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PubMed2005

Tumor-suppressive maspin regulates cell response to oxidative stress by direct interaction with glutathione S-transferase.

Maspin, a novel serine protease inhibitor, suppresses tumor progression in several cancer models, including an in vivo model for prostate cancer bone metastasis. However, the molecular mechanism of maspin remains illusive, primarily because its molecular targets are unknown. To this end, we used a full-length maspin cDNA bait to screen against both a primary prostate tumor cDNA prey library and a HeLa cDNA prey library by the yeast two-hybrid method. We found that heat shock protein 90, glutathione S-transferase (GST), and heat shock protein 70 interacted with maspin with the highest frequencies. We confirmed the maspin/GST interaction using purified proteins, human epithelial cell lines, and human prostate tissues. A maspin variant that has a point mutation of Arg(340) to Ala (Mas(R340A)) showed a significantly decreased affinity for GST. Although purified maspin had no effect on the activity of purified GST in vitro, intracellular interaction between endogenous maspin and GST correlated with an elevated total GST activity in both MDA-MB-435- and DU145-derived stably transfected cells. Consistently, tumor cells treated with purified wild type maspin, but not Mas(R340A), enhanced cellular GST activity. Maspin expression in cancer cell lines also correlated with decreased basal levels of reactive oxygen species (ROS). Furthermore, H(2)O(2) treatment not only induced GST expression but also increased intracellular maspin/GST interaction, which was inversely correlated with the level of ROS generation. Conversely, maspin knockdown by small interfering RNA increased the basal, as well as H(2)O(2)-induced, ROS generation. Furthermore, the maspin effect on ROS generation was completely abolished by a GST inhibitor, indicating an essential role of GST in maspin-mediated cellular response to oxidative stress. Consistently, oxidative stress-induced vascular endothelial growth factor A expression was significantly inhibited in maspin-expressing cells. Together, our data suggest a new mechanism by which maspin, through its direct interaction with GST, may inhibit oxidative stress-induced ROS generation and vascular endothelial growth factor A induction, thus preventing further adverse effects on tumor genetics and stromal reactivity.

Alanine↗

PubMed2005

Renormalized waves and discrete breathers in Beta-Fermi-Pasta-Ulam chains.

We demonstrate via numerical simulation that in the strongly nonlinear limit the Beta-Fermi-Pasta-Ulam (Beta-FPU) system in thermal equilibrium behaves surprisingly like weakly nonlinear waves in properly renormalized normal variables. This arises because the collective effect of strongly nonlinear interactions effectively renormalizes linear dispersion frequency and leads to effectively weak interaction among these renormalized waves. Furthermore, we show that the dynamical scenario for thermalized Beta-FPU chains is spatially highly localized discrete breathers riding chaotically on spatially extended, renormalized waves.

Journal Article↗

PubMed1983

Binding of phosphorylcholine by non-immunoglobulin molecules on mouse B cells.

Phosphorylcholine (PC), a molecule found in the cell wall of most serotypes of pneumococcus, has been used extensively as a probe for the study of network interactions during immune responses. The frequency of B lymphocytes capable of interacting with PC has not been directly examined. We used immunofluorescence to study the binding of PC and monoclonal anti-TEPC15 anti-idiotopic antibodies to murine lymphocytes. In addition to identifying PC-specific Ig molecules, PC was bound by a non-Ig molecule on the surface of a relatively large subset of B cells; this non-Ig marker shared an idiotypic determinant with the PC-binding myeloma protein HOPC8 (H8). PC-bearing R36a pneumococci bind to a similar subset of lymphocytes. This binding is inhibited specifically by PC coupled to bovine serum albumin and also by a monoclonal anti-H8 antibody. We suggest that bacterial interaction with B cells through non-Ig molecules capable of binding a dominant antigen like PC may possess functional significance, possibly during the events that lead to antibody induction by these microorganisms.

Animals↗

PubMed1983

Spatial-frequency-specific inhibition in cat striate cortex cells.

