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At least 739 records · Page 41Linked to original sources
PubMed2005

6-Methylflavanone, a more efficacious positive allosteric modulator of gamma-aminobutyric acid (GABA) action at human recombinant alpha2beta2gamma2L than at alpha1beta2gamma2L and alpha1beta2 GABA(A) receptors expressed in Xenopus oocytes.

6-Methylflavanone acted as a positive allosteric modulator of gamma-aminobutyric acid (GABA) responses at human recombinant alpha1beta2gamma2L, alpha2beta2gamma2L and alpha1beta2 GABA(A) receptors expressed in Xenopus laevis oocytes. It was essentially inactive at rho1 GABA(C) receptors. The EC50 values for 6-methylflavanone for the positive modulation of the EC(10-20) GABA responses were 22 microM, 10 microM and 6 microM and the maximum potentiations were 120%, 417% and 130% at alpha1beta2gamma2L, alpha2beta2gamma2L and alpha1beta2 GABA(A) receptors respectively. Thus 6-methylflavanone was much more efficacious as a positive modulator at alpha2beta2gamma2L than at alpha1beta2gamma2L and alpha1beta2 GABA(A) receptors. This may be significant since diazepam-induced anxiolysis is considered to be mediated via alpha2-containing GABA(A) receptors, while sedation is thought to be mediated via alpha1-containing GABA(A) receptors. We have previously reported that 6-methylflavone (1-100 microM) produced positive allosteric modulation at alpha1beta2gamma2L and alpha1beta2 GABA(A) receptors with no significant difference between the enhancement seen at either receptor subtype. In the present study, 6-methylflavone was tested at alpha2beta2gamma2L GABA(A) receptors and found to maximally potentiate the EC(10-20) GABA response by 183+/-39% which is similar to that previously observed for 6-methylflavone at alpha1beta2gamma2L GABA(A) receptors. Thus, 6-methylflavone did not show a preference for alpha2beta2gamma2L over alpha1beta2gamma2L GABA(A) receptors in terms of efficacy. Compared to 6-methylflavone, 6-methylflavanone is more efficacious as a positive allosteric modulator at alpha2beta2gamma2L GABA(A) receptors, and less efficacious at alpha1beta2gamma2L GABA(A) receptors. This may represent a relatively unique type of selectivity for positive modulators of GABA-A receptor subtypes based on efficacy as distinct from potency. As was previously shown for 6-methylflavone at alpha1beta2gamma2L GABA(A) receptors, the positive modulation of GABA responses at alpha1beta2gamma2L and alpha2beta2gamma2L GABA(A) receptors by 6-methylflavanone was insensitive to antagonism by flumazenil, indicating that this action is not mediated via "high-affinity" benzodiazepine sites.

Allosteric Regulation↗
PubMed2006

Differential behavioral effects of low efficacy positive GABAA modulators in combination with benzodiazepines and a neuroactive steroid in rhesus monkeys.

In the clinic, low efficacy positive GABAA modulators might be preferred to high efficacy positive modulators insofar as low efficacy modulators might have comparatively less abuse and dependence liability. Drug discrimination was used to examine the behavioral effects of L-838,417 and bretazenil, two low efficacy positive GABAA modulators that act at benzodiazepine sites, alone and in combination with benzodiazepines and a neuroactive steroid (alfaxolone). In rhesus monkeys (n = 5) discriminating midazolam, alfaxolone substituted for midazolam. In four monkeys, L-838,417 and bretazenil did not substitute for, but rather dose-dependently antagonized, midazolam; L-838-417 and bretazenil, as well as flumazenil, enhanced the midazolam-like effects of alfaxolone. L-838,417 and bretazenil substituted for midazolam in a fifth monkey. In a separate group of rhesus monkeys (n = 3) that received 5.6 mg kg(-1) per day of diazepam and that discriminated flumazenil, L-838,417 and bretazenil substituted for flumazenil. These results demonstrate that L-838,417, bretazenil, and flumazenil can have agonist or antagonist actions in the same animal depending upon whether they are studied in combination with a higher efficacy positive GABAA modulator acting at the same (benzodiazepine) or a different (neuroactive steroid) site. Thus, combinations of low efficacy positive modulators acting at different sites on the GABAA receptor complex could yield drug mixtures with significant therapeutic effects and with reduced abuse and dependence liability, as compared to higher efficacy positive modulators such as currently available benzodiazepines.

