bluuebunny/crossref_metadata_2025 huggingface dataset:
Is infants' native language preference in the visual modality guided by speech rhythm?
Authors: Ward Nancy , Sundara Megha
Published: October 2011

Newborns prefer to listen to their native language. We have shown that this preference for the native language also exists with visual cues alone (Ward and Sundara, 2010). Four and 8-month-old monolingual English-learning infants looked longer at a face speaking English compared to Spanish. What information in the talking faces facilitates language identification, and thus language preference in infants? Studies on visual language discrimination (Soto-Faraco et al., 2007; Ronquest et al., 2010) suggest three possibilities: (1) lexical information accessed through lip-reading, (2) language-specific movement of the articulators, and (3) rhythmic information. Infants in their first year of life cannot rely on their developing lexicon for visual language preference. Here, we investigate whether rhythmic information is guiding infants' attentional preferences. We use the preferential looking procedure to test whether monolingual English and monolingual Spanish-learning 4-month-olds show a preference for looking at a face speaking Dutch over Spanish. Monolingual Spanish-learning 4-month-olds are expected to show a native language preference for the face talking in Spanish, replicating our previous findings. Crucially, if familiarity with language rhythm is sufficient to guide preferences for talking faces, we expect monolingual English-learning infants to demonstrate a preference for rhythmically similar Dutch, when presented opposite a rhythmically different Spanish.
The acquisition of English rhythm as a function of changes in phrase-level prosody
Authors: Redford Melissa A. , Sirsa Hema , Shport Irina A.
Published: October 2011

Language rhythm emerges from a combination of lexical and phrase-level prosody. This talk will review evidence from on-going and completed studies on the acquisition of English prosody in typically developing school-age children to show that the surprisingly protracted acquisition of English rhythm is due to the extended acquisition of phrase-level prosody rather than to immature lexical stress production. Cross-sectional and longitudinal data from 20 native American-English speaking children indicate that whereas adult-like rhythm may not be fully acquired until age 8, even the youngest children have mastered lexical stress. Unlike eight-year-olds, though, younger children show less reduced vowels in function words and a less robust pattern of phrase-final lengthening. We argue, based on evidence from a separate study on stress-shifting in 25 six-year-olds and 25 adults, that younger children have yet to fully integrate lexical patterns into phrase-level prosodic structures. A lack of complete integration between lexical and phrasal levels may account for the extended acquisition of prosodically conditioned vowel reduction, which in turn could account for the prolonged acquisition of English rhythm. [Work supported by NIH Grant R01 HD061458.]
Quantifying rhythm: Interspeaker variation in %V
Authors: Renwick Margaret E L
Published: October 2011

The long-standing intuition that languages differ systematically in speech rhythm received support from an acoustic measure, %V (the ratio of vocalic material to the total duration of an utterance), which seemed to separate languages according to their perceived rhythms. Across studies, however, computations of %V values for target languages differ, raising the possibility that %V reflects not language-specific rhythmic habits, but the syllable structure of the particular utterances selected for analysis, and individual speaker differences. This paper replicates the %V methodology (using new recordings), and seeks to explain the high variability in %V by explicitly testing the link between %V, phonotactics, and individual speaker behavior. A high positive correlation is found between %V and an utterance's proportion of open syllables, while %V correlates negatively with the number of complex onsets in an utterance; these results support the hypothesis that utterance-level variation in syllable structure contributes substantially to the computed value of %V. However, the strength of this relationship varies across speakers. The goal of this paper is to determine the relative effects of utterance-level phonotactics, and individual speaker variation, on %V results, e.g., by comparing results when the same sentence is spoken by different speakers of a single language.
Comparative electromagnetic articulographic study of English rhythm as produced by native and non-native speakers
Authors: Erickson Donna , Suemitsu Atsuo , Shibuya Yoshiho , Lee Sungbok , Tanaka Yu
Published: October 2011

Previous work suggests that concurrent changes in jaw displacement and formant frequencies may manifest rhythm of spoken American English utterances [e.g., Erickson, in Proceedings of the Speech Prosody 2010, Chicago (May 2010), p. 1]. This paper compares jaw displacement and corresponding formant frequencies of monosyllabic American English words produced on low vowels in four word phrases with varying positions of emphasis as spoken by three native speakers and three Japanese speakers of English. Preliminary findings suggest an alternating pattern of strong-weak jaw displacement along with corresponding formant changes for the native speakers. This pattern was not consistently seen for the non-native speakers and seemed to vary as a function of their skill-level in spoken English.
Stimulus direction predictability dampens auditory neural responses to pitch-shifted voice feedback
Authors: Korzyukov Oleg , Sattler Lindsey , Behroozmand Roozbeh , Larson Charles
Published: October 2011

Models of neural mechanisms of voice control propose that voice auditory feedback is compared with an internal representation of the predicted voice output that is based on efference copies of motor commands. In addition, sensory memory from previous productions can also help the brain form predictions about incoming auditory feedback during vocal production. Previous studies have shown that the auditory evoked neural responses are maximally dampened in conditions where the incoming feedback closely matches the internal predictions. The present study aimed to determine if the predictability of stimulus direction influences the ERP responses to pitch shifts in voice auditory feedback. Subjects were tested with all upward stimuli, all downward stimuli, or randomized stimulus directions in separate blocks of trials. The N100 ERP response had a greater amplitude in conditions where the stimulus direction was randomized (unpredictable) compared to constant direction stimulus conditions (predictable), regardless of whether the stimuli were upwards or downwards. These findings suggest that auditory neural responses to predictable stimulus direction are dampened compared with unpredictable stimuli possibly because the predictable stimuli are suppressed by the internal predictions formed by the efference copy and/or sensory memory mechanisms.
Cross-language perception of Brazilian Portuguese vowels by Californian English speakers
Authors: Vasiliev Polina , Escudero Paola
Published: October 2011

