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Human astrovirus (HAstV) is a known cause of viral gastroenteritis in children worldwide, but HAstV can cause also severe and systemic infections in immunocompromised patients. There are three clades of HAstV: classical, MLB, and VA/HMO. While all three clades are found in gastrointestinal samples, HAstV-VA/HMO is the main clade associated with meningitis and encephalitis in immunocompromised patients. To understand how the HAstV-VA/HMO can infect the central nervous system, we investigated its sequence-divergent capsid spike, which functions in cell attachment and may influence viral tropism. Here we report the high-resolution crystal structures of the HAstV-VA1 capsid spike from strains isolated from patients with gastrointestinal and neuronal disease. The HAstV-VA1 spike forms a dimer and shares a core beta-barrel structure with other astrovirus capsid spikes but is otherwise strikingly different, suggesting that HAstV-VA1 may utilize a different cell receptor, and an infection competition assay supports this hypothesis. Furthermore, by mapping the capsid protease cleavage site onto the structure, the maturation and assembly of the HAstV-VA1 capsid is revealed. Finally, comparison of gastrointestinal and neuronal HAstV-VA1 sequences, structures, and antigenicity suggests that neuronal HAstV-VA1 strains may have acquired immune escape mutations. Overall, our studies on the HAstV-VA1 capsid spike lay a foundation to further investigate the biology of HAstV-VA/HMO and to develop vaccines and therapeutics targeting it.

Despite their worldwide prevalence and association with human disease, the molecular bases of human astrovirus (HAstV) infection and evolution remain poorly characterized. Here, we report the structure of the capsid protein spike of the divergent HAstV MLB clade (HAstV MLB). While the structure shares a similar folding topology with that of classical-clade HAstV spikes, it is otherwise strikingly different. We find no evidence of a conserved receptor-binding site between the MLB and classical HAstV spikes, suggesting that MLB and classical HAstVs utilize different receptors for host-cell attachment. We provide evidence for this hypothesis using a novel HAstV infection competition assay. Comparisons of the HAstV MLB spike structure with structures predicted from its sequence reveal poor matches, but template-based predictions were surprisingly accurate relative to machine-learning-based predictions. Our data provide a foundation for understanding the mechanisms of infection by diverse HAstVs and can support structure determination in similarly unstudied systems.

Human astroviruses are an important cause of viral gastroenteritis globally, yet few studies have investigated the serostatus of adults to establish rates of previous infection. Here, we applied biolayer interferometry immunosorbent assay (BLI-ISA), a recently developed serosurveillance technique, to measure the presence of blood plasma IgG antibodies directed towards the human astrovirus capsid spikes from serotypes 1-8 in a cross-sectional sample of a United States adult population. The seroprevalence rates of IgG antibodies were 73% for human astrovirus serotype 1, 62% for serotype 3, 52% for serotype 4, 29% for serotype 5, 27% for serotype 8, 22% for serotype 2, 8% for serotype 6, and 8% for serotype 7. Notably, seroprevalence rates for capsid spike antigens correlate with neutralizing antibody rates determined previously. This work is the first seroprevalence study evaluating all eight classical human astrovirus serotypes.

Purpose: Of the three currently recognized variants of primary progressive aphasia, behavioral differentiation between the nonfluent/agrammatic (nfvPPA) and logopenic (lvPPA) variants is particularly difficult. The challenge includes uncertainty regarding diagnosis of apraxia of speech, which is subsumed within criteria for variant classification. The purpose of this study was to determine the extent to which a variety of speech articulation and prosody metrics for apraxia of speech differentiate between nfvPPA and lvPPA across diverse speech samples. Method: The study involved 25 participants with progressive aphasia (10 with nfvPPA, 10 with lvPPA, and five with the semantic variant). Speech samples included a word repetition task, a picture description task, and a story narrative task. We completed acoustic analyses of temporal prosody and quantitative perceptual analyses based on narrow phonetic transcription and then evaluated the degree of differentiation between nfvPPA and lvPPA participants (with the semantic variant serving as a reference point for minimal speech production impairment). Results: Most, but not all, articulatory and prosodic metrics differentiated statistically between the nfvPPA and lvPPA groups. Measures of distortion frequency, syllable duration, syllable scanning, and--to a limited extent--syllable stress and phonemic accuracy showed greater impairment in the nfvPPA group. Contrary to expectations, classification was most accurate in connected speech samples. A customized connected speech metric--the narrative syllable duration--yielded excellent to perfect classification accuracy. Discussion: Measures of average syllable duration in multisyllabic utterances are useful diagnostic tools for differentiating between nfvPPA and lvPPA, particularly when based on connected speech samples. As such, they are suitable candidates for automatization, large-scale study, and application to clinical practice. The observation that both speech rate and distortion frequency differentiated more effectively in connected speech than on a motor speech examination suggests that it will be important to evaluate interactions between speech and discourse production in future research.

