@article{1953, abstract = {The respiratory burst induced by phorbol myristate acetate in mouse macrophages was inhibited by ultra-low doses (10-15 -10-13 M) of an opioid peptide [d-Ala2] methionine enkephalinamide. The effect disappeared at concentrations above and below this range. The inhibition approached 50% and was statistically significant (P < 0.001). Increasing the time of the opioid incubation with cells brought about a shift in the maximal effect to lower concentrations of the opioid (from 10-13 to 5 · 10-15 M) and led to a decrease in the value of the effect, fully in accord with the previously proposed adaptation mechanism of the action of ultra-low doses.}, author = {Efanov, Alexander and Koshkin, Aleksei and Sazanov, Leonid A and Borodulina, O I and Varfolomeev, Sergei and Zaǐtsev, Sergei}, issn = {0014-5793}, journal = {FEBS Letters}, number = {2}, pages = {114 -- 116}, publisher = {Elsevier}, title = {{Inhibition of the respiratory burst in mouse macrophages by ultra-low doses of an opioid peptide is consistent with a possible adaptation mechanism}}, doi = {10.1016/0014-5793(94)01109-5}, volume = {355}, year = {1994}, } @article{4501, abstract = {We extend the specification language of temporal logic, the corresponding verification framework, and the underlying computational model to deal with real-;time properties of reactive systems. The abstract notion of timed transition systems generalizes traditional transition systems conservatively: qualitative fairness requirements are replaced (and superseded) by quantitative lower-bound and upper-bound timing constraints on transitions. This framework can model real-time systems that communicate either through shared variables or by message passing and real-time issues such as timeouts, process priorities (interrupts), and process scheduling. We exhibit two styles for the specification of real-time systems. While the first approach uses time-bounded versions of the temporal operators, the second approach allows explicit references to time through a special clock variable. Corresponding to the two styles of specification, we present and compare two different proof methodologies for the verification of timing requirements that are expressed in these styles. For the bounded-operator style, we provide a set of proof rules for establishing bounded-invariance and bounded-responce properties of timed transition systems. This approach generalizes the standard temporal proof rules for verifying invariance and response properties conservatively. For the explicit-clock style, we exploit the observation that every time-bounded property is a safety property and use the standard temporal proof rules for establishing safety properties.}, author = {Henzinger, Thomas A and Manna, Zohar and Pnueli, Amir}, issn = {0890-5401}, journal = {Information and Computation}, number = {2}, pages = {273 -- 337}, publisher = {Elsevier}, title = {{Temporal proof methodologies for timed transition systems}}, doi = {10.1006/inco.1994.1060}, volume = {112}, year = {1994}, } @article{3475, abstract = {1. A potassium channel activated by internal Na+ ions (K+Na channel) was identified in peripheral myelinated axons of Xenopus laevis using the cell-attached and excised configurations of the patch clamp technique. 2. The single-channel conductance for the main open state was 88 pS with [K+]o = 105 mM and pS with [K+]o = 2.5 mM ([K+]i = 105 mM). The channel was selectively permeable to K+ over Na+ ions. A characteristic feature of the K+Na channel was the frequent occurrence of subconductance states. 3. The open probability of the channel was strongly dependent on the concentration of Na+ ions at the inner side of the membrane. The half-maximal activating Na+ concentration and the Hill coefficient were 33 mM and 2.9, respectively. The open probability of the channel showed only weak potential dependence. 4. The K+Na channel was relatively insensitive to external tetraethylammonium (TEA+) in comparison with voltage-dependent axonal K+ channels; the half-maximal inhibitory concentration (IC50) was 21.3 mM (at -90 mV). In contrast, the channel was blocked by low concentrations of external Ba2+ and Cs+ ions, with IC50 values of 0.7 and 1.1 mM, respectively (at -90 mV). The block by Ba2+ and Cs+ was more pronounced at negative than at positive membrane potentials. 5. A comparison of the number of K+Na channels in nodal and paranodal patches from the same axon revealed that the channel density was about 10-fold higher at the node of Ranvier than at the paranode. Moreover, a correlation between the number of K+Na channels and voltage-dependent Na+ channels in the same patches was found, suggesting co-localization of both channel types. 6. As weakly potential-dependent ('leakage') channels, axonal K+Na channels may be involved in setting the resting potential of vertebrate axons. Simulations of Na+ ion diffusion suggest two possible mechanisms of activation of K+Na channels: the local increase of Na+ concentration in a cluster of Na+ channels during a single action potential or the accumulation in the intracellular axonal compartment during a train of action potentials.