Animals↗
PubMed2006

Efficacy and the discriminative stimulus effects of negative GABAA modulators, or inverse agonists, in diazepam-treated rhesus monkeys.

In benzodiazepine (BZ)-dependent animals, the effects of negative GABA(A) modulators at BZ sites are not clearly related to differences in negative efficacy (i.e., inverse agonist activity). A flumazenil discriminative stimulus in diazepam (5.6 mg/kg/day)-treated rhesus monkeys was used to test the hypothesis that the effects of negative GABA(A) modulators at BZ sites do not vary as a function of efficacy in BZ-dependent animals. Negative GABA(A) modulators varying in efficacy were studied in combination with positive modulators acting at different modulatory sites (BZ, barbiturate, and neuroactive steroid sites). The negative modulators Ro 15-4513 (ethyl 8-azido-6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-alpha]-[1,4]benzodiazepine-3-carboxylate) and ethyl beta-carboline-3-carboxylate (beta-CCE) substituted for the flumazenil discriminative stimulus. Acute pretreatment with diazepam (3.2 and 10 mg/kg s.c., in addition to 5.6 mg/kg/day p.o.), pentobarbital (3.2 and 10 mg/kg), or pregnanolone (1 and 3.2 mg/kg) attenuated the flumazenil discriminative stimulus and also attenuated the flumazenil-like discriminative stimulus effects of Ro 15-4513 and beta-CCE. Attenuation of the discriminative stimulus effects of flumazenil, Ro 15-4513, and beta-CCE did not systematically vary as a function of negative efficacy. Compared with their discriminative stimulus effects in untreated monkeys discriminating midazolam, both pregnanolone and pentobarbital were relatively more potent than diazepam in attenuating the discriminative stimulus effects of flumazenil, Ro 15-4513, and beta-CCE in diazepam-treated monkeys. These results show that the discriminative stimulus effects of BZ-site neutral and negative modulators are not different in BZ-dependent animals trained to discriminate flumazenil, and extend the results of a previous study showing that positive modulators acting at non-BZ sites are especially potent in attenuating the effects of flumazenil in diazepam-treated monkeys (i.e., diazepam withdrawal).

Animals↗
PubMed2025

ProgModule: A novel computational framework to identify mutation driver modules for predicting cancer prognosis and immunotherapy response.

BACKGROUND: Cancer originates from dysregulated cell proliferation driven by driver gene mutations. Despite numerous algorithms developed to identify genomic mutational signatures, they often suffer from high computational complexity and limited clinical applicability. METHODS: Here, we presented ProgModule, an advanced computational framework designed to identify mutation driver modules for cancer prognosis and immunotherapy response prediction. In ProgModule, we introduced the Prognosis-Related Mutually Exclusive Mutation (PRMEM) score, which optimizes the balance between exclusive mutation coverage and the incorporation of mutation combination mechanisms critical for cancer prognosis. RESULTS: Applying to BLCA and HNSC cohorts, ProgModule successfully identified driver modules that stratify patients into distinct prognostic subgroups, and the combination of these modules could serve as an effective prognostic biomarker. Extending our method to diverse cancers, ProgModule presented robust prognostic performance and stability across model parameters, including stopping criteria and network topology. Moreover, our analysis suggested that driver modules can predict immunotherapeutic benefit more effectively than existing signatures. Further analyses based on published CRISPR data indicated that genes within these modules may serve as potential therapeutic targets. CONCLUSIONS: Altogether, ProgModule emerges as a powerful tool for identifying mutation driver modules as prognostic and immunotherapy response biomarkers, and genes within these modules may be used as potential therapeutic targets for cancer, offering new insights into precision oncology.

