Fos protein expression in the circadian clock is not associated with phase shifts induced by a nonphotic stimulus, triazolam

A mutant human lysozyme, designated as C77A-a, in which glutathione is bound to Cys95, has been shown to mimic an intermediate in the formation of a disulfide bond during folding of human (h)-lysozyme. Protein disulfide isomerase (PDI), which is believed to catalyze disulfide bond formation and associated protein folding in the endoplasmic reticulum, attacked the glutathionylated h-lysozyme C77A-a to dissociate the glutathione molecule. Structural analyses showed that the protein is folded and that the structure around the disulfide bond, buried in a hydrophobic core, between the protein and the bound glutathione is fairly rigid. Thioredoxin, which has higher reducing activity of protein disulfides than PDI, catalyzed the reduction with lower efficiency. These results strongly suggest that PDI can catalyze the disulfide formation in intermediates with compact structure like the native states in the later step of in vivo protein folding.     

Pharmacological study on circadian rhythms in mammals

Living organisms including humans drive circadian rhythm, and this rhythm influences the social structure and daily life of human beings. The suprachiasmatic nucleus (SCN) has been established as a pacemaker for mammalian circadian rhythm. There are many kinds of neurotransmitters and neuromodulators in this nucleus. The circadian systems are involved in oscillation, input (entrainment) and output (overt rhythm). Therefore in this review, pharmacological characteristics of circadian systems in relation to the SCN are discussed by focussing especially upon the roles of various neurotransmitters and modulators.     

Organization of the circadian system in insects

The circadian systems of different insect groups are summarized and compared. Emphasis is placed on the anatomical identification and characterization of circadian pacemakers, as well as on their entrainment, coupling, and output pathways. Cockroaches, crickets, beetles, and flies possess bilaterally organized pacemakers in the optic lobes that appear to be located in the accessory medulla, a small neuropil between the medulla and the lobula. Neurons that are immunoreactive for the peptide pigment-dispersing hormone (PDH) arborize in the accessory medulla and appear to be important components of the optic lobe pacemakers. The neuronal architecture of the accessory medulla with associated PDH-immunoreactive neurons is best characterized in cockroaches, while the molecular machinery of rhythm generation is best understood in fruit flies. One essential component of the circadian clock is the period protein (PER), which colocalizes with PDH in about half of the fruit fly's presumptive pacemaker neurons. PER is also found in the presumptive pacemaker neurons of beetles and moths, but appears to have different functions in these insects. In moths, the pacemakers are situated in the central brain and are closely associated with neuroendocrine functions. In the other insects, neurons associated with neuroendocrine functions also appear to be closely coupled to the optic lobe pacemakers. Some crickets and flies seem to possess central brain pacemakers in addition to their optic lobe pacemakers. With respect to neuronal organization, the circadian systems of insects show striking similarities to the vertebrate circadian system.     

A nonphotic stimulus inverts the diurnal-nocturnal phase preference in Octodon degus

Mechanisms differentiating diurnal from nocturnal species are thought to be innate components of the circadian timekeeping system and may be located downstream from the circadian pacemaker within the suprachiasmatic nucleus (SCN) of the hypothalamus. In the present study, we found that the dominant phase of behavioral activity and body temperature (Tb) is susceptible to modification by a specific modality of behavioral activity (wheel-running activity) in Octodon degus, a mammal that exhibits multiple chronotypes. Seven Octodon degus exhibited diurnal Tb and locomotor activity (LMA) circadian rhythms while entrained to a 24 h light/dark cycle (LD 12:12). When the diurnal animals were provided unrestricted access to a running wheel, the overt daily rhythms in these animals inverted to nocturnal. This nocturnal pattern was sustained in constant darkness and returned to diurnal after removal of the running wheel. Six additional animals exhibited nocturnal chronotypes in LD 12:12 regardless of access to running wheels. Wheel-running activity inverted the phase preference in the diurnal animals without changing the 24 hr mean LMA or Tb levels. Because wheel running did not increase the amplitude of the pre-existing diurnal pattern, simple masking effects on LMA and Tb cannot explain the rhythm inversion. The diurnal-nocturnal inversion occurred without reversing crepuscular-timed episodes of activity, suggesting that diurnal or nocturnal phase preference is controlled separately from the intrinsic timing mechanisms within the SCN and can be dependent on behavioral or environmental factors.     