}, author = {Koh, Duk and Jonas, Peter M and Vogel, Werner}, issn = {0022-3751}, journal = {Journal of Physiology}, pages = {183 -- 197}, publisher = {Wiley-Blackwell}, title = {{Na+-activated K+ channels localized in the nodal region of myelinated axons of Xenopus}}, doi = {10.1113/jphysiol.1994.sp020287}, volume = {479}, year = {1994}, } @article{3476, abstract = {Tight-seal whole-cell recordings were made from cleaned somata of CA3 pyramidal cells deep in hippocampal slices from 19–21-d-old rats. The cells were filled with biocytin, and their voltage responses to short current pulses were recorded. After washout of initial sag, responses scaled linearly with injected current and were stable over time. The dendritic and axonal arbors of four cells were reconstructed and measured using light microscopy. Dendritic spines and axonal boutons were counted and the additional membrane area was incorporated into the relevant segments. The morphology of each neuron was converted into a detailed branching cable model by assuming values for specific membrane capacitance Cm and resistance Rm, and cytoplasmic resistivity Ri. These parameters were optimized for each cell by directly matching the model's response to that of the real cell by means of a modified weighted least-squares fitting procedure. By comparing the deviations between model and experimental responses to control noise recordings, approximate 95% confidence intervals were established for each parameter. If a somatic shunt was allowed, a wide range of possible Rm values produced acceptable fits. With zero shunt, Cm was 0.7–0.8 microFcm-2, Ri was 170–340 omega cm, and Rm ranged between 120 and 200 k omega cm2. The electrotonic lengths of the basal and oblique dendrites were 0.2–0.3 space constants, and those of the apical tufts were 0.4–0.7 space constants. The steady-state electrical geometry of these cells was therefore compact; average dendritic tip/soma relative synaptic efficacies were > 93% for the basal and oblique dendrites, and > 81% for the tufts. With fast transient synaptic inputs, however, the models produced a wide range of postsynaptic potential shapes and marked filtering of voltage-clamp currents.}, author = {Major, Guy and Larkman, Alan and Jonas, Peter M and Sakmann, Bert and Jack, Julian}, issn = {0270-6474}, journal = {Journal of Neuroscience}, number = {8}, pages = {4613 -- 4638}, publisher = {Society for Neuroscience}, title = {{Detailed passive cable models of whole-cell recorded CA3 pyramidal neurons in rat hippocampal slices}}, doi = {10.1523/JNEUROSCI.14-08-04613.1994}, volume = {14}, year = {1994}, } @article{3642, abstract = {We develop a general population genetic framework for analyzing selection on many loci, and apply it to strong truncation and disruptive selection on an additive polygenic trait. We first present statistical methods for analyzing the infinitesimal model, in which offspring breeding values are normally distributed around the mean of the parents, with fixed variance. These show that the usual assumption of a Gaussian distribution of breeding values in the population gives remarkably accurate predictions for the mean and the variance, even when disruptive selection generates substantial deviations from normality. We then set out a general genetic analysis of selection and recombination. The population is represented by multilocus cumulants describing the distribution of haploid genotypes, and selection is described by the relation between mean fitness and these cumulants. We provide exact recursions in terms of generating functions for the effects of selection on non-central moments. The effects of recombination are simply calculated as a weighted sum over all the permutations produced by meiosis. Finally, the new cumulants that describe the next generation are computed from the non-central moments. Although this scheme is applied here in detail only to selection on an additive trait, it is quite general. For arbitrary epistasis and linkage, we describe a consistent infinitesimal limit in which the short-term selection response is dominated by infinitesimal allele frequency changes and linkage disequilibria. Numerical multilocus results show that the standard Gaussian approximation gives accurate predictions for the dynamics of the mean and genetic variance in this limit. Even with intense truncation selection, linkage disequilibria of order three and higher never cause much deviation from normality. Thus, the empirical deviations frequently found between predicted and observed responses to artificial selection are not caused by linkage-disequilibrium-induced departures from normality. Disruptive selection can generate substantial four-way disequilibria, and hence kurtosis; but even then, the Gaussian assumption predicts the variance accurately. In contrast to the apparent simplicity of the infinitesimal limit, data suggest that changes in genetic variance after 10 or more generations of selection are likely to be dominated by allele frequency dynamics that depend on genetic details.