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The purpose of this article is to explore the use of authentic audiences in higher education to support undergraduate learning. To explore the results of integrating authentic audiences in higher education, we present a collective case study in which the use of authentic audiences was employed in separate undergraduate courses at two different higher education institutions in the Eastern and Midwestern United States (N = 75). In one case, Wikipedia was employed as an authentic audience and in the other case, experienced secondary educators as well as Twitter were embedded. The goal of implementing authentic audiences in both settings and courses was to increase student engagement and foster critical thinking. Results suggest that integrating authentic audiences through these means can enhance undergraduate students' engagement and learning and may serve to capture, but not necessarily foster, students' critical thinking. Concurrently, an instructor's pedagogy must also align with tenets associated with authentic audiences, including a commitment to a coconstruction of knowledge and the purposeful selection of authentic audiences who are engaged, willing to partner, and have the necessary expertise and resources to contribute to students' learning.

Objective: Drink offers are related to increased alcohol consumption, which is linked to sexual activity among college students. However, offers of alcohol may increase the odds of sexual activity that night independent of the amount of alcohol consumed. Participants: 540 undergraduate students were recruited for a longitudinal study of daily experiences. Method: Participants completed up to four annual waves of a measurement burst daily diary study. Using these longitudinal data, we examined whether receiving a drink offer on a given night was related to greater odds of having sex. Results: Receiving a drink offer (but not the number of drinks accepted) is related to greater odds of having sex, controlling for drinking level. Conclusions: Receiving a drink offer is uniquely related to odds of having sex when controlling for the amount of alcohol participants consumed. This may have implications for psychological functioning and relationship development.

Objective: The Theory of Planned Behavior has been applied to COVID-19 protective behaviors, but evidence suggests this theory may be less predictive over time and less valid in individualistic societies. The current study applied this theory among American college students as vaccines became available and added perceived risk. Participants: 242 undergraduate students at two universities. Methods: Participants completed an online survey and analyses were conducted using PROCESS. Results: Perceived risk was indirectly related to protective behavior via intentions which were significantly impacted by positive attitudes, descriptive norms, and perceived behavioral control. Conclusions: Even within an individualistic culture and when vaccines were becoming available, the Theory of Planned Behavior predicts protective behaviors. Including risk perception also furthers understanding of this theory by identifying one factor related to norms and perceived behavioral control. These results may inform the design of interventions designed to increase compliance with pandemic-related policies and other positive behaviors.

This study explores sex-differences in (a) rates and profiles of autism symptoms as well as in (b) the contribution of intellectual quotient (IQ) to autism symptom presentation in Down syndrome (DS). Participants were 40 males and 38 females with DS, aged 6 to 23 years. Autism symptoms were rated through the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2). Results show no sex differences in the ADOS-2 Calibrated Severity Scores (CSS). However, only females with DS who are classified as DS-Only have higher scores on verbal IQ than those classified as DS + autism. Furthermore, associations between IQ and all CSSs are found for females, but not for males. Findings suggest that verbal cognition may play differential roles for females and males with DS.

This collective self-study chronicles the experiences and reflections of four women teacher educators living and working during the COVID-19 pandemic. Data collected between March 2020 and December 2021 centered on the following question: what were we, as teacher educators, experiencing professionally and personally as a result of the pandemic? The COVID-19 context presented a unique set of challenges and an additional layer of complexity highlighting intersections of policy, teacher education, and societal expectations. Findings connected to our professional identities as teacher educators included the need to reframe professional expectations and the impacts to historical narratives in teacher education. Personally, the complexity of mixing the personal and professional spheres and increased personal responsibilities emerged. Findings from this study reaffirm that when we have opportunities to access and learn from the lived experiences of others, we are better positioned to understand ourselves and the personal and professional roles we take on.