The present study investigates the perceptual assimilation and auditory categorization of Brazilian Portuguese vowels by monolingual speakers of Californian English. In the perceptual assimilation task, listeners classified 140 vowel tokens in terms of 10 native English vowel categories by choosing from written English words containing the vowels. The stimuli were isolated vowels extracted from nonce words produced by 10 male and 10 female native speakers of Brazilian Portuguese. In the auditory categorization task, the same listeners identified six Portuguese vowel contrasts which were presented in an XAB format, where X was a subset of the same natural vowel tokens from the previous task and A and B were synthesized prototypes of the Portuguese vowels. The results of the perceptual assimilation task demonstrate that Californian English listeners assimilate two out of six Portuguese vowel contrasts to more than two native vowel categories, resulting in many instances of multiple category assimilation (MCA). In the auditory categorization task, most of the contrasts with the lowest accuracy were those that showed MCA, which demonstrates that this pattern of assimilation may be the cause of Californian English listeners' perceptual difficulties with Portuguese vowels. Predictions for L2 acquisition are made.
Perceptual confusability of French nasal vowels
Authors: Inceoglu Solene
Published: October 2011

The present study investigated native and non-native speakers' perception of the French nasal vowels [ε̃-õ- ɑ̃] and the oral vowel [o]. Thirty-four L1 American English intermediate learners of French and thirty-four French native speakers were asked to identify 60 one-syllable word items containing the four vowels [ε̃-õ-ɑ̃-o] in word-final position produced by a native speaker and randomly distributed across three conditions: audio-only, audio-visual and visual-only. Identification results revealed that overall performance was better in audio-visual and audio than in visual condition and that non-native speakers showed greater identification for [õ]\ than for [ε̃] and poorer identification for [ɑ]. A confusion matrix revealed that across conditions, the vowel [ɑ] resulted in the most misidentification and was often mistaken for [ɑ]. For both native and non-native speakers [õ] was sometimes confused with its oral counterpart [o]. The data also indicate different patterns of identification of the three nasal vowels in the three conditions. For instance the visual condition was particularly helpful for identifying [ɑ]. The obtained results will be discussed in relation to existing second language acquisition research studies.
Perception of Canadian French word-final vowels by English-dominant and French-dominant bilinguals
Authors: Law Franzo
Published: October 2011

Self-identified English-dominant and French-dominant bilinguals from Montreal participated in a modified vowel identification task. Group differences in accuracy and speed for identifying experimental vowels /e, ε, o, u, y, ⊘/ were investigated relative to control vowels /i, a/, expected to be easiest and fastest to identify by both groups. Of interest was the performance on front-rounded /y-⊘/ (non-phonemic in English) and /e-ε/ (phonologically contrastive in both languages, but // is disallowed word-finally in English). Both groups performed well overall in identifying experimental vowels although the French-dominant group was comparatively more accurate and faster. The English-dominant group was slower than the French-dominant group in identifying /y/ and /e/. Mouse cursor movements captured trial-by-trial revealed that both groups often moved the cursor toward the response button for /u/ before correctly identifying /y/. Results showed that English-dominant participants demonstrated less-automatic perception of most experimental vowels. However, performance speed and mouse patterns of the French-dominant group varied among native vowel categories, implying possible interactions between automaticity and auditory salience. Productions of /e-ε/ by participants were analyzed to explore the relative robustness in production of this contrast among participants. Correlations between task performance and measures of French proficiency are explored. [Work supported by NIH F31DC008075.]
A perceptual study of monosyllabic Mandarin tones produced by three-year-old children growing up in Taiwan
Authors: Wong Puisan
Published: October 2011

Wong et al. (2005) reported that monolingual Mandarin-speaking three-year-old children in the U.S. have not produced adult-like Mandarin lexical tones in monosyllabic words. This study adopted the same methods to examine monosyllabic Mandarin tones produced by three-year-old children in Taiwan. Four hundred and thirty eight monosyllabic tones were collected from ten children and seven mothers in Taiwan. These productions and the 92 productions by the four U.S. mothers reported in Wong et al. (2005) were low-pass filtered to retain pitch information, but eliminate lexical information, and were presented to five Mandarin-speaking adults in Taiwan for tone categorization. U.S. mothers' tones were categorized with ceiling accuracies, similar to those judged by U.S. Mandarin-speaking adults reported in Wong et al. (2005). Taiwan mothers' tones were judged with lower accuracies, with the accuracy of tone 2 significantly lower than U.S. mothers'. Taiwan children's four tones were judged with 63%, 24%, 27%, and 74% accuracy, all significantly lower than US and Taiwan mothers except for tone 1. Children made more errors in tones 2 and 3 than tones 1 and 4. These findings were consistent with those in Wong et al. (2005), suggesting similar developmental patterns for children growing up in the U.S. and Taiwan.
Context effects on reduced speech perception
Authors: Ten Eyck Brian C.
Published: October 2011