}, author = {Turelli, Michael and Barton, Nicholas H}, issn = {0016-6731}, journal = {Genetics}, number = {3}, pages = {913 -- 941}, publisher = {Genetics Society of America}, title = {{Genetic and statistical analyses of strong selection on polygenic traits: What, me normal?}}, doi = {10.1093/genetics/138.3.913}, volume = {138}, year = {1994}, } @article{4037, abstract = {Frequently, data in scientific computing is in its abstract form a finite point set in space, and it is sometimes useful or required to compute what one might call the `'shape” of the set. For that purpose, this article introduces the formal notion of the family of alpha-shapes of a finite point set in R3. Each shape is a well-defined polytope, derived from the Delaunay triangulation of the point set, with a parameter alpha is-an-element-of R controlling the desired level of detail. An algorithm is presented that constructs the entire family of shapes for a given set of size n in time O(n2), worst case. A robust implementation of the algorithm is discussed, and several applications in the area of scientific computing are mentioned.}, author = {Edelsbrunner, Herbert and Mücke, Ernst}, journal = {ACM Transactions on Graphics}, number = {1}, pages = {43 -- 72}, publisher = {ACM}, title = {{Three-dimensional alpha shapes}}, doi = {10.1145/174462.156635}, volume = {13}, year = {1994}, } @article{4179, abstract = {Neurotrophin-3 (NT-3) is a member of the neurotrophin gene family and is highly expressed in the developing rat cerebellum. Here we show that brain-derived neurotrophic factor (BDNF) increased by approximately 10-fold the NT-3 mRNA levels in cultured cerebellar granule neurons isolated from postnatal rats, whereas nerve growth factor (NGF) and NT-3 itself had no effect. The effect of BDNF was additive to that of triiodothyronine (T3), which also increased NT-3 mRNA in these neurons. The drug K252a inhibited the BDNF-mediated stimulation of NT-3 expression, suggesting an involvement of trkB receptors. Nuclear run-on experiments showed that BDNF enhanced NT-3 transcription, whereas the stability of NT-3 mRNA remained unchanged. The data presented are the first demonstration that one neurotrophin regulates the expression of another and provide evidence that NT-3 production in granule neurons is regulated by both BDNF and T3.}, author = {Leingärtner, Axel and Heisenberg, Carl-Philipp J and Kolbeck, Roland and Thoenen, Hans and Lindholm, Dan}, issn = {1083-351X}, journal = {Journal of Biological Chemistry}, number = {2}, pages = {828 -- 830}, publisher = {American Society for Biochemistry and Molecular Biology}, title = {{Brain-derived neurotrophic factor increases neurotrophin-3 expression in cerebellar granule neurons}}, doi = {10.1016/s0021-9258(17)42186-7}, volume = {269}, year = {1994}, } @article{2536, abstract = {A cDNA clone for a new metabotropic glutamate receptor, termed mGluR6, was isolated from a rat retinal cDNA library by cross-hybridization with the previously isolated cDNA clone for a metabotropic glutamate receptor. The cloned mGluR6 subtype consists of 871 amino acid residues and exhibits a structural architecture common to the metabotropic receptor family, possessing a large extracellular domain preceding the seven putative membrane-spanning domains. mGluR6 shows the highest sequence similarity to mGluR4 among the metabotropic receptor subtypes and inhibits the forskolin- stimulated cyclic AMP accumulation in Chinese hamster ovary cells transfected with the cloned cDNA. mGluR6 potently reacts with L-2-amino-4- phosphonobutyrate (L-AP4) and L-serine-O-phosphate, and the potencies of these compounds are one order of magnitude greater than that of L-glutamate. Blot and in situ hybridization analyses indicated that mGluR6 mRNA is restrictedly expressed in the inner nuclear layer of the retina where ON- bipolar cells are distributed. The metabotropic receptor that responds strongly to L-AP4 and L-serine-O-phosphate in ON-bipolar cells is known to mediate glutamate synaptic transmission between photoreceptor cells and ON- bipolar cells. On the basis of the agonist selectivity of mGluR6 and its specific expression in retinal cells, the physiological role of this receptor subtype in the visual system is discussed.