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Myocardial discontinuities: a substrate for producing virtual electrodes that directly excite the myocardium by shocks.

BACKGROUND: Theoretical models suggest that an electrical stimulus causes regions of depolarization and hyperpolarization on either side of a myocardial discontinuity. This study determined experimentally whether an artificial discontinuity gives rise to an activation front in response to an electrical stimulus, consistent with the creation of such polarized regions. METHODS AND RESULTS: After a thoracotomy in six dogs, a 504-unipolar-electrode plaque was sutured to the right ventricular epicardium to map activations. From a line electrode parallel to one side of the plaque, 10 S1 stimuli were delivered, followed by S2 and S3 stimuli (S1S1, S1S2, S2S3 interval=300 ms). S1 and S3 stimuli were 25 mA; 5-ms S2 stimuli of both polarities were initially 25 mA and increased in 25 mA increments. The plaque was removed, and a transmural incision was made through the ventricular wall in the middle of the mapped region and sutured closed. The plaque was replaced and the stimulation protocol repeated. Before the incision, S2 stimuli directly activated tissue only near the stimulation site. An activation front arose at the border of the directly activated region and propagated across the plaque. As the S2 stimulus strength was increased, the size of the directly activated region increased. After the incision, sufficiently large S2 stimuli caused direct activation of tissue adjacent to the transmural incision as well as at the stimulation site. Activation fronts that arose adjacent to the transmural incision either propagated proximally toward the stimulation site and collided with the activation front originating from the stimulation wire or propagated distally away from the incision. Minimum S2 stimulus strengths activating areas adjacent to the incision were only 45+/-14% (cathode) and 39+/-18% (anode) of the strengths required to directly activate the same area before the incision was formed (P<.05). CONCLUSIONS: Myocardial discontinuities can give rise to activation fronts after a stimulus, suggesting the presence of polarized regions adjacent to the discontinuity.

Animals↗

Radiative habitable zones in martian polar environments.

The biologically damaging solar ultraviolet (UV) radiation (quantified by the DNA-weighted dose) reaches the martian surface in extremely high levels. Searching for potentially habitable UV-protected environments on Mars, we considered the polar ice caps that consist of a seasonally varying CO2 ice cover and a permanent H2O ice layer. It was found that, though the CO2 ice is insufficient by itself to screen the UV radiation, at approximately 1 m depth within the perennial H2O ice the DNA-weighted dose is reduced to terrestrial levels. This depth depends strongly on the optical properties of the H2O ice layers (for instance snow-like layers). The Earth-like DNA-weighted dose and Photosynthetically Active Radiation (PAR) requirements were used to define the upper and lower limits of the northern and southern polar Radiative Habitable Zone (RHZ) for which a temporal and spatial mapping was performed. Based on these studies we conclude that photosynthetic life might be possible within the ice layers of the polar regions. The thickness varies along each martian polar spring and summer between approximately 1.5 and 2.4 m for H2O ice-like layers, and a few centimeters for snow-like covers. These martian Earth-like radiative habitable environments may be primary targets for future martian astrobiological missions. Special attention should be paid to planetary protection, since the polar RHZ may also be subject to terrestrial contamination by probes.

Arctic Regions↗

Distribution of connective tissue proteins in chick muscle spindles as revealed by monoclonal antibodies: a unique distribution of brachionectin/tenascin.

The distribution of chick muscle spindles of eight connective tissue proteins (collagen types I, IV, V, and VI, laminin, heparan sulfate, fibronectin, and brachionectin/tenascin) was examined by immunofluorescent histochemistry. Intrafusal fibers were surrounded by layers of collagen type VI and fibronectin, and by an external lamina containing collagen type IV, laminin, and heparan sulfate. Most of these layers displayed a different pattern of staining at the sensory region of the equator than at the polar region. The crescent-like sheath that caps each intrafusal fiber and sensory terminal at the equator was strongly positive for collagen type I and weakly positive for collagen type V. The outer spindle capsule contained laminin, heparan sulfate, collagen types IV and VI, brachionectin/tenascin, fibronectin, and to a lesser degree also collagen types I and V. Brachionectin/tenascin had the narrowest distribution of any of the connective tissue macromolecules studied. It was found only in the outer capsule and in the coverings of blood vessels and nerves associated with the outer capsule.

Animals↗

Event-related neural activity associated with the Stroop task.