Purpose: The purpose of this study was to compare the utility of two automated indices of lexical diversity, the Moving-Average Type-Token Ratio (MATTR) and the Word Information Measure (WIM), in predicting aphasia diagnosis and responding to differences in severity and aphasia subtype. Method: Transcripts of a single discourse task were analyzed for 478 speakers, 225 of whom had aphasia per an aphasia battery. We calculated the MATTR and the WIM for each participant. We compared the group means among speakers with aphasia, neurotypical controls, and left-hemisphere stroke survivors with mild aphasia not detected by an aphasia battery. We examined whether each measure distinguished levels of aphasia severity and subtypes of aphasia. We used each measure to classify aphasia versus neurotypical control and compared the areas under the curve. Results: The WIM and the MATTR differentiated among people with aphasia, neurotypical controls, and people with mild aphasia. Both measures demonstrated moderately high predictive accuracy in classifying aphasia. The WIM demonstrated greater sensitivity to aphasia severity and subtype compared to the MATTR. Conclusions: The WIM and the MATTR are promising measures that quantify lexical diversity in different and complementary ways. The WIM may be more useful for quantifying the effect of treatment or disease progression, whereas the MATTR may be more useful for discriminating discourse produced by people with very mild aphasia from discourse produced by neurotypical controls. Further validation is required.

This paper discusses the value of using classroom observations as part of a multi-methodological approach to understand what influences student engagement in classroom settings. This action research aimed to gain insights into what influences students to participate in the classroom and was conducted in an Irish vocational agricultural college as part of an initiative aimed to enhance classroom engagement. Classroom observations were used to examine how students interact in classroom settings by observing student's behavioural engagement as the cognitive and affective domains of engagement are more difficult to observe. The findings were triangulated and validated with data from the teacher interviews, student focus groups, and a student survey. This paper details the multi-methodological approach taken, how classroom observations were developed and used, and the value they brought to evaluate what impacted student engagement within this context.

Purpose: Many communication disorders result in speech sound errors that listeners perceive as phonemic errors. Unfortunately, manual methods for calculating phonemic error frequency are prohibitively time consuming to use in large-scale research and busy clinical settings. The purpose of this study was to validate an automated analysis based on a string metric--the unweighted Levenshtein edit distance--to express phonemic error frequency after left hemisphere stroke. Method: Audio-recorded speech samples from 65 speakers who repeated single words after a clinician were transcribed phonetically. By comparing these transcriptions to the target, we calculated the percent segments with a combination of phonemic substitutions, additions, and omissions and derived the phonemic edit distance ratio, which theoretically corresponds to percent segments with these phonemic errors. Results: Convergent validity between the manually calculated error frequency and the automated edit distance ratio was excellent, as demonstrated by nearly perfect correlations and negligible mean differences. The results were replicated across 2 speech samples and 2 computation applications. Conclusions: The phonemic edit distance ratio is well suited to estimate phonemic error rate and proves itself for immediate application to research and clinical practice. It can be calculated from any paired strings of transcription symbols and requires no additional steps, algorithms, or judgment concerning alignment between target and production. We recommend it as a valid, simple, and efficient substitute for manual calculation of error frequency.

In this article, we describe teacher educators' collaboration for coherence around social justice teacher education in preparation for a national accreditation review. Specifically, we illuminate how we cultivated an inquiry stance and critical conversations to build a safe and trusting community, generate locally meaningful values, and reconceptualize diversity in terms of social justice. By depicting our collaborative process in clarifying a detail, we make visible how we developed social justice-oriented vision, mission, and commitment statements and a conceptual framework to transform our traditional university-based undergraduate program. Aiming to inform other programs striving for coherence for social justice, we offer insights for supporting collaboration, considering the local community and political context, and leveraging accreditation.

