Tetrandrine, a Potent Antifungal Agent, Inhibits Mycelial Growth and Virulence of Botrytis cinerea.

Tetrandrine (TET) is a potent calcium channel blocker used to treat hypertension and inflammation. Currently, TET is predominantly used to treat a variety of human diseases, and there is little information regarding the use of TET against plant pathogens. In this study, we explored the antifungal activity of TET on a plant pathogen, Botrytis cinerea. We show that administration of low concentrations of TET effectively inhibited hyphal growth of fungus grown on potato dextrose agarose and decreased the virulence of B. cinerea in tomato plants. Real-time PCR revealed that the expression of drug efflux pump-related genes (alcohol dehydrogenase 1, multidrug/pheromone exporter, pleiotropic drug resistance protein 1, and synaptic vesicle transporter) were downregulated in the presence of TET. Finally, we show that TET acts synergistically with iprodione, resulting in increased inhibition of B. cinerea both in vitro and in vivo. These results indicate that TET might act as an effective antifungal agent in reducing gray mold disease.

Convergent Total Synthesis of Yaku'amide†A.

Total synthesis of the anticancer peptide natural product yaku'amide A is reported. Its ß-tert-hydroxy amino acids were prepared by regioselective aminohydroxylation involving a chiral mesyloxycarbamate reagent. Stereospecific construction of the E- and Z-ΔIle residues was accomplished through a one-pot reaction featuring anti dehydration, azide reduction, and O→N acyl transfer. Alkene isomerization was negligible during this process. These methods enabled a highly convergent and efficient synthetic route to the natural product.

Serum uric acid is independently associated with aortic arch calcification in a cross-sectional study of middle-aged and elderly women.

BACKGROUND AND AIMS: The increased serum uric acid (SUA) level is associated with the prevalence of cardiovascular disease (CVD) risks. Aortic arch calcification (AAC) reflects subclinical coronary atherosclerosis and is linked to subsequent cardiovascular morbidity and mortality risks closely. To better understand the role of SUA on arteriosclerosis and CVD, we aim to determine the association between SUA and the presence of AAC. METHODS AND RESULTS: A total of 5920 individuals aged >45 years old without prior CVD disease were included. The prevalence rate of AAC was 14.4% in all participants and a significantly increasing trend for AAC prevalence rate was found across the SUA tertiles (p < 0.001 for trend). Subsequent subgroup analyses revealed that this positive association trend was only significant in female subjects. After adjusting for confounders, SUA is an independent predictor for the presence of AAC in overall participants and in women. CONCLUSION: SUA is independently associated with AAC in middle-aged and elderly population, especially in the women. More research needs to determine whether lower thresholds for CVD risk screening for those middle-aged and elderly women with higher SUA tertile even without hyperuricemia are warranted.

Origin of the Activity of Electrochemical Ozone Production over Rutile PbO2 Surfaces.

Ozonation water treatment technology has attracted increasing attention due to its environmental benign and high efficiency. Rutile PbO2 is a promising anode material for electrochemical ozone production (EOP). However, the reaction mechanism underlying ozone production catalyzed by PbO2 was rarely studied and not well-understood, which was in part due to the overlook of the electrochemistry-driven formation of oxygen vacancy (OV) of PbO2. Herein, we unrevealed the origin of the EOP activity of PbO2 starting from the electrochemical surface state analysis using density functional theory (DFT) calculations, activity analysis, and catalytic volcano modeling. Interestingly, we found that under experimental EOP potential (i.e., a potential around 2.2 V vs. reversible hydrogen electrode), OV can still be generated easily on PbO2 surfaces. Our subsequent kinetic and thermodynamic analyses show that these OV sites on PbO2 surfaces are highly active for the EOP reaction through an interesting atomic oxygen (O*)-O2 coupled mechanism. In particular, rutile PbO2(101) with the "in-situ" generated OV exhibited superior EOP activities, outperforming (111) and (110). Finally, by catalytic modeling, we found that PbO2 is close to the theoretical optimum of the reaction, suggesting a superior EOP performance of rutile PbO2. All these analyses are in good agreement with experimental observations.

Guizhitongluo Tablet inhibits atherosclerosis and foam cell formation through regulating Piezo1/NLRP3 mediated macrophage pyroptosis.