Sex differentiation of t-e circadian system in the golden hamster

The effect of estradiol benzoate (EB) on free-running circadian activity rhythms was studied in gonadectomized hamsters maintained in constant dim illumination. EB shortened the period (tau) of the female, but not of the male circadian activity rhythm. Responsiveness of the circadian system to EB was subject to sexual differentiation. The circadian period of wheel running by female hamsters given a single injection of testosterone propionate on the day of birth did not shorten in response to EB in adulthood. This failure to respond to EB also was observed in normal male hamsters, and was different from the response shown by normal females. Preliminary data suggest that tau of the activity rhythm of males castrated on the day of birth is shortened during EB treatment in adulthood. The differential effects of estradiol on tau are related to anatomic differences between the sexes in neural connections of the substrate for circadian rhythms.     

Vitamin B2-based blue-light photoreceptors in the retinohypothalamic tract as the photoactive pigments for setting the circadian clock in mammals

In mammals the retina contains photoactive molecules responsible for both vision and circadian photoresponse systems. Opsins, which are located in rods and cones, are the pigments for vision but it is not known whether they play a role in circadian regulation. A subset of retinal ganglion cells with direct projections to the suprachiasmatic nucleus (SCN) are at the origin of the retinohypothalamic tract that transmits the light signal to the master circadian clock in the SCN. However, the ganglion cells are not known to contain rhodopsin or other opsins that may function as photoreceptors. We have found that the two blue-light photoreceptors, cryptochromes 1 and 2 (CRY1 and CRY2), recently discovered in mammals are specifically expressed in the ganglion cell and inner nuclear layers of the mouse retina. In addition, CRY1 is expressed at high level in the SCN and oscillates in this tissue in a circadian manner. These data, in conjunction with the established role of CRY2 in photoperiodism in plants, lead us to propose that mammals have a vitamin A-based photopigment (opsin) for vision and a vitamin B2-based pigment (cryptochrome) for entrainment of the circadian clock.     

Three period homologs in mammals: differential light responses in the suprachiasmatic circadian clock and oscillating transcripts outside of brain

We have cloned and characterized the mouse cDNA of a third mammalian homolog of the Drosophila period gene and designated it mPer3. The mPER3 protein shows approximately 37% amino acid identity with mPER1 and mPER2 proteins. The three mammalian PER proteins share several regions of sequence homology, and each contains a protein dimerization PAS domain. mPer3 RNA levels oscillate in the suprachiasmatic nuclei (SCN) and eyes. In the SCN, mPer3 RNA levels are not acutely altered by light exposure at different times during subjective night. This contrasts with the acute induction by light of mPer1 and mPer2 RNA levels during early and late subjective night. mPer3 is widely expressed in tissues outside of brain. In liver, skeletal muscle, and testis, mPer RNAs exhibit prominent, synchronous circadian oscillations. The results highlight the differential light responses among the three mammalian Per genes in the SCN and raise the possibility of circadian oscillators in mammals outside of brain and retina.     

Features of the parasitic system of Ixodid ticks--Borrelia--small mammals in the Russian Northwest

