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Visualization of anisotropic pulsations in extraembryonic compartments of incubated quail eggs by NMR microimaging.

Multi-plane tagging time-of-flight and bipolar gradient phase-encoding and amplitude-weighting NMR microimaging techniques have been employed to study transport in extraembryonic compartments of fertilized quail eggs during the first seven days of incubation. After the fourth day coherent and incoherent motions became visible in certain regions, in particular in the upper part of the albumen. Coherent motions as visualized by deformations of multiplane tagging grids were specified by local velocities less than 1 mm/s at most. On the other hand, incoherent motions led to much more pronounced phenomena. The multiplane tagging grid completely faded in a region comprising the upper third of the albumen after 4.5 incubation days. Images weighted by signal attenuation owing to incoherent displacements indicate motions in the same region. The fact that a reproducible localization of the motions is only possible when signals from different transients are averaged indicates that the incoherence at least partly is temporal in nature. The signal intensity of a volume selected in the incoherent-motion region consequently fluctuates with time. The Fourier analysis of these fluctuations revealed a distinct pulsation with a frequency of 0.4 Hz.

Animals↗

Role of soil freezing events in interannual patterns of stream chemistry at the Hubbard Brook Experimental Forest, New Hampshire.

Soil freezing is a disturbance of the below ground environment, potentially resulting in increased losses of NO3- and surface water acidification. Here, we report the effects of soil freezing on interannual variation in stream chemistry at the Hubbard Brook Experimental Forest, New Hampshire. Data from 1970 to 1997 of soil frost depth, snow cover, precipitation, air temperature, and stream discharge and chemistry were used in a stepwise linear regression model to select the variables that best predicted deviations of annual stream concentrations from 4-year running averages. Variables quantifying soil freezing severity were selected as significant predictors of short-term fluctuations in stream K+, NO3-, Ca2+, and Mg2+ concentrations from 1970 to 1989, explaining 59 and 47% of the short-term variability in K+ and NO3-, respectively. Fine-root mortality and disturbance of root-soil-microbe interactions, with subsequent effects on decomposition and nutrient uptake, likely contributed to the mobilization of K+ and NO3- to streamwater following severe soil freezing events. The relationship between soil freezing and stream chemistry, however, weakened during the period 1990-1997. Because soil freezing has had inconsistent effects on stream chemistry during the period 1970-1997, it is unclear whether future changes in the frequency, duration, and depth of soil freezing events as the result of changes in the snow cover regime under a warmer climate will have significant impacts on the losses of NO3- and nutrient-base cations from temperate northern ecosystems.

Climate↗

DNA deformability at the base pair level.

A complete set of harmonic force constants describing the DNA deformation energetics at the base pair level was obtained using unrestrained atomic-resolution molecular dynamics simulations of selected duplex oligonucleotides and subsequent analysis of structural fluctuations from the simulated trajectories. The deformation was described by the six base pair conformational parameters (buckle, propeller, opening, shear, stretch, stagger). The results for 13 AT pairs and 11 GC pairs in different sequence contexts suggest that buckle and propeller are very flexible (more than roll in TA dinucleotide steps), while stretch is exceptionally stiff. Only stretch and opening stiffness were found to depend unambiguously on the base pair identity (AT vs GC). The relationship of the results to a simple plates-and-springs model of base-base interactions is discussed.

Base Pairing↗

Hardness, softness, and the fukui function in the electronic theory of metals and catalysis.

The concepts of hardness eta = (2E/N2)nu and fukui function f(r) = [rho (r)/N]nu, which have recently been associated with the theory of chemical reactivity in molecules, are extended to the theory of metals. It is shown that at T = 0, 1/eta = g(epsilon F) and f(r) = g(epsilon F, r)/g(epsilon F), where g(epsilon F), and g(epsilon F, r) are the density of states and the local density of states, at the Fermi energy epsilon F. Softness S and local softness s(r) are defined as 1/eta and Sf(r), respectively, and it is shown that (formula; see text) where the averages are over a grand canonical ensemble. It is pointed out that the postulate that f(r) or g(epsilon F, r) determines site selectivity for metals in chemisorption and catalysis is synonymous with the recent argument by Falicov and Somorjai [Falicov, L. M. & Somorjai, G. A. (1985) Proc. Natl. Acad. Sci. USA 82, 2207-2211] that such selectivity is determined by low-energy density fluctuations.

