bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein database searches using compositionally adjusted substitution matrices
Authors: Altschul Stephen F. , Wootton John C. , Gertz E. Michael , Agarwala Richa , Morgulis Aleksandr , Schäffer Alejandro A. , Yu Yi‐Kuo 
Published: October 2005

Almost all protein database search methods use amino acid substitution matrices for scoring, optimizing, and assessing the statistical significance of sequence alignments. Much care and effort has therefore gone into constructing substitution matrices, and the quality of search results can depend strongly upon the choice of the proper matrix. A long‐standing problem has been the comparison of sequences with biased amino acid compositions, for which standard substitution matrices are not optimal. To address this problem, we have recently developed a general procedure for transforming a standard matrix into one appropriate for the comparison of two sequences with arbitrary, and possibly differing compositions. Such adjusted matrices yield, on average, improved alignments and alignment scores when applied to the comparison of proteins with markedly biased compositions.Here we review the application of compositionally adjusted matrices and consider whether they may also be applied fruitfully to general purpose protein sequence database searches, in which related sequence pairs do not necessarily have strong compositional biases. Although it is not advisable to apply compositional adjustment indiscriminately, we describe several simple criteria under which invoking such adjustment is on average beneficial. In a typical database search, at least one of these criteria is satisfied by over half the related sequence pairs. Compositional substitution matrix adjustment is now available in NCBI's protein–protein version of blast.
High-synchrony cochlear compound action potentials evoked by rising frequency-swept tone bursts
Authors: Shore Susan E. , Nuttall Alfred L. 
Published: October 2005

The auditory compound action potential (CAP) represents synchronous VIIIth nerve activity. Clicks or impulses have been used in the past to produce this synchrony under the assumption that the wide spectral spread inherent in transient signals will activate a large portion of the cochlear partition. However, the observation that only auditory nerve units tuned above 3 kHz contribute to synchronous activity in the N1P1 complex of the CAP [Dolan et al., J. Acoust. Soc. Am. 73, 580–591 (1983)] suggests that temporal delays imposed by the traveling wave result in an asynchronous pattern of VIIIth nerve activation. In order to determine if units tuned below 3 kHz could be recruited into the CAP response, the present study uses tone bursts of exponentially rising frequency to hypothetically activate synchronous discharges of VIIIth nerve fibers along the length of the cochlear partition. The equations defining the frequency sweeps are calculated to be the inverse of the delay-line characteristics of the guinea pig cochlear partition.
The resultant sweeps theoretically cause a constant phase displacement of a large portion of the cochlear partition at one time. Compound action potentials recorded in response to the rising frequency sweeps were compared to CAPs evoked by corresponding falling frequency sweeps and clicks. Analysis of the CAP waveforms showed narrower N1 widths and larger N1 and P1 amplitudes for rising sweeps when compared to falling sweeps. This is consistent with the hypothesis of increased synchrony. A further test of the hypothesis was made by using high-pass masking noise to evaluate the contributions of discrete cochlear locations to the CAP (‘‘derived’’ CAP). Latency functions of the derived CAPs for clicks and falling frequency sweeps showed progressive increases in latency as the cutoff frequency of the high-pass filter was lowered. The latency of the derived CAP for these stimulus conditions reflects traveling wave delays [Aran and Cazals, ‘‘Electrocochleography: Animal studies,’’ in Evoked Electrical Activity in The Auditory Nervous System (Academic, New York, 1978)]. In contrast, derived CAPs obtained from rising sweeps showed no change in latency for any cutoff frequencies, indicating a constant delay of response for fibers with different characteristic frequencies (CFs). These results support the theoretical premise underlying the derivation of the rising sweep: Spectral energy with the appropriate temporal organization, dictated by basilar membrane traveling wave properties, will increase CAP synchrony.
Frequency selectivity of single cochlear-nerve fibers based on the temporal response pattern to two-tone signals
Authors: Greenberg Steven , Geisler C. Daniel , Deng Li 
Published: October 2005

