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1.
J Cell Sci ; 137(8)2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38563084

ABSTRACT

Angiogenesis is a tightly controlled dynamic process demanding a delicate equilibrium between pro-angiogenic signals and factors that promote vascular stability. The spatiotemporal activation of the transcriptional co-factors YAP (herein referring to YAP1) and TAZ (also known WWTR1), collectively denoted YAP/TAZ, is crucial to allow for efficient collective endothelial migration in angiogenesis. The focal adhesion protein deleted-in-liver-cancer-1 (DLC1) was recently described as a transcriptional downstream target of YAP/TAZ in endothelial cells. In this study, we uncover a negative feedback loop between DLC1 expression and YAP activity during collective migration and sprouting angiogenesis. In particular, our study demonstrates that signaling via the RhoGAP domain of DLC1 reduces nuclear localization of YAP and its transcriptional activity. Moreover, the RhoGAP activity of DLC1 is essential for YAP-mediated cellular processes, including the regulation of focal adhesion turnover, traction forces, and sprouting angiogenesis. We show that DLC1 restricts intracellular cytoskeletal tension by inhibiting Rho signaling at the basal adhesion plane, consequently reducing nuclear YAP localization. Collectively, these findings underscore the significance of DLC1 expression levels and its function in mitigating intracellular tension as a pivotal mechanotransductive feedback mechanism that finely tunes YAP activity throughout the process of sprouting angiogenesis.


Subject(s)
Focal Adhesions , GTPase-Activating Proteins , Mechanotransduction, Cellular , Tumor Suppressor Proteins , YAP-Signaling Proteins , Animals , Humans , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Cell Cycle Proteins/metabolism , Cell Cycle Proteins/genetics , Cell Movement , Feedback, Physiological , Focal Adhesions/metabolism , Focal Adhesions/genetics , GTPase-Activating Proteins/metabolism , GTPase-Activating Proteins/genetics , Human Umbilical Vein Endothelial Cells/metabolism , Mechanotransduction, Cellular/genetics , Neovascularization, Physiologic , Tumor Suppressor Proteins/metabolism , Tumor Suppressor Proteins/genetics , YAP-Signaling Proteins/metabolism
2.
Ann Pharm Fr ; 78(4): 324-334, 2020 Jul.
Article in French | MEDLINE | ID: mdl-32247514

ABSTRACT

OBJECTIVE: Describe the process for designing and creating SimUPAC 360°, a virtual reality training in anti-cancer drug production units. METHODS: A multi-centre (a University Hospital, a General Hospital and a Cancer Control Centre), inter-professional (pharmacists, hospital pharmacy technicians and health executives) working group has been set up. It was based on videoconferencing and online document sharing. The work was divided into six phases: choice of target audience and training objectives, definition of the business model, development of the scenario, shooting and editing, creation of the training tool and finally tests, adjustments and validation of the tool. RESULTS: After brainstorming, 77 errors were proposed. Three areas have been defined: covering area, storage and production area, and isolator. They contained 15 errors among the 77 proposed and 20 points of interest. The shooting was carried out over 2 days, in 2 hospitals. Assembly was carried out by a service provider specialist in real virtuality. Before to go online, the tool was tested and validated by experts. DISCUSSION: The establishment of a multi-centric and interdisciplinary working group, the choice of target audience, pedagogical objectives and business model ensure the economic viability and scientific and technical robustness of the tool. The scenario development requires to define: activity areas and then, number, difficulty and typology of errors. CONCLUSION: Creation of a virtual reality training requires a consistent and structured methodology. This methodology will make it possible to develop other training scenarios.


Subject(s)
Antineoplastic Agents/chemistry , Drug Compounding/methods , Education, Pharmacy/organization & administration , Virtual Reality , Antineoplastic Agents/adverse effects , Hospitals, University , Humans , Medication Errors/prevention & control , Models, Organizational , Pharmacists , Pharmacy Service, Hospital , Pharmacy Technicians , Teaching
3.
Transfus Clin Biol ; 27(1): 4-9, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31889619