The time course of neural activity supporting performance during the Stroop task was investigated using event-related brain potentials (ERPs). Four spatially and temporally distinct modulations were observed differentiating the ERPs elicited by incongruent trials from the ERPs elicited by congruent, neutral, or word identification trials. Two of these modulations reflected increased negativity over the fronto-central region and positivity over the fronto-polar region for incongruent trials and may reflect conflict detection and resolution processes. The other modulations, distributed over the left parietal and temporo-parietal regions, may reflect the activity of a meaning-based conceptual level system active during congruent, neutral, and word identification trials; and the activity of a perceptual level system supporting task performance when only color information can guide an efficient response on incongruent trials.

Adult↗

Jupiter: Aerosol Chemistry in the Polar Atmosphere.

Aromatic compounds have been considered a likely candidate for enhanced aerosol formation in the polar region of Jupiter. We develop a new chemical model for aromatic compounds in the Jovian auroral thermosphere/ionosphere. The model is based on a previous model for hydrocarbon chemistry in the Jovian atmosphere and is constrained by observations from Voyager, Galileo, and the Infrared Space Observatory. Precipitation of energetic electrons provides the major energy source for the production of benzene and other heavier aromatic hydrocarbons. The maximum mixing ratio of benzene in the polar model is 2x10-9, a value that can be compared with the observed value of 2+2-1x10-9 in the north polar auroral region. Sufficient quantities of the higher ring species are produced so that their saturated vapor pressures are exceeded. Condensation of these molecules is expected to lead to aerosol formation.

Journal Article↗

Locations of local anesthetic dibucaine in model membranes and the interaction between dibucaine and a Na+ channel inactivation gate peptide as studied by 2H- and 1H-NMR spectroscopies.

To study the molecular mechanisms of local anesthesia, locations of local anesthetic dibucaine in model membranes and the interactions of dibucaine with a Na+ channel inactivation gate peptide have been studied by 2H- and 1H-NMR spectroscopies. The 2H-NMR spectra of dibucaine-d9 and dibucaine-d1, which are deuterated at the butoxy group and at the 3 position in its quinoline ring, respectively, have been observed in multilamellar dispersions of the lipid mixture composed of phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine. 2H-NMR spectra of deuterated palmitic acids incorporated, as a probe, into the lipid mixture containing cholesterol have also been observed. An order parameter, SCD, for each carbon segment was calculated from the observed quadrupole splittings. Combining these results, we concluded that first, the butoxy group of dibucaine is penetrating between the acyl chains of lipids in the model membranes, and second, the quinoline ring of dibucaine is located at the polar region of lipids but not at the hydrophobic acyl chain moiety. These results mean that dibucaine is situated in a favorable position that permits it to interact with a cluster of hydrophobic amino acids (Ile-Phe-Met) within the intracellular linker between domains III and IV of Na+ channel protein, which functions as an inactivation gate. To confirm whether the dibucaine molecule at the surface region of lipids can really interact with the hydrophobic amino acids, we synthesized a model peptide that includes the hydrophobic amino acids (Ac-GGQDIFMTEEQK-OH, MP-1), the amino acid sequence of which corresponds to the linker part of rat brain type IIA Na+ channel, and the one in which Phe has been substituted by Gln (MP-2), and measured 1H-NMR spectra in both phosphate buffer and phosphatidylserine liposomes. It was found that the quinoline ring of dibucaine can interact with the aromatic ring of Phe by stacking of the rings; moreover, the interaction can be reinforced by the presence of lipids. In conclusion, we wish to propose that local anesthesia originates from the pi-stacking interaction between aromatic rings of an anesthetic molecule located at the polar headgroup region of the so-called boundary lipids and of the Phe in the intracellular linker between domains III and IV of the Na+ channel protein, prolonging the inactivated state and consequently making it impossible to proceed to the resting state.

Amino Acid Sequence↗

The Drosophila embryonic patterning determinant torsolike is a component of the eggshell.

The development of the head and tail regions of the Drosophila embryo is dependent upon the localized polar activation of Torso (Tor), a receptor tyrosine kinase that is uniformly distributed in the membrane of the developing embryo. Trunk (Trk), the proposed ligand for Tor, is secreted as an inactive precursor into the perivitelline fluid that lies between the embryonic membrane and the vitelline membrane (VM), the inner layer of the eggshell. The spatial regulation of Trk processing is thought to be mediated by the secreted product of the torsolike (tsl) gene, which is expressed during oogenesis by a specialized population of follicle cells present at the two ends of the oocyte. We show here that Tsl protein is specifically localized to the polar regions of the VM in laid eggs. We further demonstrate that although Tsl can associate with nonpolar regions of the VM, the activity of polar-localized Tsl is enhanced, suggesting the existence of another spatially restricted factor acting in this pathway. The incorporation of Tsl into the VM provides a mechanism for the transfer of spatial information from the follicle cells to the developing embryo. To our knowledge, Tsl represents the first example of an embryonic patterning determinant that is a component of the eggshell.

