Inhaltsverzeichnis


Publications 2023


Hierarchical regulation of functionally antagonistic neuropeptides expressed in a single neuron pair

Ichiro Aoki, Luca Golinelli, Eva Dunkel, Shripriya Bhat, Erschad Bassam, Isabel Beets, Alexander Gottschalk (2023). bioRxiv 2023.11.23.568473; doi: https://doi.org/10.1101/2023.11.23.568473

Structure-function analysis suggests that the photoreceptor LITE-1 is a light-activated ion channel

*Hanson, S., Scholüke, J., Liewald, J., Sharma, R., Ruse, C., Engel, M., Schüler, C., Klaus, A., Arghittu, S., Baumbach, F., Seidenthal, M., Dill, H., *Hummer, G., & *Gottschalk, A. (2023). Curr Biol 33: published online 31st July 2023. * corresponding authors. DOI: 10.1016/j.cub.2023.07.008

All-optical closed-loop voltage clamp for precise control of muscles and neurons in live animals

Bergs ACF, Liewald JF, Rodriguez-Rozada S, Liu Q, Wirt Ch, Bessel A, Zeitzsche Nl, Durmaz H, Nozownik A, Dill H, Jospin M, Vierock J, Bargmann CI, Hegemann P, Wiegert JS, Gottschalk A (2023) Nat Commun 14, 1939 (2023). https://doi.org/10.1038/s41467-023-37622-6

pOpsicle: An all-optical reporter system for synaptic vesicle recycling combining pH-sensitive fluorescent proteins with optogenetic manipulation of neuronal activity

Seidenthal M, Janosi B, Rosenkranz N, Schuh N, Elvers N, Willoughby M, Zhao X and Gottschalk A (2022) Front. Cell. Neurosci., 2023, Volume 17; https://www.frontiersin.org/articles/10.3389/fncel.2023.1120651/full

Coordinated electrical and chemical signaling between two neurons orchestrates switching of motor states

Bach M, Bergs A, Mulcahy B, Zhen M, Gottschalk A (2022) bioRxiv 2022.01.04; https://www.biorxiv.org/content/10.1101/2023.01.04.522780v2


Publications 2022

Rapid and reversible optogenetic silencing of synaptic transmission by clustering of synaptic vesicles

Vettkötter D, Schneider M, Liewald JF, Zeiler S, Guldan J, Watanabe S and Gottschalk A (2022) Nature Communications 2022-12-19;

WormRuler: A software to track body length used to characterize a super red-shifted channelrhodopsin in Caenorhabditis elegans

Seidenthal M*; Vettkötter D* and Gottschalk A (2022) microPublication Biology

Microbial Rhodopsin Optogenetic Tools: Application for Analyses of Synaptic Transmission and of Neuronal Network Activity in Behavior

Bergs A, Henss T, Glock C, Nagpal J and Gottschalk A (2022) C. elegans: 89-115

Photoactivated Adenylyl Cyclases as Optogenetic Modulators of Neuronal Activity

Henss T, Schneider M, Vettkötter D, Costa WS, Liewald JF and Gottschalk A (2022) cAMP Signaling: 61-76


Publications 2021

BiPOLES is an optogenetic tool developed for bidirectional dual-color control of neurons

Vierock J, Rodriguez-Rozada S, Dieter A, Pieper F, Sims R, Tenedini F, Bergs ACF, Bendifallah I, Zhou F, Zeitzschel N, Ahlbeck J, Augustin S, Sauter K, Papagiakoumou E, Gottschalk A, Soba P, Emiliani V, Engel AK, Hegemann P and Wiegert JS (2022) Nature communications 12 (1): 1-20

RIM and RIM-binding protein localize synaptic Cav2 channels in a differential manner to regulate transmission in neuronal circuits bioRxiv


Optogenetic tools for manipulation of cyclic nucleotides, functionally coupled to CNG‐channels. British Journal of Pharmacology

Henss T, Nagpal J, Gao S, Scheib U, Pieragnolo A, Hirschhäuser A, Schneider-Warme F, Hegemann P, Nagel G and Gottschalk A (2021) British Journal of Pharmacology, 18 March 2021

Synapsin Is Required for Dense Core Vesicle Capture and cAMP-Dependent Neuropeptide Release

Yu S-c, Liewald JF, Shao J, Steuer Costa W and Gottschalk A (2021) Journal of Neuroscience 41 (19), 4187-4201



Publications 2020

Context-dependent operation of neural circuits underlies a navigation behavior in Caenorhabditis elegans. PNAS

Ikeda M, Nakano S, Giles AC, Xu L, Steuer Costa W, Gottschalk A and Mori I. (2020) , online 2 March 2020

Transcriptional adaptation in Caenorhabditis elegans.