Responses to single and multiple spatial frequency gratings were recorded from eighty-eight cat striate cortex cells. A cell's response to a grating of its optimum spatial frequency (f) was examined both alone and in the presence of gratings of 1/4, 1/3, 1/2, 2, 3 and 4f, respectively. Some 97% (thirty-seven of thirty-eight) of all simple cells showed significant inhibition of f by one or more of the other frequencies. This inhibition was usually fairly narrowly tuned, with only one or two spatial frequencies producing significant inhibition. Thirty-four simple cells were maximally inhibited by a higher frequency, three by a lower spatial frequency. By far the most common interaction was a considerable inhibition of f by 2f and/or 3f. Of the thirty-seven simple cells showing inhibition to a complex grating, seventeen responded in a manner dependent on the relative phases of the two components. Some showed only inhibition of f; in others, the response to f was either increased or decreased, depending on the relative phase of the two frequencies. The other twenty simple cells showed phase-independent inhibition: the inhibition was of approximately equal amplitude regardless of the relative phase angle of the two grating components. Such phase-independent inhibition cannot be accounted for by linear summation within classical cortical receptive fields. Only eighteen of forty-eight (38%) of the complex cells showed significant inhibition of f by one or more other spatial frequencies. Fourteen of these (29%) were maximally inhibited by a higher spatial frequency, four (8%) by a lower spatial frequency. Inhibitory interactions in complex cells were never dependent on the relative phase of the two component gratings. Six simple cells (16%) and fourteen complex cells (29%) showed significant facilitation of the response to f by one or more (most often lower) spatial frequencies. This enhanced response was greater than the sum of the responses to each component alone, was usually broadly tuned for spatial frequency, and did not depend on the relative phase of the two components. It thus differs from the increased response sometimes seen in a phase-dependent interaction. Some of the observed spatial-frequency-specific interactions are incompatible with either a strictly hierarchical model of cortical architecture or a simple linear filter model of visual cortical processing. The asymmetry of inhibition suggests that it subserves some function other than (or in addition to) the narrowing of spatial frequency tuning functions.

Action Potentials↗

PubMed1983

Relationship between social interactions and sexual maturation in female Saguinus oedipus oedipus.

4 female Saguinus oedipus oedipus were paired with strange, unrelated males while 5 remained in their natal family groups. A comparison of the frequency of selected social interactions involving these females when sexually immature versus mature was made. The frequency of sexual and affiliative interactions in male-female pairs was basically unchanged by the female's maturation. Mother-daughter interactions were also not changed in a consistent fashion by the daughters' maturation. Females with strange, unrelated males, either alone or as part of their natal group, displayed increases in marking behavior in association with sexual maturation.

Animals↗

PubMed2006

Frequency specific impairment of automatic pitch change detection by fMRI acoustic noise: an MEG study.

The loud acoustic noise produced by the magnetic resonance scanner is a major source of interference in auditory fMRI research. Whole-head magnetoencephalography (MEG) was used to investigate the interaction between the frequency range of auditory stimulation and fMRI acoustic noise. Pure tones and 3-harmonic complexes varying between 240 and 1240 Hz in frequency were presented while participants attended to a silent subtitled film. Continuous fMRI acoustic noise was presented during half of the blocks. The activity in six regions of interest was analyzed in 100-200 and 200-300 ms time windows to evaluate the magnetic counterparts of the mismatch negativity (MMN) and P3a brain responses. The results suggested that fMRI noise significantly reduced the amplitude of these responses. The effect of the noise on the automatic processing of the tones was more prominent for the tones with frequencies higher than 500 Hz. It is recommended that in the MMN protocols using continuous fMRI acquisition the sound stimuli should be spectrally separated from the fMRI scanner noise spectrum.

Acoustic Stimulation↗

PubMed2006

Vibronic coupling in organic semiconductors: the case of fused polycyclic benzene-thiophene structures.

The nature of vibronic coupling in fused polycyclic benzene-thiophene structures has been studied using an approach that combines high-resolution gas-phase photoelectron spectroscopy measurements with first-principles quantum-mechanical calculations. The results indicate that in general the electron-vibrational coupling is stronger than the hole-vibrational coupling. In acenedithiophenes, the main contributions to the hole-vibrational coupling arise from medium- and high-frequency vibrations. In thienobisbenzothiophenes, however, the interaction of holes with low-frequency vibrations becomes significant and is larger than the corresponding electron-vibrational interaction. This finding is in striking contrast with the characteristic pattern in oligoacenes and acenedithiophenes in which the low-frequency vibrations contribute substantially only to the electron-vibrational coupling. The impact of isomerism has been studied as well.