Humans↗
PubMed1997

Role of modulation on the effect of microwaves on ornithine decarboxylase activity in L929 cells.

The effect of 835 MHz microwaves on the activity of ornithine decarboxylase (ODC) in L929 murine cell was investigated at an SAR of approximately 2.5 W/kg. The results depended upon the type of modulation employed. AM frequencies of 16 Hz and 60 Hz produced a transient increase in ODC activity that reached a peak at 8 h of exposure and returned to control levels after 24 h of exposure. In this case, ODC was increased by a maximum of 90% relative to control levels. A 40% increase in ODC activity was also observed after 8 h of exposure with a typical signal from a TDMA digital cellular telephone operating in the middle of its transmission frequency range (approximately 840 MHz). This signal was burst modulated at 50 Hz, with approximately 30% duty cycle. By contrast, 8 h exposure with 835 MHz microwaves amplitude modulated with speech produced no significant change in ODC activity. Further investigations, with 8 h of exposure to AM microwaves, as a function of modulation frequency, revealed that the response is frequency dependent, decreasing sharply at 6 Hz an 600 Hz. Exposure with 835 MHz microwaves, frequency modulated with a 60 Hz sinusoid, yielded no significant enhancement in ODC activity for exposure times ranging between 2 and 24 h. Similarly, exposure with a typical signal from an AMPS analog cellular telephone, which uses a form of frequency modulation, produced no significant enhancement in ODC activity. Exposure with 835 MHz continuous wave microwaves produced no effects for exposure times between 2 and 24 h, except for a small but statistically significant enhancement in ODC activity after 6 h of exposure. Comparison of these results suggests that effects are much more robust when the modulation causes low-frequency periodic changes in the amplitude of the microwave carrier.

Animals↗
PubMed1984

Alterations in protein kinase activity following exposure of cultured human lymphocytes to modulated microwave fields.

Cultures of human tonsil lymphocytes were exposed in a Crawford cell to a 450-MHz field (peak envelope intensity 1.0 mW/cm2), sinusoidally amplitude modulated (depth 80%) at frequencies between 3 and 100 Hz for periods up to 60 min. The Crawford cell was housed in a temperature-controlled chamber (35 degrees C) and control cultures were placed in the same chamber. Activity of cAMP-dependent protein kinase relative to controls remained unaltered by fields modulated at 16 or 60 Hz with exposures of 15, 30, and 60 min. By contrast, total non-cAMP-dependent kinase activity fell to less than 50% of unexposed control levels after 15 and 30 min exposures, but, despite continuing field exposure, returned to control or preexposure levels by 45 and 60 min. A smaller reduction (20-25%) also occurred with 60-Hz modulation and was also restricted to exposure durations of 15 and 30 min. CW 450-MHz fields were without effect. Reduced enzyme activity occurred with 16-, 40-, and 60-Hz modulation frequencies, but not with 3-, 6-, 80-, or 100-Hz modulation. The specific identity of this kinase is unknown. This rapid but transient reduction in lymphocyte protein kinase activity restricted to modulation frequencies between 16 and 60 Hz and to less than 30 min exposure is consistent with "windowing" with respect to modulation frequency and exposure duration.

Cells, Cultured↗
PubMed2002

Cytogenetic damage in human lymphocytes following GMSK phase modulated microwave exposure.