Acoustic information found in casual, conversational speech is often greatly impoverished and widely variable relative to more formal pronunciation. Previous work has highlighted the role of context in facilitating the comprehension of reduced speech at the individual word level; the experiment reported here measured the impact of varying available context on perceptual accuracy of multi-word speech reductions in American English. Forty-two subjects were exposed twice to sixteen 4–10 word reductions, the second time in one of four counterbalanced contextual conditions: (1) several seconds of audible preceding discourse; (2) an identical written transcript of the preceding discourse; (3) audible discourse of the pose-reduction clause ending; and (4) no additional context. Results were scored from subjects' typed responses based on the number of words correctly identified in each condition. By-subjects and by-items ANOVAs reveal that mean accuracy is correlated with the availability of contextual information. However, pairwise differences in mean accuracy across conditions indicate that discourse context in-and-of itself does not play a significant role in resolving multi-word speech reductions, while speaker-specific acoustic cues do. These results suggest that acoustic cues present in reduced multi-word utterances represent a preferred information source relative to syntactic or discourse context in interpreting massively reduced speech.
Lexical and metrical cues for English word segmentation by Mandarin second language learners of English
Authors: Luo Yu-Ting , Liu Chien-Tzu
Published: October 2011

This paper investigates the roles of lexical cues and metrical cues in word segmentation by Mandarin L2 learners of English with high and low English proficiency. A cross-modal form priming paradigm is adopted in the experiment. In the experiment, 33 participants (16 advanced learners, 17 beginning learners) heard a five-syllable phrase (e.g., anythingcorri, anything is the and corri is the ′), produced by a native American English speaker. After 100 ms, a three-syllable letter string (e.g., the corridor) was shown on the screen. The participants task was to decide whether a target was a real word. The contexts, primes, and targets have real word and non-word version and have either SW or WS (S: strong; W: weak) stress patterns. The results indicate that: (1) Lexical cues are the main strategy for advanced learners; (2) Beginning learners rely more on metrical cues; (3) When the stress pattern of contexts and primes are identical, it took participants less time to response. The results support previous studies that lexical and metrical are the cues listeners would rely on when doing segmentation. Furthermore, the results suggest that the strategies listeners rely on would change as they become more proficient in English.
Flash Heating Leads to Low Frictional Strength of Crustal Rocks at Earthquake Slip Rates
Authors: Goldsby David L. , Tullis Terry E.
Published: October 2011

Extreme temperatures generated over short distances may weaken faults during earthquakes.
Conical Intersection Dynamics in NO
2
Probed by Homodyne High-Harmonic Spectroscopy
Authors: Wörner H. J. , Bertrand J. B. , Fabre B. , Higuet J. , Ruf H. , Dubrouil A. , Patchkovskii S. , Spanner M. , Mairesse Y. , Blanchet V. , Mével E. , Constant E. , Corkum P. B. , Villeneuve D. M.
Published: October 2011

Coincident vibrational and electronic rearrangements in a photoexcited molecule are tracked in fine detail.
Sequential Establishment of Stripe Patterns in an Expanding Cell Population
Authors: Liu Chenli , Fu Xiongfei , Liu Lizhong , Ren Xiaojing , Chau Carlos K.L. , Li Sihong , Xiang Lu , Zeng Hualing , Chen Guanhua , Tang Lei-Han , Lenz Peter , Cui Xiaodong , Huang Wei , Hwa Terence , Huang Jian-Dong
Published: October 2011

A synthetic circuit implementing density-controlled bacterial motility autonomously produces a tunable stripe pattern.
A 100,000-Year-Old Ochre-Processing Workshop at Blombos Cave, South Africa
Authors: Henshilwood Christopher S. , d’Errico Francesco , van Niekerk Karen L. , Coquinot Yvan , Jacobs Zenobia , Lauritzen Stein-Erik , Menu Michel , García-Moreno Renata
Published: October 2011

Early humans mixed and stored ochre pigments in shells 100,000 years ago, an indication of the emergence of higher planning.
Linear Alkane Polymerization on a Gold Surface
Authors: Zhong Dingyong , Franke Jörn-Holger , Podiyanachari Santhosh Kumar , Blömker Tobias , Zhang Haiming , Kehr Gerald , Erker Gerhard , Fuchs Harald , Chi Lifeng
Published: October 2011

The confining channel geometry of a gold surface induces selective end-to-end linking of hydrocarbon chains.
Shining Light on Diabolic Points
Authors: Whitaker Benjamin J.
Published: October 2011

A direct probe of the electronic dynamics where excited states intersect has been achieved by using high-harmonic spectroscopy.
A Major Environmental Cause of Death
Authors: Martin William J. , Glass Roger I. , Balbus John M. , Collins Francis S.
Published: October 2011

Exposure to indoor air pollution from household burning and solid fuels affects nearly half of the world's population.
SevERing Mitochondria
Authors: Rambold Angelika S. , Lippincott-Schwartz Jennifer
Published: October 2011

The endoplasmic reticulum is an active participant in the division of another organelle, the mitochondrion.
Once-Ridiculed Discovery Redefined the Term Crystal
Authors: Clery Daniel
Published: October 2011

Daniel Shechtman's discovery that atoms in a solid can achieve fivefold symmetry by arranging themselves in a pattern that almost but never quite repeats—a "quasicrystal"—has netted this year's Nobel Prize in chemistry.
Beyond the Data
Authors: Mervis Jeffrey
Published: October 2011

The latest attempt to clarify how NSF assesses grant proposals for possible impacts beyond the expected scientific results has not ended a long-running debate.
Immunochromatographic IgG/IgM Test for Rapid Diagnosis of Active Tuberculosis
Authors: Ben-Selma Walid , Harizi Hedi , Boukadida Jalel
Published: October 2011

