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Users of signed and spoken languages regularly engage bodily enactment (commonly referred to as constructed action [CA] for signers and character viewpoint gestures [CVPT] for speakers) for the creation of meaning, but comparatively few studies have addressed how linguistic grammar interfaces with such gestural depictive devices across language modalities. CVPT gestures have been shown to co-occur with spoken language transitive verbs, and when a reference is definite or more accessible in the discourse. In sign, CA often alternates sequentially with fully conventionalized signs. In both CVPT and CA demonstrations, syntactic and pragmatic factors appear to be important. In this work, we consider these patterns by examining short retellings of video-based elicitation stimuli (silent-movie segments) from 10 deaf users of ASL (American Sign Language) and 20 hearing speakers of English. We describe examples of signs and words that co-occur with or precede specific instances of CA and CVPT. We also examine distributions and degrees of enactment across participants in order to consider the question of gesture threshold (Hostetter and Alibali, 2008, 2019). We provide various examples of how gestural material interfaces with linguistic grammar, which has implications for syntactic theory and possible grammatical constraints on such communicative devices.

Supplementary Methods, Figures 1-3, Table 1 from Dual Activity Lysophosphatidic Acid Receptor Pan-Antagonist/Autotaxin Inhibitor Reduces Breast Cancer Cell Migration In vitro and Causes Tumor Regression In vivo

Background: With new technological advancements, adolescents can obtain devices that give them virtually unlimited access to social media (SM) which may impact adolescent mental health. Objectives: This literature review aims to evaluate the influence of social media use on adolescent anxiety and depression. Methods: A literature search of PubMed from June 2010 through June 2020 was completed for the following MeSH terms: social media, adolescent, anxiety, depression, and mental health. English language articles that discussed adolescents aged 13 to 18 years, anxiety and/or depression and SM were included. Extracted data included the SM platform, impact on anxiety and depression, interventions, temporal and dose-response relationships, and observed versus self-reported usage. Results: The majority of articles positively associated depression (82.6%) and anxiety (78.3%) with SM use. depression corresponded with cyber-bullying (42.1%), negative social perspective (21.0%), diminished self-esteem (15.8%), and sleep disturbance (10.5%). Anxiety corresponded with a negative social perspective (44.4%), diminished self-esteem (33.3%), sleep disturbance (16.7%), and cyber-bullying (16.7%). Many studies suggested the use of interventions to reduce depression (72.7%) and anxiety (72.7%), such as screen time restrictions (n=6) and social support (n=4), but lacked evaluation of their implementation. Conclusion: Current literature suggests a positive association between adolescent SM use with anxiety and depression. Our study highlights the need for further investigation of temporal and dose-response associations between SM use and adolescent mental health, and the potential benefits of SM-driven interventions.

We present two studies exploring how participants respond when a speaker contrasts two ideas, then expresses an ambiguous preference towards one of them. Study 1 showed that, when reading a speaker’s preference as text, participants tended to choose whatever was said last as matching the speaker’s preference, reflecting the recent-mention bias of anaphora resolution. In Study 2, we asked whether this pattern changed for audio versions of our stimuli. We found that it did not. We then asked whether observers used gesture to disambiguate the speaker’s preference. Participants watched videos in which two statements were spoken. Co-speech gestures were produced during each statement, in two different locations. Next, an ambiguous preference for one option was spoken. In ‘gesture disambiguating’ trials, this statement was accompanied by a gesture in the same spatial location as the gesture accompanying the first statement. In ‘gesture non-disambiguating’ trials, no third gesture occurred. Participants chose the first statement as matching the speaker’s preference more often for gesture disambiguating compared to non-disambiguating trials. Our findings add to the literature on resolution of ambiguous anaphoric reference involving concrete entities and discourse deixis, and we extend this literature to show that gestures indexing abstract ideas are also used during discourse comprehension.

Many undergraduate chemistry students struggle to understand the concept of stereoisomers, molecules that have the same molecular formula and sequence of bonded atoms but are different in how their atoms are oriented in space. Our goal in this study is to improve stereoisomer instruction by getting participants actively involved in the lesson. Using a pretest–instruction–posttest design, we instructed participants to enact molecule rotation in three ways: (1) by imagining the molecules’ movements, (2) by physically moving models of the molecules, or (3) by gesturing the molecules’ movements. Because gender differences have been found in students’ performance in chemistry (Moss-Racusin et al., 2018), we also disaggregated our effects by gender and examined how men and women responded to each of our 3 types of instruction. Undergraduate students took a pretest on stereoisomers, were randomly assigned to one of the 3 types of instruction in stereoisomers, and then took a posttest. We found that, controlling for pretest performance, both women and men participants made robust improvements after instruction. We end with a discussion of how these findings might inform stereoisomer instruction.