This study focuses on the systematic collective reflections of four teacher educators as they interrogate their own practice engaging in community-based settings, specifically considering how these settings can serve as an additional teacher. It is informed by a theory that centers educational experiences within the community and is guided by Gutiérrez's use of the concept of third space. Connected to third spaces, the results of this study reveal that traditional PK-12 settings serve as the first spaces, the university teacher education programs as the second spaces, and the community-based settings as third spaces. Results showcase how these third spaces can be transformative for teacher educators as they consider preservice teachers' learning. Findings are drawn from a 2-year collective self-study of four teacher educators facilitating community-based field experiences in the United States and Canada. Analysis of the teacher educator reflections of their observations revealed the transformative ways in which these community-based places, as separate and unique constructs, acted as a teacher for preservice teachers when working in community-based settings. This study presents arguments for integrating community-based field experiences within teacher education, particularly as such places can support and facilitate preservice teachers' learning.

Abstract Osteoarthritis (OA) is a debilitating degenerative disease affecting multiple joint tissues, including cartilage, bone, synovium, and adipose tissues. OA presents diverse clinical phenotypes and distinct molecular endotypes, including inflammatory, metabolic, mechanical, genetic, and synovial variants. Consequently, innovative technologies are needed to support the development of effective diagnostic and precision therapeutic approaches. Traditional analysis of bulk OA tissue extracts has limitations due to technical constraints, causing challenges in the differentiation between various physiological and pathological phenotypes in joint tissues. This issue has led to standardization difficulties and hindered the success of clinical trials. Gaining insights into the spatial variations of the cellular and molecular structures in OA tissues, encompassing DNA, RNA, metabolites, and proteins, as well as their chemical properties, elemental composition, and mechanical attributes, can contribute to a more comprehensive understanding of the disease subtypes. Spatially resolved biology enables biologists to investigate cells within the context of their tissue microenvironment, providing a more holistic view of cellular function. Recent advances in innovative spatial biology techniques now allow intact tissue sections to be examined using various -omics lenses, such as genomics, transcriptomics, proteomics, and metabolomics, with spatial data. This fusion of approaches provides researchers with critical insights into the molecular composition and functions of the cells and tissues at precise spatial coordinates. Furthermore, advanced imaging techniques, including high-resolution microscopy, hyperspectral imaging, and mass spectrometry imaging, enable the visualization and analysis of the spatial distribution of biomolecules, cells, and tissues. Linking these molecular imaging outputs to conventional tissue histology can facilitate a more comprehensive characterization of disease phenotypes. This review summarizes the recent advancements in the molecular imaging modalities and methodologies for in-depth spatial analysis. It explores their applications, challenges, and potential opportunities in the field of OA. Additionally, this review provides a perspective on the potential research directions for these contemporary approaches that can meet the requirements of clinical diagnoses and the establishment of therapeutic targets for OA.

AbstractThe last decade has seen increasing use of advanced imaging techniques in platelet research. However, there has been a lag in the development of image analysis methods, leaving much of the information trapped in images. Herein, we present a robust analytical pipeline for finding and following individual platelets over time in growing thrombi. Our pipeline covers four steps: detection, tracking, estimation of tracking accuracy, and quantification of platelet metrics. We detect platelets using a deep learning network for image segmentation, which we validated with proofreading by multiple experts. We then track platelets using a standard particle tracking algorithm and validate the tracks with custom image sampling — essential when following platelets within a dense thrombus. We show that our pipeline is more accurate than previously described methods. To demonstrate the utility of our analytical platform, we use it to show that in vivo thrombus formation is much faster than that ex vivo. Furthermore, platelets in vivo exhibit less passive movement in the direction of blood flow. Our tools are free and open source and written in the popular and user-friendly Python programming language. They empower researchers to accurately find and follow platelets in fluorescence microscopy experiments.

