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Membrane contact sites (MCSs) are sites of close apposition between two organelles used to exchange ions, lipids, and information. Cells respond to changing environmental or developmental conditions by modulating the number, extent, or duration of MCSs. Because of their small size and dynamic nature, tools to study the dynamics of MCSs in live cells have been limited. Dimerization-dependent fluorescent proteins (ddFPs) targeted to organelle membranes are an ideal tool for studying MCS dynamics because they reversibly interact to fluoresce specifically at the interface between two organelles. Here, we build on previous work using ddFPs as sensors to visualize the morphology and dynamics of MCSs. We engineered a suite of ddFPs called Contact-FP that targets ddFP monomers to lipid droplets (LDs), the endoplasmic reticulum (ER), mitochondria, peroxisomes, lysosomes, plasma membrane, caveolae, and the cytoplasm. We show that these probes correctly localize to their target organelles. Using LDs as a test case, we demonstrate that Contact-FP pairs specifically localize to the interface between two target organelles. Titration of LD-mitochondria ddFPs revealed that these sensors can be used at high concentrations to drive MCSs or can be titrated down to minimally perturb and visualize endogenous MCSs. We show that Contact-FP probes can be used to: (1) visualize LD-mitochondria MCS dynamics, (2) observe changes in LD-mitochondria MCS dynamics upon overexpression of PLIN5, a known LD-mitochondrial tether, and (3) visualize two MCSs that share one organelle simultaneously (e.g., LD-mitochondria and LD-ER MCSs). Contact-FP probes can be optimized to visualize MCSs between any pair of organelles represented in the toolkit.

Higher education arts programs are implementing experiential learning (EL) programs to address skills gaps and better prepare students for careers in an evolving arts industry. However, there is a dearth of research relating to EL in the arts. As a starting point, this research explores the supports and barriers that contribute to student participation in extracurricular EL programs. This mixed methods study employed interviews and a focus group with nine students at a Mid-Atlantic performing arts conservatory, accompanied by a brief demographic survey. The findings revealed a complex web of supports and barriers impacting students' awareness of, participation in, and applications to EL programs, including individual, social, programmatic, and systemic factors. The framework of this small-scale study may serve as a model and starting place for other institutions to understand their own unique audiences and settings moving forward.

Objective: This paper describes several automation tools and software that can be considered during evidence synthesis projects and provides guidance for their integration in the conduct of scoping reviews. Study Design and Setting: The guidance presented in this work is adapted from the results of a scoping review and consultations with the JBI Scoping Review Methodology group. Results: This paper describes several reliable, validated automation tools and software that can be used to enhance the conduct of scoping reviews. Developments in the automation of systematic reviews, and more recently scoping reviews, are continuously evolving. We detail several helpful tools in order of the key steps recommended by the JBI's methodological guidance for undertaking scoping reviews including team establishment, protocol development, searching, de-duplication, screening titles and abstracts, data extraction, data charting, and report writing. While we include several reliable tools and software that can be used for the automation of scoping reviews, there are some limitations to the tools mentioned. For example, some are available in English only and their lack of integration with other tools results in limited interoperability. Conclusion: This paper highlighted several useful automation tools and software programs to use in undertaking each step of a scoping review. This guidance has the potential to inform collaborative efforts aiming at the development of evidence informed, integrated automation tools and software packages for enhancing the conduct of high-quality scoping reviews.

The burden of childhood visual impairment and disparities in access to pediatric vision care remain pressing issues in the United States. School-based vision programs (SBVPs) serve as one approach to advancing health equity. Operating at the intersection of schools and healthcare, SBVPs can increase access to pediatric vision services, improve academic performance, and facilitate referrals to community vision care providers. To maximize their impact, SBVPs must tailor their services to the individual needs and resources of local school communities. School nurses, who have strong ties to school health care services and the school community, are trusted partners in building SBVPs. This article aims to facilitate SBVP development, implementation, and sustainability processes by offering guidance for school nurses and other stakeholders who aim to build a SBVP, support local programs, or learn more about how SBVPs operate.