Serobyan V, Kontarakis Z, El-Brolosy MA, Welker JM, Tolstenkov O, Saadeldein AM, Retzer N, Gottschalk A, Wehman AM and Stainier DYR (2020)  eLife 9:e50014

RPamide neuropeptides NLP-22 and NLP-2 act through GnRH-like receptors to promote sleep and wakefulness in C. elegans.

Van der Auwera P, Frooninckx L, Buscemi K, Vance RT, Watteyne J, Mirabeau O, Temmerman L, De Haes W, Fancalszky L, Gottschalk A, Raizen DM, Nelson MD, Schoofs L and Beets I. (2020)  Sci Rep 10: 9929

BIPOLES: a tool for bidirectional dual-color optogenetic control of neurons.

Vierock J, Rodriguez-Rozada S, Pieper F, Dieter A, Bergs A, Zeitzschel N, Ahlbeck J, Sauter K, Gottschalk A, Engel AK, Hegemann P and  Wiegert S. (2020) bioRxiv, 16th July 2020


Publications 2019

Epidermal Growth Factor Signaling Promotes Sleep through a Combined Series and Parallel Neural Circuit. Curr. Biol.

Konietzna J, Fritz M, McWhirter R, Leha A, Palumbos S, Steuer Costa W, Oranth A, Gottschalk A, Miller III D, Hajnal A and Bringmann H. (2019)  December 12 online

Synapsin is required for dense core vesicle capture and cAMP-dependent neuropeptide release.

Yu S-c*, Steuer Costa W*, Liewald JF*, Shao J and Gottschalk A. (2019)  bioRxiv November 12th

A GABAergic and peptidergic sleep neuron as a locomotion stop neuron with compartmentalized Ca2+ dynamics.

Steuer Costa W*, Van der Auwera P*, Glock C, Liewald JF, Bach M, Schüler C, Wabnig S, Oranth A, Masurat F, Bringmann H, Schoofs L, Stelzer EHK, Fischer S and Gottschalk A. (2019) Nat. Communic. 10: 4095

Rhodopsin-based voltage imaging tools for use in muscles and neurons of Caenorhabditis elegans.

Azimi Hashemi N*, Bergs ACF*, Schüler C, Scheiwe AR, Steuer Costa W, Bach M, Liewald JF and Gottschalk A. (2019)  PNAS 116: 17051-60.

Robust and sensitive GFP-based cGMP sensor for real time imaging in intact Caenorhabditis elegans.

Woldemariam S, Nagpal J, Hill T, Li J, Schneider M, Shankar R, Futey M, Varshney A, Ali N, Mitchell J, Andersen K, Barsi-Rhyne B, Tran A, Steuer Costa W, Krzyzanowski M, Yu Y, Brueggemann C, Hamilton S, Ferkey D, VanHoven M, Sengupta P, Gottschalk A and L'Etoile N. (2019)  Genetics 213: 59-77

Optogenetischer Werkzeugkasten für neue experimentelle Ansätze.

Bergs ACF*, Liewald J and Gottschalk A. 2019. BIOspektrum 4.19, pp398

A photoactivatable botulinum toxin for inducible control of neurotransmission.

Liu Q, Sinnen BL, Boxer EE, Schneider MW, Grybko MJ, Buchta WC, Gibson ES, Wysoczynski CL, Ford CP, Gottschalk A, Aoto J, Tucker CL and Kennedy MJ. (2019) Neuron 101: 863-875


Publications 2018

Food sensation modulates locomotion by dopamine and neuropeptide signaling in a distributed neuronal network.

Oranth A*, Schultheis C*, Tolstenkov O, Erbguth K, Nagpal J, Hain D, Brauner M, Wabnig S, Steuer Costa W, McWhirther R, Zels S, Palumbos S, Miller DM III, Beets I and Gottschalk A. (2018) Neuron 100: 1414-1428

Expanding the Optogenetics Toolkit by Topological Inversion of Rhodopsins.

