRNA induction, insulin stimulation of SREBP-1c processing is blocked by an inhibitor of p70 S6-kinase. The data indicate that the pathways for insulin enhancement of SREBP-1c mRNA and proteolytic processing diverge after mTORC1. Stimulation of processing requires the mTORC1 target p70 S6-kinase, whereas induction of mRNA bypasses this enzyme. Insulin stimulation of both processes is blocked by glucagon. The transgenic rat system will be useful in further defining the molecular mechanism for insulin stimulation of lipid synthesis in liver in normal and diabetic states.     

Establishment of human T-cell leukemia virus type I T-cell lymphomas in severe combined immunodeficient mice

Human T-cell leukemia virus type I (HTLV-I) is recognized as the etiologic agent of adult T-cell leukemia (ATL), a disease endemic in certain regions of southeastern Japan, Africa, and the Caribbean basin. Although HTLV-I can immortalize T lymphocytes in culture, factors leading to tumor progression after HTLV-I infection remain elusive. Previous attempts to propagate the ATL tumor cells in animals have been unsuccessful. Severe combined immunodeficient (SCID) mice have previously been used to support the survival of human lymphoid cell populations when inoculated with human peripheral blood lymphocytes (PBL). SCID mice were injected intraperitoneally with PBL from patients diagnosed with ATL, HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), or from asymptomatic HTLV-I-seropositive patients. Many of these mice become persistently infected with HTLV-I. Furthermore, after human reconstitution was established in these mice, HTLV-I-infected cells displayed a proliferative advantage over uninfected human cells. Lymphoblastic lymphomas of human origin developed in animals injected with PBL from two ATL patients. The tumor cells represented outgrowth of the original ATL leukemic clone in that they had monoclonal or oligoclonal integrations of the HTLV-I provirus identical to the leukemic clone and predominantly expressed the cell surface markers, CD4 and CD25. In contrast, cell lines derived by HTLV immortalization of T cells in vitro did not persist or form tumors when inoculated into SCID mice, indicating differences between in vitro immortalized cells and ATL leukemic cells. This system represents the first small animal model to study HTLV-I tumorigenesis in vivo.