Our interdisciplinary team (which included professionals from nursing, pharmacy, allied health, and psychology) conducted in-depth, semi-structured interviews with pharmacy students (n = 14) who were presently in a clinical rotation. When conducting the phenomenological, qualitative research study, we explored how students framed their respective experiences of incorporating spirituality into their clinical work. Three themes emerged from the interviews: (1) The students reportedly viewed their main role as being more of a support person than an evangelist, (2) They framed their influence from the perspective of so-called faith flags, and (3) They perceived more opportunities for influence with their coworkers than with patients. We discuss the findings in light of published findings and also in terms of how health care workers frame the concept of “ministry.”

Large conductance, calcium/voltage-gated potassium channels (BK) regulate critical body processes, including neuronal, secretory and smooth muscle (SM) function. While BK-forming alpha subunits are ubiquitous, accessory beta1 subunits are highly expressed in SM. This makes beta1 an attractive target for pharmaceutical development to treat SM disorders, such as hypertension or cerebrovascular spasm. Compounds activating BK via beta1 have been identified, yet they exhibit low potency and off-target effects while antagonists that limit agonist activity via beta 1 remain unexplored. Beta1-dependent BK ligand-based pharmacophore modeling and ZINC database searches identified 15 commercially available hits. Concentration-response curves on BK alpha + beta1 subunit-mediated currents were obtained in CHO cells. One potent (EC

EXECUTIVE SUMMARY Even while making progress toward improved health outcomes, the United States is facing health disparities, increasing rates of chronic diseases, and rising healthcare costs. Health systems and organizations understand the positive impact that addressing social determinants of health (SDOH) can have on population health outcomes and cost savings, yet barriers exist to SDOH initiatives because of a lack of standardization and a clear framework. This essay proposes six steps for various types of healthcare organizations to take to achieve their unique SDOH goals. The framework provides examples from the SDOH literature for identifying and prioritizing health issues; conducting literature scans; calculating a projected return on investment; and selecting, implementing, and evaluating an SDOH initiative. By applying the evidence base for SDOH in developing and evaluating their efforts, healthcare organizations are better equipped to implement an SDOH initiative that improves health outcomes and decreases healthcare costs.

Medical students represent a significant part of the health-care community and are active members of the coronavirus disease 2019 (COVID-19) response. This study aimed to evaluate various factors associated with COVID-19 vaccine intention among medical students via an online anonymous survey. A total of 370 students completed the online survey, with 229 (61.89%) not vaccinated for COVID-19. Of students not yet vaccinated, 45 (19.65%) were unsure or did not intend to accept the vaccine, while 184 (80.35%) intend to be vaccinated within 6 months. Overall, female gender, health status, clinical science enrollment, and the practice of COVID-19 preventative behaviors significantly correlated with the intention to be vaccinated within 6 months. Greater perceived risk for contracting COVID-19, lesser beliefs that the COVID-19 vaccination trials were rushed, and greater beliefs that being vaccinated would help complete their medical education were uniquely associated with the intention to be vaccinated within 6 months. Collectively, this study identified several factors that influenced medical students' intention to receive the COVID-19 vaccination. This information may be used in future immunization strategies to increase the vaccination rates among this group of future medical professionals.

A 28-year-old male patient with an unclear history of psychosis was admitted to the inpatient psychiatric unit. He presented with auditory hallucinations, agitation, and bizarre and disorganized behavior. He was treated with antipsychotic medications without improvement. Magnetic resonance imaging of the brain showed hyperintensities throughout the brain parenchyma. Investigations for infectious, metabolic, autoimmune, and malignant etiologies were negative. Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis was suspected. Cerebrospinal fluid (CSF) and serum NMDA receptor antibody testing were performed. Both tests were positive, confirming anti-NMDA receptor encephalitis. The patient was treated with intravenous immunoglobulin and methylprednisolone, which resulted in the resolution of his psychosis. In the case of unexplained psychosis associated with seizures, early screening using serum and CSF testing for anti-NMDA receptor antibodies and brain magnetic resonance imaging may be an important diagnostic tool for detecting anti-NMDA receptor encephalitis. Detailed investigations of CSF and serum should be performed to rule out infectious, metabolic, and autoimmune causes. Imaging studies should also be performed to identify any tumors such as a teratoma. This approach may help identify patients with anti-NMDA receptor encephalitis masquerading as psychosis. Early diagnosis and treatment including intravenous steroids, immunosuppressants, plasmapheresis, and removal of any teratoma if present in patients with anti-NMDA receptor encephalitis can improve the overall outcome.