The physiological basis of auditory frequency selectivity was investigated by recording the temporal response patterns of single cochlear-nerve fibers in the cat. The characteristic frequency and sharpness of tuning was determined for low-frequency cochlear-nerve fibers with two-tone signals whose frequency components were of equal amplitude and starting phase. The measures were compared with those obtained with sinusoidal signals. The two-tone characteristic frequency (2TCF) is defined as the arithmetic-center frequency at which the fiber is synchronized to both signal frequencies in equal measure.
The 2TCF closely corresponds to the characteristic frequency as determined by the frequency threshold curve. Moreover, the 2TCF changes relatively little (2%–12%) over a 60-dB intensity range. The 2TCF generally shifts upward with increasing intensity for cochlear-nerve fibers tuned to frequencies below 1 kHz and shifts downward as a function of intensity for units with characteristic frequencies (CF’s) above 1 kHz. The shifts in the 2TCF are considerably smaller than those observed with sinusoidal signals. Filter functions were derived from the synchronization pattern to the two-tone signal by varying the frequency of one of the components over the fiber’s response area while maintaining the other component at the 2TCF. The frequency selectivity of the two-tone filter function was determined by dividing the vector strength to the variable frequency signal by the vector strength to the CF tone. The filter function was measured 10 dB down from the peak (2T Q10 dB) and compared with the Q10 dB of the frequency threshold curve. The correlation between the two measures of frequency selectivity was 0.72. The 2T Q10 dB does change as a function of intensity. The magnitude and direction of the change is dependent on the sharpness of tuning at low and moderate sound-pressure levels (SPL’s). The selectivity of the more sharply tuned fibers (2T Q10 dB&gt;3) diminishes at intensities above 60 dB SPL. However, the broadening of selectivity is relatively small in comparison to discharge rate-based measures of selectivity. The selectivity of the more broadly tuned units remains unchanged or improves slightly at similar intensity levels. The present data indicate that the frequency selectivity and tuning of low-frequency cochlear-nerve fibers are relatively stable over a 60-dB range of SPL’s when measured in terms of their temporal discharge properties.
Superresonant systems of scatterers. I
Authors: Tolstoy I. 
Published: October 2005

Single compact scatterers insonified at frequencies near their intrinsic radial resonance ω0 act primarily as monopole sources, amplifying the local pressure field by a factor of order (kRa)−1, a being the scatterer radius and kR the wavenumber at ω0 in the surrounding material (kRa≂1.37×10−2 for air bubbles in water). This paper deals with systems of such scatterers (bubbles, inflated balloons, thin shells in water) which, through coupling via multiple scatter, may themselves exhibit true resonant modes at frequencies close to ω0, amplifying the local pressure field by a further factor of order (kRa)−1, leading to net amplifications in excess of 103 for bubbles or balloons, i.e., of over 120 dB for the intensity. This phenomenon, referred to as superresonance, is predicted by formulas for the equivalent source strength B of each scatterer of the system, proper account being taken of multiple scatter between all elements, using a self-consistent scheme. It has long been known that for a pair of scatterers (doublet), or in periodic lattices, B exhibits maxima for certain values of x=kl (l being the distance between scatterers), which had been called resonances [Twersky, J. Opt. Soc. Am. 52, 145–171 (1962)], but are in fact only partial (quasi) resonances. It is demonstrated here that, under suitable conditions, true resonances exist; i.e., in the absence of attenuation, B exhibits real poles (the infinities are removed by introduction of acoustic damping and finite radii). The existence of such superresonances is furthered by the presence of elastic boundaries in the fluid near the system (e.g., a thin plate or a solid half-space). Multiple scatter coupling then occurs by means of guided flexural or surface waves, which offer a more efficient energy transport mechanism between scatterers than the acoustic modes (volume waves) of a homogeneous fluid fullspace.
In the latter case, a doublet of resonant bubbles, or shells, exhibits no superresonances (poles), only partial ones (quasiresonances); it takes at least three scatterers to create a true superresonant system in a fullspace, and even so there is only one resonant spacing (kl=1.8955, ω=1.0022 ω0 for an equilateral triangle of bubbles in water). But near a thin plate, both doublet and triplet configurations develop spectra of resonant spacings xn and frequencies ωn. Near an elastic solid half-space, Stoneley (Scholte) wave coupling creates similar effects. The role of small interface roughness on this phenomenon is also examined.
Synchrony suppression in complex stimulus responses of a biophysical model of the cochlea
Authors: Shamma Shihab A. , Morrish Kathleen A. 
Published: October 2005