The present study investigated, using in vitro experiments on human lymphocytes, whether exposure to a microwave frequency used for mobile communication, either unmodulated or in presence of phase only modulation, can cause modification of cell proliferation kinetics and/or genotoxic effects, by evaluating the cytokinesis block proliferation index and the micronucleus frequency. In the GSM 1800 mobile communication systems the field is both phase (Gaussian minimum shift keying, GMSK) and amplitude (time domain multiple access, TDMA) modulated. The present study investigated only the effects of phase modulation, and no amplitude modulation was applied. Human peripheral blood cultures were exposed to 1.748 GHz, either continuous wave (CW) or phase only modulated wave (GMSK), for 15 min. The maximum specific absorption rate (approximately 5 W/kg) was higher than that occurring in the head of mobile phone users; however, no changes were found in cell proliferation kinetics after exposure to either CW or GMSK fields. As far as genotoxicity is concerned, the micronucleus frequency result was not affected by CW exposure; however, a statistically significant micronucleus effect was found following exposure to phase modulated field. These results would suggest a genotoxic power of the phase modulation per se.

Adult↗
PubMed2005

Interactions between odorant functional group and hydrocarbon structure influence activity in glomerular response modules in the rat olfactory bulb.

To investigate the effect of odorant hydrocarbon structure on spatial representations in the olfactory bulb systematically, we exposed rats to odorant chemicals possessing one of four different oxygen-containing functional groups on one of five different hydrocarbon backbones. We also used several hydrocarbon odorants lacking other functional groups. Hydrocarbon structural categories included straight-chained, branched, double-bonded, alicyclic, and aromatic features. Activity throughout the entire glomerular layer was measured as uptake of [(14)C]2-deoxyglucose and was mapped into anatomically standardized data matrices for statistical comparisons across different animals. Patterns evoked by straight-chained aliphatic odorants confirmed an association of activity in particular glomerular response modules with particular functional groups. However, the amount of activity in these same modules also was affected significantly by differences in hydrocarbon structure. Thus, the molecular features recognized by receptors projecting to these response modules appear to involve both functional group and hydrocarbon structural elements. In addition, particular benzyl and cyclohexyl odorants evoked activity in dorsal modules previously associated with the ketone functional group, which represents an exception to the rule of one feature per response module that had emerged from our previous studies. These dorsal modules also responded to nitrogen-containing aromatic compounds involving pyridine and pyrazine rings. The unexpected overlap in modular responses to ketones and odorants seemingly unrelated to ketones may reflect some covert shared molecular feature, the existence of odorant sensory neurons with multiple specificities, or a mosaic of sensory neuron projections to these particular modules.

Animals↗
PubMed2006

Regulation of 2B4 (CD244)-mediated NK cell activation by ligand-induced receptor modulation.

Natural killer (NK) cell activity can be stimulated by different surface receptors. 2B4 is a member of the signaling lymphocyte activation molecule (SLAM)-related receptor family and is important for stimulating human NK cell cytotoxicity and cytokine production. Here we show that stimulation of human NK cells by antibody-mediated 2B4 cross-linking or incubation with target cells expressing the 2B4 ligand CD48 results in a strong down-modulation of 2B4 surface expression. This down-modulation is observed in NK cell lines, purified human NK cells and NK cell clones, and is accompanied by an internalization of 2B4. The modulation of 2B4 is dependent on the activity of Src-family kinases, but independent of PI3 K activity or actin polymerization. Inhibitory receptors can interfere with 2B4-mediated signals and NK cell activation. However, co-engagement of inhibitory killer cell Ig-like receptors has no influence on the down-modulation of 2B4. This suggests that the modulation of 2B4 expression is independent of inhibitory receptors. The lower surface expression of 2B4 after ligand-induced down-modulation results in reduced 2B4-mediated NK cell activation and cytotoxicity. The modulation of activating surface receptors may therefore be another mechanism for the fine-tuning of NK cell activity and may lead to the adaptation of NK cell cytotoxicity in tissues with high ligand expression.

Antigens, CD↗
PubMed1995

A common switch in activation of the response regulators NtrC and PhoB: phosphorylation induces dimerization of the receiver modules.

