Showing papers by "University College London published in 1987"

Astrocytes induce blood–brain barrier properties in endothelial cells

Abstract: The highly impermeable tight junctions between endothelial cells forming the capillaries and venules in the central nervous system (CNS) of higher vertebrates are thought to be responsible for the blood-brain barrier that impedes the passive diffusion of solutes from the blood into the extracellular space of the CNS. The ability of CNS endothelial cells to form a blood-brain barrier is not intrinsic to these cells but instead is induced by the CNS environment: Stewart and Wiley demonstrated that when avascular tissue from 3-day-old quail brain is transplanted into the coelomic cavity of chick embryos, the chick endothelial cells that vascularize the quail brain grafts form a competent blood-brain barrier; on the other hand, when avascular embryonic quail coelomic grafts are transplanted into embryonic chick brain, the chick endothelial cells that invade the mesenchymal tissue grafts form leaky capillaries and venules. It is, however, not known which cells in the CNS are responsible for inducing endothelial cells to form the tight junctions characteristic of the blood-brain barrier. Astrocytes are the most likely candidates since their processes form endfeet that collectively surround CNS microvessels. In this report we provide direct evidence that astrocytes are capable of inducing blood-brain barrier properties in non-neural endothelial cells in vivo.

Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development.

Abstract: This paper shows stage- and tissue-specific global demethylation and remethylation occurring during embryonic development. The egg genome is strikingly undermethylated and the sperm genome relatively methylated. Following a loss of genomic methylation during preimplantation development, embryonic and extraembryonic lineages are progressively and independently methylated to different final extents. Methylation continues postgastrulation and hence could be a mechanism initiating, or confirming, differential programming in the definitive germ layers. It is proposed that much of the methylation observed in somatic tissues acts to stabilize and reinforce prior events that regulate the activity of specific genes, chromosome domains or the X chromosome (in females). Fetal germ cell DNA is markedly undermethylated and we favour the idea that the germ lineage is set aside before the occurrence of extensive methylation of DNA in fetal precursor cells.

Concurrent morning increase in platelet aggregability and the risk of myocardial infarction and sudden cardiac death.

Abstract: We have previously reported that the frequencies of myocardial infarction and of sudden cardiac death are highest during the period from 6 a.m. to noon. Since platelet aggregation may have a role in triggering these disorders, we measured platelet activity at 3-hour intervals for 24 hours in 15 healthy men. In vitro platelet responsiveness to either adenosine diphosphate (ADP) or epinephrine was lower at 6 a.m. (before the subjects arose) than at 9 a.m. (60 minutes after they arose). The lowest concentration of these agents required to produce biphasic platelet aggregation decreased (i.e., aggregability increased) from a mean ±SEM of 4.7±0.6 to 3.7±0.6 μM (P<0.01) for ADP and from 3.7±0.8 to 1.8±0.5 μM (P<0.01) for epinephrine. The period from 6 to 9 a.m. was the only interval in the 24-hour period during which platelet aggregability increased significantly. We subsequently studied 10 subjects on alternate mornings after they arose at the normal time and after delayed arising. The morning increas...

Malignant lymphoma of mucosa‐associated lymphoid tissue

Abstract: Lymphomas of the gastrointestinal tract, salivary glands, lung and thyroid are grouped together as tumours arising in mucosa-associated lymphoid tissue. The great majority of them are of B-cell origin but distinctive T-cell lymphomas are also recognized in the gastrointestinal tract. These lymphomas tend to remain localized for prolonged periods but, whereas the B-cell group respond favourably to local therapy, the T-cell group are associated with severe morbidity and their overall prognosis is extremely poor. Accepted histological classifications of non-Hodgkin's lymphomas are difficult to apply to these tumours. In this paper their morphological features are reviewed; recent findings based on immunohistochemistry and DNA analysis are presented; and the biological behaviour of these tumours is discussed insofar as they offer insight into mucosal immunological mechanisms.

Recombination-line intensities for hydrogenic ions – I. Case B calculations for H I and He II

Abstract: Assuming Case B of Baker and Menzel (1938), the relative intensities of H I and He II recombination lines are determined for a larger range of temperature and density than previously considered and with the upper principle quantum number up to 50 and the lower number up to 29. Full collisional effects are included, and new collision strengths for the n = 1, 2, and 3 states of He(+) are presented. Case B theory is found to be invalidated for collisional excitation of the n = 3 levels from both n = 1 and n = 2 states under certain conditions which depend upon electron density and the Lyman-alpha escape probability, and the regimes of temperature and density for which Case B is valid are also considered.

