TY - JOUR AB - Functional cDNA clones for rat neuromedin K receptor were isolated from a rat brain cDNA library by cross-hybridization with the bovine substance K recepor cDNA. Injection of the mRNA synthesized in vitro from the cloned cDNA into Xenopus oocytes elicited electrophysiological responses to tachykinins, with the most potent sensitivity being to neuromedin K. Ligand-binding displacement in membranes of mammalian COS cells transfected with the cDNA indicated the rank order of affinity of the receptor to tachykinins; neuromedin K > substance K > substance P. The hybridization analysis showed that the neuromedin K receptor mRNA is expressed in both the brain and the peripheral tissues at different levels. The rat neuromedin K receptor consists of 452 amino acid residues and belongs to the family of G protein-coupled receptors, which are thought to have seven transmembrane domains. The sequence comparison of the rat neuromedin K, substance P, and substance K receptors revealed that these receptors are highly conserved in the seven transmembrane domains and the cytoplasmic sides of the receptors. They also show some structural characteristics, including the common presence of histidine residues in transmembrane segments V and VI and the difference in the numbers and distributions of serine and threonine residues as possible phosphorylation sites in the cytoplasmic regions. This paper thus presents the first comprehensive analysis of the molecular nature of the multiple peptide receptors that exhibit similar but pharmacologically distinguishable activities. AU - Shigemoto, Ryuichi AU - Yokota, Yoshifumi AU - Tsuchida, Kunihiro AU - Nakanishi, Shigetada ID - 2480 IS - 2 JF - Journal of Biological Chemistry SN - 0021-9258 TI - Cloning and expression of a rat neuromedin K receptor cDNA VL - 265 ER - TY - JOUR AB - The family of mammalian tachykinin receptors consists of substance P receptor (SPR), neuromedin K receptor (NKR) and substance K receptor (SKR). In this investigation, tissue and regional distributions of the mRNAs for the three rat tachykinin receptors were investigated by blot-hybridization and RNase-protection analyses using the previously cloned receptor cDNAs. SPR mRNA is widely distributed in both the nervous system and peripheral tissues and is expressed abundantly in the hypothalamus and olfactory buld, as well as in the urinary bladder, salivary glands and small and large intestines. In contrast, NKR mRNA is predominantly expressed in the nervous system, particularly in the cortex, hypothalamus and cerebellum, whereas SKR mRNA expression is restricted to the peripheral tissues, being abundant in the urinary bladder, large intestine, stomach and adenal glands. Thus, the mRNAs for the three tachykinin receptors show distinct patterns of expression between the nervous system and peripheral tissues. Blot-hybridization analysis in combination with S1 nuclease protection and primer-extension analyses revealed that there are two large forms of SKR mRNA expressed commonly in the peripheral tissues, and two additional small forms of the mRNA expressed specifically in the adrenal gland and eye. These analyses also showed that the multiple forms of SKR mRNA differ in the lengths of the 5' mRNA portions, and that the two small forms of the mRNA, if translated, encode a truncated SKR polypeptide lacking the first two transmembrane domains. This investigation thus provides the comprehensive analysis of the distribution and mode of expression of the mRNAs for the multiple peptide receptors and offers a new basis on which to interpret the diverse functions of multiple tachykinin peptides in the CNS and peripheral tissues. AU - Tsuchida, Kunihiro AU - Shigemoto, Ryuichi AU - Yokota, Yoshifumi AU - Nakanishi, Shigetada ID - 2481 IS - 3 JF - European Journal of Biochemistry SN - 0014-2956 TI - Tissue distribution and quantitation of the mRNAs for three rat tachykinin receptors VL - 193 ER - TY - JOUR AB - We previously reported a novel rat membrane protein that exhibits a voltage-dependent potassium channel activity on the basis of molecular cloning combined with an electrophysiological assay. This protein, termed I(sK) protein, is small and different from the conventional