During signal transduction, response regulators of two-component systems are phosphorylated in a conserved receiver module. Phosphorylation induces activation of the non-conserved output domain. We fused various domains of the response regulators NtrC, PhoB or CheB to the DNA binding domain of lambda repressor. Analysis of these hybrid proteins shows that the receiver modules of NtrC and PhoB are potential dimerization domains. In the unphosphorylated proteins, the ability of the receiver modules to dimerize is masked due to inhibition by their output domains. Inhibition can be relieved in two ways: phosphorylation of the receiver module or deletion of the output domain. In contrast, the receiver module of CheB lacks this ability for dimerization. We propose a model which groups response regulators into two classes. Common to both classes is the interaction between receiver and output domain in the unphosphorylated protein. In class I (e.g. NtrC and PhoB), this interaction leads to the inhibition of the receiver module. Phosphorylation relieves inhibition, thereby inducing activation via dimerization of the receiver modules. In class II (e.g. CheB), the interaction between receiver and output domain results in inhibition of the output domain. Phosphorylation relieves inhibition, thereby activating the output domain.

Adenosine Triphosphatases↗
PubMed2005

Modules, kinds, and homology.

Developmental modules are best conceptualized as homeostatic property cluster natural kinds. As is true in other fields of biology, an individual may instantiate properties of various natural kinds. Through their dissociability, developmental modules can be recruited to function as evolutionary modules. The proper analogy to developmental modules, atoms, or biological species depends on the scope over which specific developmental modules allow generalizations. The nature of the relationship between developmental modules, evolutionary modules, and taxic (phylogenetic) homology are explored. Similarity of gene expression patterns and developmental pathways as captured by biological homology may support hypotheses of taxic homology, but not the other way around.

Animals↗
PubMed1976

Responses of single units in the cat cochlear nucleus to sinusoidal amplitude modulation of tones and noise: linearity and relation to speech perception.

Responses to the sinusoidal modulation envelopes of amplitude-modulated tonend noise carriers were recorded from single units in the cochlear nucleus of the cat. The unit discharges were synchronized to the peaks of the modulation envelope. Population-averaged firing rate were independent of the modulation index of the stimulus. Temporal firing patterns, as represented by the shapes and magnitudes of modulation-cycle histograms, were strongly dependent on stimulus intesity and modulation index. Nonlinear nonsinusoidal responses to sinusoidal modulation envelopes were observed, but only at high values of sound intensity. These and other results are discussed in the context of psychological studies concerning the perception of speech information.

Acoustic Stimulation↗
PubMed2006

At-column heating and a resistively heated, liquid-cooled thermal modulator for a low-resource bench-top GC x GC.

A transportable GC x GC instrument is under development for on-site applications that would benefit from the enhanced resolution and powers of detection, which can be achieved by this method. In the present study, a low-resource GC x GC instrument using an electrically heated and liquid-cooled single-stage thermal modulator that requires no cryogenic materials is evaluated. The instrument also uses at-column heating, thus eliminating the need for a convection oven to house the two columns. The stainless-steel modulator tube is coated with PDMS, which can be heated to 350 degrees C for sample injection into the second-dimension column. The modulator is cooled to -30 degrees C by a 100 mL/min flow of PEG by means of a commercial liquid chiller and a small recirculating pump. Resistive heating of the modulator tube is provided by a programmable power supply, which uses a voltage program that results in increasing modulator temperature during an analysis. This, together with more rapid cooling by the use of a liquid cooling medium, results in reduced solute breakthrough following each heating cycle as the modulator cools to a temperature where quantitative trapping resumes. As a result, modulated peak widths at half-height of less than 40 ms are observed. Design and performance details are presented along with chromatograms of gasoline and an essential oil sample.

Journal Article↗
PubMed1994

Solution structure of a pair of fibronectin type 1 modules with fibrin binding activity.