Animals↗

Solvents effects on the conformational order of triacontyl modified silica gels as evaluated by Fourier transform infrared spectroscopy.

C30 alkyl modified silica gels have attracted much attention because of their enhanced shape selectivity for various types of analytes, which for instance cannot be separated with conventional C8 and C18 stationary phases. Since the retention processes strongly depend on the nature of solvents and composition of the stationary phases, a FTIR study was conducted to evaluate the influence of solvents on the conformational order of the alkyl chains in C30 alkyl modified silica gels. Variable temperature IR measurements are carried out between 273 and 353 K in the presence of polar and nonpolar solvents. Information about the conformational behavior of the tethered alkyl chains is derived from the analysis of the symmetric and antisymmetric CH2 stretching band regions. Polar solvents show both enhanced conformational order and disorder of the alkyl chains - irrespective of temperature - when compared to dry C30 alkyl modified silica gels, while nonpolar solvents in general give rise to enhanced conformational disorder in the alkyl chain region. Moreover, for polar solvents a correlation exists between the stretching band position, reflecting alkyl chain conformational order, and the solvent solvatochromic parameter pi*. Finally, both partition and adsorption models are considered to play an important role for the solvent-alkyl chain interactions which in turn determines the conformational order of the alkyl chains and thus the chromatographic properties of these phases.

Acetonitriles↗

Surface characteristics of oocytes from juvenile mice as observed in the scanning electron microscope.

The in vivo and in vitro development of the zona pellucida as well as the vitelline membrane surface of oocytes isolated from juvenile mice aged between 8 and 30 days p.p. were investigated by scanning electron microscopy. In vivo a consistent development of the zona pellucida surface can be observed, namely the formation of a fibrous network like structure interspersed with numerous pores. After enzymatic removal of the zona pellucida the surface of the vitelline membrane was studied. In "normal" oocytes with intact germinal vesicles, microvilli were distributed over the entire oocyte surface in all age groups investigated. After resumption of meiosis in vitro a characteristic differentiation on the vitelline membrane occurs. A glabrous polar region appears in primary oocytes and a glabrous polar body in secondary oocytes. The same differentiation in surface organization could be observed in the in vivo precociously matured oocytes.

Age Factors↗

Dithiols and monothiols are linked with GABA transport in membrane vesicles of rat brain synaptosomes.

The properties of gamma-aminobutyric acid (GABA) transport into membrane vesicles derived from synaptosomes of rat brain have been studied using membrane-permeable and -impermeable sulfhydryl reagents, dithiol-specific reagents and oxidizing reagents. GABA transport is inhibited, reversibly, by very low concentrations of the membrane-permeable trivalent arsenical, phenylarsine oxide. Preincubation with this reagent only partially protects GABA transport from inactivation by N-ethylmaleimide (NEM). Thorin, a negatively charged trivalent arsenical, has no influence on GABA transport at concentrations 100-fold higher than that of the inhibitory phenylarsine oxide. The impermeant oxidizing agent, potassium ferricyanide, did not inhibit transport whereas the permeant reagent, diamide, was inhibitory. These data indicate that the GABA transporter possesses an activity-linked dithiol in a hydrophobic region of the carrier not accessible to charged, polar reagents. p-Chloromercuribenzenesulfonate (PCMBS) also inhibits but does not protect against NEM inactivation, suggesting the occurrence of an activity-linked monothiol in a polar region of the carrier.

Animals↗

Effect of transmembrane ion gradients on Raman spectra of sealed, hemoglobin-free erythrocyte membrane vesicles.