ABSTRACT

BACKGROUND: Several successive arbovirus outbreaks have affected French Polynesia (FP) in the recent past years due to different dengue serotypes (DENV) present for several decades, Zika (ZIKV) (2013-2014) and chikungunya (CHIKV) (2014-2015) viruses with a potential impact on blood safety and blood supply due to the geographical isolation of these islands. This study reports an assessment of the impact of these outbreaks on blood products supply and infectious safety in FP and discuss the effectiveness of implemented preventive measures. METHODS: To ensure the infectious safety of blood products during outbreaks, several measures have successively been introduced as the selection of donors suspected of infection, the nucleic acid testing (NAT) and the pathogen reduction of platelets and plasmas. RESULTS: The donor deferral rate increased by 6% between 2012 and 2014 without changes in the number of collected donations. NAT excluded five blood donations reactive for DENV RNA, 42 for ZIKV and 34 for CHIKV. As Zika screening could not been implemented before the third month of the outbreak, 36 blood products from ZIKV-infected donors were transfused to 26 recipients. However, no transfusion-transmitted arbovirus has been reported. CONCLUSION: The last past arboviruses outbreaks did not have a significant impact on blood supply in FP. The measures introduced to prevent arbovirus transmission by transfusion were able to maintain infectious safety for all blood products without impairing self-sufficiency.


Subject(s)
Blood Safety , Chikungunya Fever/epidemiology , Dengue/epidemiology , Disease Outbreaks , Viremia/epidemiology , Zika Virus Infection/epidemiology , Arboviruses/drug effects , Blood Donors/supply & distribution , Blood Safety/methods , Blood-Borne Pathogens/drug effects , Chikungunya Fever/blood , Chikungunya Fever/prevention & control , Dengue/blood , Dengue/prevention & control , Donor Selection/statistics & numerical data , Furocoumarins/pharmacology , Humans , Photosensitizing Agents/pharmacology , Polynesia/epidemiology , RNA, Viral/blood , Seroepidemiologic Studies , Viremia/blood , Zika Virus Infection/blood , Zika Virus Infection/prevention & control
4.
J Neurosci ; 39(44): 8679-8689, 2019 10 30.
Article in English | MEDLINE | ID: mdl-31533976

ABSTRACT

The functional organization of human auditory cortex can be probed by characterizing responses to various classes of sound at different anatomical locations. Along with histological studies this approach has revealed a primary field in posteromedial Heschl's gyrus (HG) with pronounced induced high-frequency (70-150 Hz) activity and short-latency responses that phase-lock to rapid transient sounds. Low-frequency neural oscillations are also relevant to stimulus processing and information flow, however, their distribution within auditory cortex has not been established. Alpha activity (7-14 Hz) in particular has been associated with processes that may differentially engage earlier versus later levels of the cortical hierarchy, including functional inhibition and the communication of sensory predictions. These theories derive largely from the study of occipitoparietal sources readily detectable in scalp electroencephalography. To characterize the anatomical basis and functional significance of less accessible temporal-lobe alpha activity we analyzed responses to sentences in seven human adults (4 female) with epilepsy who had been implanted with electrodes in superior temporal cortex. In contrast to primary cortex in posteromedial HG, a non-primary field in anterolateral HG was characterized by high spontaneous alpha activity that was strongly suppressed during auditory stimulation. Alpha-power suppression decreased with distance from anterolateral HG throughout superior temporal cortex, and was more pronounced for clear compared to degraded speech. This suppression could not be accounted for solely by a change in the slope of the power spectrum. The differential manifestation and stimulus-sensitivity of alpha oscillations across auditory fields should be accounted for in theories of their generation and function.SIGNIFICANCE STATEMENT To understand how auditory cortex is organized in support of perception, we recorded from patients implanted with electrodes for clinical reasons. This allowed measurement of activity in brain regions at different levels of sensory processing. Oscillations in the alpha range (7-14 Hz) have been associated with functions including sensory prediction and inhibition of regions handling irrelevant information, but their distribution within auditory cortex is not known. A key finding was that these oscillations dominated in one particular non-primary field, anterolateral Heschl's gyrus, and were suppressed when subjects listened to sentences. These results build on our knowledge of the functional organization of auditory cortex and provide anatomical constraints on theories of the generation and function of alpha oscillations.


