bluuebunny/crossref_metadata_2025 huggingface dataset:
Tongue-Lip Pressures during Speech of Australian Aborigines
Authors: Proffit William R. , McGlone Robert E.
Published: November 2009

Electronic instruments to measure tongue and lip pressures and pressure patterns in Australian aborigines made it possible to differentiate physiologically between certain sounds. Lingual pressure patterns indicate that the /t/, /nt/ and /tj/ sounds in the Walbiri language require different articulatory gestures and are properly considered separate phonemes. Labial pressures distinguish classes of phonemes but not individual sounds. Tongue positioning within the oral cavity of aborigines reveals compensations for their different anatomy, but articulatory gestures are remarkably similar in aborigines and Americans.
Variation in Lingual Coarticulation at Certain Juncture Boundaries
Authors: Su Lo-Soun , Daniloff Raymond , Hammarberg Robert
Published: November 2009

The acoustic spectra of [m] produced by speakers of American English in various [mV] contexts was studied for coarticulatory variations caused by the [vowel] under conditions of varying juncture boundaries occurring between [m] and [vowel]. Dispersion analysis was used to estimate the coarticulatory variation in [m] spectra. Low level junctures marked by short pauses do not disrupt nasal-vowel coarticulation. However, higher level junctures such as between extraposed clauses or phrases and the body of an utterance are more often than not marked with long pauses, and concomitant reduction of nasal-vowel coarticulation.
Neutralisierung englischer Akzentunterschiede in der Nachkontur
Authors: Huss Volker
Published: November 2009

PILCH's analysis of the English intonation contour implies that the difference between the primary and secondary stresses exists only in the contour nucleus, but is inaudible elsewhere. This hypothesis has been checked and confirmed both by auditory and acoustic analysis and by the test responses of native speakers. The parameters by which primary and secondary stresses are heard as different are length and pitch change. The pitch difference disappears outside the contour nucleus, and the length relations may be reversed causing wrong identifications by the listeners.
La mimique buccale
Authors: Fónagy Ivan
Published: November 2009

The mechanism for the acoustic encoding of emotions was analyzed by means of two X-ray films containing neutral and emotional variants (anger, hate, sadness, joy, tenderness, irony) of six Hungarian phrases. Each attitude is expressed by an articulatory pattern peculiar to it. This oral gesture can be seen as superimposed on the (ideal) neutral articulation. Each concrete sound necessarily contains two pieces of information differing profoundly both at the level of content (conceptual vs. preconceptual) and of expression (arbitrary linguistics vs. non-arbitrary prelinguistic encoding). In some cases, this double encoding is reflected in ambiguous and contradictory lingual articulation.
On the Predictive Role of the Recent Theories of Aspiration
Authors: Bhatia Tej K.
Published: November 2009

The purpose of this study is to examine the predictive power of recent theories of aspiration. These theories (lag of voicing) predict that aspirated sounds will be perceived as unaspirated in word-final position, as in the case of Korean stops. Contrary to the predictions of these theories, our experiment showed that in final position in Hindi stops, such a neutralization between unaspirated and aspirated stops was absent. What is even more interesting is that the intelligibility of aspirated sounds in Hindi was the highest on the perception scale while unaspirated had a lower rank.
A Minor Figure in 19th-Century French Linguistics: A. Dufriche-Desgenettes
Authors: Koerner E.F.K.
Published: November 2009

A.DUFRICHE-DESGENETTES’ (1804-ca. 1885) life and work has remained in the dark until today, although he was a founding member of the Société de Linguistique de Paris. It was only some 70 years after his death that R. Godel in 1957, in his Sources manuscrites of the Saussurean Cours, bestowed recognition on Dufriche-Desgenettes as the inventor of the term ‘phoneme’ in a paper presented to the Paris Linguistic Society on May 24 1873. The present paper is the first attempt to bring together the essential information available about Dufriche-Desgenettes, the man and his work.
An Analysis of the Temporal Features of Ejective Consonants
Authors: Hogan John T.
Published: November 2009

This paper reports some temporal measurements of glottalic ejective consonants. Measurements of pre-release silence before stops, the time from consonant release to vowel onset, and the post-release silent interval are obtained and submitted to analyses of variance. Also several interesting properties emerge from the study. First, the silent interval between release of consonant and vowel onset is an important factor relating to the characterization of voice onset time. Second, F2 and F3 transitions do not regularly appear in the beginning of the vowel nucleus as a cue for place of articulation.
Relations entre la forme du conduit vocal et les caractéristiques acoustiques des voyelles françaises
Authors: Mrayati M. , Carré R.
Published: November 2009

The distribution inside the vocal tract of certain acoustic parameters (volume velocity, acoustic pressure, stored energy) is calculated for the French vowels. Calculations are made using a simulated lossy transmission line model of the vocal tract. The obtained results are used to study the relation between the acoustic characteristics of these vowels and the corresponding articulatory dimensions. Three aspects of this relation are developed: (1) the ‘affiliation degree’ of each formant with different sections of the vocal tract; (2) the sensitivity of each formant frequency to small changes of the vocal tract area function, and (3) the contribution of each part of the vocal tract to formant damping for each of the distributed losses. The effects of radiation impedance and wall vibration on these relations are evaluated. Use of these results is possible in the fields of speech analysis and vocal tract modeling.
Toward Defining Acoustic Phonetic Equivalence for Vowels
Authors: Broad David J.
Published: November 2009