Purpose: Aortic arch anatomical variations are of surgical importance. Many variations of the aortic arch and associated vessels may be found incidentally or post-mortem. Methods: A 61-year-old presented with symptoms suspicious of a cerebrovascular accident. Results: The patient was found to have the right internal and external carotid arteries emanating from the right subclavian artery in absence of a common carotid artery on computed tomography angiography of the neck. Conclusion: A recent comprehensive review noted 41 published cases of common carotid artery aplasia with the right internal carotid originating from the subclavian artery in only 4 of these cases. The current case represents a rare absence of the right CCA with the right ICA and ECA originating separately from the right subclavian artery.

This descriptive study explores the gestures undergraduate students produce when talking about the concept of standard deviation (SD). Gestures can be an important source of information about underlying internal representations of mathematical concepts, but thus far have not been examined in research exploring why concepts of variability (such as standard deviation) are difficult for students to learn. Thirteen undergraduates who had taken at least one course in statistics were asked to explain how they thought about SD. Speech and gesture were analyzed for their possible interpretation as encoding distance from the mean and frequency of values at different distances. We describe the different types of gestures that occurred in the data and also present a coding scheme that can be utilized for future research linking these gestures to students’ understanding of SD. We discuss how such a multimodal approach can enhance mathematics pedagogy.

G protein-coupled receptors (GPCR) are integral membrane proteins of considerable interest as targets for drug development. GPCR ligand interaction studies often have a starting point with either crystal structures or comparative models. The majority of GPCR do not have experimentally-characterized 3-dimensional structures, so comparative modeling, also called homology modeling, is a good structure-based starting point. Comparative modeling is a widely used method for generating models of proteins with unknown structures by analogy to crystallized proteins that are expected to exhibit structural conservation. Traditionally, comparative modeling template selection is based on global sequence identity and shared function. However high sequence identity localized to the ligand binding pocket may produce better models to examine protein-ligand interactions. This in silico benchmark study examined the performance of a global versus local similarity measure applied to comparative modeling template selection for 6 previously crystallized, class A GCPR (CXCR4, FFAR1, NOP, P2Y12, OPRK, and M1) with the long-term goal of optimizing GPCR ligand identification efforts. Comparative models were generated from templates selected using both global and local similarity measures. Similarity to reference crystal structures was reflected in RMSD values between atom positions throughout the structure or localized to the ligand binding pocket. Overall, models deviated from the reference crystal structure to a similar degree regardless of whether the template was selected using a global or local similarity measure. Ligand docking simulations were performed to assess relative performance in predicting protein-ligand complex structures and interaction networks. Calculated RMSD values between ligand poses from docking simulations and crystal structures indicate that models based on locally selected templates give docked poses that better mimic crystallographic ligand positions than those based on globally-selected templates in five of the six benchmark cases. However, protein model refinement strategies in advance of ligand docking applications are clearly essential as the average RMSD between crystallographic poses and poses docked into local template models was 9.7 A and typically less than half of the ligand interaction sites are shared between the docked and crystallographic poses. These data support the utilization of local similarity measures to guide template selection in protocols using comparative models to investigate ligand-receptor interactions.

Coping with the stress of real and simulated disasters is thought to be integral to the performance of emergency medicine providers. Yet, little is known about which coping strategies are employed in these scenarios and whether differential use of strategies predicts actual clinical and interpersonal performance.Thirty-four medical students were evaluated by trained simulated patients and physician observers across 111 clinical encounters during a simulated disaster. Linear Mixed Effects Modelling was used to test study hypotheses while accounting for demographic variables, psychological factors, and the dependency of multiple encounters for each participant.Results indicated that multilevel modeling was necessary. Positive thinking positively predicted observed clinical performance whereas avoidant coping was a negative predictor. Anticipatory anxiety and positive affect, but not reported coping, positively predicted student interpersonal performance.The present study indicates that the way medical students report managing the stress of disaster scenarios has clear links to their observed clinical performance above and beyond demographic and psychological factors. It further demonstrates the feasibility of empirically identifying specific coping strategies that may be important targets for disaster response training.

