U1130 UMR8246 UMCR18

Development of the Spinal Cord Organization DSCO

Main field of research: 

Neurogenetics / neurodevelopment

Keywords: 

Développement
synaptogénèse
Moelle épinière
Activité neuronale précoce
Glie

ENP label: 

2014

Research Center / Institute: 

Institut de Biologie Paris Seine

Research Unit Code: 

U1130 UMR8246 UMCR18

L’objectif général de notre équipe de recherche est de mieux comprendre les mécanismes impliqués dans l’émergence des premiers réseaux synaptiques au cours du développement du système nerveux cetral, en utilisant la moelle épinière embryonnaire comme modèle principal. Nous nous intéressons notamment aux mécanismes sous-tendant l’activité neuronale précoce et au rôle de cette activité dans la synaptogenèse et la mise en place de premiers réseaux synaptiques fonctionnels. Notre équipe s’intéresse également au rôle des interactions entre neurones et cellules gliales dans ces mêmes processus.

Leader

Leader: 

Co leader: 

Institutions

Principal Institution: 

Inserm

Affiliated institutions: 

CNRS
Université Pierre et Marie Curie

University: 

Université Pierre et Marie Curie

Doctoral School: 

ED158
Laboratory

Surname: 

Neuroscience Paris Seine
Publications

Publications: 

Czarnecki A, Le Corronc H, Rigato C, Le Bras B, Couraud F, Scain AL, Allain AE, Mouffle C, Bullier E, Mangin JM, Branchereau P, Legendre P. Acetylcholine controls GABA-, glutamate-, and glycine-dependent giant depolarizing potentials that govern spontaneous motoneuron activity at the onset of synaptogenesis in the mouse embryonic spinal cord. J Neurosci. 2014 Apr 30;34(18):6389-404. doi: 10.1523/JNEUROSCI.2664-13.2014.

SWINNEN N, SMOLDERS S, AVILA A, NOTELAERS K, PAESEN R, AMELOOT M, BRONE B, # LEGENDRE P, RIGO JM (2013) Complex invasion pattern of the cerebral cortex bymicroglial cells during development of the mouse embryo. Glia. 2013 Feb;61(2):150-63

# LE BRAS B, # FREAL A, # CZARNECHI A, # LEGENDRE P, # BULLIER E, KOMADA M, BROPHY PJ, # DAVENNE M, # COURAUD F (2013) In vivo assembly of the axon initial segment in motor neurons. Brain Struct Funct. 2013 Jun 2. [Epub ahead of print]

# RIGATO C, SWINNEN N, BUCKINX R, COUILLIN I, # MANGIN JM, RIGO JM, # LEGENDRE P, # LE-CORRONC H. P2X7 receptors do not need coupling to pannexin-1 to control microglia proliferation in the spinal cord of mouse embryos. J Neurosci. 2012 Aug 22;32(34):11559-73.

# MANGIN JM, LI P, SCAFIDI J, GALLO V (2012) Experience-dependent regulation of NG2 progenitors in the developing barrel cortex. Nat Neurosci. 2012 Sep;15(9):1192-4

# CZARNECKI A, TSCHERTER A, STREIT J (2012) Network activity and spike discharge oscillations in cortical slice cultures from neonatal rat. Eur J Neurosci. 2012 Feb;35(3):375-88

Gene Regulation and Adaptive Behaviors

Main field of research: 

Neurophysiology / systems neuroscience

Keywords: 

behavior
Epigenetics
Stress response
Molecular genetics
Glucocorticoid Receptor

ENP label: 

2014

Research Center / Institute: 

Institut de Biologie Paris Seine

Research Unit Code: 

U1130 UMR8246 UMCR18

To decipher the molecular mechanisms that allow brain gene expression to adapt to environmental challenges, we focus on the function of inducible transcription factors. Glucocorticoid hormones (GC) plays a key role in physiological and psychological responses to stress. It has multifaceted functions in the brain, most likely reflecting distinct actions in different brain areas and cell  populations.

