The yield of alkenols and cycloalkenols is substantially improved by carrying out the reaction of olefins with formaldehyde in the presence of selected catalysts. In accordance with one embodiment, alk-3-en-1-ols are produced in good yields from isobutylene and formaldehyde in the presence of organic carboxylic acid salts of Group IB metals.

The Organization of the Cochlear Receptor

Acoustic overexposure can cause a permanent loss of auditory nerve fibers without destroying cochlear sensory cells, despite complete recovery of cochlear thresholds (Kujawa and Liberman 2009), as measured by gross neural potentials such as the auditory brainstem response (ABR). To address this nominal paradox, we recorded responses from single auditory nerve fibers in guinea pigs exposed to this type of neuropathic noise (4- to 8-kHz octave band at 106 dB SPL for 2 h). Two weeks postexposure, ABR thresholds had recovered to normal, while suprathreshold ABR amplitudes were reduced. Both thresholds and amplitudes of distortion-product otoacoustic emissions fully recovered, suggesting recovery of hair cell function. Loss of up to 30% of auditory-nerve synapses on inner hair cells was confirmed by confocal analysis of the cochlear sensory epithelium immunostained for pre- and postsynaptic markers. In single fiber recordings, at 2 wk postexposure, frequency tuning, dynamic range, postonset adaptation, first-spike latency and its variance, and other basic properties of auditory nerve response were all completely normal in the remaining fibers. The only physiological abnormality was a change in population statistics suggesting a selective loss of fibers with low- and medium-spontaneous rates. Selective loss of these high-threshold fibers would explain how ABR thresholds can recover despite such significant noise-induced neuropathy. A selective loss of high-threshold fibers may contribute to the problems of hearing in noisy environments that characterize the aging auditory system.

Noise-induced cochlear neuropathy is selective for fibers with low spontaneous rates

The availability of transgenic and mutant lines makes the mouse a valuable model for study of the inner ear, and a powerful window into cochlear function can be obtained by recordings from single auditory nerve (AN) fibers. This study provides the first systematic description of spontaneous and sound-evoked discharge properties of AN fibers in mouse, specifically in CBA/CaJ and C57BL/6 strains, both commonly used in auditory research. Response properties of 196 AN fibers from CBA/CaJ and 58 from C57BL/6 were analyzed, including spontaneous rates (SR), tuning curves, rate versus level functions, dynamic range, response adaptation, phase-locking, and the relation between SR and these response properties. The only significant interstrain difference was the elevation of high-frequency thresholds in C57BL/6. In general, mouse AN fibers showed similar responses to other mammals: sharpness of tuning increased with characteristic frequency, which ranged from 2.5 to 70 kHz; SRs ranged from 0 to 120 sp/s, and fibers with low SR (<1 sp/s) had higher thresholds, and wider dynamic ranges than fibers with high SR. Dynamic ranges for mouse high-SR fibers were smaller (<20 dB) than those seen in other mammals. Phase-locking was seen for tone frequencies <4 kHz. Maximum synchronization indices were lower than those in cat but similar to those found in guinea pig.

Response properties of single auditory nerve fibers in the mouse.

Traditionally the auditory system was considered a hard-wired sensory system; this view has been challenged in recent years in light of the plasticity of other sensory systems, particularly the visual and somatosensory systems. Practical experience in clinical audiology together with the use of prosthetic devices, such as cochlear implants, contributed significantly to the present view on the plasticity of the central auditory system, which was originally based on data obtained in animal experiments. The loss of auditory receptors, the hair cells, results in profound changes in the structure and function of the central auditory system, typically demonstrated by a reorganization of the projection maps in the auditory cortex. These plastic changes occur not only as a consequence of mechanical lesions of the cochlea or biochemical lesions of the hair cells by ototoxic drugs, but also as a consequence of the loss of hair cells in connection with aging or noise exposure. In light of the aging world population and the increasing amount of noise in the modern world, understanding the plasticity of the central auditory system has its practical consequences and urgency. In most of these situations, a common denominator of central plastic changes is a deterioration of inhibition in the subcortical auditory nuclei and the auditory cortex. In addition to the processes that are elicited by decreased or lost receptor function, the function of nerve cells in the adult central auditory system may dynamically change in the process of learning. A better understanding of the plastic changes in the central auditory system after sensory deafferentation, sensory stimulation, and learning may contribute significantly to improvement in the rehabilitation of damaged or lost auditory function and consequently to improved speech processing and production.

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Plastic changes in the central auditory system after hearing loss, restoration of function, and during learning.

Collagen IV is a major structural component of all basal laminae (BLs). Six collagen IV alpha chains are present in mammals; alpha 1 and alpha 2(IV) are broadly expressed in embryos and adults, whereas alpha 3-6(IV) are restricted to a defined subset of BLs. In the glomerular BL of the kidney, the alpha 1 and alpha 2(IV) chains are replaced by the alpha 3-5(IV) chains as development proceeds. In humans, mutation of the collagen alpha 3, alpha 4, or alpha 5(IV) chain genes results in a delayed onset renal disease called Alport syndrome. We show here that mice lacking collagen alpha 3(IV) display a renal phenotype strikingly similar to Alport syndrome: decreased glomerular filtration (leading to uremia), compromised glomerular integrity (leading to proteinuria), structural changes in glomerular BL, and glomerulonephritis. Interestingly, numerous changes in the molecular composition of glomerular BL precede the onset of renal dysfunction; these include loss of collagens alpha 4 and alpha 5(IV), retention of collagen alpha 1/2(IV), appearance of fibronectin and collagen VI, and increased levels of perlecan. We suggest that these alterations contribute, along with loss of collagen IV isoforms per se, to renal pathology.

