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At least 55 records · Page 3Linked to original sources
PubMed1987

Compound action potential offset and onset tuning curves generated by simultaneous masking in the mongolian gerbil. Effects of varying the intensity of the probe stimulus from 55 to 85 dB SPL.

Action potential tuning curves (TCs) were produced by simultaneous masking of both the onset and offset of tone bursts. Offset TCs are much more sharply tuned than onset TCs when both responses are generated by stimuli at SPLs of 55 to 75 dB. The onset TC tip and the offset TC high frequency tip thresholds accurately reflect increases of the probe SPL, but the low frequency tip and the peak of the offset TC compress this change. With increasing probe SPL, the onset TC and low frequency TC tip (but not the high frequency tip and peak) of the offset TC become progressively detuned.

Acoustic Stimulation↗
PubMed2006

Functional and structural characterization of Spl proteases from Staphylococcus aureus.

Staphylococcus aureus is the major cause of nosocomial infections world-wide, with increasing prevalence of community-acquired diseases. The recent dramatic increase in multi-antibiotic resistance, including resistance to the last-resort drug, vancomycin, together with the lack of an effective vaccine highlight the need for better understanding of S.aureus pathogenicity. Comparative analysis of available bacterial genomes allows for the identification of previously uncharacterized S.aureus genes with potential roles in pathogenicity. A good example is a cluster of six serine protease-like (spl) genes encompassed in one operon, which encode for putative proteases with similarity to staphylococcal glutamylendopeptidase (V8 protease). Here, we describe an efficient expression system for the production of recombinant SplB and SplC proteases in Escherichia coli, together with structural and functional characterization of the purified enzymes. A unique mechanism of cytoplasm protection against activity of misdirected SplB was uncovered. Apparently, the co-translated signal peptide maintains protease latency until it is cleaved by the signal peptidase during protein secretion. Furthermore, the crystal structure of the SplC protease revealed a fold resembling that of the V8 protease and epidermolytic toxins. Arrangement of the active site cleft and substrate-binding pocket of SplC explains the mechanism of enzyme latency and suggests that some Spl proteases possess restricted substrate specificity similar to that of the V8 protease and epidermolytic toxins.

Amino Acid Sequence↗
PubMed1999

Effects of prolonged oral reading on F0, SPL, subglottal pressure and amplitude characteristics of glottal flow waveforms.

The effects of prolonged (5x45 minute) reading (vocal loading) on fundamental frequency (F0), sound pressure level (SPL), subglottal (intraroral) pressure (p), and two glottal flow waveform parameters (AC amplitude of glottal flow, f, and negative peak amplitude of differentiated flow (d) of normal female and male subjects (N = 80) were studied. Two rest (morning and noon) and three loading (two in the morning and one in the afternoon) samples were recorded and analyzed. The glottal waveforms were obtained by inverse filtering of the acoustic pressure waveforms of speaking voice samples. The analyses were based on measurement and inverse filtering of the first stressed syllable of "paappa" words repeated 3x5 times for normal, as soft as possible, and as loud as possible phonation. In normal phonation the parameter values changed statistically significantly due to loading. In many cases the values obtained in the morning samples changed after the first loading session. This is interpreted as a vocal "warming-up effect." Especially in soft phonation p, d, and f were sensitive indicators of vocal loading. In both normal and soft phonation, the SPL, p, d, and f values tended to rise due to prolonged reading in the morning and afternoon samples, indicating increased effort (normal phonation) and a rise in the phonatory threshold (soft phonation). The lunch break vocal rest ("rest effect") considerably affected the parameter values in many cases.

Adolescent↗
PubMed2005

Shielding design for the front end of the CERN SPL.