For rapid diagnosis and discrimination between active tuberculosis (TB) and other pulmonary diseases, we evaluated the clinical usefulness of detection of serum immunoglobulin IgG and IgM antibodies raised against mycobacterial 38-kDa, 16-kDa, and 6-kDa antigens by a commercial rapid immunochromatographic IgG/IgM test (Standard Diagnostics, South Korea) in 246 serum samples from three groups of patients: (i) 171 patients with active TB (128 with pulmonary TB [pTB] and 43 with extrapulmonary TB [epTB]), (ii) 73 patients with pulmonary non-TB diseases, and (iii) two leprosy patients. The sensitivities of IgG and IgM in patients with active TB (pTB and epTB) were 68.4% and 2.3%, respectively. IgG had the best performance characteristics, with sensitivities of 78.1% and 39.5% in sera from patients with active pTB and epTB, respectively, and a specificity of 100%. The sensitivities of IgM were poor and were similar for pTB and epTB (2.3%). In contrast, specificity was very elevated (100%). The combination of IgG with IgM did not improve its sensitivity. IgG-mediated responses against the mycobacterial 38-kDa, 16-kDa, and 6-kDa antigens might constitute a clinically useful tool for presumptive diagnosis and discrimination of active pTB from other pulmonary diseases. Moreover, based on its simplicity and rapidity of application, it could be a screening tool for active pTB in poorly equipped laboratories.
Protein Kinase R Is a Novel Mediator of CD40 Signaling and Plays a Critical Role in Modulating Immunoglobulin Expression during Respiratory Syncytial Virus Infection
Authors: Thakur Sheetal A. , Zalinger Zachary B. , Johnson Teresa R. , Imani Farhad
Published: October 2011

Effective immunoglobulin responses play a vital role in protection against most pathogens. However, the molecular mediators and mechanisms responsible for signaling and selective expression of immunoglobulin types remain to be elucidated. Previous studies in our laboratory have demonstrated that protein kinase R (PKR) plays a crucial role in IgE responses to double-stranded RNA (dsRNA)in vitro. In this study, we show that PKR plays a critical role in IgG expression bothin vivoandin vitro. PKR−/−mice show significantly altered serum IgG levels during respiratory syncytial virus (RSV) infection. IgG2a expression is particularly sensitive to a lack of PKR and is below the detection level in mock- or RSV-infected PKR−/−mice. Interestingly, we show that upon activation by anti-CD40 and gamma interferon (IFN-γ), B cells from PKR−/−mice show diminished major histocompatibility complex class II (MHC II), CD80, and CD86 levels on the cell surface compared to wild-type (WT) mice. Our data also show that PKR is necessary for optimal expression of adhesion molecules, such as CD11a and ICAM-1, that are necessary for homotypic aggregation of B cells. Furthermore, in this report we demonstrate for the first time that upon CD40 ligation, PKR is rapidly phosphorylated and activated, indicating that PKR is an early and novel downstream mediator of CD40 signaling pathways.
Identifying a Role for Toll-Like Receptor 3 in the Innate Immune Response to Chlamydia muridarum Infection in Murine Oviduct Epithelial Cells
Authors: Derbigny Wilbert A. , Shobe LaTasha R. , Kamran Jasmine C. , Toomey Katherine S. , Ofner Susan
Published: October 2011

Because epithelial cells are the major cell type productively infected withChlamydiaduring genital tract infections, the overall goal of our research was to understand the contribution of infected epithelial cells to the host defense. We previously showed that Toll-like receptor 3 (TLR3) is the critical pattern recognition receptor in oviduct epithelial (OE) cells that is stimulated duringChlamydiainfection, resulting in the synthesis of beta interferon (IFN-β). Here, we present data that implicates TLR3 in the expression of a multitude of other innate-inflammatory immune modulators including interleukin-6 (IL-6), CXCL10, CXCL16, and CCL5. We demonstrate thatChlamydia-induced expression of these cytokines is severely disrupted in TLR3-deficient OE cells, whereasChlamydiareplication in the TLR3-deficient cells is more efficient than in wild-type OE cells. Pretreatment of the TLR3-deficient OE cells with 50 U of IFN-β/ml prior to infection diminishedChlamydiareplication and restored the ability ofChlamydiainfection to induce IL-6, CXCL10, and CCL5 expression in TLR3-deficient OE cells; however, CXCL16 induction was not restored by IFN-β preincubation. Our findings were corroborated in pathway-focused PCR arrays, which demonstrated a multitude of different inflammatory genes that were defectively regulated duringChlamydiainfection of the TLR3-deficient OE cells, and we found that some of these genes were induced only when IFN-β was added prior to infection. Our OE cell data implicate TLR3 as an essential inducer of IFN-β and other inflammatory mediators by epithelial cells duringChlamydiainfection and highlight the contribution of TLR3 to the inflammatory cytokine response.
Direct Detection of Staphylococcus Osteoarticular Infections by Use of Xpert MRSA/SA SSTI Real-Time PCR
Authors: Dubouix-Bourandy Anne , de Ladoucette Aymard , Pietri Valerie , Mehdi Nazim , Benzaquen David , Guinand Régis , Gandois Jean-Marc
Published: October 2011

