The assets of the mentally handicapped: the interplay of mental illness and creativity.
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Bipolar Disorder↗
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Interplay between Na+/Ca2+ exchangers and mitochondria in Ca2+ clearance at the calyx of Held.
The clearance of Ca2+ from nerve terminals is critical for determining the build-up of residual Ca2+ after repetitive presynaptic activity. We found previously that K+-dependent Na+/Ca2+ exchangers (NCKXs) show polarized distributions in axon terminals of supraoptic magnocellular neurons and play a major role in Ca2+ clearance. The role of NCKXs in presynaptic terminals, however, has not been studied. We investigated the contribution of NCKX in conjunction with other Ca2+ clearance mechanisms at the calyx of Held by analyzing the decay of Ca2+ transients evoked by depolarizing pulses. Inhibition of Na+/Ca2+ exchange by replacing external Na+ with Li+ decreased the Ca2+ decay rate by 68%. Selective inhibition of NCKX by replacing internal K+ with TEA+ (tetraethylammonium) or Li+ decreased the Ca2+ decay rate by 42%, and the additional inhibition of the K+-independent form of Na+/Ca2+ exchanger (NCX) by reducing external [Na+] caused an additional decrease by 26%. Inhibition of plasma membrane Ca2+-ATPase (PMCA) decreased the Ca2+ decay rate by 23%, whereas inhibition of SERCA (smooth endoplasmic reticulum Ca2+-ATPase) had no effect. The contribution of mitochondria was negligible for small Ca2+ transients but became apparent at [Ca2+]i > 2.5 microM, when Na+/Ca2+ exchange became saturated. Mitochondrial contribution was also observed when the duration of Ca2+ transients was prolonged by inhibiting Na+/Ca2+ exchangers or by increasing Ca2+ buffers. These results suggest that, in response to small Ca2+ transients (<2 microM), Ca2+ loads are cleared from the calyx of Held by NCKX (42%), NCX (26%), and PMCA (23%), and that mitochondria participate when the Ca2+ load is larger or prolonged.
Animals↗
Interplay between local GABAergic interneurons and relay neurons generates gamma oscillations in the rat olfactory bulb.
Olfactory stimuli have been known for a long time to elicit oscillations in olfactory brain areas. In the olfactory bulb (OB), odors trigger synchronous oscillatory activity that is believed to arise from the coherent and rhythmic discharges of large numbers of neurons. These oscillations are known to take part in encoding of sensory information before their transfer to higher subcortical and cortical areas. To characterize the cellular mechanisms underlying gamma (30-80 Hz) local field potential (LFP) oscillations, we simultaneously recorded multiunit discharges, intracellular responses, and LFP in rat OB slices. We showed that a single and brief electrical stimulation of olfactory nerve elicited LFP oscillations in the mitral cell body layer lasting >1 sec. Both action potentials and subthreshold oscillations of mitral/tufted cells, the bulbar output neurons, were precisely synchronized with LFP oscillations. This synchronization arises from the interaction between output neurons and granule cells, the main population of local circuit inhibitory interneurons, through dendrodendritic synapses. Interestingly enough, the synchronization exerted by reciprocal synaptic interactions did not require action potentials initiated in granule cell somata. Finally, local application of a GABA(A) receptor antagonist at the mitral cell and external plexiform layers confirmed the exclusive role of the granule cell reciprocal synapses in generating the evoked oscillations. We concluded that interneurons located in the granule cell layer generate synaptic activity capable of synchronizing activity of output neurons by interacting with both their subthreshold and spiking activity.
Action Potentials↗
Lessons of slicing membranes: interplay of packing, free area, and lateral diffusion in phospholipid/cholesterol bilayers.
