Can macaques perceive place of articulation from formant transition information?

An important problem in speech perception is to determine how humans extract the perceptually invariant place of articulation information in the speech wave across variable acoustic contexts. Although analyses have been developed that attempted to classify the voiced stops /b/ versus /d/ from stimulus onset information, most of the human perceptual research to date suggests that formant transition information is more important than onset information. The purpose of the present study was to determine if animal subjects, specifically Japanese macaque monkeys, are capable of categorizing /b/ versus /d/ in synthesized consonant-vowel (CV) syllables using only formant transition information. Three monkeys were trained to differentiate CV syllables with a "go-left" versus a "go-right" label. All monkeys first learned to differentiate a /za/ versus /da/ manner contrast and easily transferred to three new vowel contexts /[symbol: see text], epsilon, I/. Next, two of the three monkeys learned to differentiate a /ba/ versus /da/ stop place contrast, but were unable to transfer it to the different vowel contexts. These results suggest that animals may not use the same mechanisms as humans do for classifying place contrasts, and call for further investigation of animal perception of formant transition information versus stimulus onset information in place contrasts.

Slowing of axonal transport is a very early event in the toxicity of ALS-linked SOD1 mutants to motor neurons.

Mutations in copper/zinc superoxide dismutase 1 (SOD1), primary causes of human amyotrophic lateral sclerosis (ALS), provoke motor neuron death through an unidentified toxic property. The known neurofilament-dependent slowing of axonal transport, combined with the prominent misaccumulation of neurofilaments in ALS, suggests that an important aspect of toxicity may arise from damage to transport. Here we verify this hypothesis for two SOD1 mutations linked to familial ALS. Reduced transport of selective cargoes of slow transport, especially tubulin, arises months before neurodegeneration. For one mutant, this represents the earliest detectable abnormality. Thus, damage to the cargoes or machinery of slow transport is an early feature of toxicity mediated by mutant SOD1.

Neurofilament-dependent radial growth of motor axons and axonal organization of neurofilaments does not require the neurofilament heavy subunit (NF-H) or its phosphorylation.

Neurofilaments are essential for establishment and maintenance of axonal diameter of large myelinated axons, a property that determines the velocity of electrical signal conduction. One prominent model for how neurofilaments specify axonal growth is that the 660-amino acid, heavily phosphorylated tail domain of neurofilament heavy subunit (NF-H) is responsible for neurofilament-dependent structuring of axoplasm through intra-axonal crossbridging between adjacent neurofilaments or to other axonal structures. To test such a role, homologous recombination was used to generate NF-H-null mice. In peripheral motor and sensory axons, absence of NF-H does not significantly affect the number of neurofilaments or axonal elongation or targeting, but it does affect the efficiency of survival of motor and sensory axons. Loss of NF-H caused only a slight reduction in nearest neighbor spacing of neurofilaments and did not affect neurofilament distribution in either large- or small-diameter motor axons. Since postnatal growth of motor axon caliber continues largely unabated in the absence of NF-H, neither interactions mediated by NF-H nor the extensive phosphorylation of it within myelinated axonal segments are essential features of this growth.

Absence of neurofilaments reduces the selective vulnerability of motor neurons and slows disease caused by a familial amyotrophic lateral sclerosis-linked superoxide dismutase 1 mutant.

Mutations in superoxide dismutase 1 (SOD1), the only proven cause of amyotrophic lateral sclerosis (ALS), provoke disease through an unidentified toxic property. Neurofilament aggregates are pathologic hallmarks of both sporadic and SOD1-mediated familial ALS. By deleting NF-L, the major neurofilament subunit required for filament assembly, onset and progression of disease caused by familial ALS-linked SOD1 mutant G85R are significantly slowed, while selectivity of mutant-mediated toxicity for motor neurons is reduced. In NF-L-deleted animals, levels of the two remaining neurofilament subunits, NF-M and NF-H, are markedly reduced in axons but are elevated in motor neuron cell bodies. Thus, while neither perikaryal nor axonal neurofilaments are essential for SOD1-mediated disease, the absence of assembled neurofilaments both diminishes selective vulnerability and slows SOD1(G85R) mutant-mediated toxicity to motor neurons.