We evaluated the Xpert MRSA/SA SSTI real-time PCR assay (Cepheid, Sunnyvale, CA) directly on perioperative bone and joint samples. The sensitivity and specificity for detection of methicillin-susceptible
Staphylococcus aureus
(MSSA), methicillin-resistant
Staphylococcus aureus
(MRSA), and methicillin-resistant coagulase-negative
Staphylococcus
were, respectively, 100% and 98.3%, 100% and 100%, and 100% and 95.3%. The median total test turnaround time was 72 min for PCR versus 79 h for culture. Using these rapid results, appropriate antibiotic treatment could be rapidly initiated.
Divergent Rifamycin Susceptibilities of Clostridium difficile Strains in Canada and Italy and Predictive Accuracy of Rifampin Etest for Rifamycin Resistance
Authors: Miller Mark A. , Blanchette Ruth , Spigaglia Patrizia , Barbanti Fabrizio , Mastrantonio Paola
Published: October 2011

We tested the activities of rifampin (RIF) and rifaximin (RFX) against 180
Clostridium difficile
clinical isolates selected from Canadian and Italian culture collections. MICs were determined by CLSI agar dilution for both drugs and by Etest for RIF. Sixteen of 85 Italian isolates (18.8%) showed high-level resistance to both rifamycins (MICs, >16 μg/ml), compared to 2 of 95 (2.1%) Canadian isolates. Two new
rpoB
mutations were identified in rifamycin-resistant isolates. RIF susceptibility by Etest correlated completely with susceptibility to both rifamycins determined by agar dilution.
Five-Year Outbreak of Community- and Hospital-Acquired Mycobacterium porcinum Infections Related to Public Water Supplies
Authors: Brown-Elliott Barbara A. , Wallace Richard J. , Tichindelean Carmen , Sarria Juan C. , McNulty Steven , Vasireddy Ravikaran , Bridge Linda , Mayhall C. Glenn , Turenne Christine , Loeffelholz Michael
Published: October 2011

Mycobacterium porcinum
is a rarely encountered rapidly growing
Mycobacterium
(RGM). We identified
M. porcinum
from 24 patients at a Galveston university hospital (University of Texas Medical Branch) over a 5-year period.
M. porcinum
was considered a pathogen in 11 (46%) of 24 infected patients, including 4 patients with community-acquired disease. Retrospective patient data were collected, and water samples were cultured. Molecular analysis of water isolates, clustered clinical isolates, and 15 unrelated control strains of
M. porcinum
was performed. Among samples of hospital ice and tap water, 63% were positive for RGM, 50% of which were
M. porcinum
. Among samples of water from the city of Galveston, four of five households (80%) were positive for
M. porcinum
. By pulsed-field gel electrophoresis (PFGE), 8 of 10 environmental
M. porcinum
were determined to belong to two closely related clones. A total of 26 of 29 clinical isolates subjected to PFGE (including isolates from all positive patients) were clonal with the water patterns, including patients with community-acquired disease. Fifteen control strains of
M. porcinum
had unique profiles. Sequencing of
hsp65
,
recA
, and
rpoB
revealed the PFGE outbreak clones to have identical sequences, while unrelated strains exhibited multiple sequence variants.
M. porcinum
from 22 (92%) of 24 patients were clonal, matched hospital- and household water-acquired isolates, and differed from epidemiologically unrelated strains.
M. porcinum
can be a drinking water contaminant, serve as a long-term reservoir (years) for patient contamination (especially sputum), and be a source of clinical disease. This study expands concern about public health issues regarding nontuberculous mycobacteria. Multilocus gene sequencing helped define clonal populations.
Evaluation of Mycobacterium tuberculosis Typing Methods in a 4-Year Study in Schleswig-Holstein, Northern Germany
Authors: Roetzer Andreas , Schuback Sieglinde , Diel Roland , Gasau Frauke , Ubben Tanja , di Nauta Alessia , Richter Elvira , Rüsch-Gerdes Sabine , Niemann Stefan
Published: October 2011

In order to evaluate the discriminatory power of different methods for genotyping of
Mycobacterium tuberculosis
complex (MTBC) isolates, we compared the performance of (i) IS
6110
DNA fingerprint typing, (ii) spoligotyping, and (iii) 24-loci mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) typing in a long-term study on the epidemiology of tuberculosis (TB) in Schleswig-Holstein, the northernmost federal state of Germany. In total, we analyzed 277 MTBC isolates collected from patients between the years 2006 and 2010. The collection comprised a broad spectrum of 13 different genotypes, among which strains of the Haarlem genotype (31%) were most prominent, followed by strains belonging to the Delhi and Beijing lineages (7% and 6%, respectively). On the basis of IS
6110
restriction fragment length polymorphism (RFLP) and spoligotyping analyses, 211 isolates had unique patterns (76%) and 66 isolates (24%) were in 20 clusters. MIRU-VNTR combined with spoligotyping analyses revealed 202 isolates with unique patterns (73%) and 75 isolates in 18 clusters (27%). Overall, there was 93.1% concordance between the typing results obtained; 198 strains were identified as unique, and 60 isolates were clustered by both typing combinations (including all 31 isolates with confirmed epidemiological links). Of the remaining 19 isolates with discrepant results, 15 were falsely clustered by MIRU-VNTR (six Beijing genotype strains) and four were clustered by IS
6110
RFLP (low IS
6110
copy number) only. In conclusion, in the study population investigated, a minority of isolates, especially of the Beijing genotype, clustered by standard 24-loci MIRU-VNTR and without an obvious epidemiological link may require second-line typing by IS
6110
RFLP or hypervariable MIRU-VNTR loci.
Cleavage and Activation of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein by Human Airway Trypsin-Like Protease
Authors: Bertram Stephanie , Glowacka Ilona , Müller Marcel A. , Lavender Hayley , Gnirss Kerstin , Nehlmeier Inga , Niemeyer Daniela , He Yuxian , Simmons Graham , Drosten Christian , Soilleux Elizabeth J. , Jahn Olaf , Steffen Imke , Pöhlmann Stefan
Published: October 2011

The highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) poses a constant threat to human health. The viral spike protein (SARS-S) mediates host cell entry and is a potential target for antiviral intervention. Activation of SARS-S by host cell proteases is essential for SARS-CoV infectivity but remains incompletely understood. Here, we analyzed the role of the type II transmembrane serine proteases (TTSPs) human airway trypsin-like protease (HAT) and transmembrane protease, serine 2 (TMPRSS2), in SARS-S activation. We found that HAT activates SARS-S in the context of surrogate systems and authentic SARS-CoV infection and is coexpressed with the viral receptor angiotensin-converting enzyme 2 (ACE2) in bronchial epithelial cells and pneumocytes. HAT cleaved SARS-S at R667, as determined by mutagenesis and mass spectrometry, and activated SARS-S for cell-cell fusion in
cis
and
trans
, while the related pulmonary protease TMPRSS2 cleaved SARS-S at multiple sites and activated SARS-S only in
trans
. However, TMPRSS2 but not HAT expression rendered SARS-S-driven virus-cell fusion independent of cathepsin activity, indicating that HAT and TMPRSS2 activate SARS-S differentially. Collectively, our results show that HAT cleaves and activates SARS-S and might support viral spread in patients.
Genomic Sequencing and Characterization of Cynomolgus Macaque Cytomegalovirus
Authors: Marsh Angie K. , Willer David O. , Ambagala Aruna P. N. , Dzamba Misko , Chan Jacqueline K. , Pilon Richard , Fournier Jocelyn , Sandstrom Paul , Brudno Michael , MacDonald Kelly S.
Published: October 2011

Cytomegalovirus (CMV) infection is the most common opportunistic infection in immunosuppressed individuals, such as transplant recipients or people living with HIV/AIDS, and congenital CMV is the leading viral cause of developmental disabilities in infants. Due to the highly species-specific nature of CMV, animal models that closely recapitulate human CMV (HCMV) are of growing importance for vaccine development. Here we present the genomic sequence of a novel nonhuman primate CMV from cynomolgus macaques (
Macaca fascicularis
; CyCMV). CyCMV (Ottawa strain) was isolated from the urine of a healthy, captive-bred, 4-year-old cynomolgus macaque of Philippine origin, and the viral genome was sequenced using next-generation Illumina sequencing to an average of 516-fold coverage. The CyCMV genome is 218,041 bp in length, with 49.5% G+C content and 84% protein-coding density. We have identified 262 putative open reading frames (ORFs) with an average coding length of 789 bp. The genomic organization of CyCMV is largely colinear with that of rhesus macaque CMV (RhCMV). Of the 262 CyCMV ORFs, 137 are homologous to HCMV genes, 243 are homologous to RhCMV 68.1, and 200 are homologous to RhCMV 180.92. CyCMV encodes four ORFs that are not present in RhCMV strain 68.1 or 180.92 but have homologies with HCMV (UL30, UL74A, UL126, and UL146). Similar to HCMV, CyCMV does not produce the RhCMV-specific viral homologue of cyclooxygenase-2. This newly characterized CMV may provide a novel model in which to study CMV biology and HCMV vaccine development.
Measles Virus V Protein Inhibits NLRP3 Inflammasome-Mediated Interleukin-1β Secretion
Authors: Komune Noritaka , Ichinohe Takeshi , Ito Minako , Yanagi Yusuke
Published: October 2011

Inflammasomes are cytosolic protein complexes that stimulate the activation of caspase-1, which in turn induces the secretion of the inflammatory cytokines Interleukin-1β (IL-1β) and IL-18. Recent studies have indicated that the inflammasome known as the NOD-like-receptor-family, pyrin domain-containing 3 (NLRP3) inflammasome recognizes several RNA viruses, including the influenza and encephalomyocarditis viruses, whereas the retinoic acid-inducible gene I (RIG-I) inflammasome may detect vesicular stomatitis virus. We demonstrate that measles virus (MV) infection induces caspase-1-dependent IL-1β secretion in the human macrophage-like cell line THP-1. Gene knockdown experiments indicated that IL-1β secretion in MV-infected THP-1 cells was mediated by the NLRP3 inflammasome but not the RIG-I inflammasome. MV produces the nonstructural V protein, which has been shown to antagonize host innate immune responses. The recombinant MV lacking the V protein induced more IL-1β than the parental virus. THP-1 cells stably expressing the V protein suppressed NLRP3 inflammasome-mediated IL-1β secretion. Furthermore, coimmunoprecipitation assays revealed that the V protein interacts with NLRP3 through its carboxyl-terminal domain. NLRP3 was located in cytoplasmic granular structures in THP-1 cells stably expressing the V protein, but upon inflammasome activation, NLRP3 was redistributed to the perinuclear region, where it colocalized with the V protein. These results indicate that the V protein of MV suppresses NLRP3 inflammasome-mediated IL-1β secretion by directly or indirectly interacting with NLRP3.
Functional Genomics Reveals an Essential and Specific Role for Stat1 in Protection of the Central Nervous System following Herpes Simplex Virus Corneal Infection
Authors: Pasieka Tracy Jo , Cilloniz Cristian , Carter Victoria S. , Rosato Pamela , Katze Michael G. , Leib David A.
Published: October 2011