Determining whether or not two arbitrary vowel tokens are phonetically equivalent is the crucial step in classifying vowels phonetically. Acoustic phonetic equivalence for vowel sounds is discussed in the light of data on formant frequency variability. Random variation between repetitions of the same item by the same speaker or between imitations of the same item by different speakers determines a range of practical limits on the sizes of acoustic phonetic equivalence classes. Vowel imitation is suggested as an approach to defining vowel equivalence across speakers. Effects of prosody and context can be handled cither by estimating vowel targets or by permitting an intended or perceived vowel type to have a number of condition-dependent variants. The consequences of these options are discussed in terms of their practicality and consistency with basic phonetic concepts.
Nouvelle contribution à la théorie des «locus»
Authors: Emerit Etienne
Published: November 2009

Johansson’s experiments reveal that /d/ is identified mostly thanks to its transitions, in opposition to /b/ and /g/, a consideration which sustains the author’s opinion. By means of EVA III, he first synthesized /da/ and /du/ after DELATTREs rules, then after natural patterns. The latter turn out to be quite more intelligible, a consideration which shows that the extrapolated ‘loci’ which Delattre had to use in order to avoid categorization confusions, are not able to ensure ‘maximal’ consonantic perception; his experiments must have been altered by confusion between ‘transitions’ and ‘sonorous attacks’. The author considers logatoms as ‘aggregate patterns’, tackles formantic anamorphosis and ‘balance’, and gives notice of the realization of an ‘evagraphic dictionary’ intended for computer speech.
The Acoustic Status of the Mute-e in French
Authors: Malécot Andre , Chollet Gérard
Published: November 2009

A recent article in Phonetica has shown the effect of linguistic and paralinguistic factors on the frequency of elision of the French mute-e. The present study deals primarily with its spectral characteristics and identifiability. It also describes a new computer-assisted technique of acoustic analysis which advantageously replaces conventional spectrograms. The results of the study show that the entity in question has hardly half the phonetic individuality of other French vowels, and while it is closest in color to /ø/, it is only half as discrete.
Tonal Distinctions in Cantonese
Authors: Vance Timothy J.
Published: November 2009

The experiment reported here is a perceptual study of the six contrastive tones of Cantonese. The monosyllable [jλu] was synthesized, and a large number of closely spaced Fo contours were applied to it. Listeners were asked to identify each synthetic stimulus as one of six Cantonese words which all have the segmental shape [jλu] and differ only in tone. The response data were used to compare two impressionistic accounts of the tonal distinctions and determine which reflects actual Fo more accurately. In general, the results accord fairly well with straightforward predictions made from the impressionistic accounts, but there is one major exception. It appears that something in addition to differences in Fo is involved in distinguishing the low-low tone from the other tones.
Baseldeutsche Phonologie
Authors: Pilch Herbert
Published: November 2009

This paper attempts a new departure both in German dialectology and in phonemic analysis: (i) It is based on an open corpus of spontaneous, colloquial speech. (ii) The segmentals (phonemes and clusters) are integrated into the hierarchy of supra-segmentals (syllable types, shape types, intonation contours). (iii) Phonemic variability is recognized within the dialect. Its major isoglosses are restated in terms of phoneme correlations. (iv) Certain unstressed words do occur in isolation. (v) Vowel length is recognized as redundant, but the difference between the dental /t/ and the alveolar /t/ is distinctive. (vi) The inventories of stressed and unstressed vowels differ radically, the unstressed suffixes containing the vowels /i a/ only. (vii) The peripheral status is analyzed of the aspirates (other than /kh/), of the affricates /tš kχ/, and of the lenis /t š n/, but none of these phonemes is limited to loanwords.(viii) The fusion is analyzed of adjacent stops in initial k- and {-clusters.
Andegerebenha Vowel Phonology
Authors: Breen J.G.
Published: November 2009

The most common vowel system in Australian languages and the system ancestral to other Australian vowel systems is the triangular system /i-u-a/, with or without phonemic length. This paper shows that this is not appropriate for Andegerebenha, considers the suitability of a two-vowel system /a-a/, and rejects this in favour of one vowel plus length /a-a·/ The short vowel is greatly influenced in quality by the adjacent consonants; the longer one much less so. The consonant inventory is augmented by the addition of a number of labialised consonants, which embody the rounding of earlier *u. Conversely, the phoneme/γ/, a velar glide, was introduced when an earlier *w acquired the feature [-round] of adjacent vowels.
Segmentation und phonetische Klassifikation mit dem DAWID-System
Authors: Glave R.D. , Lancé D.
Published: November 2009

The DAWID speech recognition system, which is briefly described in this paper, performs an acoustical analysis which in some respect can be compared with a phonetic transcription. The limitations of this comparison are discussed. The segmentation and phonetic classification performance of the system is investigated on the basis of 5,520 spoken words (46 different one- and two-syllable words, 12 male speakers). The system performance is examined with the aid of varying classes of speech sounds embedded in different phonetic context. The results indicate that the DAWID system reliably transforms some classes of speech sounds into sequences of symbols, the elements of which represent ‘quasi-allophonic’ sound classes.
La perception des glissandos descendants dans les contours prosodiques (The Perception of Falling Glissandos in Prosodic Contours)
Authors: Rossi M.
Published: November 2009