Subject(s)
Alpha Rhythm , Speech Perception/physiology , Temporal Lobe/physiology , Acoustic Stimulation , Adult , Auditory Cortex/physiology , Auditory Pathways/physiology , Evoked Potentials, Auditory , Female , Gamma Rhythm , Humans , Male , Middle Aged , Young Adult
6.
Med Trop (Mars) ; 67(2): 137-44, 2007 Apr.
Article in French | MEDLINE | ID: mdl-17691431

ABSTRACT

Leptospirosis is a severe zoonotic disease that constitutes a major public health problem for the island populations of French Polynesia. Due to protean clinical manifestations and the risk of misdiagnosis with dengue fever, endemic viral disease, laboratory studies are necessary to confirm diagnosis of leptospirosis. At the request of the Pacific Public Health Surveillance Network, a prospective study was conducted in the population of Raieatea in the Windward Islands and the Marquis Islands to determine the epidemiological features of the disease and to define appropriate control measures. A total of 113 patients were enrolled in study between March 2004 and March 2005. Thirty-three cases were confirmed based on demonstration of serum DNA or seroconversion. The estimated annual incidence of leptospirosis was 1.7 per 1000 inhabitants. Cases involved mainly (75%) young men (mean age, 30.5 years) and occurred predominantly during the rainy season. Swimming in fresh water was the only factor showing significant correlation (p < 0.02) with positive diagnosis of leptospirosis. The most frequently identified serotype was Leptospira icterohemorrahgiae (43% of strains), thus suggesting that the rat was the most common human transmission vector. However other serotypes were found, underlining the presence of diverse reservoirs and casting doubt on the efficacy of immunization using a monovalent vaccine. These findings also indicate that enhancement of prevention and control measures for leptospirosis is needed.


Subject(s)
Leptospirosis/epidemiology , Adolescent , Adult , Aged , Animals , Child , Child, Preschool , Disease Reservoirs , Disease Vectors , Female , Humans , Incidence , Infant , Leptospirosis/diagnosis , Leptospirosis/transmission , Male , Middle Aged , Polynesia/epidemiology , Prospective Studies , Public Health , Risk Factors , Seasons , Swimming
7.
Anal Chem ; 79(14): 5444-8, 2007 Jul 15.
Article in English | MEDLINE | ID: mdl-17579484

ABSTRACT

A general strategy to localize and quantify carbon-centered radicals within proteins is described. The methodology was first exemplified on amino acids and then on a peptide. This method is applicable to any protein system regardless of size, and the site of hydrogen abstraction by *OH on all residues within proteins is easily and accurately detected.


Subject(s)
Amino Acids/chemistry , Carbon/analysis , Proteins/chemistry , Animals , Free Radicals/analysis , Peptides/chemistry , Tritium/analysis
8.
Biochimie ; 87(3-4): 393-402, 2005.
Article in English | MEDLINE | ID: mdl-15781327

ABSTRACT

Despite a deep knowledge on the 3D-structure of several catalytic domains of MMPs, the development of highly specific synthetic active-site-directed inhibitors of MMPs, able to differentiate the different members of this protease family, remains a strong challenge. Due to the flexible nature of MMP active-site, the development of specific MMP inhibitors will need to combine sophisticated theoretical and experimental approaches to decipher in each MMP the specific structural and dynamic features that can be exploited to obtain the desired selectivity.


Subject(s)
Drug Design , Matrix Metalloproteinase Inhibitors , Protease Inhibitors/chemical synthesis , Amino Acid Sequence , Binding Sites , Catalytic Domain , Forecasting , Matrix Metalloproteinases/chemistry , Models, Molecular , Molecular Sequence Data , Molecular Structure , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , Protein Conformation , Protein Structure, Secondary , Protein Structure, Tertiary , Static Electricity , Zinc/chemistry
9.
Cell Mol Life Sci ; 61(16): 2010-9, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15316651

ABSTRACT

Solid-phase synthesis of phosphinic peptides was introduced 10 years ago. A major application of this chemistry has been the development of potent synthetic inhibitors of zinc metalloproteases. Specific properties of the inhibitors produced in recent years are reviewed, supporting the notion that phosphinic pseudo-peptides are useful tools for studying the structural and functional biology of zinc proteases.


Subject(s)
Metalloendopeptidases/antagonists & inhibitors , Peptides/metabolism , Phosphinic Acids/metabolism , Zinc/metabolism , Animals , Chromatography, High Pressure Liquid , Humans , Hydroxamic Acids/chemistry , Hydroxamic Acids/metabolism , Metalloendopeptidases/metabolism , Peptides/chemistry , Phosphinic Acids/chemistry
10.
Biochemistry ; 38(37): 12174-9, 1999 Sep 14.
Article in English | MEDLINE | ID: mdl-10508422

