bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-Scale Analysis Reveals Sst2 as the Principal Regulator of Mating Pheromone Signaling in the Yeast
Saccharomyces cerevisiae
Authors: Chasse Scott A. , Flanary Paul , Parnell Stephen C. , Hao Nan , Cha Jiyoung Y. , Siderovski David P. , Dohlman Henrik G. 
Published: February 2006

ABSTRACT

A common property of G protein-coupled receptors is that they become less responsive with prolonged stimulation. Regulators of G protein signaling (RGS proteins) are well known to accelerate G protein GTPase activity and do so by stabilizing the transition state conformation of the G protein α subunit. In the yeast
Saccharomyces cerevisiae
there are four RGS-homologous proteins (Sst2, Rgs2, Rax1, and Mdm1) and two Gα proteins (Gpa1 and Gpa2). We show that Sst2 is the only RGS protein that binds selectively to the transition state conformation of Gpa1. The other RGS proteins also bind Gpa1 and modulate pheromone signaling, but to a lesser extent and in a manner clearly distinct from Sst2. To identify other candidate pathway regulators, we compared pheromone responses in 4,349 gene deletion mutants representing nearly all nonessential genes in yeast. A number of mutants produced an increase (
sst2
,
bar1
,
asc1
, and
ygl024w
) or decrease (
cla4
) in pheromone sensitivity or resulted in pheromone-independent signaling (
sst2
,
pbs2
,
gas1
, and
ygl024w
). These findings suggest that Sst2 is the principal regulator of Gpa1-mediated signaling in vivo but that other proteins also contribute in distinct ways to pathway regulation.
Candida albicans VAC8
Is Required for Vacuolar Inheritance and Normal Hyphal Branching
Authors: Barelle Caroline J. , Richard Mathias L. , Gaillardin Claude , Gow Neil A. R. , Brown Alistair J. P. 
Published: February 2006

ABSTRACT

Hyphal growth is prevalent during most
Candida albicans
infections. Current cell division models, which are based on cytological analyses of
C. albicans
, predict that hyphal branching is intimately linked with vacuolar inheritance in this fungus. Here we report the molecular validation of this model, showing that a specific mutation that disrupts vacuolar inheritance also affects hyphal division. The armadillo repeat-containing protein Vac8p plays an important role in vacuolar inheritance in
Saccharomyces cerevisiae
. The
VAC8
gene was identified in the
C. albicans
genome sequence and was resequenced. Homozygous
C. albicans vac8
Δ deletion mutants were generated, and their phenotypes were examined. Mutant
vac8
Δ cells contained fragmented vacuoles, and minimal vacuolar material was inherited by daughter cells in hyphal or budding forms. Normal rates of growth and hyphal extension were observed for the mutant hyphae on solid serum-containing medium. However, branching frequencies were significantly increased in the mutant hyphae. These observations are consistent with a causal relationship between vacuolar inheritance and the cell division cycle in the subapical compartments of
C. albicans
hyphae. The data support the hypothesis that cytoplasmic volume, rather than cell size, is critical for progression through G
1
.
Effect of all-transretinoic acid on tissue dynamics of choriocarcinoma cell lines: an organotypic model
Authors: Chiu P M , Feng H C , Benbrook D M , Ngan H Y S , Khoo U S , Xue W C , Tsao S W , Chan K W , Cheung A N Y 
Published: February 2006

