4,5,6,7-Tetrahydro-7-oxobenzo[b]thien-4-ylurea; Sulbenox,a novel animal growth stimulant

Summary The title compound, a metabolite of 4,5,6,7-tetrahydrobenzo[b]thien-4-ylurea, was synthesized and found to be an effective growth promoter in sheep, mice, and rats. In sheep it gave over a 6-week growth period at 15 and 60 ppm in the diet an economically and statistically significant growth response.United States adopted name (USAN).We thank Dr T.J. Bentley, D.J. France, and Dr L.D. Spicer for synthesis and structural elucidation work, Dr M.W. Bullock and G.W. Cox for metabolism studies, Drs J. Harter, D. Ingle, J.M. Pensack and L. Wozniak and their associates for biological data, and Drs D.J. Thoennes and M.L. Thomson for spectral data and interpretations.     

Origin and development of neuroepithelial bodies in fetal rabbit lungs

Summary Light-microscope studies concerning the embryological development of fetal rabbit lungs revealed the occurrence of argyrophilic neuroepithelial bodies in an early gestational stage (i.e. already in the glandular period and from the 18th day onwards). Their morphological characteristics and further differentiation towards birth are detailed.Supported by a grant from the Nationaal Fonds voor Wetenschappelijk Onderzoek — Fonds voor Geneeskundig Wetenschappelijk Onderzoek (Belgium). We thank E. Swinnen. H. Van den Bosch and M.R. Van hamme for technical, G. Pison for photographical and L. Lauwers for secretarial assistance.     

Quinone tanning in Agnatha

Summary The buccal teeth and notochordal sheath of the marine hagfish,Petromyzon marinus (L.) are phenolically tanned like the cuticle of insects and other arthropods.Acknowledgments. We are grateful to Dr Bill Lovejoy for generously supplyingP. marinus L. A.R.V. is thankful to Prof. R.G. Michael for encouragement.Previously called A. Sannasi.     

Resolution of small G1 and G2 populations of L1210 leukemia by flow microfluorometric analysis aided by velocity sedimentation

L1210 leukemic cells grown in vitro were subjected to kinetic analysis using a flow microfluorometer. A single broad peak was found for the DNA content distribution if unfractionated cells were used; prior fractionation using lg velocity sedimentation allowed the separation of small peaks with smaller (G1) and larger (G2) DNA contents from the dominant S phase peak with intermediate DNA content.     

Trans-epoxide hydrolase: A key indicator enzyme for herbivory in arthropods

Summary An epoxide hydrolase selective for a trans-epoxide substrate is more commonly associated with arthropod herbivory than is a cis-selective epoxide hydrolase. The distinct selectivities in epoxide hydrolase activities between herbivorous pests and entomophagous arthropods used in their biological control may aid design of integrated pest management systems.We thank E.G. Grafius, F. Matsumura, J.R. Miller, K.L. Strickler and S.G. Wellso together with M.E. Whalon and D. Young at Michigan State University for insects and aid in identification respectively. T.L. Burger, Sr. and D. Perkins, both of the USDA, also supplied insects, and the NSF (DAR-8011600) provided support. R. Feyereisen and D. Vincent of the Department of Entomology, Oregon State University provided helpful commentary. C.A. Mullin is presently at the Pesticide Research Laboratory, Department of Entomology, The Pennsylvania State University, University Park, PA, 16802, USA. This is paper No. 10926 of the Mich. Agric. Exp. Stn and No. 6790 of the Oregon Agric. Exp. Stn journal series.     

Depletion of synaptic vesicles at the frog (Rana pipiens) neuromuscular junctions by tetraphenylboron

Summary At the frog neuromuscular junction tetraphenylboron produced a decrease in miniature endplate potential amplitude, accompanied by a decrease in the number but not the size of synaptic vesicles.This work was supported by NIH Grants Nos NS-07740 and NS-05707 to R. L. P. and was done during the tenure of a Research Fellowship of Muscular Dystrophy Associations of America, a Wellcome Research Travel Grant and a grant from the Carnegie Trust for the Universities of Scotland to I. G. M. The assistance of Dr.R. M. Schnitzler, W. G. Boldosser andP. M. Spannbauer is gratefully acknowledged.     