ABSTRACT

The influence of Gln215 in stromelysin-3 (MMP-11), a residue located in the S1' subsite, was determined by producing three single mutants of this position. As compared to wild-type stromelysin-3, the kinetic parameters K(M) and k(cat) for the degradation of the fluorogenic substrate Dns-Pro-Leu-Ala-Leu-Trp-Ala-Arg-NH(2) (Dns-Leu) by these mutants indicated that the Gln/Leu substitution led to a 4-fold decrease in catalytic efficiency, whereas the mutations Gln/Tyr and Gln/Arg increased this parameter by a factor 10. The cleavage of alpha1-protease inhibitor (alpha1-PI), a natural substrate of stromelysin-3, by these mutants was also determined. Their relative activities for the degradation of alpha1-PI correspond to those observed with the synthetic substrate Dns-Leu. The catalytic efficiency of wild-type stromelysin-3 and its mutants to cleave the P1' analogue of Dns-Leu, containing the unusual amino acid Cys(OMeBn) (Dns-Cys(OMeBn)), was also determined. The values of the specificity factor, calculated as the ratio (k(cat)/K(M))Dns-Cys(OMeBn))/(k(cat)/K(M))Dns-Leu, were observed to vary from 26 for the wild-type stromelysin-3 to 120 for the Gln/Leu mutant and 25 for the Gln/Arg mutant. The Gln/Tyr mutant did not cleave the substrate when its P1' position is substituted by the unusual amino acid Cys(OMeBn). Altogether these observations established that both the catalytic activity and the specificity of stromelysin-3 are dependent on the nature of the residue in position 215. Finally, the cleavage efficiency of the Dns substrates by three representative matrixins, namely, MMP-14 (215 = Leu), MMP-1 (215 = Arg), and MMP-7 (215 = Tyr), was determined. Interestingly, the trends observed for these enzymes were similar to those established for the three mutants of stromelysin-3, pointing out the influence of position 215 toward the selectivity in this family of enzymes.


Subject(s)
Glutamine/genetics , Metalloendopeptidases/genetics , Metalloendopeptidases/metabolism , Mutagenesis, Site-Directed , Animals , Catalysis , Dansyl Compounds/metabolism , Enzyme Activation/genetics , Fluorescent Dyes/metabolism , Glutamine/chemistry , Glutamine/metabolism , Glutamine/physiology , Hydrolysis , Kinetics , Leucine/genetics , Matrix Metalloproteinase 11 , Metalloendopeptidases/chemistry , Mice , Oligopeptides/metabolism , Substrate Specificity/genetics , alpha 1-Antitrypsin/metabolism
11.
J Clin Microbiol ; 37(10): 3366-8, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10488208

ABSTRACT

Nocardiopsis dassonvillei is an environmental aerobic actinomycete seldom isolated in cutaneous and pulmonary infections. We herein report the first N. dassonvillei blood isolate in a patient hospitalized for cholangitis. Although morphological characteristics and biochemical tests allowed a presumptive identification of this isolate, cell wall fatty acid chromatographic analysis confirmed identification at the genus level, and 16S rRNA gene sequencing achieved definite identification. This study illustrates the usefulness of 16S rRNA gene sequencing as a routine method for the identification of actinomycetes.


Subject(s)
Actinomycetales/isolation & purification , Bacteremia/microbiology , Actinomycetales/genetics , DNA, Bacterial/analysis , Humans , Male , Middle Aged , RNA, Ribosomal, 16S/genetics
12.
J Med Chem ; 42(14): 2610-20, 1999 Jul 15.
Article in English | MEDLINE | ID: mdl-10411481

ABSTRACT

Several phosphinic pseudo-tripeptides of general formula R-XaaPsi(PO(2)-CH(2))Xaa'-Yaa'-NH(2) were synthesized and evaluated for their in vitro activities to inhibit stromelysin-3, gelatinases A and B, membrane type-1 matrix metalloproteinase, collagenases 1 and 2, and matrilysin. With the exception of collagenase-1 and matrilysin, phosphinic pseudo-tripeptides behave as highly potent inhibitors of matrix metalloproteinases, provided they contain in P(1)' position an unusual long aryl-alkyl substituent. Study of structure-activity relationships regarding the influence of the R and Xaa' substituents in this series may contribute to the design of inhibitors able to block only a few members of the matrix metalloproteinase family.