Purpose: Diagnostic recommendations for acquired apraxia of speech (AOS) have been contradictory concerning whether speech sound errors are consistent or variable. Studies have reported divergent findings that, on face value, could argue either for or against error consistency as a diagnostic criterion. The purpose of this study was to explain discrepancies in error consistency results based on the unit of analysis (segment, syllable, or word) to help determine which diagnostic recommendation is most appropriate. Method: We analyzed speech samples from 14 left-hemisphere stroke survivors with clinical diagnoses of AOS and aphasia. Each participant produced 3 multisyllabic words 5 times in succession. Broad phonetic transcriptions of these productions were coded for consistency of error location and type using the word and its constituent syllables and sound segments as units of analysis. Results: Consistency of error type varied systematically with the unit of analysis, showing progressively greater consistency as the analysis unit changed from the word to the syllable and then to the sound segment. Consistency of error location varied considerably across participants and correlated positively with error frequency. Conclusions: Low to moderate consistency of error type at the word level confirms original diagnostic accounts of speech output and sound errors in AOS as variable in form. Moderate to high error type consistency at the syllable and sound levels indicate that phonetic error patterns are present. The results are complementary and logically compatible with each other and with the literature.

Purpose: This study was conducted to evaluate the clinical utility of error variability for differentiating between apraxia of speech (AOS) and aphasia with phonemic paraphasia. Method: Participants were 32 individuals with aphasia after left cerebral injury. Diagnostic groups were formed on the basis of operationalized measures of recognized articulatory and prosodic characteristics of AOS and phonemic paraphasia. Sequential repetitions of multisyllabic words were elicited as part of a motor speech evaluation and transcribed phonetically. Four metrics of variability at the syllable and word levels were derived from these transcripts. Results: The measures yielded different magnitudes of variability. There were no group differences between participants who displayed speech profiles consistent with AOS and participants who displayed speech profiles indicative of aphasia with phonemic paraphasia. Rather, correlation coefficients and analyses of covariance showed that the variability metrics were significantly mediated by overall error rate. Additionally, variability scores for individuals with salient diagnoses of AOS and conduction aphasia were inconsistent with current diagnostic guidelines. Conclusions: The results do not support diagnostic validity of error variability for differentiating between AOS and aphasia with phonemic paraphasia. Future research using error variability metrics should account for overall error rate in the analysis and matching of participant groups. (Contains 8 tables and 1 figure.)

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels contribute to the rhythmic firing of pacemaker neurons and cardiomyocytes. Mutations in HCN channels are associated with cardiac arrhythmia and epilepsy. HCN channels belong to the superfamily of voltage-gated K+ channels, most of which are activated by depolarization. HCN channels, however, are activated by hyperpolarization. The mechanism behind this reversed gating polarity of HCN channels is not clear. We here show that sea urchin HCN (spHCN) channels with mutations in the C-terminal part of the voltage sensor use the same voltagesensor movement to either close or open in response to hyperpolarizations depending on the absence or presence of cAMP. Our results support that non-covalent interactions at the C-terminal end of the voltage sensor are critical for HCN gating polarity. These interactions are also critical for the proper closing of the channels because these mutations exhibit large constitutive currents. Since a similar voltage-sensor movement can cause both depolarization- and hyperpolarizationactivation in the same channel, this suggests that the coupling between the voltage sensor and the pore is changed to create channels opened by different polarities. We also show an identical voltage-sensor movement in activated and inactivated spHCN channels and suggest a model for spHCN activation and inactivation. Our results suggest the possibility that channels open by opposite voltage dependence, such as HCN and the related EAG channels, use the same voltage-sensor movement but different coupling mechanisms between the voltage sensor and the gate. [ABSTRACT FROM AUTHOR]

This article presents an assignment in which students are to research and report on a chemical reaction whose increased or decreased rate is of practical importance. Specifically, students are asked to represent the reaction they have chosen with an acceptable chemical equation, identify a factor that influences its rate and explain how and why it does so, and describe the relevance of the reaction occurring at a slower or faster rate under this condition. The assignment is designed to develop and assess a number of valuable skills and understandings, including the ability to write effectively. (Contains 2 notes.)