Background:All-transretinoic acid (ATRA) is a natural vitamin A derivative that has a profound effect on the regulation of cell growth, differentiation and death.Aim:To investigate the tissue dynamic and cellular invasion effects of ATRA in choriocarcinoma (CCA), an aggressive trophoblastic tumour, by using a three-dimensional organotypic culture model system and cell invasion assay, respectively.Methods:An organotypic culture model of two CCA cell lines, JAR and JEG, was established. The effects of 1 μM ATRA on proliferation, differentiation and apoptosis on this CCA model were assessed by morphological assessment of the mitotic and apoptotic figures as well as by Ki-67 and caspase-related M30 cytoDeath antibody immunohistochemistry and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay. The effect of ATRA on p53 and its regulated protein product, WAF1/Cip1, was also evaluated with DO7 and p21WAF1antibodies, respectively. Moreover, the effect of ATRA on cellular (CCA) invasion was also investigated with Cell Invasion Kit on the JEG cell line.Results:ATRA was found to induce marked apoptosis in organotypic cultures of both cell lines, as evidenced by increased M30-positive cells (p<0.0001) and increased TUNEL-positive cells (p<0.0001) in treated cultures; to decrease proliferation, as evidenced by decreased Ki-67-positive cells (p<0.0001); and to decrease p53-DO7 immunoreactivity (p<0.0001) and increase p21WAF1(p<0.0001) immunoreactivity. 1.5 μM ATRA was found to effectively inhibit JEG cell invasion in the cell invasion assay.Conclusion:ATRA treatment was found to inhibit invasion and proliferation and enhance apoptosis, probably by the activation of caspases and induction of differentiation. ATRA and synthetic retinoids may be alternative agents for the treatment of CCA.
Timing and Communicative Functions of Pitch Contours
Authors: Kohler K. 
Published: February 2006

Abstract
A new research paradigm is applied to F0 synchronization with articulation, inpeak and valley contours, under four principles: (a) Timing of F0 contours enters thedefinitions of the pitch categories. (b) These phonetic exponents are linked to com-municativefunctions. (c) The listener plays a pivotal role. (d) Contextualization oftest stimuli is essential for pitch data collection. Data are presented and interpretedfrom an experimental investigation of the substance-function relationship in theperception of peak and valley shift series by German listeners, using the semanticdifferential technique. The findings of the substance-function relationship areexplained with reference to the frequency codeand to auditory enhancement,i.e.syntagmatic contrast of high-low or low-high pitch trajectories in synchronizationwith articulatory landmarks of accented syllables.
Exploring the Influence of Vocal Emotion Expression on Communicative Effectiveness
Authors: Biersack S. , Kempe V. 
Published: February 2006

AbstractThis study explores whether speaker emotion influences communicative effectiveness. Two hundred participants rated their current emotional state and gave a description of a route on a simple map. The quality of the linguistic content of the descriptions was assessed using Latent Semantic Analysis. Six hundred participants provided route drawings based on the map descriptions. Median route deviation served as a measure of communicative effectiveness. Eighty addi-tional participants rated invariant parts of the descriptions for perceived speaker happiness. Path analysis revealed that while speaker emotion did not affect the linguistic content of the descriptions, it had an effect on communicative effective-ness both through the effects of vocal cues directly as well as mediated by per-ceived happiness of speech. Specifically, higher first formants were associated with higher reported and perceived happiness as well as higher communicative effectiveness. Jitter, on the other hand, was negatively related to the perception of happiness and positively related to communicative effectiveness. These findings suggest that mood-related modulation of phonation and articulation can influence the effectiveness of communication in addition to message content.
From Words to Actions: The Phonetics of Eigenlijk in Two Communicative Contexts
Authors: Plug L. 
Published: February 2006

AbstractThis paper presents the results of an investigation into the distribution of phonetic variants of the Dutch discourse marker eigenlijk, combining phonetic and conversation analytic methods. The paper shows that the phonetic form of eigenlijkdepends to some extent on the sequential environment in which the item is used; moreover, it shows that in the case of two such environments, the forms of eigenlijk are representative of tempo and reduction patterns spanning entire turns or turn-constructional units. These patterns can be related to the interactive function of the turns; thus, the findings presented here contribute to our as yet limited knowledge of the phonetic correlates of communicative actions.
Acoustic Patterns and Communicative Functions of Phrase-Final F0 Rises in German: Activating and Restricting Contours
Authors: Dombrowski E. , Niebuhr O. 
Published: February 2006

