Sociolectal and Dialectal Variation in Prosody.

As in many linguistics subfields, studies of prosody have mainly focused on majority languages and dialects and on speakers who hold power in social structures. The goal of this Special Issue is to diversify prosody research in terms of the languages and dialects being investigated, as well as the social structures that influence prosodic variation. The Special Issue brings together prosody researchers and researchers exploring sociological variation in prosody, with a focus on the prosody of marginalized dialects and on prosodic differences based on gender, sexuality, race, and ethnicity. The papers in this volume don't just advance our understanding of critical issues in sociolinguistics, but they also challenge some of the received wisdom in the exploration of sociolinguistic influences on prosody. Not only does this collection highlight the value of this work to informing theories of prosodic variation and change, but the collected papers also provide examples of methodological innovations in the field that will be valuable for all prosody researchers.

Range in the Use and Realization of BIN in African American English.

This paper jointly considers syntactic, semantic, and phonological/phonetic factors in approaching an understanding of BIN, a remote past marker in African American English that has been described as "stressed." It brings together data from the Corpus of Regional African American Language (CORAAL) and a production study in a small African American English-speaking community in southwest Louisiana to investigate the use and phonetic realization of BIN constructions. Only 20 instances of BIN constructions were found in CORAAL. This sparsity was not simply due to a dearth of semantic contexts for BIN in the interviews, since 122 instances of semantically equivalent been + temporal adverbial variants were also found. These results raise questions about the extent to which BIN constructions and been + temporal adverbial variants are used in different pragmatic and discourse contexts as well as in different speech styles. The production study elicited BIN and past participle been constructions in controlled syntactic and semantic environments. The phonetic realization of BIN was found to be distributed over the entire utterance rather than localized to BIN. BIN utterances were distinguished from past participle been utterances by having higher ratios of fundamental frequency (F0), intensity, and duration in BIN/been relative to preceding and following material in the utterance. In both studies, BIN utterances were generally realized with a high F0 peak on BIN and a reduced F0 range in the post-BIN region, with variability in the presence and kinds of F0 movements utterance-initially and utterance-finally, as well as in F0 downtrends in the post-BIN region.

The role of creaky voice in Cantonese tonal perception.

There are few studies on the role of phonation cues in the perception of lexical tones in tonal languages where pitch is the primary dimension of contrast. This study shows that listeners are sensitive to creaky phonation in native tonal perception in Cantonese, a language in which the low falling tone, Tone 4, has anecdotally been reported to be sometimes creaky. First, in a multi-speaker corpus of lab speech, it is documented that creak occurs systematically more often on Tone 4 than other tones. Second, for stimuli drawn from this corpus, listeners identified Tone 4 with 20% higher accuracy when it was realized with creak than when it was not. Third, in a two-alternative forced choice task of identifying stimuli as Tone 4 or Tone 6 (the low level tone) isolating creak from any concomitant pitch cues, listeners had a higher proportion of Tone 4 responses for creaky stimuli. Finally, listeners had more Tone 4 responses for creaky stimuli with longer durations of nonmodal phonation. These results underscore that differences in voice quality contribute to human perception of tone alongside f0. Automatic tonal recognition and clinical applications for tone would benefit from attention to voice quality beyond f0 and pitch.

Tyrosine sulfation is prevalent in human chemokine receptors important in lung disease.

Post-translational sulfation of tyrosines affects the affinity and binding of at least some chemokine receptors to their ligand(s) and has been hypothesized to be a feature in all chemokine receptors. This binding initiates downstream signaling cascades. By this mechanism, tyrosine sulfation can influence the cells involved in acute and chronic events of cellular immunity. These events include leukocyte trafficking and airway inflammation important in asthma and chronic obstructive pulmonary disease (COPD). We are using computational methods to convert the poorly defined hypothesis of more widespread sulfation of chemokine receptors to more specific assessments of how closely the sequence environment of each tyrosine residue resembles the sequence environment of tyrosine residues proven to be sulfated. Thus, we provide specific and readily tested hypotheses about the tyrosine residues in all of the chemokine receptors. Tyrosine sulfation was predicted with high scores in the N-terminus domain of 13 out of 18 human chemokine receptor proteins using a position-specific scoring matrix, which was determined to be 94.2% accurate based on Receiver Operating Characteristic analysis. The remaining chemokine receptors have sites exhibiting features of tyrosine sulfation. These putative sites demonstrate clustering in a manner consistent with known tyrosine sulfation sites and conservation both within the chemokine receptor family and across mammalian species. Human chemokine receptors important in asthma and COPD, such as CXCR1, CXCR2, CXCR3, CXCR4, CCR1, CCR2, CCR3, CCR4, CCR5, and CCR8, contain at least one known or predicted tyrosine sulfation site. Recognition that tyrosine sulfation is found in most clinically relevant chemokine receptors could help the development of specific receptor-ligand antagonists to modulate events important in airway diseases.

Contributions of ATM mutations to familial breast and ovarian cancer.

This study addresses the prevalence of ATM mutations and the association with breast cancer in Austrian families selected for a history of breast or ovarian cancer or both [hereditary breast and ovarian cancer (HBOC)]. In 270 HBOC families previously screened for BRCA1 and BRCA2 mutations, 137 different sequence alterations of ATM were identified. Seven of these were mutations presumed to cause ataxia telangiectasia based on their effect on the ATM protein, including five that caused a protein truncation and two missense mutations in the catalytic kinase domain of the highly conserved COOH terminus of the protein. The seven mutations were found in 10 families (3.7%). In addition, one missense variant, L1420F, was observed in 13 HBOC families (4.8%) but was not observed in any of the 122 healthy volunteers with no history of breast cancer. In addition, the variant segregated with breast cancer in some of the families, suggesting that it may be pathogenic for breast cancer. Sixty-two additional variants of potential significance were observed in 65 HBOC families, but not in healthy controls. These variants included 24 sequence alterations with possible effects on splicing or protein-protein interactions. This study indicates that there is a significant prevalence of ATM mutations in breast and ovarian cancer families and adds to a growing body of evidence that ATM mutations confer increased susceptibility to breast cancer.

Prediction of tyrosine sulfation in seven-transmembrane peptide receptors.

Posttranslational modification by tyrosine sulfation regulates many important protein protein interactions and modulates the binding affinity and specificity of seventransmembrane peptide receptors. We developed a log-odds position-specific-scoring-matrix (PSSM) to accurately predict tyrosine sulfation using 62 tyrosine sites known to be sulfated and 421 tyrosine sites known not to be sulfated. We predict that 49 tyrosines of 32 seven-transmembrane peptide receptors are sulfated. Although we did not incorporate characteristics of confirmed sulfation sites such as clustering and conservation across species into our PSSM, our predicted sites nevertheless exhibited these characteristics. The observed conservation suggests that there are strong evolutionary pressures to preserve selected biological activity of seven-transmembrane receptors. The predicted tyrosine sulfation sites predominantly occur in the extracellular tail and extracellular loop 2, regions consistent with their association with binding pockets of the receptor.