This pooled analysis, from a systematic review, examines anti-N-Methyl D-Aspartate Receptor (NMDAR) encephalitis presentation in children and adolescents.A comprehensive literature search from database inception through December 31, 2019, using PubMed, PsycInfo, and OVID was performed. Case reports and case series were included. Sample characteristics are described. Prodromal and presenting symptoms between partial recovery and full recovery are compared. The association between presenting symptoms and abnormal MRI, abnormal EEG, and tumor presence are determined.The sample (n=283) had a mean age of 10.8 years with 75.3% females. The most common prodromal and presenting symptom was seizure (29.7% and 63.3%, respectively). Partial and full recovery did not differ for prodromal and presenting symptoms. Multivariate logistic regression analysis found that (1) delusion were significantly associated with higher odds and aggressive behavior was associated with lower odds for abnormal findings on magnetic resonance imaging (MRI); (2) waxing and waning of symptoms were significantly associated with higher odds for abnormal electroencephalograms (EEG), and (3) increased age and psychosis were each significantly associated with increased odds, and sleep disturbance and orofacial dyskinesia with lower odds for tumor presence.Given the pattern of findings, routinely obtaining MRI and EEG should be considered for anti-NMDAR encephalitis in children and adolescents presenting with delusion and waxing and waning of symptoms, respectively. Investigation of tumors should be considered in patients with anti-NMDAR encephalitis especially when psychosis is present.La présente analyse combinée, tirée d’une revue systématique, examine la présentation d’une encéphalite anti-récepteur de N-méthyl-D-aspartate (NMDA) chez les enfants et les adolescents.Une recherche détaillée de la littérature à compter des débuts des bases de données jusqu’au 31 décembre 2019, dans PubMed, PsycInfo, et OVID a été menée. Les rapports de cas et les séries de cas sont inclus, et les caractéristiques de l’échantillon sont décrites. Les symptômes avant-coureurs et ceux présentés entre le rétablissement partiel et complet sont comparés. L’association entre les symptômes présentés et une IRM anormale, un EEG anormal, et la présence d’une tumeur est déterminée.L’échantillon (n = 283) avait un âge moyen de 10,8 ans et était à 75,3 % de sexe féminin. Les symptômes avant-coureurs et présentés les plus communs étaient les convulsions (29,7 % et 63,3 %, respectivement). Le rétablissement partiel et complet ne différait pas pour les symptômes avant-coureurs et présentés. L’analyse de régression logistique multivariée a constaté que (1) le délire était significativement associé à des probabilités plus élevées, et le comportement agressif à des probabilités plus faibles de résultats anormaux à l’imagerie par résonance magnétique (IRM); (2) les variations des symptômes étaient significativement associées à des probabilités plus élevées d’électro-encéphalogrammes (EEG) anormaux; et (3) l’âge et la psychose avancés étaient chacun significativement associés à des probabilité accrues, mais le trouble du sommeil et la dyskinésie bucco-faciale étaient eux associés à des probabilités plus faibles de la présence d’une tumeur.Étant donné le modèle des résultats, obtenir automatiquement une IRM et un EEG devrait être envisagé chez les enfants et les adolescents présentant un délire et une variation des symptômes, respectivement. L’investigation de tumeurs devrait être envisagée chez les patients de l’encéphalite anti-récepteur NMDAR surtout en présence de psychose.

AIM Inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and celiac disease (CeD) more commonly affect women of reproductive age. The aim of our study is to evaluate the association between ectopic pregnancy (EP) in women with IBD, IBS, and CeD. METHODS We searched MEDLINE, Web of Science, and CINAHL from the database inception date through December 31, 2020. Peer-reviewed publications and abstracts written in English, regarding the association between EP and IBD, IBS, and CeD with controls were included. Quality assessment was conducted based on GRADE criteria. Analyses included odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity between studies was presented with I2 . RESULTS We included five population-based cohort studies. The odds of EP significantly increased in Crohn's disease (CD), but not ulcerative colitis (UC) as compared to IBD-free controls. The odds of EP significantly increased in IBS as compared to women without IBS. No significant difference was observed for odds of EP in women with and without CeD. CONCLUSIONS Possible evidence of associations between EP and CD as well as IBS were observed; however, not with UC and CeD. Pregnant women with chronic inflammatory bowel pathologies may warrant cautious monitoring.