}, author = {Nakajima, Yoshiaki and Iwakabe, Hideki and Akazawa, Chihiro and Nawa, Hiroyuki and Shigemoto, Ryuichi and Mizuno, Noboru and Nakanishi, Shigetada}, issn = {0021-9258}, journal = {Journal of Biological Chemistry}, number = {16}, pages = {11868 -- 11873}, publisher = {American Society for Biochemistry and Molecular Biology}, title = {{Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for L-2-amino-4- phosphonobutyrate}}, doi = {10.1016/S0021-9258(19)50280-0}, volume = {268}, year = {1993}, } @article{2537, abstract = {The metabotropic glutamate receptors are coupled to intracellular signal transduction via G-proteins and consist of a family of at least five different subtypes, termed mGluR1-mGluR5. We studied the signal transduction mechanism and pharmacological characteristics of the rat mGluR3 and mGluR4 subtypes in Chinese hamster ovary cells permanently expressing the cloned receptors. Both mGluR3 and mGluR4 inhibit the forskolin-stimulated accumulation of intracellular cAMP formation in response to agonist interaction. Consistent with the high degree of sequence similarity to mGluR2, mGluR3 closely resembles mGluR2 in its agonist selectivity; the potency rank order of agonists is L-glutamate > trans-1-aminocyclopentane- 1,3-dicarboxylate > ibotenate > quisqualate. mGluR4 is totally different in its agonist specificity from any other member of the metabotropic receptors. This receptor potently reacts with L-2-amino-4-phosphonobutyrate(L-AP4) in a stereo-selective manner and moderately responds to L-serine-O-phosphate. mGluR4 thus corresponds well to the putative L-AP4 receptor characterized from brain preparations. Blot and in situ hybridization analyses indicated that both mRNAs are widely distributed in the rat brain. mGluR3 mRNA is highly expressed in neuronal cells of the cerebral cortex and the caudate- putamen, and in granule cells of the hippocampal dentate gyrus. The expression pattern of mGluR4 mRNA is more restricted, and this expression is prominent in the cerebellum, olfactory bulb, and thalamus. Furthermore, the mGluR3 mRNA, unlike the other mRNAs for the metabotropic receptors, is highly expressed in glial cells throughout the brain regions. The metabotropic glutamate receptor subtypes can thus be classified into three subgroups according to the similarity in their amino acid sequences, signal transduction, and agonist selectivity: mGluR1/mGluR5, mGluR2/mGluR3, and mGluR4. The mRNAs for the individual receptor subtypes, however, show overlapping but distinct patterns of expression in the rat CNS.}, author = {Tanabe, Yasuto and Nomura, Akinori and Masu, Masayuki and Shigemoto, Ryuichi and Mizuno, Noboru and Nakanishi, Shigetada}, issn = {0270-6474}, journal = {Journal of Neuroscience}, number = {4}, pages = {1372 -- 1378}, publisher = {Society for Neuroscience}, title = {{Signal transduction, pharmacological properties, and expression patterns of two rat metabotropic glutamate receptors, mGluR3 and mGluR4}}, doi = {10.1523/JNEUROSCI.13-04-01372.1993}, volume = {13}, year = {1993}, } @article{2538, abstract = {Rat mRNAs encoding two subtypes of the endothelin (ET) receptor (ET(A) and ET(B)) were studied in the rat ovary and fallopian tube by means of Northern blotting and in situ hybridization. The mRNA transcripts for the endothelin- 1-specific type receptor (ET(A)) in pooled RNA from the ovary and fallopian tube were 4.2 and 5.2 kilonucleotides, and that for the nonselective type receptor (ET(B)) was 4.7 kilonucleotides; these were similar to transcripts for endothelin receptors from other tissues. ET(A) mRNA expression was abundant in the muscle cell layer of the fallopian tube, but low in the ovary. On the other hand, ET(B) mRNA was abundant in the granulosa cells in the developing follicles, but low in atretic follicles and absent in the fallopian tube. These results demonstrated that the mRNAs for the two subtypes of the rat endothelin receptor have different expression profiles in the ovary and fallopian tube. ETs may mainly affect the granulosa cells in the dominant follicles as well as the muscle cells of the fallopian tube through ET(B) and ET(A), respectively.}, author = {Iwai, Masazumi and Hori, Seiji and Shigemoto, Ryuichi and Kanzaki, Hideharu and Mori, Takahide and Nakanishi, Shigetada}, issn = {0006-3363}, journal = {Biology of Reproduction}, number = {4}, pages = {675 -- 680}, publisher = {Society for the Study of Reproduction}, title = {{Localization of endothelin receptor messenger ribonucleic acid in the rat ovary and fallopian tube by in situ hybridization}}, doi = {10.1095/biolreprod49.4.675}, volume = {49}, year = {1993}, } @article{2539, abstract = {cDNA clones for four different N-methyl-D-aspartate (NMDA) receptor subunits (NMDAR2A-NMDAR2D) were isolated through polymerase chain reactions followed by molecular screening of a rat brain cDNA library. These subunits are only about 15% identical with the key subunit of the NMDA receptor (NMDAR1) but are highly homologous (~50% homology) with one another. They also commonly possess large hydrophilic domains at both amino- and carboxyl- terminal sides of the four putative transmembrane segments. NMDAR2A and NMDAR2C expressed individually in Xenopus oocytes showed no electrophysiological response to agonists. However, these subunits in combined expression with NMDAR1 markedly potentiated the NMDAR1 activity and produced functional variability in the affinity of agonists, the effectiveness of antagonists, and the sensitivity to Mg2+ blockade. Thus, NMDAR1 is essential for the function of the NMDA receptor, and multiple NMDAR2 subunits potentiate and differentiate the function of the NMDA receptor by forming different heteromeric configurations with NMDAR1. Northern blotting and in situ hybridization analyses revealed that the expressions of individual mRNAs for the NMDAR2 subunits overlap in some brain regions but are also specialized in many other regions. This investigation demonstrates the anatomical and functional differences of the NMDAR2 subunits, which provide the molecular basis for the functional diversity of the NMDA receptor.