We employ 100-ns molecular dynamics simulations to study the influence of cholesterol on structural and dynamic properties of dipalmitoylphosphatidylcholine bilayers in the fluid phase. The effects of the cholesterol content on the bilayer structure are considered by varying the cholesterol concentration between 0 and 50%. We concentrate on the free area in the membrane and investigate quantities that are likely to be affected by changes in the free area and free volume properties. It is found that cholesterol has a strong impact on the free area properties of the bilayer. The changes in the amount of free area are shown to be intimately related to alterations in molecular packing, ordering of phospholipid tails, and behavior of compressibility moduli. Also the behavior of the lateral diffusion of both dipalmitoylphosphatidylcholine and cholesterol molecules with an increasing amount of cholesterol can in part be understood in terms of free area. Summarizing, our results highlight the central role of free area in comprehending the structural and dynamic properties of membranes containing cholesterol.
1,2-Dipalmitoylphosphatidylcholine↗
The interplay between viscoelastic and thermodynamic properties determines the birefringence of F-actin gels.
F-actin gels of increasing concentrations (25-300 microM) display in vitro a progressive onset of birefringence due to orientational ordering of actin filaments. At F-actin concentrations <100 microM, this birefringence can be erased and restored at will by sonication and gentle flow, respectively. Hence, the orientational ordering does not result from a thermodynamic transition to a nematic phase but instead is due to mechanical stresses stored in the gels. In contrast, at F-actin concentrations > or =100 microM, gels display spontaneous birefringence recovery, at rest, which is the sign of true nematic ordering, in good agreement with statistical physics models of the isotropic/nematic transition. Well-aligned samples of F-actin gels could be produced and their small-angle x-ray scattering patterns are quite anisotropic. These patterns show no sign of filament positional short-range order and could be modeled by averaging the form factor with the Maier-Saupe nematic distribution function. The derived nematic order parameter S of the gels ranged from S = 0.7 at 300 microM to S = 0.4 at 25 microM. Both birefringence and small-angle x-ray scattering data indicate that, even in absence of cross-linking proteins, spontaneous cooperative alignment of actin filaments may arise in motile regions of living cells where F-actin concentrations can reach values of a few 100 microM.
Actins↗
Dynamics of the emission spectrum of a single LH2 complex: interplay of slow and fast nuclear motions.
We have studied the relationship between the realizations of static disorder and the emission spectra observed for a single LH2 complex. We show that the experimentally observed spectral fluctuations reflect realizations of the disorder in the B850 ring associated with different degrees of exciton delocalization and different effective coupling of the excitons to phonon modes. The main spectral features cannot be explained using models with correlated disorder associated with elliptical deformations of the ring. A quantitative explanation of the measured single-molecule spectra is obtained using the modified Redfield theory and a model of the B850 ring with uncorrelated disorder of the site energies. The positions and spectral shapes of the main exciton components in this model are determined by the disorder-induced shift of exciton eigenvalues in combination with phonon-induced effects (i.e., reorganization shift and broadening, that increase in proportion to the inverse delocalization length of the exciton state). Being dependent on the realization of the disorder, these factors produce different forms of the emission profile. In addition, the different degree of delocalization and effective couplings to phonons determines a different type of excitation dynamics for each of these realizations. We demonstrate that experimentally observed quasistable conformational states are characterized by excitation energy transfer regimes varying from a coherent wavelike motion of a delocalized exciton (with a 100-fs pass over half of the ring) to a hopping-type motion of the wavepacket (with a 350-fs jump between separated groups of 3-4 molecules) and self-trapped excitations that do not move from their localization site.
Bacterial Proteins↗
Interplay between shear stress and adhesion on neutrophil locomotion.