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Molecular and functional defects in kidneys of mice lacking collagen alpha 3(IV): implications for Alport syndrome.

Frequency-specific auditory brainstem responses (ABR) (frequency range 2-31.5 kHz) were used to describe age-dependent alterations in frequency sensitivity in CBA/ca (to 30 months) and C57BL/6J (to 16 months) mouse genotypes. The two strains displayed an age-related loss similar to that of humans, with a primary decline in high-frequency sensitivity. CBA mice showed a slow, yet gradual decrease in sensitivity to high- followed by low-frequency until 18 months of age and a rapid deterioration at all frequencies thereafter. C57 mice demonstrated precocious aging in auditory sensitivity in an unsteady rather than gradual manner. By testing the same individuals on repeated occasions it was shown that, for C57 mice, the degenerative process was more precipitous with three phases, and that the individual variability was larger than that of CBA mice. It is suggested that the two mouse genotypes can be used to express the different aspects of human presbycusis in individual variability and modes of gradual or staggered progression.

Age-related loss of auditory sensitivity in two mouse genotypes.

Eighth nerve fiber firing features in normal-hearing rabbits.

The shift in latency of wave V in ABR upon the reversal of stimulus phase was investigated in a normal-hearing reference material (65 ears) and in 20 ears of conductive hearing loss, 29 ears of steep high-frequency hearing loss and 17 ears of acoustic neurinoma or cerebellopontine angle tumor. In addition, reproducibility was studied in the reference material. The stimulus was a 2.0-kHz haversine wave at 75 or 35 dB nHL delivered at the rate of 20 Hz. 2000 responses were averaged for each stimulus phase. Electrodes were placed on the vertex and on ipsilateral mastoid. Stimulus wave form was determined in a 6-cc coupler and in a few cases with a miniature electrete microphone in the ear canal. In the reference material, a significant difference of the wave V latency between the condensation (C) and rarefaction (R) stimulus was observed. When taking the absolute difference, the mean value was 0.15 ms at 75 dB nHL. This time difference corresponds to a frequency of 3-4 kHz. In high frequency cochlear loss, the C-R difference increased in proportion to the downward shift in frequency of the high frequency slope of the audiogram. In conductive hearing loss, the C-R difference was similar to that of the reference material. In retrocochlear cases, the C-R difference was unpredictable, but was remarkably often small compared with the V latency. It was concluded that the difference in wave V latency between C and R clicks provides information about the excitation pattern in the inner ear but it is not reliable enough to give more than a rough estimate of the individual frequency of generation of ABR. The results are arguments against the use of the alternating stimulus phase as a routine procedure.

Auditory Brainstem Response (ABR) to Rarefaction and Condensation Clicks in Normal and Abnormal Ears

The stapedius reflex test, brainstem audiometry and the opto-vestibular tests for identifying acoustic neurinomas (AN) were evaluated and compared in a study of 21 patients with radiologically or surgically verified AN and a pure tone average not exceeding 60 dB HL. The stapedius reflex test results were interpreted according to the criteria developed at this clinic. The stimuli for the auditory brainstem response (ABR) were 2 kHz haversine waves and 4 kHz square waves. The vestibular examination consisted of a caloric test and the recording of eye-tracking and gaze nystagmus. In the cases studied the stapedius reflex test gave 1 false-negative result and ABR none. The ENG gave 3 false-negatives whereas the results of speech discrimination tests were misleading in no fewer than 1/3 of the cases. The results of the different tests were directly correlated but correlation coefficients did not exceed 0.65. Tumours larger than 15–20 mm showed a different test pattern than those below that size: stapedius refl...

Stapedius Reflex Test, Brainstem Audiometry and Opto-Vestibular Tests in Diagnosis of Acoustic Neurinomas: A Comparison of Test Sensitivity in Patients with Moderate Hearing Loss

Rabbits were exposed to 2‐ to 7‐kHz noise either for a short duration at a high sound‐pressure level (15 or 30 min at 115 dB SPL), or a long duration at a low level (512 h at 85 dB SPL). The high‐level exposure produced a hearing loss in the frequency range 2–6 kHz, whereas the low‐level exposure gave maximum hearing loss at 12–20 kHz. The 115‐dB exposure caused significantly more damage to inner hair cells than the 85‐dB exposure. The implications of the present results for evaluating audiograms, equal‐energy hypothesis, risk criteria, and subjective auditory features are pointed out.

Erik Borg

Papers

Age-related loss of auditory sensitivity in two mouse genotypes.

Eighth nerve fiber firing features in normal-hearing rabbits.

Auditory Brainstem Response (ABR) to Rarefaction and Condensation Clicks in Normal and Abnormal Ears

Stapedius Reflex Test, Brainstem Audiometry and Opto-Vestibular Tests in Diagnosis of Acoustic Neurinomas: A Comparison of Test Sensitivity in Patients with Moderate Hearing Loss

Noise level, inner hair cell damage, audiometric features, and equal‐energy hypothesis