Optical coherence-domain reflectometry: a new optical evaluation technique.

Abstract: An optical evaluation technique is described that is suitable for determining the positions and magnitudes of reflection sites within miniature optical assemblies. This method utilizes the coherence effects exhibited by a broadband optical source and is referred to as optical coherence-domain reflectometry. Background theory is given, and experimental results have demonstrated a resolution of 10 μm with an optical dynamic range of more than 100 dB.

Single unit activity in the rat hippocampus during a spatial memory task

Abstract: Single unit activity was recorded from complex spike cells in the hippocampus of the rat while the animal was performing a spatial memory task. The task required the animal to choose the correct arm of a 4 arm plus-shaped maze in order to obtain reward. The location of the goal arm was varied from trial to trial and was identified by 6 controlled spatial cues which were distributed around the enclosure and which were rotated in step with the goal. On some trials these spatial cues were present throughout the trial (spatial reference memory trials) while on other trials they were present during the first part of the trial but were removed before the rat was allowed to choose the goal (spatial working memory trials). On these latter trials the animal had to remember the location of the cues and/or goal during the delay in order to choose correctly. 55 units were recorded during sufficient reference memory trials for the relationship between their firing pattern and different spatial aspects of the environment to be determined. 33 units had fields with significant relations to the controlled cues while 16 had significant relations to the static background cues, those cues in the environment which did not change position from trial to trial. Of 43 units which could be tested for their relation to the shape of the maze arms themselves, 15 showed such a relationship. Therefore the place units can be influenced by different aspects of the spatial environment but those related to the task requirement appear to be more potent. Interaction effects between the different spatial factors also influenced the firing pattern of some units. Of particular interest was the interaction between the controlled cues and the static background cues found in some cells since this might shed some light on how the hippocampus enables the rat to solve the memory task. 30 units with place fields related to the controlled cues were recorded during successful performance on spatial working memory trials as well as during spatial reference memory trials. The place fields of 90% of these units were maintained during the retention phase of the memory trials. During the recording of some units, other types of trial were given as well. On control trials, the cues were removed before the rat was placed on the maze. These trials provided controls for the potential influence of information left behind by the controlled cues and for the influence of the animal's behaviour on the unit activity. They also provided information about the unit firing in the absence of the controlled spatial cues and about the animal's choice of goal under these circumstances. During control trials, the units typically maintained their place fields but these fields had no relation to the experimenter-defined goal. The rat's choice of goal arm at the end of the trial, however, continued to show the usual spatial relationship to the fields. The data from these control trials, taken together with the interaction between the controlled cues and the static background cues seen in some of the cells and the characteristic mistakes made by each rat, suggest that the animal enters the task on each trial with an expected or preferred orientation of the controlled spatial cues relative to the background cues and that it must reorient its cognitive map of the environment or search for a different map when the actual orientation of the controlled cues departs from this default condition. Detour trials differed from working memory trials in that the animal was not immediately allowed to choose the goal at the end of the retention period but was forced to enter a non-goal arm instead. These trials ruled out the possibility that the animal was remembering the specific turn required to reach the goal and demonstrated that the place fields for the entire maze are set up as a result of exposure to the controlled spatial cues in any one of the start arms. Overall, the results provide strong support for the cognitive map theory of hippocampal function. In particular, they demonstrate that the representations of places within an environment are connected together to form a map, that the orientation of this map relative to an environment can be changed from trial to trial, and that this orientation is “remembered” following the removal of the controlled spatial cues.

Dynamic receptive field plasticity in rat spinal cord dorsal horn following C-primary afferent input

Abstract: The central terminals of cutaneous primary afferent neurons are spatially ordered in the dorsal horn in a highly organized fashion such that a point-to-point map represents the body surface. This afferent terminal somatotopic map correlates with the map of the receptive fields of the cells on which they terminate. The location, size and modality of the cutaneous receptive fields of dorsal horn neurons necessarily depend upon the anatomical presence of afferent nerve fibres which deliver information from the periphery, directly or indirectly, to the cells. However the receptive field size and modality of a cell do not depend only on anatomical connections. Excitatory and inhibitory interneurons, descending influences and facilitations or depressions of synaptic contacts can alter receptive field properties. Here we show that prolonged and substantial cutaneous receptive field changes can be produced by brief inputs from peripheral unmyelinated afferent fibres.

