@article{2565, abstract = {Immunoreactivity for the metabotropic glutamate receptor 7 (mGluR7) and that for phosphate-activated glutaminase (PAG) were examined in the trigeminal (TG), dorsal root (DRG), nodose (NG), superior cervical, celiac, and pelvic ganglia of the rat. Virtually all neuronal cell bodies showed mGluR7-like immunoreactivity (mGluR7-LI) in these ganglia. On the other hand, PAG-like immunoreactivity (PAG) was seen in almost all neuronal cell bodies in the TG, DRG and NG, but not in the other ganglia. Co-existence of mGluR7- and PAG-LI in the TG, DRG and NG was confirmed by a double-immunofluorescence immunohistochemical method. The results indicate that virtually all sensory ganglion neurons are glutamatergic and equipped with mGluR7.}, author = {Li, Jin and Ohishi, Hitoshi and Kaneko, Takeshi and Shigemoto, Ryuichi and Neki, Akio and Nakanishi, Shigetada and Mizuno, Noboru}, issn = {0304-3940}, journal = {Neuroscience Letters}, number = {1-2}, pages = {9 -- 12}, publisher = {Elsevier}, title = {{Immunohistochemical localization of a metabotropic glutamate receptor, mGluR7, in ganglion neurons of the rat; with special reference to the presence in glutamatergic ganglion neurons}}, doi = {10.1016/0304-3940(95)12299-0}, volume = {204}, year = {1996}, } @article{2566, abstract = {The present study indicated presynaptic localization of a metabotropic glutamate receptor, mGluR8, in projection neurons of the main olfactory bulb of rat. An antibody was produced by using a peptide corresponding to C-terminal 23 amino acids of mouse mGluR8. It was confirmed that the C-terminal 23 amino acids of rat mGluR8 were the same as those of mouse mGluR8 except for one, and that the antibody specifically recognized mGluR8 in the rat rhinencephalon. In layer Ia of the piriform cortex (a target area of projection fibers from the main olfactory bulb), mGluR8-like immunoreactivity (mGluR8-LI) was reduced after transection of the lateral olfactory tract, and mGluR8-LI was observed in axon terminals which were filled with round synaptic vesicles and made asymmetric synapses with dendritic spines.}, author = {Kinoshita, Ayae and Ohishi, Hitoshi and Neki, Akio and Nomura, Sakashi and Shigemoto, Ryuichi and Takada, Masahiko and Nakanishi, Shigetada and Mizuno, Noboru}, issn = {0304-3940}, journal = {Neuroscience Letters}, number = {1}, pages = {61 -- 64}, publisher = {Elsevier}, title = {{Presynaptic localization of a metabotropic glutamate receptor, mGluR8, in the rhinencephalic areas: A light and electron microscope study in the rat}}, doi = {10.1016/0304-3940(96)12489-7}, volume = {207}, year = {1996}, } @article{2567, abstract = {Trigeminothalamic and spinothalamic-tact neurons provided with substance P receptor (SPR) were examined in the rat by SPR immunofluorescence histochemistry combined with Fluoro-Gold (FG) fluorescent retrograde labeling. After FG injection in the thalamic regions, FG-labeled cells with SPR-like immunoreactivity were seen mainly in laminae I and m of the medullary and spinal dorsal horns and lateral spinal nucleus. In these regions, about one-fourth to one-third of FG-labeled cells showed SPR-like immunoreactivity.}, author = {Li, Jin and Ding, Yu and Shigemoto, Ryuichi and Mizuno, Noboru}, issn = {0006-8993}, journal = {Brain Research}, number = {1-2}, pages = {207 -- 212}, publisher = {Elsevier}, title = {{Distribution of trigeminothalamic and spinothalamic-tract neurons showing substance P receptor-like immunoreactivity in the rat}}, doi = {10.1016/0006-8993(96)00064-9}, volume = {719}, year = {1996}, } @article{2568, abstract = {Localization of a metabotropic glutamate receptor, mGluR4a, was immunohistochemically examined in the rat cerebellum with an antibody, which was produced by using a synthetic peptide corresponding to a C-terminal sequence of rat mGluR4a. Marked mGluR4a-like immunoreactivity (mGluRLta-LI) was seen in neuropil of the molecular layer of the cerebellar cortex. Electron microscopically, mGluR4a-LI was observed in many axon terminals in the molecular layer. These axon terminals showing mGluR4a-LI were filled with round synaptic vesicles and were in asymmetric synaptic contacts most frequently with dendritic spines. The results indicate that mGluR4a are located presynaptically in the parallel fibers arising from the granule cells in the cerebellar cortex.