Biophysical Interpretation of the Dependence of Synergy on the Intensity of Applied Agents

Biophysics - This review analyzes the general patterns of synergism, whose manifestation under the simultaneous actions of various agents does not depend on the biological objects and the effect...     

The Nature and Duration of Gene Action for Vernalization Response in Wheat

Four near-isogenic lines of wheat were studied to determinethe nature and duration of gene action for vernalization responseunder 2 weekly vernalization periods from 0 to 10 weeks. With time to floral initiation the Vrn 1 Vrn 2 and Vrn 1 vrn2 genotypes showed a cumulative response whereby days to floralinitiation decreased as the period of vernalization increased.The vrn 1 Vrn 2 and the vrn 1 vrn 2 genotypes also showed acumulative response for periods of vernalization less than 6weeks for the former and 8 weeks for the latter. Days to earemergence was closely related to days to floral initiation dueto the constancy of the period from floral initiation to earemergence across all lines and treatments and, consequently,they gave similar measures of the relative strength of vernalizationresponse. It appears that genes for vernalization response ceaseto act after floral initiation. The implications of these findings to breeding for increasedadaptability and yield in wheat are discussed. Triticum aestivum, wheat isogenic lines, vernalization, floral initiation, ear emergence, gene action     

Shiftwork Duration and the Awakening Cortisol Response Among Police Officers

Police officers are required to work irregular hours, which induces stress, fatigue, and sleep disruption, and they have higher rates of chronic disease and mortality. Cortisol is a well-known “stress hormone” produced via activation of the hypothalamic-pituitary-adrenal axis. An abnormal secretion pattern has been associated with immune system dysregulation and may serve as an early indicator of disease risk. This study examined the effects of long- and short-term shiftwork on the cortisol awakening response among officers (n = 68) in the Buffalo Cardio-Metabolic Occupational Police Stress (BCOPS) pilot study (2001–2003). The time each officer spent on day (start time: 04:00–11:59?h), afternoon (12:00–19:59?h), or night (20:00–03:59?h) shifts was summarized from 1994 to examination date to characterize long-term (mean: 14 ± 9 yrs) and short-term (3, 5, 7, or 14 days prior to participation) shiftwork exposures. The cortisol awakening response was characterized by summarizing the area under the curve (AUC) for samples collected on first awakening, and at 15-, 30-, and 45-min intervals after waking. Data were collected on a scheduled training or off day. The cortisol AUC with respect to ground (AUC_G) summarized total cortisol output after waking, and the cortisol AUC with respect to increase (AUC_I) characterized the waking cortisol response. Officers also completed the Center for Epidemiologic Studies Depression scale. Waking cortisol AUC values were lower among officers working short-term night or afternoon shifts than day shifts, with maximal differences occurring after 5 days of shiftwork. The duration of long-term shiftwork was not associated with the cortisol awakening response, although values were attenuated among officers with more career shift changes. (Author correspondence: burch@mailbox.sc.edu)     

The Velocity of Light Intensity Increase Modulates the Photoprotective Response in Coastal Diatoms

In aquatic ecosystems, the superimposition of mixing events to the light diel cycle exposes phytoplankton to changes in the velocity of light intensity increase, from diurnal variations to faster mixing-related ones. This is particularly true in coastal waters, where diatoms are dominant. This study aims to investigate if coastal diatoms differently activate the photoprotective responses, xanthophyll cycle (XC) and non-photochemical fluorescence quenching (NPQ), to cope with predictable light diel cycle and unpredictable mixing-related light variations. We compared the effect of two fast light intensity increases (simulating mixing events) with that of a slower increase (corresponding to the light diel cycle) on the modulation of XC and NPQ in the planktonic coastal diatom Pseudo-nitzschia multistriata. During each light treatment, the photon flux density (PFD) progressively increased from darkness to five peaks, ranging from 100 to 650 µmol photons m⁻² s⁻¹. Our results show that the diel cycle-related PFD increase strongly activates XC through the enhancement of the carotenoid biosynthesis and induces a moderate and gradual NPQ formation over the light gradient. In contrast, during mixing-related PFD increases, XC is less activated, while higher NPQ rapidly develops at moderate PFD. We observe that together with the light intensity and its increase velocity, the saturation light for photosynthesis (Ek) is a key parameter in modulating photoprotection. We propose that the capacity to adequately regulate and actuate alternative photoprotective ‘safety valves’ in response to changing velocity of light intensity increase further enhances the photophysiological flexibility of diatoms. This might be an evolutionary outcome of diatom adaptation to turbulent marine ecosystems characterized by unpredictable mixing-related light changes over the light diel cycle.     