A minimal biophysical model of the cochlea is used to investigate the validity of the hypothesis that a single compressive nonlinearity at the hair cell level can explain some of the suppression phenomena in cochlear responses to complex stimuli. The dependencies of the model responses on the amplitudes and frequencies of two-tone stimuli resemble in many respects the behavior of the experimental data, and can be traced to explicit biophysical parameters in the model. Most discrepancies between theory and experiment stem from simplifications in parameters of the minimal model that play no direct role in the hypothesis. The analysis and simulations predict further results which, pending experimental verification, may provide a more direct test of the influence of the compressive nonlinearity on the relative amplitudes of the synchronous response components, and hence of its role in synchrony suppression. For instance, regardless of the overall absolute levels of a two-tone stimulus applied to this type of model, the ratio of the amplitudes at the input and the ratio of the corresponding responses at the output remain approximately constant and equal (the output ratio changes by at most 6 dB in favor of the stronger tone).
Other nonlinear responses to multitonal stimuli can also be reproduced, such as ‘‘spectral edge enhancement’’ [Horst et al., Peripheral Auditory Mechanisms (Springer, Berlin, 1985)] and some aspects of three-tone suppression [Javel et al., Mechanisms of Hearing (Monash U. P., Australia, 1983)]. In contrast to the complex behavior of suppression with increasing sound intensity and the drastic influence of the compressive nonlinearity on the absolute response measures on the auditory nerve (e.g., average rate and synchrony profiles), the percepts of complex sounds are relatively stable. This suggests that the invariant relative response measures are more likely used in the encoding and CNS extraction of the spectrum of complex stimuli such as speech.
Mg-Protoporphyrin IX and Heme ControlHEMA, the Gene Encoding the First Specific Step of Tetrapyrrole Biosynthesis, inChlamydomonas reinhardtii
Authors: Vasileuskaya Zinaida , Oster Ulrike , Beck Christoph F. 
Published: October 2005

ABSTRACTHEMAencodes glutamyl-tRNA reductase (GluTR), which catalyzes the first step specific for tetrapyrrole biosynthesis in plants, archaea, and most eubacteria. In higher plants, GluTR is feedback inhibited by heme and intermediates of chlorophyll biosynthesis. It plays a key role in controlling flux through the tetrapyrrole biosynthetic pathway. This enzyme, which inChlamydomonas reinhardtiiis encoded by a single gene (HEMA), exhibits homology to GluTRs of higher plants and cyanobacteria.HEMAmRNA accumulation was inducible not only by light but also by treatment of dark-adapted cells with Mg-protoporphyrin IX (MgProto) or hemin. The specificity of these tetrapyrroles as inducers was demonstrated by the absence of induction observed upon the feeding of protoporphyrin IX, the precursor of both heme and MgProto, or chlorophyllide. TheHEMAmRNA accumulation following treatment of cells with light and hemin was accompanied by increased amounts of GluTR. However, the feeding of MgProto did not suggest a role for Mg-tetrapyrroles in posttranscriptional regulation. The induction by light but not that by the tetrapyrroles was prevented by inhibition of cytoplasmic protein synthesis. Since MgProto is synthesized exclusively in plastids and heme is synthesized in plastids and mitochondria, the data suggest a role of these compounds as organellar signals that control expression of the nuclearHEMAgene.
Candida albicans
-Conditioned Medium Protects Yeast Cells from Oxidative Stress: a Possible Link between Quorum Sensing and Oxidative Stress Resistance
Authors: Westwater Caroline , Balish Edward , Schofield David A. 
Published: October 2005