CERN is designing a 2.2-GeV Superconducting Proton Linac (SPL) with a beam power of 4 MW, to be used for the production of a neutrino superbeam. The SPL front end will initially accelerate 2 x 10(14) negative hydrogen ions per second up to an energy of 120 MeV. The FLUKA Monte Carlo code was employed for shielding design. The proposed shielding is a combined iron-concrete structure, which also takes into consideration the required RF wave-guide ducts and access labyrinths to the machine. Two beam-loss scenarios were investigated: (1) constant beam loss of 1 Wm(-1) over the whole accelerator length and (2) full beam loss occurring at various locations. A comparison with results based on simplified approaches is also presented.

Computer Simulation↗
PubMed2001

The nuclear factor kappa B and Spl binding sites do not appear to be involved in virus suppression by CD8 T lymphocytes.

CD8 T lymphocytes suppress primate lentivirus replication in a non-cytotoxic manner. This antiviral activity, mediated by a CD8 cell antiviral factor (CAF), involves an arrest in viral transcription. Present studies indicate that the CD8 T cell non-cytotoxic antiviral activity and CAF inhibit the replication of an SIV mutant virus lacking the nuclear factor kappa B (NF-kappaB) and Spl binding domains. The results strongly suggest that the NF-B and Spl binding sites are not involved in virus suppression by CD8 T lymphocytes.

Animals↗
PubMed1998

Validity and repeatability of level-independent HL to SPL transforms.

OBJECTIVE: The purpose of this study was to evaluate the reliability and validity of the real ear to coupler difference (RECD) and the real ear to dial difference (REDD) in predicting real ear SPL (RESPL). DESIGN: The RESPL, RECD, and REDD were measured in the right ear of 24 normal-hearing subjects using probe microphone equipment and both insert and supra-aural earphones. The phones and probe tube were removed and replaced, and the RECD and REDD were remeasured. RESULTS: RESPL was predicted using the RECD for insert earphone data and the REDD for supra-aural earphone data. Reliability estimates were calculated as the difference between test and retest values for the RECD and REDD. Validity estimates were calculated as the difference between measured and predicted RESPL. Results indicate that the RECD and REDD have equal and high reliability and validity in predicting RESPL. CONCLUSIONS: It is concluded that the RECD and REDD may be used as level-independent HL to SPL transforms as a substitute for in situ audiometric procedures.

Adult↗
PubMed2001

HERP, a novel heterodimer partner of HES/E(spl) in Notch signaling.

HERP1 and -2 are members of a new basic helix-loop-helix (bHLH) protein family closely related to HES/E(spl), the only previously known Notch effector. Like that of HES, HERP mRNA expression is directly up-regulated by Notch ligand binding without de novo protein synthesis. HES and HERP are individually expressed in certain cells, but they are also coexpressed within single cells after Notch stimulation. Here, we show that HERP has intrinsic transcriptional repression activity. Transcriptional repression by HES/E(spl) entails the recruitment of the corepressor TLE/Groucho via a conserved WRPW motif, whereas unexpectedly the corresponding-but modified-tetrapeptide motif in HERP confers marginal repression. Rather, HERP uses its bHLH domain to recruit the mSin3 complex containing histone deacetylase HDAC1 and an additional corepressor, N-CoR, to mediate repression. HES and HERP homodimers bind similar DNA sequences, but with distinct sequence preferences, and they repress transcription from specific DNA binding sites. Importantly, HES and HERP associate with each other in solution and form a stable HES-HERP heterodimer upon DNA binding. HES-HERP heterodimers have both a greater DNA binding activity and a stronger repression activity than do the respective homodimers. Thus, Notch signaling relies on cooperation between HES and HERP, two transcriptional repressors with distinctive repression mechanisms which, either as homo- or as heterodimers, regulate target gene expression.