The aim of this study is to determine wether the threshold and pitch of falling glissandos are identical to those calculated for rising ones - and consequently to test the hypothesis that rising glissandos are less well perceived than falling ones. The results show a threshold between 18 and 19 Hz for a duration of 200 ms, with an initial frequency of 139 Hz. The pitch corresponds to the frequency of a point at two thirds of the duration of the vowel. These results confirm those obtained for rising glissandos. The above hypothesis is not verified. In conclusion, a model of hearing is proposed which account for the modes of perception of glissandos.
In Search of the Acoustic Correlates of Stress: Fundamental Frequency, Amplitude, and Duration in the Connected Utterance of Some Native and Non-Native Speakers of English
Authors: Adams Corinne , Munro R.R.
Published: November 2009

In this investigation of the correlates of stress, account was taken of both production and perception aspects of the phenomenon in the connected utterance of a group each of native and non-native speakers of English. Measurement of the fundamental frequency, amplitude, and duration of the syllables stressed by these subjects revealed that duration was by far the most frequently used cue and that amplitude was the least used. The two groups differed significantly both in the incidence and placement of stress, although no evidence was found to suggest that native and non-native speakers consistently employ different acoustic parameters to signal this feature at the sentence level.
A la recherche de traits pertinents prosodiques du français parisien
Authors: Fónagy I. , Fónagy J. , Sap J.
Published: November 2009

An attempt was made to determine the prosodic features that distinguish modalities and emotive attitudes through controlled variation of fundamental frequency and overall sound pressure in a sample of four synthesized French sentences. The following tendencies were observed: (a) judgements ‘interrogative’ in disjunctive sentences were essentially more frequent with a steeper rise in fundamental frequency (interval/time) in the first stressed syllable; (b) in the case of certain melodic cliches, assertive and interrogative sentences were distinguished by characteristic intrasyllabic (constant vs. rising) fundamental frequency changes; (c) basic emotions such as anger, joy could not be distinguished on the basis of mere changes in the fundamental frequency; more complex social attitudes, however, can be differenciated in this way, and (d) if two fundamental frequency curves differed only in their angularity (in suddenness of change of direction) then sentences with a more angular fundamental frequency curve were rated as being significantly more aggressive than their smoother counterparts.
Interpreting Raw Fundamental-Frequency Tracings of Danish
Authors: Thorsen Nina
Published: November 2009

This paper describes a procedure with which complex raw fundamental-frequency (F₀) tracings of Danish can be split into their components, namely (1) coarticulatory F₀ variations; (2) intrinsic F₀ level differences between segments (vowels); (3) F₀ movements pertaining to individual segments (vowels); (4) F₀ patterns associated with stress groups, and (5) the intonation contour of the sentence. ‘Stød’ is not considered here. The problems inherent in such a procedure are discussed as are the hypotheses concerning physiological production models of the speech signal and its perceptual correlates.
Über die artikulatorische Ähnlichkeit deutscher Vokale (On the articulatory similarity of German vowels)
Authors: Rietveld A.C.M.
Published: November 2009

In this article we describe an investigation into the proprioceptive articulatory similarity often German vowels. When processed with a multidimensional scaling technique, the similarity scores of 46 subjects led to the construction of a proprioceptive space, the dimensions of which are discussed in this article. The application of a hierarchical Cluster Analysis resulted in three main clusters, which we labelled front, middle and back. The vowels of the same cluster show a higher similarity than vowels taken from different clusters. The dimensions of the proprioceptive space and the classes resulting from the cluster analysis are correlated with some physical features of the vowels in question.
Strategy Relationships in the Acquisition of /CV/, /CVCV/, /CVC/ and Other Structures: a Case Study
Authors: Roberts E.W.
Published: November 2009

A concentrated study of the various utterance forms used by a single subject during the period 1 year, 11 months to 2 years, 1 month indicates that they interdigitate in a manner that is interesting both from structural and paradigmatic viewpoints. Consonant harmony is shown to have priority over vowel harmony and both are crucially dependent on the presence of an initial /C-/, exclusive of the optional glides [?] and [h]. Medial and final /C/s are seen to be preferentially dental (with final palatalisation) and final /V/ to be preferentially [i], i.e. also palatal. Final /C/ contrasts develop first in the /VC/ structure and differential /V/ systems in forms containing /VV/ sequences or in the /VCV/ structure.
Coarticulatory Effects of Vowel Quality on Velar Function
Authors: Bell-Berti Fredericks , Baer Thomas , Harris Katherine S. , Niimi Seiji
Published: November 2009

Velar elevation data were collected for 12 utterance pairs contrasting in vowel quality. It is well-known that velar position for any phonetic segment is determined by at least two factors: the nature of the segment itself and the phonetic environment in which the segment occurs. Thus, velar elevation increases through the series of segment types: nasals, open vowels, close vowels, obstruents; and velar elevation for English vowels is affected by adjacent nasals. In these data, vowel quality was found to affect velar position during adjacent consonants: that is, the velum was lower for both nasals and obstruents in an environment of open vowels than in an environment of close vowels.
Acoustic Analysis of the Spanish Diphthongs
Authors: Borzone de Manrique Ana María
Published: November 2009