Despite evidence of the benefits of early care and education (ECE) for child development and family employment, the supply of providers is scarce and variable; leading many families with young children to experience limited and inequitable access. To examine the multidetermined nature of access, this study leverages a multidimensional, family-centered definition and a nationally representative sample of families of preschoolers from the Early Childhood Longitudinal Study -- Birth Cohort to examine (1) patterns of access-related features present in preschool-age children's ECE arrangements, and (2) child characteristics, household circumstances, and care setting type that may be related to patterns of access. Latent class analysis model enumeration revealed five latent classes of children's nonparental care arrangements along features of accessibility: "High Across Most Access Features" (26.4 %), "Single, Long-Term Provider" (30.1 %), "Limited Across Most Access Features" (11.6 %), "Low Affordability, Multiple Providers" (10.1 %), and "High Affordability, Recent Transition" (21.8 %). These results suggested many children were in ECE that met multiple dimensions of access, with others in care arrangements that reflected trade-offs. Children were also differentially classified into types of ECE arrangements in relation to care setting type, race/ethnicity, income, household urbanicity, and parental employment. The implications of investigating ECE access as a multidimensional construct, and recommendations for how ECE providers and policy can more closely align with family needs are discussed.

The science of reading (SOR) refers to the sum of what we know about how people learn to read based on empirical studies across multiple disciplines. The purpose of this review was to identify research evidence to inform the SOR for multilingual learners (MLs). We reviewed 30 systematic reviews related to reading and reading instruction for MLs conducted primarily in K-5 U.S. classrooms. Results identified four broad clusters of components related to English reading comprehension as well as instructional practices and programs effective in addressing each component. Clusters included oral language, phonological awareness, decoding and oral reading fluency, and reading comprehension. Notably, oral language and reading skills in both MLs' first language and in English were essential components of the SOR for MLs. Implications for theory and research as well as policy, curriculum, and instruction are provided.

There has been little attention to personality in research on school refusal (SR). This study examined personality traits among 41 adolescents receiving cognitive-behavioral therapy (CBT) during participation in a School Refusal Program in the Netherlands. Traits were examined via clinical scales and 2-point code types derived from the Minnesota Multiphasic Personality Inventory--Adolescent. The influence of personality traits on treatment outcome was examined at post-treatment and 1-year follow-up. At pretreatment, eight of the 10 clinical scales were disproportionately skewed toward the "high to very high" range relative to a norm group. Social introversion and depressive symptomatology were significantly increased relative to the norm group, and nearly one-half of the adolescents were characterized by code type 2-3/3-2 (depression/hysteria) or 2-0/0-2 (depression/social introversion). Adolescents characterized by a 2-0/0-2 code type were almost twice as likely (odds ratio = 1.78) to be treatment responders at post-treatment. There was no relation between personality traits and treatment outcome at follow-up. The small sample size limits generalization of the study's findings. If the results are replicated, personality traits may provide useful indications for personalizing treatment when employing interventions recommended in CBT manuals for SR.

Early childhood special education (ECSE) professionals were forced to drastically change their methods of providing services as a result of the COVID-19 pandemic. In this qualitative study, we conducted interviews to understand how the COVID-19 pandemic has impacted ECSE professionals both personally and professionally. ECSE professionals described challenges as well as unexpected positive outcomes associated with continuing to work in the midst of the COVID-19 pandemic. Professionals also explained the importance of increasing parent interaction through coaching interventions while engaging in remote service delivery. The findings conclude with professionals' discussions of how the field may be impacted by the pandemic in the future. Results were discussed in the context of service provision and implications for supporting professionals who work with young children with disabilities.

Most students with emotional and behavioral disorders (EBD) have challenging classroom behaviors and poor postschool outcomes. Self-determination promotes positive classroom behavior and successful postschool outcomes. By incorporating choice-making, an element of self-determination, teachers across grade levels can address behavioral issues and promote positive postschool outcomes for students with EBD. This article provides guidance on how to incorporate choice-making for students with EBD.

Purpose: Processing real-world sounds requires acoustic and higher-order semantic information. We tested the theory that individuals with autism spectrum disorder (ASD) show enhanced processing of acoustic features and impaired processing of semantic information. Methods: We used a change deafness task that required detection of speech and non-speech auditory objects being replaced and a speech-in-noise task using spoken sentences that must be comprehended in the presence of background speech to examine the extent to which 7-15 year old children with ASD (n = 27) rely on acoustic and semantic information, compared to age-matched (n = 27) and IQ-matched (n = 27) groups of typically developing (TD) children. Within a larger group of 7-15 year old TD children (n = 105) we correlated IQ, ASD symptoms, and the use of acoustic and semantic information. Results: Children with ASD performed worse overall at the change deafness task relative to the age-matched TD controls, but they did not differ from IQ-matched controls. All groups utilized acoustic and semantic information similarly and displayed an attentional bias towards changes that involved the human voice. Similarly, for the speech-in-noise task, age-matched--but not IQ-matched--TD controls performed better overall than the ASD group. However, all groups used semantic context to a similar degree. Among TD children, neither IQ nor the presence of ASD symptoms predict the use of acoustic or semantic information. Conclusion: Children with and without ASD used acoustic and semantic information similarly during auditory change deafness and speech-in-noise tasks.

