Management of adrenal cysts

Electrophoretic mobility data of SR vesicles reconstituted with uncharged and two mixtures of charged and uncharged lipids (Brethes, D., Dulon, D., Johannin, G., Arrio, B., Gulik-Krzywicki, T., Chevallier, J. 1986. Study of the electrokinetic properties of reconstituted sarcoplasmic reticulum vesicles. Arch. Biochem. Biophys. 246:355-356) were analyzed in terms of four models of the membrane-water interface: (I) a smooth, negatively charged surface; (II) a negatively charged surface of lipid bilayer covered with an electrically neutral surface frictional layer; (III) an electrically neutral lipid bilayer covered with a neutral frictional layer containing a sheet of negative charge at some distance above the surface of the bilayer; (IV) an electrically neutral lipid bilayer covered with a homogeneously charged frictional layer. The electrophoretic mobility was predicted from the numerical integration of Poisson-Boltzmann and Navier-Stokes equations. Experimental results were consistent only with predictions based on Model-III with charged sheet about 4 nm above the bilayer and frictional layer about 10 nm thick. Assuming that the charge of the SR membrane is solely due to that on Ca++-ATPase pumps, the dominant SR protein, the mobility data of SR and reconstituted SR vesicles are consistent with 12 electron charges/ATPase. This value compares well to the net charge of the cytoplasmic portion of ATPase estimated from the amino acid sequence (-11e). The position of the charged sheet suggests that the charge on the ATPase is concentrated in the middle of the cytoplasmic portion. The frictional layer of SR can be also assigned to the cytoplasmic portion of Ca++-ATPase. The layer has been characterized with hydrodynamic shielding length of 1. 1 nm. Its thickness is comparable to the height of the cytoplasmic portion of Ca++-ATPase.     

Phospholipase A2 action on planar lipid bilayers generates a small, transitory current that is voltage independent

Addition of either bee venom or Trimeresurus flavoviridis phospholipase A2 (PLA2) to the solution bathing the front side of a voltage-clamped, planar lipid bilayer consistently produced a transitory current lasting approximately 100 s. This current is consistent with anions moving through the membrane to the rear side. The peak current is independent of holding potential. PLA2 activity on phospholipid membranes not only produced a current but also led to membrane rupture within 300 s. The current depends on Ca2+ and lipid type. Addition of PLA2 in the absence of Ca2+ or to membranes made of nonsubstrate lipids (e.g., glycerol monooleate or lysophosphatidylcholine) produced no current and did not break the bilayer. Peak current height, signal decay time, and time to membrane rupture all depended on PLA2 dose, whereas total charge produced was constant. This current does not flow through ion channels because there are no channels present and the current is not voltage dependent. The evidence is consistent with the hypothesis that the current is generated by the movement of ionized fatty acid produced by PLA2 action. These results demonstrate a simple method to measure enzyme activity in the presence of different substrates and varied environmental conditions.     

Energetics of inclusion-induced bilayer deformations

The material properties of lipid bilayers can affect membrane protein function whenever conformational changes in the membrane-spanning proteins perturb the structure of the surrounding bilayer. This coupling between the protein and the bilayer arises from hydrophobic interactions between the protein and the bilayer. We analyze the free energy cost associated with a hydrophobic mismatch, i.e., a difference between the length of the protein's hydrophobic exterior surface and the average thickness of the bilayer's hydrophobic core, using a (liquid-crystal) elastic model of bilayer deformations. The free energy of the deformation is described as the sum of three contributions: compression-expansion, splay-distortion, and surface tension. When evaluating the interdependence among the energy components, one modulus renormalizes the other: e.g., a change in the compression-expansion modulus affects not only the compression-expansion energy but also the splay-distortion energy. The surface tension contribution always is negligible in thin solvent-free bilayers. When evaluating the energy per unit distance (away from the inclusion), the splay-distortion component dominates close to the bilayer/inclusion boundary, whereas the compression-expansion component is more prominent further away from the boundary. Despite this complexity, the bilayer deformation energy in many cases can be described by a linear spring formalism. The results show that, for a protein embedded in a membrane with an initial hydrophobic mismatch of only 1 A, an increase in hydrophobic mismatch to 1.3 A can increase the Boltzmann factor (the equilibrium distribution for protein conformation) 10-fold due to the elastic properties of the bilayer.     