BACKGROUND: Atherosclerosis (AS) is the main pathological basis for the development of cardiovascular diseases. Vascular inflammation is an important factor in the formation of AS, and macrophage pyroptosis plays a key role in AS due to its unique inflammatory response. Guizhitongluo Tablet (GZTLT) has shown clinically effective in treating patients with AS, but its mechanism is elusive. PURPOSE: This study was to determine the effects of GZTLT on atherosclerotic vascular inflammation and pyroptosis and to understand its underlying mechanism. MATERIALS AND METHODS: The active constituents of GZTLT were analysed by means of UPLC-HRMS. In vivo experiments were performed using ApoE-/- mice fed a high fat diet for 8 weeks, followed by treatment with varying concentrations of GZTLT orally by gavage and GsMTx4 (GS) intraperitoneally and followed for another 8 weeks. Oil red O, Haematoxylin-eosin (HE) and Masson staining were employed to examine the lipid content, plaque size, and collagen fibre content of the mouse aorta. Immunofluorescence staining was utilised to identify macrophage infiltration, as well as the expression of Piezo1 and NLRP3 proteins in aortic plaques. The levels of aortic inflammatory factors were determined using RT-PCR and ELISA. In vitro, foam cell formation in bone marrow-derived macrophages (BMDMs) was observed using Oil Red O staining. Intracellular Ca2+ measurements were performed to detect the calcium influx in BMDMs, and the expression of NLRP3 and its related proteins were detected by Western blot. RESULTS: The UPLC-HRMS analysis revealed 31 major components of GZTLT. Our data showed that GZTLT inhibited aortic plaque formation in mice and increased plaque collagen fibre content to stabilise plaques. In addition, GZTLT could restrain the expression of serum lipid levels and suppress macrophage foam cell formation. Further studies found that GZTLT inhibited macrophage infiltration in aortic plaques and suppressed the expression of inflammatory factors. It is noteworthy that GZTLT can restrain Piezo1 expression and reduce Ca2+ influx in BMDMs. Additionally, we found that GZTLT could regulate NLRP3 activation and pyroptosis by inhibiting Piezo1. CONCLUSION: The present study suggests that GZTLT inhibits vascular inflammation and macrophage pyroptosis through the Piezo1/NLRP3 signaling pathway, thereby delaying AS development. Our finding provides a potential target for AS treatment and drug discovery.

Piezo1 specific deletion in macrophage protects the progression of liver fibrosis in mice.

Background and Aims: Liver fibrosis is the common pathological pathway of chronic liver diseases and its mechanisms of which have not been fully declared. Macrophages play essential roles in progression of liver fibrosis partially by sensing abnormal mechanical signals. The aim of the study is to investigate the functions of macrophage Piezo1, a mechano-sensitive ion channel, in liver fibrosis. Approach and Results: Immunofluorescence in human and murine fibrotic liver samples revealed that expression of macrophage Piezo1 was increased. Myeloid-specific Piezo1 knockout (Piezo1ΔLysM) attenuated liver fibrosis by decreased collagen deposition and epithelial-mesenchymal transition (EMT). In Piezo1ΔLysM mice, less inflammation during development of liver fibrosis was observed by lessened macrophage infiltration, decreased M1 polarization and expression of inflammatory cytokines. RNA-seq data showed macrophage Piezo1 regulated transcription of cathepsin S (CTSS). Piezo1ΔLysM inhibited expression and activity of CTSS in vitro and in vivo and regulated T cell activity. Furthermore, inhibition of CTSS reversed macrophage inflammatory response driven by Piezo1 activation and LPS. Macrophage Piezo1 activation promoted CTSS secretion due to increased activity of Ca2+-dependent calpain protease induced by Ca2+ influx to cleave lysosome-associated membrane protein-1 (LAMP1). Pharmacological inhibition of calpain activity partially blocked Piezo1 mediated CTSS secretion. Conclusions: Macrophage Piezo1 deficiency limits the progression of liver fibrosis by inhibited inflammatory response and decreased secretion of CTSS. These findings suggest that targeting Piezo1 channel may be a potential strategy for treating hepatic fibrosis.

Myeloid Piezo1 Deletion Protects Renal Fibrosis by Restraining Macrophage Infiltration and Activation.