AbstractAcoustic features and communicative functions of phrase-final F0 rises startingbefore an accented-vowel onset are analysed in a corpus of German unscriptedspeech. Two conversational conditions are examined: turn-yielding and turn-holding.The most important feature distinguishing rises in these two conditions is therange proportion, which differentiates between two patterns as follows: (1) raisedpitch on the accented syllable and restrained pitch movement in the tail of thecontour, (2) lowered pitch on the accented syllable and extended pitch movementin the tail. The first pattern is seen as a restrictivegesture, e.g. preventing the dia-loguepartner from turn taking. The second one is viewed as an activatinggesture,inviting the coparticipant to contribute.
Exploring Prosody in Interaction Control
Authors: Edlund J. , Heldner M. 
Published: February 2006

Abstract
This paper investigates prosodic aspects of turn-taking in conversation with aview to improving the efficiency of identifying relevant places at which a machinecan legitimately begin to talk to a human interlocutor. It examines the relationshipbetween interaction control, the communicative function of which is to regulatethe flow of information between interlocutors, and its phonetic manifestation.Specifically, the listener’s perception of such interaction control phenomena ismodelled. Algorithms for automatic online extraction of prosodic phenomenaliable to be relevant for interaction control, such as silent pauses and intonationpatterns, are presented and evaluated in experiments using Swedish map taskdata. We show that the automatically extracted prosodic features can be used toavoid many of the places where current dialogue systems run the risk of interrupt-ingtheir users, as well as to identify suitable places to take the turn.
A Re-Evaluation of the Nature of Speech Errors in Normal and Disordered Speakers
Authors: Pouplier M. , Hardcastle W. 
Published: February 2006

AbstractIt is well known that speech errors in normal and aphasic speakers share cer-tain key characteristics. Traditionally, many of these errors are regarded as serial misorderings of abstract phonological segments, which maintain the phonetic well-formedness of the utterance. The current paper brings together the results of several articulatory studies undertaken independently for both subject popula-tions. These show that, in an error, instead of one segment substituting for another, two segments are often produced simultaneously even though only one segment may be heard. Such data pose problems for current models of speech production by suggesting that the commonly assumed dichotomous distinction between phonological and phonetic errors may not be tenable in the current form or may even be altogether redundant.
Observed Relationships between the El Niño–Southern Oscillation and the Extratropical Zonal-Mean Circulation
Authors: L’Heureux Michelle L. , Thompson David W. J. 
Published: February 2006

Abstract
There is increasing evidence indicating that the climate response to variations in the El Niño–Southern Oscillation (ENSO) includes not only thermally forced zonal wind anomalies in the subtropics but also eddy-driven zonal wind anomalies that extend into the mid–high latitudes of both hemispheres. In this study, new insights into the observed seasonally varying signature of ENSO in the extratropical zonal-mean circulation are provided and the associated linkages with the dominant patterns of extratropical variability are examined.
The zonal-mean extratropical atmospheric response to ENSO is characterized by two principal features: an equivalent barotropic dipole in the Southern Hemisphere (SH) zonal-mean zonal flow with centers of action located near ∼40° and ∼60° during austral summer, and a weaker, but analogous, dipole in the Northern Hemisphere (NH) with centers of action located near ∼25° and ∼45° during early and late boreal winter. Both structures are accompanied by eddy momentum flux anomalies that exhibit a remarkable degree of hemispheric symmetry. In the SH, the extratropical signature of ENSO projects strongly onto the primary mode of large-scale variability, the southern annular mode (SAM). During the austral summer, roughly 25% of the temporal variability in the SAM is linearly related to fluctuations in the ENSO cycle. An analogous relationship is not observed in association with the principal mode of climate variability in the NH, the northern annular mode (NAM).
It is argued that the seasonally varying impact of ENSO on the extratropical circulation is consistent with the impact of the thermally forced subtropical wind anomalies on the dissipation of equatorward-propagating wave activity at subtropical latitudes.
Extension of Drought Records for Central Asia Using Tree Rings: West-Central Mongolia*
Authors: Davi N. K. , Jacoby G. C. , Curtis A. E. , Baatarbileg N. 
Published: February 2006