Sealed hemoglobin-free erythrocyte vesicles have been isolated. Imposition of transmembrane cation gradients increases the intensity of Raman scattering in the CH3-stretching region as observed with unsealed ghosts at temperatures greater than 38 degrees C and pH less than 7.0 [Verma, S. P. & Wallach, D. F. H. (1976) Proc. Natl. Acad. Sci. USA 73, 3358--3561]. Modifications in the amide I and amide III frequencies consistent with increased helicity of membrane proteins are observed upon imposition of a cation gradient. Spectrin-free vesicles also demonstrate cation gradient-sensitive intensity changes in the CH3-stretching region. However, no evidence for cation gradient-related protein conformation changes is found with these vesicles. The transmembrane potential of these vesicles has been altered by variations in anion composition and the electrogenic activity of Na+,K+-ATPase. The membrane potential was monitored by cyanine dye fluorescence. Imposition of a membrane potential (negative inside) also increased the intensity of Raman scattering in the CH3-stretching region. These results suggest that a transmembrane potential (negative inside) and/or cation gradient can energize membranes by compression of the apolar region and transfer of protein methyl residues into polar regions.

Erythrocyte Membrane↗

Mechanism of the formation of contractile ring in dividing cultured animal cells. II. Cortical movement of microinjected actin filaments.

The contractile ring in dividing animal cells is formed primarily through the reorganization of existing actin filaments (Cao, L.-G., and Y.-L. Wang. 1990. J. Cell Biol. 110:1089-1096), but it is not clear whether the process involves a random recruitment of diffusible actin filaments from the cytoplasm, or a directional movement of cortically associated filaments toward the equator. We have studied this question by observing the distribution of actin filaments that have been labeled with fluorescent phalloidin and microinjected into dividing normal rat kidney (NRK) cells. The labeled filaments are present primarily in the cytoplasm during prometaphase and early metaphase, but become associated extensively with the cell cortex 10-15 min before the onset of anaphase. This process is manifested both as an increase in cortical fluorescence intensity and as movements of discrete aggregates of actin filaments toward the cortex. The concentration of actin fluorescence in the equatorial region, accompanied by a decrease of fluorescence in polar regions, is detected 2-3 min after the onset of anaphase. By directly tracing the distribution of aggregates of labeled actin filaments, we are able to detect, during anaphase and telophase, movements of cortical actin filaments toward the equator at an average rate of 1.0 micron/min. Our results, combined with previous observations, suggest that the organization of actin filaments during cytokinesis probably involves an association of cytoplasmic filaments with the cortex, a movement of cortical filaments toward the cleavage furrow, and a dissociation of filaments from the equatorial cortex.

Actin Cytoskeleton↗

Interfacial conditions between a press-fit acetabular cup and bone during daily activities: implications for achieving bone in-growth.

Interfacial gaps and relative micromotions during activities are widely believed to restrict the boney in-growth process of non-cemented acetabular cups. Using finite element modeling of the cup-bone system, relative micromotions and interfacial gaps are calculated for walking slow, normal and fast and for climbing upstairs, downstairs and standing up from a chair. A 2mm press-fit is simulated and interfacial conditions in the immediate postoperative period (i.e. prior to boney in-growth) calculated between paired nodes covering the whole of the interface. In regions of 'safe' micromotions and 'allowable' gaps, boney in-growth is simulated by specifying zero relative displacement between nodal pairs. The modified model is then resubjected to the loads associated with climbing upstairs, which was shown to be the worst activity. Interfacial conditions are recalculated for subsequent iterations. The procedure is repeated until no further in-growth is predicted. The final pattern of in-growth calculated with the model compares reasonably well with histological evidence from explanted canine cups (Cha et al., 1998. Transactions of the Orthopaedic Research Society, 23, p. 373). Bridging between adjacent regions of in-growth is observed. Notably, in-growth occurs at most of the periphery but not in the polar region. The lack of polar in-growth is caused by the interfacial gap assumed to exist after cup implantation. It is suggested that increasing/decreasing hip-joint loads would have little effect on this lack of polar in-growth. However, excessive micromotions as a result of high hip-joint loads cause a lack of in-growth in the anterior region of the periphery in the model. Although such results were not found in the canine study, if relevant to the general human population, the avoidance of harsh weight-bearing activities may encourage complete peripheral in-growth but is speculated to do little for polar in-growth.

Acetabulum↗

Control of pattern formation in urodele limb ontogeny: a review and a hypothesis.

From a review of the literature, the hypothesis is advanced that the forelimb region of the urodele embryo acquires its transverse axial polarity and pattern by the action of posterior and dorsal polarizing regions. The anterior-posterior and dorsal-ventral axes are determined simultaneously and their determination is a prerequisite for proximal-distal outgrowth. Outgrowth of the limb bud is accompanied by the generation, between proximal and distal boundaries, of a set of positional values specifying proximal-distal axial polarity and pattern. The proximal boundary is the initial positional value carried by the cells of the limb area. The distal boundary is imposed upon the outermost layer of limb disc cells by the overlying ectoderm.