Some Models for Rainfall Based on Stochastic Point Processes

Abstract: Stochastic models are discussed for the variation of rainfall intensity at a fixed point in space. First, models are analysed in which storm events arise in a Poisson process, each such event being associated with a period of rainfall of random duration and constant but random intensity. Total rainfall intensity is formed by adding the contributions from all storm events. Then similar but more complex models are studied in which storms arise in a Poisson process, each storm giving rise to a cluster of rain cells and each cell being associated with a random period of rain. The main properties of these models are determined analytically. Analysis of some hourly rainfall data from Denver, Colorado shows the clustered models to be much the more satisfactory.

Sexual practices, sexually transmitted diseases, and the incidence of anal cancer.

Abstract: To elucidate the risk factors for anal cancer, we interviewed and obtained blood specimens from 148 persons with anal cancer and from 166 controls with colon cancer in whom these diseases were diagnosed during 1978-1985. We found that in men, a history of receptive anal intercourse (related to homosexual behavior) was strongly associated with the occurrence of anal cancer (relative risk, 33.1; 95 percent confidence interval, 4.0 to 272.1). Anal intercourse was only weakly associated with the risk of anal cancer in women (relative risk, 1.8; 95 percent confidence interval, 0.7 to 4.2). Among the subjects with squamous-cell anal cancer, 47.1 percent of homosexual men, 28.6 percent of heterosexual men, and 28.3 percent of women gave a history of genital warts, as compared with only 1 to 2 percent of controls and no patients with transitional-cell anal cancer. In patients without a history of warts, anal cancer was associated with a history of gonorrhea in heterosexual men (relative risk, 17.2; 95 percent confidence interval, 2.0 to 149.4) and with seropositivity for herpes simplex type 2 (relative risk, 4.1; 95 percent confidence interval, 1.9 to 8.8) and Chlamydia trachomatis (relative risk, 2.3; 95 percent confidence interval, 1.1 to 4.8) in women. Current cigarette smoking was a substantial risk factor in both women (relative risk, 7.7; 95 percent confidence interval, 3.5 to 17.2) and men (relative risk, 9.4; 95 percent confidence interval, 2.3 to 38.5). We conclude that homosexual behavior in men is a risk factor for anal cancer, and that squamous-cell anal cancer is also associated with a history of genital warts, an association suggesting that papillomavirus infection is a cause of anal cancer. Certain other genital infections and cigarette smoking are also associated with anal cancer.

Subcutaneous formalin-induced activity of dorsal horn neurones in the rat: differential response to an intrathecal opiate administered pre or post formalin.

Abstract: Many studies of pain and nociception use short-lasting acute stimuli which may have limited relevance to prolonged or chronic pain states. Using extracellular single-unit recording in the dorsal horn of the rat lumbar spinal cord the present study examines the response of neurones to a long-lasting nociceptive stimulus, i.e., 50 microliter 5% formalin injected into the corresponding receptive field in the ipsilateral hind paw, and modulation of this response by an opioid. Formalin produced a distinct biphasic excitatory response in all convergent neurones tested; an immediate acute or phasic peak of neuronal firing (mean maximum 22 spikes/sec) 0-10 min post injection, and a second more prolonged tonic excitatory response (mean maximum 12 spikes/sec) over a period 20-65 min after formalin. Cells only activated by innocuous stimuli were not excited by formalin indicating the involvement of C fibre afferents in the excitatory response of convergent neurones to formalin. Both the biphasic nature and the time course of the neuronal response are similar to those observed in behavioural studies. Intrathecal DAGO (Tyr-D-AlaGlyMePheGly-ol), a potent and selective mu opioid receptor agonist, applied 20 min prior to formalin completely inhibited both peaks of excitation. Co-administration of intrathecal naloxone with the agonist restored the biphasic response. By contrast, when the administration of naloxone was delayed to 2 min post formalin so that inhibition of the first peak by DAGO pretreatment occurred, there was no subsequent second peak of activity although antagonism of the opioid would have occurred. When DAGO was applied 2 min post formalin so the initial acute response occurred, the inhibitory effect of the agonist on the second peak was far less. Thus the relative ability of DAGO to modulate the biphasic excitatory response of cells to formalin depends on whether the agonist is administered prior to or after the formalin and the appearance of the second peak may depend on the presence of the first. These results are discussed in light of the role of these neurones in nociception, opioid effects and changes in neural systems following peripheral stimuli.