BACKGROUND AND AIMS: Long-term treatment with H(+)-K(+)-adenotriphosphatase (ATPase) inhibitors, such as omeprazole or lansoprazole, for severe gastroesophageal reflux disease is now widely used. Whether such treatment will result in vitamin B12 deficiency is controversial. We studied whether long-term treatment with omeprazole alters serum vitamin B12 levels in patients with Zollinger-Ellison syndrome. METHODS: In 131 consecutive patients treated with either omeprazole (n = 111) or histamine H2-receptor antagonists (n = 20), serum vitamin B12 and folate levels and complete blood counts were determined after acid secretion had been controlled for at least 6 months. These studies were repeated yearly. Serum vitamin B12 and folate levels were correlated with the type of antisecretory drug and the extent of inhibition of acid secretion. RESULTS: The mean duration of omeprazole treatment was 4.5 years, and for H2-receptor antagonists 10 years. Vitamin B12 levels, but not serum folate levels or any hematological parameter, were significantly (P = 0.03) lower in patients treated with omeprazole, especially those with omeprazole-induced sustained hyposecretion (P = 0.0014) or complete achlorhydria (P < 0.0001). In 68 patients with two determinations at least 5 years apart, vitamin B12 levels decreased significantly (30%; P = 0.001) only in patients rendered achlorhydric. The duration of omeprazole treatment was inversely correlated with vitamin B12 levels (P = 0.013), but not folate levels. Eight patients (6%) developed subnormal B12 levels during follow-up. CONCLUSIONS: Long-term omeprazole treatment leads to significant decreases in serum vitamin B12 but not folate levels. These results suggest patients with Zollinger-Ellison syndrome treated with H(+)-K(+)-ATPase inhibitors should have serum vitamin B12 levels monitored. Furthermore, these results raise the possibility that other patients treated chronically with H(+)-K(+)-ATPase inhibitors may develop B12 deficiency.     

Fluvial Entrainment of Protruding Fractured Rock

Fluvial entrainment of fractured rock assessed in terms of bed shear stress, stream power, and time-averaged bed uplift pressures indicates that rock-block stability reduces with increasing protrusion and decreasing surface length (in the direction of flow), with protrusion of only a nominal portion of the block required to significantly decrease block stability. Variations in block uplift pressure coefficient with normalized block protrusion and block surface length can be used to predict the height of a block (of protrusion P and known surface lengths) at the point of entrainment for an open-channel flow (of average depth h and velocity U). Alternatively, entrainment of prismoidal particles of square section in plan by fully turbulent open-channel flows (of R?>100) can be predicted using (θC?0.002) = 0.0015?(Pvb/L)?1, where θC is the critical dimensionless shear stress, R? is the grain Reynolds number, L is the particle upper-surface side length, and Pvb is the particle protrusion relative to the virtual-bed level at which the average flow velocity is zero (approximately the tops of the supporting or surrounding particles for the present prismoidal blocks). Owing to the potential occurrence of cavitation on prototype block surfaces, it is recommended that quantitative scaling of the present results be conservatively limited to prototype average velocities (U) of less than approximately 6 m/s (with scale ratios λU2 = λL = 29). In contrast to existing practice, particle protrusion needs to be accounted for when assessing the erodibility of a channel bed using stream-power-based methods such as the erodibility index method reported by Annandale in 1995.     

Characterization of the circadian system of NGFI-A and NGFI-A/NGFI-B deficient mice

Maintenance of a cytoplasmic redox balance is a necessity for sustained cellular metabolism. Glycerol formation is the only way by which Saccharomyces cerevisiae can maintain this balance under anaerobic conditions. Aerobically, on the other hand, several different redox adjustment mechanisms exist, one of these being the glycerol 3-phosphate (G3P) shuttle. We have studied the importance of this shuttle under aerobic conditions by comparing growth properties and glycerol formation of a wild-type strain with that of gut2 delta mutants, lacking the FAD-dependent glycerol 3-phosphate dehydrogenase, assuming that the consequent blocking of G3P oxidation is forcing the cells to produce glycerol from G3P. To impose different demands on the redox adjustment capability we used various carbon sources having different degrees of reduction. The results showed that the shuttle was used extensively with reduced substrate such as ethanol, whereas the more oxidized substrates lactate and pyruvate, did not provoke any activity of the shuttle. However, the absence of a functional G3P shuttle did not affect the growth rate or growth yield of the cells, not even during growth on ethanol. Presumably, there must be alternative systems for maintaining a cytoplasmic redox balance, e.g. the so-called external NADH dehydrogenase, located on the outer side of the inner mitochondrial membrane. By comparing the performance of the external NADH dehydrogenase and the G3P shuttle in isolated mitochondria, it was found that the former resulted in high respiratory rates but a comparably low P/O ratio of 1.2, whereas the shuttle gave low rates but a high P/O ratio of 1.7. Our results also demonstrated that of the two isoforms of NAD-dependent glycerol 3-phosphate dehydrogenase, only the enzyme encoded by GPD1 appeared important for the shuttle, since the enhanced glycerol production that occurs in a gut2 delta strain proved dependent on GPD1 but not on GPD2.     