Leader

Leader: 

Institutions

Principal Institution: 

Inserm

Affiliated institutions: 

CNRS
Université Pierre et Marie Curie
Laboratory

Surname: 

Neuroscience Paris Seine
Publications

Publications: 

#Barik J, Marti F, Morel C, Fernandez SP, #Lanteri C, #Godeheu G, #Tassin JP, Mombereau C, Faure P, #Tronche F. Chronic stress triggers social aversion via GR in dopaminoceptive neurons. Science, 2013 339(6117):332-5

#Carrillo MA, #Pasco M, Arnoux I, #Maatouk L, Sanz Diez A, Delahaye M, Herrero MT, Newman TA, Calvo CF, Audinat E, #Tronche F, #Vyas S. Potent and multiple regulatory actions of microglial glucocorticoid receptors during CNS inflammation. Cell Death & Differentiation, 2013 20(11):1546-1557.

Revest JM, Le Roux A, Roullot-Lacarriere V, Kaouane N, Vallee M, Kasanetz F, Rouge-Pont F, #Tronche F, Desmedt A and Piazza PV. BDNF-TrkB signaling through Erk1/2MAPK phosphorylation mediates the enhancement of fear memory induced by glucocorticoids. Molecular Psychiatry, 2013, doi: 10.1038, in press

Valtat B, Riveline JP, Zhang P, Singh A, Armanet M, Venteclef N, Besseiche A, Kelly D, #Tronche F, Ferré P, Gautier JF, Bréant B, Blondeau B. Fetal PGC-1? Overexpression Programs Adult Pancreatic ?-cell Dysfunction. Diabetes. 2013 62:1206-16

Romanò N, Yip SH, Hodson DJ, Guillou A, #Parnaudeau S, #Tronche F, Bonnefont X, Bunn SJ, Grattan DR, Mollard P, Martin AO. Electrical robustness during phenotypic plasticity of hypothalamic dopaminergic neurons. J Neuroscience, 33(10):4424-4433.

Cerebellum, Navigation and Memory

Main field of research: 

Neurophysiology / systems neuroscience

Keywords: 

Learning, Memory, Brain Plasticity, Behaviour, Neuropathology
spatial navigation
Cerebellum
hippocampus

ENP label: 

2012

Research Unit Code: 

U1130 UMR8246 UMCR18



Leader

Leader: 

Institutions

Principal Institution: 

UPMC

Affiliated institutions: 

CNRS
Inserm

University: 

Université Pierre et Marie Curie

Doctoral School: 

ED158
Publications

Publications: 

Spatio-temporal navigation as behavioral cognitive marker. Bellassen V., Igloi K., de Souza LC., Dubois B., Rondi-Reig L. J. Neuroscience, 32(6):19421952

Cerebellum Shapes Hippocampal Spatial Code. Rochefort C., Arnaud Arabo A., André M., Poucet B.,  Save E. and Rondi-Reig L. Science 2011     334, 385-389 Faculty of 1000: F1000.com/13357388 http://www.newscientist.com/article/dn21075-mouse-manoeuvres-in-the-  dark-reveal-brains-map-links.html 2011.

Early individual detection of age-related memory Neurobiology of Aging, Fouquet C, Petit GH; Auffret, Gaillard, Rovira, Mariani J., Rondi-Reig L. 2011 Oct;32(10):1881-95. 

Role of the Cerebellar Cortex in Conditioned Goal-directed Behavior. Burguière E., Arabo A., Jarlier F. , De Zeeuw C.I, Rondi-Reig L. J. Neuroscience, 30(40):13265-13271, Highlighted by J. Neuroscience editor: http://www.jneurosci.org.gate1.inist.fr/content/30/40/i.full 2010 

Lateralized Human Hippocampal Activity Predicts Navigation Based on Sequence or Place Memory V Igloi K., Doellers C., Berthoz A., Rondi-Reig L.*, Burgess N.* (*co-last authors)  Proc. Natnl. Acad. Sci. (USA) , 107(32):14466-71, 2010

 

Liens vidéos:

http://videotheque.cnrs.fr/index.php?urlaction=doc&id_doc=2914

http://www.rts.ch/emissions/36-9/3981100-quand-la-memoire-se-trouble.html



 



Cerebellum, Navigation and Memory

Main field of research: 

Neurophysiology / systems neuroscience

Keywords: 

spatial memory
spatial navigation

ENP label: 

2008

Research Center / Institute: 

Institut de Biologie Paris Seine

Research Unit Code: 

U1130 UMR8246 UMCR18

We aim at understanding the neural bases of navigation and spatial memory. The principal objective of our work is to provide a comprehensive characterization of how the cerebellum participates to spatial cognition.