}, author = {Kinoshita, Ayae and Ohishi, Hitoshi and Nomura, Sakashi and Shigemoto, Ryuichi and Nakanishi, Shigetada and Mizuno, Noboru}, issn = {0304-3940}, journal = {Neuroscience Letters}, number = {3}, pages = {199 -- 202}, publisher = {Elsevier}, title = {{Presynaptic localization of a metabotropic glutamate receptor, mGluR4a, in the cerebellar cortex: A light and electron microscope study in the rat}}, doi = {10.1016/0304-3940(96)12519-2}, volume = {207}, year = {1996}, } @article{2569, abstract = {Morphological substrates for interactions between γ-aminobutyric acid (GABA) and substance P upon neurons expressing substance Preceptor (SPR) in the nucleus of the solitary tract (NST) were investigated by immunocytochemical electron microscopy. In the NST of the rat, many GABA-like immunoreactive axon terminals were in symmetric synaptic contacts with dendritic profiles; they were observed on nearly a half of the SPR-like immunoreactive dendritic profiles in the medial part of the caudal half of the NST.}, author = {Jia, Hong and Wang, Bai and Rao, Zhi and Shi, Ji and Shigemoto, Ryuichi and Kaneko, Takeshi and Mizuno, Noboru}, issn = {0304-3940}, journal = {Neuroscience Letters}, number = {1}, pages = {49 -- 52}, publisher = {Elsevier}, title = {{GABAergic synapses upon neurons expressing substance P receptors in the nucleus of the solitary tract: An immunocytochemical electron microscope study in the rat}}, doi = {10.1016/0304-3940(96)12654-9}, volume = {210}, year = {1996}, } @article{2570, abstract = {The probability of synaptic neurotransmitter release from nerve terminals is regulated by presynaptic receptors responding to transmitters released from the same nerve terminal or from terminals of other neurons. The release of glutamate, the major excitatory neurotransmitter, is suppressed by presynaptic auto receptors. Here we show that a metabotropic glutamate receptor (mGluR7) in the rat hippocampus is restricted to the presynaptic grid, the site of synaptic vesicle fusion. Pyramidal cell terminals presynaptic to mGluR1α-expressing interneurons have at least a ten-fold higher level of presynaptic mGluR7 than terminals making synapses with pyramidal cells and other types of interneuron. Distinct levels of mGluR7 are found at different synapses made by individual pyramidal axons or even single boutons. These results raise the possibility that presynaptic neurons could regulate the probability of transmitter release at individual synapses according to the postsynaptic target}, author = {Shigemoto, Ryuichi and Kulik, Ákos and Roberts, John and Ohishi, Hitoshi and Nusser, Zoltán and Kaneko, Takeshi and Somogyi, Péter}, issn = {0028-0836}, journal = {Nature}, number = {6582}, pages = {523 -- 525}, publisher = {Nature Publishing Group}, title = {{Target-cell-specific concentration of a metabotropic glutamate receptor in the presynaptic active zone}}, doi = {10.1038/381523a0}, volume = {381}, year = {1996}, } @article{2571, abstract = {Subtype 2 of the metabotropic glutamate receptor (mGluR2) is expressed in the presynaptic elements of hippocampal mossy fiber-CA3 synapses. Knockout mice deficient in mGluR2 showed no histological changes and no alterations in basal synaptic transmission, paired-pulse facilitation, or tetanus-induced long-term potentiation (LTP) at the mossy fiber-CA3 synapses. Long-term depression (LTD) induced by low-frequency stimulation, however, was almost fully abolished. The mutant mice performed normally in water maze learning tasks. Thus, the presynaptic mGluR2 is essential for inducing LTD at the mossy fiber-CA3 synapses, but this hippocampal LTD does not seem to be required for spatial learning.