Ambystoma↗

Global geographic differences in marine metals toxicity.

Biochemical reaction rates, metabolic rates, and other rates of biological activity increase exponentially with temperature. It has thus been hypothesized that toxicity to chemical contaminants may increase from polar to temperate to tropical species; however, until recently, polar data to test this hypothesis were not available. This study examined differences in the acute sensitivities of marine invertebrates to four metals (Cu, Cd, Zn, Pb) for polar, temperate and tropical species; data deficiencies for polar regions prohibited comparisons using chronic end-points or other chemicals. Differences between the three geographic regions were not predictable based on temperature (other factors such as differences in dissolved organic carbon concentrations also affect toxicity). There appears to be no universal, predictable pattern of increased toxicity from polar to tropical regions. Toxicity data from one geographic region will not be universally protective of other regions.

Adaptation, Physiological↗

A new grouping of intrafusal muscle fibers based on developmental studies of muscle spindles in the cat.

The development of muscle spindles was studied using the tenuissimus muscle of the cat. Observations show that the intrafusal muscle fibers develop as two separate groups: one group represented by a single nuclear bag fiber while the second group comprises the second nuclear bag fiber in association with all the nuclear chain fibers. This grouping is most pronounced in the fetus and is clearly seen in neonatal kittens (i.e., up to 2 weeks of age). As the intrafusal fibers begin to separate from each other, the groupings become less noticeable, although this basic pattern is often retained in the adult. The pattern of intrafusal fiber grouping is most noticeable in the equatorial regions of the spindle and least noticeable in the polar regions. This is not the grouping of fibers which would have been expected from a consideration of existing reports on muscle spindles. The implications for spindle form and function are considered.

Animals↗

Sequential 123I-iododexetimide scans in temporal lobe epilepsy: comparison with neuroimaging scans (MR imaging and 18F-FDG PET imaging).

PURPOSE: Muscarinic acetylcholine receptors (mAChRs) play an important role in the generation of seizures. Single-photon emission computed tomography (SPECT) with 12I-iododexetimide (IDEX) depicts tracer uptake by mAChRs. Our aims were to: (a) determine the optimum time for interictal IDEX SPECT imaging; (b) determine the accuracy of IDEX scans in the localisation of seizure foci when compared with video EEG and MR imaging in patients with temporal lobe epilepsy (TLE); (c) characterise the distribution of IDEX binding in the temporal lobes and (d) compare IDEX SPECT and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in identifying seizure foci. METHODS: We performed sequential scans using IDEX SPECT imaging at 0, 3, 6 and 24 h in 12 consecutive patients with refractory TLE undergoing assessment for epilepsy surgery. Visual and region of interest analyses of the mesial, lateral and polar regions of the temporal lobes were used to compare IDEX SPECT, FDG PET and MR imaging in seizure onset localisation. RESULTS: The 6-h IDEX scan (92%; kappa=0.83, p=0.003) was superior to the 0-h (36%; kappa=0.01, p>0.05), 3-h (55%; kappa=0.13, p>0.05) and 24-h IDEX scans in identifying the temporal lobe of seizure origin. The 6-h IDEX scan correctly predicted the temporal lobe of seizure origin in two patients who required intracranial EEG recordings to define the seizure onset. Reduced ligand binding was most marked at the temporal pole and mesial temporal structures. IDEX SPECT was superior to interictal FDG PET (75%; kappa=0.66, p=0.023) in seizure onset localisation. MR imaging was non-localising in two patients in whom it was normal and in another patient in whom there was bilateral symmetrical hippocampal atrophy. CONCLUSION: The 6-h IDEX SPECT scan is a viable alternative to FDG PET imaging in seizure onset localisation in TLE.

Adult↗

On the use of regular solution theory as a theoretical frame for the analysis of membrane phenomena.

The structural heterogeneity of the phospholipid membrane causes difficulties in the analysis of membrane functions. These difficulties can be overcome by using probes which dissolve preferentially into one of the regions, provided that a general theory correlating probe behaviour to membrane structure exists. The use of regular solution theory (RST) as a theoretical frame for membrane analysis is examined below, and it is concluded that some, but not all, of the relations furnished by the theory are useful for membrane analysis. Using these relations, it is concluded that the hydrophobic region of the membrane has a stabilizing effect. The polar region is less stable and changes faster than the hydrophobic region. Diffusion rates are smaller in the hydrophobic region.

Diffusion↗