G protein-coupled receptors (GPCR) are the largest family of cell surface receptors in vertebrates. Their abundance and role in nearly all physiological systems make GPCR the largest protein family targeted for development of pharmaceuticals. Ligand discovery aimed at identification of chemical tools and drug leads is aided by molecular docking simulations that allow critical analysis of the potential interactions between small molecules and proteins in resulting complexes. However, blind assessments of ligand pose quality and affinity prediction have thus far not provided broadly generalizable performance expectations for docking into experimentally-characterized GPCR targets. Likewise, the relative importance of receptor activation state and ligand function differences have also not been systematically assessed. This study compares performance when docking ligands of varied function into varied GPCR activation states in the absence of extensive resampling of the input GPCR structure, and only limited sidechain flexibility after ligand placement. Simulations were performed using 37 experimental structures of 11 Class A GPCR crystallized in multiple activation states (giving rise to 37 self-docking and 68 cross docking simulations). Our results show that one specific subset of cross-docking simulations gave results of similar quality to self-docking. Median ligand RMSD values for top-scored poses were 1.2 Å and 2.0 Å for self-docking and State

Integral membrane proteins in the G Protein-Coupled Receptor (GPCR) class are attractive drug development targets. However, computational methods applicable to ligand discovery for many GPCR targets are restricted by limited numbers of known ligands. Pharmacophore models can be developed using variously sized training sets and applied in database mining to prioritize candidate ligands for subsequent validation. This in silico study assessed the impact of key pharmacophore modeling decisions that arise when known ligand numbers for a target of interest are low. GPCR included in this study are the adrenergic alpha-1A, 1D and 2A, adrenergic beta 2 and 3, kappa, delta and mu opioid, serotonin 1A and 2A, and the muscarinic 1 and 2 receptors, all of which have rich ligand data sets suitable to assess the performance of protocols intended for application to GPCR with limited ligand data availability. Impact of ligand function, potency and structural diversity in training set selection was assessed to define when pharmacophore modeling targeting GPCR with limited known ligands becomes viable. Pharmacophore elements and pharmacophore model selection criteria were also assessed. Pharmacophore model assessment was based on percent pharmacophore model generation failure, as well as Güner-Henry enrichment and goodness-of-hit scores. Three of seven pharmacophore element schemes evaluated in MOE 2018.0101, Unified, PCHD, and CHD, showed substantially lower failure rates and higher enrichment scores than the others. Enrichment and GH scores were used to compare construction protocol for pharmacophore models of varying purposes- such as function specific versus nonspecific ligand identification. Notably, pharmacophore models constructed from ligands of mixed functions (agonists and antagonists) were capable of enriching hitlists with active compounds, and therefore can be used when available sets of known ligands are limited in number.

Our interdisciplinary team (which included professionals from nursing, pharmacy, allied health, and psychology) conducted in-depth, semi-structured interviews with pharmacy students (n = 14) who were presently in a clinical rotation. When conducting the phenomenological, qualitative research study, we explored how students framed their respective experiences of incorporating spirituality into their clinical work. Three themes emerged from the interviews: (1) The students reportedly viewed their main role as being more of a support person than an evangelist, (2) They framed their influence from the perspective of so-called faith flags, and (3) They perceived more opportunities for influence with their coworkers than with patients. We discuss the findings in light of published findings and also in terms of how health care workers frame the concept of "ministry."

When faced with an ambiguous pronoun, comprehenders use both multimodal cues (e.g., gestures) and linguistic cues to identify the antecedent. While research has shown that gestures facilitate language comprehension, improve reference tracking, and influence the interpretation of ambiguous pronouns, literature on reference resolution suggests that a wide set of linguistic constraints influences the successful resolution of ambiguous pronouns and that linguistic cues are more powerful than some multimodal cues. To address the outstanding question of the importance of gesture as a cue in reference resolution relative to cues in the speech signal, we have previously investigated the comprehension of contrastive gestures that indexed abstract referents – in this case expressions of personal preference – and found that such gestures did facilitate the resolution of ambiguous statements of preference. In this study, we extend this work to investigate whether the effect of gesture on resolution is diminished when the gesture indexes a statement that is less likely to be interpreted as the correct referent. Participants watched videos in which a speaker contrasted two ideas that were either neutral (e.g., whether to take the train to a ballgame or drive) or moral (e.g., human cloning is (un)acceptable). A gesture to the left or right side co-occurred with speech expressing each position. In gesture-disambiguating trials, an ambiguous phrase (e.g., I agree with that, where that is ambiguous) was accompanied by a gesture to one side or the other. In gesture non-disambiguating trials, no third gesture occurred with the ambiguous phrase. Participants were more likely to choose the idea accompanied by gesture as the stimulus speaker’s preference. We found no effect of scenario type. Regardless of whether the linguistic cue expressed a view that was morally charged or neutral, observers used gesture to understand the speaker’s opinion. This finding contributes to our understanding of the strength and range of cues, both linguistic and multimodal, that listeners use to resolve ambiguous references.

