Adaptive Response of a Gene Network to Environmental Changes by Fitness-Induced Attractor Selection

Cells switch between various stable genetic programs (attractors) to accommodate environmental conditions. Signal transduction machineries efficiently convey environmental changes to the gene regulation apparatus in order to express the appropriate genetic program. However, since the number of environmental conditions is much larger than that of available genetic programs so that the cell may utilize the same genetic program for a large set of conditions, it may not have evolved a signaling pathway for every environmental condition, notably those that are rarely encountered. Here we show that in the absence of signal transduction, switching to the appropriate attractor state expressing the genes that afford adaptation to the external condition can occur. In a synthetic bistable gene switch in Escherichia coli in which mutually inhibitory operons govern the expression of two genes required in two alternative nutritional environments, cells reliably selected the “adaptive attractor” driven by gene expression noise. A mathematical model suggests that the “non-adaptive attractor” is avoided because in unfavorable conditions, cellular activity is lower, which suppresses mRNA metabolism, leading to larger fluctuations in gene expression. This, in turn, renders the non-adaptive state less stable. Although attractor selection is not as efficient as signal transduction via a dedicated cascade, it is simple and robust, and may represent a primordial mechanism for adaptive responses that preceded the evolution of signaling cascades for the frequently encountered environmental changes

Inhibitory Receptors Are Expressed by Trypanosoma cruzi-Specific Effector T Cells and in Hearts of Subjects with Chronic Chagas Disease

We had formerly demonstrated that subjects chronically infected with Trypanosoma cruzi show impaired T cell responses closely linked with a process of T cell exhaustion. Recently, the expression of several inhibitory receptors has been associated with T cell dysfunction and exhaustion. In this study, we have examined the expression of the cytotoxic T lymphocyte antigen 4 (CTLA-4) and the leukocyte immunoglobulin like receptor 1 (LIR-1) by peripheral T. cruzi antigen-responsive IFN-gamma (IFN-γ)-producing and total T cells from chronically T. cruzi-infected subjects with different clinical forms of the disease. CTAL-4 expression was also evaluated in heart tissue sections from subjects with severe myocarditis. The majority of IFN-γ-producing CD4+ T cells responsive to a parasite lysate preparation were found to express CTLA-4 but considerably lower frequencies express LIR-1, irrespective of the clinical status of the donor. Conversely, few IFN-γ-producing T cells responsive to tetanus and diphtheria toxoids expressed CTLA-4 and LIR-1. Polyclonal stimulation with anti-CD3 antibodies induced higher frequencies of CD4+CTAL-4+ T cells in patients with severe heart disease than in asymptomatic subjects. Ligation of CTLA-4 and LIR-1 with their agonistic antibodies, in vitro, reduces IFN-γ production. Conversely, CTLA-4 blockade did not improved IFN-γ production in response to T. cruzi antigens. Subjects with chronic T. cruzi infection had increased numbers of CD4+LIR-1+ among total peripheral blood mononuclear cells, relative to uninfected individuals and these numbers decreased after treatment with benznidazole. CTLA-4 was also expressed by CD3+ T lymphocytes infiltrating heart tissues from chronically infected subjects with severe myocarditis. These findings support the conclusion that persistent infection with T. cruzi leads to the upregulation of inhibitory receptors which could alter parasite specific T cell responses in the chronic phase of Chagas disease

Electrically controlled light scattering from thermoreversible liquid-crystal gels

Thermoreversible gels of the liq.-crystal LC-E7 with 1,3:2,4-Di-O-benzylidene-D-sorbitol (DBS) form white light-scattering films that are reversibly switchable to a clear state by ac elec. fields. The light scattering by the gelled films is an intrinsic material property that originates in the phase diagram of the system displaying a monotectic-type equil. (\"mesotectic\") among a liq., a solid, and a mesophase at extremely low concns. of DBS. Electrooptical characteristics and demonstrated viscoelastic behavior of the films produced indicate the applicability of DBS/LC-E7 in large area scattering-based flat panel displays and projection systems. [on SciFinder (R)

CTLA-4 (CD152) expression in peripheral blood T cells in Kawasaki disease

Kawasaki disease (KD) is an acute febrile illness of early childhood caused by vasculitis. Whether or not peripheral blood T cells are activated in acute KD remains uncertain, as some reports have presented evidence of peripheral blood T cell activation, whereas others suggest that the level of peripheral blood T cell activation is low during acute KD. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4, CD152) is a surface molecule of activated T cells. We therefore investigated intracellular CTLA-4 expression in the peripheral blood T cells of patients with acute KD as a marker of T cell activation. We collected blood samples from 20 patients with KD and six with Epstein–Barr virus infectious mononucleosis (EBV-IM) who were admitted to our hospital, as well as 13 healthy children. We determined the intracellular expression of CTLA-4 in T cells by flow cytometry. We demonstrated that the intracellular expression of CTLA-4 is up-regulated in peripheral blood CD3(+) T cells, CD4(+) T cells and CD8(+) T cells at the early part of the acute stage in KD. However, the mean percentages of intracellular T cells expressing CTLA-4 in EBV-IM patients were about fourfold higher than those in T cells from patients with acute KD. Our results suggested that the level of activation of peripheral blood T cells is very low during acute KD