Journal Article↗

PubMed1995

Effects of association, frequency, and stimulus quality on naming words in the presence or absence of pseudowords.

According to classical dual-route theory, effects of associative priming and frequency on the naming of printed words arise from lexical access and should be weak or absent when word names are assembled prelexically. Assembled naming would be more likely in a shallow orthography, especially in the presence of nonwords. This hypothesis was examined with the shallow Serbo-Croatian orthography. Interactions between association, frequency, and stimulus quality were also examined in both Serbo-Croatian and English. Contrary to classical dual-route theory, both lexical effects were found for naming words in Serbo-Croatian, with or without nonwords. Neither interaction was significant in Serbo-Croatian and only association x quality was significant in English. Discussion focused on (a) the claim that lexical effects on naming in a shallow orthography constitute prima facie evidence against either prelexical phonology or the orthographic depth hypothesis, and (b) the possible factorization of frequency and active associative knowledge in naming words.

Adolescent↗

PubMed1992

Analysis of electromagnetic heating patterns inside a cryopreserved organ.

Computer analysis of the induced electromagnetic field and heating distribution inside cryopreserved organs subjected to electromagnetic illumination at frequencies of 84 MHz, 434 MHz and 2.45 GHz were carried out using a spherical model for the organ, with special reference to heating in a single-mode resonant cavity. The interaction between the frequency of the incident field and the size and dielectric properties of the sample was investigated. It is shown that uniform heating of organs is likely to be achieved at lower frequencies, as might be expected. However, the ratio between the power penetration depth for plane waves and the size of the organ is not a sufficient basis on which to judge quantitatively the uniformity of the power absorption. Hot or cold spots can occur within the organ even when this ratio is greater than unity; the wavelength in the material is also an important factor. The results from this study indicate that the use of a resonant cavity as a heating applicator has advantages over plane-wave illumination. A sharp upper limit can be set to the frequency suitable for rapid and uniform heating of a given organ.

Animals↗

PubMed1989

Normative thresholds in the 8- to 20-kHz range as a function of age.

Using a prototype high-frequency audiometer, auditory thresholds in the 8- to 20-kHz range were obtained from 240 subjects ranging in age from 10-60 years. These measurements were obtained in interest of developing a normative database for frequencies above 8 kHz, and to evaluate intersubject variability as a function of age. An analysis of variance (ANOVA) revealed significant effects of frequency, age, and sex, and a significant frequency-by-age interaction. The largest changes in sensitivity with age occurred between 40 to 59 years. Below approximately 15 kHz, the intersubject variability of threshold estimates increased as a function of both age and frequency. Further analysis revealed that the age-related changes in variability were related to absolute thresholds rather than to age per se. When data are converted to dB HL (relative to the youngest group tested), the region of maximum hearing loss shifts to lower frequencies with increasing age, and threshold shifts with age are greatest in the 13- to 17-kHz range.

Adolescent↗

PubMed2005

Feeding patterns and performance of cows in controlled cow traffic in automatic milking systems.

Two groups of dairy cows monitored from 3 to 19 wk postpartum were subjected to 2 different cow traffic routines in an automatic milking system with control gates and an open waiting area. Using different time settings in the control gates, the groups of cows were separated by average milking frequency; cows in the high milking frequency routine had a minimum of 4 h between milkings (MF(4)) and were milked 3.2 +/- 0.1 times daily, whereas cows in the low milking frequency routine had at least 8 h between milkings (MF8) and were milked 2.1 +/- 0.1 times daily. Cows in the 2 groups were switched to the opposite milking frequency control for wk 18 and 19. The increased milking frequency resulted in a higher milk yield of about 9% through 16 wk of early lactation Although the higher milk yield was not significant when measured as energy-corrected milk, significant interactions of milking frequency and study period for milk yield and energy-corrected milk yield were consistent with a yield response when cows were milked more frequently. Meal criteria estimated for each individual cow were used to group feeding visits into meals. During MF4, cows fed in fewer meals per day and had longer meals than during MF8. The control gates were used efficiently, with only a few passages not resulting in actual meals. Although the voluntary meal intervals seemed to be short, the average milking frequency was far below that theoretically possible. This was explained by individual differences in milking frequency and long intervals from when a cow was redirected in a control gate until it arrived in the milking unit. A wide individual range in the voluntary interval between the first and the second meal in the milking cycle suggests that fixed time limits for control gates set on group level have no justifiable biological basis. It was also concluded that primiparous cows were well adapted to the automatic milking system after 2 wk in the barn.