}, author = {Ishii, Takahiro and Moriyoshi, Koki and Sugihara, Hidemitsu and Sakurada, Kazuhir and Kadotani, Hiroshi and Yokoi, Mineto and Akazawa, Chihiro and Shigemoto, Ryuichi and Mizuno, Noboru and Masu, Masayuki and Nakanishi, Shigetada}, issn = {0021-9258}, journal = {Journal of Biological Chemistry}, number = {4}, pages = {2836 -- 2843}, publisher = {American Society for Biochemistry and Molecular Biology}, title = {{Molecular characterization of the family of the N-methyl-D-aspartate receptor subunits}}, doi = {10.1016/s0021-9258(18)53849-7 }, volume = {268}, year = {1993}, } @article{4589, abstract = {The theory of the natural numbers with linear order and monadic predicates underlies propositional linear temporal logic. To study temporal logics that are suitable for reasoning about real-time systems, we combine this classical theory of infinite state sequences with a theory of discrete time, via a monotonic function that maps every state to its time. The resulting theory of timed state sequences is shown to be decidable, albeit nonelementary, and its expressive power is characterized by ω-regular sets. Several more expressive variants are proved to be highly undecidable. This framework allows us to classify a wide variety of real-time logics according to their complexity and expressiveness. Indeed, it follows that most formalisms proposed in the literature cannot be decided. We are, however, able to identify two elementary real-time temporal logics as expressively complete fragments of the theory of timed state sequences, and we present tableau-based decision procedures for checking validity. Consequently, these two formalisms are well-suited for the specification and verification of real-time systems. Copyright © 1993 Academic Press. All rights reserved.}, author = {Alur, Rajeev and Henzinger, Thomas A}, issn = {0890-5401}, journal = {Information and Computation}, number = {1}, pages = {35 -- 77}, publisher = {Elsevier}, title = {{Real-time logics: Complexity and expressiveness}}, doi = {10.1006/inco.1993.1025}, volume = {104}, year = {1993}, } @article{3474, abstract = {1. Excitatory postsynaptic currents (EPSCs) were recorded in CA3 pyramidal cells of hippocampal slices of 15- to 24-day-old rats (22 degrees C) using the whole-cell configuration of the patch clamp technique. 2. Composite EPSCs were evoked by extracellular stimulation of the mossy fibre tract. Using the selective blockers 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and D-2-amino-5-phosphonopentanoic acid (APV), a major alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptor-mediated component and a minor NMDA receptor-mediated component with slower time course were distinguished. For the AMPA/kainate receptor-mediated component, the peak current-voltage (I-V) relation was linear, with a reversal potential close to 0 mV. The half-maximal blocking concentration of CNQX was 353 nM. 3. Unitary EPSCs of the mossy fibre terminal (MF)-CA3 pyramidal cell synapse were evoked at membrane potentials of -70 to -90 mV by low-intensity extracellular stimulation of granule cell somata using fine-tipped pipettes. The EPSC peak amplitude as a function of stimulus intensity showed all-or-none behaviour. The region of low threshold was restricted to a few micrometres. This suggests that extracellular stimulation was focal, and that the stimulus-evoked EPSCs were unitary. 4. Latency and rise time histograms of EPSCs evoked by granule cell stimulation showed narrow unimodal distributions within each experiment. The mean latency was 4.2 +/- 1.0 ms, and the mean 20-80% rise time was 0.6 +/- 0.1 ms (23 cells). When fitted within the range 0.7 ms to 20 ms after the peak, the decay of the EPSCs with the fastest rise (rise time 0.5 ms or less) could be described by a single exponential function; the mean time constant was in the range 3.0-6.6 ms with a mean of 4.8 ms (8 cells). 5. Peak amplitudes of the EPSCs evoked by suprathreshold granule cell stimulation fluctuated between trials. The apparent EPSC peak conductance in normal extracellular solution (2 mM Ca2+, 1 mM Mg2+), excluding failures, was 1 nS. Reducing the Ca2+ concentration and increasing the Mg2+ concentration reduced the mean peak amplitude in a concentration-dependent manner. 6. Peaks in EPSC peak amplitude distributions were apparent in low Ca2+ and high Mg2+. Using the criteria of equidistance and the presence of peaks and dips in the autocorrelation function, five of nine EPSC peak amplitude distributions were judged to be quantal.