Phenomenon of masking in the reproduction of tactile signals

The study of central masking and of its mechanisms is of interest in connection with the problem of transmitting information through the cutaneous communication channel. The subjects were children aged from seven to eight and from thirteen to fourteen with normal hearing, as well as deaf children. Latency and errors to localizing signals from isolated or paired action of four vibrators were determined in three series of experiments, using three, six and ten altenatives. A dependence of the precision of localization on the amount of information has been found: deteriorated identification is more pronounced in junior schoolchildren and in those with abnormal development. Matrices of the errors provide material for plottingildterial for plotting charts of convergence of afferent inputs. To elucidate the mechanisms of central masking, a comparison was made between the results of psychophysical and microphysiological experiments. Data analysis leads to the conslusion that the phenomenon of masking is determined by two factors: (1) the nature of the convergence of afferent inputs on the neuronal brain structures; (2) the level of formation of psychic operations which provide for singling out distinctive characteristics of signals, with subsequent decision regarding the certain class to which they belong, and with their recognition.     

Peroxynitrite increases the degradation of aconitase and other cellular proteins by proteasome

We report that exposure of aconitase to moderate concentrations of peroxynitrite, 3-morpholinosydnonimine (SIN-1; a superoxide- and nitric oxide-liberating substance), or hydrogen peroxide, inhibits the enzyme and enhances susceptibility to proteolytic digestion by the isolated 20 S proteasome. Exposure to more severe levels of oxidative stress, from these same agents, causes further inhibition of the enzymatic activity of aconitase but actually decreases its proteolytic breakdown by proteasome. It should be noted that the superoxide and nitric oxide liberated by SIN-1 decomposition react to form a steady flux of peroxynitrite. S-Nitroso-N-acetylpenicillamine, a compound that liberates nitric oxide alone, causes only a small loss of aconitase activity (25% or less) and has no effect on the proteolytic susceptibility of the enzyme. Proteasome also seems to be the main protease in cell lysates that can degrade aconitase after it has been oxidatively modified by exposure to peroxynitrite, SIN-1, or hydrogen peroxide. Using cell lysates isolated from K562 cells treated for several days with an antisense oligodeoxynucleotide to the initiation codon region of the C2 subunit of proteasome (a treatment which diminishes proteasome activity by 50-60%), the enhanced degradation of moderately damaged aconitase was essentially abolished. Other model proteins as well as complex mixtures of proteins, such as cell lysates, also exhibit enhanced proteolytic susceptibility after moderate SIN-1 treatment. Therefore we conclude that peroxynitrite reacts readily with proteins and that mild modification by peroxynitrite results in selective recognition and degradation by proteasome.     

Characterization of variable immunodominant antigens of Cowdria ruminantium by ELISA and immunoblots

Cross-immunization experiments have revealed a significant antigenic diversity of the isolate of Cowdria ruminantium which needs to be characterized for the development of vaccines. We identified polymorphic immunodominant antigens by ELISA and immunoblot. Using serum from a goat immune to the Gardel stock of Cowdria (isolated in Guadeloupe) adsorbed on antigen of the Senegal stock of this pathogen, distinct serogroups were revealed by ELISA among six isolates from different geographical origins. Furthermore, a goat serum directed against the Senegal stock and adsorbed on Gardel antigens was shown to be specific for the Senegal stock, thus confirming the existence of serotypes in Cowdria. The Major Antigenic Protein 1 (MAP1) of Cowdria was shown to have variable antigenic determinants. Also in a group of variable proteins ranging from 23 to 29 kDa, one antigen of 26-27 kDa had a determinant specific for the Gardel isolate. These polymorphic antigens may be relevant components of Cowdria ruminantium for a vaccine as the sera revealing these antigens originated from a goal surviving a lethal challenge. However, the presence of T-cell epitopes and the ability of the these antigens to confer protection to ruminants remain to be investigated. The production of a rabbit antiserum against this group of polypeptides will be of great use for their purification and for the screening of expression libraries.     

On the selective effects of a patterned masking stimulus.