The spectral analysis of the 14 Spanish diphthongs was undertaken under two different speaking rates. The central frequency and relative intensity of the first (F1) and second (F2) formant were measured as well as the duration of the onset and offset steady states, the transition between them, and the total duration of the diphthong. The values in hertz per millisecond for the rate of change of the F2 transition were also obtained. Results show that the formant pattern, rate of change and temporal relations between both steady states contribute to the characterization of Spanish diphthongs; the distinction between diphthongs and vowel sequences in hiatus depends on the temporal relationship.
Sprachlaute und Sprachsignale – Zur Perspektive einer neuen Phonometrie
Authors: Tillmann H.G.
Published: November 2009

Descriptive phonetics and instrumental phonetics have two entirely different empirical domains as their subject matters. On this basis, Zwirner’s central problem of the theoretical relationship between sound category and sound realisation is re-formulated and discussed. It is shown how the traditional descriptive procedures of segmentation and decomposition can be connected with the segments of digital speech signals and the features analysed from them.
The Reorganization Times of Bite-Block Vowels
Authors: Lubker James F.
Published: November 2009

This investigation attempts to determine, via classical reaction-time techniques, whether speakers require longer times to initiate the production of so-called ‘bite-block’ vowels than they do for normal vowels. The results suggest that speakers do spend measurable amounts of time in neurophysiological reorganization for such vowels. These results are discussed in terms of some current models for speech motor control.
Acoustic Measurements of Articulator Motions
Authors: Schroeder Manfred R. , Strube Hans Werner
Published: November 2009

Methods for estimating articulatory data from acoustic measurements are reviewed. First, relations between the vocal-tract area function and formant or impedance data are pointed out. Then the possibility of determining a (discretized) area function from the speech signal itself is considered. Finally, we look at the estimation of certain articulatory parameters rather than the area function. By using a regression method, such parameters can even be estimated independently of any vocal-tract model. Results for real-speech data are given.
Use of Visual Information for Phonetic Perception
Authors: Summerfield Quentin
Published: November 2009

The accuracy with which naive listeners can report sentences presented 12 dB below a background of continuous prose was compared with accuracy in four audio visually supplemented conditions. With monochrome displays of the talker showing (i) the face, (ii) the lips and (iii) four points at the centres of the lips and the corners of the mouth, accuracy improved by 43, 31 and 8%, respectively. No improvement was produced by optical information on syllabic timing. The results suggest that optical concomitants of articulation specify linguistic information to normal listeners. This conclusion was reinforced in a second experiment in which identification functions were obtained for continua of synthetic syllables ranging between [aba], [ada] and [aga], presented both in isolation and in combination with video recordings. Audio-visually, [b] was only perceived when lip closure was specified optically and, if lip closure was specified optically, [b] was generally perceived. Perceivers appear to make use of articulatory constraints upon the combined audio-visual specification of phonetic events, suggesting that optical and acoustical displays are co-perceived in a common metric closely related to that of articulatory dynamics.
Dimensions in the Perception of Fortis and Lenis Plosives
Authors: Kohler Klaus J.
Published: November 2009

The analysis of the production of fortis and lenis plosives in German has shown the importance of the duration ratio vowel/ (vowel + closure) for the distinction. To complement these results a perception test was carried out in which 29 native speakers identified a randomised sequence of 220 stimuli from tape as one of the phrases ‘Diese Gruppe kann ich nicht leid(e)n (leit(e)n)’. The stimuli were obtained from the two naturally produced originals by changing the ratios and the length of voicing in the plosive through computer processing. The test results indicate very conclusively that judgment can be reversed simply by changing the ratio to the appropriate ones found in production. There is a hierarchy of perceptual dimensions: duration ratio > formant transition > voicing.
The Goal of Phonetics, Its Unification and Application
Authors: Lindblom Björn
Published: November 2009

The long-term task of phonetics is to contribute towards the construction of a theory of the use and form of spoken language. The choice of this objective is primarily scientifically motivated but is reinforced by the prospect of using phonetic knowledge for educational, clinical and technological purposes. Phonetics is relevant to the general study of spoken language in two ways: It enters into describing how language is used by speakers, listeners and learners (the psychology and physics of speech behavior) and accounting for how language is formed by the social and biological constraints on their vocal/auditory performance (the phylogeny and ontogeny of language form). Such a program is today served by phonetics oriented towards both natural science and behavioral experimentation and by general linguistics dominated by its quest for autonomy and a place in the tradition of speculative philosophy. While the immensity of the subject matter of spoken language certainly makes a multiplicity of empirical approaches mandatory, it is equally true that a broader paradigm lending theoretical unification to the mosaic of research cultures must be sought. This appears to be the case particularly with regard to the full exploitation of the theoretical and practical relevance of phonetics. The main point of the present paper is that such unification can be achieved by rejecting all attempts at making linguistics autonomous and hostile to ‘extralinguistic’ explanation and by embedding the study of language and speech, and thus phonetics, within the framework of biological functionalism.
Cortical Activity in the Left and Right Hemispheres during Language-Related Brain Functions
Authors: Lassen Niels A. , Larsen Bo
Published: November 2009

The blood flow to a given brain region increases as the level of neural activity is augmented. Hence mapping of variations in regional cerebral blood flow affords a means of imaging the activity of various brain regions during various types of brain work. The paper summarizes the patterns of cortical activity seen during various language functions, emphasizing the practically symmetrical involvement in both hemispheres. A case of auditive agnosia (with complete cortical word deafness but preserved pure tone thresholds) is presented. The patient’s normal speech constitutes evidence that auditory feedback (absent in his case) is not a prerequisite for speaking.
Modern Methods of Investigation in Speech Production
Authors: Fujimura Osamu
Published: November 2009