Specialized membrane junctions in the avian cerebellum

Summary Pentalaminar specialized membrane junctions-tight junctions — are described in the granular layer of the pigeon cerebellum. The presence of these axo-dendritique and dendrosomatic contacts suggest the existence of electrotonic coupling in the pigeon cerebellum.This work received financial support from the Instituto de Alta Cultura, Lisbon, Project No. PMC5-I.Acknowledgements. I am greatly indebted to Prof.E. G. Gray and Prof.A. Sousa Pinto for helpful advice and criticism. The technical assistance of Mrs.M. M. Pacheco, M. G. Rodrigues, M. L. Brito and Mr.Bessa Nunes is gratefully acknowledged.     

Molecular basis of parathyroid hormone receptor signaling and trafficking: a family B GPCR paradigm

The parathyroid hormone (PTH) receptor type 1 (PTHR), a G protein-coupled receptor (GPCR), transmits signals to two hormone systems—PTH, endocrine and homeostatic, and PTH-related peptide (PTHrP), paracrine—to regulate different biological processes. PTHR responds to these hormonal stimuli by activating heterotrimeric G proteins, such as G_S that stimulates cAMP production. It was thought that the PTHR, as for all other GPCRs, is only active and signals through G proteins on the cell membrane, and internalizes into a cell to be desensitized and eventually degraded or recycled. Recent studies with cultured cell and animal models reveal a new pathway that involves sustained cAMP signaling from intracellular domains. Not only do these studies challenge the paradigm that cAMP production triggered by activated GPCRs originates exclusively at the cell membrane but they also advance a comprehensive model to account for the functional differences between PTH and PTHrP acting through the same receptor.     

Hsp27 suppresses the formation of inclusion bodies induced by expression of R120G alpha B-crystallin,a cause of desmin-related myopathy

The R120G mutation in the small heat shock protein (sHSP) alpha B-crystallin has been identified in a family suffering from desmin-related myopathy. In this study, we characterized the features of transiently expressed R120G alpha B-crystallin in mammalian cells. In addition, we examined interactions of this mutant alpha B-crystallin with Hsp27, another representative sHSP. In HeLa cells, transiently expressed R120G alpha B-crystallin was mainly fractionated in the insoluble fraction, although wild-type alpha B-crystallin was predominantly found in the soluble fraction. In immunofluorescence studies, we found 15-25% of R120G alpha B-crystallin-expressing cells to contain multiple cytosolic inclusion bodies, in which Hsp27 was also localized. When R120G alpha B-crystallin and Hsp27 were transiently co-expressed in HeLa cells, the amount of R120G alpha B-crystallin in the soluble fraction was greater than with expression of R120G alpha B-crystallin alone. Moreover, co-expression resulted in reduced formation of inclusion bodies, suggesting that Hsp27 acts as a molecular chaperone for R120G alpha B-crystallin.     

Second‐Generation Prediction Markets for Information Aggregation: A Comparison of Payoff Mechanisms

Initial applications of prediction markets (PMs) indicate that they provide good forecasting instruments in many settings, such as elections, the box office, or product sales. One particular characteristic of these ‘first‐generation’ (G1) PMs is that they link the payoff value of a stock's share to the outcome of an event. Recently, ‘second‐generation’ (G2) PMs have introduced alternative mechanisms to determine payoff values which allow them to be used as preference markets for determining preferences for product concepts or as idea markets for generating and evaluating new product ideas. Three different G2 payoff mechanisms appear in the existing literature, but they have never been compared. This study conceptually and empirically compares the forecasting accuracy of the three G2 payoff mechanisms and investigates their influence on participants' trading behavior. We find that G2 payoff mechanisms perform almost as well as their G1 counterpart, and trading behavior is very similar in both markets (i.e. trading prices and trading volume), except during the very last trading hours of the market. These results indicate that G2 PMs are valid instruments and support their applicability shown in previous studies for developing new product ideas or evaluating new product concepts. Copyright © 2011 John Wiley & Sons, Ltd.     