Lysophosphatidic acid (LPA) is a phospholipid that acts as an extracellular signaling molecule and activates the family of lysophosphatidic acid receptors (LPA(1–6)). These G protein-coupled receptors (GPCRs) are broadly expressed and are particularly important in development as well as in the nervous, cardiovascular, reproductive, gastrointestinal, and pulmonary systems. Here, we report on a photoswitchable analogue of LPA, termed AzoLPA, which contains an azobenzene photoswitch embedded in the acyl chain. AzoLPA enables optical control of LPA receptor activation, shown through its ability to rapidly control LPA-evoked increases in intracellular Ca(2+) levels. AzoLPA shows greater activation of LPA receptors in its light-induced cis-form than its dark-adapted (or 460 nm light-induced) trans-form. AzoLPA enabled the optical control of neurite retraction through its activation of the LPA(2) receptor.

The lysophospholipase D autotaxin (ATX) generates lysophosphatidic acid (LPA) that activates six cognate G-protein coupled receptors (GPCR) in cancerous cells, promoting their motility and invasion. Four novel compounds were generated aided by molecular docking guided design and synthesis techniques to obtain new dual inhibitors of ATX and the lysophosphatidic acid receptor subtype 1 (LPAR1). Biological evaluation of these compounds revealed two compounds, 10 and 11, as new ATX enzyme inhibitors with potencies in the range of 218–220 nM and water solubility (>100 µg/mL), but with no LPAR1 inhibitory activity. A QSAR model was generated that included four newly designed compounds and twenty-one additional compounds that we have reported previously. The QSAR model provided excellent predictability of the pharmacological activity and potency among structurally related drug candidates. This model will be highly useful in guiding the synthesis of new ATX inhibitors in the future.

G protein-coupled receptors (GPCR) comprise the largest family of membrane proteins and are of considerable interest as targets for drug development. However, many GPCR structures remain unsolved. To address the structural ambiguity of these receptors, computational tools such as homology modeling and loop modeling are often employed to generate predictive receptor structures. Here we combined both methods to benchmark a protocol incorporating homology modeling based on a locally selected template and extracellular loop modeling that additionally evaluates the presence of template ligands during these modeling steps. Ligands were also docked using three docking methods and two pose selection methods to elucidate an optimal ligand pose selection method. Results suggest that local template-based homology models followed by loop modeling produce more accurate and predictive receptor models than models produced without loop modeling, with decreases in average receptor and ligand RMSD of 0.54 A and 2.91 A, respectively. Ligand docking results showcased the ability of MOE induced fit docking to produce ligand poses with atom root-mean-square deviation (RMSD) values at least 0.20 A lower (on average) than the other two methods benchmarked in this study. In addition, pose selection methods (software-based scoring, ligand complementation) selected lower RMSD poses with MOE induced fit docking than either of the other methods (averaging at least 1.57 A lower), indicating that MOE induced fit docking is most suited for docking into GPCR homology models in our hands. In addition, target receptor models produced with a template ligand present throughout the modeling process most often produced target ligand poses with RMSD values ≤ 4.5 A and Tanimoto coefficients > 0.6 after selection based on ligand complementation than target receptor models produced in the absence of template ligands. Overall, the findings produced by this study support the use of local template homology modeling in combination with de novo ECL2 modeling in the presence of a ligand from the template crystal structure to generate GPCR models intended to study ligand binding interactions.

When children tell stories, they gesture; their gestures can predict how their narrative abilities will progress. Five-year-olds who gestured from the point of view of a character (CVPT gesture) when telling stories produced better-structured narratives at later ages (Demir, Levine, & Goldin-Meadow, 2014). But does gesture just predict narrative structure, or can asking children to gesture in a particular way change their narratives? To explore this question, we instructed children to produce CVPT gestures and measured their narrative structure. Forty-four kindergarteners were asked to tell stories after being trained to produce CVPT gestures, gestures from an observer’s viewpoint (OVPT gestures), or after no instruction in gesture. Gestures were coded as CVPT or OVPT, and stories were scored for narrative structure. Children trained to produce CVPT gestures produced more of these gestures, and also had higher narrative structure scores compared to those who received the OVPT training. Children returned for a follow-up session one week later and narrated the stories again. The training received in the first session did not impact narrative structure or recall for the events of the stories. Overall, these results suggest a brief gestural intervention has the potential to enhance narrative structure. Due to the fact that stronger narrative abilities have been correlated with greater success in developing writing and reading skills at later ages, this research has important implications for literacy and education.