Effects of team size on the maximum weight bar lifting strength of military personnel.

Teamwork is an essential element in the majority of critical Army lifting tasks. Therefore, an understanding of the relationship between individual and team lifting capacity is of great tactical importance. Twenty-three male and 17 female U.S. Army soldiers were randomly assigned to single- and mixed-gender teams of two, three, and four persons. Individual lifting strength was the one-repetition-maximum (1RM) load lifted from floor to knuckle height using a weight bar. A square-shaped bar was used for two- and four-person lifting, and a triangular-shaped bar was used for three-person lifting. Team lifting strength as a percentage of the sum of individual lifting strength (%sum) did not change with team size. The %sum for teams of men (87.3%) was less than for teams of women (91.1%, p < 0.05). The %sums for both single-gender teams (all men and all women) were greater (p < 0.01) than for mixed-gender teams (80.2%). The number of people lifting a large object was increased to four with no decrease in the effectiveness of the individual lifter beyond that found for two persons. The 1RM loads presented in this paper were lifted under ideal conditions by young soldiers and do not represent norms for an industrial population.

Behavioral measures of vowel sensitivity in Mongolian gerbils (Meriones unguiculatus): effects of age and genetic origin.

Absolute thresholds for complex vowel stimuli were compared in Mongolian gerbils (Meriones unguiculatus) as a function of age and genetic origin. For a group of 12-month-old 'domestic' gerbils obtained from Tumblebrook Farms, lowest thresholds averaging 14 dB SPL occurred for the vowel /alpha/, which had its most intense formant (F1) at 730 Hz. Thresholds increased to 22 dB SPL for /i/, which had its two most intense formants (F1 and F3) at 270 and 3000 Hz, respectively. Highest thresholds of 30 dB SPL occurred for /u/, which had its most intense formant (F1) at 300 Hz. Thresholds increased by about 10 dB per year through the ages of 12-36 months, with most of the loss occurring for /alpha/ and /u/. The domestic gerbils' /alpha/ thresholds corresponded well to those measured in aging gerbils in electrophysiological studies. Vowel thresholds were also measured in a group of first-generation offspring of 'wild' gerbils imported from Asia, first tested at the ages of 18-24 months. Thresholds were similar to those of the 12-month-old domestic gerbils, and showed no hearing loss with age up to 36 months. The wild gerbils were also free of ear impactions, which commonly occurred in the domestic gerbils. The hearing loss with age in the domestic gerbils may have a genetic basis, and might be due to inbreeding in the domestic strain, in contrast to the hybrid vigor of the wild gerbils.

Neurofilament subunit NF-H modulates axonal diameter by selectively slowing neurofilament transport.

To examine the mechanism through which neurofilaments regulate the caliber of myelinated axons and to test how aberrant accumulations of neurofilaments cause motor neuron disease, mice have been constructed that express wild-type mouse NF-H up to 4.5 times the normal level. Small increases in NF-H expression lead to increased total neurofilament content and larger myelinated axons, whereas larger increases in NF-H decrease total neurofilament content and strongly inhibit radial growth. Increasing NF-H expression selectively slow neurofilament transport into and along axons, resulting in severe perikaryal accumulation of neurofilaments and proximal axonal swellings in motor neurons. Unlike the situation in transgenic mice expressing modest levels of human NF-H (Cote, F., J.F. Collard, and J.P. Julien. 1993. Cell. 73:35-46), even 4.5 times the normal level of wild-type mouse NF-H does not result in any overt phenotype or enhanced motor neuron degeneration or loss. Rather, motor neurons are extraordinarily tolerant of wild-type murine NF-H, whereas wild-type human NF-H, which differs from the mouse homolog at > 160 residue positions, mediates motor neuron disease in mice by acting as an aberrant, mutant subunit.

