Overexpression of the high-affinity Fcgamma receptor (CD64) is associated with leukocyte dysfunction in sepsis.

The morbidity and mortality from sepsis and multiple organ dysfunction syndrome (MODS) continues to be high. An increase in FcgammaRI+ (CD64+) monocytes was demonstrated in septic patients, and an association between cell number, their secretory activity, and poor outcome has been described. In the present investigation further characterization of CD64+ leukocytes has been attempted. The study was aimed at examining the phagocytic activity (PA) and reactive oxygen species (ROS) production by monocytes (Mo) and neutrophils (Neu) in sepsis and sepsis-induced acute respiratory distress syndrome (ARDS) related to the pattern of CD64 expression. Twenty-three post-traumatic or post-operative male and female patients with sepsis were enrolled. The control group consisted of 10 healthy volunteers. Arterial blood samples were taken during the septic episode for flow cytometric analysis of surface leukocyte antigens, phagocytosis, and ROS production. CD64 expression on Mo and Neu was markedly increased in septic patients (P = 0.029 and P = 0.0005), and even more in sepsis with ARDS (P = 0.011). In healthy individuals, PA of CD64+ Neu was higher, than of CD64- cells (P = 0.021). In septic patients, decreased PA was detected in CD64+ Mo and Neu (P = 0.013 and P = 0.040, respectively). CD64+ Neu of patients in ARDS exhibited the most prominent PA depression (P = 0.048). ROS production in non-separated Mo and Neu was increased in sepsis (P = 0.026 and P = 0.004, respectively). In healthy individuals CD64+ Neu and stimulated CD64+ Mo demonstrated increased ROS synthesis compared to matched CD64- cells (P = 0.001 and P = 0.042, respectively). Although ROS production by CD64+ leukocytes in sepsis was also increased compared to CD64- cells, significantly less ROS was generated compared to healthy subjects (P = 0.021). In conclusion, overexpression of CD64 on blood Mo and Neu from patients with sepsis and ARDS is associated with depressed PA and decreased oxidative response.

An unexpected extended conformation for the third TPR motif of the peroxin PEX5 from Trypanosoma brucei.

A number of helix-rich protein motifs are involved in a variety of critical protein-protein interactions in living cells. One of these is the tetratrico peptide repeat (TPR) motif that is involved, amongst others, in cell cycle regulation, chaperone function and post-translation modifications. So far, these helix-rich TPR motifs have always been observed to be a compact unit of two helices interacting with each other in antiparallel fashion. Here, we describe the structure of the first three TPR-motifs of the peroxin PEX5 from Trypanosoma brucei, the causative agent of sleeping sickness. Peroxins are proteins involved in peroxisome, glycosome and glyoxysome biogenesis. PEX5 is the receptor of the proteins targeted to these organelles by the "peroxisomal targeting signal-1", a C-terminal tripeptide called PTS-1. The first two of the three TPR-motifs of T. brucei PEX5 appear to adopt the canonical antiparallel helix hairpin structure. In contrast, the third TPR motif of PEX5 has a dramatically different conformation in our crystals: the two helices that were supposed to form a hairpin are folded into one single 44 A long continuous helix. Such a conformation has never been observed before for a TPR motif. This raises interesting questions including the potential functional importance of a "jack-knife" conformational change in TPR motifs.

Hydrogen transfer between methanogens and fermentative heterotrophs in hyperthermophilic cocultures.

Interactions involving hydrogen transfer were studied in a coculture of two hyperthermophilic microorganisms: Thermotoga maritima, an anaerobic heterotroph, and Methanococcus jannaschii, a hydrogenotrophic methanogen. Cell densities of T. maritima increased 10-fold when cocultured with M. jannaschii at 85 degrees C, and the methanogen was able to grow in the absence of externally supplied H(2) and CO(2). The coculture could not be established if the two organisms were physically separated by a dialysis membrane, suggesting the importance of spatial proximity. The significance of spatial proximity was also supported by cell cytometry, where the methanogen was only found in cell sorts at or above 4.5 microm in samples of the coculture in exponential phase. An unstructured mathematical model was used to compare the influence of hydrogen transport and metabolic properties on mesophilic and hyperthermophilic cocultures. Calculations suggest the increases in methanogenesis rates with temperature result from greater interactions between the methanogenic and fermentative organisms, as evidenced by the sharp decline in H(2) concentration in the proximity of a hyperthermophilic methanogen. The experimental and modeling results presented here illustrate the need to consider the interactions within hyperthermophilic consortia when choosing isolation strategies and evaluating biotransformations at elevated temperatures.