A previous study [Rawool, V. W. (2016). Auditory processing deficits: Assessment and intervention. New York, NY: Thieme Medical Publishers, Inc., pp. 186-187] demonstrated objective assessment of binaural summation through right contralateral acoustic reflex thresholds (ARTs) in women. The current project examined if previous findings could be generalised to men and to the left ear.Cross-sectional.Sixty individuals participated in the study. Left and right contralateral ARTs were obtained in two conditions. In the alternated condition, the probe tone presentation was alternated with the presentation of the reflex activating clicks. In the simultaneous condition, the probe tone and the clicks were presented simultaneously. Binaural summation was calculated by subtracting the ARTs obtained in the simultaneous condition from the ARTs obtained in the alternated condition.MANOVA on ARTs revealed no significant gender or ear effects. The ARTs were significantly lower/better in the simultaneous condition compared to the alternated condition.Binaural summation was 4 dB or higher in 88% of the ears and 6 dB or higher in 76% of ears. Stimulation of six out of the total 120 (0.5%) ears resulted in worse thresholds in the simultaneous condition compared with the alternating condition, suggesting binaural interference.

Speakers perform manual gestures in the physical space nearest them, called gesture space. We used a controlled elicitation task to explore whether speakers use gesture space in a consistent way (assign spaces to ideas and use those spaces for those ideas) and whether they use space in a contrastive way (assign different spaces to different ideas when using contrastive speech) when talking about abstract referents. Participants answered two questions designed to elicit contrastive, abstract discourse. We investigated manual gesture behavior. Gesture hand, location on the horizontal axis, and referent in corresponding speech were coded. We also coded contrast in speech. Participants’ overall tendency to use the same hand (t(17) = 13.12, p = .001, 95% CI [.31, .43], d = 2.53) and same location (t(17) = 7.47, p = .001, 95% CI [.27, .47], d = 1.69) when referring to an entity was higher than expected frequency. When comparing pairs of gestures produced with contrastive speech to pairs of gestures produced with non-contrastive speech, we found a greater tendency to produce gestures with different hands for contrastive speech: (t(17) = 4.19, p = .001, 95% CI [.27, .82], d = 1.42). We did not find associations between dominant side and positive concepts or between left, center, and right space and past, present, and future, respectively, as predicted by previous studies. Taken together, our findings suggest that speakers do produce spatially consistent and contrastive gestures for abstract as well as concrete referents. They may be using spatial resources to assist with abstract thinking, and/or to help interlocutors with reference tracking. Our findings also highlight the complexity of predicting gesture hand and location, which appears to be the outcome of many competing variables.

Autotaxin (ATX, aka. ENPP2) is the main source of the lipid mediator lysophosphatidic acid (LPA) in biological fluids. This study reports on inhibitors of ATX derived by lead optimization of the benzene-sulfonamide in silico hit compound 3. The new analogues provide a comprehensive structure–activity relationship of the benzene-sulfonamide scaffold that yielded a series of highly potent ATX inhibitors. The three most potent analogues (3a, IC(50) ~ 32 nM; 3b, IC(50) ~ 9 nM; and 14, IC(50) ~ 35 nM) inhibit ATX-dependent invasion of A2058 human melanoma cells in vitro. Two of the most potent compounds, 3b and 3f (IC(50) ~ 84 nM), lack inhibitory action on ENPP6 and ENPP7 but possess weak antagonist action specific to the LPA(1) G protein-coupled receptor. In particular, compound 3b potently reduced in vitro chemotherapeutic resistance of 4T1 breast cancer stem-like cells to paclitaxel and significantly reduced B16 melanoma metastasis in vivo.

The presence of a human figure in a scene appears to change how people describe it. About 20% of participants take the human figure's viewpoint (Tversky and Hard in Cognition 110:124-129, 2009. http://doi.org/10.1016/j.cognition.2008.10.008). Five exploratory studies compare descriptions of a scene with no person to descriptions of a scene with a person. About 20% of participants are predicted to use the person's point of view in the "person" conditions. Study 1 replicates the original pattern. Study 2 shows that the pattern holds when object/scene are changed, and that the figure's gaze towards/away from the object does not change the pattern. Studies 3 and 4 show the pattern holds when the object has different positions and when it is moving. Study 5 shows the pattern holds when the describer is talking to an interlocutor, in both speech and co-speech gesture, and when the person is using gesture alone. The presence of a human figure in a scene appears to be a robust variable in shaping spatial descriptions.