Mathematical modelling of cancer invasion and metastasis: an interdisciplinary workshop held at the University of Warwick, Coventry, UK. 11-13 September 1996

A microneedle puncture of the fibroblast or sea urchin egg surface rapidly evokes a localized exocytotic reaction that may be required for the rapid resealing that follows this breach in plasma membrane integrity (Steinhardt, R.A,. G. Bi, and J.M. Alderton. 1994. Science (Wash. DC). 263:390-393). How this exocytotic reaction facilitates the resealing process is unknown. We found that starfish oocytes and sea urchin eggs rapidly reseal much larger disruptions than those produced with a microneedle. When an approximately 40 by 10 microm surface patch was torn off, entry of fluorescein stachyose (FS; 1, 000 mol wt) or fluorescein dextran (FDx; 10,000 mol wt) from extracellular sea water (SW) was not detected by confocal microscopy. Moreover, only a brief (approximately 5-10 s) rise in cytosolic Ca2+ was detected at the wound site. Several lines of evidence indicate that intracellular membranes are the primary source of the membrane recruited for this massive resealing event. When we injected FS-containing SW deep into the cells, a vesicle formed immediately, entrapping within its confines most of the FS. DiI staining and EM confirmed that the barrier delimiting injected SW was a membrane bilayer. The threshold for vesicle formation was approximately 3 mM Ca2+ (SW is approximately 10 mM Ca2+). The capacity of intracellular membranes for sealing off SW was further demonstrated by extruding egg cytoplasm from a micropipet into SW. A boundary immediately formed around such cytoplasm, entrapping FDx or FS dissolved in it. This entrapment did not occur in Ca2+ -free SW (CFSW). When egg cytoplasm stratified by centrifugation was exposed to SW, only the yolk platelet-rich domain formed a membrane, suggesting that the yolk platelet is a critical element in this response and that the ER is not required. We propose that plasma membrane disruption evokes Ca2+ regulated vesicle-vesicle (including endocytic compartments but possibly excluding ER) fusion reactions. The function in resealing of this cytoplasmic fusion reaction is to form a replacement bilayer patch. This patch is added to the discontinuous surface bilayer by exocytotic fusion events.     

Preservation of human skin structure and function in organ culture

Human keratinocytes can be maintained in monolayer culture under serum-free conditions for an extended period of time. Under low Ca2+ conditions (e.g., 0.05-0.15 mM), an undifferentiated state is maintained and the cells proliferate optimally. When the Ca2+ concentration is raised to approximately 1.0 mM, differentiation occurs and growth shows. Human dermal fibroblasts can also be maintained in monolayer culture under serum-free conditions, but in contrast to keratinocytes, a physiological level of extracellular Ca2+ (above approximately 1.0 mM) is required. A variety of growth factors stimulate proliferation of both cell types but do not replace the Ca2+ requirement of the fibroblast population. All-trans retinoic acid also promotes proliferation of both cell types and, most interestingly, replaces the requirement-for a physiological level of Ca2+ in the fibroblast cultures. Human skin can be maintained in organ culture for an extended period of time under serum-free conditions. Conditions optimized for fibroblast proliferation (either physiological Ca2+ or all-trans retinoic acid) are required. In the presence of culture conditions optimized for the epithelial cell component, both the epidermis and dermis rapidly lyse. These data suggest that the fibroblast is the critical component in maintaining homeostasis of skin, and that maintenance of the epidermis as well as the dermis depends on the viability and functioning of these cells.     