Repeated high-force eccentric exercise: effects on muscle pain and damage.

Abstract: Five women and three men (aged 24–43 yr) performed maximal eccentric contractions of the elbow flexors (for 20 min) on three occasions, spaced 2 wk apart. Muscle pain, strength and contractile prop...

Characterization of a panel of highly variable minisatellites cloned from human DNA.

Abstract: Summary Five of the most variable loci detected in human DNA by hybridization with DNA fingerprint probes have been cloned and characterized. Each locus consists of a tandem-repetitive minisatellite, with repeat units ranging in length from 9 to 45 base pairs depending on the locus. All of these cloned minisatellites act as locus-specific hybridization probes, and detect extremely variable Mendelian loci with heterozygosities ranging from 90 to 99%. These five hypervariable loci, together with a previously-isolated minisatellite designated pΛg3, are dispersed over four autosomes (chromosomes 1, 5, 7 and 12). Syntenic pairs on chromosomes 1 and 7 show no detectable pair-wise linkage, and thus these hypervariable loci show no evidence of clustering within the genome and should provide valuable markers for mapping inherited disease. The locus-specific minisatellites act as very sensitive hybridization probes, and can be pooled to detect several hypervariable loci simultaneously. The applications of these probes in individual identification, paternity testing and analysis of cell chimaerism are discussed, and are illustrated by an analysis of forensic specimens from two victims who had been sexually assaulted and murdered. We are very grateful to Professor J. Dausset and Dr H. Cann at the Human Polymorphism Study Centre, Paris. for the generous provision of DNA samples from the panel of CEPH families, to Dr Mary Davis for providing DNA from the JDA hybrids, and also to the following people who kindly allowed us to use their hybrids. Dr Ellen Solomon. Dr Nigel Spurr. Dr P. Goodfellow, Dr Denise Sheer, Dr John Cowell and Dr Ben Carritt. We also thank Anabel Kearney who did the enzyme analysis on the hybrids, and Lynne West who did the karyotyping. We are also grateful to the Leicestershire Constabulary for their permission to cite details of the forensic analysis. A.J.J. is a Lister Institute Research Fellow, and this work was supported by a grant to A.J.J. from the Medical Research Council. The minisatellite probes are the subject of Patent Applications, and commercial enquiries should be addressed to the Lister Institute of Preventive Medicine, Brockley Hill, Stanmore. Middlesex, H A7 4JD, U.K.

Evidence for migration of oligodendrocyte--type-2 astrocyte progenitor cells into the developing rat optic nerve.

Abstract: Formation of myelinated tracts in central nervous system (CNS) regions such as the optic nerve seems to depend on two glial cell types, both of which derive from a common progenitor cell. This oligodendrocyte–type-2 astrocyte (O–2A) progenitor cell gives rise to oligodendrocytes, which produce internodal myelin sheaths, and to type-2 astrocytes, which extend fine processes in the region of the nodal axolemma1,2. The optic nerve also contains a third glial cell, the type-1 astrocyte, which derives from a separate precursor1. These three glial cells develop in a fixed sequence over a two-week period3: type-1 astrocytes appear at embryonic day 16 (E16), oligodendrocytes at the day of birth (E21 or postnatal day P0), and type-2 astrocytes between P8 and P10. Type-1 astrocytes secrete a potent mitogen which causes expansion of the O–2A progenitor cell population in vitro4,5. Here, we report that dividing O–2A progenitor cells are highly motile and seem to migrate from the brain into the optic nerve, beginning at its chiasmal end. Our results indicate that long-distance migration along the neural axis is characteristic only of progenitors of the O–2A lineage and may serve to distribute these cells to regions of the CNS that will become myelinated. These results also suggest that the intrinsic neuroepithelial cells of the optic stalk may be even more restricted than previously thought, giving rise only to type-1 astrocytes.

