Is there a relationship between the supramolecular organization of the mitochondrial ATP synthase and the formation of cristae?

Blue native polyacrylamide gel electrophoresis (BN-PAGE) analyses of detergent mitochondrial extracts have provided evidence that the yeast ATP synthase could form dimers. Cross-linking experiments performed on a modified version of the i-subunit of this enzyme indicate the existence of such ATP synthase dimers in the yeast inner mitochondrial membrane. We also show that the first transmembrane segment of the eukaryotic b-subunit (bTM1), like the two supernumerary subunits e and g, is required for dimerization/oligomerization of ATP synthases. Unlike mitochondria of wild-type cells that display a well-developed cristae network, mitochondria of yeast cells devoid of subunits e, g, or bTM1 present morphological alterations with an abnormal proliferation of the inner mitochondrial membrane. From these observations, we postulate that an anomalous organization of the inner mitochondrial membrane occurs due to the absence of ATP synthase dimers/oligomers. We provide a model in which the mitochondrial ATP synthase is a key element in cristae morphogenesis.     

How does the mitochondrial ADP/ATP carrier distinguish transportable ATP and ADP from untransportable AMP and GTP?Dynamic modeling of the recognition/translocation process in the major substrate binding region

To understand the transport mechanism of the bovine heart mitochondrial ADP/ATP carrier at the atomic level, we studied the four-dimensional features of the interaction of various purine nucleotides with the adenine nucleotide binding region (ABR) consisting of Arg(151)-Asp(167) in the second loop facing the matrix side. After three-dimensional modeling of ABR based on the experimental results, its structural changes on interaction with purine nucleotides were examined by molecular dynamics computation at 300 K. ATP/ADP were translocated to a considerable degree from the matrix side to the inner membrane region accompanied by significant backbone conformational changes, whereas neither appreciable translocation nor a significant conformational change was observed with the untransportable nucleotides AMP/GTP. The results suggested that binding of the terminal phosphate group and the adenine ring of ATP/ADP with Arg(151) and Lys(162), respectively, and subsequent interaction of a phosphate group(s) other than the terminal phosphate with Lys(162) triggered the expansion and subsequent contraction of the backbone conformation of ABR, leading to the translocation of ATP/ADP. Based on a simplified molecular dynamic simulation, we propose a dynamic model for the initial recognition process of ATP/ADP with the carrier.     

Phospholipid composition of highly purified mitochondrial outer membranes of rat liver and Neurospora crassa. Is cardiolipin present in the mitochondrial outer membrane?

Isolated mitochondrial outer membrane vesicles (OMV) are a suitable system for studying various functions of the mitochondrial outer membrane. For studies on mitochondrial lipid import as well as for studies on the role of lipids in processes occurring in the outer membrane, knowledge of the phospholipid composition of the outer membrane is indispensable. Recently, a mild subfractionation procedure was described for the isolation of highly purified OMV from mitochondria of Neurospora crassa (Mayer, A., Lill, R. and Neupert, W. (1993) J. Cell Biol. 121, 1233–1243). This procedure, which consists of swelling and mechanical disruption of mitochondria followed by two steps of sucrose density gradient centrifugation, was adapted for the isolation of OMV from rat liver mitochondria. Using the appropriate enzyme markers it is shown that the resulting OMV are obtained in a yield of 25%, and that their purity is superior to that of previous OMV preparations. Analysis of the phospholipid composition of the OMV showed that phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol are the major phospholipid constituents, and that cardiolipin is only present in trace amounts. The phospholipid composition is very similar to that of the highly purified OMV from mitochondria of Neurospora crassa, although the latter still contain a small amount of cardiolipin.     