Innate immune deficiencies result in a spectrum of severe clinical outcomes following infection. In particular, there is a strong association between loss of the signal transducer and activator of transcription (Stat) pathway, breach of the blood-brain barrier (BBB), and virus-induced neuropathology. The gene signatures that characterize resistance, disease, and mortality in the virus-infected nervous system have not been defined. Herpes simplex virus type 1 (HSV-1) is commonly associated with encephalitis in humans, and humans and mice lacking Stat1 display increased susceptibility to HSV central nervous system (CNS) infections. In this study, two HSV-1 strains were used, KOS (wild type [WT]), and Δvhs, an avirulent recombinant lacking the virion host shutoff (vhs) function. In addition, two mouse strains were used: strain 129 (control) and a Stat1-deficient (Stat1
−/−
) strain. Using combinations of these virus and mouse strains, we established a model of infection resulting in three different outcomes: viral clearance without neurological disease (Δvhs infection of control mice), neurological disease followed by viral clearance (Δvhs infection of Stat1
−/−
mice and WT infection of control mice), or neurological disease followed by death (WT infection of Stat1
−/−
mice). Through the use of functional genomics on the infected brain stems, we determined gene signatures that were representative of the three infection outcomes. We demonstrated a pathological signature in the brain stem of Stat1-deficient mice characterized by upregulation of transcripts encoding chemokine receptors, inflammatory markers, neutrophil chemoattractants, leukocyte adhesion proteins, and matrix metalloproteases. Additionally, there was a greater than 100-fold increase in the inflammatory markers interleukin 1β (IL-1β) and IL-6. Consistent with this gene signature, we demonstrated profound CNS inflammation with a concomitant lethal breach of the BBB. Taken together, our results indicated an essential role for normal Stat1-dependent signaling in mediating a nonpathological immune response to viral CNS infection.
Motor vehicle injuries in Qatar: time trends in a rapidly developing Middle Eastern nation
Authors: Mamtani Ravinder , Al-Thani Mohammed H , Al-Thani Al-Anoud Mohammed , Sheikh Javaid I , Lowenfels Albert B
Published: October 2011

Despite their wealth and modern road systems, traffic injury rates in Middle Eastern countries are generally higher than those in Western countries. The authors examined traffic injuries in Qatar during 2000–2010, a period of rapid population growth, focusing on the impact of speed control cameras installed in 2007 on overall injury rates and mortality. During the period 2000–2006, prior to camera installation, the mean (SD) vehicular injury death rate per 100 000 was 19.9±4.1. From 2007 to 2010, the mean (SD) vehicular death rates were significantly lower: 14.7±1.5 (p=0.028). Non-fatal severe injury rates also declined, but mild injury rates increased, perhaps because of increased traffic congestion and improved notification. It is possible that speed cameras decreased speeding enough to affect the death rate, without affecting overall injury rates. These data suggest that in a rapidly growing Middle Eastern country, photo enforcement (speed) cameras can be an important component of traffic control, but other measures will be required for maximum impact.
Late Neogene volcanics and interbedded palaeosols near Mount Kenya
Authors: Mahaney W. C. , Barendregt René W. , Villeneuve Mike , Dostal Jaroslav , Hamilton T. S. , Milner Michael W.
Published: October 2011

Two lava flows with interbedded palaeosols outcrop
c.
40 km SW of Mount Kenya, near the Amboni River north of Mweiga, Kenya along the Nyeri/Thompson Falls Road, at 0°18′S; 37°48′E. These flows, overlain by loess, are principally trachyandesite and form the base of the Mount Kenya Volcanic Series which, in the early literature, is described as being of probable Miocene/Pliocene age. Here we report
39
Ar/
40
Ar dates (
c.
5.2–5.5 Ma) and reversed magnetizations which establish a Latest Miocene to Earliest Pliocene age for these flows. Weathering characteristics of palaeosols interbedded with the lavas indicate generally dry climatic conditions during the Late Miocene, punctuated with humid events during the Pliocene and Quaternary. These Late Miocene–Quaternary palaeosols depict a relatively long and complex weathering history, followed by loess deposition. The palaeosols appear to have been episodically deflated, initially in phase with the deposition of lavas when surfaces were devoid of vegetation and later during periods of climatic deterioration when wind systems intensified. Such weathering histories within palaeosol profiles are also documented on nearby Mount Kenya, where well-weathered lower palaeosol horizons developed on Matuyama-age tills are overlain by much younger less-weathered horizons developed on Brunhes-age loess. The geochronology of Late Miocene lavas reported here provides maximum ages for weathering histories of palaeosols formed in a xeric tropical highland climate.
Tectonosedimentary expressions of the evolution of the Fungurume foreland basin in the Lufilian Arc, Neoproterozoic–Lower Palaeozoic, Central Africa
Authors: Wendorff Marek
Published: October 2011