Preschoolers who display extremely inhibited behavior are at risk for the development of anxiety disorders. However, behavioral inhibition (BI) is a multifaceted characteristic. Some children with BI are fearful when confronted by unfamiliar adults, peers, and objects; others are fearful when separated from their parents. In the present study, we examined specific features of BI that predicted observed friendship formation among preschoolers who are behaviorally inhibited. We also examined whether teacher ratings of classroom behaviors predicted friendship formation. Sixty highly inhibited children (35 female, M[subscript age] = 52.57 months) were observed during eight weekly free-play sessions with initially unfamiliar inhibited peers. Free-play periods occurred before weekly intervention sessions for children with BI and their parents. An observational protocol was developed to identify children who made a friend during the eight weekly sessions. Before the first session, different subtypes of BI were assessed by parents; preschool teachers assessed the children's classroom behaviors with familiar peers. Twenty-six children met the criteria for having made and kept a friend. Probit regression analyses revealed that parent ratings of BI among unfamiliar peers and teacher ratings of children's social anxiety before the intervention were associated with a decreased probability of making a friend. No evidence was found linking children's responses to the intervention and friendship formation. Results suggest that extremely inhibited preschoolers are capable of making friends. Implications for future research and intervention efforts that focus on individual differences of children with BI are discussed.

IntroductionUnderstanding attitudes toward participation among diverse preclinical Alzheimer's disease (AD) trial participants could yield insights to instruct future recruitment.MethodsUsing data from the Anti-Amyloid Treatment in Asymptomatic AD (A4) Study, we examined differences among mutually exclusive racial and ethnic groups in views and perceptions of amyloid imaging (VPAI), a measure of motivations to undergo amyloid biomarker testing in the setting of preclinical AD. We used linear regression to quantify differences at baseline.ResultsCompared to non-Hispanic or Latino (NH) White participants, Hispanic or Latino (3.52 points, 95% confidence interval [CI]: [2.61, 4.42]); NH Asian (2.97 points, 95% CI: [1.71, 4.22]); and NH Black participants (2.79 points, 95% CI: [1.96, 3.63]) participants demonstrated higher levels of endorsement of the VPAI items at baseline.DiscussionDifferences may exist among participants from differing ethnic and racial groups in motivations to undergo biomarker testing in the setting of a preclinical AD trial.HighlightsRepresentative samples in AD clinical trials are vital to result in generalizability. We assessed motivations to undergo amyloid imaging in a preclinical AD trial. Racial and ethnic minority groups showed higher endorsement of VPAI items. Differences were driven by perceived risk, plan/prepare, and curiosity domains. Few observations among racial and ethnic groups changed after biomarker disclosure.

In this study, we investigated whether and how the storm surge induced by Hurricane Katrina could change if it occurs in a future warmer climate, and the sensitivity of the changes to atmospheric forcing resolution. Climate model simulations of Hurricane Katrina at 27 km, 4.5 km, and 3 km resolutions were used to drive storm surge simulations in historical and future climates using the ADvanced CIRCulation (ADCIRC) model. We found that peak surge height increased significantly in the future with all forcing resolutions. However, the future projection is 22% greater in the 3 km forcing, typical of regional climate models, compared to the 27 km forcing, typical of state-of-the-art global climate models. Additionally, the spatial extent of the future change is highly sensitive to forcing resolution, extending most broadly under the 27 km forcing. Furthermore, we found that storm surge duration decreases in the future with all forcing resolutions due to increasing TC translation speed and decreasing ocean lifetime. However, the future change in the surge duration is sensitive to the forcing resolution, decreasing by 31% in the 27 km forcing and 6% in the 3 km forcing.