The Physiological and Biochemical Response of Standardbred Horses to Exercise of Varying Speed and Duration

LINDHOLM, ARNE and BENGT SALTIN: The physiological and biochemical response of standardbred horses to exercise of varying speed and duration. Acta vet. scand. 1974, 15, 310–324. — Welltrained standardbred horses were studied to examine the metabolic response to excercise of various speeds and duration. Comparisons between interval (400, 700, 1,000 and 2,000 m) and continuous trotting (1 hr., 2 hrs.) and racing were made. Muscle and rectal temperatures were recorded before and immediately after each work bout. Heart rate was linearly related to trotting speed, and maximal heart rate (240 beats × min.−1) was achieved when trotting at least 700 m at close to maximal speed (12.0–12.5 m×sec.−1). Biopsy specimens from the gluteus medius muscle and venous blood were obtained before and after each work bout. Muscle and blood lactate values were markedly increased first at speeds close to maximal speed (11.4–12.5 m×sec.−1). Trotting 6×700 m at 12.5 m×sec.−1 produced as high muscle and blood lactate values as 23.7 and 19.0 mmol×kg−1 wet weight and l−1, respectively. Corresponding values after a race were about 15 mmol×kg−1 (muscle) and l−1 (blood). Glycogen utilization was related to work intensity and was most pronounced during the first work bouts. At a speed of 12 m×sec.−1 and trotting 2000 m, there was a glycogen utilization of near 12 mmol glucose units × kg−1 × min.−1 wet muscle. It is concluded that interval training over a distance of 700–1000 m repeated 4–6 times with a trotting speed close to maximal speed (11.4–12.5 m×sec.−1) appears to be optimal. ATP; CP; blood lactate; glycogen utilization; heart rate; horse skeletal muscle; muscle lactate; racing training.     

Effect of the Intensity and Duration of Light at Various Temperatures on the Germination of Oldenlandia corymbosa L. Seeds

At temperatures below 35 to 40°C, fairly intense continuous white light (13 watts per square meter) inhibits germination of Oldenlandia corymbosa L. seeds, and the lower the temperature, the greater the inhibition. However, such lighting may enable seeds to germinate later in the dark; their degree of germinability depends both on the duration of lighting and on the temperature during lighting and after transfer to the dark.     

不同光照强度下三角叶滨藜光合作用对盐激胁迫的响应

以溶液培养的三角叶滨藜植株为材料研究了不同光照条件下其叶片光合作用对盐(NaCl)激胁迫的即刻反应及变化规律.结果表明,三角叶滨藜光合作用对盐激胁迫的响应有8 min左右的滞后期.在光照强度为100umol·m-2·-1和100 mmol·L-1浓度NaCl共同作用下,三角叶滨藜叶片净光合速率略有上升;但随NaCl浓度和光照强度进一步增加,其净光合速率呈下降趋势,且光照越强,盐胁迫导致的净光合速率下降幅度越大.同时,弱光下或强光低浓度NaCl胁迫下,盐激胁迫导致的净光合速率下降主要是气孔限制引起的;而强光下,高浓度的NaCl胁迫导致的净光合速率下降在盐激胁迫处理的前30-40 min主要由气孔限制引起.40 min后则主要由非气孔限制引起.可见,不同光照强度和NaCl浓度胁迫下三角叶滨藜叶片光合作用响应规律不同,引起净光合速率下降机制各异.     

Cue Reactivity Is Associated with Duration and Severity of Alcohol Dependence: An fMRI Study

Introduction

With the progression of substance dependence, drug cue-related brain activation is thought to shift from motivational towards habit pathways. However, a direct association between cue-induced brain activation and dependence duration has not yet been shown. We therefore examined the relationship between alcohol cue-reactivity in the brain, cue-induced subjective craving and alcohol dependence duration and severity. Since alcohol dependence is highly comorbid with depression/anxiety, which may modulate brain responses to alcohol cues, we also examined the relation between comorbid depression/anxiety and cue-reactivity.