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The use of monoclonal antibodies to identify antigens in perfused fixed tissue is currently very challenging. Recently, many antigen retrieval methods have been described that require heating the tissue on slides using a microwave oven. Here, we describe a protocol for antigen retrieval that uses a commercially available solution called Citra and a DNA thermal cycler to heat the tissue sections. This method (i) allows for precise control of the temperature and time (unlike the microwave oven), (ii) uses very small quantities of the antigen retrieval solution, (iii) stains either free-floating sections or sections mounted on slides and (iv) achieves uniform staining throughout the tissue. In the paraformaldehyde-pegused fixed rat cerebellum, the monoclonal antibody glial jibrillary acidic protein conveys the clarity of the Bergmann and stellate glia in the strata. Scanning confocal images through the center of the tissue demonstrates the depth of antibody penetration achieved using this method. Finally, using a monoclonal antibody against the simian virus 40 (SV40) T antigen allowed positive, unequivocal identification of a grafted cell line, immortalized using SV40 T protein, thus demonstrating the true value of this method in an experimental paradigm.

Background This retrospective review aimed to assess if open payments made by industry arthroplasty companies to physicians and hospital systems were significantly affected by implant type and geographic variation. Methods Data was obtained from the Centers for Medicare and Medicaid Services (CMS) publicly available open payment datasets (2016-2019). Geographic locations were identified using regions as defined by the US Census Bureau. A linear regression was calculated to predict the open payment made based on the created variable region, the most used implant type (reverse vs anatomic, n > 30 to be included), and their hypothesized interaction. Results A significant regression equation was found for the hypothesized interaction between implant and region, F (13,11 186) = 3.446, P

WinEcon is a Windows-based introductory Economics CAL package designed for use in higher education. It is the product of the Economics Consortium of the TLTP (Teaching and Learning Technology Programme) consisting of eight university Economics departments. Each of these has been responsible for producing some of the 25 chapters (tutorials) of the finished product. Content is based on covering the common core of introductory Economics as revealed by a survey of higher-education Economics departments. WinEcon is provided, with an accompanying workbook, for a nominal registration fee in the UK. The package is important insofar as it is aimed at all first-year undergraduates studying Economics, which encompasses not only those taking straight Economics degrees but large numbers of students following introductory Economics as part of a Business Studies or Combined Studies course. With no competition to speak of, WinEcon is likely to become a significant feature of the learning experience of a large tranche of the undergraduate population, across a number of degree schemes. Indeed, for many of these students WinEcon will constitute their first major experience of CAL.

Abstract Background The ShK toxin from Stichodactyla helianthus has established the therapeutic potential of sea anemone venom peptides, but many lineage-specific toxin families in Actiniarians remain uncharacterised. One such peptide family, sea anemone 8 (SA8), is present in all five sea anemone superfamilies. We explored the genomic arrangement and evolution of the SA8 gene family in Actinia tenebrosa and Telmatactis stephensoni, characterised the expression patterns of SA8 sequences, and examined the structure and function of SA8 from the venom of T. stephensoni. Results We identified ten SA8-family genes in two clusters and six SA8-family genes in five clusters for T. stephensoni and A. tenebrosa, respectively. Nine SA8 T. stephensoni genes were found in a single cluster, and an SA8 peptide encoded by an inverted SA8 gene from this cluster was recruited to venom. We show that SA8 genes in both species are expressed in a tissue-specific manner and the inverted SA8 gene has a unique tissue distribution. While the functional activity of the SA8 putative toxin encoded by the inverted gene was inconclusive, its tissue localisation is similar to toxins used for predator deterrence. We demonstrate that, although mature SA8 putative toxins have similar cysteine spacing to ShK, SA8 peptides are distinct from ShK peptides based on structure and disulfide connectivity. Conclusions Our results provide the first demonstration that SA8 is a unique gene family in Actiniarians, evolving through a variety of structural changes including tandem and proximal gene duplication and an inversion event that together allowed SA8 to be recruited into the venom of T. stephensoni.

Head-to-tail macrocyclization of proteins and peptides can increase their structural stability, however, potential polymerization can lead to reduced yields. Here, the authors report the engineering of self-cyclizing ‘autocyclase’ proteins to generate macrocyclic peptides and proteins with favorable reaction kinetics for suppressing polymerization.