The influence of the acyl chain composition of cardiolipin on the stability of mitochondrial complexes; An unexpected effect of cardiolipin in α-ketoglutarate dehydrogenase and prohibitin complexes

The role of cardiolipin acyl chain composition in assembly/stabilization of mitochondrial complexes was investigated using three yeast deletion mutants (acb1Δ strain; taz1Δ strain; and acb1Δtaz1Δ strain). Deletion of the TAZ1 gene, involved in cardiolipin acyl chain remodeling, is known to increase the content of monolyso-cardiolipin (MLCL) at the expense of CL, and to decrease the unsaturation of the remaining CL. Deletion of the ACB1 gene encoding the acyl-CoA-binding protein, involved in fatty acid elongation, decreases the average length of the CL acyl chains. Furthermore, a TAZ1ACB1 double deletion mutant strain was used in this study which has both a decrease in the length of the CL acyl chains and an increase in MLCL. BN/SDS PAGE analysis revealed that cardiolipin is important for the prohibitin–m-AAA protease complex, the α-ketoglutarate dehydrogenase complex and respiratory chain supercomplexes. The results indicate that the decreased level of complexes in taz1Δ and acb1Δtaz1Δ mitochondria is due to a decreased content of CL or the presence of MLCL.     

Is there an association between variables of postural control and strength in adolescents?

Is there an association between variables of postural control and strength in adolescents? The risk of sustaining sport injuries is particularly high in adolescents. Deficits in postural control and muscle strength represent 2 important intrinsic injury risk factors. Therefore, the purpose of this study was to investigate the relationship between variables of static and dynamic postural control and isometric and dynamic muscle strength and to find out whether there is an association between measures of postural control and muscle strength. Twenty-eight adolescents participated in this study (age 16.8 ± 0.6 years; body mass index 20.5 ± 1.8 kg · m(-2)). Biomechanic tests included the measurements of maximal isometric leg extension force (MIF) and rate of force development (RFDmax) of the leg extensors on a leg press with the feet resting on a force platform, vertical jumping force, and height (countermovement jump [CMJ]) on a force plate and the assessment of static (1-legged stance on a balance platform) and dynamic (mediolateral perturbation impulse on a balance platform) postural control. The significance level was set at p < 0.05. No significant associations were observed between measures of static and dynamic postural control. Significant positive correlations were detected between variables of isometric and dynamic muscle strength with r-values ranging from 0.441 to 0.779 (p < 0.05). Based on these models, a 100-N increase in MIF of the leg extensors was associated with 3.9, 4.2, and 6.5% better maximal CMJ force, CMJ height, and RFDmax, respectively. No significant correlations were observed between variables of postural control and muscle strength. The nonsignificant correlation between static/dynamic postural control and muscle strength implies that primarily dynamic measures of postural control should be incorporated in injury risk assessment and that postural control and muscle strength are independent of each other and may have to be trained complementary for lower extremity injury prevention and rehabilitation purposes.     

Is there an association between variables of postural control and strength in prepubertal children?

The risk of sustaining falls and sports-related injuries is particularly high in children. Deficits in balance and muscle strength represent 2 important intrinsic fall and injury-risk factors. Therefore, the purpose of this study was to investigate the relationship between variables of static and dynamic postural control and isometric and dynamic muscle strength and to find out whether there is an association between measures of postural control and muscle strength in prepubertal children. Thirty children participated in this study (age 6.7 ± 0.5 years; body mass index 16.0 ± 1.8 kg·m(-2)). Biomechanic tests included the measurements of maximal isometric torque and rate of force development (RFD) of the plantar flexors on an isokinetic device, jumping power and height (countermovement jump [CMJ]) on a force plate, and the assessment of static and dynamic posture during bipedal stance on a balance platform. The significance level was set at p < 0.05. No significant associations were observed between variables of static and dynamic postural control. Significant positive correlations were detected between the RFD of the plantar flexors and CMJ height (r = 0.425, p < 0.01). No statistically significant associations were found between measures of postural control and muscle strength. The nonsignificant correlations between static and dynamic postural control and muscle strength imply that primarily dynamic measures of postural control should be incorporated in fall and injury-risk assessment and that postural control and muscle strength appear to be independent of each other and may have to be trained in a complementary manner for fall and injury-preventive purposes.     

Is there a preferential interaction between cholesterol and tryptophan residues in membrane proteins?