Methodologies of speech research with respect to the production processes are discussed, with an emphasis on the recent development of new instrumental techniques. It is argued that systematic studies of large amounts of speech data are necessary to understand the basic characteristics of speech. The traditional notion of phoneme-size segments seems inappropriate for interpreting multidimensional articulatory movements by a concatenative model. Experimental means such as a computer-controlled X-ray microbeam technique and advanced statistical processing, in combination with a new theoretical framework of phonetic description, promise future development.
The Relations between Area Functions and the Acoustic Signal
Authors: Fant Gunnar
Published: November 2009

To derive speech wave data from area function specifications and the reverse, to predict the area function from the speech wave, are fundamental problems of acoustic theory of speech production. Deviations from ideal resonator theory in terms of vocal tract boundary conditions and source filter interactions are discussed. Perturbation theory is related to special problems of male-female vocal tract scaling. Shortcomings of the inverse transforms are discussed. Merits of lossy transmission line theory over standard linear prediction procedures are emphasized. The use of bandwidths for removing ambiguities is illustrated in simple models. A limited amount of bandwidth data supplementing formant frequency data and model related vocal tract constraints appears to be optimal.
New Methods of Analysis in Speech Acoustics
Authors: Wakita Hisashi
Published: November 2009

This paper gives a tutorial review of the linear prediction method in its application to acoustical analysis of sampled speech. The paper explains how the formant frequencies and the fundamental frequency can be estimated from sampled speech waves by the use of linear prediction. Advantages and disadvantages of the method are discussed together with the problems in estimating the above parameters. Application examples are also given.
Genetic Association and Interaction Analysis of
USF1
and
APOA5
on Lipid Levels and Atherosclerosis
Authors: Laurila Pirkka-Pekka , Naukkarinen Jussi , Kristiansson Kati , Ripatti Samuli , Kauttu Tuuli , Silander Kaisa , Salomaa Veikko , Perola Markus , Karhunen Pekka J. , Barter Philip J. , Ehnholm Christian , Peltonen Leena
Published: November 2009

Objective—

USF1
is a ubiquitous transcription factor governing the expression of numerous genes of lipid and glucose metabolism.
APOA5
is a well-established candidate gene regulating triglyceride (TG) levels and has been identified as a downstream target of upstream stimulatory factor. No detailed studies about the effect of
APOA5
on atherosclerotic lesion formation have been conducted, nor has its potential interaction with
USF1
been examined.

Methods and Results—

We analyzed allelic variants of
USF1
and
APOA5
in families (n=516) ascertained for atherogenic dyslipidemia and in an autopsy series of middle-aged men (n=300) with precise quantitative measurements of atherosclerotic lesions. The impact of previously associated
APOA5
variants on TGs was observed in the dyslipidemic families, and variant rs3135506 was associated with size of fibrotic aortic lesions in the autopsy series. The
USF1
variant rs2516839, associated previously with atherosclerotic lesions, showed an effect on TGs in members of the dyslipidemic families with documented coronary artery disease. We provide preliminary evidence of gene-gene interaction between these variants in an autopsy series with a fibrotic lesion area in the abdominal aorta (
P
=0.0028), with TGs in dyslipidemic coronary artery disease subjects (
P
=0.03), and with high-density lipoprotein cholesterol (
P
=0.008) in a large population cohort of coronary artery disease patients (n=1065) in which the interaction for TGs was not replicated.

Conclusion—

Our findings in these unique samples reinforce the roles of
APOA5
and
USF1
variants on cardiovascular phenotypes and suggest that both genes contribute to lipid levels and aortic atherosclerosis individually and possibly through epistatic effects.
Leptin Enhances the Potency of Circulating Angiogenic Cells Via Src Kinase and Integrin αvβ5
Authors: Heida Nana-Maria , Leifheit-Nestler Maren , Schroeter Marco R. , Müller Jan-Peter , Cheng I-Fen , Henkel Sarah , Limbourg Anne , Limbourg Florian P. , Alves Frauke , Quigley James P. , Ruggeri Zaverio M. , Hasenfuss Gerd , Konstantinides Stavros , Schäfer Katrin
Published: November 2009

Objective—

To investigate the capacity of the adipokine leptin to promote angiogenesis by modulating the function of circulating angiogenic cells (CACs).

Methods and Results—

In vitro, leptin specifically promoted CAC adhesion to tubular endothelial structures and migration along outgrowing sprouts of endothelial cells. In vivo, stimulation of CACs with leptin increased their capacity to promote new vessel formation in the chorioallantoic membrane of chicken embryos and to improve neovascularization of ischemic murine hind limbs. These effects required the phosphorylation of αvβ5 integrins, which depended on the interaction of leptin with its receptor ObR, and on Janus kinase (JAK) 2– and phospholipase C (PLC) γ-mediated activation of Src kinase. Protein tyrosine phosphatase 1B, a negative regulator of leptin signaling, was overexpressed in CACs from obese, hyperleptinemic individuals, and this was associated with insensitivity of CACs to the angiogenic effects of leptin. Weight loss (by 30±15 kg) normalized protein tyrosine phosphatase 1B expression in CACs and restored their responsiveness to leptin. A similar dose-dependent response was found after incubation of CACs from obese subjects with a protein tyrosine phosphatase 1B inhibitor ex vivo.