Chemical Phenomena↗

Pregnancy-related steroids are potential negative regulators of B lymphopoiesis.

B lymphopoiesis is selectively suppressed in normal pregnant mice, suggesting that fluctuations in systemic hormone levels might influence local events within bone marrow. This has now been tested by sustained experimental elevation of sex steroids by hormone-containing pellet implants. We found that while numbers of total nucleated cells declined after treatment with estrone, beta-estradiol, or estriol, there was preferential suppression of B-lymphocyte lineage precursors. Progesterone pellets had no effect when used alone, but mice exposed to progesterone were sensitive to several-logarithm lower concentrations of estrogen. Changes in subpopulations of B-lymphocyte lineage cells with hormone pellets were similar to those previously recorded in pregnancy. B-lymphocyte lineage precursors in male and female mice were sensitive to these sex hormones. Acute treatment with single injections of water-soluble beta-estradiol allowed temporal effects on B-lineage cells to be documented. With this protocol, total numbers of nucleated cells and myeloid progenitor cells remained unchanged. Interleukin 7-responsive precursors dramatically declined within 1 day of injection, suggesting that estrogen influences that stage in the B-lymphocyte lineage. There was a subsequent sharp drop in small pre-B cells 4 days after this transient elevation in estrogen. These experiments demonstrate that B lymphopoiesis is sensitive to negative regulation by sex steroids. They extend findings made with pregnant animals and parallel previous studies of the thymus. Sex steroids might contribute to control of steady-state lymphopoiesis, and fluctuations in their levels could have implications for human disease.

Animals↗

Lognormal model for determining dose-response curves from epidemiological data and for health risk assessment.

A practical method is proposed for determining human dose-response curves based on reasonable assumptions and simplifications. The epidemiological data needed are the fractions of the population suffering an adverse response from exposures to two or more patterns of fluctuating concentrations of a pollutant, and the statistical parameters of each pattern. The method calculates the two parameters of the threshold type dose-response curve of the pollutant, represented by a cumulative lognormal distribution. This distribution was derived from a reasonable statistical model. The calculation does not require any arbitrary safety factors and yields central values. The dose-response parameters then may be used to calculate the health risk rate of exposure to any other fluctuating concentration pattern. Another method is proposed to select appropriate threshold limit values (TLVs) using calculations involving these parameters. Examples are given to illustrate the calculations. Results with hypothetical data gave apparently reasonable results. They showed the importance not only of the geometric mean concentration but also of the geometric standard deviations of both the concentrations and of the dose-response curve, that greatly influence the results. It is believed that results of useful accuracy should be obtained. Health risk rates are readily understood. They are useful for cost-benefit calculations. Relative rates can be used to compare the hazards of different operations and different plants. The method may make possible the development of standards specifying maximum allowable risk rates.

Cost-Benefit Analysis↗

Feeding, growth, and the thermal environment of cabbage white caterpillars, Pieris rapae L.

Laboratory studies of temperature effects on short-term feeding and growth rates were combined with field data on thermal environments to explore the consequences of temperature variation for growth of caterpillars of the cabbage white butterfly, Pieris rapae. Mean short-term (24-h) consumption and growth rates of fourth-instar P. rapae feeding on collard leaves increased continuously with increasing temperatures between 10 degrees and 35 degrees C, peaked at 35 degrees C, and declined rapidly with temperatures above 35 degrees C. Physical models can mimic temperatures of real fifth-instar caterpillars under collard leaves within 1 degrees -2 degrees C in sunny summer conditions in Seattle, Washington. Continuous recordings of operative temperatures of model caterpillars in a collard garden suggest that, at the timescale of the duration of the fifth instar (5-8 d in the field), P. rapae caterpillars frequently experience temperatures spanning a 25 degrees C range, they spend most of their time at temperatures well below those that maximize growth, and they encounter substantial variation in the frequency distribution of operative temperatures between time periods. Combining these data on growth rate as a function of temperature and the distribution of operative temperatures in the field, I illustrate how growth rates at higher temperatures can make disproportionate contributions to the overall mean growth rates even when higher temperatures are relatively infrequent. Fluctuating thermal conditions may generate variable patterns of selection on reaction norms for growth rate in the field.

Adaptation, Physiological↗

Is there a place for different isoforms of FSH in clinical medicine? IV. The clinician's point of view.