Auditory psychophysics and perception.

In this review of auditory psychophysics and perception, we cite some important books, research monographs, and research summaries from the past decade. Within auditory psychophysics, we have singled out some topics of current importance: Cross-Spectral Processing, Timbre and Pitch, and Methodological Developments. Complex sounds and complex listening tasks have been the subject of new studies in auditory perception. We review especially work that concerns auditory pattern perception, with emphasis on temporal aspects of the patterns and on patterns that do not depend on the cognitive structures often involved in the perception of speech and music. Finally, we comment on some aspects of individual difference that are sufficiently important to question the goal of characterizing auditory properties of the typical, average, adult listener. Among the important factors that give rise to these individual differences are those involved in selective processing and attention.

Influence of spectral locus and F0 changes on the pitch and timbre of complex tones.

Harmonic complex tones comprising components in different spectral regions may differ considerably in timbre. While the pitch of "residue" tones of this type has been studied extensively, their timbral properties have received little attention. Discrimination of F0 for such tones is typically poorer than for complex tones with "corresponding" harmonics [A. Faulkner, J. Acoust. Soc. Am. 78, 1993-2004 (1985)]. The F0 DLs may be higher because timbre differences impair pitch discrimination. The present experiment explores effects of changes in spectral locus and F0 of harmonic complex tones on both pitch and timbre. Six normally hearing listeners indicated if the second tone of a two-tone sequence was: (1) same, (2) higher in pitch, (3) lower in pitch, (4) same in pitch but different in "something else," (5) higher in pitch and different in "something else," or (6) lower in pitch and different in "something else" than the first. ("Something else" is assumed to represent timbre.) The tones varied in spectral loci of four equal-amplitude harmonics m, m + 1, m + 2, and m + 3 (m = 1,2,3,4,5,6) and ranged in F0 from 200 to 200 +/- 2n Hz (n = 0,1,2,4,8,16,32). Results show that changes in F0 primarily affect pitch, and changes in spectral locus primarily affect timbre. However, a change in spectral locus can also influence pitch. The direction of locus change was reported as the direction of pitch change, despite no change in F0 or changes in F0 in the opposite direction for delta F0 < or = 0-2%. This implies that listeners may be attending to the "spectral pitch" of components, or to changes in a timbral attribute like "sharpness," which are construed as changes in overall pitch in the absence of strong F0 cues. For delta F0 > or = 2%, the direction of reported pitch change accord with the direction of F0 change, but the locus change continued to be reported as a timbre change. Rather than spectral-pitch matching of corresponding components, a context-dependent spectral evaluation process is thus implied in discernment of changes in pitch and timbre. Relative magnitudes of change in derived features of the spectrum such as harmonic number and F0, and absolute features such as spectral frequencies are compared. What is called "spectral pitch," contributes to the overall pitch, but also appears to be an important dimension of the multidimensional percept, timbre.

Studies in auditory timing: 1. Simple patterns.

Listeners' accuracy in discriminating one temporal pattern from another was measured in three psychophysical experiments. When the standard pattern consisted of equally timed (isochronic) brief tones, whose interonset intervals (IOIs) were 50, 100, or 200 msec, the accuracy in detecting an asynchrony or deviation of one tone in the sequence was about as would be predicted from older research on the discrimination of single time intervals (6%-8% at an IOI of 200 msec, 11%-12% at an IOI of 100 msec, and almost 20% at an IOI of 50 msec). In a series of 6 or 10 tones, this accuracy was independent of position of delay for IOIs of 100 and 200 msec. At 50 msec, however, accuracy depended on position, being worst in initial positions and best in final positions. When one tone in a series of six has a frequency different from the others, there is some evidence (at IOI = 200 msec) that interval discrimination is relatively poorer for the tone with the different frequency. Similarly, even if all tones have the same frequency but one interval in the series is made twice as long as the others, temporal discrimination is poorer for the tones bordering the longer interval, although this result is dependent on tempo or IOI. Results with these temporally more complex patterns may be interpreted in part by applying the relative Weber ratio to the intervals before and after the delayed tone. Alternatively, these experiments may show the influence of accent on the temporal discrimination of individual tones.