Précis of Relevance: Communication and Cognition

Abstract: In Relevance: Communication and Cognition, we outline a new approach to the study of human communication, one based on a general view of human cognition Attention and thought processes, we argue, automatically turn toward information that seems relevant: that is, capable of yielding cognitive effects – the more, and the more economically, the greater the relevance We analyse both the nature ofcognitive effects and the inferential processes by which they are derivedCommunication can be achieved by two different means: by encoding and decoding messages or by providing evidence for an intended inference about the communicator's informative intention Verbal communication, we argue, exploits both types of process The linguistic meaning of an utterance, recovered by specialised decoding processes, serves as the input to unspecialised central inferential processes by which the speaker's intentions are recognisedFundamental to our account of inferential communication is the fact that to communicate is to claimsomeone's attention, and hence to imply that the information communicated is relevant We call this idea, that communicated information comes with a guarantee of relevance, the principle of relevance We show that every utterance has at most a single interpretation consistent with the principle of relevance, which is thus enough on its own to account for the interaction of linguistic meaning with contextual factors in disambiguation, reference assignment, the recovery of implicatures, the interpretation ofmetaphor and irony, the recovery of illocutionary force, and other linguistically underdetermined aspects of utterance interpretation

Electrogenic glutamate uptake is a major current carrier in the membrane of axolotl retinal glial cells

Abstract: Glutamate is taken up avidly by glial cells in the central nervous system. Glutamate uptake may terminate the transmitter action of glutamate released from neurons, and keep extracellular glutamate at concentrations below those which are neurotoxic. We report here that glutamate evokes a large inward current in retinal glial cells which have their membrane potential and intracellular ion concentrations controlled by the whole-cell patch-clamp technique. This current seems to be due to an electrogenic glutamate uptake carrier, which transports at least two sodium ions with every glutamate anion carried into the cell. Glutamate uptake is strongly voltage-dependent, decreasing at depolarized potentials: when fully activated, it contributes almost half of the conductance in the part of the glial cell membrane facing the retinal neurons. The spatial localization, glutamate affinity and magnitude of the uptake are appropriate for terminating the synaptic action of glutamate released from photoreceptors and bipolar cells. These data challenge present explanations of how the b-wave of the electroretinogram is generated, and suggest a mechanism for non-vesicular voltage-dependent release of glutamate from neurons.

Human muscle strength training: the effects of three different regimens and the nature of the resultant changes.

Abstract: 1. Increases in strength and size of the quadriceps muscle have been compared during 12 weeks of either isometric or dynamic strength training. 2. Isometric training of one leg resulted in a significant increase in force (35 +/- 19%, mean +/- S.D., n = 6) with no change in the contralateral untrained control leg. 3. Quadriceps cross-sectional area was measured from mid-thigh X-ray computerized tomography (c.t.) scans before and after training. The increase in area (5 +/- 4.6%, mean +/- S.D., n = 6) was smaller than, and not correlated with, the increase in strength. 4. The possibility that the stimulus for gain in strength is the high force developed in the muscle was examined by comparing two training regimes, one where the muscle shortened (concentric) and the other where the muscle was stretched (eccentric) during the training exercise. Forces generated during eccentric training were 45% higher than during concentric training. 5. Similar changes in strength and muscle cross-sectional area were found after the two forms of exercise. Eccentric exercise increased isometric force by 11 +/- 3.6% (mean +/- S.D., n = 6), and concentric training by 15 +/- 8.0% (mean +/- S.D., n = 6). In both cases there was an approximate 5% increase in cross-sectional area. 6. It is concluded that as a result of strength training the main change in the first 12 weeks is an increase in the force generated per unit cross-sectional area of muscle. The stimulus for this is unknown but comparison of the effects of eccentric and concentric training suggest it is unlikely to be solely mechanical stress or metabolic fluxes in the muscle.

Multiple-conductance channels activated by excitatory amino acids in cerebellar neurons.

Abstract: In the mammalian central nervous system amino acids such as L-glutamate and L-aspartate are thought to act as fast synaptic transmitters. It has been suggested that at least three pharmacologically-distinguishable types of glutamate receptor occur in central neurons and that these are selectively activated by the glutamate analogues N-methyl-D-aspartate (NMDA), quisqualate and kainate. These three receptor types would be expected to open ion channels with different conductances. Hence if agonists produce similar channel conductances this would suggest they are acting on the same receptor. Another possibility is suggested by experiments on spinal neurons, where GABA (gamma-amino butyric acid) and glycine appear to open different sub-conductance levels of one class of channel while acting on different receptors. By analogy, several types of glutamate receptor could also be linked to a single type of channel with several sub-conductance states. We have examined these possibilities in cerebellar neurons by analysing the single-channel currents activated by L-glutamate, L-aspartate, NMDA, quisqualate and kainate in excised membrane patches. All of these agonists are capable of opening channels with at least five different conductance levels, the largest being about 45-50 pS. NMDA predominantly activated conductance levels above 30 pS while quisqualate and kainate mainly activated ones below 20 pS. The presence of clear transitions between levels favours the idea that the five main levels are all sub-states of the same type of channel.