Ionic requirements for RNA binding, cleavage, and ligation by the hairpin ribozyme

Metal ion requirements for RNA binding, cleavage, and ligation by the hairpin ribozyme have been analyzed. RNA cleavage is observed when Mg2+, Sr2+, or Ca2+ are added to a 40 mM Tris-HCl buffer, indicating that these divalent cations were capable of supporting the reaction. No reaction was observed when other ions (Mn2+, Co2+, Cd2+, Ni2+, Ba2+, Na+, K+, Li+, NH4+, Rb+, and Cs+) were tested. In the absence of added metal ions, spermidine can induce a very slow ribozyme-catalyzed cleavage reaction that is not quenched by chelating agents (EDTA and EGTA) that are capable of quenching the metal-dependent reaction. Addition of Mn2+ to a reaction containing 2 mM spermidine increases the rate of the catalytic step by at least 100-fold. Spermidine also reduces the magnesium requirement for the reaction and strongly stimulates activity at limiting Mg2+ concentrations. There are no special ionic requirements for formation of the initial ribozyme-substrate complex--analysis of complex formation using native gels and kinetic assays shows that the ribozyme can bind substrate in 40 mM Tris-HCl buffer. Complex formation is inhibited by both Mn2+ and Co2+. Ionic requirements for the ribozyme-catalyzed ligation reaction are very similar to those for the cleavage reaction. We propose a model for catalysis by the hairpin ribozyme that is consistent with these findings. Formation of an initial ribozyme-substrate complex occurs without the obligatory involvement of divalent cations. Ions (e.g., Mg2+) can then bind to form a catalytically proficient complex, which reacts and dissociates.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glutathione modulates ryanodine receptor from skeletal muscle sarcoplasmic reticulum. Evidence for redox regulation of the Ca2+ release mechanism

In this report, we demonstrate the ability of the cellular thiol glutathione to modulate the ryanodine receptor from skeletal muscle sarcoplasmic reticulum. Reduced glutathione (GSH) inhibited Ca2+-stimulated [3H]ryanodine binding to the sarcoplasmic reticulum and inhibited the single-channel gating activity of the reconstituted Ca2+ release channel. The effects of GSH on both the [3H]ryanodine binding and single-channel measurements were dose-dependent, exhibiting an IC50 of approximately 2.4 mM in binding experiments. Scatchard analysis demonstrated that GSH decreased the binding affinity of ryanodine for its receptor (increased Kd) and lowered the maximal binding occupancy (Bmax). In addition, GSH did not modify the Ca2+ dependence of [3H]ryanodine binding. In single-channel experiments, GSH (5-10 mM), added to the cis side of the bilayer lipid membrane, lowered the open probability (Po) of a Ca2+ (50 microM)-stimulated Ca2+ channel without modifying the single-channel conductance. Subsequent perfusion of the cis chamber with an identical buffer, containing 50 microM Ca2+ without GSH, re-established Ca2+-stimulated channel gating. GSH did not inhibit channel activity when added to the trans side of the bilayer lipid membrane. Similar to GSH, the thiol-reducing agents dithiothreitol and beta-mercaptoethanol also inhibited high affinity [3H]ryanodine binding to sarcoplasmic reticulum membranes. In contrast to GSH, glutathione disulfide (GSSG) was a potent stimulator of high affinity [3H]ryanodine binding and it also stimulated the activity of the reconstituted single Ca2+ release channel. These results provide direct evidence that glutathione interacts with reactive thiols associated with the Ca2+ release channel/ryanodine receptor complex, which are located on the cytoplasmic face of the SR, and support previous observations (Liu, G, Abramson, J. J., Zable, A. C., and Pessah, I. N. (1994) Mol. Pharmacol. 45, 189-200) that reactive thiols may be involved in the gating of the Ca2+ release channel.     

Intracellular calcium, currents, and stimulus-response coupling in endothelial cells