Abstract
Central Asian drought has had drastic impacts on vast regions over recent years. Longer records and insight into temporal drought patterns could aid greatly in anticipating extreme events and agrarian planning. Mongolia is representative of the central Asian region, and tree-ring resources are used herein to extend the climate record and test for solar influence and/or Pacific Ocean teleconnections. Absolutely dated tree-ring-width chronologies from five sampling sites in west-central Mongolia were used in precipitation models and an individual model was made using the longest of the five tree-ring records (1340–2002). The tree-ring sites are in or near the Selenge River basin, the largest river in Mongolia and a major input into Lake Baikal in Siberia. Regression models resulted in a reconstruction of streamflow that extends from 1637 to 1997 and explains 49% of the flow variation. Spectral analysis indicated significant variation in the frequencies common to Pacific Ocean variations [Pacific decadal oscillation (PDO) and ENSO] and also some quasi-solar and lunar-nodal periodicities similar to previous Mongolian hydrometeorological reconstructions in eastern Mongolia based on tree rings.
Evaluating markers for the early detection of cancer: overview of study designs and methods
Authors: Baker Stuart G , Kramer Barnett S , McIntosh Martin , Patterson Blossom H , Shyr Yu , Skates Steven 
Published: February 2006

Background The field of cancer biomarker development has been evolving rapidly. New developments both in the biologic and statistical realms are providing increasing opportunities for evaluation of markers for both early detection and diagnosis of cancer. Purpose To review the major conceptual and methodological issues in cancer biomarker evaluation, with an emphasis on recent developments in statistical methods together with practical recommendations. Methods We organized this review by type of study: preliminary performance, retrospective performance, prospective performance and cancer screening evaluation. Results For each type of study, we discuss methodologic issues, provide examples and discuss strengths and limitations. Conclusion Preliminary performance studies are useful for quickly winnowing down the number of candidate markers; however their results may not apply to the ultimate target population, asymptomatic subjects. If stored specimens from cohort studies with clinical cancer endpoints are available, retrospective studies provide a quick and valid way to evaluate performance of the markers or changes in the markers prior to the onset of clinical symptoms. Prospective studies have a restricted role because they require large sample sizes, and, if the endpoint is cancer on biopsy, there may be bias due to overdiagnosis. Cancer screening studies require very large sample sizes and long follow-up, but are necessary for evaluating the marker as a trigger of early intervention.
Assessing diagnostic accuracy and the clinical value of positron emission tomography imaging in patients with solitary pulmonary nodules (SNAP)
Authors: Kymes Steven M , Lee Kelvin , Fletcher James W ,   SNAP (CSP 027) Study Group
Published: February 2006

Background Diagnostic tests, particularly diagnostic imaging modalities such as computed tomography (CT) and positron emission tomography (PET), have the potential to make important contributions to improved patient care and medical decision making. The expense of these tests is justified to the extent that they improve diagnostic and treatment decisions, and ultimately health outcomes. Clinical studies evaluating the accuracy of diagnostic tests and assessing their influence on decision making are essential to setting health policy and directing patient care. Purpose We present the design and participant baseline characteristics of the Department of Veterans Affairs Cooperative Study 027 (Prospective Study of the Diagnostic Accuracy of 18F-Fluorodeoxyglucose (FDG) – Positron Emission Tomography (PET) Imaging in the Management of Patients with Solitary Pulmonary Nodules (SNAP). Methods SNAP is a prospective, multi-site diagnostic trial to evaluate the efficacy of PET and CT for characterizing solitary pulmonary nodules. The study incorporated an assessment of the impact of these imaging modalities on clinical decision making. Results Between January 1999 and June 2001, 10 SNAP sites enrolled 532 participants with a mean age of 66 years (SD ± 11.3), of whom 97.3% were male. A history of smoking was claimed by 93.6% of participants, with 45.7% of all participants smoking at time of enrollment. Those still smoking had an average exposure of 56.8 pack-years, while those who had quit smoking prior to enrollment had an exposure of 58.1 pack-years. Limitations The study design reduced most common biases, but some degree of selection bias and verification bias remained. We sought to minimize verification bias by use of a dual reference standard. Conclusion SNAP is a diagnostic test study that was designed to minimize bias and to assess a test's impact on clinical decision making, providing the kind of information most needed by clinicians and health policy makers.
Heterogeneity in disease free survival between centers: lessons learned from an EORTC breast cancer trial
Authors: Legrand Catherine , Duchateau Luc , Sylvester Richard , Janssen Paul , van der Hage Jos A , van de Velde Cornelis JH , Therasse Patrick 
Published: February 2006