BACKGROUND: Macrophages play important roles in renal fibrosis, partially by sensing mechanical forces, including shear stress and increased stiffness. The mechanically activated cationic channel Piezo1 drives vascular formation and blood pressure regulation to inflammatory responses, or cancer, but its role in macrophages in fibrotic kidney is elusive. Here, we hypothesized that Piezo1 in macrophages may have functions in renal fibrosis. METHODS: We established a genetically engineered mouse model with Piezo1 specific knockout in myeloid cells and challenged with unilateral ureteric obstruction operation and folic acid treatment to induce the renal fibrosis, aiming to investigate the function of the mechanical-sensitive protein Piezo1 in macrophages in renal fibrosis and its underlying mechanisms. RESULTS: Myeloid Piezo1 was indispensable for renal fibrosis generation. Piezo1 gene deletion in the myeloid lineage was protective in mice with renal fibrosis. Further analyses revealed that macrophage accumulation in the injured kidney depended on the Piezo1-regulated C-C motif chemokine ligand 2, C-C motif chemokine receptor 2 pathway, and Notch signaling cascade. Moreover, Piezo1 deletion restrained macrophage inflammation and consequently suppressed kidney fibrosis and epithelial-mesenchymal transition. In vitro assays showed that Piezo1 deficiency blocked lipopolysaccharide and Piezo1 activation-induced inflammatory responses in bone marrow-derived macrophages. Mechanistically, Piezo1 regulated inflammation through the Ca2+-dependent intracellular cysteine protease, as the pharmacological inhibition of calpain blocked the proinflammatory role of Piezo1. CONCLUSIONS: This study characterized the important function of Piezo1 in renal fibrosis. Targeting the Piezo1 channels by genetic or pharmacological manipulations may be a promising strategy for the treatment of renal fibrosis.

Visual phonetic processing localized using speech and nonspeech face gestures in video and point-light displays.

The talking face affords multiple types of information. To isolate cortical sites with responsibility for integrating linguistically relevant visual speech cues, speech and nonspeech face gestures were presented in natural video and point-light displays during fMRI scanning at 3.0T. Participants with normal hearing viewed the stimuli and also viewed localizers for the fusiform face area (FFA), the lateral occipital complex (LOC), and the visual motion (V5/MT) regions of interest (ROIs). The FFA, the LOC, and V5/MT were significantly less activated for speech relative to nonspeech and control stimuli. Distinct activation of the posterior superior temporal sulcus and the adjacent middle temporal gyrus to speech, independent of media, was obtained in group analyses. Individual analyses showed that speech and nonspeech stimuli were associated with adjacent but different activations, with the speech activations more anterior. We suggest that the speech activation area is the temporal visual speech area (TVSA), and that it can be localized with the combination of stimuli used in this study.

Perception of Place of Articulation for Plosives and Fricatives in Noise.

This study aims at uncovering perceptually-relevant acoustic cues for the labial versus alveolar place of articulation distinction in syllable-initial plosives {/b/,/d/,/p/,/t/} and fricatives {/f/,/s/,/v/,/z/} in noise. Speech materials consisted of naturally-spoken consonant-vowel (CV) syllables from four talkers where the vowel was one of {/a/,/i/,/u/}. Acoustic analyses using logistic regression show that formant frequency measurements, relative spectral amplitude measurements, and burst/noise durations are generally reliable cues for labial/alveolar classification. In a subsequent perceptual experiment, each pair of syllables with the labial/alveolar distinction (e.g., /ba,da/) was presented to listeners in various levels of signal-to-noise-ratio (SNR) in a 2-AFC task. A threshold SNR was obtained for each syllable pair using sigmoid fitting of the percent correct scores. Results show that the perception of the labial/alveolar distinction in noise depends on the manner of articulation, the vowel context, and interaction between voicing and manner of articulation. Correlation analyses of the acoustic measurements and threshold SNRs show that formant frequency measurements (such as F1 and F2 onset frequencies and F2 and F3 frequency changes) become increasingly important for the perception of labial/alveolar distinctions as the SNR degrades.

CFP is a prognostic biomarker and correlated with immune infiltrates in Gastric Cancer and Lung Cancer.