Subject(s)
Metalloendopeptidases/antagonists & inhibitors , Oligopeptides/chemical synthesis , Phosphines/chemical synthesis , Protease Inhibitors/chemical synthesis , Kinetics , Magnetic Resonance Spectroscopy , Oligopeptides/chemistry , Phosphines/chemistry , Protease Inhibitors/chemistry , Structure-Activity Relationship
13.
J Neurophysiol ; 79(2): 659-69, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9463429

ABSTRACT

Epileptiform burst discharges were elicited in CA1 hippocampal pyramidal cells in the slice preparation by perfusion with Mg2+-free saline. Intracellular recordings revealed paroxysmal depolarization shifts (PDSs) that either occurred spontaneously or were evoked by stimulation of Schaffer collaterals. These bursts involved activation of N-methyl-D-aspartate receptors because burst discharges were reduced or abolished by -2-amino-5-phosphonovaleric acid. Bath application of carbachol caused an increase in spontaneous activity that was predominantly due to gamma-aminobutyric acid-A-receptor-mediated spontaneous inhibitory postsynaptic potentials (sIPSPs). A marked reduction in sIPSPs (31%) was observed after each epileptiform burst discharge, which subsequently recovered to preburst levels after approximately 4-20 s. This sIPSP suppression was not associated with any change in postsynaptic membrane conductance. A suppression of sIPSPs also was seen after burst discharges evoked by brief (100-200 ms) depolarizing current pulses. N-ethylmaleimide, which blocks pertussis-toxin-sensitive G proteins, significantly reduced the suppression of sIPSPs seen after a burst response. When increases in intracellular Ca2+ were buffered by intracellular injection of ethylene glycol bis(beta-aminoethyl)ether-N,N,N',N'-tetraacetic acid, the sIPSP suppression seen after a single spontaneous or evoked burst discharge was abolished. Although we cannot exclude other Ca2+-dependent mechanisms, this suppression of sIPSPs shared many of the characteristics of depolarization-induced suppression of inhibition (DSI) in that it involved activation of G proteins and was dependent on increases in intracellular calcium. These findings suggest that a DSI-like process may be activated by the endogenous burst firing of CA1 pyramidal neurons.


Subject(s)
Epilepsy/physiopathology , Evoked Potentials/physiology , Pyramidal Cells/physiology , Receptors, GABA-A/physiology , Action Potentials/drug effects , Action Potentials/physiology , Animals , Calcium/physiology , Carbachol/pharmacology , Ethylmaleimide/pharmacology , Evoked Potentials/drug effects , GTP-Binding Proteins/antagonists & inhibitors , Magnesium/physiology , Male , Membrane Potentials/drug effects , Membrane Potentials/physiology , Pyramidal Cells/drug effects , Rats , Rats, Sprague-Dawley , Receptors, GABA-A/drug effects , gamma-Aminobutyric Acid/physiology
14.
J Biol Chem ; 273(5): 2763-8, 1998 Jan 30.
Article in English | MEDLINE | ID: mdl-9446583

ABSTRACT

The influence of the substrate P1' position on the specificity of two zinc matrix metalloproteases, membrane type-1 matrix metalloprotease (MT1-MMP) and stromelysin-3 (ST3), was evaluated by synthesizing a series of fluorogenic substrates of general formula dansyl-Pro-Leu-Ala-Xaa-Trp-Ala-Arg-NH2, where Xaa in the P1' position represents unusual amino acids containing either long arylalkyl or alkyl side chains. Our data demonstrate that both MT1-MMP and ST3 cleave substrates containing in their P1' position unusual amino acids with extremely long side chains more efficiently than the corresponding substrates with natural phenylalanine or leucine amino acids. In this series of substrates, the replacement of leucine by S-para-methoxybenzyl cysteine increased the kcat/Km ratio by a factor of 37 for MT1-MMP and 9 for ST3. The substrate with a S-para-methoxybenzyl cysteine residue in the P1' position displayed a kcat/Km value of 1.59 10(6) M-1 s-1 and 1.67 10(4) M-1 s-1, when assayed with MT1-MMP and ST3, respectively. This substrate is thus one of the most rapidly hydrolyzed substrates so far reported for matrixins, and is the first synthetic peptide efficiently cleaved by ST3. These unexpected results for these two matrixins suggest that extracellular proteins may be cleaved by matrixins at sites containing amino acids with unusual long side chains, like those generated in vivo by some post-translational modifications.