Leukocyte locomotion over the lumen of inflamed endothelial cells is a critical step, following firm adhesion, in the inflammatory response. Once firmly adherent, the cell will spread and will either undergo diapedesis through individual vascular endothelial cells or will migrate to tight junctions before extravasating to the site of injury or infection. Little is known about the mechanisms of neutrophil spreading or locomotion, or how motility is affected by the physical environment. We performed a systematic study to investigate the effect of the type of adhesive ligand and shear stress on neutrophil motility by employing a parallel-plate flow chamber with reconstituted protein surfaces of E-selectin, E-selectin/PECAM-1, and E-selectin/ICAM-1. We find that the level and type of adhesive ligand and the shear rate are intertwined in affecting several metrics of migration, such as the migration velocity, random motility, index of migration, and the percentage of cells moving in the direction of flow. On surfaces with high levels of PECAM-1, there is a near doubling in random motility at a shear rate of 180 s(-1) compared to the motility in the absence of flow. On surfaces with ICAM-1, neutrophil random motility exhibits a weaker response to shear rate, decreasing slightly when shear rate is increased from static conditions to 180 s(-1), and is only slightly higher at 1000 s(-1) than in the absence of flow. The random motility increases with increasing surface concentrations of E-selectin and PECAM-1 under static and flow conditions. Our findings illustrate that the endothelium may regulate neutrophil migration in postcapillary venules through the presentation of various adhesion ligands at sites of inflammation.
Cell Adhesion↗
Meal timing, fasting and glucocorticoids interplay in serum leptin concentrations and diurnal profile.
BACKGROUND: In a previous study, we reported a 4-fold increase in serum leptin following total parenteral nutrition given after surgery. We hypothesised that the perioperative fasting and stress contributed to this, possibly mediated by increased serum insulin and cortisol. OBJECTIVE: To test the hypothesis that fasting, in combination with glucocorticoids, sensitises the leptin response to subsequent energy intake. DESIGN: Healthy volunteers were randomised into two groups, one group received dexamethasone (DEX), 0.1 mg twice daily for 3 days, while the other group served as a control. Each group was then subdivided into two feeding protocols. Protocol 1, where a standard meal was given at 0, 24, 36 and 48 h and protocol 2 where the same meal was given at 0 and 48 h. Blood samples were drawn before, as well as every other hour during the study period for determination of serum leptin, insulin, glucose and cortisol concentrations. RESULTS: In all groups serum leptin increased significantly following each meal (P<0.01). The rise in serum leptin in response to the standard meal was higher when the meal was taken in the evening (P<0.001) or following longer duration of fasting (P<0.02). In those fasting for 48 h, leptin decreased by 60% and showed no diurnal variation. DEX intake increased leptin concentrations in those fasting for short periods (P<0.02) but not for 48 h. CONCLUSIONS: Long durations of fasting sensitise the response of leptin to subsequent energy intake and abolish the DEX-induced upregulation of leptin. Meal timing is an important factor determining the leptin diurnal rhythm, but other factors must contribute since the leptin response to a standard meal taken in the evening was greater than to the same meal taken in the morning.
Blood Glucose↗
Children's sleep: an interplay between culture and biology.
Pediatricians provide a major source of knowledge for parents about children's behavior and development, although their advice is largely based on their own cultural values and beliefs in interaction with their personal and clinical experience. This review presents cross-cultural aspects of children's sleep behavior in industrialized and complex modern societies and provides a basis for understanding dimensions and mechanisms of cultural differences. We submit that it is the interaction between culture and biology that establishes behavioral and developmental norms and expectations regarding normal and problematic children's sleep. Pediatricians need to recognize the cultural environment in which children live and be knowledgeable about how cultural beliefs and values of both families and physicians interact with the needs and biological characteristics of individual children.
Adolescent↗
Respiratory syncytial virus and innate immunity: a complex interplay of exploitation and subversion.
Respiratory syncytial virus causes significant disease in infants, the elderly and select groups of immunocompromised patients. Healthy individuals are also naturally infected with respiratory syncytial virus repeatedly throughout life. Therefore, safe and effective vaccines and therapies are needed. However, a number of factors have prevented development of such antiviral interventions to date. These include a failed vaccine trial, the very young age of the primary target population (neonates), the inability of natural infection to induce long-term protective immunity, and an incomplete understanding of virus-host interactions. The identification of pattern recognition receptors has led to significant increases in our understanding of induction and regulation of innate immune responses. This review will address the impact of these findings on respiratory syncytial virus research.
Adjuvants, Immunologic↗
Apoptotic cell and phagocyte interplay: recognition and consequences in different cell systems.