This study uses experiments from the Energy Exascale Earth System Model (E3SM) to compare the influence on tropical cyclone (TC) activity of: (i) the atmospheric effect of aerosols under specified sea-surface temperatures (SSTs); and (ii) the net effect of greenhouse gases (GhGs) (including changes in SSTs). The experiments were performed using the CMIP6 Shared Socioeconomic Pathway SSP5-8.5 emissions scenario with GhG-induced SST warming specified and atmospheric aerosol effects simulated but without explicit ocean coupling. Insignificant changes in global TC frequency are found in response to the atmospheric effect of future aerosols and GhGs, as significant regional responses in TC frequency counteract each other. Future GhGs contribute to more frequent TCs in the North Atlantic, and reductions over the Northwestern Pacific and Southern Indian Ocean. The atmospheric effect of future aerosols drives more frequent TCs over the Northwestern Pacific and reductions over the Northeast Pacific and North Atlantic. Along with increases in TC intensity, global TC precipitation (TCP) is projected to increase by 52.8% (14.1%/K) due to the combined effect of future aerosols and GhGs. Although both forcings contribute to TCP increases (14.7–19.3% from reduced aerosols alone and 28.1–33.3% from increased GhGs alone), they lead to different responses in the spatial structure of TCP. TCP increases preferentially in the inner-core due to increased GhGs, whereas TCP decreases in the inner-core and increases in the outer-bands in response to the atmospheric effects of decreased aerosols. These changes are distinct from those caused by aerosol-induced SST changes, which have been considered in other studies.

Neuropilin-1 acts as a coreceptor with vascular endothelial growth factor receptors to facilitate binding of its ligand, vascular endothelial growth factor. Neuropilin-1 also binds to heparan sulfate, but the functional significance of this interaction has not been established. A combinatorial library screening using heparin oligosaccharides followed by molecular dynamics simulations of a heparin tetradecasaccharide suggested a highly conserved binding site composed of amino acid residues extending across the b1 and b2 domains of murine neuropilin-1. Mutagenesis studies established the importance of arginine513 and lysine514 for binding of heparin to a recombinant form of Nrp1 composed of the a1, a2, b1, and b2 domains. Recombinant Nrp1 protein bearing R513A,K514A mutations showed a significant loss of heparin-binding, heparin-induced dimerization, and heparin-dependent thermal stabilization. Isothermal calorimetry experiments suggested a 1:2 complex of heparin tetradecasaccharide:Nrp1. To study the impact of altered heparin binding in vivo, a mutant allele of Nrp1 bearing the R513A,K514A mutations was created in mice (Nrp1D) and crossbred to Nrp1+/- mice to examine the impact of altered heparan sulfate binding. Analysis of tumor formation showed variable effects on tumor growth in Nrp1D/D mice, resulting in a frank reduction in tumor growth in Nrp1D/- mice. Expression of mutant Nrp1D protein was normal in tissues, suggesting that the reduction in tumor growth was due to the altered binding of heparin/heparan sulfate to neuropilin-1. These findings suggest that the interaction of neuropilin-1 with heparan sulfate modulates its stability and its role in tumor formation and growth.

El Niño–Southern Oscillation (ENSO) influences seasonal Atlantic tropical cyclone (TC) activity by impacting environmental conditions important for TC genesis. However, the influence of future climate change on the teleconnection between ENSO and Atlantic TCs is uncertain, as climate change is expected to impact both ENSO and the mean climate state. We used the Weather Research and Forecasting Model on a tropical channel domain to simulate 5-member ensembles of Atlantic TC seasons in historical and future climates under different ENSO conditions. Experiments were forced with idealized sea surface temperature configurations based on the Community Earth System Model (CESM) Large Ensemble representing: a monthly varying climatology, eastern Pacific El Niño, central Pacific El Niño, and La Niña. The historical simulations produced fewer Atlantic TCs during eastern Pacific El Niño compared to central Pacific El Niño, consistent with observations and other modeling studies. For each ENSO state, the future simulations produced a similar teleconnection with Atlantic TCs as in the historical simulations. Specifically, La Niña continues to enhance Atlantic TC activity, and El Niño continues to suppress Atlantic TCs, with greater suppression during eastern Pacific El Niño compared to central Pacific El Niño. In addition, we found a decrease in the Atlantic TC frequency in the future relative to historical regardless of ENSO state, which was associated with a future increase in northern tropical Atlantic vertical wind shear and a future decrease in the zonal tropical Pacific sea surface temperature (SST) gradient, corresponding to a more El Niño–like mean climate state. Our results indicate that ENSO will remain useful for seasonal Atlantic TC prediction in the future.

Although the 2021 Western North America (WNA) heat wave was predicted by weather forecast models, questions remain about whether such strong events can be simulated by global climate models (GCMs) at different model resolutions. Here, we analyze sets of GCM simulations including historical and future periods to check for the occurrence of similar events. High- and low-resolution simulations both encounter challenges in reproducing events as extreme as the observed one, particularly under the present climate. Relatively stronger amplitudes are observed during the future periods. Furthermore, high- and low-resolution short initialized GCM simulations are both able to reasonably predict such strong events and their associated high-pressure ridge over the WNA with a 1 week forecast lead time. Moisture sensitivity experiments further indicate a drier atmospheric moisture condition results in substantially higher near-surface temperatures in the simulated heat events.