Complement factor properdin (CFP), encodes plasma glycoprotein, is a critical gene that regulates the complement pathway of the innate immune system. However, correlations of CFP in cancers remain unclear. In this study, the expression pattern and prognostic value of CFP in pan-cancer were analyzed via the Oncomine, PrognoScan, GEPIA and Kaplan-Meier plotters. In addition, we used immunohistochemical staining to validate CFP expression in clinical tissue samples. Finally, we evaluated the correlations between CFP and cancer immune infiltrates particularly in stomach adenocarcinoma (STAD) and lung adenocarcinoma (LUAD) by using GEPIA and TIMER databases. The results of database analysis and immunohistochemistry showed that the expression level of CFP in STAD and LUAD was lower than that in normal tissues. Low expression level of CFP was associated with poorer overall survival (OS), first progression (FP), post progression survival (PPS) and was detrimental to the prognosis of STAD and LUAD, specifically in stage 3, stage T3, stage N2 and N3 of STAD (P<0.05). Moreover, expression of CFP had significant positive correlations with the infiltration levels of CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells (DCs) in STAD and LUAD. Furthermore, gene markers of infiltrating immune cells exhibited different CFP-related immune infiltration patterns such as tumor-associated-macrophages (TAMs). These results suggest that CFP can serve as a prognostic biomarker for determining prognosis and immune infiltration in STAD and LUAD.

Comparison of landmark-based and automatic methods for cortical surface registration.

Group analysis of structure or function in cerebral cortex typically involves, as a first step, the alignment of cortices. A surface-based approach to this problem treats the cortex as a convoluted surface and coregisters across subjects so that cortical landmarks or features are aligned. This registration can be performed using curves representing sulcal fundi and gyral crowns to constrain the mapping. Alternatively, registration can be based on the alignment of curvature metrics computed over the entire cortical surface. The former approach typically involves some degree of user interaction in defining the sulcal and gyral landmarks while the latter methods can be completely automated. Here we introduce a cortical delineation protocol consisting of 26 consistent landmarks spanning the entire cortical surface. We then compare the performance of a landmark-based registration method that uses this protocol with that of two automatic methods implemented in the software packages FreeSurfer and BrainVoyager. We compare performance in terms of discrepancy maps between the different methods, the accuracy with which regions of interest are aligned, and the ability of the automated methods to correctly align standard cortical landmarks. Our results show similar performance for ROIs in the perisylvian region for the landmark-based method and FreeSurfer. However, the discrepancy maps showed larger variability between methods in occipital and frontal cortex and automated methods often produce misalignment of standard cortical landmarks. Consequently, selection of the registration approach should consider the importance of accurate sulcal alignment for the specific task for which coregistration is being performed. When automatic methods are used, the users should ensure that sulci in regions of interest in their studies are adequately aligned before proceeding with subsequent analysis.

Critical Role of AdipoR1 in Regulating Th17 Cell Differentiation Through Modulation of HIF-1α-Dependent Glycolysis.

We previously reported that adiponectin (AD) promotes naïve T cell differentiation into Th17 cells and participates in synovial inflammation and the bone erosion process in patients with rheumatoid arthritis. Here, we use a T cell lineage adiponectin receptor 1 (AdipoR1) conditional knockout model to investigate the role of AdipoR1 in Th17 differentiation. RNA-sequencing (RNA-seq) demonstrated that AdipoR1 knockout reduced the expression of a variety of T cell related genes, with Rorc showing the greatest level of down-regulation. AdipoR1 deficiency inhibited Th17 cell differentiation in vitro and ameliorated joint inflammation in antigen-induced arthritis mice. Moreover, AdipoR1-deficent CD4+T cells displayed reduced Hypoxia-Inducible Factor-1α expression leading to glycolysis inhibition during naïve CD4+T cell differentiation into Th17 cells. We describe a novel function of AdipoR1 in regulating Th17 cell differentiation through modulating HIF-1α-dependent glycolysis.

MicroRNA-15a/16/SOX5 axis promotes migration, invasion and inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes.

Fibroblast-like synoviocytes (FLSs) are key effector cells in the pathogenesis of rheumatoid arthritis (RA) and display a unique aggressive tumor-like phenotype with remarkable hyperplasia, increased cell migration and invasion. How FLSs undergo these changes in RA remains unknown. We previously reported a novel function of transcription factor SOX5 in RA-FLSs that promote cell migration and invasion. In this study, we found that miR-15a/16 directly targets the SOX5 3'UTR and suppresses SOX5 expression. Moreover, miR-15a/16 is significantly down-regulated in RA-FLSs, which negatively correlates with SOX5 expression. Transfection with miR-15a/16 mimics in RA-FLSs inhibits cell migration, invasion, IL-1ß and TNFα expression. Overexpression SOX5 in RA-FLSs decreases miR-15a/16 expression and rescues miR-15a/16-mediated inhibitory effect. Furthermore, RA patients with the lower baseline serum miR-15a/16 level present poor response of 3 months disease-modifying antirheumatic drugs (DMARDs) therapy. Collectively, this study reveals that miR-15a/16/SOX5 axis functions as a key driver of RA-FLSs invasion, migration and inflammatory response in a mutual negative feedback loop and correlates with DMARDs treatment response in RA.