Cell death by apoptosis is characterized by specific biochemical changes, including the exposure of multiple ligands, expected to tag the dying cell for prompt recognition by phagocytes. In non-pathological conditions, an efficient clearance is assured by the redundant interaction between apoptotic cell ligands and multiple receptor molecules present on the engulfing cell surface. This review concentrates on the molecular interactions operating in mammalian and non-mammalian systems for apoptotic cell recognition, as well as on the consequences of their signaling. Furthermore, some cellular models where the exposure of the phosphatidylserine (PS) phospholipid, a classical hallmark of the apoptotic phenotype, is not followed by cell death will be discussed.
Animals↗
Apoptotic mimicry: an altruistic behavior in host/Leishmania interplay.
Apoptosis is the most common phenotype observed when cells die through programmed cell death. The morphologic and biochemical changes that characterize apoptotic cells depend on the activation of a diverse set of genes. Apoptosis is essential for multicellular organisms since their development and homeostasis are dependent on extensive cell renewal. In fact, there is strong evidence for the correlation between the emergence of multicellular organisms and apoptosis during evolution. On the other hand, no obvious advantages can be envisaged for unicellular organisms to carry the complex machinery required for programmed cell death. However, accumulating evidence shows that free-living and parasitic protozoa as well as yeasts display apoptotic markers. This phenomenon has been related to altruistic behavior, when a subpopulation of protozoa or yeasts dies by apoptosis, with clear benefits for the entire population. Recently, phosphatidylserine (PS) exposure and its recognition by a specific receptor (PSR) were implicated in the infectivity of amastigote forms of Leishmania, an obligatory vertebrate intramacrophagic parasite, showing for the first time that unicellular organisms use apoptotic features for the establishment and/or maintenance of infection. Here we focus on PS exposure in the outer leaflet of the plasma membrane--an early hallmark of apoptosis--and how it modulates the inflammatory activity of phagocytic cells. We also discuss the possible mechanisms by which PS exposure can define Leishmania survival inside host cells and the evolutionary implications of apoptosis at the unicellular level.
Animals↗
Presidential address. Sex and schistosomes: an interesting biological interplay with control implications.
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Amino Acid Sequence↗
Role of the hypothalamus in pituitary-thyroid interplay.
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Hypothalamus↗
The hormonal regulation of the oestrogen receptor in rat liver: an interplay involving growth hormone, thyroid hormones and glucocorticoids.
The regulation of the formation of the hepatic oestrogen receptor (ER) in adult female rats was studied by assaying steady state levels of ER and ER messenger RNA under different endocrine conditions. Hypophysectomy (HX) drastically reduced ER levels from 67.5 +/- 7.9 to 8.4 +/- 0.5 (means +/- S.E.M.) fmol/mg cytosolic protein. Continuous infusion of growth hormone (GH) to HX animals tripled ER and doubled ER mRNA levels. Treatment with triiodothyronine (T3) in a high dose (10 micrograms/day) doubled ER mRNA levels. The effects of T3 were dose-dependent, since a lower dose (1 microgram/day) increased neither ER nor ER mRNA levels. ER mRNA concentrations were increased by GH to 481 +/- 44% and by T3 to 372 +/- 35% of HX control levels 4 h after single injections of the hormones in HX animals. The glucocorticoid dexamethasone (DEX) alone increased neither ER nor ER mRNA levels in HX animals. DEX and GH in combination increased ER 5-fold and ER mRNA 2-fold compared with control levels in HX animals, whereas DEX and T3 in combination increased neither ER nor ER mRNA levels. Treatment with prolactin affected neither ER nor ER mRNA levels in HX rats. Insulin-like growth factor I (IGF-I) mRNA and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA levels were measured. GAPDH mRNA levels were increased 2.5-fold in HX rats by DEX and T3 in combination and almost 2-fold by DEX and GH in combination. IGF-I mRNA levels in HX rats were increased 4.5-fold by continuous infusion of GH alone, 6-fold by GH and T3 in combination, and 2.5-fold by GH and DEX in combination. These data indicate that both GH and T3 act directly on the liver to increase ER mRNA levels. GH, the most important of these hormones, also acts at the translational and/or post-translational level to increase ER protein levels. DEX treatment suppresses the stimulatory effects of T3, but not of GH.