Brown J, Behnam R, Coddington L, Tervo DGR, Martin K, Proskurin M, Kuleshova E, Park J, Phillips J, Bergs ACF, Gottschalk A, Dudman JT and Karpova AY. Cell 175: 1131-1140

Circuit Degeneracy Facilitates Robustness and Flexibility of Navigation Behavior in C. elegans.

Ikeda M, Nakano S, Giles AC, Steuer Costa W, Gottschalk A and Mori I.  bioRxiv August 5, 2018

Functionally asymmetric motor neurons contribute to coordinating locomotion of Caenorhabditis elegans.

Tolstenkov O, Van der Auwera P, Steuer Costa W, Bazhanova O, Gemeinhard T, Bergs ACF and Gottschalk A. (2018) eLife 7: e34997

 

Endophilin A and B join forces with clathrin to mediate synaptic vesicle recycling in Caenorhabditis elegans.

Yu S-c*, Jánosi B*, Liewald J, Wabnig S, Gottschalk A. (2018)  Front Molec Neurosci 11: 196. (17.5.2018)

Rhodopsin optogenetic toolbox v2.0 for light-sensitive excitation and inhibition in Caenorhabditis elegans.

Bergs ACF, Schultheis C, Fischer E, Tsunoda SP, Erbguth K, Husson SJ, Govorunova E, Spudich JL, Nagel G, Gottschalk A*, Liewald JF*. (2018) PLoS ONE 13(2): e0191802


Publications 2017

An optogenetic arrhythmia model to study catecholaminergic polymorphic ventricular tachycardia mutations.

Fischer E, Gottschalk A* and Schueler C* (2017)  Sci. Rep. 7: 17514

Fast cAMP modulation of neurotransmission via neuropeptide signals and vesicle loading.

Steuer Costa W, Yu S-c, Liewald JF and Gottschalk A. (2017)  Curr. Biol. 27: 495-507


Publications 2016

RIC-3 phosphorylation enables dual regulation of excitation and inhibition of C. elegans muscle.

Safdie G, Liewald JF, Kagan S, Battat E, Gottschalk A and Treinin M. (2016) Mol. Biol. Cell 27: 2994-3003

Photoswitchable diacylglycerols enable optical control of protein kinase

Frank JA, Yushchenko DA, Hodson DJ, Lipstein N, Nagpal J, Rutter GA, Rhee J-S, Gottschalk A, Brose N, Schultz C and Trauner D. (2016)  C. Nat. Chem. Biol. 12: 755-62


Publications 2015

Arrhythmogenic effects of mutated L-type Ca2+-channels on an optogenetically paced muscular pump in Caenorhabditis elegans.

Schüler C*, Fischer E*, Shaltiel L, Steuer Costa W and Gottschalk A. (2015)  Sci. Rep. 5:14427

Microbial Rhodopsin Optogenetic Tools: Application for Analyses of Synaptic Transmission and of Neuronal Network Activity in Behavior.

Glock C, Nagpal J and Gottschalk A (2015)  In: C. elegans: Methods and Applications, Methods Mol. Biol. (Biron D, Haspel G, eds.), vol. 1327

Optogenetic manipulation of cGMP in cells and animals by the tightly light-regulated guanylyl-cyclase opsin CyclOp.

Gao S#, Nagpal J#, Schneider M, Kozjak-Pavlovic J, Nagel G* and Gottschalk A*. (2015)  Nat. Communic. 6: 8046

A photosensitive degron enables acute light-induced protein degradation in the nervous system.

Hermann A, Liewald JF and Gottschalk A. (2015)  Curr. Biol. 25: R733–R752

High-throughput all-optical analysis of synaptic transmission and synaptic vesicle recycling in Caenorhabditis elegans.

Wabnig S, Liewald JF, Yu S-c and Gottschalk A (2015)  PLoS ONE 10(8): e0135584

AzoCholine enables optical control of alpha 7 nicotinic acetylcholine receptors in neural networks.

Damijonaitis A, Broichhagen J, Urushima T, Hüll K, Nagpal J, Laprell L, Schönberger M, Woodmansee DH, Rafiq A, Sumser MP, Kummer W, Gottschalk A and Trauner D. (2015 Mar 5)  ACS Chem. Neurosci. 6(5):701-7

A consistent muscle activation strategy underlies crawling and swimming in Caenorhabditis elegans.