Investigated previous findings which suggest that a patterned masking stimulus, presented immediately following tachistoscopic presentation of letter rows, produces large decrements in the recall of letters from the central positions in the rows but has little effect on recall from either end of the displays. 4 experiments with 92 undergraduate Ss confirm the existence of a selective masking effect. The effect was obtained following exposure durations which varied from 30-200 msec. and with both full- and partial-report techniques. Also the selective masking effect was limited to multiletter displays in that it was shown that single letters were masked equally well across the positions used for an entire row. Results suggest that both ends of multiletter displays are processed and identified before the center positions of the displays are processed. (French summary) (15 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

On the molecular basis and regulation of cellular capacitative calcium entry: roles for Trp proteins

During the last 2 years, our laboratory has worked on the elucidation of the molecular basis of capacitative calcium entry (CCE) into cells. Specifically, we tested the hypothesis that CCE channels are formed of subunits encoded in genes related to the Drosophila trp gene. The first step in this pursuit was to search for mammalian trp genes. We found not one but six mammalian genes and cloned several of their cDNAs, some in their full length. As assayed in mammalian cells, overexpression of some mammalian Trps increases CCE, while expression of partial trp cDNAs in antisense orientation can interfere with endogenous CCE. These findings provided a firm connection between CCE and mammalian Trps. This article reviews the known forms of CCE and highlights unanswered questions in our understanding of intracellular Ca2+ homeostasis and the physiological roles of CCE.     

In progressive nephropathies, overload of tubular cells with filtered proteins translates glomerular permeability dysfunction into cellular signals of interstitial inflammation

Progression to end-stage renal failure is the final common pathway of many forms of glomerular disease, independent of the type of initial insult. Progressive glomerulopathies have in common persistently high levels of urinary protein excretion and tubulointerstitial lesions at biopsy. Among the cellular mechanisms that may determine progression regardless of etiology, the traffic of excess proteins filtered from glomerulus in renal tubule may have functional importance by initiating interstitial inflammation in the early phase of parenchymal injury. This study analyzes the time course and sites of protein accumulation and interstitial cellular infiltration in two different models of proteinuric nephropathies. In remnant kidneys after 5/6 renal mass ablation, albumin and IgG accumulation by proximal tubular cells was visualized in the early stage, preceding interstitial infiltration of MHC-II-positive cells and macrophages. By double-staining, infiltrates developed at or near tubules containing intracellular IgG or luminal casts. This relationship persisted thereafter despite more irregular distribution of infiltrate. Similar patterns were found in an immune model (passive Heymann nephritis), indicating that the interstitial inflammatory reaction develops at the sites of protein overload, regardless of the type of glomerular injury. Osteopontin was detectable in cells of proximal tubules congested with protein in both models at sites of interstitial infiltration, and by virtue of its chemoattractive action this is likely mediator of a proximal tubule-dependent inflammatory pathway in response to protein load. Protein overload of tubules is a key candidate process translating glomerular protein leakage into cellular signals of interstitial inflammation. Mechanisms underlying the proinflammatory response of tubular cells to protein challenge in diseased kidney should be explored, as well as ways of limiting protein reabsorption/deposition to prevent consequent inflammation and progressive disease.     

On the relation between metacontrast masking and suppression of visible persistence.

Does the introduction of additional contours in a display sequence (an operation known to reduce the strength of suppression in metacontrast) also reduce suppression of visible persistence? In three experiments, duration of visible persistence was estimated by a method in which successful performance depends on the temporal integration of a pattern whose elements are displayed in two successive frames. In this procedure, the arrival of the trailing frame is known to exert a suppressive influence on the visible persistence of the leading frame. Embedding the elements of the leading frame within additional contours (a line grid) reduced the degree of suppression exerted by the trailing frame. This did not occur when the grid was part of the trailing display. We conclude that suppression of visible persistence and metacontrast masking belong to the same class of events. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Beyond the attentional blink: visual masking by object substitution

If 2 targets are to be identified among distractors displayed in rapid sequence, correct identification of the 1st target hinders identification of the 2nd. To obtain this attentional blink (AB), the 1st target must be masked with a simultaneous (integration) or a delayed (interruption) mask indifferently. In 3 experiments, it was shown that the 2nd target must also be masked, but that the precise form of masking is important: An AB occurs with interruption but not with integration masking. This nonequivalence of masking paradigms parallels that found in studies of masked priming, a phenomenon arguably related to the AB. The results are explained by a revised 2-stage model (M. M. Chun & M. C. Potter, 1995).     