}, author = {Jonas, Peter M and Major, Guy and Sakmann, Bert}, issn = {0022-3751}, journal = {Journal of Physiology}, pages = {615 -- 663}, publisher = {Wiley-Blackwell}, title = {{Quantal components of unitary EPSCs at the mossy fibre synapse on CA3 pyramidal cells of rat hippocampus}}, doi = {10.1113/jphysiol.1993.sp019965}, volume = {472}, year = {1993}, } @article{4177, abstract = {Thyroid hormones play an important role in brain development, but the mechanism(s) by which triiodothyronine (T3) mediates neuronal differentiation is poorly understood. Here we demonstrate that T3 regulates the neurotrophic factor, neurotrophin-3 (NT-3), in developing rat cerebellar granule cells both in cell culture and in vivo. In situ hybridization experiments showed that developing Purkinje cells do not express NT-3 mRNA but do express trkC, the putative neuronal receptor for NT-3. Addition of recombinant NT-3 to cerebellar cultures from embryonic rat brain induces hypertrophy and neurite sprouting of Purkinje cells, and upregulates the mRNA encoding the calcium-binding protein, calbindin-28 kD. The present study demonstrates a novel interaction between cerebellar granule neurons and developing Purkinje cells in which NT-3 induced by T3 in the granule cells promotes Purkinje cell differentiation.}, author = {Lindholm, Dan and Castrén, Eero and Tsoulfas, Pantelis and Kolbeck, Roland and Berzaghi, Maria and Leingärtner, Axel and Heisenberg, Carl-Philipp J and Tesarollo, Lino and Parada, Luis and Thoenen, Hans}, issn = {0021-9525}, journal = {Journal of Cell Biology}, number = {2}, pages = {443 -- 450}, publisher = {Rockefeller University Press}, title = {{Neurotrophin-3 induced by tri-iodothyronine in cerebellar granule cells promotes Purkinje cell differentiation}}, doi = {10.1083/jcb.122.2.443}, volume = {122}, year = {1993}, } @article{4303, abstract = {In a stably subdivided population with symmetric migration, the chance that a favoured allele will be fixed is independent of population structure. However, random extinction introduces an extra component of sampling drift, and reduces the probability of fixation. In this paper, the fixation probability is calculated using the diffusion approximation; comparison with exact solution of the discrete model shows this to be accurate. The key parameters are the rates of selection, migration and extinction, scaled relative to population size (S = 4Ns, M = 4Nm, Λ = 4Nλ); results apply to a haploid model, or to diploids with additive selection. If new colonies derive from many demes, the fixation probability cannot be reduced by more than half. However, if colonies are initially homogeneous, fixation probability can be much reduced. In the limit of low migration and extinction rates (M, Λ 1), it is 2s/{1 + (Λ/MS)(1 −exp(−S))}, whilst in the opposite limit (S 1), it is 4sM/{Λ(Λ + M)}. In the limit of weak selection (M, Λ 1), it is 4sM/{Λ(Λ + M)}. These factors are not the same as the reduction in effective population size (Ne/N), showing that the effects of population structure on selected alleles cannot be understood from the behaviour of neutral markers.}, author = {Barton, Nicholas H}, issn = {0016-6723}, journal = {Genetics Research}, number = {2}, pages = {149 -- 158}, publisher = {Cambridge University Press}, title = {{The probability of fixation of a favoured allele in a subdivided population}}, doi = {10.1017/S0016672300031748}, volume = {62}, year = {1993}, } @article{2533, abstract = {A cDNA clone for a new metabotropic glutamate receptor, mGluR5, was isolated through polymerase chain reaction-mediated DNA amplification by using primer sequences conserved among the metabotropic glutamate receptor (mGluR) family and by the subsequent screening of a rat brain cDNA library. The cloned receptor consists of 1171 amino acid residues and exhibits a structural architecture common to the mGluR family, possessing a large extracellular domain preceding the seven putative membrane-spanning segments. mGluR5 shows the highest sequence similarity to mGluR1 among the mGluR members and is coupled to the stimulation of phosphatidylinositol hydrolysis/ Ca2+ signal transduction in Chinese hamster ovary cells transfected with the cloned cDNA. This receptor also resembles mGluR1 in its agonist selectivity and antagonist responses; the potency rank order of agonists for mGluR5 was determined to be quisqualate > L-glutamate ≥ ibotenate > trans-1-aminocyclopentane-1,3-dicarboxylate. Blot and in situ hybridization analyses indicated that mGluR5 mRNA is widely distributed in neuronal cells of the central nervous system and is expressed differently from mGluR1 mRNA in many brain regions. This investigation thus demonstrates that there is an additional mGluR subtype which closely resembles mGluR1 in its signal transduction and pharmacological properties and is expressed in specialized neuronal cells in the central nervous system.