Subject(s)
Amino Acids/metabolism , Metalloendopeptidases/metabolism , Oligopeptides/metabolism , Amino Acids/chemistry , Binding Sites , Chromogenic Compounds/metabolism , Dansyl Compounds/metabolism , Matrix Metalloproteinase 11 , Matrix Metalloproteinases, Membrane-Associated , Metalloproteins/metabolism , Substrate Specificity , Zinc
15.
J Neurophysiol ; 77(6): 2945-65, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9212248

ABSTRACT

The spike discharge regularity of 254 tonically firing units in the inferior colliculus (IC) of the anesthetized guinea pig was studied in response to tones presented at best frequency (BF) to the ear contralateral to the recorded IC. Regularity of firing was measured by calculating the coefficient of variation (CV) as a function of time over the course of a unit's response. Two hundred and fifteen units (56 under urethan and 159 under chloralose anesthesia) in the central nucleus of the IC (CNIC) were studied in detail. In response to tones at 15-25 dB above threshold, 80% of units in the urethan sample fired regularly (CV < 0.5) during their sustained response, and 46% were highly regular (CV < or = 0.35). For chloralose the values were 68% and 23%, respectively. Units recorded under urethan were significantly more regular than those recorded under chloralose. For units in the sample with a measurable onset CV, 63% were regular and 44% highly regular under urethan, and 73% were regular and 54% highly regular under chloralose. The units' peristimulus time histogram (PSTH) patterns were classified into subdivisions of four categories: choppers [9%: chop-sustained (Cs), chop-onset (Co)]; pausers [42%: pauser-chop-sustained (P/Cs), pauser-chop-onset (P/Co), pauser-no-chop]; ON-sustained (43%: primary-type, L-type, h-type); and sustained (6%). The presence of chopping was a reliable predictor of regularity: Cs and P/Cs units were highly regular throughout their response, whereas Co and P/Co units were highly regular at onset and became less regular. Some units in the other PSTH categories were highly regular despite the absence of chopping, and units with virtually identical PSTHs showed very different sustained CVs. Regularity was measured as a function of firing rate in 71 units. In 23%, regularity remained constant when firing rate changed with stimulus level. Forty-six percent fired more regularly as firing rate increased, 8% fired less regularly, and 23% of units showed no consistent relationship between CV and firing rate. Regularity did not correlate with the neurons' frequency response areas or BFs. Regular firing was also found in a smaller sample of units recorded in cortices surrounding the CNIC. We conclude that regular firing is a characteristic feature of most neurons in the IC. Regularity is a specific feature correlated with four PSTH types (Cs, Co, P/Cs, and P/Co). Other PSTH types may or may not exhibit regularity.


Subject(s)
Attention/physiology , Dominance, Cerebral/physiology , Inferior Colliculi/physiology , Pitch Perception/physiology , Synaptic Transmission/physiology , Animals , Auditory Pathways/physiology , Brain Mapping , Evoked Potentials, Auditory/physiology , Female , Guinea Pigs , Male , Neurons/physiology , Sound Spectrography
16.
Hear Res ; 93(1-2): 167-80, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8735077

ABSTRACT

We describe the descending projections from the central nucleus of the inferior colliculus (CNIC) in guinea pig. Focal injections of the tracer biocytin, made in physiologically defined frequency regions of the CNIC, labelled laminated axonal terminal fields in the ipsilateral dorsal nucleus of the lateral lemniscus, and bilaterally in the ventral nucleus of the trapezoid body and the dorsal cochlear nucleus. Labelling was also present in the rostral periolivary nucleus, but we could not distinguish a clear border between the terminal fields in this nucleus and those in the ventral nucleus of the trapezoid body. Labelling observed in the ventral nucleus of the lateral lemniscus, and to a lesser extent in the dorsal nucleus of the lateral lemniscus, was accompanied by retrogradely labelled somata and therefore we cannot conclude unequivocally that the CNIC projects to these lemniscal nuclei. Where the labelling was ordered topographically, its position varied as a function of the best frequency at the injection site. High-frequency regions in the CNIC project to the medial parts of the ventral nucleus of the trapezoid body and dorsal cochlear nucleus, while low-frequency regions in the CNIC project to the lateral parts of the ventral nucleus of the trapezoid body and dorsal cochlear nucleus. Additional axonal labelling with terminal boutons, but with no apparent topographical arrangement, was present in the ipsilateral horizontal cell group, sagulum, and also bilaterally in the superficial granule cell layer of the ventral cochlear nucleus and layer 2 of the dorsal cochlear nucleus. Our findings are consistent with the existence of tonotopically organised feedback projections from the CNIC to the brainstem nuclei that project to it.