The tertiary structure of the fourth and fifth type 1 module pair from the N terminus of human fibronectin, has been determined by two-dimensional homonuclear 1H nuclear magnetic resonance (NMR) spectroscopy. Comparison of each module fold with those of two other type 1 modules shows that the type 1 "consensus" structure is conserved in the pair. The modules connect end-to-end to form an elongated structure with a limited clockwise twist around the long axis, from N to C terminus. The short five residue linker sequence forms a tight loop and the relative orientation of the two modules is maintained by fixed and intimate hydrophobic contacts, dominated by a non-conserved tryptophan residue from the fourth type 1 module. The protein binds specifically to fibrin in an ELISA and surface accessible residues that may be involved in this and other protein interactions can be identified. The structure provides an insight into how chains of type 1 modules may link up in intact fibronectin.

Amino Acid Sequence↗
PubMed1998

Solution structure and dynamics of linked cell attachment modules of mouse fibronectin containing the RGD and synergy regions: comparison with the human fibronectin crystal structure.

We report the three-dimensional solution structure of the mouse fibronectin cell attachment domain consisting of the linked ninth and tenth type III modules, mFnFn3(9,10). Because the tenth module contains the RGD cell attachment sequence while the ninth contains the synergy region, mFnFn3(9,10) has the cell attachment activity of intact fibronectin. Essentially complete signal assignments and approximately 1800 distance and angle restraints were derived from multidimensional heteronuclear NMR spectra. These restraints were used with a hybrid distance geometry/simulated annealing protocol to generate an ensemble of 20 NMR structures having no distance or angle violations greater than 0.3 A or 3 degrees. Although the beta-sheet core domains of the individual modules are well-ordered structures, having backbone atom rmsd values from the mean structure of 0.51(+/-0.12) and 0.40(+/-0.07) A, respectively, the rmsd of the core atom coordinates increases to 3.63(+/-1.41) A when the core domains of both modules are used to align the coordinates. The latter result is a consequence of the fact that the relative orientation of the two modules is not highly constrained by the NMR restraints. Hence, while structures of the beta-sheet core domains of the NMR structures are very similar to the core domains of the crystal structure of hFnFn3(9,10), the ensemble of NMR structures suggests that the two modules form a less extended and more flexible structure than the fully extended rod-like crystal structure. The radius of gyration, Rg, of mFnFn3(9,10) derived from small-angle neutron scattering measurements, 20.5(+/-0.5) A, agrees with the average Rg calculated for the NMR structures, 20.4 A, and is ca 1 A less than the value of Rg calculated for the X-ray structure. The values of the rotational anisotropy, D ||/D perpendicular, derived from an analysis of 15N relaxation data, range from 1.7 to 2.1, and are significantly less than the anisotropy of 2.67 predicted by hydrodynamic modeling of the crystal coordinates. In contrast, hydrodynamic modeling of the NMR coordinates yields anisotropies in the range of 1.9 to 2.7 (average 2.4(+/-0.2)), with NMR structures bent by more than 20 degrees relative the crystal structure having calculated anisotropies in best agreement with experiment. In addition, the relaxation parameters indicate that several loops in mFnFn3(9,10), including the RGD loop, are flexible on the nanosecond to picosecond time-scale. Taken together, our results suggest that, in solution, the limited set of interactions between the mFnFn3(9,10) modules position the RGD and synergy regions to interact specifically with cell surface integrins, and at the same time permit sufficient flexibility that allows mFnFn3(9,10) to adjust for some variation in integrin structure or environment.

Amino Acid Sequence↗
PubMed2000

Four crystal structures of the 60 kDa flavoprotein monomer of the sulfite reductase indicate a disordered flavodoxin-like module.