}, author = {Abe, Takaaki and Sugihara, Hidemitsu and Nawa, Hiroyuki and Shigemoto, Ryuichi and Mizuno, Noboru and Nakanishi, Shigetada}, issn = {0021-9258}, journal = {Journal of Biological Chemistry}, number = {19}, pages = {13361 -- 13368}, publisher = {American Society for Biochemistry and Molecular Biology}, title = {{Molecular characterization of a novel metabotropic glutamate receptor mGluR5 coupled to inositol phosphate/Ca2+ signal transduction}}, doi = {10.1016/S0021-9258(18)42219-3}, volume = {267}, year = {1992}, } @article{2535, abstract = {We report the molecular characterization of two novel rat helix-loop-helix (HLH) proteins, designated HES-1 and HES-3, that show structural homology to the Drosophila hairy and Enhancer of split [E(spl)] proteins, both of which are required for normal neurogenesis. HES-1 mRNA, expressed in various tissues of both embryos and adults, is present at a high level in the epithelial cells, including the embryonal neuroepithelial cells, as well as in the mesoderm-derived tissues such as the embryonal muscle. In contrast, HES-3 mRNA is produced exclusively in cerebellar Purkinje cells. HES-1 represses transcription by binding to the N box, which is a recognition sequence of E(spl) proteins. Interestingly, neither HES-1 nor HES-3 alone interacts efficiently with the E box, but each protein decreases the transcription induced by E-box-binding HLH activators such as E47. Furthermore, HES-1 also inhibits the functions of MyoD and MASH1 and effectively diminishes the myogenic conversion of C3H10T1/2 cells induced by MyoD. These results suggest that HES-1 may play an important role in mammalian development by negatively acting on the two different sequences while HES-3 acts as a repressor in a specific type of neurons.}, author = {Sasai, Yoshiki and Kageyama, Ryoichiro and Tagawa, Yoshiaki and Shigemoto, Ryuichi and Nakanishi, Shigetada}, issn = {0890-9369}, journal = {Genes and Development}, number = {12 B}, pages = {2620 -- 2634}, publisher = {Cold Spring Harbor Laboratory Press}, title = {{Two mammalian helix-loop-helix factors structurally related to Drosophila hairy and Enhancer of split}}, doi = {10.1101/gad.6.12b.2620}, volume = {6}, year = {1992}, } @article{2722, abstract = {A version of the one-dimensional Rayleigh gas is considered: a point particle of mass M (molecule), confined to the unit interval [0,1], is surrounded by an infinite ideal gas of point particles of mass 1 (atoms). The molecule interacts with the atoms and with the walls via elastic collision. Central limit theorems are proved for a wide class of additive functionals of this system (e.g. the number of collisions with the walls and the total length of the molecular path).}, author = {Erdös, László and Tuyen, Dao}, issn = {0010-3616}, journal = {Communications in Mathematical Physics}, number = {3}, pages = {451 -- 466}, publisher = {Springer}, title = {{Central limit theorems for the one-dimensional Rayleigh gas with semipermeable barriers}}, doi = {10.1007/BF02099260}, volume = {143}, year = {1992}, } @article{3470, abstract = {Currents activated by glutamate receptor (GluR) agonists were recorded from outside-out patches isolated from the soma of visually identified pyramidal neurones of the (CA3 and CA1 region of rat hippocampal slices. α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). L-glutamate (L-Glu), and kainate (KA) were delivered either by bath application through perfusion of the recording chamber or by rapid application via a piezo-driven two-barrelled fast application system. 2. Bath application of each of the three agonists activated inward currents in all patches (n = 134) at holding potentials of -50 or -60 mV. The current amplitude increased in size between 3 to 30 μM-AMPA and 100 μM to 1 mM-KA. With this slow mode of bath application, the responses showed no apparent desensitization even at saturating concentrations of AMPA (30 μM) and KA (1 mM). 3. The ratio of currents activated by 30 μM-AMPA and 300 μM-KA showed a characteristic difference between CA3 and CA1 neurones. The ratio was 0.242 ± 0.028 (mean ± S.E.M., n = 16) for CA3 cell patches and 0.097 ± 0.012 (n = 8) for CA1 cell patches indicating that GluRs in the two cell populations are different. 4. The steady-state current-voltage relations (I-Vs) for AMPA- and KA-activated currents showed pronounced outward rectification for both cell types (when the main cations are Na+ in the bath and Cs+ in the pipette solution). The current reversed close to 0 mV and the ratio of chord conductances 80 mV on either side of the reversal potential was 2.66 for KA-activated currents in CA3 cell patches and 2.60 in CA1 cell patches. AMPA-activated currents showed a time-dependent increase after steps to positive membrane potentials and a decrease after steps to negative voltages, indicating that a gating process is responsible for outward rectification of the steady-state I-IV. 5. The permeability (P) of GluR channels was high for Na+ as compared to Cs+ for both cell types (P(Na)/P(Cs) = 0.88 and 0.84). The permeability was low for N-methyl-D-glucamine+ (P(NMG)/P(Cs) ≤ 0.03) and Ca2+ (P(Ca)/P(Cs) ≤0.05). 6. The current noise level increased during application of AMPA or KA. Apparent single-channel conductances obtained from fluctuation analysis were higher for AMPA than for KA, but similar for both cell types. In CA3 cell patches, AMPA activated channels with an apparent chord conductance of 7.2 pS, KA of 3.0 pS conductance. 