Motor cortex stimulation in intact man. 2. Multiple descending volleys.

Abstract: Using an isometric strain gauge, we measured the twitch force produced in the first dorsal interosseous (FDI) muscle by a single anodal shock to the contralateral scalp At high intensities of stimulation this twitch can greatly exceed the force produced by supramaximal stimulation of peripheral nerve This indicates that a single cortical shock can cause repetitive firing of some or all FDI motoneurons Such repetitive firing was demonstrated using a collision technique in which a supramaximal ulnar nerve stimulus was given at the wrist shortly after a cortical shock The antidromic volley from the peripheral nerve stimulation failed to obliterate completely the response to cortical stimulation Additional EMG activity was visible in the normally silent period between ulnar M and F waves This activity must have been due to the presence of repetitive volleys of activity set up in spinal motoneurons by the cortical shock Such activity summates with the twitch produced by the ulnar M wave to produce a very large force twitch of the muscle Multiple firing of some motoneurons can be observed in some individuals at cortical stimulation intensities below that necessary to evoke activity in all the motoneurons in the FDI pool Multiple firing probably was caused by repetitive excitatory inputs impinging on spinal motoneurons These could be demonstrated using poststimulus time histogram techniques on single motor units Low intensities of cortical stimulation produced a single short duration (mean 18 ms) peak of increased motor unit firing 20 to 30 ms after the shock At high intensities, this was followed by extra peaks some 4 to 5 ms later H reflex testing showed that the threshold of the initial descending volley, produced by the cortical stimulus was uninfluenced by a voluntary contraction These results are discussed with reference to the D and I waves recorded from pyramidal tract after anodal stimulation of the exposed cortex in animals

Deletion of a DNA sequence at the chromosomal region 3p21 in all major types of lung cancer

Abstract: In childhood malignancies such as retinoblastoma and Wilms tumour, of which both familial and sporadic forms exist, recessive mutations of presumed differentiation genes have been implicated in tumorigenesis1,2. A proportion of cases appear with microscopically visible chromosome deletions which indicate the regions where the genes concerned are located. Mutation or loss of one allele causes a cancer predisposition. For tumour development functional loss of the remaining normal allele is also required. In cancers with both familial and sporadic forms, molecular-genetic studies have shown that deletion is often one of the mutational events2–5.Although familial and sporadic forms have never been distinguished in lung cancer, deletions of the short arm of chromosome 3 have been described for small cell lung cancer (SCLC) (refs 6, 7), but their general occurrence in SCLC has been disputed8–10. Using a molecular-genetic approach, we here present evidence for a consistent deletion at the chromosomal region 3p21, not only in SCLC11, but in all major types of lung cancer.

The accessible surface area and stability of oligomeric proteins

Abstract: Protein structures are stabilized by hydrophobic and van der Waals forces, and by hydrogen bonds. The relation between these ther-modynamic quantities and the actual three-dimensional structure of proteins can not be calculated precisely. However, certain empirical relations have been discovered. Hydrophobic energy is gained by the reduction of surface in contact with water1. For monomeric proteins, the area of the surface accessible to solvent, and of that buried in the interior, is a simple function of molecular weight. Proteins with different shapes and secondary structures, but of the same molecular weight, have the same accessible surface area2–5. It has been argued that there is no similar relationship for large oligomeric proteins6. In this paper we show that the surface areas of oligomeric proteins, and the areas of the surface buried within them, are directly related to relative molecular mass. Although oligomers of the same molecular weight bury the same amounts of surface, the proportions buried within and between subunits vary. This has important implications for the role of subunit interfaces in the stability and activity of oligomeric proteins.

Evidence for the presence of a reversible Ca2+-dependent pore activated by oxidative stress in heart mitochondria

Abstract: Rat heart mitochondria became permeabilized to sucrose when incubated with 100 nmol of Ca2+/mg of protein in the presence of Pi. Ca2+ chelation with EGTA restored impermeability to sucrose, which became entrapped in the matrix space. t-Butylhydroperoxide markedly promoted permeabilization in the presence of Ca2+ but not in its absence, and Ca2+-plus-t-butylhydroperoxide-induced permeabilization was reversed by EGTA. The data suggest that Ca2+ and oxidative stress synergistically promote the reversible opening of an inner membrane pore.