This research article reports results of a study centered on an undergraduate instructor who facilitated a practice- based field experience with undergraduate preservice teachers (n=125) in an urban museum setting, working with middle school students with a public museum school. In addition to exploring this practice-based field experience, we also examined ways the setting functioned as a third space for teaching and learning. Also discussed are some of the changes the instructor made to maximize student learning in this third space. Results indicate that implementing practice-based learning in undergraduate education serves to extend and support teaching and learning. Moreover, practice-based learning experiences provide additional learning opportunities, including connecting undergraduates’ chosen careers with professionals working in the field. The outcomes of this study also indicate that when implementing and facilitating practice-based learning opportunities there are some pedagogical shifts instructors will need to make, including increasing one’s flexibility and adaptability as well as intentionally utilizing the additional third space(s) as text and teacher, when and where possible.

Abstract The primary goal of this study was to determine whether expressive language skills contribute to adaptive behavior (e.g., socialization and daily living skills) in children, adolescents, and young adults with Down syndrome (DS) whilst controlling for age and nonverbal cognitive ability. Expressive language was assessed using the psychometrically validated Expressive Language Sampling (ELS) conversation and narration procedures. The language produced was transcribed and analyzed to yield measures of expressive vocabulary, syntax, and intelligibility. Socialization and daily living skills of participants with DS were measured with the Vineland Adaptive Behavior Scales, 2nd edition (VABS-2) parent/caregiver rating form. Our results show that the three ELS measures were significantly correlated with multiple measures from the VABS-2 when controlling for age. Several correlations remained significant even when nonverbal cognitive ability was included as a control variable. Our results suggest that expressive language skills contribute to adaptive behavior in children, adolescents, and young adults with DS regardless of age and some of these associations are not explained solely by overall cognitive delays. Further studies including longitudinal data are needed to extend our results.

Chronic pain is prevalent in older adults. Treatment, especially with opioids, is often ineffective and poses considerable negative consequences in this population. To improve treatment, it is important to understand why older adults are at a heightened risk for developing chronic pain. Insomnia is a major modifiable risk factor for chronic pain that is ubiquitous among older adults. Insomnia can also lead to heightened systemic inflammation and affective disturbance, both of which may further exacerbate pain conditions in older adults. Endotoxin exposure can be used as an experimental model of systemic inflammation and affective disturbance. The current study aims to understand how insomnia status and endotoxin-induced changes in inflammation and affect (increased negative affect and decreased positive affect) may interact to impact pain facilitatory and inhibitory processes in older adults. Longitudinal data will also assess how pain processing, affective, and inflammatory responses to endotoxin may predict the development of pain and/or depressive symptoms. The current study is a randomized, double-blinded, placebo-controlled, mechanistic clinical trial in men and women, with and without insomnia, aged 50 years and older. Participants were randomized to either 0.8ng/kg endotoxin injection or saline placebo injection. Daily diaries were used to collect variables related to sleep, mood, and pain at two-week intervals during baseline and 3-, 6-, 9-, and 12-months post-injection. Primary outcomes during the experimental phase include conditioned pain modulation, temporal summation, and affective pain modulation ∼5.5 hours after injection. Primary outcomes for longitudinal assessments are self-reported pain intensity and depressive symptoms. The current study uses endotoxin as an experimental model for pain. In doing so, it aims to extend the current literature by: (1) including older adults, (2) investigating insomnia as a potential risk factor for chronic pain, (3) evaluating the role of endotoxin-induced affective disturbances on pain sensitivity, and (4) assessing sex differences in endotoxin-induced hyperalgesia. Clinicaltrials.gov: NCT03256760. Trial sponsor: NIH R01AG057750-01.