Butler VJ, Branicky R, Yemini E, Liewald JF, Gottschalk A, Kerr RA, Chklovskii DB and Schafer WR. (2015 Jan 6)  J. R. Soc. Interface 12(102)


Publications 2014

Photoactivated Adenylyl Cyclases as Optogenetic Modulators of Neuronal Activity.

Steuer Costa W, Liewald JF and Gottschalk A. (2014)  in: Photswitching Proteins (Sidney Cambridge, Editor). Springer Protocols. Methods Mol. Biol. 1148, p. 161-75

C. elegans nicotinic acetylcholine receptors are required for nociception.

Cohen E, Chatzigeorgiou M, Husson SJ, Steuer Costa W, Gottschalk A, Schafer WR and Treinin M. (2014)  Mol. Cell. Neurosci. 59C: 85-96

Synthetic retinal analogs modify the spectral and kinetic characteristics of microbial rhodopsin optogenetic tools.

AzimiHashemi N, Erbguth K, Vogt A, Riemensperger T, Rauch E, Woodmansee D, Nagpal J, Brauner M, Sheves M, Fiala A, Kattner L, Trauner D, Hegemann P, Gottschalk A* and Liewald J*. (2014)  Nat. Communic. 5: 5810

Optogenetische Analyse der Funktion neuronaler Netzwerke und der synaptischen Transmission in Caenorhabditis elegans.

Gottschalk A. (2014)  Neuroforum 4/2014: 278-286

Optogenetic analyses of neuronal network function and synaptic transmission in Caenorhabditis elegans.

Gottschalk A. (2014)  e-Neuroforum 5: 77-85


Publications 2013

Optogenetic actuation, inhibition, modulation and readout for neuronal networks generating behavior in the nematode Caenorhabditis elegans.

de Bono M, Schafer WR and Gottschalk A. (2013)  In "Optogenetics"; Hegemann P, Sigrist S (editors), De Gruyter, Dahlem Workshop Reports

In vivo synaptic recovery following optogenetic hyperstimulation.

Kittelmann M, Liewald JF, Hegermann J, Schultheis C, Brauner M, Steuer Costa W, Wabnig S, Eimer S, and Gottschalk A.  (2013)  PNAS 110: E3007-E3016

Sensory Neuron Fates Are Distinguished by a Transcriptional Switch that Regulates Dendrite Branch Stabilization.

Smith CJ, O’Brien T, Chatzigeorgiou M, Spencer WC, Feingold-Link E, Husson SJ, Hori S, Mitani S, Gottschalk A, Schafer WR and Miller DM. (2013) Neuron 79: 266–280

Optogenetic manipulation of neural activity in C. elegans: from synapse to circuits and behavior.

Husson SJ, Gottschalk A and Leifer AM. (2013) Biol. Cell 105(6): 235-50

Genetically encoded calcium indicators for multi-color neural activity imaging in combination with optogenetics.

Akerboom, J, Carreras Calderon N, Tian L, Wabnig S, Prigge M, Tolö J, Gordus A, Orger MB, Severi KE, Macklin JJ, Patel R, Pulver SR, Wardill TJ, Fischer E, Schüler C, Chen T-W, Sarkisyan, KS, Marvin JS, Bargmann, CI, Kim DK, Kügler S, Lagnado L, Hegemann P, Gottschalk A, Schreiter ER and Looger LL. (2013) Front. Molec. Neurosci. 6: 2


Publications 2012

RAB5 and RAB10 cooperate to regulate neuropeptide release in Caenorhabditis elegans.

Sasidharan N, Sumakovic M, Hannemann M, Hegermann J, Liewald JF, Olendrowitz C, Koenig S, Grant BD, Rizzoli SO, Gottschalk A and Eimer S. (2012) PNAS 109: 18944-9

Bimodal activation of different neuron classes with the spectrally red-shifted Channelrhodopsin chimera C1V1 in Caenorhabditis elegans.

Erbguth K, Prigge M, Schneider F, Hegemann P and Gottschalk A. (2012) PLoS ONE 7: e46827

Specific expression of Channelrhodopsin-2 in single neurons of Caenorhabditis elegans.