This contribution presumably operates, at different levels, including the computation of sensory-motor signals and a functional influence on forebrain areas supporting memory and executive functions (e.g. hippocampus and/or associative cortices).

Leader

Leader: 

Personal

ENP Students: 

Institutions

Principal Institution: 

UPMC

Affiliated institutions: 

CNRS
Inserm

University: 

Université Pierre et Marie Curie

Doctoral School: 

ED158
Laboratory

Surname: 

Neuroscience Paris Seine
Publications

Publications: 

Liens vidéos:

- « les-chemins-de-l-orientation »

UNIVERSCIENCE - Cité des sciences - Sens de l’orientation ? Où ça ?

Bibliothèque Médicis  « sciences-bibliotheque-medicis_news »

http://videotheque.cnrs.fr/index.php?urlaction=doc&id_doc=2914

Science à Coeur: http://video.upmc.fr/differe.php?collec=CS_C_sac4&video=10

Traut N., Beggiato A., Bourgeron T., Delorme R., Rondi-Reig L., Paradis AL, Toro R. (accepted) Cerebellar volume in autism: Meta-analysis and analysis of the ABIDE cohort, Biological psychiatry [IF: 11.4]

Bellassen V., Igloi K., de Souza LC., Dubois B., Rondi-Reig L. Spatio-temporal navigation as behavioral cognitive marker J. Neuroscience, 32(6):19421952, 2012 [IF: 6.9]

de Lavilléon G, Lacroix MM, Rondi-Reig L*, Benchenane K*. Explicit memory creation during sleep demonstrates a causal role of place cells in navigation. Nat Neurosci. 18(4):493-5. 2015 [IF: 16.7]

Iglói K., Doeller C.F., Paradis A.L., Benchenane K., Berthoz A., Burgess N. and Rondi-Reig L. Interaction between hippocampus and cerebellum Crus I in sequence-based but not place-based navigation. Cerebral cortex, 25(11):4146-54, 2015  [IF: 8.28]

Cabral H.O., Vinck M., Fouquet C., Pennartz C.M.A., Rondi-Reig L., and Battaglia F.P. Oscillatory dynamics and place field maps reflect sequence and place memory processing in hippocampal ensembles under NMDA receptor control. Neuron, 81(2):402-15, 2014 [IF: 15.05]

 

Physiopathology of psychiatric diseases

Main field of research: 

Neurological and psychiatric diseases

Keywords: 

Depression
schizophrenia
animal models
Interindividual Vulnerability
Integrated studies

ENP label: 

2012

Research Unit Code: 

U1130 UMR8246 UMCR18

 Our team carries out preclinical studies to better understand psychiatric diseases and to discover innovative therapies. We develop animal models and characterize synaptic targets which play a role in neurotransmission (mostly neurotransmitter transporters). This work is also carried out in humans using genetic and anatomical approaches, specifically focusing on autism and mental retardation.



Institutions

Principal Institution: 

Inserm

Affiliated institutions: 

CNRS
Université Pierre et Marie Curie
Laboratory

Surname: 

Neuroscience Paris Seine
Publications

Publications: 

Bacq A, Balasse L, Biala G, Guiard B, Gardier AM, Schinkel A, Louis F, Vialou V, Martres MP, Chevarin C, Hamon M, Giros B, Gautron S. Organic cation transporter 2 controls brain norepinephrine and serotonin clearance and antidepressant response. Mol Psychiatry 2012;17(9):926-939.

Baudin A, Blot K, Verney C, Estevez L, Santa-Maria J, Gressens P, Giros B, Otani S, Dauge V, Naudon L. Maternal deprivation induces deficits in temporal memory and cognitive flexibility and exaggerates synaptic plasticity in the rat medial prefrontal cortex.Neurobiol Learn Mem 2012.

Berthet A, Bezard E, Porras G, Fasano S, Barroso-Chinea P, Dehay B, Martinez A, Thiolat ML, Nosten-Bertrand M, Giros B,Baufreton J, Li Q, Bloch B, Martin-Negrier ML. L-DOPA impairs proteasome activity in parkinsonism through D1 dopamine receptor. J Neurosci 2012;32(2):681-691.