Polyporus Polysaccharide Ameliorates Bleomycin-Induced Pulmonary Fibrosis by Suppressing Myofibroblast Differentiation via TGF-ß/Smad2/3 Pathway.

Pulmonary fibrosis is a major cause of morbidity and mortality in systemic sclerosis (SSc) with no effective medication. Polyporus polysaccharide (PPS), extracted from Chinese herbs, has immune regulation, anticancer, antioxidant and antiinflammatory activities. This study aims to investigate antifibrotic effects of PPS. We show that PPS markedly ameliorates bleomycin-induced lung fibrosis in mice. Myofibroblasts are the effector cells responsible for excessive deposition of extracellular matrix (ECM) proteins in fibrotic diseases. In vitro evidence reveals that PPS exerts potent antifibrotic effects by inhibiting fibroblast-to-myofibroblast transition, suppressing ECM deposition, and repressing lung fibroblast proliferation and migration. We also find that PPS inhibits TGF-ß1-induced Smad2/3 activating. This study is the first to demonstrate an antifibrotic role of PPS in lungs, thus warranting further therapeutic evaluation.

Visual speech discrimination and identification of natural and synthetic consonant stimuli.

From phonetic features to connected discourse, every level of psycholinguistic structure including prosody can be perceived through viewing the talking face. Yet a longstanding notion in the literature is that visual speech perceptual categories comprise groups of phonemes (referred to as visemes), such as /p, b, m/ and /f, v/, whose internal structure is not informative to the visual speech perceiver. This conclusion has not to our knowledge been evaluated using a psychophysical discrimination paradigm. We hypothesized that perceivers can discriminate the phonemes within typical viseme groups, and that discrimination measured with d-prime (d') and response latency is related to visual stimulus dissimilarities between consonant segments. In Experiment 1, participants performed speeded discrimination for pairs of consonant-vowel spoken nonsense syllables that were predicted to be same, near, or far in their perceptual distances, and that were presented as natural or synthesized video. Near pairs were within-viseme consonants. Natural within-viseme stimulus pairs were discriminated significantly above chance (except for /k/-/h/). Sensitivity (d') increased and response times decreased with distance. Discrimination and identification were superior with natural stimuli, which comprised more phonetic information. We suggest that the notion of the viseme as a unitary perceptual category is incorrect. Experiment 2 probed the perceptual basis for visual speech discrimination by inverting the stimuli. Overall reductions in d' with inverted stimuli but a persistent pattern of larger d' for far than for near stimulus pairs are interpreted as evidence that visual speech is represented by both its motion and configural attributes. The methods and results of this investigation open up avenues for understanding the neural and perceptual bases for visual and audiovisual speech perception and for development of practical applications such as visual lipreading/speechreading speech synthesis.

Selective access to E- and Z-ΔIle-containing peptides via a stereospecific E2 dehydration and an O → N acyl transfer.

A concise synthesis of peptides that contain E- or Z-dehydroisoleucine (ΔIle) residues is reported. The key reaction is an unusual anti dehydration of ß-tert-hydroxy amino acid derivatives that is mediated by the Martin sulfurane. A subsequent tandem Staudinger reduction-O → N acyl transfer process forges an amide bond to the ΔIle residue with minimal E/Z alkene isomerization. Density functional calculations attribute the stereospecific dehydration to a highly asynchronous E2 anti process.

Auditory Perceptual Learning for Speech Perception Can be Enhanced by Audiovisual Training.

Speech perception under audiovisual (AV) conditions is well known to confer benefits to perception such as increased speed and accuracy. Here, we investigated how AV training might benefit or impede auditory perceptual learning of speech degraded by vocoding. In Experiments 1 and 3, participants learned paired associations between vocoded spoken nonsense words and nonsense pictures. In Experiment 1, paired-associates (PA) AV training of one group of participants was compared with audio-only (AO) training of another group. When tested under AO conditions, the AV-trained group was significantly more accurate than the AO-trained group. In addition, pre- and post-training AO forced-choice consonant identification with untrained nonsense words showed that AV-trained participants had learned significantly more than AO participants. The pattern of results pointed to their having learned at the level of the auditory phonetic features of the vocoded stimuli. Experiment 2, a no-training control with testing and re-testing on the AO consonant identification, showed that the controls were as accurate as the AO-trained participants in Experiment 1 but less accurate than the AV-trained participants. In Experiment 3, PA training alternated AV and AO conditions on a list-by-list basis within participants, and training was to criterion (92% correct). PA training with AO stimuli was reliably more effective than training with AV stimuli. We explain these discrepant results in terms of the so-called "reverse hierarchy theory" of perceptual learning and in terms of the diverse multisensory and unisensory processing resources available to speech perception. We propose that early AV speech integration can potentially impede auditory perceptual learning; but visual top-down access to relevant auditory features can promote auditory perceptual learning.