}, author = {Yokoi, Mineto and Kobayashi, Kazuto and Manabe, Toshiya and Takahashi, Tomoyuki and Sakaguchi, Isako and Katsuura, Goro and Shigemoto, Ryuichi and Ohishi, Hitoshi and Nomura, Sakashi and Nakamura, Kenji and Nakao, Kazuki and Katsuki, Motoya and Nakanishi, Shigetada}, issn = {0036-8075}, journal = {Science}, pages = {645 -- 647}, publisher = {American Association for the Advancement of Science}, title = {{Impairment of hippocampal mossy fiber LTD in mice lacking mGluR2}}, doi = {10.1126/science.273.5275.645}, volume = {273}, year = {1996}, } @article{2572, abstract = {The distribution of the mRNA for a pituitary adenylate cyclase- activating polypeptide (PACAP) receptor (PACAP-R) was examined in the rat brain, and also in the hypophysis and pineal gland, by in situ hybridization with a specific 35S-labeled riboprobe which was generated from a rat PACAP-R cDNA clone. In the brain, expression of PACAP-R mRNA was most prominent in the periglomerular and granule cells of the olfactory bulb, granule cells of the dentate gyrus, supraoptic nucleus, and area postrema. The expression was also intense in the piriform, cingulate, and retrosplenial cortices, pyramidal cells in CA2, non-pyramidal cells in CA1- CA3, neuronal cells in the hilus of the dentate gyrus, lateral septal nucleus, intercalated amygdaloid nucleus, anterodorsal thalamic nucleus, most of the midline and intralaminar thalamic nuclei, many regions of the hypothalamus, dorsal motor nucleus of the vagus nerve, hypoglossal nucleus, and lateral reticular nucleus. No significant expression was detected in the mitral and tufted cells in the olfactory bulb, pyramidal cells in CA1 and CA3, posterior nuclear group of the thalamus, dorsal lateral geniculate nucleus, and Purkinje, Golgi, and granule cells in the cerebellar cortex. Moderate-to-weak expression was further observed in many other regions of the brain. In the cerebellar cortex, presumed Bergmann gila cells showed moderate expression. In the hypophysis, the expression was moderate in the anterior lobe, and weak to moderate in the posterior lobe; no significant expression was observed in the intermediate lobe. In the pineal gland, the expression was very weak, if any. Thus, the expression of PACAP-R was detected not only on neuronal cells but also on some particular glial cells. The present study has shown, for the first time, the exact site of PACAP-R expression in the brain and hypophysis. Although the functional significance of PACAP and PACAP-R in the brain still remains to be clarified, the present results are considered to provide some direction for future functional studies.}, author = {Hashimoto, Hitoshi and Nogi, Hiroyuki and Mori, Kensaku and Ohishi, Hitoshi and Shigemoto, Ryuichi and Yamamoto, Kyohei and Matsuda, Toshio and Mizuno, Noboru and Nagata, Shigekazu and Baba, Akemichi}, issn = {0021-9967}, journal = {Journal of Comparative Neurology}, number = {4}, pages = {567 -- 577}, publisher = {Wiley-Blackwell}, title = {{Distribution of the mRNA for a pituitary adenylate cyclase-activating polypeptide receptor in the rat brain: An in situ hybridization study}}, doi = {10.1002/(SICI)1096-9861(19960805)371:4<567::AID-CNE6>3.3.CO;2-M}, volume = {371}, year = {1996}, } @article{2573, abstract = {Developmental changes of the distribution pattern of substance P receptor (SPR) were investigated immunohistochemically in the rat striatum. The SPR immunoreactivity in the striatum first emerged at postnatal day 1 and transiently showed a patchy pattern of distribution until it displayed the adult pattern of homogeneous distribution by the end of the third postnatal week. The SPR-immunoreactive patches were most marked in the medial and dorsolateral parts of the striatum, as well as in the subcallosal streak. They matched tyrosine hydroxylase-enriched areas and, conversely, avoided calbindin-enriched zones. No neurons within the SPR-immunoreactive patches contained either choline acetyltransferase or somatostatin, which is known to be contained in intrinsic neurons in the striatum. The vast majority of SPR-immunoreactive patch neurons also contained DARPP-32, a phosphoprotein that is expressed in striatal projection neurons with D1 dopamine receptor. The results indicate that SPR-immunoreactive patches which appear transiently in the developing striatum are in register with the striatal patch compartment, and that SPR immunoreactivity within these patches may be expressed on projection neurons rather than intrinsic neurons. Such SPR immunoreactivity in projection neurons in striatal patches may fade out in adulthood.