3T3 Cells↗
PubMed2004

her3, a zebrafish member of the hairy-E(spl) family, is repressed by Notch signalling.

her3 encodes a zebrafish bHLH protein of the Hairy-E(Spl) family. During embryogenesis, the gene is transcribed exclusively in the developing central nervous system, according to a fairly simple pattern that includes territories in the mesencephalon/rhombencephalon and the spinal cord. In all territories, the her3 transcription domain encompasses regions in which neurogenin 1 (neurog1) is not transcribed, suggesting regulatory interactions between the two genes. Indeed, injection of her3 mRNA leads to repression of neurog1 and to a reduction in the number of primary neurones, whereas her3 morpholino oligonucleotides cause ectopic expression of neurog1 in the rhombencephalon. Fusions of Her3 to the transactivation domain of VP16 and to the repression domain of Engrailed show that Her3 is indeed a transcriptional repressor. Dissection of the Her3 protein reveals two possible mechanisms for transcriptional repression: one mediated by the bHLH domain and the C-terminal WRPW tetrapeptide; and the other involving the N-terminal domain and the orange domain. Gel retardation assays suggest that the repression of neurog1 transcription occurs by binding of Her3 to specific DNA sequences in the neurog1 promoter. We have examined interrelationships of her3 with members of the Notch signalling pathway by the Gal4-UAS technique and mRNA injections. The results indicate that Her3 represses neurog1 and, probably as a consequence of the neurog1 repression, deltaA, deltaD and her4. Moreover, Her3 represses its own transcription as well. Surprisingly, and in sharp contrast to other members of the E(spl) gene family, transcription of her3 is repressed rather than activated by Notch signalling.

Animals↗
PubMedDate not supplied

Plasmodium falciparum: production of human antibodies specific for the MSP-3 protein in the Hu-SPL-SCID mouse.

Human immunity against Plasmodium falciparum malaria is mediated by IgG antibodies. One of the major targets of protective antibodies is the MSP-3 protein. Anti-MSP-3 human monoclonal antibodies could therefore be valuable for passive immunotherapy, particularly of drug resistant malaria. Human monoclonal antibodies were previously produced in the Hu-SPL-SCID model reconstituted with human splenocytes, immunized by highly immunogenic neo-antigen or a recall antigen. We report here that this model can also be successfully employed to induce human antibody-secreting cells specific of low immunogenicity neo-antigens, such as MSP-3. These cells represent a new and valuable source of human monoclonal anti-malaria antibodies.

Animals↗
PubMed2002

Drosophila Sir2 is required for heterochromatic silencing and by euchromatic Hairy/E(Spl) bHLH repressors in segmentation and sex determination.

Yeast SIR2 is a NAD+-dependent histone deacetylase required for heterochromatic silencing at telomeres, rDNA, and mating-type loci. We find that the Drosophila homolog of Sir2 (dSir2) also encodes deacetylase activity and is required for heterochromatic silencing, but unlike ySir2, is not required for silencing at telomeres. We show that dSir2 interacts genetically and physically with members of the Hairy/Deadpan/E(Spl) family of bHLH euchromatic repressors, key regulators of Drosophila development. dSir2 is an essential gene whose loss of function results in both segmentation defects and skewed sex ratios, associated with reduced activities of the Hairy and Deadpan bHLH repressors. These results indicate that Sir2 in higher organisms plays an essential role in both euchromatic repression and heterochromatic silencing.

Animals↗
PubMed1983

Effect of spermine, ethylenediamine tetraacetate, urea, and high salt on the activity of ribonuclease SPL on Mg2+- containing undenatured total E. coli and rat liver RNAs.

Using RNAase SPL, a recently described nuclease from bovine seminal plasma, that can recognize certain Mg2+-dependent structural features in native naturally occurring RNAs, it is shown that these features are wholly or partially destroyed by 8 M urea, 1 mM spermine, 0.35 M KCl or NaCl, and 10 mM EDTA, urea and spermine being the most effective and EDTA the least; these features are not destroyed by heating and rapid cooling unless a medium with a high ionic strength is used. Since the buffer used so far for reconstitution of ribosomes contains 0.35 M KCl, it seems possible that a partial opening up of ribosomal RNAs may be necessary for ribosome assembly.

Animals↗
PubMed2005

Inhibition of neurogenesis at the zebrafish midbrain-hindbrain boundary by the combined and dose-dependent activity of a new hairy/E(spl) gene pair.