Psychophysics of the McGurk and other audiovisual speech integration effects.

When the auditory and visual components of spoken audiovisual nonsense syllables are mismatched, perceivers produce four different types of perceptual responses, auditory correct, visual correct, fusion (the so-called McGurk effect), and combination (i.e., two consonants are reported). Here, quantitative measures were developed to account for the distribution of the four types of perceptual responses to 384 different stimuli from four talkers. The measures included mutual information, correlations, and acoustic measures, all representing audiovisual stimulus relationships. In Experiment 1, open-set perceptual responses were obtained for acoustic /bɑ/ or /lɑ/ dubbed to video /bɑ, dɑ, gɑ, vɑ, zɑ, lɑ, wɑ, ðɑ/. The talker, the video syllable, and the acoustic syllable significantly influenced the type of response. In Experiment 2, the best predictors of response category proportions were a subset of the physical stimulus measures, with the variance accounted for in the perceptual response category proportions between 17% and 52%. That audiovisual stimulus relationships can account for perceptual response distributions supports the possibility that internal representations are based on modality-specific stimulus relationships.

Quantified acoustic-optical speech signal incongruity identifies cortical sites of audiovisual speech processing.

A fundamental question about human perception is how the speech perceiving brain combines auditory and visual phonetic stimulus information. We assumed that perceivers learn the normal relationship between acoustic and optical signals. We hypothesized that when the normal relationship is perturbed by mismatching the acoustic and optical signals, cortical areas responsible for audiovisual stimulus integration respond as a function of the magnitude of the mismatch. To test this hypothesis, in a previous study, we developed quantitative measures of acoustic-optical speech stimulus incongruity that correlate with perceptual measures. In the current study, we presented low incongruity (LI, matched), medium incongruity (MI, moderately mismatched), and high incongruity (HI, highly mismatched) audiovisual nonsense syllable stimuli during fMRI scanning. Perceptual responses differed as a function of the incongruity level, and BOLD measures were found to vary regionally and quantitatively with perceptual and quantitative incongruity levels. Each increase in the level of incongruity resulted in an increase in overall levels of cortical activity and in additional activations. However, the only cortical region that demonstrated differential sensitivity to the three stimulus incongruity levels (HI>MI>LI) was a subarea of the left supramarginal gyrus (SMG). The left SMG might support a fine-grained analysis of the relationship between audiovisual phonetic input in comparison with stored knowledge, as hypothesized here. The methods here show that quantitative manipulation of stimulus incongruity is a new and powerful tool for disclosing the system that processes audiovisual speech stimuli.

Similarity structure in visual speech perception and optical phonetic signals.

A complete understanding of visual phonetic perception (lipreading) requires linking perceptual effects to physical stimulus properties. However, the talking face is a highly complex stimulus, affording innumerable possible physical measurements. In the search for isomorphism between stimulus properties and phoneticeffects, second-order isomorphism was examined between theperceptual similarities of video-recorded perceptually identified speech syllables and the physical similarities among the stimuli. Four talkers produced the stimulus syllables comprising 23 initial consonants followed by one of three vowels. Six normal-hearing participants identified the syllables in a visual-only condition. Perceptual stimulus dissimilarity was quantified using the Euclidean distances between stimuli in perceptual spaces obtained via multidimensional scaling. Physical stimulus dissimilarity was quantified using face points recorded in three dimensions by an optical motion capture system. The variance accounted for in the relationship between the perceptual and the physical dissimilarities was evaluated using both the raw dissimilarities and the weighted dissimilarities. With weighting and the full set of 3-D optical data, the variance accounted for ranged between 46% and 66% across talkers and between 49% and 64% across vowels. The robust second-order relationship between the sparse 3-D point representation of visible speech and the perceptual effects suggests that the 3-D point representation is a viable basis for controlled studies of first-order relationships between visual phonetic perception and physical stimulus attributes.