Methods

We compared 30 alcohol dependent patients with 15 healthy controls and 15 depression/anxiety patients during a visual alcohol cue-reactivity task using functional magnetic resonance imaging blood oxygenated level-dependent responses and subjective craving as outcomes. Within the alcohol dependent group we correlated cue-reactivity with alcohol dependence severity and duration, with cue-induced craving and with depression/anxiety levels.

Results

Alcohol dependent patients showed greater cue-reactivity in motivational brain pathways and stronger subjective craving than depression/anxiety patients and healthy controls. Depression/anxiety was not associated with cue-reactivity, but depression severity in alcohol dependent patients was positively associated with craving. Within alcohol dependence, longer duration of alcohol dependence was associated with stronger cue-related activation of the posterior putamen, a structure involved in habits, whereas higher alcohol dependence severity was associated with lower cue-reactivity in the anterior putamen, an area implicated in goal-directed behavior preceding habit formation.

Conclusion

Cue-reactivity in alcohol dependence is not modulated by comorbid depression or anxiety. More importantly, the current data confirm the hypothesis of a ventral to dorsal striatal shift of learning processes with longer dependence duration, which could underlie increasingly habitual substance use with progressing substance dependence.     

Population Size and Selection Intensity Effects on Long-Term Selection Response in Mice

Long-term response to within full-sib family selection for increased postweaning gain was evaluated in lines having different effective population sizes (N_e) and selection intensities (i). Line designations were I4(4), I8(2), I16(2), M4(4), M8(2) and M16(2), where I and M indicate selection of the top 50% and 25%, respectively; 4, 8 and 16 represent the number of parental pairs per replicate and number of replicates is given in parentheses. Realized within full-sib family heritabilities (h_R²) in the first phase of selection (0-14 generations) were larger in 16-pair lines than in 4- and 8-pair lines. In the second phase of selection (>14 generations), h_R² declined significantly (P<.01) in all lines, and only the I16 and M16 lines had h_R² values significantly (P<.01) greater than zero. Realized genetic correlations involving number born, 12-day litter weight, weaning weight and six-week weight tended to decline in the second phase of selection. The I16, M16 and control (C16) replicates were crossed in all combinations at generation 14. Crosses were then selected within litters for high postweaning gain. The h_R² values in the crossbred lines were all larger than those in the second selection phase for M16-1, M16-2 and I16-1, but not for I16-2. Within each N_e level, total response was significantly (P<.01) less for I lines compared with M lines. Total response increased as N_e increased, within each level of i. Relatively small differences in realized i values among N_e lines could not account for this result. The difference in total response among the N_e lines at a given selection intensity may be due to inbreeding depression and a combination of interactions involving "drift" and selection. By crossing replicates of the M lines with the C16 control, the effects of inbreeding depression were removed. Inbreeding depression and genetic drift, as defined herein, were equally important in accounting for differences among N_e lines in total response.     

Genetic Differences in the Duration of the Lymphocyte Heat Shock Response in Mice

Lymphocytes from adult mice bearing a known difference in genetic susceptibility to teratogen-induced exencephaly (SWV/SD, and DBA/2J) were evaluated for changes in protein synthesis following an in vivo heat treatment. Particular attention was paid to changes indicative of the heat shock response, a highly conserved response to environmental insult consisting of induction of a few, highly conserved proteins with simultaneous decreases in normal protein synthesis. The duration of heat shock protein induction in lymphocytes was found to be increased by 1 hr in the teratogen-sensitive SWV/SD strain as compared to the resistant DBA/2J strain. Densitometric analysis revealed a significant decrease in the relative synthesis of at least two non-heat shock proteins (36 kD and 45 kD) in the SWV/SD lymphocytes as compared to DBA/2J cells. The increased sensitivity of protein synthesis to hyperthermia in the SWV/SD lymphocytes were lost in the F1 progeny of reciprocal crosses between SWV/SD and DBA/2J mouse strains. Sensitivity to hyperthermia-induced exencephaly is recessive to resistance in these crosses. The relationship between altered protein synthesis and teratogen susceptibility is discussed.     