El Khoury MA, Gorgievski V, Moutsimilli L, Giros B, Tzavara ET. Interactions between the cannabinoid and dopaminergic systems: Evidence from animal studies. Prog Neuropsychopharmacol Biol Psychiatry 2012;38(1):36-50.

Farley S, Dumas S, El Mestikawy S, Giros B. Increased expression of the Vesicular Glutamate Transporter-1 (VGLUT1) in the prefrontal cortex correlates with differential vulnerability to chronic stress in various mouse strains: effects of fluoxetine and MK-801.
Neuropharmacology 2012;62(1):503-517.

Neurophysiology and Behaviors

Main field of research: 

Neurophysiology / systems neuroscience

ENP label: 

2007

Research Center / Institute: 

Institut de Biologie Paris Seine

Research Unit Code: 

U1130 UMR8246 UMCR18

Dopamine (DA) projections from the midbrain (including ventral tegmental area - VTA and substantia nigra - SN) to striatum and frontal cortex play a major role in behavioral actions controlled by reward and in the formation of habits. The dopaminergic system is also involved in drug addiction.

Leader

Leader: 

Personal

ENP Students: 

Institutions

Principal Institution: 

Inserm

Affiliated institutions: 

CNRS
Université Pierre et Marie Curie
Laboratory

Surname: 

Neuroscience Paris Seine

Initiatives d'Excellence: 

DHU Pepsy
Publications

Publications: 

Naudé J, Tolu S, Dongelmans M, Torquet N, Valverde S, Rodriguez G, Pons S, Maskos U, Mourot A, Marti F, Faure P. Nicotinic receptors in the ventral tegmental area promote uncertainty-seeking. Nat Neurosci. 2016 Mar;19(3):471-8. doi: 10.1038/nn.4223. Epub 2016 Jan 18.

Eddine R, Valverde S, Tolu S, Dautan D, Hay A, Morel C, Cui Y, Lambolez B, Venance L, Marti F, Faure P. A concurrent excitation and inhibition of dopaminergic subpopulations in response to nicotine. Sci Rep. 2015 Feb 2;5:8184. doi: 10.1038/srep08184.

Naudé J, Dongelmans M, Faure P. Nicotinic alteration of decision-making.  Neuropharmacology. 2014 Dec 9. pii: S0028-3908(14)00437-7. doi: 10.1016/j.neuropharm.2014.11.021.

Morel C, Fattore L, Pons S, Hay YA, Marti F, Lambolez B, De Biasi M, Lathrop M, Fratta W, Maskos U, Faure P. Nicotine consumption is regulated by a human polymorphism in dopamine neurons. Mol Psychiatry. 2014 Aug;19(8):930-6. doi: 10.1038/mp.2013.158. Epub 2013 Dec 3.

Ey E Yang M Katz AM Woldeyohannes L Silverman JL Leblond CS Faure P Torquet N Sourd AM Bourgeron T Crawley JN  (2012) : Absence of Deficits in Social Behaviors and Ultrasonic Vocalizations in Later Generations of Mice Lacking Neuroligin4. Genes Brain Behav. 2012 Sep 18. doi: 10.1111/j.160 

Schmeisser MJ Ey E Wegener S Bockmann J Stempel AV Kuebler A Janssen AL Udvardi PT Shiban E Spilker C Balschun D Skryabin BV Dieck St Smalla KH Montag D Leblond CS Faure P Torquet N Le Sourd AM Toro R (2012) : Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2. Nature.;486(7402):256-60. doi: 10.1038/nature11015

 Tolu S Eddine R Marti F David V Graupner M Pons S Baudonnat M Husson M Besson M Reperant C Zemdegs J Pages C Hay YA Lambolez B Caboche J Gutkin B Gardier AM Changeux JP Faure P Maskos U  (2012) : Co-activation of VTA DA and GABA neurons mediates nicotine reinforcement. Mol Psychiatry. 2012 Jul 3. doi: 10.1038/mp.2012.8

Bourgeois JP Meas-Yeadid V Lesourd AM Faure P Pons S Maskos U Changeux JP Olivo-Marin JC Granon S  (2011) : Modulation of the Mouse Prefrontal Cortex Activation by Neuronal Nicotinic Receptors during Novelty Exploration but not by Exploration of a Familiar Environment. Cereb Cortex. 2011 Aug 1.