Conclusion—

Our results point to the ObR–Src kinase–αvβ5 cross talk as a distinct novel component of the network of specific interactions between integrins and cytokine receptors in angiogenesis.
Loss of Stearoyl-CoA Desaturase-1 Attenuates Adipocyte Inflammation
Authors: Liu Xueqing , Miyazaki Makoto , Flowers Matthew T. , Sampath Harini , Zhao Minghui , Chu Kiki , Paton Chad M. , Joo Diane Seohee , Ntambi James M.
Published: November 2009

Background and Purpose—

Adipose inflammation is crucial to the pathogenesis of metabolic disorders. This study aimed at identify the effects of stearoyl-CoA desaturase-1 (SCD1) on the inflammatory response of a paracrine network involving adipocytes, macrophages, and endothelial cells.

Methods and Results—

Loss of SCD1 in both genetic (Agouti) and diet-induced obesity (high-fat diet) mouse models prevented inflammation in white adipose tissue and improved its basal insulin signaling. In SCD1-deficient mice, white adipose tissue exhibited lower inflammation, with a reduced response to lipopolysaccharide in isolated adipocytes, but not in peritoneal macrophages. Mimicking the in vivo paracrine regulation of white adipose tissue inflammation, SCD1-deficient adipocyte-conditioned medium attenuated the induction of tumor necrosis factor (TNF) α/interleukin 1β gene expression in RAW264.7 macrophages and reduced the adhesion response in endothelial cells. We further demonstrated that the adipocyte-derived oleate (18:1n9), but not palmitoleate (16:1n7), mediated the inflammation in macrophages and adhesion responses in endothelial cells.

Conclusions—

Loss of SCD1 attenuates adipocyte inflammation and its paracrine regulation of inflammation in macrophages and endothelial cells. The reduced oleate level is linked to the inflammation-modulating effects of SCD1 deficiency.
Claudin-5 as a Novel Estrogen Target in Vascular Endothelium
Authors: Burek Malgorzata , Arias-Loza Paula A. , Roewer Norbert , Förster Carola Y.
Published: November 2009

Objective—

Estrogens have multiple effects on vascular physiology and function. In the present study, we look for direct estrogen target genes within junctional proteins.

Methods and Results—

We use murine endothelial cell lines of brain and heart origin, which express both subtypes of estrogen receptor, ERα and ERβ. Treatment of these cells with 17β-estradiol (E2) led to an increase in transendothelial electric resistance and a most prominent upregulation of the tight junction protein claudin-5 expression. A significant increase of claudin-5 promoter activity, mRNA, and protein levels was detected in cells from both vascular beds. In protein lysates and in immunoreactions on brain sections from ovariectomized E2-treated mice, we noticed an increase in claudin-5 protein and mRNA content. Treatment of cells with a specific ERβ agonist, diarylpropionitrile, revealed the same effect as E2 stimulation. Moreover, we detected significantly lower claudin-5 mRNA and protein content in ERβ knockout mice.

Conclusions—

We describe claudin-5 as a novel estrogen target in vascular endothelium and show in vivo (brain endothelium) and in vitro (brain and heart endothelium) effects of estrogen on claudin-5 levels. The estrogen-induced increase in junctional protein levels may lead to an improvement in vascular structural integrity and barrier function of vascular endothelium.
Metabolism of Very-Low-Density Lipoprotein and Low-Density Lipoprotein Containing Apolipoprotein C-III and Not Other Small Apolipoproteins
Authors: Mendivil Carlos O. , Zheng Chunyu , Furtado Jeremy , Lel Julian , Sacks Frank M.
Published: November 2009

Objective—

We aimed to clarify the influence of apolipoprotein C-III (apoCIII) on human apolipoprotein B metabolism.

Methods and Results—

We studied the kinetics of 4 very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) types containing: (1) otherApos−CIII−: none of apoCIII, apoAII, apoCI, apoCII, or apoE; (2) otherApos+CIII−: no apoCIII but at least one of the others; (3) otherApos−CIII+: apoCIII, but not any others; and (4) otherApos+CIII+: apoCIII and at least one other. VLDL and IDL otherApos−CIII+ and otherApos−CIII− had similar rates of lipolytic conversion to smaller particles. However, light LDL otherApos−CIII+ compared with otherApos−CIII− had much faster conversion to dense LDL as did light LDL otherApos+CIII+ compared with otherApos+CIII−. VLDL and IDL otherApos−CIII+ had minimal direct removal from circulation, whereas VLDL and IDL otherApos+CIII−, rich in apoE, showed fast clearance. Lipoproteins in fraction otherApos+CIII+ also rich in apoE had very low clearance.

Conclusions—

The results suggest that apoCIII strongly inhibits hepatic uptake of VLDL and IDL overriding the opposite influence of apoE when both are present. The presence of apoCIII on dense VLDL is not associated with slow conversion to IDL, a lipoprotein lipase-dependent process; but when on light LDL, apoCIII is associated with enhanced conversion to dense LDL, a process involving hepatic lipase.
CD11c Expression in Adipose Tissue and Blood and Its Role in Diet-Induced Obesity
Authors: Wu Huaizhu , Perrard Xiaoyuan Dai , Wang Qun , Perrard Jerry L. , Polsani Venkateshwar R. , Jones Peter H. , Smith C. Wayne , Ballantyne Christie M.
Published: November 2009

Objective—

To examine CD11c, a β
2
-integrin, on adipose tissue (AT) leukocytes and blood monocytes and its role in diet-induced obesity.