桂花光合特性的光温响应

对丹桂光合特性光温响应的研究结果表明：1）净光合速率最适温度为24～28℃,在22～42℃之间,净光合速率、胞间CO2浓度、气孔导度和水分利用效率与温度的关系为二次多项式方程,暗呼吸速率和蒸腾速率与温度成线性关系;2）在控制条件下,随着温度的升高,光补偿点升高,光饱和点、表观量子效率、最大净光合速率下降.在自然条件下,丹桂光合日进程出现明显的光合“午休”,“午休”主要由非气孔限制引起,表观量子效率和光化学效率下降表明光抑制是午间非气孔限制形成和发展的深层原因.     

The Relationship between Stimulus Intensity and Oriented Phototactic Response (Topotaxis) in Chlamydomonas

Two techniques have been used to study the quantitative relationship between stimulus intensity and oriented phototactic response (topotaxis) in Chlamydomonas. The net response of a cell population was monitored photometrically and was recorded continuously against time. The responses of individual cells were observed through a microscope and their swimming tracks were recorded on film. The net response of the population is positive at low stimulus intensity and negative at high intensity. The direction of response can be reversed within two seconds by raising or lowering the intensity. The intensity-response curve for phototaxis is similar to the dose-response curve for phototropism. The net response has no distinct threshold; it increases linearly with log intensity; then it decreases and finally becomes negative. The individual-cell studies reveal that the intensity-dependent increase in net topotactic response is due primarily to an increase in the number of cells responding and in the directness of their swimming path. As stimulus intensity is raised, the swimming path becomes increasingly well-aligned with the stimulus beam, whether net response is positive throughout the intensity range tested, negative throughout that range, or changing from positive to negative. Changes in swimming rate do not contribute significantly to the intensity-dependent changes in net response. Swimming rate shows virtually no change throughout the intensity range of positive topotaxis and shows only a small increase in the negative range. However, a transient decrease in swimming rate (stop response) is often observed at the onset of stimulation. The implications of these results for the orientation mechanism are discussed.     

On the Pressure Response in the Brain due to Short Duration Blunt Impacts

When the head is subject to non-penetrating (blunt) impact, contusion-type injuries are commonly identified beneath the impact site (the coup) and, in some instances, at the opposite pole (the contre-coup). This pattern of injury has long eluded satisfactory explanation and blunt head injury mechanisms in general remain poorly understood. There are only a small number of studies in the open literature investigating the head''s response to short duration impacts, which can occur in collisions with light projectiles. As such, the head impact literature to date has focussed almost exclusively on impact scenarios which lead to a quasi-static pressure response in the brain. In order to investigate the response of the head to a wide range of impact durations, parametric numerical studies were performed on a highly bio-fidelic finite element model of the human head created from in vivo magnetic resonance imaging (MRI) scan data with non-linear tissue material properties. We demonstrate that short duration head impacts can lead to potentially deleterious transients of positive and negative intra-cranial pressure over an order of magnitude larger than those observed in the quasi-static regime despite reduced impact force and energy. The onset of this phenomenon is shown to be effectively predicted by the ratio of impact duration to the period of oscillation of the first ovalling mode of the system. These findings point to dramatically different pressure distributions in the brain and hence different patterns of injury depending on projectile mass, and provide a potential explanation for dual coup/contre-coup injuries observed clinically.     

Computational Identification of Mechanistic Factors That Determine the Timing and Intensity of the Inflammatory Response

Timely resolution of inflammation is critical for the restoration of homeostasis in injured or infected tissue. Chronic inflammation is often characterized by a persistent increase in the concentrations of inflammatory cells and molecular mediators, whose distinct amount and timing characteristics offer an opportunity to identify effective therapeutic regulatory targets. Here, we used our recently developed computational model of local inflammation to identify potential targets for molecular interventions and to investigate the effects of individual and combined inhibition of such targets. This was accomplished via the development and application of computational strategies involving the simulation and analysis of thousands of inflammatory scenarios. We found that modulation of macrophage influx and efflux is an effective potential strategy to regulate the amount of inflammatory cells and molecular mediators in both normal and chronic inflammatory scenarios. We identified three molecular mediators − tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and the chemokine CXCL8 − as potential molecular targets whose individual or combined inhibition may robustly regulate both the amount and timing properties of the kinetic trajectories for neutrophils and macrophages in chronic inflammation. Modulation of macrophage flux, as well as of the abundance of TNF-α, TGF-β, and CXCL8, may improve the resolution of chronic inflammation.