}, author = {Tokuno, Hironobu and Takada, Masahiko and Kaneko, Takeshi and Shigemoto, Ryuichi and Mizuno, Noboru}, issn = {0165-3806}, journal = {Developmental Brain Research}, number = {1}, pages = {107 -- 117}, publisher = {Elsevier}, title = {{Patchy distribution of substance P receptor immunoreactivity in the developing rat striatum}}, doi = {10.1016/0165-3806(96)00080-6}, volume = {95}, year = {1996}, } @article{2574, abstract = {lonotropic and metabotropic (mGluR1a) glutamate receptors were reported to be segregated from each other within the postsynaptic membrane at individual synapses. In order to establish whether this pattern of distribution applies to the hippocampal principal cells and to other postsynaptic metabotropic glutamate receptors, the mGluR1a/b/c and mGluR5 subtypes were localized by immunocytochemistry. Principal cells in all hippocampal fields were reactive for mGluR5, the strata oriens and radiatum of the CA1 area being most strongly immunolabelled. Labelling for mGluR1b/c was strongest on some pyramids in the CA3 area, weaker on granule cells and absent on CA1 pyramids. Subpopulations of non-principal cells showed strong mGluR1 or mGluR5 immunoreactivity. Electron microscopic pre-embedding immunoperoxidase and both pre- and postembedding immunogold methods consistently revealed the extrasynaptic location of both mGluRs in the somatic and dendritic membrane of pyramidal and granule cells. The density of immunolabelling was highest on dendritic spines. At synapses, immunoparticles for both mGluR1 and mGluR5 were found always outside the postsynaptic membrane specializations. Receptors were particularly concentrated in a perisynaptic annulus around type 1 synaptic junctions, including the invaginations at 'perforated' synapses. Measurements of immunolabelling on dendritic spines showed decreasing levels of receptor as a function of distance from the edge of the synaptic specialization. We propose that glutamatergic synapses with an irregular edge develop in order to increase the circumference of synaptic junctions leading to an increase in the metabotropic to ionotropic glutamate receptor ratio at glutamate release sites. The perisynaptic position of postsynaptic metabotropic glutamate receptors appears to be a general feature of glutamatergic synaptic organization and may apply to other G-protein-coupled receptors. © European Neuroscience Association.}, author = {Luján, Rafael and Nusser, Zoltán and Roberts, John and Shigemoto, Ryuichi and Somogyi, Péter}, issn = {0953-816X}, journal = {European Journal of Neuroscience}, number = {7}, pages = {1488 -- 1500}, publisher = {Wiley-Blackwell}, title = {{ Perisynaptic location of metabotropic glutamate receptors mGluR1 and mGluR5 on dendrites and dendritic spines in the rat hippocampus}}, doi = {10.1111/j.1460-9568.1996.tb01611.x}, volume = {8}, year = {1996}, } @article{2725, abstract = {We prove that the two dimensional free magnetic Schrödinger operator, with a fixed constant magnetic field and Dirichlet boundary conditions on a planar domain with a given area, attains its smallest possible eigenvalue if the domain is a disk. We also give some rough bounds on the lowest magnetic eigenvalue of the disk.}, author = {László Erdös}, journal = {Calculus of Variations and Partial Differential Equations}, number = {3}, pages = {283 -- 292}, publisher = {Springer}, title = {{Rayleigh-type isoperimetric inequality with a homogeneous magnetic field}}, doi = {10.1007/BF01254348}, volume = {4}, year = {1996}, } @article{2726, abstract = {We investigate whether the eigenfunctions of the two-dimensional magnetic Schrödinger operator have a Gaussian decay of type exp(-Cx2) at infinity (the magnetic field is rotationally symmetric). We establish this decay if the energy (E) of the eigenfunction is below the bottom of the essential spectrum (B), and if the angular Fourier components of the external potential decay exponentially (real analyticity in the angle variable). We also demonstrate that almost the same decay is necessary. The behavior of C in the strong field limit and in the small (B - E) limit is also studied.}, author = {Erdös, László}, issn = {1016-443X}, journal = {Geometric and Functional Analysis}, number = {2}, pages = {231 -- 248}, publisher = {Birkhäuser}, title = {{Gaussian decay of the magnetic eigenfunctions}}, doi = {10.1007/BF02247886}, volume = {6}, year = {1996}, } @article{11761, abstract = {We prove that in an undirected graph there are at most O(n²) cuts of size strictly less than of the size of the minimum cut.