Entrainment of Particles into Flotation Froths

Abstract

Papers on entrainment in conventional froth flotation are reviewed and the results related to the structure of froths and their water content. The strong correlation observed between the recovery of gangue and the recovery of water, in both batch and continuous tests, is discussed and compared with the effect of water recovery on the recovery of hydrophobic (valuable) particles. Data on the structure and water content of flotation froths is summarized and an explanation sought for the way in which water, and hence entrained particles, are transported from pulp to froth column to concentrate.     

Snow Entrainment Coefficient Estimated by Field Observations and Wind Tunnel Experiments

The boundary condition for concentration of snow particles at the bed is necessary to calculate snowdrifts by a numerical analysis model. The flux type or the gradient type boundary conditions are reasonable. An idea of an entrainment coefficient of snow particle at the snow surface is useful. The values of the coefficient are considered to be a function of the density and viscosity of the working fluid and the properties of snow particles. In this paper, the values of the coefficient are estimated based on the k–ε turbulence model and the distribution of snow particle flux observed at the Mizuho Station, Antarctica in 2000, assuming the steady, fully developed flow over a flat snow surface. The snow entrainment coefficient is two or three orders smaller than the sand entrainment coefficient in a river. The reason is that the specific weight of snow particles in air is much larger than that of sand particles in water.     

转炉出钢过程中涡流卷渣的数值模拟研究

为了提高转炉出钢挡渣效率,改善钢水质量,需要研发出更高效低耗的新型挡渣方法。利用CFD流体模拟软件Fluent6.3,通过基于压力的分离隐式求解器,采用k-ε双方程模拟出炉内钢液不同初始液位下静态出钢过程。通过对出钢过程的流场分析,从数学模拟的角度阐述了初始液位不同高度下的漩涡形成时间、漩涡的运动轨迹、出钢过程转炉内钢液的运动特征,针对涡流引起卷渣现象的研究,为今后研制新型挡渣方法提供了理论指导。     

Effects of the scheduling of meal-feeding at different phases of the circadian system in rats

This study was designed to determine whether or not a number of diverse rhythmic variables in the rat could be synchronized to meal timing. This was tested by restricting the availability of food; once during each 24-hour period an unrestricted quantity of food was made available for a 4-hour period to four different groups at different phases of the light-dark cycle, and the rhythms of the variables studied in the different groups were compared. Liver glycogen and serum glucose did synchronize to or were strongly influenced by feeding schedules; corticosterone and the several enzymes measured seemed to reflect an interaction of both the restricted feeding schedule and the light-dark cycle. The mitotic index in the corneal epithelium in all groups remained remarkably synchronized to the light-dark cycle and was altered only minimally by restricted meal timing. All groups on restricted feeding schedules gained less weight than the group fed ad libitum and maintained on a light-dark cycle. These studies caution against assuming that all body functions react in the same manner to different synchronizers; and they emphasize that one must not generalize about the synchronizing effect of meal-timing or even the light-dark cycle.     