Follicle stimulating hormone (FSH) plays an important role in gametogenesis in both men and women. In men it is required for the establishment and probably maintenance of spermatogenesis. In women it stimulates the growth of ovarian follicles and fluctuations in its secretion are involved in the selection of the ovulatory follicle. It is now possible by recombinant DNA technology to synthesize a range of isoforms of FSH with differing biological action and half-life which would provide a greater degree of flexibility in the treatment of women with anovulatory infertility. Longer acting isoforms of FSH would find clinical application in the treatment of hypogonadotrophic men.

Female↗

Sister chromatid exchanges, chromosome aberrations and micronuclei in female lymphocytes: correlations with biological rhythms, miscarriages and contraceptive pill use.

Our study looked at the variation in peripheral blood lymphocytes, during the menstrual cycle, of frequencies of sister chromatid exchanges (SCE) and micronuclei (MN) in 819 women and cells with aberrant chromosomes (CA) in a selected sample of 136 volunteers. We observed significant fluctuations in SCE and CA frequencies: SCEs reached a maximum value at the end of menstruation and a low at the time of ovulation, whereas CAs showed a continuous increase from the beginning of the menstrual cycle up to the time of ovulation and a progressive decrease thereafter. MN frequency did not fluctuate in a statistically significant way. No statistically significant differences in SCE, CA and MN frequencies were observed when fertile women were compared with women taking the contraceptive pill or those in menopause and no difference was found between women who had undergone physiological or surgically induced menopause. Moreover, no difference was found between women with a history of miscarriages and matched controls. These data together suggest that the natural variations in sexual hormone levels, but not those due to the contraceptive pill or their reduction at menopause, can contribute in modulating the baseline frequencies of SCEs and CAs. Moreover, these data suggest that the increased risks either of producing a chromosome imbalance in the progeny (eliciting miscarriages) or of occurrence of gynaecological diseases is not predictable by evaluating cytogenetic end-points in peripheral blood lymphocytes.

Abortion, Spontaneous↗

The disinfection by-products dichloro-, dibromo-, and bromochloroacetic acid impact intestinal microflora and metabolism in Fischer 344 rats upon exposure in drinking water.

Human consumption of chlorinated drinking water has been linked epidemiologically to bladder, kidney, and rectal cancers. The disinfection by-product (DBP) dichloroacetic acid is a hepatocarcinogen in Fischer 344 rats and B6C3F1 mice. The objective of this study is to determine the effect of the DBPs dichloro-, bromochloro-, and dibromoacetic acids (DCA, BCA, DBA) on intestinal microbial populations and their metabolism, with emphasis on enzymes involved in the bioactivation of procarcinogens and promutagens. One-month-old male Fischer 344 rats were provided water ad libitum containing 1 g/l DCA, BCA, or DBA for up to 5 weeks. At 1, 3, and 5 weeks of treatment, beta-glucuronidase (GLR), beta-galactosidase (GAL), beta-glucosidase (GLU), nitroreductase (NR), azoreductase (AR), and dechlorinase (DC) activities were determined in cecal and small and large intestinal homogenates. After 5 weeks of treatment, intestinal populations were enumerated on selective media. Cecal GAL (DCA, BCA, DBA) and GLR (DCA, DBA) activities were reduced after 1 and 3 weeks of treatment and GAL activity was elevated at 5 weeks (BCA). Large intestinal GAL (DCA, BCA) and GLU (DCA, BCA, DBA) activities were elevated after 5 weeks of treatment. Week 5 cecal AR (DCA, BCA, DBA), NR (DCA), and DC (DCA, DBA) activities were reduced. Even though some significant changes in intestinal populations were observed, use of selective media was not sensitive enough to explain fluctuations in enzyme activity. Haloacetic acids in the drinking water alter intestinal metabolism, which could influence bioactivation of promutagens and procarcinogens in the drinking water.

Acetates↗

Effects of the respiratory cycle on cardiac output measurements: reproducibility of data enhanced by timing the thermodilution injections in dogs.