 Exley R Maubourguet N David V Eddine R Evrard A Pons S Marti F Threlfell S Cazala P McIntosh JM Changeux JP Maskos U Cragg SJ Faure P  (2011) : Distinct contributions of nicotinic acetylcholine receptor subunit {alpha}4 and subunit {alpha}6 to the reinforcing effects of nicotine. Proc Natl Acad Sci U S A. 2011 Apr 18.

Glial Plasticity and Neuro-Oncology

Main field of research: 

Neurophysiology / systems neuroscience

Keywords: 

Astrocyte, glioma, metabolism, epigenetic, proteomic

ENP label: 

2009

Research Center / Institute: 

Institut de Biologie Paris Seine

Research Unit Code: 

U1130 UMR8246 UMCR18

The main focus of our research is the plasticity and development of human brain tumors
We are interested in understanding how interactions between cell intrinsic and extrinsic signaling pathways control the stem and tumor-initiating properties of glioma stem cells.

Leader

Leader: 

Co leader: 

Institutions

Principal Institution: 

Inserm

Affiliated institutions: 

CNRS
Université Pierre et Marie Curie
Laboratory

Surname: 

Neuroscience Paris Seine
Publications

Publications: 

Assad Kahn S, Costa SL, Gholamin S, Nitta RT, Dubois LG, Fève M, Zeniou M, Coelho PL, El-Habr E, Cadusseau J, Varlet P, Mitra SS, Devaux B, Kilhoffer MC, Cheshier SH, Moura-Neto V, Haiech J, Junier MP, Chneiweiss H.The anti-hypertensive drug prazosin inhibits glioblastoma growth via the PKCδ-dependent inhibition of the AKT pathway.EMBO Mol Med. 2016 May 2;8(5):511-26. doi: 10.15252/emmm.201505421.

Turchi L, Debruyne DN, Almairac F, Virolle V, Fareh M, Neirijnck Y, Burel-Vandenbos F, Paquis P, Junier MP, Van Obberghen-Schilling E, Chneiweiss H,Virolle T. Tumorigenic Potential of miR-18A* in Glioma Initiating Cells Requires NOTCH-1 Signaling. Stem Cells. 2013 31:1252-65.

Thirant C, Galan-Moya EM, Dubois LG, Pinte S, Chafey P, Broussard C, Varlet P, Devaux B,Soncin F, Gavard J, Junier MP,Chneiweiss H. Differential proteomic analysis of human glioblastoma and neural stem cells reveals HDGF as a novel angiogenic secreted factor.Stem Cells. 2012 May;30(5):845-53.

Fareh M, Turchi L, Virolle V, Debruyne D, Almairac F, de-la-Forest Divonne S, Paquis P, Preynat-Seauve O, Krause KH, Chneiweiss H, Virolle T The. miR 302-367 cluster drastically affects self-renewal and infiltration properties of glioma-initiating cells through CXCR4 repression and consequent disruption of the SHH-GLI-NANOG network.Cell Death Differ. 2012 Feb;19(2):232-44.

Galan-Moya EM, Le Guelte A, Lima-Fernandes E, Thirant C, Dwyer J, Bidere N, Couraud PO, Scott M, Junier MP Chneiweiss H, Gavard J.?Brain endothelial cells maintain glioblastoma stem-like cell expansion through the mTOR pathway. EMBO Report 2011,12: 470-6.

Silvestre DC, Pineda Marti JR, Hoffschir F, Studler JM,Mouthon MA, Pflumio F, Junier MP, Chneiweiss H,Boussin FD. Alternative Lengthening of Telomeres in Human Glioma Stem Cells. Stem Cells. 2011 Mar;29(3):440-

Normal and pathological glutamatergic systems

Main field of research: 

Neurophysiology / systems neuroscience

Keywords: 

brain
neurotransmission
Glutamate
Neurological psychiatric diseases
Vesicular glutamate transporter

ENP label: 

2007

Research Center / Institute: 

Institut de Biologie Paris Seine

Research Unit Code: 

U1130 UMR8246 UMCR18

Glutamate is the major neurotransmitter of CNS. Before its exocytotic release in the synaptic cleft, glutamate is loaded into synaptic vesicles by three transporters named VGLUT1-3. In the rodent brain, VGLUT1-3 are distributed in three complementary glutamatergic systems showing little overlap. VGLUT1 is essentially cortical, VGLUT2 subcortical and VGLUT3 is present in neurons using other transmitters than glutamate (cholinergic interneurons from the striatum, GABAergic interneurons from the hippocampus and cortex and serotonergic neurons).