Schmitt C, Schultheis C, Pokala N, Husson SJ, Liewald JF, Bargmann, CI and Gottschalk A. (2012) PLoS ONE 7: e43164

Light controlled tools.

Brieke C, Rohrbach F, Gottschalk A, Mayer G and Heckel A. (2012)
Angew. Chem. Int. Ed. 51: 8446-8476

Keeping track of worm trackers.

Husson S, Steuer Costa W, Schmitt C and Gottschalk A. (2012) www.WormBook.org

Microbial light-activatable proton pumps as neuronal inhibitors to functionally dissect neuronal networks in C. elegans.

Husson SJ, Liewald JF, Schultheis C, Stirman JN, Lu H and Gottschalk A. (2012) PLoS ONE 7: e40937

Optogenetic analysis of a nociceptor neuron and network reveals ion channels acting downstream of primary sensors.

Husson S, Steuer Costa W, Wabnig S, Stirman JN, Watson JD, Spencer WC, Akerboom J, Looger LL, Treinin M, Miller III DM, Lu H and Gottschalk A. (2012) Curr. Biol. 22: 743-752

A multispectral optical illumination system with precise spatiotemporal control for the manipulation of optogenetic reagents.

Stirman J, Crane M, Husson S, Gottschalk A and Lu H. (2012) Nat. Prot. 7: 207-220.


Publications 2011

C. elegans selects distinct crawling and swimming gaits via dopamine and serotonin.

Vidal-Gadea A, Topper S, Young L, Crisp A, Kressin L, Elbel E, Maples T, Brauner M, Erbguth K, Axelrod A, Gottschalk A, Siegel D and Pierce-Shimomura J. (2011) PNAS 108: 17504-17509.

Optogenetic analysis of GABAB receptor signalling in Caenorhabditis elegans motor neurons.

Schultheis C, Brauner M, Liewald JF and Gottschalk A. J. Neurophysiol. 106: 817-827. Epub 2011 May 25. pdf

Optogenetic long-term manipulation of behavior and animal development.

Schultheis C, Liewald JF, Bamberg, E, Nagel G and Gottschalk A. PLoS One 6(4): e18766. pdf

Real-time multimodal optical control of neurons and muscles in freely behaving Caenorhabditis elegans.

Stirman J, Crane M, Husson S, Wabnig S, Schultheis C, Gottschalk A*, Lu H*.  (*corresponding authors) Nat. Methods. 8:153-8. Epub 2011 Jan 16. pdf

PACα - an optogenetic tool for in vivo manipulation of cellular cAMP levels, neurotransmitter release, and behavior in Caenorhabditis elegans.

Weissenberger S, Schultheis C, Liewald J, Erbguth K, Nagel G and Gottschalk A. J. Neurochem. 116(4):616-25. doi: 10.1111/j.1471-4159.2010.07148.x. Epub 2011 Jan 20. pdf


Publications 2010

High-throughput study of synaptic transmission at the neuromuscular junction enabled by optogenetics and microfluidics.

Stirman J, Brauner M, Gottschalk A and Lu H. J. Neurosci Meth. 191(1):90-3. Epub 2010 Jun 9. pdf


Publications 2009-2003

An ER-resident membrane protein complex regulates nicotinic actylcholine receptor subunit composition at the synapse.

Almedom RB, Liewald J, Hernando G, Schultheis C, Rayes D, Pan J, Schedletzky T, Hutter H, Bouzat C and Gottschalk A. EMBO J. 2009 Sep 2;28(17):2636-49. Epub 2009 Jul 16. pdf

The Conserved RIC-3 Coiled-Coil Domain Mediates Receptor specific Interactions with Nicotinic Acetylcholine Receptors.

Biala Y, Liewald JF, Ben-Ami HC, Elishevitz E, Shteingauz A, Gottschalk A and Treinin M. Mol Biol Cell. 2009 Mar;20(5):1419-27. Epub 2008 Dec 30. pdf


Optogenetic analysis of synaptic function.

Liewald JF, Brauner M, Stephens GJ, Bouhours M, Schultheis C, Zhen M and Gottschalk A. Nat. Meth. (2008) 5: 895-902. pdf


Intestinal Signaling to GABAergic Neurons Regulates a Rhythmic Behavior in C. elegans.

Mahoney TR, Luo S, Round EK, Brauner M, Gottschalk A, Thomas JH and Nonet ML. PNAS (2008) 105: 16350-16355. pdf

Multimodal fast optical interrogation of neural circuitry.