Relationship of standardized mitotic indices to other prognostic factors in breast cancer.

OBJECTIVE: To examine the relationship between mitotic index (MI), calculated from direct microscopic counts, and other prognostic features in breast cancer. DESIGN: Mitotic index was based on direct microscopic observations of mitotic figures in 10 consecutive microscopic fields, and the average cell number was determined by counts of population density in three of those fields. Tumor grade and type were established from tissue sections, whereas metastases were detected in lymph node biopsy, chest roentgenograms, and bone scan. Estrogen receptor (ER) and progesterone receptor (PgR) levels were determined by flow cytometry. RESULTS: The MI for 242 patients ranged from 0.2 to 37.6, with a mean of 5.8 mitoses per 1000 cells. More than 85% of the tumors with an MI below 1.0 were diploid and contained an S-phase fraction of 6.7% or less. In contrast, more than 75% of tumors with an MI above 5.0 were aneuploid with more than 6.7% of cells in S-phase. There was an inverse relationship between ER and PgR status and MI. Eighty percent of tumors with an MI less than 1.0 were both ER and PgR positive while only 25% of those with an MI above 10.0 were both ER and PgR positive. Receptor-positive tumors with high S-phase and MI values had ER and PgR levels below 100 fmol/mg. CONCLUSIONS: Lower MI values calculated from direct cell counts are correlated with negative node status, diploid DNA content, low S-phase fraction, and positive receptor status. Thus, there is a significant relationship between objective MI values and several other factors that predict the probability of breast tumor recurrence.

Expression of PAC 1, an epitope associated with two synapse-enriched glycoproteins and a neuronal cytoskeleton-associated polypeptide in developing forebrain neurons.

The monoclonal antibody PAC 1 (postsynaptic density and cytoskeleton enriched) recognizes an epitope present on two postsynaptic density-enriched glycoproteins of 130,000 (postsynaptic density-enriched glycoprotein 130) and 117,000 mol. wt (postsynaptic density-enriched glycoprotein 117), and a cytoskeleton-enriched polypeptide of 155,000 mol. wt (cp155). The PAC 1 antibody has been used to study the development of the PAC 1 antigens in the developing rat forebrain in vivo and in tissue culture. cp155 is detected by embryonic day 14 and its level continues to rise until the sixth postnatal week. Postsynaptic density-enriched glycoproteins 130 and 117 are also expressed in embryonic brain although the level of postsynaptic density-enriched glycoprotein 130 initially increases more rapidly than that of postsynaptic density-enriched glycoprotein 117. Peak values are observed at postnatal days 4 (postsynaptic density-enriched glycoprotein 117) and 9 (postsynaptic density-enriched glycoprotein 130). The level of post synaptic density-enriched glycoprotein 117 subsequently decreases to some 50% of the peak value by postnatal day 42. Immunocytochemical studies show that PAC 1 immunoreactivity in developing cerebral cortex, detectable by postnatal day 0, is primarily associated with the perikarya and dendrites of pyramidal cells. The immunoreactivity develops as patches of PAC 1-positive neurons, uniform staining of the cortex only being fully established after postnatal day 9. Double-immunofluorescence labelling studies of forebrain cultures prepared from embryonic day 18 animals shows that many, but not all, growth-associated protein 43-positive neurons exhibit PAC 1 immunoreactivity. Some non-neuronal cells also stain with the PAC 1 monoclonal antibody. The growth cones of cultured neurons exhibit PAC 1 immunoreactivity and the PAC 1 antigens are detected on immunodeveloped western blots of isolated growth cones. The PAC 1 epitope is intracellular, but immunoreactivity does not co-localize with F-actin as detected by rhod-amine-phalloidin or with tubulin immunoreactivity. Postsynaptic density-enriched glycoprotein 130 is readily detected on PAC 1 immunodeveloped western blots of forebrain cultures maintained for up to 14 days in vitro. Postsynaptic density-enriched glycoprotein 117 is only poorly expressed by these cultures. The PAC 1 glycoproteins are present in forebrain synaptic membranes and postsynaptic densities at an early stage of development. The synaptic membrane level of postsynaptic density-enriched glycoprotein 130 and postsynaptic density-enriched glycoprotein 117 increases markedly between postnatal days 3 and 8. The level of both glycoproteins detected in postsynaptic densities remain virtually constant from postnatal days 9-90. These results are consistent with functional roles for these molecules in neuronal and synapse development.