Methods and Results—

High-fat diet–induced obese C57BL/6 mice, CD11c-deficient mice, and obese humans were studied. CD11c, leukocytes, and chemokines/cytokines were examined in AT and/or blood by flow cytometry, RNase protection assay, quantitative polymerase chain reaction, or enzyme-linked immunosorbent assay. Obese C57BL/6 mice had increased CD11c in AT and blood compared with lean controls. CD11c messenger RNA positively correlated with monocyte chemoattractant protein 1 in human visceral AT. Obese humans with metabolic syndrome had a higher CD11c level on blood monocytes compared with lean humans. Low-fat diet–induced weight loss reduced blood monocyte CD11c in obese mice and humans. Mouse and human monocyte CD11c levels and mouse AT CD11c messenger RNA correlated with insulin resistance. CD11c deficiency in mice did not alter weight gain but decreased inflammation, evidenced by a lower T-cell number and reduced levels of major histocompatibility complex class II, C-C chemokine ligand 2 (CCL5), CCL4, and interferon γ in AT, and ameliorated insulin resistance and glucose intolerance associated with diet-induced obesity.

Conclusions—

Diet-induced obesity increased CD11c in both AT and blood in mice and humans. CD11c plays an important role in T-cell accumulation and activation in AT, and contributes to insulin resistance associated with obesity.
Human Apolipoprotein A-II Determines Plasma Triglycerides by Regulating Lipoprotein Lipase Activity and High-Density Lipoprotein Proteome
Authors: Julve Josep , Escolà-Gil Joan Carles , Rotllan Noemi , Fiévet Catherine , Vallez Emmanuelle , de la Torre Carolina , Ribas Vicent , Sloan John H. , Blanco-Vaca Francisco
Published: November 2009

Introduction—

Apolipoprotein (apo) A-II is the second most abundant high-density lipoprotein (HDL) apolipoprotein. We assessed the mechanism involved in the altered postprandial triglyceride-rich lipoprotein metabolism of female human apoA-II-transgenic mice (hapoA-II-Tg mice), which results in up to an 11-fold increase in plasma triglyceride concentration. The relationships between apoA-II, HDL composition, and lipoprotein lipase (LPL) activity were also analyzed in a group of normolipidemic women.

Methods and Results—

Triglyceride-rich lipoprotein catabolism was decreased in hapoA-II-Tg mice compared to control mice. This suggests that hapoA-II, which was mainly associated with HDL during fasting and postprandially, impairs triglyceride-rich lipoprotein lipolysis. HDL isolated from hapoA-II-Tg mice impaired bovine LPL activity. Two-dimensional gel electrophoresis, mass spectrometry, and immunonephelometry identified a marked deficiency in the HDL content of apoA-I, apoC-III, and apoE in these mice. In normolipidemic women, apoA-II concentration was directly correlated with plasma triglyceride and inversely correlated with the HDL-apoC-II+apoE/apoC-III ratio. HDL-mediated induction of LPL activity was inversely correlated with apoA-II and directly correlated with the HDL-apoC-II+apoE/apoC-III ratio. Purified hapoA-II displaced apoC-II, apoC-III, and apoE from human HDL2. Human HDL3 was, compared to HDL2, enriched in apoA-II but poorer in apoC-II, apoC-III, and apoE.

Conclusion—

ApoA-II plays a crucial role in triglyceride catabolism by regulating LPL activity, at least in part, through HDL proteome modulation.
Hemorphin 7 Reflects Hemoglobin Proteolysis in Abdominal Aortic Aneurysm
Authors: Dejouvencel Tiphaine , Féron Delphine , Rossignol Patrick , Sapoval Marc , Kauffmann Claude , Piot Jean-Marie , Michel Jean-Baptiste , Fruitier-Arnaudin Ingrid , Meilhac Olivier
Published: November 2009

Objective—

In human abdominal aortic aneurysm, the accumulation of blood-derived cells and proteases within the mural thrombus plays a pivotal role in the evolution toward vessel wall rupture. We sought to identify peptides released from abdominal aortic aneurysm specimens, characterized by an intraluminal thrombus.

Methods and Results—

Intraluminal thrombus samples were analyzed by differential proteomics, using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. A 1309-Da peptide was detected in larger amounts in the newly formed luminal thrombus layer relative to older layers. It was identified as being LVVYPWTQRF (known as LVV-Hemorphin 7), a peptide generated from hemoglobin by cathepsin D. By immunohistochemical analysis, we showed that Hemorphin 7 (H7) colocalizes with cathepsin D and cathepsin G in the luminal layer of the intraluminal thrombus. In vitro, cathepsin G was able to generate H7 peptides at pH 7.4, whereas cathepsin D was only active in acidic conditions. Finally, H7 peptides were shown to be increased 3- to 4-fold in sera of abdominal aortic aneurysm patients relative to controls, and their levels were positively correlated with the volume of the thrombus.

Conclusion—

Our results suggest that circulating H7 peptides may reflect proteolysis of hemoglobin in the aneurysmal intraluminal thrombus and may be used as a biological marker of pathological vascular remodeling.
Thiazolidinediones Reduce Pathological Neovascularization in Ischemic Retina Via an Adiponectin-Dependent Mechanism
Authors: Higuchi Akiko , Ohashi Koji , Shibata Rei , Sono-Romanelli Saki , Walsh Kenneth , Ouchi Noriyuki
Published: November 2009

Background—

The insulin-sensitizing agents referred to as thiazolidinediones (TZDs) possess antiatherogenic and anti-inflammatory actions that contribute to protection against diabetic macrovascular complications. However, little is known about the effects of TZDs on retinal microvessel disorders.