G protein-coupled receptors (GPCR) are important drug discovery targets. Despite progress, many GPCR structures have not yet been solved. For these targets, comparative modeling is used in virtual ligand screening to prioritize experimental efforts. However, the structure of extracellular loop 2 (ECL2) is often poorly predicted. This is significant due to involvement of ECL2 in ligand binding for many Class A GPCR. Here we examine the performance of loop modeling protocols available in the Rosetta (cyclic coordinate descent [CCD], KIC with fragments [KICF] and next generation KIC [NGK]) and Molecular Operating Environment (MOE) software suites (de novo search). ECL2 from GPCR crystal structures served as the structure prediction targets and were divided into four sets depending on loop length. Results suggest that KICF and NGK sampled and scored more loop models with sub-angstrom and near-atomic accuracy than CCD or de novo search for loops of 24 or fewer residues. None of the methods were able to sample loop conformations with near-atomic accuracy for the longest targets ranging from 25 to 32 residues based on 1000 models generated. For these long loop targets, increased conformational sampling is necessary. The strongly conserved disulfide bond between Cys3.25 and Cys45.50 in ECL2 proved an effective filter. Setting an upper limit of 5.1 A on the S–S distance improved the lowest RMSD model included in the top 10 scored structures in Groups 1–4 on average between 0.33 and 1.27 A. Disulfide bond formation and geometry optimization of ECL2 provided an additional incremental benefit in structure quality.

Does being instructed to gesture encourage those with low gesture rates to produce more gestures? If participants do gesture more when asked to, do they produce the same kinds of gestures? Does this vary as a function of the type of discourse being produced? We asked participants to take part in three tasks, a quasi-conversational task, a spatial problem solving task, and a narrative task, in two phases. In the first they received no instruction, and in the second they were asked to gesture. The instruction to gesture did not change gesture rate or gesture type across phases. We suggest that while explicitly asking participants to gesture may not always achieve higher gesture rates, it also does not negatively impact natural behavior.

An extensive Internet search was conducted to obtain pre-admission information and acceptance statistics from 260 graduate programmes in speech-language pathology accredited by the American Speech-Language-Hearing Association (ASHA) in the United States. ASHA is the national professional, scientific and credentialing association for members and affiliates who are audiologists; speech-language pathologists; speech, language and hearing scientists; audiology and speech-language pathology support personnel and students. Data were collected for analysis from Internet websites of individual academic programmes and ASHA’s EdFind, an online directory for undergraduate and graduate programmes in communication sciences and disorders in the United States. Frequency counts were used to analyse the data. Since graduate programmes are not required by ASHA to report or publish entrance requirements, the information included on the individual websites and ASHA’s EdFind varies widely among the programmes with som...

Lipids have a variety of physiological roles, ranging from structural and biophysical contributions to membrane functions to signaling contributions in normal and abnormal physiology. This review highlights some of the contributions made by Robert Bittman to our understanding of lipid assemblies through the production of synthetic lipid analogs in the sterol, sphingolipid, and glycolipid classes. His contributions have included the development of a fluorescent cholesterol analog that shows strong functional analogies to cholesterol that has allowed live imaging of cholesterol distribution in living systems, to stereospecific synthetic approaches to both sphingolipid and glycolipid analogs crucial in defining the structure-activity relationships of lipid biological targets.

Objective To determine whether the use of family members as educators in a structured educational intervention would increase neonatology fellows' confidence in performing core communication skills targeted to guide family decision-making. Study design Neonatology fellows at two centers participated in simulation-based training utilizing formally trained family members of former patients. Fellows completed self-assessment surveys before participating, immediately following participation, and 1-month following the training. Family members also evaluated fellow communication. Results For each core competency assessed, there was a statistically significant increase in self-perceived preparedness from pre-course to post-course assessments. Fellows additionally endorsed using skills learned in the curriculum in daily clinical practice. Family educators rated fellow communication highest in empathetic listening and nonverbal communication. Conclusions Participation in a communication skills curriculum utilizing formally trained family members as educators for medical trainees successfully increased fellows' self-perceived preparedness in selected core competencies in communication. Family educators provided useful, generalizable feedback.

Lipids have a variety of physiological roles, ranging from structural and biophysical contributions to membrane functions to signaling contributions in normal and abnormal physiology. This review highlights some of the contributions made by Robert Bittman to our understanding of lipid assemblies through the production of synthetic lipid analogs in the sterol, sphingolipid, and glycolipid classes. His contributions have included the development of a fluorescent cholesterol analog that shows strong functional analogies to cholesterol that has allowed live imaging of cholesterol distribution in living systems, to stereospecific synthetic approaches to both sphingolipid and glycolipid analogs crucial in defining the structure-activity relationships of lipid biological targets.