Animal Feed↗

PubMed1996

Feeding frequency affects cultured rat pituitary cells in low gravity.

In this report, we describe the results of a rat pituitary cell culture experiment done on STS-65 in which the effect of cell feeding on the release of the six anterior pituitary hormones was studied. We found complex microgravity-related interactions between the frequency of cell feeding and the quantity and quality (i.e. biological activity) of some of the six hormones released in flight. Analyses of growth hormone (GH) released from cells into culture media on different mission days using gel filtration and ion exchange chromatography yielded qualitatively similar results between ground and flight samples. Lack of cell feeding resulted in extensive cell clumping in flight (but not ground) cultures. Vigorous fibroblast growth occurred in both ground and flight cultures fed 4 times. These results are interpreted within the context of autocrine and/or paracrine feedback interactions. Finally, the payload specialist successfully prepared a fresh trypsin solution in microgravity, detached the cells from their surface and reinserted them back into the culture chamber. These cells reattached and continued to release hormone in microgravity. In summary, this experiment shows that pituitary cells are microgravity sensitive and that coupled operations routinely associated with laboratory cell culture can also be accomplished in low gravity.

Adrenocorticotropic Hormone↗

PubMed2006

Selection on gamete recognition proteins depends on sex, density, and genotype frequency.

Gamete recognition proteins can evolve at astonishing rates and lie at the heart of reproductive isolation and speciation in diverse taxa. However, the source of selection driving this evolution remains unknown. We report on how the sperm bindin genotype influences reproductive success under natural conditions. An interaction between genotype frequency and spawning density determines how sperm bindin genotype influences reproductive success. Common genotypes are selected under sperm-limited conditions, whereas rare genotypes are selected under conditions of intense sperm competition and sexual conflict. Variation in the evolutionary rates of bindin may reflect historic differences in sperm availability.

Alleles↗

PubMed2005

Cortico-cortical coupling in Parkinson's disease and its modulation by therapy.

The role of changes in inter-regional cortical synchronization in the pathophysiology of Parkinson's disease and the mechanism of action of dopaminergic therapy and high frequency subthalamic nucleus (STN) stimulation is unclear. We hypothesized that synchronization between distributed cortical areas would correlate with parkinsonism and that changes in synchronization with treatment would correlate with improvements in parkinsonism. To this end, we recorded scalp EEG in parkinsonian patients off treatment (16 patients, 31 sides) and then separately during high frequency stimulation (HFS) of the STN (16 patients, 31 sides) and following drug treatment (12 patients, 24 sides). All recordings were made at rest to avoid the confounding effects of differences in task performance. The motor Unified Parkinson's Disease Rating Scale (UPDRS) score was determined in each state. We found that EEG-EEG coherence over approximately 10-35 Hz correlated with the severity of parkinsonism, and reductions in cortical coupling over this frequency range with both l-dopa and STN stimulation correlated with clinical improvement. These results suggest that both dopaminergic therapy and STN stimulation may support the restoration of normal cortico-cortical interactions in the frequency domain. This mechanistic similarity may underscore the strong clinical correlation between the therapeutic effects of these treatment modalities.

Adult↗

PubMed2001

The effects of age and gender on sleep EEG power spectral density in the middle years of life (ages 20-60 years old).