}, author = {Henzinger, Monika H and Williamson, David P.}, issn = {0020-0190}, journal = {Information Processing Letters}, number = {1}, pages = {41--44}, publisher = {Elsevier}, title = {{On the number of small cuts in a graph}}, doi = {10.1016/0020-0190(96)00079-8}, volume = {59}, year = {1996}, } @inproceedings{11804, abstract = {This paper shows how a general technique, called lock-step search, used in dynamic graph algorithms, can be used to improve the running time of two problems arising in program verification and communication protocol design. (1)We consider the nonemptiness problem for Streett automata: We are given a directed graph G = (V, E) with n = ¦V¦ and m = ¦E¦, and a collection of pairs of subsets of vertices, called Streett pairs,〈L i , U i 〉, i = 1.k. The question is whether G has a cycle (not necessarily simple) which, for each 1 ≤ i ≤ k, if it contains a vertex from L i then it also contains a vertex of U i . Let b=Σ i=1..k |L i |+|U i |. The previously best algorithm takes time O((m + b) min{n, k}). We present an algorithm that takes time 𝑂(𝑚min{𝑚𝑙𝑜𝑔𝑛,‾‾‾‾‾‾√𝑘,𝑛}+𝑏𝑚𝑖𝑛{𝑙𝑜𝑔𝑛,𝑘}). (2)In communication protocol pruning we are given a directed graph G = (V, E) with l special vertices. The problem is to efficiently maintain the strongly-connected components of the special vertices on a restricted set of edge deletions. Let m i be the number of edges in the strongly connected component of the ith special vertex. The previously best algorithm repeatedly recomputes the strongly-connected components which leads to a running time of O(Σ i m 2i). We present an algorithm with time 𝑂(𝑙√∑𝑖𝑚1.5𝑖).}, author = {Henzinger, Monika H and Telle, Jan Arne}, booktitle = {5th Scandinavian Workshop on Algorithm Theory}, isbn = {9783540614227}, issn = {1611-3349}, location = {Reykjavik, Iceland}, pages = {16–27}, publisher = {Springer Nature}, title = {{Faster algorithms for the nonemptiness of streett automata and for communication protocol pruning}}, doi = {10.1007/3-540-61422-2_117}, volume = {1097}, year = {1996}, } @inproceedings{11910, abstract = {We state a new sampling lemma and use it to improve the running time of dynamic graph algorithms. For the dynamic connectivity problem the previously best randomized algorithm takes expected time O(log3 n) per update, amortized over Ω(m) updates. Using the new sampling lemma, we improve its running time to O(log2 n). There exists a lower bound in the cell probe model for the time per operation of Ω(log n/ log log n) for this problem. Similarly improved running times are achieved for 2-edge connectivity, k-weight minimum spanning tree, and bipartiteness.}, author = {Henzinger, Monika H and Thorup, Mikkel}, booktitle = {23rd International Colloquium on Automata, Languages, and Programming}, isbn = {9783540614401}, issn = {1611-3349}, location = {Paderborn, Germany}, pages = {290--299}, publisher = {Springer Nature}, title = {{Improved sampling with applications to dynamic graph algorithms}}, doi = {10.1007/3-540-61440-0_136}, volume = {1099}, year = {1996}, } @inproceedings{11927, abstract = {We are given a set 7 = {Tl , Tz, . . . , Tk} of rooted binary trees, each Ti leaf-labeled by a subset L(x) c {1,2 )...) n}. IfT is a tree on {1,2, . . , n}, we let T]L denote the subtree of T induced by the nodes of L and all their ancestors. The consensus tree problem asks whether there exists a tree T* such that for every I, T’ IC(Ti) is homeomorphic to Ti. We present algorithms which test if a given set of trees has a consensus tree and if so, construct one. The deterministic algorithm takes time min{O(mn’/‘), O(m + n2 logn)}, where m = Ci IZl and uses linear space. The randomized algorithm takes time O(m log3 n) and uses linear space. The previous best for this problem was an 1981 O(mn) algorithm by Aho et al. Our faster deterministic algorithm uses a new efficient algorithm for the following interesting dynamic graph problem: Given a graph G with n nodes and m edges and a sequence of b batches of one or more edge deletions, then after each batch, either find a new component that has just been created