Vascular endothelium appears to be a unique organ. It not only responds to numerous hormonal and chemical signals but also senses changes in physical parameters such as shear stress, producing mediators that modulate the responses of numerous cells, including vascular smooth muscle, platelets, and leukocytes. In many cases, the initial response of endothelial cells to these diverse signals involves elevation of cytosolic Ca2+ and activation of Ca(2+)-dependent enzymes, including nitric oxide synthase and phospholipase A2. Both the release of Ca2+ from intracellular stores, most likely the endoplasmic reticulum, and the influx of Ca2+ from the extracellular space contribute to the [Ca2+]i increase. The most important trigger for Ca2+ release is inositol 1,4,5-trisphosphate, which is generated by the action of phospholipase C, a plasmalemmal enzyme activated in many cases by the receptor-G protein cascade. Ca2+ influx appears to be related to the activity of receptor-G protein-enzyme complex and to the degree of fullness of the endoplasmic reticulum but does not involve voltage-gated Ca2+ channels. The magnitude of the Ca2+ influx depends on the electrochemical gradient, which is modulated by the membrane potential, Vm. Under basal conditions, Vm is dominated by a large inward rectifier K+ current. Some stimuli, e.g., acetylcholine, have been shown to hyperpolarize Vm, thus increasing the electrochemical gradient for Ca2+, which appears to be modulated by activation of Ca(2+)-dependent K+ and Cl- currents. However, the lack of potent and specific blockers for many of the described or postulated channels (e.g., nonselective cation channel, Ca(2+)-activated Cl- channel) makes an estimation of their effect on endothelial cell function rather difficult. Possible future directions of research and clinical implications are discussed.     

New light on mitochondrial calcium

The possibility of specifically addressing recombinant probes to mitochondria is a novel, powerful way to study these organelles within living cells. We first showed that the Ca(2+)-sensitive photoprotein aequorin, modified by the addition of a mitochondrial targeting sequence, allows to monitor specifically the Ca2+ concentration in the mitochondrial matrix ([Ca2+]m) of living cells. With this tool, we could show that, upon physiological stimulation, mitochondria undergo a major rise in [Ca2+]m, well in the range of the Ca2+ sensitivity of the matrix dehydrogenases, in a wide variety of cell types, ranging from non excitable, e.g., HeLa and CHO, and excitable, e.g., cell lines to primary cultures of various embryological origin, such as myocytes and neurons. This phenomenon, while providing an obvious mechanism for tuning mitochondrial activity to cell needs, appeared at first in striking contrast with the low affinity of mitochondrial Ca2+ uptake mechanisms. Based on indirect evidence, we proposed that the mitochondria might be close to the source of the Ca2+ signal and thus exposed to microdomains of high [Ca2+], hence allowing the rapid accumulation of Ca2+ into the organelle. In order to verify this intriguing possibility, we followed two approaches. In the first, we constructed a novel aequorin chimera, targeted to the mitochondrial intermembrane space (MIMS), i.e., the region sensed by the low-affinity Ca2+ uptake systems of the inner mitochondrial membrane. With this probe, we observed that, upon agonist stimulation, a portion of the MIMS is exposed to saturating Ca2+ concentrations, thus confirming the occurrence of microdomains of high [Ca2+] next to mitochondria. In the second approach, we directly investigated the spatial relationship of the mitochondria and the ER, the source of agonist-releasable Ca2+ in non-excitable cells. For this purpose, we constructed GFP-based probes of organelle structure; namely, by targeting to these organelles GFP mutants with different spectral properties, we could label them simultaneously in living cells. By using an imaging system endowed with high speed and sensitivity, which allows to obtain high-resolution 3D images, we could demonstrate that close contacts (< 80 nm) occur in vivo between mitochondria and the ER.     

Molecular theory of lipid-protein interaction and the Lalpha-HII transition

We present a molecular-level theory for lipid-protein interaction and apply it to the study of lipid-mediated interactions between proteins and the protein-induced transition from the planar bilayer (Lalpha) to the inverse-hexagonal (HII) phase. The proteins are treated as rigid, membrane-spanning, hydrophobic inclusions of different size and shape, e.g., "cylinder-like," "barrel-like," or "vase-like." We assume strong hydrophobic coupling between the protein and its neighbor lipids. This means that, if necessary, the flexible lipid chains surrounding the protein will stretch, compress, and/or tilt to bridge the hydrophobic thickness mismatch between the protein and the unperturbed bilayer. The system free energy is expressed as an integral over local molecular contributions, the latter accounting for interheadgroup repulsion, hydrocarbon-water surface energy, and chain stretching-tilting effects. We show that the molecular interaction constants are intimately related to familiar elastic (continuum) characteristics of the membrane, such as the bending rigidity and spontaneous curvature, as well as to the less familiar tilt modulus. The equilibrium configuration of the membrane is determined by minimizing the free energy functional, subject to boundary conditions dictated by the size, shape, and spatial distribution of inclusions. A similar procedure is used to calculate the free energy and structure of peptide-free and peptide-rich hexagonal phases. Two degrees of freedom are involved in the variational minimization procedure: the local length and local tilt angle of the lipid chains. The inclusion of chain tilt is particularly important for studying noncylindrical (for instance, barrel-like) inclusions and analyzing the structure of the HII lipid phase; e.g., we find that chain tilt relaxation implies strong faceting of the lipid monolayers in the hexagonal phase. Consistent with experiment, we find that only short peptides (large negative mismatch) can induce the Lalpha --> HII transition. At the transition, a peptide-poor Lalpha phase coexists with a peptide-rich HII phase.     