Cardiac output (Q) was measured with the thermodilution technique at 4 points during the respiratory cycle in dogs. Boluses of an ice-cold solution were injected at mid- and end-inspiration while the animals were on intermittent positive-pressure ventilation (IPPV) or after induction of positive end-expiratory pressure (PEEP), with and without induction of experimental respiratory failure. Values were mot constant at end-inspiration. During IPPV without respiratory failure, the standard error of 74 measurements at end-inspiration was 5.1% and of 74 measurements randomly selected was 9.8%. Continuous infusion resulted in similar fluctuations in Q (r = 0.92). Values obtained during experimental respiratory failure were not significantly different. The authors conclude that timing the bolus injections with the respiratory cycle enhances the reproducibility of Q values obtained with the thermodilution technique.

Animals↗

Kinetics of the shear banding instability in startup flows.

Motivated by recent light scattering experiments on semidilute wormlike micelles, we study the early stages of the shear banding instability using the nonlocal Johnson-Segalman model with a "two-fluid" coupling of flow to micellar concentration. We perform a linear stability analysis for coupled fluctuations in shear rate gamma;, micellar strain W, and concentration phi about an initially homogeneous state. This resembles the Cahn-Hilliard (CH) analysis of fluid-fluid demixing (although we discuss important differences). First, assuming the initial state to lie on the intrinsic constitutive curve, we calculate the "spinodal" onset of instability in sweeps along this curve. We then consider start-up "quenches" into the unstable region. Here the instability in general occurs before the intrinsic constitutive curve can be attained, so we analyze the fluctuations with respect to the time-dependent start-up flow. We calculate the selected length and time scales at which inhomogeneity first emerges. When the coupling between flow and concentration is switched off, fluctuations in the "mechanical variables" gamma; and W are independent of those in phi, and are unstable when the intrinsic constitutive curve has negative slope; but no length scale is selected. Coupling to the concentration enhances this instability at short length scales, thereby selecting a length scale, consistent with the recent light scattering experiments. The spinodal region is then broadened by an extent that increases with proximity to an underlying (zero-shear) CH fluid-fluid (phi) demixing instability. Far from demixing, the broadening is slight and the instability is still mechanically dominated (by deltagamma; and deltaW) with only small deltaphi. Close to demixing, instability sets in at a very low shear rate, where it is dominated instead by deltaphi. In this way, the model captures a smooth crossover from shear banding instabilities that are perturbed by concentration coupling to demixing instabilities that are induced by shear.

Journal Article↗

Fluctuations of local density of states and C0 speckle correlations are equal.

We establish a conceptual relation between the fluctuations of the local density of states (LDOS) and the intensity correlations in speckle patterns resulting from the multiple scattering of waves in random media. We show that among the known types of speckle correlations (C1, C2, C3, and C0) only contributes to LDOS fluctuations in the infinite medium. We propose to exploit the equivalence of LDOS fluctuations and the C0 intensity correlation as a "selection rule" for scattering processes contributing to C0.

Journal Article↗

Genetic Regulation of Development in Sorghum bicolor (IX. The ma3R Allele Disrupts Diurnal Control of Gibberellin Biosynthesis).

The diurnal regulation of gibberellin (GA) concentrations in Sorghum bicolor was studied in a mutant lacking a light-stable 123-kD phytochrome (ma3Rma3R), wild-type (ma3ma3,Ma3Ma3), and heterozygous (ma3ma3R) cultivars. GAs were determined in shoots of 14-d-old plants by gas chromatography-selected ion-monitoring-mass spectrometry. GA12 levels fluctuated rhythmically in Ma3Ma3, ma3ma3, and,ma3Rma3R; Peak levels occured 3 to 9 h after lights-on. In some experiments, GA53 levels followed a similar pattern. There was no rhythmicity in levels of GA19 and GA8 in any genotype. In ma3ma3 and Ma3Ma3, GA20 levels increased at lights-on, peaked in the afternoon, and decreased to minimum levels in darkness. In ma3Rma3R, peak GA20 levels occured at lights-on, 9 h earlier than in the wild-type genotypes. The pattern for GA1 levels closely followed GA20 levels in all cultivars. One copy of ma3 restored near wild-type regulation of GA20 levels. GA rhythms persisted in 25-d-old ma3ma3 plants. Since absence of the 123-kD phytochrome disrupted diurnal regulation of the GA19 -> GA20 step, the ma3Rma3R genotype may be viewed as being phase shifted in the rhythmic levels of GA20 and GA1 rather than as simply overproducing them.

Journal Article↗

Isolation and genetic analysis of Chlamydomonas reinhardtii strains resistant to cadmium.

