Homeostasis of naive and memory CD4+ T cells: IL-2 and IL-7 differentially regulate the balance between proliferation and Fas-mediated apoptosis

Cytokines play a crucial role in the maintenance of polyclonal naive and memory T cell populations. It has previously been shown that ex vivo, the IL-7 cytokine induces the proliferation of naive recent thymic emigrants (RTE) isolated from umbilical cord blood but not mature adult-derived naive and memory human CD4(+) T cells. We find that the combination of IL-2 and IL-7 strongly promotes the proliferation of RTE, whereas adult CD4(+) T cells remain relatively unresponsive. Immunological activity is controlled by a balance between proliferation and apoptotic cell death. However, the relative contributions of IL-2 and IL-7 in regulating these processes in the absence of MHC/peptide signals are not known. Following exposure to either IL-2 or IL-7 alone, RTE, as well as mature naive and memory CD4(+) T cells, are rendered only minimally sensitive to Fas-mediated cell death. However, in the presence of the two cytokines, Fas engagement results in a high level of caspase-dependent apoptosis in both RTE as well as naive adult CD4(+) T cells. In contrast, equivalently treated memory CD4(+) T cells are significantly less sensitive to Fas-induced cell death. The increased susceptibility of RTE and naive CD4(+) T cells to Fas-induced apoptosis correlates with a significantly higher IL-2/IL-7-induced Fas expression on these T cell subsets than on memory CD4(+) T cells. Thus, IL-2 and IL-7 regulate homeostasis by modulating the equilibrium between proliferation and apoptotic cell death in RTE and mature naive and memory T cell subsets.     

Kinetic modelling of Amadori N-(1-deoxy-D-fructos-1-yl)-glycine degradation pathways. Part II--kinetic analysis

A kinetic model for N-(1-deoxy-D-fructos-1-yl)-glycine (DFG) thermal decomposition was proposed. Two temperatures (100 and 120 degrees C) and two pHs (5.5 and 6.8) were studied. The measured responses were DFG, 3-deoxyosone, 1-deoxyosone, methylglyoxal, acetic acid, formic acid, glucose, fructose, mannose and melanoidins. For each system the model parameters, the rate constants, were estimated by non-linear regression, via multiresponse modelling. The determinant criterion was used as the statistical fit criterion. Model discrimination was performed by both chemical insight and statistical tests (Posterior Probability and Akaike criterion). Kinetic analysis showed that at lower pH DFG 1,2-enolization is favoured whereas with increasing pH 2,3-enolization becomes a more relevant degradation pathway. The lower amount observed of 1-DG is related with its high reactivity. It was shown that acetic acid, a main degradation product from DFG, was mainly formed through 1-DG degradation. Also from the estimated parameters 3-DG was found to be the main precursor in carbohydrate fragments formation, responsible for colour formation. Some indication was given that as the reaction proceeded other compounds besides DFG become reactants themselves with the formation among others of methylglyoxal. The multiresponse kinetic analysis was shown to be both helpful in deriving relevant kinetic parameters as well as in obtaining insight into the reaction mechanism.     

Hormonal changes during 17 days of head-down bed-rest

We investigated in six men the impact of 17 days of head-down bed rest (HDBR) on the daily rhythms of the hormones involved in hydroelectrolytic regulation. This HDBR study was designed to mimic a real space flight. Urine samples were collected at each voiding before, during and after HDBR. Urinary excretion of Growth Hormone (GH), Cortisol, 6 Sulfatoxymelatonin, Normetadrenaline (NMN) and Metadrenaline (NM) was determined. A decrease in urinary cortisol excretion during the night of HDBR was noted. For GH, a rhythm was found before and during HDBR. The rhythm of melatonin, evaluated with the urine excretion of 6 Sulfatoxymelatonin (aMT6S), the main hepatic metabolite, persisted throughout the experiment without any modification to the level of phase. A decrease during the night was noted for normetadrenaline urinary derivates, but only during the HDBR.     

Why are shrews so small? The costs and benefits of small size in northern temperateSorex species in the context of foraging habits and prey supply

This paper reviews the ecological advantages and disadvantages of very small body size inSorex Linnaeus, 1758 shrews living at high latitudes with cold winters. It examines the feeding and foraging habits of small and large shrews in the context of prey supply, location of winter prey sources, territory requirements, habitat exploitation and inter-specific competition. Data on feeding habits and prey availability show that the major costs of small size are a reduction in food niche breadth and prey biomass resulting from restrictions on the type and size of prey eaten, and large territory requirements. Major benefits of small size are the ability to subsist on small, numerous and accessible arthropods with high encounter rates, enabling coexistence with larger congeners and exploitation of low-productivity habitats less suitable for larger earthworm-eating species. Small size, coupled with low per capita food intake, is shown to be of special adaptive value in cold winters when food supply is restricted mostly to small arthropods, and earthworms are few.     

IGF1 receptor expression protects against microenvironmental stress found in the solid tumor

The insulin-like growth factor 1 receptor (IGF1R) is a tyrosine kinase, transmembrane receptor expressed in most body tissues and required for normal growth of cells. In cell culture, overexpression of the receptor has been shown to promote transformation and enhance cell survival in response to selected cytotoxic agents. As tumors develop, abnormalities in vascularization lead to a heterogeneous environment that includes areas of hypoxia, low pH and low glucose. Here we report that the overexpression of the IGF1R promotes increased survival in cells exposed to hypoxia, low pH and low glucose. Furthermore, cells lacking the receptor due to targeted disruption of the IGF1R gene do not survive as well as normal cells in such conditions. In addition, we find that cells can activate the IGF1R gene promoter in response to these conditions, and immunoblot analyses show increased receptor protein levels in cell exposed to hypoxia. Our results suggest a pathway of cancer cell adaptation to the tumor microenvironment in which conditions of the environment may induce expression of IGF1R, and this subsequent overexpression of the receptor may increase cell survival in such conditions.