Effects of frequency on free-field masking

As three-dimensional auditory displays become more prevalent, there will be an increasing need to understand the interactions that can be expected among spatially separated sounds. A two-alternative, forced-choice, adaptive staircase procedure was used to measure the detectability of a 165-ms click-train signal masked by a continuous Gaussian noise, as a function of the spatial separation between the signal and the masker in the free field. Horizontal separations within the horizontal plane and vertical separations within the median plane were examined for low-, mid-, and high-frequency stimuli. Masking was reduced by as much as 18 dB when the signal and masker were separated horizontally. Sizable reductions in masking (6-9 dB) were also observed for vertical separations. The largest reductions in masking were observed for the high-frequency stimuli. The data are compared with the results of headphone-based studies of binaural masking. Implications for the design of auditory displays are considered.     

On the cellular mechanism for the effect of acidosis on vascular tone

The role of smooth muscle [Ca2+]i and membrane potential for the relaxation to hypercapnic (increased CO2) and normocapnic (unchanged CO2) acidosis is not complete understood. It is often stated that membrane hyperpolarization plays an important role but this has not been vigorously tested. In this study we investigated isolated rat cerebral small arteries under isobaric conditions. Lumen diameter was measured simultaneously with either [Ca2+]i or membrane potential, and acidosis was induced by increasing PCO2 or reducing HCO3- of the bathing solution or by adding HCI to a nominally bicarbonate-free solution. Confocal microscopy verified loading of smooth muscle cells with fluorescent dyes. Acidosis always reduced myogenic tone at transmural pressures between 20 and 120 mmHg. Acidification at a transmural pressure of 40 mmHg caused an increase in diameter and a decrease in [Ca2+]i. This was also seen in the presence of L-NNA and after depolarization with 50 mM K+. The response to hypercapnic and normocapnic acidosis was similar. However, while hypercapnic acidosis caused hyperpolarization, normocapnic acidosis caused depolarization. Dilatation, decrease of [Ca2+]i and depolarization, was also seen with reduction of pH in bicarbonate-free solution. We conclude that the isobaric relaxation to both hypercapnic and normocapnic acidosis is most likely mediated by a reduction of [Ca2+]i. Membrane potential may on the other hand not play a major role for this reduction of [Ca2+]i and it is possible that molecular CO2 has an effect on the membrane potential.     

The BCR/ABL oncogene alters interaction of the adapter proteins CRKL and CRK with cellular proteins

The Philadelphia chromosome translocation generates a chimeric oncogene, BCR/ABL, which causes chronic myelogenous leukemia (CML). In primary leukemic neutrophils from patients with CML, the major tyrosine phosphorylated protein is CRKL, an SH2-SH3-SH3 adapter protein which has an overall homology of 60% to CRK, the human homologue of the v-crk oncogene. In cell lines transformed by BCR/ABL, CRKL was tyrosine phosphorylated, while CRK was not. We looked for changes in CRK- and CRKL-binding proteins in Ba/F3 hematopoietic cell lines which were transformed by BCR/ABL. Anti-CRK II or anti-CRKL immunoprecipitates were probed by far Western blotting with CRK II- or CRKL-GST fusion proteins to display CRK- and CRKL-coprecipitating proteins. There was a striking qualitative difference in the proteins coprecipitating with CRKL and CRK II. In untransformed cells, three major proteins coprecipitated with CRKL, identified as C3G, SOS and c-ABL. Each of these proteins was found to interact with the CRKL-SH3 domains, but not the SH2 domain. After BCR/ABL transformation, the CRKL SH3-domain binding proteins did not change, with the exception that BCR/ABL now coprecipitated with CRKL. Compared to CRKL, very few proteins coprecipitated with CRK II in untransformed, quiescent cells. After BCR/ABL transformation, both the CRKL- and CRK-SH2 domains bound to a new complex of proteins of approximate molecular weight 105-120 kDa. The major protein in this complex was identified as p120CBL. Thus, in these hematopoietic cell lines, CRKL is involved to a greater extent than CRK II in normal signaling pathways that involve c-ABL, C3G and SOS. In BCR/ABL-transformed cells, CRKL but not CRK II, appears to form complexes which potentially link BCR/ABL, c-ABL, C3G, and SOS to the protooncoprotein, p120CBL.     