potassium channel proteins but induces selective permeation of potassium ions on its expression in Xenopus oocytes. In this investigation, we examined cellular localization of rat I(sK) protein by preparing three different types of antibody that specifically reacts with a distinct part of rat I(sK) protein. Immunohistochemical analysis using these antibody preparations demonstrated that rat I(sK) protein is confined to the apical membrane portion of epithelial cells in the proximal tubule of the kidney, the submandibular duct and the uterine endometrium. The observed tissue distribution of rat I(sK) protein was consistent with that of the I(sK) protein mRNA determined by blot hybridization analysis. In epithelial cells, the sodium, potassium-ATPase pump in the basolateral membrane generates a sodium gradient across the epithelial cell and allows sodium ions to enter the cell through the apical membrane. Thus, taking into account the cellular localization of the I(sK) protein, together with its electrophysiological properties, we discussed a possible function of the I(sK) protein, namely that this protein is involved in potassium permeation in the apical membrane of epithelial cells through the depolarizing effect of sodium entry. AU - Sugimoto, Tetsuo AU - Tanabe, Yasuto AU - Shigemoto, Ryuichi AU - Iwai, Masazumi AU - Takumi, Toru AU - Ohkubo, Hiroaki AU - Nakanishi, Shigetada ID - 2528 IS - 1 JF - Journal of Membrane Biology SN - 0022-2631 TI - Immunohistochemical study of a rat membrane protein which induces a selective potassium permeation: Its localization in the apical membrane portion of epithelial cells VL - 113 ER - TY - JOUR AB - We consider a multidimensional system consisting of a particle of mass M and radius r (molecule), surrounded by an infinite ideal gas of point particles of mass m (atoms). The molecule is confined to the unit ball and interacts with its boundary (barrier) via elastic collision, while the atoms are not affected by the boundary. We obtain convergence to equilibrium for the molecule from almost every initial distribution on its position and velocity. Furthermore, we prove that the infinite composite system of the molecule and the atoms is Bernoulli. AU - Erdös, László AU - Tuyen, Dao ID - 2721 IS - 5-6 JF - Journal of Statistical Physics SN - 0022-4715 TI - Ergodic properties of the multidimensional rayleigh gas with a semipermeable barrier VL - 59 ER - TY - JOUR AB - Hybrid zones can yield estimates of natural selection and gene flow. The width of a cline in gene frequency is approximately proportional to gene flow (σ) divided by the square root of per-locus selection ( &s). Gene flow also causes gametic correlations (linkage disequilibria) between genes that differ across hybrid zones. Correlations are stronger when the hybrid zone is narrow, and rise to a maximum roughly equal to s. Thus cline width and gametic correlations combine to give estimates of gene flow and selection. These indirect measures of σ and s are especially useful because they can be made from collections, and require no field experiments. The method was applied to hybrid zones between color pattern races in a pair of Peruvian Heliconius butterfly species. The species are Mullerian mimics of one another, and both show the same changes in warning color pattern across their respective hybrid zones. The expectations of cline width and gametic correlation were generated using simulations of clines stabilized by strong frequency-dependent selection. In the hybrid zone in Heliconius erato, clines at three major color pattern loci were between 8.5 and 10.2 km wide, and the pairwise gametic correlations peaked at R & 0.35. These measures suggest that s & 0.23 per locus, and that σ & 2.6 km. In erato, the shapes of the clines agreed with that expected on the basis of dominance. Heliconius melpomene has a nearly coincident hybrid zone. In this species, cline widths at four major color pattern loci varied between 11.7 and 13.4 km. Pairwise gametic correlations peaked near R & 1.00 for tightly linked genes, and at R & 0.40 for unlinked genes, giving s & 0.25 per locus and σ & 3.7 km. In melpomene, cline shapes did not perfectly fit theoretical shapes based on dominance; this