Recently, several indications have been found that suggest a preferential interaction between cholesterol and tryptophan residues located near the membrane-water interface. The aim of this study was to investigate by direct methods how tryptophan and cholesterol interact with each other and what the possible consequences are for membrane organization. For this purpose, we used cholesterol-containing model membranes of dimyristoylphosphatidylcholine (DMPC) in which a transmembrane model peptide with flanking tryptophans [acetyl-GWW(LA)8LWWA-amide], called WALP23, was incorporated to mimic interfacial tryptophans of membrane proteins. These model systems were studied with two complementary methods. (1) Steady-state and time-resolved F?rster resonance energy transfer (FRET) experiments employing the fluorescent cholesterol analogue dehydroergosterol (DHE) in combination with a competition experiment with cholesterol were used to obtain information about the distribution of cholesterol in the bilayer in the presence of WALP23. The results were consistent with a random distribution of cholesterol which indicates that cholesterol and interfacial tryptophans are not preferentially located next to each other in these bilayer systems. (2) Solid-state 2H NMR experiments employing either deuterated cholesterol or indole ring-deuterated WALP23 peptides were performed to study the orientation and dynamics of both molecules. The results showed that the quadrupolar splittings of labeled cholesterol were not affected by an interaction with tryptophan-flanked peptides and, vice versa, that the quadrupolar splittings of labeled indole rings in WALP23 are not significantly influenced by addition of cholesterol to the bilayer. Therefore, both NMR and fluorescence spectroscopy results independently show that, at least in the model systems studied here, there is no evidence for a preferential interaction between cholesterol and tryptophans located at the bilayer interface.     

Synergistic interaction between the potato glycoalkaloids α-solanine and α-chaconine in relation to lysis of phospholipid/sterol liposomes

At pH 7.2, the steroidal glycoalkaloid α-chaconine disrupted phosphatidylcholine/cholesterol liposomes whereas α-solanine was virtually without effect. A glycoalkaloid mixture extracted from potato sprouts and comprising approximately equal amounts of solanine and chaconine had, at 150 μM, a lytic effect the same as a 150 μM solution of chaconine only. The apparent synergistic interaction between the two compounds was confirmed using 1:1 mixtures of authentic solanine and chaconine from different sources and of different batches. Combinations (1:1) of solanine or chaconine and tomatine or digitonin (both of which lysed liposomes) or β₂-chaconine (which is non-lytic) did not produce synergistic effects. The synergism between solanine and chaconine was observed only when the two compounds were present together, although the order of addition into the test system did not appear crucial. Pretreatment of liposomes with one glycoalkaloid and its subsequent removal did not permanently sensitize the membranes to the second glycoalkaloid. The magnitude of the synergism was dependent on the relative amounts of solanine and chaconine with maximal effects where chaconine comprised 40% or more of the mixture.     

Is there a trade-off between species diversity and genetic diversity in forest tree communities?

The two most important components of biodiversity, species diversity and genetic diversity, have generally been treated as separate topics, although a coordination between both components is believed to be critical for ecosystem stability and resilience. Based on a new trait concept that allows for the assessment of genetic diversity across species, the relationship between species diversity and genetic diversity was examined in eight forest tree communities composed of different tree genera including both climax and pioneer species. It was intended to check whether a trade-off exists between the two diversity components as was found in a few studies on animal species.Using several isozyme-gene systems as genetic markers, the genetic diversity across species within each of the tree communities was determined by two measures, the commonly used intraspecific genetic diversity averaged over species and the recently developed transspecific genetic diversity per species. Both data sets were compared with the corresponding community-specific species diversity resulting in a positive relationship between the two diversity components. A statistically significant positive correlation was established between the transspecific genetic diversity per species and the species diversity for three isozyme-gene systems. Beyond that, consistent results were obtained using different parameters of the diversity measure which characterize the total, the effective and the number of prevalent variants. The number of prevalent variants reflected most significantly the non-randomness of the observed diversity patterns.These findings can be explained by the observation that the pioneer tree species reveal a by far higher genetic diversity than the climax tree species, which means that an increase in species diversity, due to the addition of several pioneer species at the expense of one or two climax species, goes along with an increase in the level of genetic diversity. Forest tree communities with the highest degree of species diversity exhibit therefore the highest transspecific genetic diversity per species. This result was discussed with regard to the particular composition and stability of forest tree communities.     