Zhang F, Wang LP, Brauner M, Liewald JF, Kay K, Watzke N, Wood PG, Bamberg E, Nagel G, Gottschalk A and Deisseroth K. Nature. 2007 Apr 5;446(7136):633-9. pdf

Der lichtgesteuerte Fadenwurm: Einblicke in das Nervensystem von C. elegans

Gottschalk A. Forschung Frankfurt 1/2007. pdf

Regulation of nicotinic receptor rafficking by the transmembrane Golgi protein UNC-50.

Eimer S, Gottschalk A, Hengartner M, Horvitz HR, Richmond J, Schafer WR and Bessereau J-L. EMBO J. (2007) 26: 4313-4323. pdf

Visualization of integral and peripheral cell surface proteins in live Caenorhabditis elegans.

Gottschalk A and Schafer WR. J. Neurosci. Meth. 2006 Jun 30;154(1-2):68-79. Epub 2006 Feb 8. pdf

Identification and characterization of novel nicotinic receptor-associated proteins in Caenorhabditis elegans.    

Gottschalk A*, Almedom RB, Schedletzky T, Anderson SD, Yates III JR and Schafer WR.*   
EMBO J. (2005) advanced online publication; doi:10.1038/sj.emboj.7600741. (*shared corresponding authorship) pdf

Light-activation of Channelrhodopsin-2 in excitable cells of Caenorhabditis elegans triggers rapid behavioral responses.

Nagel G, Brauner M, Liewald J, Adeishvili N, Bamberg E and Gottschalk A. Curr. Biol. 15, (2005), 2279-2284. pdf

eat-2 and eat-18 are Required for Nicotinic Neurotransmission in the Caenorhabditis elegans Pharynx

McKay J, Raizen D, Gottschalk A, Schafer WR and Avery L. Genetics, 166 (2004), 161-69. pdf


Pre C. elegans (yeast spliceosomes: 1997 – 2002)

Direct probing of RNA structure and RNA-protein interactions in purified HeLa cell's and yeast spliceosomal U4/U6.U5 tri-snRNP particles.

Mougin A, Gottschalk A, Fabrizio P, Lührmann R and Branlant, C. J. Mol. Biol., 317 (2002), 631-49.

The yeast U5 snRNP coisolated with the U1 snRNP has an unexpected protein composition and includes the splicing factor Aar2p.

Gottschalk A, Kastner B, Lührmann R and Fabrizio P. RNA, 7, (2001), 1554-65.

A novel yeast U2 snRNP protein, Snu17p, is required for the first catalytic step of splicing and for progression of spliceosome assembly.

Gottschalk A, Bartels C, Neubauer G, Lührmann R, Fabrizio P. Mol. Cell. Biol., 21 (2001), 3037-46.

Identification by mass spectrometry and functional analysis of novel proteins of the yeast [U4/U6.U5] tri-snRNP.

Gottschalk A, Neubauer G, Banroques J, Lührmann R, Fabrizio P. EMBO J., 18 (1999), 4535-48.

Interaction of the U1 snRNP with nonconserved intronic sequences affects 5' splice site selection.

Puig O, Gottschalk A, Fabrizio P and Séraphin B. Genes Dev., 13 (1999), 569-580.

Cbf5p, a potential pseudouridine synthase, and Nhp2p, a putative RNA- binding protein, are present together with Gar1p in all H BOX/ACA-motif snoRNPs and constitute a common bipartite structure.

Watkins NJ, Gottschalk A, Neubauer G, Kastner B, Fabrizio P, Mann M and Lührmann R. RNA, 4 (1998), 1549-68.

A comprehensive biochemical and genetic analysis of the yeast U1 snRNP reveals five novel proteins.

Gottschalk A, Tang J, Puig O, Salgado J, Neubauer G, Colot HV, Mann M, Séraphin B, Rosbash M, Lührmann R and Fabrizio P.
RNA, 4 (1998), 374-93.

Identification of the proteins of the yeast U1 small nuclear ribonucleoprotein complex by mass spectrometry.

Neubauer G, Gottschalk A, Fabrizio P, Séraphin B, Lührmann R and Mann M. Proc. Natl Acad. Sci. USA, 94 (1997), 385-90.