Sea anemones are known to produce a diverse array of toxins with different cysteine-rich peptide scaffolds in their venoms. The serine peptidase inhibitors, specifically Kunitz inhibitors, are an important toxin family that is believed to function as defensive peptides, as well as prevent proteolysis of other secreted anemone toxins. In this study, we isolated three serine peptidase inhibitors named Anthopleura cascaia peptide inhibitors I, II, and III (ACPI-I, ACPI-II, and ACPI-III) from the venom of the endemic Brazilian sea anemone A. cascaia. The venom was fractionated using RP-HPLC, and the inhibitory activity of these fractions against trypsin was determined and found to range from 59% to 93%. The spatial distribution of the anemone peptides throughout A. cascaia was observed using mass spectrometry imaging. The inhibitory peptides were found to be present in the tentacles, pedal disc, and mesenterial filaments. We suggest that the three inhibitors observed during this study belong to the venom Kunitz toxin family on the basis of their similarity to PI-actitoxin-aeq3a-like and the identification of amino acid residues that correspond to a serine peptidase binding site. Our findings expand our understanding of the diversity of toxins present in sea anemone venom and shed light on their potential role in protecting other venom components from proteolysis.

Ionotropic glutamate receptors include α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR), kainate receptors (KAR), and N-methyl-D-aspartate receptors (NMDAR). All function as cation channels; AMPAR and KAR are more permeable to sodium and NMDAR to calcium ions. Compared to the brain, receptor assemblies in platelets are unusual, suggesting distinctive functionalities. There is convincing evidence that AMPAR and KAR amplify platelet function and thrombus formation in vitro and in vivo. Transgenic mice lacking GluA1 and GluK2 (AMPAR and KAR subunits, respectively) have longer bleeding times and prolonged time to thrombosis in an arterial model. In humans, rs465566 KAR gene polymorphism associates with altered in vitro platelet responses suggesting enhanced aspirin effect. The NMDAR contribution to platelet function is less well defined. NMDA at low concentrations (≤10 μM) inhibits platelet aggregation and high concentrations (≥100 μM) have no effect. However, open NMDAR channel blockers interfere with platelet activation and aggregation induced by other agonists in vitro; anti-GluN1 antibodies interfere with thrombus formation under high shear rates ex vivo; and rats vaccinated with GluN1 develop iron deficiency anemia suggestive of mild chronic bleeding. In this review, we summarize data on glutamate receptors in platelets and propose a unifying model that reconciles some of the opposing effects observed.

The thrombin receptor, protease-activated receptor 4 (PAR4), is important for platelet activation and is the target of emerging anti-thrombotic drugs. A frequently occurring single nucleotide polymorphism (SNP; rs773902) causes a function-altering PAR4 sequence variant (NC_000019.10:p.Ala120Thr), whereby platelets from Thr120-expressing individuals are hyper-responsive to PAR4 agonists and hypo-responsive to some PAR4 antagonists than platelets from Ala120-expressing individuals. This altered pharmacology may impact PAR4 inhibitor development, yet the underlying mechanism(s) remain unknown. We tested whether PAR4 surface expression contributes to the altered receptor function. Quantitative flow cytometry was used to determine the absolute number of PAR4 on platelets from individuals subsequently genotyped at rs773902. We detected 539 ± 311 PAR4 per platelet (mean ± SD, n = 84). This number was not different across rs773902 genotypes. This first determination of cellular PAR4 numbers indicates variations in platelet surface expression do not explain the altered pharmacology of the rs773902 PAR4 sequence variant.

Electronic coherence signatures can be directly identified in the time–frequency maps measured in two-dimensional electronic spectroscopy (2DES). Here, we demonstrate the theory and discuss the advantages of this approach via the detailed application to the fast-femtosecond beatings of a wide variety of electronic coherences in ensemble dimers of quantum dots (QDs), assembled from QDs of 3 nm in diameter, with 8% size dispersion in diameter. The observed and computed results can be consistently characterized directly in the time–frequency domain by probing the polarization in the 2DES setup. The experimental and computed time–frequency maps are found in very good agreement, and several electronic coherences are characterized at room temperature in solution, before the extensive dephasing due to the size dispersion begins. As compared to the frequency–frequency maps that are commonly used in 2DES, the time–frequency maps allow exploiting electronic coherences without additional post-processing and with fewer 2DES measurements. Towards quantum technology applications, we also report on the modeling of the time–frequency photocurrent response of these electronic coherences, which paves the way to integrating QD devices with classical architectures, thereby enhancing the quantum advantage of such technologies for parallel information processing at room temperature.