Is there an influence of historical events on contemporary fish species richness in rivers? Comparisons between Western Europe and North America

Freshwater fish species richness on 132 West European and North American rivers is analysed using eleven variables related to contemporary ecology (nine) and history (two). This is done in order to examine the relative and joint effects of both historical and ongoing processes on the contemporary richness of these two regional fish faunas. Relationships are quantified by simple and stepwise multiple regression procedures. Species-area curves are presented for the fish faunas within both continents. We show that ecological factors statistically explain most of the variation in freshwater fish species richness for both continents. Effects of historical factors are shown to be statistically significant, but add only a little to the variance already explained by ecological factors. Our analyses further indicate that rivers (which flow directly into the ocean) support fewer species of fish than do similarly sized tributaries. The immigration-extinction hypothesis appears to provide a plausible explanation for this observed pattern. The fact that in our final model, a continental effect is still highly significant, leads us not to exclude the possibility of some other historical influences in generating different overall species richness levels on the two continents.     

Molecular evolution of cytochrome c oxidase subunit I in primates: is there coevolution between mitochondrial and nuclear genomes?

Phylogenetic analyses carried out on cytochrome c oxidase (COX) subunit I mitochondrial genes from 14 primates representing the major branches of the order and four outgroup nonprimate eutherians revealed that transversions and amino acid replacements (i.e., the more slowly occurring sequence changes) contained lower levels of homoplasy and thus provided more accurate information on cladistic relationships than transitions (i.e., the more rapidly occurring sequence changes). Several amino acids, each with a high likelihood of functionality involving the binding of cytochrome c or interaction with COX VIII, have changed in Anthropoidea, the primate suborder grouping New World monkey, Old World monkey, ape, and human lineages. They are conserved in other mammalian lineages and in nonanthropoid primates. Maximum-likelihood ancestral COX I nucleotide sequences were determined utilizing a near most parsimonious branching arrangement for the primate sequences that was consistent with previously hypothesized primate cladistic relationships based on larger and more diverse data sets. Relative rate tests of COX I mitochondrial sequences showed an elevated nonsynonymous (N) substitution rate for anthropoid-nonanthropoid comparisons. This finding for the largest mitochondrial (mt) DNA-encoded subunit is consistent with previous observations of elevated nonsynonymous substitution/synonymous substitution (S) rates in primates for mt-encoded COX II and for the nuclear-encoded COX IV and COX VIIa-H. Other COX-related proteins, including cytochrome c and cytochrome b, also show elevated amino acid replacement rates or N/S during similar time frames, suggesting that this group of interacting genes is likely to have coevolved during primate evolution.     

Is there an alternative to increasing the sample size in microarray studies?

Our answer to the question posed in the title is negative. This intentionally provocative note discusses the issue of sample size in microarray studies from several angles. We suggest that the current view of microarrays as no more than a screening tool be changed and small sample studies no longer be considered appropriate.     

Is there a primary role of the mitochondrial genome in Alzheimer’s disease?

The “mitochondrial cascade hypothesis” could explain many of the biochemical, genetic and pathological features of sporadic Alzheimer’s disease (AD). Somatic mutations in mitochondrial DNA (mtDNA) could cause energy failure, increased oxidative stress and accumulation of amyloid β, which in a vicious cycle reinforces mtDNA damage and oxidative stress. Despite the evidence of mitochondrial dysfunction in AD, and despite the cognitive impairment frequently reported in patients with mtDNA mutation, no causative mutation in the mtDNA have been linked to AD. Indeed, results of studies on the role of mtDNA polymorphisms or haplogroups in AD are controversial. In this minireview, we summarize the actual knowledge about the involvement of mtDNA in AD pathology.     

