ISD: a software package for Bayesian NMR structure calculation

Summary: The conventional approach to calculating biomolecularstructures from nuclear magnetic resonance (NMR) data is oftenviewed as subjective due to its dependence on rules of thumbfor deriving geometric constraints and suitable values for theoryparameters from noisy experimental data. As a result, it canbe difficult to judge the precision of an NMR structure in anobjective manner. The inferential Structure determination (ISD)framework, which has been introduced recently, addresses thisproblem by using Bayesian inference to derive a probabilitydistribution that represents both the unknown structure andits uncertainty. It also determines additional unknowns, suchas theory parameters, that normally need to be chosen empirically.Here we give an overview of the ISD software package, whichimplements this methodology. Availability: http://www.bioc.cam.ac.uk/isd Contact: wolfgang.rieping{at}bioc.cam.ac.uk, michael.habeck{at}tuebingen.mpg.de Associate Editor: Alfonso Valencia     

Differentiation and cancer

Summary Cancer is discussed from a standpoint of a postembryonic differentiation. A differentiation requires the interaction of an exogenous inductive stimulus with competent precursor cell, which then evolve a new tissue with unique, stable heritable properties distinguishable from the progenitor. Evidence is cited pinpointing the normal stem cells of tissues as the competent target precursor cells in carcinogenesis. The resultant phenotype differs from its progenitor and has stable and unique characteristics. All of the characteristics associated with malignancy are expressed during some stage of development, suggesting that the normal genome contains the information necessary for malignant expression, and that the mechanism of malignancy is probably an alteration of control of genomic expression. Malignant tissue, like normal tissue, maintains itself by proliferation and differentiation of its stem cells; at least, that is what was observed in two tumors examined. In each of these tumors the differentiated progeny of the malignant stem cells proved to be benign. A third tumor was adapted to growth in vitro and under the conditions of the experiments could be modulated by altering the in vitro conditions. These data suggest that direction of the naturally occurring differentiation that occurs in tumors may be a suitable therapeutic alternative to cytotoxic chemotherapy. Presented in the Symposium on Regulation in Tumor Cells at the 22nd Annual Meeting of the Tissue Culture Association, Lake Placid, New York. Supported in part by Grant E105 from the American Cancer Society and Grant AM 13112 from the United States Public Health Service. Supported by a Traineeship from National Institutes of Health Training Grant GM 00977.     

Differentiation mechanisms and malignancy

This review considers the relationship between differentiation mechanisms and the genesis and maintenance of tumor phenotype. To a certain extent, carcinomas preserve differentiation markers of normal tissue, and hemoblastoses precisely reflect the direction and differentiation level of their precursor cells. Both tumor types retain the ability to differentiate. Mechanisms of T and B cell differentiation are reviewed considering the activation of protooncogenes by translocation to the region of tissue-specific genes including the immunoglobulin (Ig) and T cell receptor (TCR) genes. Apart from the classical oncogenes (MYC, PRAD, BCL-2), heterologous differentiation of trans-factors can be activated in a similar manner. Their activation at inappropriate time and place induces oncogenic transformation in a number of hemoblastoses. Chimeric genes and fused proteins are analyzed, including their genesis by specific translocation resulting in transformation and their role in differentiation and maintenance of the tumor phenotype. Induction of terminal differentiation in leukemia can have significant therapeutic effect. These hemoblastoses include hairy cell leukemia, promyelocytic leukemia, and in part chronic myeloid leukemia. Specific attention is given to the role of intercellular interactions in the control of tumor growth and maintenance of a differentiated state of the cells. It is suggested that alterations in these interactions during tumor progression simultaneously stimulate malignant growth and decrease differentiation level, thus inducing re-expression of embryonic antigens in the tumors.     

阿拉伯半乳糖蛋白与植物细胞分化

阿拉伯半乳糖蛋白（ａｒａｂｉｎｏｇａｌａｃｔａｎ－ｐｒｏ－ｔｅｉｎｓ,ＡＧＰｓ）是广泛存在于高等动植物中的一种糖蛋白。该文就其化学组成、特性、合成、代谢和功能的研究进展作了介绍。     

Viral Infection and Cell Differentiation

The dependence of viral reproduction and success of viral infection on cell differentiation is briefly reviewed at the example of picornaviruses—small RNA viruses of animals. In particular, the role of the cell factors in viral tropism, control of viral RNA translation, and the pattern of infected cell death are discussed.