The effects of age and gender on sleep EEG power spectral density were assessed in a group of 100 subjects aged 20 to 60 years. We propose a new statistical strategy (mixed-model using fixed-knot regression splines) to analyze quantitative EEG measures. The effect of gender varied according to frequency, but no interactions emerged between age and gender, suggesting that the aging process does not differentially influence men and women. Women had higher power density than men in delta, theta, low alpha, and high spindle frequency range. The effect of age varied according to frequency and across the night. The decrease in power with age was not restricted to slow-wave activity, but also included theta and sigma activity. With increasing age, the attenuation over the night in power density between 1.25 and 8.00 Hz diminished, and the rise in power between 12.25 and 14.00 Hz across the night decreased. Increasing age was associated with higher power in the beta range. These results suggest that increasing age may be related to an attenuation of homeostatic sleep pressure and to an increase in cortical activation during sleep.

Adult↗

PubMed1988

The social supports of suicide attempters: the different roles of family and friends.

The social support patterns of a sample of 101 suicide attempters were compared with the patterns of a control sample on the basis of structured interview data. Network characteristics and the extent of support in different functional categories were examined as to their absolute and relative power to discriminate between the suicide attempters and the controls. A clear separation of the functions of kin and of friends/acquaintances emerged. The crucial difference between the attempters and the controls lay in the number of friends with whom the subjects had agreeable everyday interactions and in the number of kin that provided crisis support, both psychological and instrumental. Other support differences between the two groups were of secondary importance. While there was no overall difference in the frequency of social interactions between the two groups, the size of the social network differed greatly. Consequences for the conceptualization and measurement of social support as well as for the prevention of suicidal behavior are discussed.

Adult↗

PubMed2005

Word frequency and the lateralization of lexical processes.

Despite the extensive clinical and neuropsychological evidence for major differences in language function between the left and right hemispheres, it has proven difficult to demonstrate reliable differences in lexical processing. It is particularly surprising that frequency has been found to have no differential effects upon word recognition in the hemispheres, in view of the evidence that this variable has significant effects upon lexical processing. It is possible, however, that any interaction between word frequency and hemispheric processes is too subtle or too complex to be revealed by the simple dichotomous studies previously attempted. This study manipulated word frequency across seven levels in an effort to provide a fine-grained insight into the relationship between word frequency and lexical processing in the hemispheres. The results revealed a clear additivity between visual field and word frequency across all levels of frequency, for both RT and errors. Such findings create difficulties for the interpretation of studies of lateralized lexical access in general, and are particularly hard to reconcile with lateral asymmetries revealed in other aspects of lexical processing. It is proposed that a resolution of this problem may depend upon the development of theories that emphasise the notion of laterally distributed word representations, rather than discrete lexical structures on each side of the brain.

Adolescent↗

PubMed1994

Interactions between cladribine (2-chlorodeoxyadenosine) and standard antileukemic drugs in primary cultures of human tumor cells from patients with acute myelocytic leukemia.

The semiautomated fluorometric microculture cytotoxicity assay (FMCA), based on the measurement of fluorescence generated from cellular hydrolysis of fluorescein diacetate (FDA) to fluorescein in microtiter plates, was used for in vitro evaluation of Cladribine (2-chlorodeoxyadenosine, CdA) interactions with five standard antileukemic drugs: amsacrine (Am), etoposide (VP16), daunorubicin (Dnr), cytosine arabinoside (AraC), and mitoxantrone (Mit). Samples from 31 patients with acute myelocytic leukemia (AML) were tested with continuous drug exposure. A large heterogeneity with respect to cell kill was observed for all combinations tested. An additive model provided a significantly better fit of the data compared to the effect of the most active single agent of the combination (Dmax) only for CdA+AraC. When the frequency of additive and synergistic interactions were calculated according to the multiplicative concept for drug interactions, the highest frequencies were observed for CdA+AraC and CdA+Dnr. This interaction pattern was confirmed by isobologram analysis. Cross-resistance analysis revealed high correlations between CdA and AraC whereas the correlations were weaker between CdA and the other drugs. The highest frequency of synergistic interactions was obtained for AraC+CdA, despite their cross-resistance. Of the non-cross-resistant drugs tested, Dnr appears to be the most effective adjunct to CdA in terms of interactions at the cellular level.

Adolescent↗