Explores the basics in technology convergence in making today's college and university campuses more "intelligent." Two key components required for effective technology convergence are described as are the benefits of convergence on campus safety and security and utility cost management. (GR)

In this article, we describe teacher educators' collaboration for coherence around social justice teacher education in preparation for a national accreditation review. Specifically, we illuminate how we cultivated an inquiry stance and critical conversations to build a safe and trusting community, generate locally meaningful values, and reconceptualize diversity in terms of social justice. By depicting our collaborative process in clarifying a detail, we make visible how we developed social justice-oriented vision, mission, and commitment statements and a conceptual framework to transform our traditional university-based undergraduate program. Aiming to inform other programs striving for coherence for social justice, we offer insights for supporting collaboration, considering the local community and political context, and leveraging accreditation. [ABSTRACT FROM AUTHOR]

Key points: The TASK‐1 channel gene (KCNK3) has been identified as a possible disease‐causing gene in heritable pulmonary arterial hypertension (PAH).In the present study, we show that novel mutated TASK‐1 channels, seen in PAH patients, have a substantially reduced current compared to wild‐type TASK‐1 channels.These mutated TASK‐1 channels are located at the plasma membrane to the same degree as wild‐type TASK‐1 channels.ONO‐RS‐082 and alkaline pH 8.4 both activate TASK‐1 channels but do not recover current through mutant TASK‐1 channels.We show that the guanylate cyclase activator, riociguat, a novel treatment for PAH, enhances current through TASK‐1 channels but does not recover current through mutant TASK‐1 channels. Pulmonary arterial hypertension (PAH) affects ∼15–50 people per million. KCNK3, the gene that encodes the two pore domain potassium channel TASK‐1 (K2P3.1), has been identified as a possible disease‐causing gene in heritable PAH. Recently, two new mutations have been identified in KCNK3 in PAH patients: G106R and L214R. The present study aimed to characterize the functional properties and regulation of wild‐type (WT) and mutated TASK‐1 channels and determine how these might contribute to PAH and its treatment. Currents through WT and mutated human TASK‐1 channels transiently expressed in tsA201 cells were measured using whole‐cell patch clamp electrophysiology. Localization of fluorescence‐tagged channels was visualized using confocal microscopy and quantified with in‐cell and on‐cell westerns. G106R or L214R mutated channels were located at the plasma membrane to the same degree as WT channels; however, their current was markedly reduced compared to WT TASK‐1 channels. Functional current through these mutated channels could not be restored using activators of WT TASK‐1 channels (pH 8.4, ONO‐RS‐082). The guanylate cyclase activator, riociguat, enhanced current through WT TASK‐1 channels; however, similar to the other activators investigated, riociguat did not have any effect on current through mutated TASK‐1 channels. Thus, novel mutations in TASK‐1 seen in PAH substantially alter the functional properties of these channels. Current through these channels could not be restored by activators of TASK‐1 channels. Riociguat enhancement of current through TASK‐1 channels could contribute to its therapeutic benefit in the treatment of PAH. Key points: The TASK‐1 channel gene (KCNK3) has been identified as a possible disease‐causing gene in heritable pulmonary arterial hypertension (PAH).In the present study, we show that novel mutated TASK‐1 channels, seen in PAH patients, have a substantially reduced current compared to wild‐type TASK‐1 channels.These mutated TASK‐1 channels are located at the plasma membrane to the same degree as wild‐type TASK‐1 channels.ONO‐RS‐082 and alkaline pH 8.4 both activate TASK‐1 channels but do not recover current through mutant TASK‐1 channels.We show that the guanylate cyclase activator, riociguat, a novel treatment for PAH, enhances current through TASK‐1 channels but does not recover current through mutant TASK‐1 channels. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the ability of Chiropractic College Assessment Test (CCAT) to explain academic success within a chiropractic basic science curriculum. Methods: The CCAT examination was administered to 202 subjects from I chiropractic college on the first day of classes. Zero-order Pearson correlations were used to examine for associations between the prechiropractic grade point average (GPA), CCAT scores, and basic science GPA. Multiple regression techniques were applied to determine the predictive efficacy of CCAT scores on basic science GPA. Results: Study results indicate a correlation between prechiropractic GPA, CCAT scores (r 0.348. P < .001), and basic science GPA (r = 0.559, P < .001). Correlation was also noted between CCAT scores mid basic science GPA (r = 0.537, P < .001). Using multiple regression, together the variables (age, postsecondary education, prechiropractic GPA, and CCAT scores) accounted for a significant portion (R2 = 0.483, P < .00l) of the total variance in basic science GPA. Furthermore, the CCAT scores accounted for significant unique explanation (change R2 = 0.081, P < .001) beyond that offered by the traditionally used prechiropractic GPA. Conclusion: The CCAT examination provides a valuable a priori indicator of success within the basic science curriculum of this particular chiropractic program Consideration should be given to adopting the CCAT examination as one of a number of heuristic guides students and college officials use in making enrollment decisions. [ABSTRACT FROM AUTHOR]