Induction of apoptotic DNA fragmentation and c-jun downregulation in human myeloid leukemia cells by the permeant Ca2+ chelator BAPTA/AM

The permeant Ca2+ chelator acetoxymethyl-1,2-bis(2-aminopheoxy)ethane- N,N,N',N'-tetraacetic acid (BAPTA/AM), an agent previously used to characterize drug-induced apoptosis in neoplastic cells, has been examined with respect to induction of DNA fragmentation and cytotoxicity in the human leukemia cell lines HL-60 and U937. Exposure of cells to various concentrations of BAPTA/AM for 6 h resulted in a biphasic induction of internucleosomal DNA cleavage, with maximal damage occurring at 10-microM concentrations. Higher BAPTA/AM concentrations were associated with the loss of internucleosomal cleavage products, but with the appearance of larger (i.e., 50-kilobase) fragments on pulsed-field gel electrophoresis. Cells exposed to 10 microM BAPTA/AM exhibited classic apoptotic morphology, whereas cells exposed to 50-microM concentrations displayed atypical features (e.g., cell swelling, chromatin clumping); in each case, substantial cytotoxicity was noted. The actions of BAPTA/AM did not depend upon the presence of extracellular Ca2+, nor were they affected by impermeant Ca2+ chelators. Measurement of cytosolic Ca2+ by Fura-2/AM or Indo-1 revealed late but not early increases in intracellular Ca2+ in BAPTA/AM-treated cells. Finally, BAPTA/AM-induced apoptosis was accompanied by the concentration-dependent downregulation of the immediate early response gene c-jun. These findings suggest a complex role for Ca2+ chelators such as BAPTA/AM in the regulation of human myeloid leukemic cell apoptosis, and indicate that this agent may selectively antagonize internucleosomal DNA fragmentation without interfering with other aspects of the apoptotic response and/or cell lethality.     

On the recollection of specific- and partial-source information

Memory judgments can be based on information that is more or less specific with respect to the source of an item. The authors introduce a procedure and multinomial model for measuring specific- and partial-source information. In 2 experiments, participants heard words spoken by 4 different voices: 2 male voices and 2 female voices. During the test, participants were required to remember who spoke the test items (e.g., Male 1, Male 2, Female 1, Female 2, or new word). Participants often remembered information about the gender of the source (i.e., partial-source information) when they did not remember information that identified the source itself (i.e., specific-source information). Dividing attention during retrieval impaired participants' memory for specific-source information (i.e., voice information) but did not affect memory for partial-source information (i.e., gender information).     

Vitamin and mineral transfer during fetal development and the early postnatal period in pigs

There are periods during pregnancy when sows may have a temporally high requirement for certain vitamins and minerals. Proteins transferring retinol and Fe to the developing pig fetus have been discovered, whereas transport mechanisms for other vitamins and minerals are probably present but have not yet been identified. Sow body tissues can serve as a reservoir for many micronutrients, but it is not known whether these reserves can supply an adequate quantity during critical fetal developmental periods. There is a low placental transfer of vitamin E to the fetus even if the dietary concentration fed to a gestating animal is high, but colostrum and milk concentrations can be increased when the nutrient is fed to sows. If the dam's diet contains inadequate Ca or P, the concentration of these elements in the developing fetus and milk will not be affected. Consequently, sow bone demineralization will occur under conditions of dietary inadequacy of Ca and P. Other nutrients can be depleted from sow tissue reservoirs over several parities (e.g., Se), resulting in low quantities being provided in the milk for nursing pigs. Scientific information involving adequate vitamin and mineral nutrition for female pigs to improve conception rate and embryonal survival that will result in optimum fetal and postnatal pig development can be considered to be in its infancy.     