ABSTRACT

Candida albicans
, the most frequent fungal pathogen of humans, encounters high levels of oxidants following ingestion by professional phagocytes and through contact with hydrogen peroxide-producing bacteria. In this study, we provide evidence that
C. albicans
is able to coordinately regulate the oxidative stress response at the global cell population level by releasing protective molecules into the surrounding medium. We demonstrate that conditioned medium, which is defined as a filter-sterilized supernatant from a
C. albicans
stationary-phase culture, is able to protect yeast cells from both hydrogen peroxide and superoxide anion-generating agents. Exponential-phase yeast cells preexposed to conditioned medium were able to survive levels of oxidative stress that would normally kill actively growing yeast cells. Heat treatment, digestion with proteinase K, pH adjustment, or the addition of the oxidant scavenger alpha-tocopherol did not alter the ability of conditioned medium to induce a protective response. Farnesol, a heat-stable quorum-sensing molecule (QSM) that is insensitive to proteolytic enzymes and is unaffected by pH extremes, is partly responsible for this protective response. In contrast, the QSM tyrosol did not alter the sensitivity of
C. albicans
cells to oxidants. Relative reverse transcription-PCR analysis indicates that
Candida-
conditioned growth medium induces the expression of
CAT1
,
SOD1
,
SOD2
, and
SOD4
, suggesting that protection may be mediated through the transcriptional regulation of antioxidant-encoding genes. Together, these data suggest a link between the quorum-sensing molecule farnesol and the oxidative stress response in
C. albicans
.
The
Candida albicans
Vacuole Is Required for Differentiation and Efficient Macrophage Killing
Authors: Palmer G. E. , Kelly M. N. , Sturtevant J. E. 
Published: October 2005

ABSTRACT

Yeast-hypha differentiation is believed to be necessary for the normal progression of
Candida albicans
infections. The emergence and extension of a germ tube from a parental yeast cell are accompanied by dynamic changes in vacuole size and morphology. Although vacuolar function is required during this process, it is unclear if it is vacuolar expansion or some other vacuolar function that is important. We previously described a
C. albicans vps11
Δ mutant which lacked a recognizable vacuole compartment and with defects in multiple vacuolar functions. These include sensitivities to stress, reduced proteolytic activities, and severe defects in filamentation. Herein we utilize a partially functional
VPS11
allele (
vps11hr
) to help define which vacuolar functions are required for differentiation and which influence interaction with macrophages. Mutant strains harboring this allele are not osmotically or temperature sensitive and have normal levels of secreted aspartyl protease and carboxypeptidase Y activity but have a fragmented vacuole morphology. Moreover, this mutant is defective in filamentation, suggesting that the major role the vacuole plays in yeast-hypha differentiation may relate directly to its morphology. The results of this study support the hypothesis that vacuole expansion is required during germ tube emergence. Both
vps11
mutants were severely attenuated in their ability to kill a macrophage cell line. The viability of the
vps11
Δ mutant was significantly reduced during macrophage interaction compared to that in the control strains, while the
vps11hr
mutant was unaffected. This implies some vacuolar functions are required for
Candida
survival within the macrophage, while additional vacuolar functions are required to inflict injury on the macrophage.
Ras1-Induced Hyphal Development in
Candida albicans
Requires the Formin Bni1
Authors: Martin Ronny , Walther Andrea , Wendland Jürgen 
Published: October 2005

ABSTRACT

Formins are downstream effector proteins of Rho-type GTPases and are involved in the organization of the actin cytoskeleton and actin cable assembly at sites of polarized cell growth. Here we show using in vivo time-lapse microscopy that deletion of the
Candida albicans
formin homolog
BNI1
results in polarity defects during yeast growth and hyphal stages. Deletion of the second
C. albicans
formin,
BNR1
, resulted in elongated yeast cells with cell separation defects but did not interfere with the ability of
bnr1
cells to initiate and maintain polarized hyphal growth. Yeast
bni1
cells were swollen, showed an increased random budding pattern, and had a severe defect in cytokinesis, with enlarged bud necks. Induction of hyphal development in
bni1
cells resulted in germ tube formation but was halted at the step of polarity maintenance. Bni1-green fluorescent protein is found persistently at the hyphal tip and colocalizes with a structure resembling the Spitzenkörper of true filamentous fungi. Introduction of constitutively active
ras1