or determine that there is no such component. For this problem, we have a simple algorithm with running time O(n2 log n + be min{ n2, m log n}), where be is the number of batches which do not result in a new component. For our particular application, bc 5 1. If all edges are deleted, then the best previously known deterministic algorithm requires time O(mJ;ii) to solve this problem. computational evolutionary biology. The first application is in the problem of inferring consensus of trees when there can be disagreement[l6]. There have, been several models suggested for this problem[2, 3, 4, 8, ?, 11, 17, 181, of which one is called the Local Consensus Tree[l5]. The local consensus tree model presumes that the user provides a local consensus rule which determines the form of the output tree on (perhaps) each triple of leaves, and the objective is to determine whether a tree exists which is consistent with each of the constraints. We will show that we can construct the local consensus tree of k trees on n species in O(kn3) time, improving on the O(lcn3 + n”) running time if we use the Aho et al algorithm. The second application is a heuristic for constructing the maximum likelihood tree based upon combining solutions to small subproblems. This is a simple and yet potentially significantly interesting approach to the evolutionary tree construction problem. }, author = {Henzinger, Monika H and King, Valerie and Warnow, Tandy}, booktitle = {7th Annual ACM-SIAM Symposium on Discrete Algorithms}, isbn = {0898713668}, location = {Atlanta, GA, United States}, pages = {333 --340}, publisher = {Society for Industrial and Applied Mathematics}, title = {{Constructing a tree from homeomorphic subtrees, with applications to computational evolutionary biology}}, year = {1996}, } @article{1943, abstract = {Transhydrogenase from beef-heart mitochondria was solubilised with Triton X-100 and purified by column chromatography. The detergent-dispersed enzyme catalysed the reduction of acetylpyridine adenine dinucleotide (AcPdAD+) by NADH, but only in the presence of NADP+. Experiments showed that this reaction was cyclic; NADP(H), whilst remaining bound to the enzyme, was alternately reduced by NADH and oxidised by AcPdAD+. A period of incubation of the enzyme with NADPH at pH 6.0 led to inhibition of the simple transhydrogenation reaction between AcPdAD+ and NADPH. However, after such treatment, transhydrogenase acquired the ability to catalyse the (NADPH-dependent) reduction of AcPdAD+ by NADH. It is suggested that this is a similar cycle to the one described above. Evidently, the binding affinity for NADP+ increases as a consequence of the inhibition process resulting from prolonged incubation with NADPH. The pH dependences of simple and cyclic transhydrogenation reactions are described. Though more complex than those in Escherichia coli transhydrogenase, they are consistent with the view [Hutton, M., Day, J.M., Bizouarn, T. and Jackson, J.B. (1994) Eur. J. Biochem. 219, 1041–10511] that, also in the mitochondrial enzyme, binding the release of NADP+ and NADP are accompanied by binding and release of a proton. The enzyme was successfully reconstituted into liposomes by a cholate dilution procedure. The proteoliposomes catalysed cyclic NADPH-dependent reduction of AcPdAD+ by NADH only when they were tightly coupled. However, they catalysed cyclic NADP+-dependent reduction of AcPdAD+ by NADH only when they were uncoupled eg. by addition of carbonylcyanide-p-trifluoromethoxyphenyl hydrazone. These observations are evidence that the proton binding and release which accompany NADP+ binding and release, respectively, take place on the inside of the vesicle, and that they are components of the electrogenic processes of the enzyme.