Objective—

To investigate whether TZDs modulate retinal vessel formation in a mouse model of oxygen-induced retinopathy.

Methods and Results—

Neonatal mice were subjected to ischemia-induced retinopathy to produce pathological neovascular tuft formation. Pioglitazone, 10 mg/kg per day, rosiglitazone, 10 mg/kg per day, or vehicle was given by gavage once a day from postnatal day 7 to postnatal day 17. Systemic treatment of wild-type (WT) mice with TZDs led to a significant decrease in pathological retinal neovascularization during ischemia compared with vehicle treatment, which was accompanied by increased plasma levels of the fat-derived hormone adiponectin (APN). In contrast to WT mice, TZDs had no effects on ischemia-induced pathological retinal vessel formation in APN-knockout (KO) mice. Pioglitazone reduced tumor necrosis factor (TNF) α expression in ischemic retina in WT mice but not in APN-KO mice. Furthermore, pioglitazone increased plasma APN levels in TNF-α–KO mice but did not affect ischemia-induced pathological retinal neovascularization in this strain.

Conclusion—

These data show that TZDs attenuate pathological retinal microvessel formation through APN-mediated modulation of TNF-α production.
S100B Interaction With the Receptor for Advanced Glycation End Products (RAGE)
Authors: Tsoporis J.N. , Izhar S. , Leong-Poi H. , Desjardins J.-F. , Huttunen H.J. , Parker T.G.
Published: November 2009

Rationale
:

Post–myocardial infarction ventricular remodeling is associated with the expression of a variety of factors including S100B that can potentially modulate myocyte apoptosis.

Objective
:

This study was undertaken to investigate the expression and function of S100B and its receptor, the receptor for advanced glycation end products (RAGE) in both postinfarction myocardium and in a rat neonatal myocyte culture model.

Methods and Results
:

In a rat model of myocardial infarction following coronary artery ligation, we demonstrate in periinfarct myocytes, upregulation of RAGE, induction of S100B, and release into plasma with consequent myocyte apoptosis. Using a coimmunoprecipitation strategy, we demonstrate a direct interaction between S100B and RAGE. In rat neonatal cardiac myocyte cultures, S100B at concentrations ≥50 nmol/L induced myocyte apoptosis, as evidenced by increased terminal DNA fragmentation, TUNEL, cytochrome
c
release from mitochondria to cytoplasm, phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and p53, increased expression and activity of proapoptotic caspase-3, and decreased expression of antiapoptotic Bcl-2. Transfection of a full-length cDNA of RAGE or a dominant-negative mutant of RAGE resulted in increased or attenuated S100B-induced myocyte apoptosis, respectively. Inhibition of ERK1/2 by U0126/PD-98059 or overexpression of a dominant negative p53 comparably inhibited S100B-induced myocyte apoptosis.

Conclusions
:

These results suggest that interaction of RAGE and its ligand S100B after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53 signaling. This receptor-mediated mechanism is uniquely amenable to therapeutic intervention.
CXCL4 Downregulates the Atheroprotective Hemoglobin Receptor CD163 in Human Macrophages
Authors: Gleissner Christian A. , Shaked Iftach , Erbel Christian , Böckler Dittmar , Katus Hugo A. , Ley Klaus
Published: November 2009

Rationale
:

CXCL4 is a platelet-derived chemokine that promotes macrophage differentiation from monocytes. Deletion of the
PF4
gene that encodes CXCL4 reduces atherosclerotic lesions in
ApoE
−/−
mice.

Objective
:

We sought to study effects of CXCL4 on macrophage differentiation with possible relevance for atherogenesis.

Methods and Results
:

Flow cytometry for expression of surface markers in macrophage colony–stimulating factor (M-CSF)– and CXCL4-induced macrophages demonstrated virtually complete absence of the hemoglobin scavenger receptor CD163 in CXCL4-induced macrophages. mRNA for CD163 was downregulated as early as 2 hours after CXCL4. CD163 protein reached a minimum after 3 days, which was not reversed by treatment of cells with M-CSF. The CXCL4 effect was entirely neutralized by heparin, which bound CXCL4 and prevented CXCL4 surface binding to monocytes. Pretreatment of cells with chlorate, which inhibits glycosaminoglycan synthesis, strongly inhibited CXCL4-dependent downregulation of CD163. Similar to recombinant CXCL4, releasate from human platelets also reduced CD163 expression. CXCL4-differentiated macrophages were unable to upregulate the atheroprotective enzyme heme oxygenase-1 at the RNA and protein level in response to hemoglobin–haptoglobin complexes. Immunofluorescence of human atherosclerotic plaques demonstrated presence of both CD68
+
CD163
+
and CD68
+
CD163
−
macrophages.
PF4
and
CD163
gene expression within human atherosclerotic lesions were inversely correlated, supporting the in vivo relevance of CXCL4-induced downregulation of CD163.

Conclusions
:

CXCL4 may promote atherogenesis by suppressing CD163 in macrophages, which are then unable to upregulate the atheroprotective enzyme heme oxygenase-1 in response to hemoglobin.