Erythromycin-induced immune hemolytic anemia.

A 3-year-old female receiving Pediazole (erythromycin ethylsuccinate and sulfisoxazole) for tonsillitis and otitis media developed severe hemolytic anemia. No serum drug-dependent antibodies could be demonstrated with an in vitro 'immune-complex' method using Pediazole, pure erythromycin ethylsuccinate or pure sulfisoxazole. However, a method using red cells coated with erythromycin base showed in vitro lysis of the erythromycin-coated red cells. This is only the second case of immune hemolytic anemia associated with erythromycin and the first where in vitro drug-dependent hemolysis was demonstrable.

The effects of pentylenetetrazol on molluscan neurons. I. Intracellular recording and stimulation.

The effects of the convulsant drug pentylenetetrazol (PTZ) were studied in neurons from isolated ganglia of the nudibranch molluscs, Archidoris montereyensis and Anisodoris nobilis, using conventional techniques of intracellular recording and constant current stimulation. PTZ was selected because it causes changes in the intracellularly recorded responses similar to the depolarization shifts recorded in mammalian epileptic neurons. When perfusate containing 120-140 mM PTZ is introduced, the intracellular recording is characterized by an initial silent period followed by small oscillations in membrane potential and irregular firing of spikes. Within 5-15 min, bursts of 2-3 spikes occurred followed by the appearance of episodic prolonged depolarizations with superimposed high-frequency spikes. In the presence of PTZ the prolonged depolarizations were evoked by intracellular stimulation and at the termination of conditioning hyperpolarizations. The prolonged depolarizations were also recorded in neurons isolated from all synpatic input by axonal ligation. Prolonged depolarizations showed threshold behavior since they can be terminated early by an intracellularly applied hyperpolarizing current.

The effects of pentylenetetrazol on molluscan neurons. II. Voltage clamp studies.

The effects of pentylenetetrazol (PTZ) upon the steady and transient outward ionic currents during PTZ-induced prolonged depolarizations were investigated using voltage clamp techniques. PTZ causes a 5-35% reduction in gL and a 40-60% reduction in steady-state gK. There is also a marked reduction in the activation of gA of Connor and Stevens6 at all clamp potentials; a shortening of the time constant for the inactivation of gA; and a 10-15 mV shift in the depolarizing direction of the curve relating the steady-state inactivation of gA to membrane potential. The equilibrium potentials for both gA and gK are depolarized by 20 mV in PTZ solution. Equation and voltage clamp data for normal repetitive firing were integrated with the normal and PTZ-alered data. Solution to these equations demonstrated: (1) normal repetitive firing in response to a constant current stimulus; and (2) PTZ-altered repetitive firing that was in the direction of, and for the most part, similar to the observed behavior.

Coherent optical target recognition through a phase distorting medium.

This paper presents a technique for distinguishing targets in a limited class, in case conventional imaging is unsuccessful due to a phase distorting medium closely overlaying the observation system. The procedure is to record the spatial density spectrum of a coherently illuminated object, construct its fourier transform, and then compare the resulting autocorrelation function with a limited number of possible autocorrelation functions. For a simple object, experimental results illustrate the effect that a close-lying phase distortion has on the conventional image as compared to that on the autocorrelation function.