Background Large phase III clinical trials convey a lot of important information besides the main analysis of the treatment effect. For example, the use of multicenter clinical trial data to identify prognostic indices is now common. In addition, the study of heterogeneity in patient outcome between centers has received considerable attention in recent years. In this paper, we explain and illustrate a method used to investigate such heterogeneity with data from an early breast cancer clinical trial. Methods The inclusion of a random effect for center in a Cox proportional hazards model allows us to study the heterogeneity in time-to-event outcomes between centers. Such a model has the major advantage that it provides a measure of the spread of outcomes over centers. This technique is illustrated using data from EORTC trial 10854, a randomized phase III trial comparing perioperative chemotherapy with no perioperative chemotherapy for early breast cancer; 2793 patients were entered by 14 centers. Results Substantial heterogeneity between centers was detected for disease-free survival. This can be explained by the geographical area in which the center is located, with better outcomes achieved in France as compared with southern Europe and South Africa. None of the prognostic factors considered could explain this heterogeneity. Conclusion Although clinical trials are run with the objective of removing as much heterogeneity as possible, some heterogeneity in the outcome of patients between centers may remain, as was the case in our study. The use of a random effect for center within a Cox PH model is an excellent method to investigate this heterogeneity. Such types of analyses, although exploratory, provide further insight into possible factors which may have an impact on the patient's outcome.
The Emerging Role of the Endocannabinoid System in Endocrine Regulation and Energy Balance
Authors: Pagotto Uberto , Marsicano Giovanni , Cota Daniela , Lutz Beat , Pasquali Renato 
Published: February 2006

During the last few years, the endocannabinoid system has emerged as a highly relevant topic in the scientific community. Many different regulatory actions have been attributed to endocannabinoids, and their involvement in several pathophysiological conditions is under intense scrutiny. Cannabinoid receptors, named CB1 receptor and CB2 receptor, first discovered as the molecular targets of the psychotropic component of the plant Cannabis sativa, participate in the physiological modulation of many central and peripheral functions. CB2 receptor is mainly expressed in immune cells, whereas CB1 receptor is the most abundant G protein-coupled receptor expressed in the brain. CB1 receptor is expressed in the hypothalamus and the pituitary gland, and its activation is known to modulate all the endocrine hypothalamic-peripheral endocrine axes. An increasing amount of data highlights the role of the system in the stress response by influencing the hypothalamic-pituitary-adrenal axis and in the control of reproduction by modifying gonadotropin release, fertility, and sexual behavior.The ability of the endocannabinoid system to control appetite, food intake, and energy balance has recently received great attention, particularly in the light of the different modes of action underlying these functions. The endocannabinoid system modulates rewarding properties of food by acting at specific mesolimbic areas in the brain. In the hypothalamus, CB1 receptor and endocannabinoids are integrated components of the networks controlling appetite and food intake. Interestingly, the endocannabinoid system was recently shown to control metabolic functions by acting on peripheral tissues, such as adipocytes, hepatocytes, the gastrointestinal tract, and, possibly, skeletal muscle. The relevance of the system is further strenghtened by the notion that drugs interfering with the activity of the endocannabinoid system are considered as promising candidates for the treatment of various diseases, including obesity.