Seasonal hibernation in mammals is under a unique adaptation system that protects organisms from various harmful events, such as lowering of body temperature (Tb), during hibernation. However, the precise factors controlling hibernation remain unknown. We have previously demonstrated a decrease in hibernation-specific protein (HP) complex in the blood of chipmunks during hibernation. Here, HP is identified as a candidate hormone for hibernation. In chipmunks kept in constant cold and darkness, HP is regulated by an individual free-running circannual rhythm that correlates with hibernation. The level of HP complex in the brain increases coincident with the onset of hibernation. Such HP regulation proceeds independently of Tb changes in constant warmth, and Tb decreases only when brain HP is increased in the cold. Blocking brain HP activity using an antibody decreases the duration of hibernation. We suggest that HP, a target of endogenously generated circannual rhythm, carries hormonal signals essential for hibernation to the brain.

Phospholipids of many cold-tolerant organisms have been reported to contain more unsaturated fatty acids than cold-susceptible organisms, a phenomenon known to maintain membrane fluidity at low temperature. However, we have obtained results to the contrary through a comparison of the membrane phospholipids of six temperate and subtropical species belonging to the Drosophila melanogaster species group. With enhancement of cold tolerance, the percentages of monoenoic acids increased but the percentages of dienoic acids decreased, that is, the number of double bonds in the phospholipid decreased without a marked variation in the percentages of unsaturated fatty acids. Concomitantly, the percentage of fatty acids containing 16 carbon atoms increased, while that of fatty acids with 18 carbon atoms decreased. Since phosphatidylethanolamine is a dominant phospholipid in Drosophila, these changes probably contribute to keeping the homeoviscosity of the cellular membranes in a manner different to that in phosphatidylcholine-rich membranes, thereby increasing cold tolerance.Keywords : Drosophila ; cold tolerance; phosphatidylethanolamine-rich membrane; unsaturated fatty acid ; chain length of fatty acid.Colonisation in temperate or arctic regions would not have 1992; Giorgione et al., 1995). In the present study, using six species related to Drosophila melanogaster, we examined the been successful if organisms had not evolved a mechanism for cold tolerance to cope with severe winters. However, biochemi-qualitative changes in phospholipids associated with the acquisition of cold tolerance. cal and molecular mechanisms for cold tolerance are not yet well understood. In insects, it is well known that overwintering individuals accumulate low-molecular-mass cryoprotectants, such as glycerol, sorbitol, inositol, or trehalose, which provide MATERIALS AND METHODS colligative depression of freezing and supercooling points and Animals. The six experimental species were classified into also stabilise the native state of proteins or membranes to prethree groups according to their distributions ( Fig. 1) and cold vent denaturation as a consequence of low temperature (for rehardiness (Kimura, 1988): cool-temperate (Drosophila subauraviews see Lee et al., 1986; Lee, 1991; Storey and Storey, 1991). ria, D. biauraria and D. triauraria), warm-temperate (D. rufa However, the accumulation of cryoprotectants is not the only and D. lutescens) and subtropical species (D. takahashii). Except mechanism for cold tolerance. In fact, we have reported that for their subtropical populations, the cool-temperate species encool-temperate, warm-temperate and subtropical species of Droter deep reproductive diapause in response to short day lengths sophila accumulate trehalose in late autumn, but its level does for overwintering, while the warm-temperate species enter shalnot correlate with the extent of their cold tolerance (Kimura et low reproductive diapause (Kimura, 1988). The subtropical popal., 1992). Another plausible hypothesis is that maintaining t...

The mammalian translation initiation factor 4A (eIF4A) is a prototype member of the DEAD-box RNA helicase family that couples ATPase activity to RNA binding and unwinding. In the crystal form, eIF4A has a distended "dumbbell" structure consisting of two domains, which probably undergo a conformational change, on binding ATP, to form a compact, functional structure via the juxtaposition of the two domains. Moreover, additional conformational changes between two domains may be involved in the ATPase and helicase activity of eIF4A. The molecular basis of these conformational changes, however, is not understood. Here, we generated RNA aptamers with high affinity for eIF4A by in vitro RNA selection-amplification. On binding, the RNAs inhibit ATP hydrolysis. One class of RNAs contains members that exhibit dissociation constant of 27 nM for eIF4A and severely inhibit cap-dependent in vitro translation. The binding affinity was increased on Arg substitution in the conserved motif Ia of eIF4A, which probably improves a predicted arginine network to bind RNA substrates. Selected RNAs, however, failed to bind either domain of eIF4A that had been split at the linker site. These findings suggest that the selected RNAs interact cooperatively with both domains of eIF4A, either in the dumbbell or the compact form, and entrap it into a dead-end conformation, probably by blocking the conformational change of eIF4A. The selected RNAs, therefore, represent a new class of specific inhibitors that are suitable for the analysis of eukaryotic initiation, and which pose a potential therapeutic against malignancies that are caused by aberrant translational control.

No abstract

Intelectin is an extracellular animal lectin found in chordata. Although human and mouse intelectin-1 recognize galactofuranosyl residues included in cell walls of various microorganisms, the physiological function of mammalian intelectin had been unclear. In this study, we found that human intelectin-1 was a serum protein and bound to Mycobacterium bovis bacillus Calmette-Guérin (BCG). Human intelectin-1-binding to BCG was inhibited by Ca(2+)-depletion, galactofuranosyl disaccharide, ribose, or xylose, and was dependent on the trimeric structure of human intelectin-1. Although monomeric, mouse intelectin-1 bound to BCG, with its C-terminal region contributing to efficient binding. Human intelectin-1-transfected cells not only secreted intelectin-1 into culture supernatant but also expressed intelectin-1 on the cell surface. The cell surface intelectin-1 was not a glycosylphosphatidylinositol-anchored membrane protein. Intelectin-1-transfected cells captured BCG more than untransfected cells, and the BCG adherence was inhibited by an inhibitory saccharide of intelectin-1. Intelectin-1-preincubated cells took up BCG more than untreated cells, but the adhesion of intelectin-1-bound BCG was the same as that of untreated BCG. Mouse macrophages phagocytosed BCG more efficiently in medium containing mouse intelectin-1 than in control medium. These results indicate that intelectin is a host defense lectin that assists phagocytic clearance of microorganisms.