The intervening zone (IZ) is a pool of progenitor cells located at the midbrain-hindbrain boundary (MHB) and important for MHB maintenance, midbrain-hindbrain growth and the generation of midbrain-hindbrain neurons. Recently, we implicated the Hairy/E(spl) transcription factor Her5 in the formation of the medial (most basal) part of the IZ (MIZ) in zebrafish; the molecular bases for lateral IZ (LIZ) formation, however, remain unknown. We now demonstrate that her5 is physically linked to a new family member, him, displaying an identical MHB expression pattern. Using single and double knockdowns of him and her5, as well as a him+her5 deletion mutant background (b404), we demonstrate that Him and Her5 are equally necessary for MIZ formation, and that they act redundantly in LIZ formation in vivo. We show that these processes do not involve cross-regulation between Him and Her5 expression or activities, although Him and Her5 can heterodimerize with high affinity. Increasing the function of one factor when the other is depleted further shows that Him and Her5 are functionally interchangeable. Together, our results demonstrate that patterning and neurogenesis are integrated by the her5-him gene pair to maintain a progenitor pool at the embryonic MHB. We propose a molecular mechanism for this process where the global 'Him+Her5' activity inhibits ngn1 expression in a dose-dependent manner and through different sensitivity thresholds along the medio-lateral axis of the neural plate.

Amino Acid Sequence↗
PubMed1999

her4, a zebrafish homologue of the Drosophila neurogenic gene E(spl), is a target of NOTCH signalling.

her4 encodes a zebrafish bHLH protein of the hairy-E(spl) family. The gene is transcribed in a complex pattern in the developing nervous system and in the hypoblast. During early neurogenesis, her4 expression domains include the regions of the neural plate from which primary neurons arise, suggesting that the gene is involved in directing their development. Indeed, misexpression of specific her4 variants leads to a reduction in the number of primary neurons formed. The amino-terminal region of her4, including the basic domain, and the region between the putative helix IV and the carboxy-terminal tetrapeptide wrpw are essential for this effect, since her4 variants lacking either of these regions are non-functional. However, the carboxy-terminal wrpw itself is dispensable. We have examined the interrelationships between deltaD, deltaA, notch1, her4 and neurogenin1 by means of RNA injections. her4 is involved in a regulatory feedback loop which modulates the activity of the proneural gene neurogenin, and as a consequence, of deltaA and deltaD. Activation of notch1 leads to strong activation of her4, to suppression of neurogenin transcription and, ultimately, to a reduction in the number of primary neurons. These results suggest that her4 acts as a target of notch-mediated signals that regulate primary neurogenesis.

Animals↗
PubMed2000

Barbu: an E(spl) m4/m(alpha)-related gene that antagonizes Notch signaling and is required for the establishment of ommatidial polarity.

The Notch signaling pathway is required, in concert with cell-type-specific transcriptional regulators and other signaling processes, for multiple cell fate decisions during mesodermal and ectodermal tissue development. In many instances, Notch signaling occurs initially in a bidirectional manner and then becomes unidirectional upon amplification of small inherent differences in signaling activity between neighboring cells. In addition to ligands and extracellular modulators of the Notch receptor, several intracellular proteins have been identified that can positively or negatively influence the activity of the Notch pathway during these dynamic processes. Here, we describe a new gene, Barbu, whose product can antagonize Notch signaling activity during Drosophila development. Barbu encodes a small and largely cytoplasmic protein with sequence similarity to the proteins encoded by the transcription units m4 and m(alpha) of the E(spl) complex. Ectopic expression studies with Barbu provide evidence that Barbu can antagonize Notch during lateral inhibition processes in the embryonic mesoderm, sensory organ specification in imaginal discs and cell type specification in developing ommatidia. Barbu loss-of-function mutations cause lethality and disrupt the establishment of planar polarity and photoreceptor specification in eye imaginal discs, which may also be a consequence of altered Notch signaling activities. Furthermore, in the embryonic neuroectoderm, Barbu expression is inducible by activated Notch. Taken together, we propose that Barbu functions in a negative feed-back loop, which may be important for the accurate adjustment of Notch signaling activity and the extinction of Notch activity between successive rounds of signaling events.