Not sop Rejoinder to Hartley on masking by continuous noise.

Argues that the results discussed by L. R. Hartley (see record 1981-07079-001) are consistent with the composite model of E. C. Poulton (see record 1979-32826-001). Continuous noise and articulatory suppression both appear to reduce proactive interference, presumably by masking the echoic storage of the words in working memory that are carried over from the previous list. (17 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Photoacoustic analysis of proteins: volumetric signals and fluorescence quantum yields

A series of proteins has been examined using time-resolved, pulsed-laser volumetric photoacoustic spectroscopy. Photoacoustic waveforms were collected to measure heat release for calculation of fluorescence quantum yields, and to explore the possibility of photoinduced nonthermal volume changes occurring in these protein samples. The proteins studied were the green fluorescent protein (GFP); intestinal fatty acid binding protein (IFABP), and adipocyte lipid-binding protein (ALBP), each labeled noncovalently with 1-anilinonaphthalene-8-sulfonate (1,8-ANS) and covalently with 6-acryloyl-2-(dimethylamino)naphthalene (acrylodan); and acrylodan-labeled IFABP and ALBP with added oleic acid. Of this group of proteins, only the ALBP labeled with 1,8-ANS showed significant nonthermal volume changes at the beta = 0 temperature (approximately 3.8 degrees C) for the buffer used (10 mM Tris-HCI, pH 7.5) (beta is the thermal cubic volumetric expansion coefficient). For all of the proteins except for acrylodan-labeled IFABP, the fluorescence quantum yields calculated assuming simple energy conservation were anomalously high, i.e., the apparent heat signals were lower than those predicted from independent fluorescence measurements. The consistent anomalies suggest that the low photoacoustic signals may be characteristic of fluorophores buried in proteins, and that photoacoustic signals derive in part from the microenvironment of the absorbing chromophore.     

Identification of cellular proteins that bind the central conserved region of p53

The bacterial fusion protein between glutathione S-transferase and the central conserved region of human p53(GST-p53) was purified and fixed on the beads and then used in the binding assay with radiolabeled cell extract from human hepatocarcinoma cell line, Hep3B. The binding assay disclosed the presence of cellular proteins that interact with GST-p53 but not with GST. SV40 large T antigen abrogated the bindings of two cellular proteins with molecular weights of 50 kda and 40 kda. The binding of the proteins to p53 was observed in a cell cycle-dependent manner. These two proteins are candidate cellular proteins which regulate the function of p53.     

Effects of stapedius-muscle contractions on the masking of auditory-nerve responses

There has been little exploration of the mechanisms by which stapedius muscle contractions reduce the masking of responses to high-frequency sounds by low-frequency sounds. To fill this gap in knowledge, controlled stapedius contractions were elicited with direct shocks in anesthetized cats, and measurements were made of the effects of these contractions on the masking of single auditory-nerve fibers and on the attenuation of middle-ear transmission. The results show that the stapedius-induced reductions of masking can be much larger than the attenuations of low-frequency sound. With a 300-Hz band of masking noise centered at 500 Hz, and signal tones at 6 or 8 kHz, unmasking effects over 40 dB were observed for sounds 100 dB SPL or less. The data suggest that much larger unmasking might occur. The observed unmasking can be explained completely by a linear stapedius-induced attenuation of sound transmission through the middle ear and a nonlinear growth rate of masking for auditory-nerve fibers. No central effects are required. It is argued that the reduction of the upward spread of masking is probably one of the most important functions of the stapedius muscle.     

Effect of background components on spatial-frequency masking

Previous studies of spatial-frequency masking and adaptation have shown that the contrast-detection threshold elevates maximally when the test spatial frequency is the same as the masking (or adapting) frequency but changes only slightly when they are separated by two or more octaves. At low spatial frequencies, however, the peak of the threshold-elevation function does not obey this rule: there is a well-established peak shift in the threshold-elevation functions toward higher spatial frequencies. We investigated whether this shift might be due to the masking effects caused by the background field, which contributes energy at the very low end of the spectrum. We first measured the effect of a 3-cycles/deg (c/deg) mask on detection of a range of test frequencies, compared with unmasked detection thresholds. We then measured the combined effect of a 2-c/deg and a 3-c/deg mask on detection, compared with detection with just the 2-c/deg mask. The comparison in the second case still tests the effect of the 3-c/deg mask, but the presence of the hidden 2-c/deg mask causes the peak masking effect to shift toward higher frequencies. This result provides a proof of concept for the hypothesis that the peak shift at low spatial frequencies is caused by the low-frequency energy in the background field, which is present in both masked and unmasked conditions. A five-parameter quantitative model of frequency masking is presented that describes the pure contrast-detection function, the frequency-masking functions at mask frequencies of 0.25, 0.5, 2, and 3 c/deg, and the peak-shift phenomenon.     

