A neuronal ryanodine receptor mediates light-induced phase delays of the circadian clock

Circadian clocks are complex biochemical systems that cycle with a period of approximately 24 hours. They integrate temporal information regarding phasing of the solar cycle, and adjust their phase so as to synchronize an organism's internal state to the local environmental day and night. Nocturnal light is the dominant regulator of this entrainment. In mammals, information about nocturnal light is transmitted by glutamate released from retinal projections to the circadian clock in the suprachiasmatic nucleus of the hypothalamus. Clock resetting requires the activation of ionotropic glutamate receptors, which mediate Ca2+ influx. The response induced by such activation depends on the clock's temporal state: during early night it delays the clock phase, whereas in late night the clock phase is advanced. To investigate this differential response, we sought signalling elements that contribute solely to phase delay. We analysed intracellular calcium-channel ryanodine receptors, which mediate coupled Ca2+ signalling. Depletion of intracellular Ca2+ stores during early night blocked the effects of glutamate. Activators of ryanodine receptors induced phase resetting only in early night; inhibitors selectively blocked delays induced by light and glutamate. These findings implicate the release of intracellular Ca2+ through ryanodine receptors in the light-induced phase delay of the circadian clock restricted to the early night.     

Direct synthesis of hydrogen peroxide from H2 and O2 using zeolite-supported Au-Pd catalysts

The direct synthesis of hydrogen peroxide from H₂ and O₂ using zeolite-supported Au-Pd catalysts is described using two zeolites, ZSM-5 and zeolite Y, using an impregnation method of preparation. The addition of Pd to Au for these catalysts significantly enhances the productivity for hydrogen peroxide. The use of zeolites as a support for Au-Pd gives higher rates of hydrogen peroxide formation when compared with alumina-supported Au catalysts prepared using a similar method. The addition of metals other than Pd is also investigated, but generally Au-Pd catalysts give the highest activity for the synthesis of hydrogen peroxide. The addition of Ru and Rh have no significant effect, but the addition of Pt does enhance the activity for the selective formation of hydrogen peroxide.     

Traffic of dynamin within individual Drosophila synaptic boutons relative to compartment-specific markers

Presynaptic terminals contain several specialized compartments, which have been described by electron microscopy. We show in an identified Drosophila neuromuscular synapse that several of these compartments-synaptic vesicle clusters, presynaptic plasma membrane, presynaptic cytosol, and axonal cytoskeleton-labeled by specific reagents may be resolved from one another by laser scanning confocal microscopy. Using a panel of compartment-specific markers and Drosophila shibire(ts1) mutants to trap an intermediate stage in synaptic vesicle recycling, we have examined the localization and redistribution of dynamin within single synaptic varicosities at the larval neuromuscular junction. Our results suggest that dynamin is not a freely diffusible molecule in resting nerve terminals; rather, it appears localized to synaptic sites by association with yet uncharacterized presynaptic components. In shi(ts1) nerve terminals depleted of synaptic vesicles, dynamin is quantitatively redistributed to the plasma membrane. It is not, however, distributed uniformly over presynaptic plasmalemma; instead, fluorescence images show "hot spots" of dynamin on the plasma membrane of vesicle-depleted nerve terminals. We suggest that these dynamin-rich domains may mark the active zones for synaptic vesicle endocytosis first described at the frog neuromuscular junction.     

Glucocorticoids and aging

In this review we analyze the morphologic changes, hypothalamic-pituitary-adrenal (HPA) axis functions, glucocorticoid (GC) receptors, and steroidogenic enzyme activities in both animals and humans during aging. In rodent studies, older animals tend to show: 1) hypertrophy of adrenal zona fasciculata (ZF) cells; 2) neuronal loss in the hypothalamic area; 3) loss of GC receptors in the hippocampus; 4) raised circulating adrenocorticotropic hormone (ACTH) and GC levels, and increased release of corticotropin-releasing hormone from the hypothalamus; 5) reduced suppression of endogenous GC secretion after administration of dexamethasone; 6) decreased attenuation of response to chronic stress; and 7) increased activity of P450scc and 21-hydroxylase. According to the GC cascade hypothesis, stress and GCs facilitate the aging process in rats. Stress induces downregulation of GC receptors in the hippocampus, then impairs GC feedback on stress-induced HPA axis activation. Finally, an increase in the basal level of corticosterone and extended GC secretion following stress occurs. Because activation of the hippocampus decreases HPA axis function, the unrestrained elevation of GC concentration and the reduction in the level of GC receptors in the hippocampus may gradually weaken the feedback mechanisms and halt the response to stress. In humans, there are conflicting reports of HPA axis function during aging, so it is difficult to make a final conclusion regarding the relationship between aging and HPA axis function.     