Subject(s)
Cochlear Nucleus/physiology , Inferior Colliculi/physiology , Olivary Nucleus/physiology , Animals , Auditory Cortex/surgery , Axons/ultrastructure , Cochlear Nucleus/cytology , Cochlear Nucleus/drug effects , Female , Guinea Pigs , Inferior Colliculi/drug effects , Lysine/administration & dosage , Lysine/analogs & derivatives , Lysine/toxicity , Male , Olivary Nucleus/cytology , Olivary Nucleus/drug effects , Tissue Fixation
17.
J Neurophysiol ; 75(2): 902-19, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8714663

ABSTRACT

1. To determine the contribution of inhibition to the generation of the temporal response patterns of neurons in the inferior colliculus (IC), the effects of iontophoretically applied gamma-aminobutyric acid (GABA), glycine, and the GABAA and glycine receptor antagonists, bicuculline and strychnine were studied on 121 neurons in the IC of urethan-anesthetised guinea pig. 2. The neurons temporal discharge patterns were classified into six categories on the basis of their peristimulus time histograms (PSTHs). 1) Onset units fired at the stimulus onset and could be divided into two subtypes: narrow (1-2 spikes only) or broad (response lasting up to approximately 30 ms). 2) Pauser units had a precisely timed onset peak separated from a lower level of sustained activity by either a marked reduction or complete cessation of firing. 3) Chopper units had three or more clearly defined peaks near stimulus onset or evidence of regularly spaced peaks over the duration of the stimulus. 4) Onset-chopper units had three clearly defined peaks at onset but no sustained firing. 5) On-sustained units had a clearly defined single onset peak followed by a lower level of sustained activity. 6) Sustained units fired throughout the stimulus, but lacked an onset peak. 3. Iontophoretic application of GABA and glycine produced a dose-dependent reduction in firing rate in 76% (42/55) and 79% (11/14) of units, respectively. Application of bicuculline or strychnine increased the discharge rate in 91% (64/70) and 94% (16/17) of neurons, respectively. 4. The effects of bicuculline and strychnine on PSTH class were studied in detail on 70 neurons. Changes in discharge rate were accompanied by changes in PSTH in 49% (34/70) of neurons tested with bicuculline and 41% (7/17) tested with strychnine. Pauser units were the most affected with 69% changing their PSTH class, but some units in all PSTH classes, except the chopper group, exhibited changes in PSTH pattern after application of bicuculline. The majority of units (approximately 50%) that changed PSTH pattern in the presence of bicuculline became chopper units. Units of all PSTH classes could become choppers, but the proportion of units showing this change was dependent on the unit's control response pattern. All seven units that changed PSTH class with strychnine also became choppers. Changes in PSTH, including the appearance of a chopper pattern, did not depend on either a unit's control discharge rate or the magnitude of the change in discharge rate induced by the antagonists. 5. Bicuculline and strychnine had no significant effect on latency for units in the chopper, onset-chopper, onset, pauser, and on-sustained groups. A few sustained and unclassified units that had long predrug latencies did show marked reductions in latency when tested with bicuculline. 6. The majority of units did not fire spontaneously, and neither bicuculline or strychnine produced a significant increase in spontaneous rate. 7. In many units, the changes in firing rate did not occur equally over the duration of the response. Firing rates at the onset and in the last quarter of the sustained response were compared. Three effects of bicuculline and strychnine were observed. For 80% of units the largest change in firing rate occurred in the sustained response, while in 14% of units the change was greatest at onset.


Subject(s)
Evoked Potentials, Auditory/drug effects , Glycine/pharmacology , Inferior Colliculi/drug effects , Neural Inhibition/drug effects , Neurons/drug effects , gamma-Aminobutyric Acid/pharmacology , Acoustic Stimulation , Animals , Bicuculline/pharmacology , Female , GABA Antagonists/pharmacology , Guinea Pigs , Inferior Colliculi/cytology , Iontophoresis , Male , Reaction Time/drug effects , Strychnine/pharmacology , Time Factors
18.
J Comp Neurol ; 357(1): 124-44, 1995 Jun 19.
Article in English | MEDLINE | ID: mdl-7673462