In Chlamydomonas reinhardtii, cadmium induces reduction of growth, reduction of chlorophyll content, and lethality. The toxicity was higher in a cell wall-deficient strain than in the wild type. By growing the cells on agar medium containing cadmium at concentrations inducing high lethality, stable resistant clones were isolated. The resistance was due to a nuclear mutation (cadAR) which probably preexisted in the wild-type cell population, as suggested by the fluctuation test. A double mutant (cadAR cadBR) was selected on media containing higher concentrations of cadmium. The cadBR mutation, which is unlinked to cadAR, determines a resistance intermediate between the CadAR mutant and the wild-type strain. Both cadAR and cadBR mutations are partially dominant.

Cadmium↗

Endogenous timekeepers in photosynthetic organisms.

Circadian and photoperiodic timing mechanisms were first described in photosynthetic organisms. These organisms depend upon sunlight for their energy, so adaptation to daily and seasonal fluctuations in light must have generated a strong selective pressure. Studies of the endogenous timekeepers of photosynthetic organisms provide evidence for both a fitness advantage and for selective pressures involved in early evolution of circadian clocks. Photoperiodic timing mechanisms in plants appear to use their circadian timers as the ruler by which the day/night length is measured. As in animals, the overall clock system in plants appears to be complex; the system includes multiple oscillators, several input pathways, and a myriad of outputs. Genes have now been isolated from plants that are likely to encode components of the central clockwork or at least that act very close to the central mechanism. Genetic and biochemical analyses of the central clockwork of a photosynthetic organism are most highly advanced in cyanobacteria, where a cluster of clock genes and interacting factors have been characterized.

Arabidopsis↗

Failing transcervical thymectomy in myasthenia gravis. An evaluation of transsternal re-exploration.

Twenty cases of failing transcervical thymectomy are reported. They were selected for transsternal re-exploration from a series of 95 patients who had previously undergone transcervical thymectomy because of myasthenia gravis (MG). A specific method for pre-operative detection of remnants of the non-tumorous thymic gland is lacking, but the applied clinical selection criteria were so far reliable: generalized, disabling, fluctuating MG despite cholinesterase inhibitor and/or immunosuppressive treatment, and no or inconsistent improvement after transcervical thymectomy. At transsternal re-exploration the commonest findings were intact lower thymic lobes with persistent venous drainage into the brachiocephalic vein. Presence of thymic tissue was histologically confirmed in all the excised specimens (weight range 10-60, mean 23 g), and the examination showed thymic hyperplasia in 18 cases, fatty involution of the gland in two, and a lympho-epithelial thymoma in one case. The re-operation was followed by objectively registrable improvement in all but one of the 20 patients during observation periods of 8-75 (mean 21) months. There was statistically significant reduction in disability scores (means 8.2-4.9) and in need for anticholinesterase medication (to 67% of pretreatment dose). Immunosuppression became unnecessary in 6 of 11 patients and could be reduced in 4 patients. The incidence of failure in transcervical thymectomy was alarmingly high (27%), and more re-operations are anticipated. Since the transcervical approach involves a high risk of incomplete thymectomy, its use should be abandoned. However, in most of the patients with re-operation, subsequent progress has been sufficiently promising for advocacy of sternotomy whenever the clinical criteria of failure are fulfilled.

Adolescent↗

[Progressive hearing loss].

Progressive sensorineural hearing loss (SNHL) is defined as hearing loss of unknown etiology with fairly high-speed progression. Its diagnostic criteria consist of the following: that it is 1) progressive, 2) with bilateral involvement, and 3) of unknown etiology. Due to recent advances in diagnostics, imaging and management, SNHL has gained much interest from otologists in the last few years. They provide new insight into the physiology and pathophysiology of hearing. SNHL which is sudden in onset, fluctuating, and/or progressive complicates medical management, hearing aid selection, and individualized educational planning for a hearing-impaired patient. Existing hypotheses on the etiology of SNHL are judged on experimental, clinical, laboratory and radiological evidence. Cardiovascular and rheologic diseases, hereditary disorders, immunological phenomena, infections, environmental causes like noise, ototoxic drugs and industrial substances and systemic maladies must be included in the diagnostic reflections. Potential concepts of treatment include rheologic medications and corticosteroids. Hearing aids and timely cochlear implant operation are further possible forms of treatment.

Acute Disease↗