The number of parallel fibre-Purkinje dendrite synapses. A morphometric evaluation

Summary Quantitative parameters concerning synapses were studied in the cerebellar molecular layer of 4 cats using ultrastructural morphometric methods. The number of parallel fibre-Purkinje dendrite synapses was estimated to be about 200,000.This study was granted by I.N.I.C. (Centro de Morfologia Experimental—MbP₁ e Centro de Anatomia Patológica e Oncologia-MbP₃).The authors thank Mrs M.L. Brito, Mrs M.A. Nascimento, Mrs M.G. Rodrigues and Mr L.B. Nunes for their technical assistance.     

Mammalian olfactory receptors: pharmacology, G protein coupling and desensitization

The vertebrate olfactory system recognizes and discriminates between thousands of structurally diverse odorants. Detection of odorants in mammals is mediated by olfactory receptors (ORs), which comprise the largest superfamily of G protein-coupled receptors (GPCRs). Upon odorant binding, ORs couple to G proteins, resulting in an increase in intracellular cAMP levels and subsequent receptor signaling. In this review, we will discuss recently published studies outlining the molecular basis of odor discrimination, focusing on pharmacology, G protein activation, and desensitization of ORs. A greater understanding of the molecular mechanisms underlying OR activity may help in the discovery of agonists and antagonists of ORs, and of GPCRs with potential therapeutic applications.     

Hormone-induced subcellular redistribution of trimeric G proteins

Trimeric guanine nucleotide-binding proteins (G proteins) function as the key regulatory elements in a number of transmembrane signaling cascades where they convey information from agonist-activated receptors to effector molecules. The subcellular localization of G proteins is directly related to their functional role, i.e., the dominant portion of the cellular pool of G proteins resides in the plasma membrane. An intimate association of G protein subunits with the plasma membrane has been well known for a long time. However, results of a number of independent studies published in the past decade have indicated clearly that exposure of intact target cells to agonists results in subcellular redistribution of the cognate G proteins from plasma membranes to the light-vesicular membrane fractions, in internalization from the cell surface into the cell interior and in transfer from the membrane to the soluble cell fraction (high-speed supernatant), i.e., solubilization. Solubilization of G protein α subunits as a consequence of stimulation of G protein-coupled receptors (GPCRs) with agonists has also been observed in isolated membrane preparations. The membrane-cytosol shift of G proteins was detected even after direct activation of these proteins by non-hydrolyzable analogues of GTP or by cholera toxin-induced ADP-ribosylation. In addition, prolonged stimulation of GPCRs with agonists has been shown to lead to down-regulation of the relevant G proteins. Together, these data suggest that G proteins might potentially participate in a highly complex set of events, which are generally termed desensitization of the hormone response. Internalization, subcellular redistribution, solubilization, and down-regulation of trimeric G proteins may thus provide an additional means (i.e., beside receptor-based mechanisms) to dampen the hormone or neurotransmitter response after sustained (long-term) exposure. Received 31 August 2001; received after revision 31 October 2001; accepted 7 November 2001     

The identification of ecdysterone (20-hydroxyecdysone) in 3 species of molluscs (Gastropoda: Pulmonata)