Escherichia coli NADPH-sulfite reductase (SiR) is a 780 kDa multimeric hemoflavoprotein composed of eight alpha-subunits (SiR-FP) and four beta-subunits (SiR-HP) that catalyses the six electron reduction of sulfite to sulfide. Each beta-subunit contains a Fe4S4 cluster and a siroheme, and each alpha-subunit binds one FAD and one FMN as prosthetic groups. The FAD gets electrons from NADPH, and the FMN transfers the electrons to the metal centers of the beta-subunit for sulfite reduction. We report here the 1.94 A X-ray structure of SiR-FP60, a recombinant monomeric fragment of SiR-FP that binds both FAD and FMN and retains the catalytic properties of the native protein. The structure can be divided into three domains. The carboxy-terminal part of the enzyme is composed of an antiparallel beta-barrel which binds the FAD, and a variant of the classical pyridine dinucleotide binding fold which binds NADPH. These two domains form the canonic FNR-like module, typical of the ferredoxin NADP+ reductase family. By analogy with the structure of the cytochrome P450 reductase, the third domain, composed of seven alpha-helices, is supposed to connect the FNR-like module to the N-terminal flavodoxine-like module. In four different crystal forms, the FMN-binding module is absent from electron density maps, although mass spectroscopy, amino acid sequencing and activity experiments carried out on dissolved crystals indicate that a functional module is present in the protein. Our results clearly indicate that the interaction between the FNR-like and the FMN-like modules displays lower affinity than in the case of cytochrome P450 reductase. The flexibility of the FMN-binding domain may be related, as observed in the case of cytochrome bc1, to a domain reorganisation in the course of electron transfer. Thus, a movement of the FMN-binding domain relative to the rest of the enzyme may be a requirement for its optimal positioning relative to both the FNR-like module and the beta-subunit.

Amino Acid Sequence↗
PubMed1996

Detection of frequency modulation in the FM-bat Phyllostomus discolor.

In a two-alternative forced-choice procedure lesser spear-nosed bats, Phyllostomus discolor, had to discriminate between a pure tone stimulus and a sinusoidally frequency-modulated signal generated at the same carrier frequency as the tone. Modulation depths of the SFM stimuli were reduced until the animals' performance dropped below the 75%-correct level which was used to determine difference limens for detection of frequency modulation (FMDL). The dependence of FMDLs on modulation and carrier frequency was systematically investigated. For a carrier frequency of 18.5 kHz, average FMDLs increased from 95 Hz at a modulation frequency of 10 Hz to 820 Hz at a modulation frequency of 2000 Hz which corresponds to Weber ratios (2 delta f/f) of 0.005 and 0.044 respectively. Further, difference limens were found to increase linearly in proportion to carrier frequency throughout a major part (9-74 kHz) of the species' hearing range. In comparison to other mammals, P. discolor has a pronounced capability for frequency discrimination which might be related to the extensive use of individually distinct frequency-modulated communication calls and audio-vocal learning.

Acoustic Stimulation↗
PubMed1993

Respiratory-modulated and phrenic afferent-driven neurons in the cervical spinal cord (C4-C6) of the fluorocarbon-perfused guinea pig.

The potential contributions of cervical spinal interneurons to the neural control of respiration have been investigated by extracellularly recording the patterns of activity of neurons in the C4-C6 spinal cord during fictive respiration in the fluorocarbon-perfused, adult guinea pig. Two types of neurons were recorded: respiratory-modulated neurons, whose activity was modulated with respiration, and phrenic-driven neurons, which were excited by electrical stimulation of the phrenic nerve. Respiratory-modulated neurons (n = 20) could be divided into inspiratory, expiratory, and phase-spanning neurons, based on their patterns of activity during fictive respiration. Respiratory-modulated neurons showed varying dependencies on the type of breathing; during spontaneous augmented breaths, one-half exhibited patterns of activity that were significantly different to those seen during normal, fictive respiration, whereas the other half of the respiratory-modulated neurons showed similar patterns of activity during both normal and augmented breaths. Phrenic-driven neurons (n = 22) could be divided into short-latency (7-12 ms), moderate-latency (12-25 ms), and inhibited neurons, but were only occasionally and weakly modulated with respiration. The results suggest that respiratory-modulated C4-C6 spinal neurons may contribute to the neural control of respiration, with different subpopulations specialized for different types of respiratory tasks, and that phrenic-driven neurons may be interposed in sensory or reflex pathways, such as the spinothalamic tract or phrenic-to-phrenic inhibitory reflex.

Animals↗