Biological significance of divalent metal ion binding to 14-3-3 proteins in relationship to nitrate reductase inactivation

In this report we address two questions regarding the regulation of phosphorylated nitrate reductase (pNR; EC 1.6.6.1) by 14-3-3 proteins. The first concerns the requirement for millimolar concentrations of a divalent cation in order to form the inactive pNR:14-3-3 complex at pH 7.5. The second concerns the reduced requirement for divalent cations at pH 6.5. In answering these questions we highlight a possible general mechanism involved in the regulation of 14-3-3 binding to target proteins. We show that divalent cations (e.g. Ca2+, Mg2+ and Mn2+) bind directly to 14-3-3s, and as a result cause a conformational change, manifested as an increase in surface hydrophobicity. A similar change is also obtained by decreasing the pH from pH 7.5 to pH 6.5, in the absence of divalent cations, and we propose that protonation of amino acid residues brings about a similar effect to metal ion binding. A possible regulatory mechanism, where the 14-3-3 protein has to be "primed" prior to binding a target protein, is discussed.     

Semantic effects in single-word naming.

Three experiments demonstrated that, for lower frequency words, reading aloud is affected not only by spelling-sound typicality but also by a semantic variable, imageability. Participants were slower and more error prone when naming exception words with abstract meanings (e.g., scarce ) than when naming either abstract regular words (e.g., scribe ) or imageable exception words (e.g., soot ). It is proposed that semantic representations of words have the largest impact on translating orthography to phonology when this translation process is slow or noisy (i.e., for low-frequency exceptions) and that words with rich semantic representations (i.e., high-imageability words) are most likely to benefit from this interaction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Localization in the II-III loop of the dihydropyridine receptor of a sequence critical for excitation-contraction coupling

Skeletal and cardiac muscles express distinct isoforms of the dihydropyridine receptor (DHPR), a type of voltage-gated Ca2+ channel that is important for excitation-contraction (EC) coupling. However, entry of Ca2+ through the channel is not required for skeletal muscle-type EC coupling. Previous work (Tanabe, T., Beam, K. G., Adams, B. A., Niidome, T., and Numa, S. (1990) Nature 346, 567-569) revealed that the loop between repeats II and III (II-III loop) is an important determinant of skeletal-type EC coupling. In the present study we have further dissected the regions of the II-III loop critical for skeletal-type EC coupling by expression of cDNA constructs in dysgenic myotubes. Because Ser687 of the skeletal II-III loop has been reported to be rapidly phosphorylated in vitro, we substituted this serine with alanine, the corresponding cardiac residue. This alanine-substituted skeletal DHPR retained the ability to mediate skeletal-type EC coupling. Weak skeletal-type EC coupling was produced by a chimeric DHPR, which was entirely cardiac except for a small amount of skeletal sequence (residues 725-742) in the II-III loop. Skeletal-type coupling was stronger when both residues 725-742 and adjacent residues were skeletal (e.g. a chimera containing skeletal residues 711-765). However, residues 725-742 appeared to be critical because skeletal-type coupling was not produced either by a chimera with skeletal residues 711-732 or by one with skeletal residues 734-765.     

Consensus information, prediction, and causal attribution: A review of the literature and issues.

Suggests that it is useful to distinguish between 2 types of consensus information—normative expectancies (e.g., E. E. Jones and D. McGillis's 1976 prior probability concept) and explicit base rates (e.g., H. H. Kelley's 1967 conception of observed covariation across actors). Normative expectancies, which may be derived from a knowledge of one's own behavior (i.e., the false-consensus effect) or the behavior of others, provide a basis for prediction and causal inference. Explicit, sample-based consensus may also be employed, but under somewhat restrictive conditions: (a) when prior expectations are neutralized and/or (b) when the consensus manipulation is particularly strong, salient, easily translatable, representative of the criterial population, and causally relevant. Additional issues are reviewed (e.g., the cognitive strategies by which observers reject base rates), and recommendations for research (e.g., how normative expectancies develop) are noted. (62 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Attention, automaticity, and levels of representation in number processing.