}, author = {Sazanov, Leonid A and Jackson, Baz}, issn = {0005-2728}, journal = {Biochimica et Biophysica Acta - Bioenergetics}, number = {3}, pages = {304 -- 312}, publisher = {Elsevier}, title = {{Cyclic reactions catalysed by detergent-dispersed and reconstituted transhydrogenase from beef heart mitochondria; implications for the mechanism of proton translocation}}, doi = {10.1016/0005-2728(95)00096-2}, volume = {1231}, year = {1995}, } @article{6162, abstract = {The tra-1 gene is the terminal global selector of somatic sex in Caenorhabditis elegans: High tra-1 activity elicits female somatic development while low tra-1 activity elicits male development. Previous genetic studies defined a cascade of negatively interacting genes that regulates tra-1 activity in response to the primary sex-determining signal. Here, we investigate the last step in this regulatory cascade, by studying rare gain-of-function (gf) mutations of tra-1 that direct female somatic development irrespective of the upstream sex-determining signal. These mutations appear to abolish negative regulation of tra-1 in male tissues. We identify the lesions associated with 29 of these mutations and find that all affect a short stretch of amino acid residues present in both protein products of the tra-1 gene. Twenty-six alleles are associated with single nonconservative amino acid substitutions. Two alleles affect tra-1 RNA splicing and generate messages that omit part or all of the exon encoding this short stretch. These results suggest that sexual regulation of tra-1 is achieved post-translationally, by an inhibitory protein-protein interaction. The amino acid stretch altered by the tra-1(gf) mutations may define a site of interaction for negative regulators of tra-1. The stretch includes a potential phosphorylation site for glycogen synthase kinase 3 and may be conserved in the human gene GLI3, a homolog of tra-1 identified previously.}, author = {de Bono, Mario and Zarkower, D. and Hodgkin, J.}, issn = {08909369}, journal = {Genes and Development}, number = {2}, pages = {155--167}, publisher = {CSH Press}, title = {{Dominant feminizing mutations implicate protein-protein interactions as the main mode of regulation of the nematode sex-determining gene tra-1}}, doi = {10.1101/gad.9.2.155}, volume = {9}, year = {1995}, } @inbook{3454, abstract = {The study of gene expression and regulation in the central nervous system (CNS) is a daunting task because of the diversity of neuronal phenotypes and the complexity of many protein classes. Molecular cloning revealed the presence of a large number of different protein families in the CNS, each comprising several members. Ligand-gated ion channels may serve as an example to illustrate this point (for review, see Unwin, 1993). Heterologous expression combined with electrophysiological analysis suggests that ligand-gated channels are multimeric proteins with functional properties depending on the subunit composition. Very little is known, however, about how the functional properties of the recombinant and native receptors relate to each other. Thus, it is of eminent importance to elucidate the subunit expression profile in different types of neurons in the CNS and to correlate this with the functional properties of the native receptors.}, author = {Monyer, Hannah and Jonas, Peter M}, booktitle = {Single-channel recording}, editor = {Sakmann, Bert and Neher, Erwin}, isbn = {978-0-306-44870-6}, pages = {357 -- 373}, publisher = {Plenum}, title = {{Polymerase chain reaction analysis of ion channel expression in single neurons of brain slices}}, doi = {10.1007/978-1-4419-1229-9_16}, year = {1995}, } @inbook{3455, abstract = {At a synapse, the transmitter is stored in synaptic vesicles and is released into the synaptic cleft almost instantaneously upon fusion of these vesicles with the presynaptic membrane. Subsequently, the transmitter diffuses to ligand-gated ion channels in the postsynaptic density, binds to them, and thereby causes channel activation. Unfortunately, we have estimates neither of the exact amount of transmitter in the synaptic vesicle nor of the concentration in the synaptic cleft reaching the postsynaptic receptors, and in some cases even the identity of the transmitter is unknown. These questions may be addressed by modeling of release and diffusion. Such a theoretical approach, however, is based on several assumptions, some of which lack experimental evidence.}, author = {Jonas, Peter M}, booktitle = {Single-channel recording}, editor = {Sakmann, Bert and Neher, Erwin}, isbn = {978-0-306-44870-6}, pages = {231 -- 243}, publisher = {Plenum}, title = {{Fast application of agonists to isolated membrane patches}}, doi = {10.1007/978-1-4419-1229-9_10}, year = {1995}, }