Amino Acid Sequence↗
PubMed2002

Hairy/E(spl)-related (Her) genes are central components of the segmentation oscillator and display redundancy with the Delta/Notch signaling pathway in the formation of anterior segmental boundaries in the zebrafish.

We have examined the expression of a Hairy/E(spl)-related (Her) gene, her7, in the zebrafish and show that its expression in the PSM cycles similarly to her1 and deltaC. A decrease in her7 function generated by antisense oligonucleotides disrupts somite formation in the posterior trunk and tail, and disrupts the dynamic expression domains of her1 and deltaC, suggesting that her7 plays a role in coordinating the oscillations of neighboring cells in the presomitic mesoderm. This phenotype is reminiscent of zebrafish segmentation mutants with lesions in genes of the Delta/Notch signaling pathway, which also show a disruption of cyclic her7 expression. The interaction of HER genes with the Delta/Notch signaling system was investigated by introducing a loss of her7 function into mutant backgrounds. This leads to segmental defects more anterior than in either condition alone. Combining a decrease of her7 function with reduction of her1 function results in an enhanced phenotype that affects all the anterior segments, indicating that Her functions in the anterior segments are also partially redundant. In these animals, gene expression does not cycle at any time, suggesting that a complete loss of oscillator function had been achieved. Consistent with this, combining a reduction of her7 and her1 function with a Delta/Notch mutant genotype does not worsen the phenotype further. Thus, our results identify members of the Her family of transcription factors that together behave as a central component of the oscillator, and not as an output. This indicates, therefore, that the function of the segmentation oscillator is restricted to the positioning of segmental boundaries. Furthermore, our data suggest that redundancy between Her genes and genes of the Delta/Notch pathway is in part responsible for the robust formation of anterior somites in vertebrates.

Animals↗
PubMedDate not supplied

Further studies of the effects of continuous white noise of moderate intensity (70--80 dB SPL) on the cochlea in young guinea pigs. Time course and distribution of hair cell degeneration.

Guinea pigs aged one week were exposed to white noise at a maximum of 76 dB SPL for 7 days and were then killed 3, 8 and 16 weeks later for histological examination of the cochlea by the surface preparation method. Appreciable increases in outer hair cell losses were observed in the apical turn 3/3 1/2, chiefly in the outer two rows, between the 3rd and 8th week, but not between the 8th and 16th week. No significant losses were seen in control groups corresponding to 3- and 8-week periods, although in the control group of 16 weeks' survival, small deficits, attributable to natural ageing, were seen in the apical half-turn, 3 1/2.

Acoustic Stimulation↗
PubMed1981

The SPL hearing meter.

An instrument, the SPL Hearing Meter, was devised for the measurement of hearing threshold with a hearing aid earphone in order to make a direct comparison between the hearing threshold and the output sound pressure level of a hearing aid. The author found this a handy tool for selection and adjustment of hearing aids.

Audiology↗
PubMed1981

Magnitude estimates of loudness adaption at 60 dB SPL.

Previous reports indicate that adaptation measured by the technique of successive magnitude estimations is not found above 30 dB SL (Fishken et al., 1977; and others). Although the present study confirmed this finding at 60 dB SPL for the original procedure, it was found that a modification of the magnitude estimation procedure resulted in significant loudness adaptation at this intensity. Introduction of a 20-dB increment for 5 s, every 30 s, resulted in a marked and statistically significant decline in successive loudness judgements of the 60-dB tone. In addition, the decline in reported loudness magnitude was cumulative and progressive throughout the 7-min duration of the monaural stimulus. This is typical of classical results found with simultaneous dichotic loudness balances.

Adult↗