Participants performed same–different judgments for pairs of numerals in 2 conditions: numerical matching (responding "same" to pairs such as 2–TWO), or physical matching (responding "different" to pairs such as 2–TWO). In most cases, a distance effect was obtained, with the different responses being slower when the 2 numbers were numerically close together (e.g., 1–2) than when they were further apart (e.g., 1–8). This indicates that numbers were automatically converted mentally into quantities, even when the participants had been told to attend exclusively to their physical characteristics. As postulated by several models of number processing, (e.g., Dehaene, see PA, Vol 80:4300; McCloskey, see PA, Vol 80:6390) Arabic and verbal numerals thus appear to converge toward a common semantic representation of quantities. However, the present results suggest that an asemantic transcoding route might allow for a direct mapping of Arabic and verbal numbers, perhaps by means of a common phonological representation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nitrophorin-2: a novel mixed-type reversible specific inhibitor of the intrinsic factor-X activating complex

Nitrophorin-2 (NP-2), isolated from salivary glands of the blood-sucking insect Rhodnius prolixus, has been shown to be a specific inhibitor of the intrinsic factor X-(FX)-activating complex. The inhibitory effect of NP-2 is most potent in the presence of both FVIIIa and phospholipids (artificial phospholipid vesicles or activated human platelets). Detailed kinetic analyses of the inhibitory mechanism of NP-2 demonstrated a decrease in both Vmax and K(m) of activated FIX-(FIXa)-catalyzed FX activation in the presence of FVIIIa and phospholipid vesicles, characteristic of a hyperbolic mixed-type reversible inhibitor. NP-2 exhibits a higher binding affinity for the enzyme-substrate complex, i.e., FIXa/FVIIIa/ Ca2+/phospholipids/FX complex (Ki' = 6.2 nM) than for the enzyme complex, i.e., FIXa/FVIIIa/Ca2+/ phospholipids (Ki = 16.5 nM). The same inhibitory kinetic mechanism is valid in platelet-mediated FIXa-catalyzed FX activation (Ki' = 5.9 nM and Ki = 12.6 nM, respectively). The fact that NP-2 increases the concentrations (EC50) of FIXa, FVIIIa, and phospholipid vesicles required for half-maximal rates of FX activation suggests that NP-2 interferes with the functioning of all three major components of the intrinsic FX-activating complex. NP-2 was found to inhibit FX activation when either phospholipids or FVIIIa are present, but not in the absence of both factors. Taken together, we conclude that NP-2 is a unique, potent, and highly specific inhibitor of the intrinsic FX-activating complex that inhibits FIXa bound either to the phospholipid or activated platelet surface or to the cofactor FVIIIa by interfering with the assembly of FX-activating complex on these surfaces.     

The Influence of the Phonological Characteristics of a Language on the Functional Units of Reading: A Study in French.

Taft (1992) reported results supporting the idea that the "Body of the BOSS" (BOB) is an important unit in the visual recognition of English polysyllabic words. "BOSS" refers to the orthographically-defined first syllable of a word (e.g., the lam of lament); "Body" refers to the part of that syllable which follows the initial consonant(s) (e.g., the am of lam). The primary evidence supporting this notion was that the pronunciation of an ambiguously pronounceable nonword could be biased by the pronunciation of a preceding word when they shared their BOB, but not when they shared their phonologically-defined first syllable. Three experiments were conducted in French, to examine whether the syllable dominates as a unit of orthographic representation when the language has a clear phonological syllable structure. To construct ambiguously pronounceable nonwords, upper case letters were used and the first syllable always contained an E, which could be pronounced either as é or e. Nonwords (e.g., MERANE) were preceded by an upper case version of a word sharing a BOB (e.g., feroce) or a first syllable (e.g., méduse). The pronunciation of the nonword's E was biased by the syllable and not by the BOB, implying that the syllable, but not the BOB, is a relevant structure in the processing of visually presented French words. (PsycINFO Database Record (c) 2010 APA, all rights reserved)