Is there an opiate receptor in the snail Megalobulimus sanctipauli? Action of morphine and naloxone

The effects of morphine sulfate (10, 15 and 20 mg/kg) or saline control (5 mg/kg) on the latency of the anterior body-lifting response to heat (avoidance response) were determined in four groups of snails Megalobulimus sanctipauli (n = 6) individually placed on a metal plate mounted on the surface of a water bath at 52 ± 1°C. The effects of pre-treatment with naloxone hydrochloride (5 mg/kg) or saline (2.5 ml/kg) control on the responses to morphine (15 mg/kg) were determined in two different groups of animals (n = 6). Administration of morphine resulted in an increase in the avoidance behavior latency with maximum effects occuring at 15 mg/kg, 10–15 min after injection. The effects of morphine disappeared within 90–120 min. Saline treatment had no detectable effects on the latency of the response to an aversive stimulus. Naloxone significantly blocked (P < 0.05, Student paired t-test) the increase in avoidance behavior latency. The present results indicate that: 1. morphine has an antinociceptive effect on the response of Megalobulimus sanctipauli to an aversive thermal stimulus; and 2. the morphine-induced “analgesia” may be caused by the stimulation of μ opiate receptors.     

Is there a link between the type of habitat and the patterns of abundance of holothurians in shallow rocky reefs?

The presence of a mosaic of habitats, largely determined by sea urchin grazing, across shallow rocky reefs may potentially influence in differences in the distribution patterns of invertebrates. The aim of this paper was to assess, using a correlative approach, whether the type of habitat influences the abundance patterns of holothurians in the eastern Atlantic. We hypothesized that abundances of large (> 10 cm) holothurians varied among four types of habitat (3 vegetated habitats with low abundances of the sea urchin D. antillarum vs. ‘barrens’ with hyperabundances of sea urchins), and that these differences were consistent at a hierarchy of spatial scales, including two islands and several replicated sites within each type of habitat and island. Three species of large holothurians were found, accounting for a total of 300 specimens. We found remarkable differences in abundances of holothurians between the ‘barrens’ and the three vegetated habitats. This pattern was strongest for the numerically dominant species, Holothuria sanctorii. Total abundances of holothurians were between 5 and 46 times more abundant in ‘barrens’ compared with the vegetated habitats. Inter-habitat differences were species-specific with some inconsistent patterns from one island to the other. The total abundances of holothurians tended to increase with the abundance of sea urchins within ‘barrens’. Our study suggests that there may be a link, at least for the dominant species Holothuria sanctorii, between the distribution and abundances of large holothurians and the habitat across shallow-waters of the eastern Atlantic.     

Is there chaos in the brain? I. Concepts of nonlinear dynamics and methods of investigation

In the light of results obtained during the last two decades in a number of laboratories, it appears that some of the tools of nonlinear dynamics, first developed and improved for the physical sciences and engineering, are well-suited for studies of biological phenomena. In particular it has become clear that the different regimes of activities undergone by nerve cells, neural assemblies and behavioural patterns, the linkage between them, and their modifications over time, cannot be fully understood in the context of even integrative physiology, without using these new techniques. This report, which is the first of two related papers, is aimed at introducing the non expert to the fundamental aspects of nonlinear dynamics, the most spectacular aspect of which is chaos theory. After a general history and definition of chaos the principles of analysis of time series in phase space and the general properties of chaotic trajectories will be described as will be the classical measures which allow a process to be classified as chaotic in ideal systems and models. We will then proceed to show how these methods need to be adapted for handling experimental time series; the dangers and pitfalls faced when dealing with non stationary and often noisy data will be stressed, and specific criteria for suspecting determinism in neuronal cells and/or assemblies will be described. We will finally address two fundamental questions, namely i) whether and how can one distinguish, deterministic patterns from stochastic ones, and, ii) what is the advantage of chaos over randomness: we will explain why and how the former can be controlled whereas, notoriously, the latter cannot be tamed. In the second paper of the series, results obtained at the level of single cells and their membrane conductances in real neuronal networks and in the study of higher brain functions, will be critically reviewed. It will be shown that the tools of nonlinear dynamics can be irreplaceable for revealing hidden mechanisms subserving, for example, neuronal synchronization and periodic oscillations. The benefits for the brain of adopting chaotic regimes with their wide range of potential behaviours and their aptitude to quickly react to changing conditions will also be considered.