deviation might be explained by long-distance migration and/or strong epistasis. Compared with erato, sample sizes in melpomene are lower and the genetics of its color patterns are less well understood. In spite of these problems, selection and gene flow are clearly of the same order of magnitude in the two species. The relatively high per locus selection coefficients agree with ``major gene'' theories for the evolution of Mullerian mimicry, but the genetic architecture of the color patterns does not. These results show that the genetics and evolution of mimicry are still only sketchily understood. AU - Mallet, James AU - Barton, Nicholas H AU - Lamas, Gerado AU - Santisteban, José AU - Muedas, Manuel AU - Eeley, Harriet ID - 3650 IS - 4 JF - Genetics SN - 0016-6731 TI - Estimates of selection and gene flow from measures of cline width and linkage disequilibrium in Heliconius hybrid zones VL - 124 ER - TY - JOUR AB - Selection on polygenic characters is generally analyzed by statistical methods that assume a Gaussian (normal) distribution of breeding values. We present an alternative analysis based on multilocus population genetics. We use a general representation of selection, recombination, and drift to analyze an idealized polygenic system in which all genetic effects are additive (i.e., both dominance and epistasis are absent), but no assumptions are made about the distribution of breeding values or the numbers of loci or alleles. Our analysis produces three results. First, our equations reproduce the standard recursions for the mean and additive variance if breeding values are Gaussian; but they also reveal how non-Gaussian distributions of breeding values will alter these dynamics. Second, an approximation valid for weak selection shows that even if genetic variance is attributable to an effectively infinite number of loci with only additive effects, selection will generally drive the distribution of breeding values away from a Gaussian distribution by creating multilocus linkage disequilibria. Long-term dynamics of means can depart substantially from the predictions of the standard selection recursions, but the discrepancy may often be negligible for short-term selection. Third, by including mutation, we show that, for realistic parameter values, linkage disequilibrium has little effect on the amount of additive variance maintained at an equilibrium between stabilizing selection and mutation. Each of these analytical results is supported by numerical calculations. AU - Turelli, Michael AU - Barton, Nicholas H ID - 3649 IS - 1 JF - Theoretical Population Biology SN - 0040-5809 TI - Dynamics of polygenic characters under selection VL - 38 ER - TY - JOUR AB - It is widely held that each gene typically affects many characters, and that each character is affected by many genes. Moreover, strong stabilizing selection cannot act on an indefinitely large number of independent traits. This makes it likely that heritable variation in any one trait is maintained as a side effect of polymorphisms which have nothing to do with selection on that trait. This paper examines the idea that variation is maintained as the pleiotropic side effect of either deleterious mutation, or balancing selection. If mutation is responsible, it must produce alleles which are only mildly deleterious (s & 10(-3)), but nevertheless have significant effects on the trait. Balancing selection can readily maintain high heritabilities; however, selection must be spread over many weakly selected polymorphisms if large responses to artificial selection are to be possible. In both classes of pleiotropic model, extreme phenotypes are less fit, giving the appearance of stabilizing selection on the trait. However, it is shown that this effect is weak (of the same order as the selection on each gene): the strong stabilizing selection which is often observed is likely to be caused by correlations with a limited number of directly selected traits. Possible experiments for distinguishing the alternatives are discussed. AU - Barton, Nicholas H ID - 3651 IS - 3 JF - Genetics SN - 0016-6731 TI - Pleiotropic models of quantitative variation VL - 124 ER - TY - CONF AB - This paper proves an O(m 2/3 n 2/3+m+n) upper