7. Fast agonist application revealed desensitization of GluR channels which was dependent on the type of agonist, currents activated by AMPA and L-Glu rose rapidly to a peak and then desensitized to a steady-state current. In contrast, currents activated by fast application of KA rose to a plateau and did not desensitize. The steady state current expressed as a percentage of the peak current was higher for L-Glu than for AMPA and slightly higher for CA3 than for CA1 cell patches. For CA3 cell patches, this fraction amounted to 6.2 %, with 300 μM-L-Glu and 2.8%, with 300 μM-AMPA. For CA1 cell patches, corresponding values were 3.6 and 1.9 % 8. The dose response relations for the peak current activated by AMPA and L-Glu and the steady-state current activated by KA were similar for CA3 and CA1 cell patches. The order of potency was AMPA > L-Glu ≃ KA for both cell types EC50 values 189, 342 and 344 μM for CA3 cell patches and 183, 424 and 474 μM for CA1 cell patches). In all cases, the Hill coefficients ranged between 12 and 1.7. 8. The rise of AMPA and L-Glu-activated currents became faster with increasing agonist concentration for both cell types. With L-Glu, rise times decreased from about 3 ms at 100 μM to 500 μs at 3 mM. The delay for agonist concentrations ≥ 300 μM was described by the sum of two exponential functions. The time constant of the predominant fast component was slightly concentration dependent and decreased from about 12 ms at 300 μM to 8 ms at 3 mM-L-Glu. 10. The current voltage relations of the peak currents activated by 300 μM-AMPA were linear for both cell types with a reversal potential close to OmV. 11. It is concluded that the GluR channels in pyramidal cells of hippocampal CA3 and CA1 regions are distinet but share many pharmacological and functional properties. Comparison of the properties of native and recombinant GluRs suggests that in both CA3 and CA1 regions GluR channels are hetero-oligomers containing the GluR-B subunit.}, author = {Jonas, Peter M and Sakmann, Bert}, issn = {0022-3751}, journal = {Journal of Physiology}, pages = {143 -- 171}, publisher = {Wiley-Blackwell}, title = {{Glutamate receptor channels in isolated patches from CA1 and CA3 pyramidal cells of rat hippocampal slices}}, doi = {10.1113/jphysiol.1992.sp019294 }, volume = {455}, year = {1992}, } @article{3471, abstract = {1. Outside-out patches were isolated from granule cells of dentate gyrus and pyramidal cells of CA3 and CA1 regions of rat hippocampal slices. Patches were exposed briefly to L-glutamate using a piezo-driven double-barrelled application pipette. 2. Applications of glutamate (1 mM) of 1 ms duration activated patch currents which rose and decayed rapidly. The 20-80% rise time of these glutamate receptor (GluR)-mediated currents was usually 0.2-0.6 ms. At -50 mV the peak current varied from 10 to 500 pA in different patches. 3. The peak current-voltage relation for brief pulses of 1 mM glutamate was virtually linear in normal extracellular solution for patches from the three cell types (-100 to 60 mV). 4. The permeability of GluR channels activated at the peak to Ca2+, relative to K+, was less than 0.1 for all three cell types (under bi-ionic conditions with Ca2+ on the extracellular side and K+ on the intracellular side of the membrane). 5. The offset decay time constant of the current following 1 ms pulses of 1 mM glutamate was brief, with mean values of 3.0 +/- 0.8, 2.5 +/- 0.7, and 2.3 +/- 0.7 ms for dentate, CA3 and CA1 cell patches, respectively. Offset time constants were independent of membrane potential and independent of glutamate concentration (200 microM and 1 mM) for the three cell types. 6. Applications of 1 mM glutamate of 100 ms duration showed that glutamate responses desensitized rapidly. The time constants for desensitization were 9.4 +/- 2.7, 11.3 +/- 2.8, and 9.3 +/- 2.8 ms for patches from dentate, CA3 and CA1 cells respectively. Desensitization time constants were only weakly dependent on glutamate concentration (200 microM and 1 mM) for the three cell types. Thus offset time constants are about four times faster than desensitization time constants for both glutamate concentrations. 7. Double pulse application of glutamate indicated that even a 1 ms pulse of 1 mM glutamate causes partial (about 60%) desensitization of GluR channels. The time course of recovery from desensitization was slower in dentate gyrus granule cell patches than in CA3 or CA1 pyramidal cell patches. 8. Desensitization was studied at equilibrium by exposing patches to low glutamate concentrations for at least 15 s before a 1 ms test pulse of 1 mM glutamate.}, author = {Colquhoun, D. and Jonas, Peter M and Sakmann, Bert}, issn = {0022-3751}, journal = {Journal of Physiology}, pages = {261 -- 287}, publisher = {Wiley-Blackwell}, title = {{Action of brief pulses of glutamate on AMPA/kainate receptors in patches from different neurones of rat hippocampal slices}}, doi = {10.1113/jphysiol.1992.sp019417}, volume = {458}, year = {1992}, }