The Lufilian Arc is a part of the Neoproterozoic–Lower Palaeozoic Pan-African orogenic system within southern and central Africa. The succession of the Lufilian orogen, the Katanga Supergroup, contains large bodies of fragmental rocks recently interpreted as syntectonic conglomerates, which reveal the existence of two previously unrecognized basins and shed new light on tectonic evolution of the belt. Rifting between the Congo Craton in the north and the Kalahari Craton in the south at
c.
880 Ma resulted in the opening of two rift basins: the Roan rift and the succeeding Nguba rift. During post-735 Ma orogenesis, north-advancing nappes supplied detritus into the Fungurume foreland basin in the northern part of the Lufilian Arc. The coarse-clastic sequence of the Fungurume Group includes olistostromes that contain olistoliths of the pre-existing Katangan rocks, rest upon a syntectonic unconformity and are overridden by the Katangan nappes/thrust sheets. Strong tectonic deformations of strata within the olistoliths reflect their provenance from the orogenic source of the Katangan nappes. By contrast, the olistostrome matrix is essentially intact even when olistostrome occurs as a part of a tight fold. These structural relations suggest that nappe overthrusting and further deformation of the foreland occurred soon after deposition of the olistostrome sediments, and prior to their lithification.
Ranking approaches for GIR
Authors: Larson Ray R.
Published: October 2011

At the core of any information retrieval system is its method for ranking results in response to a user's query. Geographic Information Retrieval (GIR) systems have an added complexity for this task since the information to be included in the ranking process goes beyond text and word frequency information to encompass geographic proximity, containment and other spatial operations. The need to combine both geographic and text components into GIR systems has led to some interesting hybrid approaches in addition to the "pure" spatial ranking methods based on spatial similarity. In this short survey I will look at some of the methods that have been reported in the literature and used in GIR evaluations including GeoCLEF and NTCIR GeoTime.
Increased thermogenic capacity of brown adipose tissue under low temperature and its contribution to arousal from hibernation in Syrian hamsters
Authors: Kitao Naoya , Hashimoto Masaaki
Published: October 2011

Brown adipose tissue (BAT) is thought to play a significant physiological role during arousal when body temperature rises from the extremely low body temperature that occurs during hibernation. The dominant pathway of BAT thermogenesis occurs through the β3-adrenergic receptor. In this study, we investigated the role of the β3-adrenergic system in BAT thermogenesis during arousal from hibernation both in vitro and in vivo. Syrian hamsters in the hibernation group contained BAT that was significantly greater in overall mass, total protein, and thermogenic uncoupling protein-1 than BAT from the warm-acclimated group. Although the ability of the β3-agonist CL316,243 to induce BAT thermogenesis at 36°C was no different between the hibernation and warm-acclimated groups, its maximum ratio over the basal value at 12°C in the hibernation group was significantly larger than that in the warm-acclimated group. Forskolin stimulation at 12°C produced equivalent BAT responses in these two groups. In vivo thermogenesis was assessed with the arousal time determined by the time course of BAT temperature or heart rate. Stimulation of BAT by CL316,243 significantly shortened the time of arousal from hibernation compared with that induced by vehicle alone, and it also induced arousal in deep hibernating animals. The β3-antagonist SR59230A inhibited arousal from hibernation either in part or completely. These results suggest that BAT in hibernating animals has potent thermogenic activity with a highly effective β3-receptor mechanism at lower temperatures.
Effect of high and low sodium intake on urinary aquaporin-2 excretion in healthy humans
Authors: Graffe Carolina Cannillo , Bech Jesper Nørgaard , Pedersen Erling Bjerregaard
Published: October 2011

The degree of water transport via aquaporin-2 (AQP2) water channels in renal collecting duct principal cells is reflected by the level of the urinary excretion of AQP2 (u-AQP2). In rats, the AQP2 expression varies with sodium intake. In humans, the effect of sodium intake on u-AQP2 and the underlying mechanisms have not previously been studied. We measured the effect of 4 days of high sodium (HS) intake (300 mmol sodium/day; 17.5 g salt/day) and 4 days of low sodium (LS) intake (30 mmol sodium/day; 1.8 g salt/day) on u-AQP2, fractional sodium excretion (FENa), free water clearance (CH2O), urinary excretion of PGE2(u-PGE2) and cAMP (u-cAMP), and plasma concentrations of vasopressin (AVP), renin (PRC), ANG II, aldosterone (Aldo), atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) in a randomized, crossover study of 21 healthy subjects, during 24-h urine collection and after hypertonic saline infusion. The 24-h urinary sodium excretion was significantly higher during HS intake (213 vs. 41 mmol/24 h). ANP and BNP were significantly lower and PRC, ANG II, and Aldo were significantly higher during LS intake. AVP, u-cAMP, and u-PGE2were similar during HS and LS intake, but u-AQP2 was significantly higher during HS intake. The increases in AVP and u-AQP2 in response to hypertonic saline infusion were similar during HS and LS intake. In conclusion, u-AQP2 was increased during HS intake, indicating that water transport via AQP2 was increased. The effect was mediated by an unknown AVP-independent mechanism.
In situ enhancement of pulmonary surfactant function using temporary flow reversal
Authors: Glindmeyer Henry W. , Smith Bradford J. , Gaver Donald P.
Published: October 2011

Acute respiratory distress syndrome is a pulmonary disease with a mortality rate of ∼40% and 75,000 deaths annually in the United States. Mechanical ventilation restores airway patency and gas transport but leads to ventilator-induced lung injury. Furthermore, surfactant replacement therapy is ineffective due to surfactant delivery difficulties and deactivation by vascular proteins leaking into the airspace. Here, we demonstrated that surfactant function can be substantially improved (up to 50%) in situ in an in vitro pulmonary airway model using unconventional flows that incorporate a short-term retraction of the air-liquid interface, leading to a net decrease in cellular damage. Computational fluid dynamic simulations provided insights into this method and demonstrated the physicochemical hydrodynamic foundation for the improved surfactant microscale transport and mobility. This study may provide a starting point for developing novel ventilation waveforms to improve surfactant function in edematous airways.