Pluripotency, differentiation, and reprogramming: A gene expression dynamics model with epigenetic feedback regulation

Characterization of pluripotent states, in which cells can both self-renew and differentiate, and the irreversible loss of pluripotency are important research areas in developmental biology. In particular, an understanding of these processes is essential to the reprogramming of cells for biomedical applications, i.e., the experimental recovery of pluripotency in differentiated cells. Based on recent advances in dynamical-systems theory for gene expression, we propose a gene-regulatory-network model consisting of several pluripotent and differentiation genes. Our results show that cellular-state transition to differentiated cell types occurs as the number of cells increases, beginning with the pluripotent state and oscillatory expression of pluripotent genes. Cell-cell signaling mediates the differentiation process with robustness to noise, while epigenetic modifications affecting gene expression dynamics fix the cellular state. These modifications ensure the cellular state to be protected against external perturbation, but they also work as an epigenetic barrier to recovery of pluripotency. We show that overexpression of several genes leads to the reprogramming of cells, consistent with the methods for establishing induced pluripotent stem cells. Our model, which involves the inter-relationship between gene expression dynamics and epigenetic modifications, improves our basic understanding of cell differentiation and reprogramming

Contribution of RING domain to retrovirus restriction by TRIM5α depends on combination of host and virus

AbstractThe anti-retroviral restriction factor TRIM5α contains the RING domain, which is frequently observed in E3 ubiquitin ligases. It was previously proposed that TRIM5α restricts human immunodeficiency virus type 1 (HIV-1) via proteasome-dependent and -independent pathways. Here we examined the effects of RING domain mutations on retrovirus restriction by TRIM5α in various combinations of virus and host species. Simian immunodeficiency virus isolated from macaque (SIVmac) successfully avoided attacks by RING mutants of African green monkey (AGM)-TRIM5α that could still restrict HIV-1. Addition of proteasome inhibitor did not affect the anti-HIV-1 activity of AGM-TRIM5α, whereas it disrupted at least partly its anti-SIVmac activity. In the case of mutant human TRIM5α carrying proline at the position 332, however, both HIV-1 and SIVmac restrictions were eliminated as a result of RING domain mutations. These results suggested that the mechanisms of retrovirus restriction by TRIM5α vary depending on the combination of host and virus

Relative clause processing in Brazilian Portuguese and Japanese

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, February 1999.Includes bibliographical references (p. 120-125).This dissertation considers ambiguity resolution in regard to two issues. First, it investigates factors that lead the human parser to favour some types of interpretations over others when faced with some types of ambiguous input. Second it examines the reanalysis process that takes place when initial biases lead to incorrect interpretations. The first part of the dissertation (Chapter 1) proposes that reanalysis is a process that requires the maximal satisfaction of constraints (similar to first pass parsing as in Gibson & Pearlmutter, 1998; MacDonald, Pearlmutter & Seidenberg, 1994) rather than the minimization of the number of operations involved as has been suggested previously (Frazier, 1994; Fodor & A. Inoue, 1994). Three experiments in Japanese using main/embedded clause ambiguities are reported in support of this claim. The second part of the dissertation (Chapters 2, 3 and 4) uses a well-established generalization as a starting point, namely, that a modifying phrase is preferentially attached to the closest available site. A recent question in the literature has been to determine ways of parameterizing this principle in order to account for cross-linguistic variations observed in the attachment of relative clauses (Cuetos & Mitchell, 1988). In Chapter 2, the potential parametrizations that may explain the phenomenon at hand are restricted based on data from Brazilian Portuguese. In Chapter 3, an experiment in Japanese investigates the locality preference in this head-final language. Finally, in Chapter 4, it will be suggested that ambiguities in relative clause attachment are not only well suited to investigate cross-linguistic phenomena but also various properties of the human parser that lie beyond the realm of grammatical well-formedness, and two on-going projects are briefly described.by Edson T. Miyamoto.Ph.D

Study of Beam Profile Measurement at Interaction Point in International Linear Collider

At the international linear collider, measurement of the beam profile at the interaction point is a key issue to achieve high luminosity. We report a simulation study on a new beam profile monitor, called the pair monitor, which uses the hit distribution of the electron-positron pairs generated at the interaction point. We obtained measurement accuracies of 5.1%, 10.0%, and 4.0% for the horizontal, vertical, and longitudinal beam size, respectively, for 50 bunch crossings.Comment: 13 pages, 8 figures, 2 table