Maternal entrainment of the developing circadian system in the Siberian hamster (Phodopus sungorus)

The aim of these studies was to investigate maternal entrainment of developing circadian locomotor activity rhythms in the Siberian hamster. In Experiment 1, mothers were transferred from a 16:8 LD cycle into constant dim red light (DD) from the day of parturition, and wheel-running activity of the mother and pups was individually monitored from the time of weaning. The phases of the individual pups' rhythms were found to be synchronized both to the phase of the mother and to the phase of lights off (ZT 12) of the photo cycle that the mother was exposed to until the day of parturition. To investigate whether this synchrony might reflect direct effects of light acting upon the fetal circadian system in late gestation, the experiment was repeated but with mothers placed into DD early in pregnancy (< or = day 7 of gestation). The results were similar to the first study, suggesting that the mother rather than the photo cycle during the latter part of gestation entrains the developing circadian system. The third experiment investigated whether this entrainment occurred during the postnatal period. Breeding pairs were maintained on alternative light-dark cycles, LD and DL, that were 12 h out of phase. Litters born to mothers on one light-dark cycle were exchanged on the day of birth with foster mothers from the reversed light-dark cycle, then raised in DD. Control litters exchanged between mothers from the same light-dark cycle had similar litter synchrony as shown by nonfostered litters of Experiment 1. However, pups cross-fostered with mothers on reversed LD cycles showed a very different distribution of pup phases. Pups were not synchronized to their natural mother but to their foster mother. Moreover, pups were more scattered over the 24-h period and were found to be significantly synchronized to the phase of the reversed LD cycle. These results demonstrate the occurrence of postnatal entrainment in the Siberian hamster. The increased scatter produced by the cross-fostering paradigm results from some litters being completely entrained to the phase of the foster mother, some with an intermediate distribution between the phase of the natural and foster mothers, and a minority being associated with the phase of the natural mother. These results suggest that Siberian hamster pups are initially synchronized either prenatally or at birth but that the mother continues to provide entrainment signals during the postnatal period.     

Aminopeptidases in the mammals

The BAX system for screening Salmonella is one of the first commercial PCR-based systems for the detection of food-borne pathogens. It is able to give a confirmed result within 28 h. There was 98.6% and 95.8% agreement between the BAX system and conventional cultural analysis for the detection of Salmonella in artificially inoculated and uninoculated food samples, respectively. In both cases, the BAX system generated more positive detections than cultural analysis. The speed of assay, case of use and high specificity and sensitivity of the BAX system for the detection of food-borne Salmonella make it an attractive method for routine food microbiology laboratories.     

Near-Bed Turbulence Characteristics at the Entrainment Threshold of Sediment Beds

This experimental study is devoted to quantification of the near-bed turbulence characteristics at an entrainment threshold of noncohesive sediments. Near the bed, the departure in the distributions of the observed time-averaged streamwise velocity from the logarithmic law is more for immobile beds than for entrainment-threshold beds. In the Reynolds shear stress distributions, a damping that occurs near the bed for sediment entrainment is higher than that for immobile beds. Quadrant analysis reveals that in the near-bed flow zone, ejections and sweeps on immobile beds cancel each other, giving rise to the outward interactions, whereas sweeps are the dominant mechanism toward sediment entrainment. The bursting duration for entrainment-threshold beds is smaller than that for immobile beds. On the other hand, the bursting frequency for entrainment-threshold beds is larger than that for immobile beds. The third-order correlations indicate that during sediment entrainment, a streamwise acceleration associated with a downward flux and advection of streamwise Reynolds normal stress is prevalent. The streamwise and the downward vertical fluxes of turbulent kinetic energy (TKE) increase with sediment entrainment. The TKE budget proves that for sediment entrainment, the pressure energy diffusion changes drastically to a negative magnitude, indicating a gain in turbulence production.     

Olfactory cues mediate food selection by young chicks

An illness-induced aversion paradigm was used to assess the possible influence of olfactory cues on food selection by young chicks. At 2-3 days posthatching, chicks were exposed briefly to food scented with a novel odor (orange) followed by an injection of LiCl or saline. LiCl-injected chicks subsequently displayed stronger avoidance of orange-scented food than did the controls. Chicks in a second experiment were preexposed to novel-scented food, then either injected with LiCl or not injected. The LiCl chicks, but not the controls, later avoided food associated with the preexposure odor (relative to food treated with an unfamiliar odorant). Two- to three-day-old chicks are capable of associating specific food odors with negative consequences and modify their feeding behavior as a function of such experience.