Amplification of the inflammatory cellular redox state by human immunodeficiency virus type 1-immunosuppressive tat and gp160 proteins

In the course of our studies on oxidative stress as a component of pathological processes in humans, we showed that microintrusion into cells with microcapillary and ultramicroelectrochemical detection could mimic many types of mechanical intrusion leading to an instant (0.1 s) and high (some femtomoles) burst release of H2O2. Specific inhibitors of NADPH enzymes seem to support the assumption that this enzyme is one of the main targets of our experiments. Also, human immunodeficiency virus type 1 (HIV-1) gp160 inhibits the cooperative response of uninfected T cells as well as Tat protein release by infected cells does. In this study, we analyzed in real time, lymphocyte per lymphocyte, the T-cell response following activation in relation to the redox state. We showed that the immunosuppressive effects of HIV-1 Tat and gp160 proteins and oxidative stress are correlated, since the native but not the inactivated Tat and gp160 proteins inhibit the cellular immune response and enhance oxidative stress. These results are consistent with a role of the membrane NADPH oxidase in the cellular response to immune activation.     

Interaction of cellular proteins with the leukemia specific fusion proteins DEK-CAN and SET-CAN and their normal counterpart, the nucleoporin CAN

The recurrent chromosomal translocation (6;9) is associated with acute myeloid leukemia and results in expression of the DEK-CAN fusion protein. This oncoprotein consists of almost the entire DEK protein fused to the C-terminal two-thirds of the CAN protein. In much the same way, CAN is fused to SET in a patient with acute undifferentiated leukemia, producing a SET-CAN fusion protein. Interestingly, CAN is associated with the nuclear pore complex (NPC) and we recently established its crucial role in nucleocytoplasmic transport processes and cell cycle progression. As a first step in the biochemical analysis of the oncogenic mechanism associated with translocation (6;9), we set out to identify proteins that interact with CAN and its fusion proteins. We found that two proteins specifically co-immunoprecipitate with CAN. One had a molecular mass of 88 kDa protein (CC88) and was determined to associate with the central region of CAN that contains several protein interaction motifs. A second protein of 112 kDa (CC112) was found to interact with the C-terminal nucleoporin-specific repeat of CAN, a region that is supposed to function in nucleocytoplasmic transport. CC112 also interacts with the DEK-CAN and SET-CAN fusion proteins. This finding suggests that CC112 may contribute an essential function to the leukemogenic effect of DEK-CAN and SET-CAN.     

Suppression and the upward spread of masking

The purpose of this study is to clarify the role of suppression in the growth of masking when a signal is well above the masker in frequency (upward spread of masking). Classical psychophysical models assume that masking is primarily due to the spread of masker excitation, and that the nonlinear upward spread of masking reflects a differential growth in excitation between the masker and the signal at the signal frequency. In contrast, recent physiological studies have indicated that upward spread of masking in the auditory nerve is due to the increasing effect of suppression with increasing masker level. This study compares thresholds for signals between 2.4 and 5.6 kHz in simultaneous and nonsimultaneous masking for conditions in which the masker is either at or well below the signal frequency. Maximum differences between simultaneous and nonsimultaneous masking were small (< 6 dB) for the on-frequency conditions but larger for the off-frequency conditions (15-32 dB). The results suggest that suppression plays a major role in determining thresholds at high masker levels, when the masker is well below the signal in frequency. This is consistent with the conclusions of physiological studies. However, for signal levels higher than about 40 dB SPL, the growth of masking for signals above the masker frequency is nonlinear even in the nonsimultaneous-masking conditions, where suppression is not expected. This is consistent with an explanation based on the compressive response of the basilar membrane, and confirms that suppression is not necessary for nonlinear upward spread of masking.