bound on the number of incidences between m points and n hyperplanes in four dimensions, assuming all points lie on one side of each hyperplane and the points and hyperplanes satisfy certain natural general position conditions. This result has application to various three-dimensional combinatorial distance problems. For example, it implies the same upper bound for the number of bichromatic minimum distance pairs in a set of m blue and n red points in three-dimensional space. This improves the best previous bound for this problem. AU - Edelsbrunner, Herbert AU - Sharir, Micha ID - 4067 SN - 978-3-540-52921-7 T2 - Proceedings of the International Symposium on Algorithms TI - A hyperplane Incidence problem with applications to counting distances VL - 450 ER - TY - JOUR AB - We consider several problems involving points and planes in three dimensions. Our main results are: (i) The maximum number of faces boundingm distinct cells in an arrangement ofn planes isO(m 2/3 n logn +n 2); we can calculatem such cells specified by a point in each, in worst-case timeO(m 2/3 n log3 n+n 2 logn). (ii) The maximum number of incidences betweenn planes andm vertices of their arrangement isO(m 2/3 n logn+n 2), but this number is onlyO(m 3/5– n 4/5+2 +m+n logm), for any>0, for any collection of points no three of which are collinear. (iii) For an arbitrary collection ofm points, we can calculate the number of incidences between them andn planes by a randomized algorithm whose expected time complexity isO((m 3/4– n 3/4+3 +m) log2 n+n logn logm) for any>0. (iv) Givenm points andn planes, we can find the plane lying immediately below each point in randomized expected timeO([m 3/4– n 3/4+3 +m] log2 n+n logn logm) for any>0. (v) The maximum number of facets (i.e., (d–1)-dimensional faces) boundingm distinct cells in an arrangement ofn hyperplanes ind dimensions,d>3, isO(m 2/3 n d/3 logn+n d–1). This is also an upper bound for the number of incidences betweenn hyperplanes ind dimensions andm vertices of their arrangement. The combinatorial bounds in (i) and (v) and the general bound in (ii) are almost tight. AU - Edelsbrunner, Herbert AU - Guibas, Leonidas AU - Sharir, Micha ID - 4066 IS - 1 JF - Discrete & Computational Geometry SN - 0179-5376 TI - The complexity of many cells in arrangements of planes and related problems VL - 5 ER - TY - JOUR AB - We show that the total number of edges ofm faces of an arrangement ofn lines in the plane isO(m 2/3– n 2/3+2 +n) for any>0. The proof takes an algorithmic approach, that is, we describe an algorithm for the calculation of thesem faces and derive the upper bound from the analysis of the algorithm. The algorithm uses randomization and its expected time complexity isO(m 2/3– n 2/3+2 logn+n logn logm). If instead of lines we have an arrangement ofn line segments, then the maximum number of edges ofm faces isO(m 2/3– n 2/3+2 +n (n) logm) for any>0, where(n) is the functional inverse of Ackermann's function. We give a (randomized) algorithm that produces these faces and takes expected timeO(m 2/3– n 2/3+2 log+n(n) log2 n logm). AU - Edelsbrunner, Herbert AU - Guibas, Leonidas AU - Sharir, Micha ID - 4072 IS - 1 JF - Discrete & Computational Geometry SN - 0179-5376 TI - The complexity and construction of many faces in arrangements of lines and of segments VL - 5 ER - TY - CONF AB - A number of rendering algorithms in computer graphics sort three-dimensional objects by depth and assume that there is no cycle that makes the sorting impossible. One way to resolve the problem caused by cycles is to cut the objects into smaller pieces. The problem of estimating how many such cuts are always sufficient is addressed. A few related algorithmic and combinatorial geometry problems are considered. AU - Chazelle, Bernard AU - Edelsbrunner, Herbert AU - Guibas, Leonidas AU - Pollack, Richard AU - Seidel, Raimund AU - Sharir, Micha AU - Snoeyink, Jack ID - 4073 SN - 0-8186-2082-X T2 - 31st Annual Symposium on Foundations of Computer Science TI - Counting and cutting cycles of lines and rods in space ER - TY - JOUR AB - Let S be a set of n closed intervals on the x-axis. A ranking assigns to each interval, s, a distinct rank, p(s)∊ [1, 2,…,n]. We say that s can see t if p(s)