A heightened hedonic response to sweet tastes has been associated with increased alcohol preference and alcohol consumption in both humans and animals. The principal goal of this study was to examine blood oxygenation level dependent (BOLD) activation to high- and low-concentration sweet solutions in subjects who are either positive (FHP) or negative (FHN) for a family history of alcoholism. Seventy-four non-treatment seeking, community-recruited, healthy volunteers (22.8±1.6 SD years; 43% men) rated a range of sucrose concentrations in a taste test and underwent functional magnetic resonance imaging (fMRI) during oral delivery of water, 0.83M, and 0.10M sucrose. Sucrose compared to water produced robust activation in primary gustatory cortex, ventral insula, amygdala, and ventral striatum. FHP subjects displayed greater bilateral amygdala activation than FHN subjects in the low sucrose concentration (0.10M). In secondary analyses, the right amygdala response to the 0.10M sucrose was greatest in FHP women. When accounting for group differences in drinks per week, the family history groups remained significantly different in their right amygdala response to 0.10M sucrose. Our findings suggest that the brain response to oral sucrose differs with a family history of alcoholism, and that this response to a mildly reinforcing primary reward might be an endophenotypic marker of alcoholism risk. Keywords: Alcohol, fMRI, Sweet, Taste, Gustatory

Tornadoes are a co-occurring extreme that can be produced by landfalling tropical cyclones (TCs). These tornadoes can exacerbate the loss of life and property damage caused by the TC from which they were spawned. It is uncertain how the severe weather environments of landfalling TCs may change in a future climate and how this could impact tornado activity from TCs. In this study, we investigated four TCs that made landfall in the U.S. and produced large tornado outbreaks. We performed four-member ensembles of convective-allowing (4-km resolution) regional climate model simulations representing each TC in the historical climate and a mid-twenty-first century future climate. To identify potentially tornadic storms, or TC-tornado (TCT) surrogates, we used thresholds for three-hourly maximum updraft helicity and radar reflectivity, as tornadoes are not resolved in the model. We found that the ensemble-mean number of TCT-surrogates increased substantially (56–299%) in the future, supported by increases in most-unstable convective available potential energy, surface-to-700-hPa bulk wind shear, and 0–1-km storm-relative helicity in the tornado-producing region of the TCs. On the other hand, future changes in most-unstable convective inhibition had minimal influence on future TCT-surrogates. This provides robust evidence that tornado activity from TCs may increase in the future. Furthermore, TCT-surrogate frequency between 00Z and 09Z increased for three of the four cases, suggesting enhanced tornado activity at night, when people are asleep and more likely to miss warnings. All of these factors indicate that TC-tornadoes may become more frequent and a greater hazard in the future, compounding impacts from future increases in TC winds and precipitation.

African easterly waves (AEWs) are known precursors to Atlantic tropical cyclones (TCs), and are therefore often directly connected to extreme weather events that can be both deadly and destructive. It is well established that not all AEWs develop into TCs, and there has been substantial research that has addressed the different characteristics and environments of developing and non-developing waves. In this study, however, we specifically examine 41-years of developing AEWs to provide a better understanding of the relationship between the developing wave and the environment, and the resulting TC. To conduct this research, we identified TCs with AEW origins from the observational record between 1980 and 2020. We then used an objective tracking algorithm to identify the developing AEWs in reanalysis data. We found a statistically significant relationship between the strength of the developing AEWs, TC genesis location and landfall, and sea surface temperature (SST) during TC genesis. Weaker AEWs tend to develop into TCs closer to the Americas in a region with warmer SSTs than those of the stronger AEWs, which tend to develop into TCs closer to Africa. Consequently, the TCs that develop from weaker AEWs are more likely to make landfall due to the close proximity of their genesis locations to the Americas.

Students sometimes engage in challenging behaviors that require teachers to select and design appropriate behavior management interventions. Teachers may choose from various evidence-based intervention strategies when addressing students' challenging behaviors. Reinforcement-based strategies are preferred due to their desirable long-term outcomes. However, teachers may (intentionally or unintentionally) select punishment-based interventions as a quick option to reduce challenging behaviors. Because of the undesirable effects sometimes observed with punishment-based interventions, it is critical that teachers only choose them when warranted and subsequently implement them ethically. This article provides teachers with 11 questions to consider when selecting an effective, efficient, and least-restrictive behavior change intervention.