Leader

Leader: 

Institutions

Principal Institution: 

Inserm

Affiliated institutions: 

CNRS
Université Pierre et Marie Curie
Laboratory

Surname: 

Neuroscience Paris Seine
Publications

Publications: 

Siksou L., Silm K., Biesemann C., Nehring R.B., Wojcik S.M., Triller A., El Mestikawy S., Marty S. and Herzog, E. European J Neuroscience 12199. (2013)

El Mestikawy et al.From glutamate co-release to vesicular synergy: vesicular glutamate transporters.Nat Rev Neurosci. 2011 Apr;12(4): pp. 204-16

Herzog et al.In Vivo Imaging of Intersynaptic Vesicle Exchange Using VGLUT1Venus Knock-In Mice J Neurosci. (2011) Oct 26;31(43):15544-59

Bernard V. et al.Distinct localization of collagen Q and PRiMA forms of acetylcholinesterase at the neuromuscular junction.Mol. Cell. Neurosci. 46: (2011); pp. 272-281

Dobbertin A. … et Bernard V. Targeting of Acetylcholinesterase in Neurons: a Dual Function for PRiMA and its AChE Recognition Domain in vivo. J. Neurosci. 29: (2009); pp. 4519 –4530.

Amilhon et al. VGLUT3 (vesicular glutamate transporter type 3) contribution to the regulation of serotonergic transmission and anxiety J Neurosci (2010) 30: pp. 2198-210.

Cortical Network and Neurovascular Coupling

Main field of research: 

Neurophysiology / systems neuroscience

Keywords: 

cerebral cortex
electrophysiology
Optogenetics
neuronal circuits
blood perfusion and metabolism,

ENP label: 

2011

Research Unit Code: 

U1130 UMR8246 UMCR18

The team “Cortical network and Neurovascular Coupling” studies neuronal circuits and their relationships with the glio-vascular network in the cerebral cortex. Our previous work has advanced our knowledge of neocortical neuronal types, of their sensitivity to afferent signals, of their places in the functional architecture of intracortical peptidergic transmission, and of their differential roles in neurovascular coupling.

Institutions

Principal Institution: 

Inserm

Affiliated institutions: 

CNRS
Université Pierre et Marie Curie

University: 

Université Pierre et Marie Curie

Doctoral School: 

ED158
Laboratory

Surname: 

Neuroscience Paris Seine

Initiatives d'Excellence: 

IHU Institut de Neurosciences Translationnelles de Paris
Publications

Publications: 

Pohlkamp T, Dávid C, Cauli B#, Gallopin T, Bouché E, Karagiannis A#, May P, Herz J, Frotscher M, Staiger JF, Bock HH.Characterization and Distribution of Reelin-Positive Interneuron Subtypes in the Rat Barrel Cortex. Cereb Cortex. 2013 Jun 26.

Battaglia D, Karagiannis A#, Gallopin T, Gutch HW, Cauli B#. Beyond the frontiers of neuronal types. Front Neural Circuits.2013;7:13. doi: 10.3389/fncir.2013.00013.

Tolu S, Eddine R, Marti F, David V, Graupner M, Pons S, Baudonnat M, Husson M, Besson M, Reperant C, Zemdegs J, Pagès C,Hay YA#, Lambolez B#, Caboche J, Gutkin B, Gardier AM, Changeux JP, Faure P, Maskos U. Co-activation of VTA DA and GABA neurons mediates nicotine reinforcement. Mol Psychiatry. 2013 Mar;18(3):382-93.

Szabo A, Somogyi J, Cauli B#, Lambolez B#, Somogyi P, Lamsa KP. Calcium-permeable AMPA receptors provide a common mechanism for LTP in glutamatergic synapses of distinct hippocampal interneuron types. J Neurosci. 2012 May 9;32(19):6511-6.

Macé E, Montaldo G, Cohen I#, Baulac M, Fink M, Tanter M. Functional ultrasound imaging of the brain. Nat Methods. 2011 Jul 3;8(8):662-4.