ABSTRACT

We present a comprehensive description of the local (intrinsic and commissural) connections in the central nucleus of the inferior colliculi (CNICs) in guinea pig. Focal injections of the anterograde tracer biocytin were made into physiologically identified loci of the CNIC and the spatial organisation of the labeled fibres was revealed with computer-assisted three-dimensional (3-D) reconstruction. The intrinsic fibres form a series of V-shaped laminar plexuses composed of fibres bearing both terminal and en passant boutons. Each laminar plexus has a central wing located in the CNIC that extends into the dorsal cortex and an external wing located in the external cortex. The edge where the two wings intersect delimits the lateral border of the central nucleus with the external cortex. The density of labeled terminals was consistently lower in the cortices than in the CNIC. The laminar plexus connects points of similar frequency within the CNIC. Seen in 3-D, the location, orientation, shape, and area of the laminar plexus vary as a function of best frequency. The commissural fibres ending in the contralateral IC to the injection also form a laminar plexus which is symmetrical to the ipsilateral plexus. Electrolytic lesions placed in the contralateral IC at sites with best frequencies corresponding to those of the injection coincided with the terminals of the commissural fibres in most instances. Possible patterns for the organisation of these connections (point-to-point and diverging) are discussed. Three systems of peripheral axons to the laminar plexus are described: parallel, oblique, and perpendicular to the central wing. The novel parallel system has terminals in both ICs that run parallel to the central wing. It might constitute the anatomical basis for across-frequency interactions. The oblique and perpendicular systems are fibres of passage projecting to the commissure and brachium of the IC, respectively.


Subject(s)
Axons/ultrastructure , Guinea Pigs/anatomy & histology , Image Processing, Computer-Assisted , Inferior Colliculi/ultrastructure , Acoustic Stimulation , Animals , Female , Lysine/analogs & derivatives , Male
19.
Ann Dermatol Venereol ; 119(3): 191-5, 1992.
Article in French | MEDLINE | ID: mdl-1605521

ABSTRACT

Paederus sabaeus is a coleopter of the Staphylinidae family. With its toxins present in the hemolymph (pederin, pseudopederin, pederone), it causes a delayed vesicular inflammatory dermatosis. The contact between skin and toxin is only possible when the insect is injured or killed, which occurs most frequently when it is crushed on the skin. In November 1989, in Conakry, a huge proliferation of this insect was responsible for an epidemic of Paederus dermatitis. The European sailors working in the port of this town were affected preferentially, as well as the entire European population for sociocultural reasons. The clinical picture is very characteristic when the lesions are linear or "kissing lesions" on both sides of the folded part of an articular joint. This dermatosis is more frequent on the uncovered parts of the body. Healing is spontaneous, requiring 7 to 10 days, if there are no further infections.


Subject(s)
Coleoptera , Dermatitis/etiology , Disease Outbreaks , Animals , Dermatitis/epidemiology , Europe/ethnology , Guinea , Humans , Male
20.
Eur J Biochem ; 83(2): 601-7, 1978 Feb.
Article in English | MEDLINE | ID: mdl-204484

ABSTRACT

Reduced 3-thionicotinamide--adenine dinucleotide (sNADH) is shown to be fluorescent, with an emission maximum at 510 nm when excited in the region of the absorption maximum (398 nm), and with a very low quantum yield, (3.4 +/- 0.5) x 10(-4). The interaction between sNADH and octopine dehydrogenase was investigated by ultraviolet-difference spectroscopy and fluorescence. Some surprising fluorescence features were found when sNADH was bound to the enzyme in the presence of D-octopine, as follows. (a) There is an unusually high enhancement of the dinucleotide fluorescence (by at least a factor of 100) attended by a 40-nm blue shift of the emission maximum. (b) The protein fluorescence is quenched almost completely. (c) The bound coenzyme analog undergoes a photoreaction, which proceeds differently from that occurring the free form. These features appear to be unique to the octopine.sNADH complex, as for example they are not present when sNADH is bound to horse liver alcohol dehydrogenase, or when NADH is bound to octopine dehydrogenase. The possible origin of these fluorescence features is discussed. Binding and kinetic studies were carried out with sNAD and sNADH. It was found that sNAD neither binds nor acts kinetically as a coenzyme. sNADH exhibits relatively good binding, with Km and Ki values close to those of the natural coenzyme, but the turnover number is 460 times smaller than that with NADH. The kinetic consequences of these findings are discussed. The sNADH dissociation constants were determined as a function of temperature, and appear to be practically temperature-independent in the range 10--40 degrees C. It seems thus, in agreement with previous studies, that the interaction between octopine dehydrogenase and coenzymes proceeds athermically, regardless of the structure, affinity, and chemical reactivity of the coenzyme. The possible biological and chemical meaning of this finding is discussed.


Subject(s)
Amino Acid Oxidoreductases , NAD/analogs & derivatives , Thionucleotides , Amino Acid Oxidoreductases/metabolism , Amino Acids, Dicarboxylic , Kinetics , Oxidation-Reduction , Protein Binding , Spectrometry, Fluorescence
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