Studies in auditory timing: 2. Rhythm patterns.

Listeners discriminated between 6-tone rhythmic patterns that differed only in the delay of the temporal position of one of the tones. On each trial, feedback was given and the subject's performance determined the amount of delay on the next trial. The 6 tones of the patterns marked off 5 intervals. In the first experiment, patterns comprised 3 "short" and 2 "long" intervals: 12121, 21121, and so forth, where the long (2) was twice the length of a short (1). In the second experiment, patterns were the complements of the patterns in the first experiment and comprised 2 shorts and 3 longs: 21212, 12212, and so forth. Each pattern was tested 45 times (5 positions of the delayed tone x 3 tempos x 3 replications). Consistent with previous work on simple interval discrimination, absolute discrimination (delta t in milliseconds) was poorer the longer the intervals (i.e., the slower the tempo). Measures of relative discrimination (delta t/t, where t was the short interval, the long interval, or the average of 2 intervals surrounding the delayed tone) were better the slower the tempo. Beyond these global results, large interactions of pattern with position of the delayed tone and tempo suggest that different models of performance are needed to explain behavior at the different tempos. A Weber's law model fit the slow-tempo data better than did a model based on positions of "natural accent" (Povel & Essens, 1985).

Detection of binaural signals partially masked by a reproducible noise maker: the influence of the phase angle alpha.

The present experiment was an attempt to examine the detectability of partially masked tonal signals in a background of masking noise in both homophasic and masking conditions as the angle of addition between the signal and masker was manipulated. In the present study, the masking noises were samples of reproducible ("frozen") noise.

Poststimulatory pitch shifts for pure tones.

Changes in the pitch of a short tone pulse (25 msec, 1000 HZ), following a leading tone, were measured at various leading-tone frequencies and for various time intervals between the leading tone and the tone pulse. The results show that poststimulatory pitch shifts away from the pitch of the leading tone are significant and reproducible. It is suggested that poststimulatory pitch shifts may influence the results of various psychoacoustic experiments on pitch perception.

Acoustical research in the life sciences.

This paper briefly reviews research progress during the past 50 years in physiological and psychological acoustics. Special attention is paid to the physiology of the auditory system, sound conduction in the ear, cochlear mechanics, masking, auditory localization, psychoacoustic behavior in animals, speech perception, medical applications, coupling between psychophysics and physiology, temporal aspects of sensory attitudes, and ecological acoustics.

Some figural properties of auditory patterns.

Listeners identified one of six permutations of three frequencies, presented as brief three-note melodies. Identification performance remained high in spite of transposition of the original three frequencies throughout a two-octave range, so long as the musical intervals or frequency ratios between the adjacent pairs of frequencies remained constant. Even when those intervals were compressed or expanded, while remaining about equal to each other, identification was quite good for the range between the lowest and highest frequency of no more than approximately 1/3 octave. Performance decreased sharply when the span was much wider. Unequal intervals, where the low and middle frequencies were closer together or farther apart than the middle and high frequencies, did not retain good identification performance. When the three-tone patterns were embedded in longer sequences of seven or eight tones, the identification performance was best when the pattern occurred at the beginning or the end of the sequence, and when the range of frequencies from which the irrelevant background tones were chosen lay outside the range of pattern frequencies. Under conditions where the background frequencies were fixed and the pattern frequencies were moved, thus combining the manipulation of embedding with that of transposition of the pattern, overlap of pattern and background frequencies was still the principal cause of deterioration in performance. The findings are related to some analogies to the perceptual rules of Gestalt theory, as well as to certain aspects of musical practice.