Deformation of concrete and cement paste loaded at constant temperatures from 140 to 724°C

Constant temperature creep of unsealed pure cement paste, gravel and lightweight concretes obtained under constant uniaxial compressive load are reported for temperatures between 140°C and 724°C. The work suggests that it is possible, within certain limits, to uncouple the time, stress and temperature functions of constant high temperature creep, which can be represented mathematically by a simple multiple of the three functions. The time functions of all three mixes were best represented by a power law with an exponent slightly influenced by temperature. It is suggested that the temperature function may not be sufficiently described by the Arrhenius relation during first heating. The temperature function indicated a sharp increase in creep for gravel concrete above 350°C caused by break-up of the aggregate. However, the sharp increase in creep for both lightweight concrete and cement paste above 600°C is seated in the cement paste and appears to be a function of “current” temperature. A rheological criterion therefore limits the structural usefulness of Portland cement concretes to temperatures below 600°C. Similarities in constant high temperature creep behaviour with other materials have been noted.     

A chemometric approach to understanding the bioelimination of anionic,water‐soluble dyes by a biomass—Part 3: Direct dyes**

Using a new, rapid and robust laboratory method for assessing the bioelimination of water‐soluble dyes, the level of bioelimination of a series of direct dyes has been determined and a chemometric analysis has been conducted on the bioelimination results to correlate bioelimination with chemical structure. Bioelimination varies from 0 to 95% and correlates, for the majority of the direct dyes studied, with their size/charge ratio. The bioelimination of direct dyes is enhanced by large size/charge ratios, the presence of aromatic amino functions and extended azo (naphthalene) chromophores.     

Serum HIV-1 RNA levels and time to development of AIDS in the Multicenter Hemophilia Cohort Study

Normal women produce small amounts of active androgens. When androgen levels are elevated, such as for example in the polycystic ovary syndrome, this is followed by the development of male physical characteristics and muscle mass, structure and function as well as android adipose tissue distribution and function. Psychological features and stress reactions also seem similar to those of men. Such women have an increased risk of developing hypertension, non-insulin-dependent diabetes mellitus and cardiovascular disease. Recent data have shown that these physical, and psychological characteristics, as well as risk of ill health, are also found in the population of women selected at random. Women in the lowest quintiles of levels of sex-hormone-binding globulin--an indicator inversely related to active androgens--are at risk of developing hypertension, non-insulin-dependent diabetes mellitus and cardiovascular mortality. The mechanism probably includes muscular insulin resistance, following a relative androgen excess. It is thus apparent that androgens, even within the highest levels of the nonselected population of women, are powerful predictors of serious disease development. The population at risk might be as large as about 20% of middle-aged women. This is an area of female disease risk which requires more attention in screening and intervention procedures.     

BDNF attenuates functional and structural disorders in nerves of galactose-fed rats

Galactose intoxication of rats was used to disrupt metabolism of Schwann cells and skeletal muscle, two sites that contain the polyol-forming enzyme aldose reductase (AR). Galactose-fed rats develop a neuropathy characterized by nerve conduction deficits and axonal atrophy. To investigate the possibility that galactose metabolism by AR influences axonal function and structure by altering production of neurotrophic factors, the impact of galactose intoxication on nerve and muscle BDNF levels and the effects of exogenous BDNF treatment on galactose neuropathy were examined using biochemical, electrophysiologic and morphometric techniques. Galactose feeding increased BDNF protein in peripheral nerve and muscle. Exogenous BDNF treatment attenuated motor nerve conduction velocity deficits in the sciatic nerve of galactose-fed animals and myelin splitting of motor axons in the ventral root. In contrast, sensory nerve conduction velocity (SNCV) deficits in the sciatic nerve and myelin splitting in the central projections of sensory neurons were not prevented by BDNF treatment. BDNF treatment did not attenuate reduced axonal caliber in the sciatic nerve, but did ameliorate the diminution of the caliber of central sensory projections in the dorsal root. These findings point to the potential use of BDNF in the treatment of peripheral neuropathies.