Abstract Aims The United States of America is currently in an opioid epidemic. Heroin remains the most lethal opioid option with its death rate increasing by over 500% in the last decade. The rewarding and reinforcing effects of heroin are thought to be mediated by its ability to increase dopamine concentration in the nucleus accumbens shell. By activating Gi/o‐coupled μ‐opioid receptors, opioids are thought to indirectly excite midbrain dopamine neurons by removing an inhibitory GABAergic tone. The partial μ‐opioid receptor agonist buprenorphine is a substitution‐based therapy for heroin dependence that is thought to produce a steady‐state level of μ‐opioid receptor activation. But it remains unclear how buprenorphine alters dopamine release relative to heroin and how buprenorphine alters the dopamine‐releasing effects of heroin. Because buprenorphine is a partial agonist at the μ‐opioid receptor and heroin is a full agonist, we predicted that buprenorphine would function as a weak dopamine releaser relative to heroin, while functioning as a competitive antagonist if administered in advance of heroin. Methods We performed fast‐scan cyclic voltammetry in awake and behaving rats to measure how heroin, buprenorphine HCl, and their combination affect transient dopamine release events in the nucleus accumbens shell. We also performed a complimentary pharmacokinetic analysis comparing opioid plasma levels at time points correlated to our neurochemical findings. Results Both buprenorphine and heroin produced changes in the frequency of transient dopamine release events, although the effect of buprenorphine was weak and only observed at a low dose. In comparison with vehicle, the frequency of dopamine release events maximally increased by ~25% following buprenorphine treatment and by ~60% following heroin treatment. Distinct neuropharmacological effects were observed in the high‐dose range. The frequency of dopamine release events increased linearly with heroin dose but biphasically with buprenorphine dose. We also found that buprenorphine pretreatment occluded the dopamine‐releasing effects of heroin, but plasma levels of buprenorphine had returned to baseline at this time point. Conclusion These findings support the notion that low‐dose buprenorphine is a weak dopamine releaser relative to heroin and that buprenorphine pretreatment can block the dopamine‐releasing effects of heroin. The finding that high‐dose buprenorphine fails to increase dopamine release might explain its relatively low abuse potential among opioid‐dependent populations. Because high‐dose buprenorphine decreased dopamine release before occluding heroin‐evoked dopamine release, and buprenorphine was no longer detected in plasma, we conclude that the mechanisms through which buprenorphine blocks heroin‐evoked dopamine release involve multifaceted pharmacokinetic and pharmacodynamic interactions.

Saliva is an attractive specimen type for asymptomatic surveillance of COVID-19 in large populations due to its ease of collection and its demonstrated utility for detecting RNA from SARS-CoV-2. Multiple saliva-based viral detection protocols use a direct-to-RT-qPCR approach that eliminates nucleic acid extraction but can reduce viral RNA detection sensitivity. To improve test sensitivity while maintaining speed, we developed a robotic nucleic acid extraction method for detecting SARS-CoV-2 RNA in saliva samples with high throughput. Using this assay, the Free Asymptomatic Saliva Testing (IGI FAST) research study on the UC Berkeley campus conducted 11,971 tests on supervised self-collected saliva samples and identified rare positive specimens containing SARS-CoV-2 RNA during a time of low infection prevalence. In an attempt to increase testing capacity, we further adapted our robotic extraction assay to process pooled saliva samples. We also benchmarked our assay against nasopharyngeal swab specimens and found saliva methods require further optimization to match this gold standard. Finally, we designed and validated a RT-qPCR test suitable for saliva self-collection. These results establish a robotic extraction-based procedure for rapid PCR-based saliva testing that is suitable for samples from both symptomatic and asymptomatic individuals.

Introduction by the guest editor to the special issue on empirical aesthetics.