Summary Ecdysterone has been identified in the schistosomiasis vectorBiomphalaria glabrata Say and inHelix aspersa Müller as well as inLymmaea stagnalis L. by chromatography, bioassay, radioimmunoassay, derivatization and by mass spectroscopy. Analysis of the food, faeces and hepatopancreas suggest that the sterol is derived from the diet. The probable function of ecdysterone in relation to calcification of the shell is discussed in this paper.We wish to thank Professor P. Karlson and Dr J. Koolman (Phillips University, Marburg-Lahn, FRG) for providing facilities for RIA. The initial study was begun at the University of Sussex and continued at the Courtauld Institute of Biochemistry, Middlesex Hospital Medical School, London, while D.L.W. was supported by the Ministry of Overseas Development. London and the Medical Research Council of Great Britain (grant G974/525/T). We thank Mr P. Mellon for the mass spectrum and Dr G.B. Russell for his interest in the earlier part of this study. We also thank Professor E. Scherer and Dr Q. Uwe (University of Essen, FRG) for their help in the irradiation ofL. stagnalis.Gauss Str. 82, D-4630 Bochum 5 (Federal Republic of Germany). Research results usingL. stagnalis were submitted for the Philips Europa Wettbewerb für junge Forscher und Erfinder (1979) in a thesis entitled Zur Frage der Existenz von Steroiden und Gonadoliberin bei der Grossen Schlammschnecke (Lymmaea stagnalis L.): ein Beitrag zur Evolution der Insekten- und Wirbeltierhormone.     

Changes in cAMP concentration in the rat preoptic area during synchronized and desynchronized sleep

Summary cAMP concentration was found to be significantly lower during desynchronized sleep than during synchronized sleep in the preoptic area of rats kept at normal laboratory temperature. No significant changes in cerebral cortex cAMP concentraion were observed in the same experimental conditions.This work was supported by grants from Consiglio Nazionale delle Ricerche and Ministero della Pubblica Istruzione.The authors wish to thank G. Mancinelli and L. Sabattini for technical assistance and M. Luppi for secretarial assistance.     

Antiparasitic agents. 4. Injectable phenylguanidine anthelmintics

Summary A series of phenylguanidine anthelminties has been discovered to be active by injection against nematode and trematode species.For the previous paper in this series, see R. D. Haugwitz, B. V. Maurer, G. A. Jacobs, V. L. Narayanan, L. R. Cruthers and J. Szanto, J. med. Chem.22, 1113 (1979).     

Electrical response of bat retina to spectral stimulation: comparison of four microchiropteran species

Summary Electrical responses of the retinas of 4 species of microchiropteran bats stimulated by spectrally restricted light flashes were found to diverge systematically from the rhodopsin absorption spectrum. The divergence was progressively greater across the 4 species. The results appeared explainable by assuming a second photoreceptor class and photopigment which was present in progressively greater numbers in the retinas ofEptesicus fuscus, Desmodus rotundus, Artibeus jamaicensis andCarollia perspicillata.This work was made possible by equipment provided by grant No. EY 01228 from the U.S.P.H.S., Bob Hope Fight for Sight award No. G 522 and a grant from Research to Prevent Blindness, Inc. Portions of this work were presented at the Fifth International Bat Research Conference, Albuquerque, New Mexico, August 11, 1978.The authors would like to express appreciation to Drs A.M. Potts, J. B. Longley, R. S. Crockett and T. G. Wheeler for helpful suggestions and to Drs J. H. Richardson, J. G. Cooper, L. Kundrotas, Mr B. Spoonamore and Mr W. Lopez-Forment for facilitating collection and importation of the Mexican bats.     

Inhibition of cytokinesis in plant cells by 6-dimethylaminopurine and puromycin

Summary Binucleate cells are produced in garlic root tip cells with puromycin and with 6-dimethylaminopurine (6-DMAP), the purine component of puromycin. The possibility that the effect of puromycin on cytokinesis is due to 6-DMAP-which appears to be without short term effects on protein synthesis-is discussed.This work was supported by AI 031871 from the Centre National de la Recherche Scientifique (M-C.B.) and the University René Descartes (M-C.B. and F.L.), Paris.The authors would like to thank Miss G. Daouse and Miss M. Delage for excellent technical assistance.