G13V

in the
bni1
strain or addition of cyclic AMP to the growth medium did not bypass
bni1
hyphal growth defects. Similarly, these agents were not able to suppress hyphal growth defects in the
wal1
mutant which is lacking the Wiskott-Aldrich syndrome protein (WASP) homolog. These results suggest that the maintenance of polarized hyphal growth in
C. albicans
requires coordinated regulation of two actin cytoskeletal pathways, including formin-mediated secretion and WASP-dependent endocytosis.
HdaA, a Major Class 2 Histone Deacetylase of
Aspergillus nidulans
, Affects Growth under Conditions of Oxidative Stress
Authors: Tribus Martin , Galehr Johannes , Trojer Patrick , Brosch Gerald , Loidl Peter , Marx Florentine , Haas Hubertus , Graessle Stefan 
Published: October 2005

ABSTRACT

Histone deacetylases (HDACs) catalyze the removal of acetyl groups from the ε-amino group of distinct lysine residues in the amino-terminal tail of core histones. Since the acetylation status of core histones plays a crucial role in fundamental processes in eukaryotic organisms, such as replication and regulation of transcription, recent research has focused on the enzymes responsible for the acetylation/deacetylation of core histones. Very recently, we showed that HdaA, a member of the
Saccharomyces cerevisiae
HDA1-type histone deacetylases, is a substantial contributor to total HDAC activity in the filamentous fungus
Aspergillus nidulans.
Now we demonstrate that deletion of the
hdaA
gene indeed results in the loss of the main activity peak and in a dramatic reduction of total HDAC activity. In contrast to its orthologs in yeast and higher eukaryotes, HdaA has strong intrinsic activity as a protein monomer when expressed as a recombinant protein in a prokaryotic expression system. In vivo, HdaA is involved in the regulation of enzymes which are of vital importance for the cellular antioxidant response in
A. nidulans
. Consequently, Δ
hdaA
strains exhibit significantly reduced growth on substrates whose catabolism generates molecules responsible for oxidative stress conditions in the fungus. Our analysis revealed that reduced expression of the fungal catalase CatB is jointly responsible for the significant growth reduction of the
hdaA
mutant strains.
Prespore Cell Fate Bias in G
1
Phase of the Cell Cycle in
Dictyostelium discoideum
Authors: Chen Guokai , Kuspa Adam 
Published: October 2005

ABSTRACT

By generating a population of
Dictyostelium
cells that are in the G
1
phase of the cell cycle we have examined the influence of cell cycle status on cell fate specification, cell type proportioning and its regulation, and terminal differentiation. The lack of observable mitosis during the development of these cells and the quantification of their cellular DNA content suggests that they remain in G
1
throughout development. Furthermore, chromosomal DNA synthesis was not detectable these cells, indicating that no synthesis phase had occurred, although substantial mitochondrial DNA synthesis did occur in prespore cells. The G
1
-phase cells underwent normal morphological development and sporulation but displayed an elevated prespore/prestalk ratio of 5.7 compared to the 3.0 (or 3:1) ratio normally observed in populations dominated by G
2
-phase cells. When migrating slugs produced by G
1
-phase cells were bisected, each half could reestablish the 5.7 (or 5.7:1) prespore/prestalk ratio. These results demonstrate that
Dictyostelium
cells can carry out the entire developmental cycle in the G
1
phase of the cell cycle and that passage from G
2
into G
1
phase is not required for sporulation. Our results also suggest that the population asymmetry provided by the distribution of cells around the cell cycle at the time of starvation is not strictly required for cell type proportioning. Finally, when developed together with G
2
-phase cells, G
1
-phase cells preferentially become prespore cells and exclude G
2
-phase cells from the prespore-spore cell population, suggesting that G
1
-phase cells have an advantage over G
2
-phase cells in executing the spore cell differentiation pathway.