Animals↗
Interplay between Senecio jacobaea and plant, soil, and aboveground insect community composition.
To elucidate the factors that affect the performance of plants in their natural environment, it is essential to study interactions with other neighboring plants, as well as with above- and belowground higher trophic organisms. We used a long-term field experiment to study how local plant community diversity influenced colonization by the biennial composite Senecio jacobaea in its native range in The Netherlands in Europe. We tested the effect of sowing later-succession plant species (0, 4, or 15 species) on plant succession and S. jacobaea performance. Over a period of eight years, the percent cover of S. jacobaea was relatively low in communities sown with 15 or 4 later-succession plant species compared to plots that were not sown, but that were colonized naturally. However, after four years of high abundance, the density of S. jacobaea in unsown plots started to decline, and the size of the individual plants was smaller than in the plots sown with 15 or 4 plant species. In the unsown plots, densities of aboveground leaf-mining, flower-feeding, and stem-boring insects on S. jacobaea plants were lower than on plants in sown plots, and there was a strong positive relationship between plant size and levels of herbivory. In a greenhouse experiment, we grew S. jacobaea in sterilized soil inoculated with soil from the different sowing treatments of the field experiment. Biomass production was lower when S. jacobaea test plants were grown in soil from the unsown plots than in soil from the sown plots (4 or 15 species). Molecular analysis of the fungal and bacterial communities revealed that the composition of fungal communities in unsown plots differed significantly from those in sown plots, suggesting that soil fungi could have been involved in the relative growth reduction of S. jacobaea in the greenhouse bioassay. Our results show that, in its native habitat, the abundance of S. jacobaea depends on the initial composition of the plant community and that, on a scale of almost a decade, its interactions with plant and soil communities and aboveground invertebrates may influence the dynamics of this colonizing species.
Animals↗
Temperature-dependent sex determination: the interplay of steroid hormones and temperature.
Sex determination is the product of coordinated gene expression. Mutational analyses have yielded great progress in our understanding of mammalian sex determination, and insight into the evolution of this sex chromosome system would be valuable. Mammals arose from turtle-like reptiles, and in many turtles the incubation temperature of the egg determines the sex of the offspring, a process known as temperature-dependent sex determination. There is mounting evidence that sex steroid hormones are the physiological equivalent of incubation temperature and serve as the proximate trigger for male and female sex determination. Temperature appears to accomplish this end by acting on genes coding for steroidogenic enzymes and sex steroid hormone receptors. The ability to manipulate sex determination in turtles both by temperature and by sex steroid hormones extends our understanding of the evolution as well as the physiology and molecular biology of sex determination.
Amino Acid Sequence↗
The interplay between primary and secondary cytokines. Cytokines involved in the regulation of monocyte recruitment.
Cytokines and chemokines play significant roles in the recruitment of leucocytes from the circulation and are therefore crucial determinants of inflammatory reactions and immunity. As knowledge of the actions of these agents and their regulatory mechanisms increases, so does the opportunity to devise pharmacological means of intervening in the activities of these molecules. It is now believed, for instance, that the actions of the classical pro-inflammatory cytokine interleukin (IL)-1 are inhibited by the expression and presentation of a 'decoy' receptor, which acts as a 'molecular trap' for IL-1. There is evidence to suggest that IL-6, formerly considered a purely anti-inflammatory cytokine, also has proinflammatory properties. Furthermore, regulation of the chemokine system, which can be achieved by regulating agonist production or altering the expression of chemokine receptors, has recently been demonstrated. These and other new findings, which may prove to have considerable relevance as regards current or future strategies for the treatment of inflammation, infection, neoplasia etc., are presented and discussed in this article.
Chemokine CCL2↗