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Engagement with socioscientific issues (SSI) is seen as an important citizenship goal of SSI-based science education. In this experimental study, Dutch students (age 8 to 13) participated in lesson series in which they learned about and discussed SSI, such as issues related to the textile industry and wastewater. Attitudes toward SSI indicating engagement were measured among relatively large experimental (n = 236) and control (n = 192) groups prior to and after the intervention. Multilevel analyses showed a positive effect of SSI-based teaching on collective efficacy and no effects on the other seven attitude components. Furthermore, we investigated whether the effects depended on students' SSI-related resources. Students' profiles for use of sources of knowledge (USK) moderated the effect of condition on self-efficacy and--depending on analysis type--on personal relevance, positive feelings, and collective efficacy. The positive impact occurred mainly for students with low USK. We discuss implications thereof for SSI education.

Abstract Immunization programs against SARS-CoV-2 with commercial intramuscular vaccines prevent disease but are less efficient in preventing infections. Mucosal vaccines can provide improved protection against transmission, ideally for different variants of concern (VOCs) and related sarbecoviruses. Here, we report a multi-antigen, intranasal vaccine, NanoSTING-SN (NanoSTING-Spike-Nucleocapsid), eliminates virus replication in both the lungs and the nostrils upon challenge with the pathogenic SARS-CoV-2 Delta VOC. We further demonstrate that NanoSTING-SN prevents transmission of the SARS-CoV-2 Omicron VOC (BA.5) to vaccine-naïve hamsters. To evaluate protection against other sarbecoviruses, we immunized mice with NanoSTING-SN. We showed that immunization affords protection against SARS-CoV, leading to protection from weight loss and 100% survival in mice. In non-human primates, animals immunized with NanoSTING-SN show durable serum IgG responses (6 months) and nasal wash IgA responses cross-reactive to SARS-CoV-2 (XBB1.5), SARS-CoV and MERS-CoV antigens. These observations have two implications: (1) mucosal multi-antigen vaccines present a pathway to reducing transmission of respiratory viruses, and (2) eliciting immunity against multiple antigens can be advantageous in engineering pan-sarbecovirus vaccines.

Abstract Respiratory viral infections cause morbidity and mortality worldwide. Despite the success of vaccines, vaccination efficacy is weakened by the rapid emergence of viral variants with immunoevasive properties. The development of an off-the-shelf, effective, and safe therapy against respiratory viral infections is thus desirable. Here, we develop NanoSTING, a nanoparticle formulation of the endogenous STING agonist, 2′−3′ cGAMP, to function as an immune activator and demonstrate its safety in mice and rats. A single intranasal dose of NanoSTING protects against pathogenic strains of SARS-CoV-2 (alpha and delta VOC) in hamsters. In transmission experiments, NanoSTING reduces the transmission of SARS-CoV-2 Omicron VOC to naïve hamsters. NanoSTING also protects against oseltamivir-sensitive and oseltamivir-resistant strains of influenza in mice. Mechanistically, NanoSTING upregulates locoregional interferon-dependent and interferon-independent pathways in mice, hamsters, as well as non-human primates. Our results thus implicate NanoSTING as a broad-spectrum immune activator for controlling respiratory virus infection.

A new species of Eriotheca (Bombacoideae, Malvaceae) from montane wet forests in the Atlantic Forest of Bahia, northeastern Brazil, is described and illustrated. It is known from only three populations situated between 750 m and 850 m in elevation on mountain summits and categorized as Endangered (EN) based on IUCN criteria. Eriotheca paganuccii is distinct from all congeners by the combination of coriaceous to strongly coriaceous leaves and remarkable few-seeded, globose to subglobose woody capsules that contain scanty kapok and the largest seeds known in the genus to date. The affinities of E. paganuccii to morphologically similar species as well as the importance of obtaining phenologically complete collections are discussed.

Agonists of the secretin receptor have potential applications for diseases of the cardiovascular, gastrointestinal, and metabolic systems, yet no clinically-active non-peptidyl agonists of this receptor have yet been developed. In the current work, we have identified a new small molecule lead compound with this pharmacological profile. We have prepared and characterized a systematic structure-activity series around this thiadiazole scaffold to better understand the molecular determinants of its activity. We were able to enhance the in vitro activity and to maintain the specificity of the parent compound. We found the most active candidate to be quite stable in plasma, although it was metabolized by hepatic microsomes. This chemical probe should be useful for in vitro studies and needs to be tested for in vivo pharmacological activity. This could be an important lead toward the development of a first-in-class orally active agonist of the secretin receptor, which could be useful for multiple disease states.

Abstract Class B G protein-coupled receptors can form dimeric complexes important for high potency biological effects. Here, we apply pharmacological, biochemical, and biophysical techniques to cells and membranes expressing the prototypic secretin receptor (SecR) to gain insights into secretin binding to homo-dimeric and monomeric SecR. Spatial proximity between peptide and receptor residues, probed by disulfide bond formation, demonstrates that the secretin N-terminus moves from adjacent to extracellular loop 3 (ECL3) at wild type SecR toward ECL2 in non-dimerizing mutants. Analysis of fluorescent secretin analogs demonstrates stable engagement of the secretin C-terminal region within the receptor extracellular domain (ECD) for both dimeric and monomeric receptors, while the mid-region exhibits lower mobility while docked at the monomer. Moreover, decoupling of G protein interaction reduces mobility of the peptide mid-region at wild type receptor to levels similar to the mutant, whereas it has no further impact on the monomer. These data support a model of peptide engagement whereby the ability of SecR to dimerize promotes higher conformational dynamics of the peptide-bound receptor ECD and ECLs that likely facilitates more efficient G protein recruitment and activation, consistent with the higher observed functional potency of secretin at wild type SecR relative to the monomeric mutant receptor.

Species identification is fundamental to all aspects of biology and conservation. The process can be challenging, particularly in groups including many closely related or similar species. The problem is confounded by the absence of an up-to-date taxonomic revision, but even with such a resource all but professional botanists may struggle to recognise key species, presenting a substantial barrier to vital work such as surveys, threat assessments, and seed collection for ex situ conservation. Genus Erica: An Identification Aid is a tool to help both amateurs and professionals identify (using a limited number of accessible characteristics) and find information about the 851 species and many subspecific taxa of the genus Erica. We present an updated version 4.00, with new features including integrating distribution data from GBIF and iNaturalist, links to taxonomic resources through World Flora Online, and a probability function for identifications, that is freely available for PCs. It remains a work in progress: We discuss routes forward for collaboratively improving this resource.

Cation-disordered rock-salt cathodes (DRX) are promising materials that could deliver high capacities (>250 mAh g-1) with Earth abundant elements and materials. However, their electrochemical performances, other than the capacity, should be improved to be competitive cathodes, and many strategies have been introduced to enhance DRXs. Fluorination has been shown to inhibit oxygen loss and increase power density. Nevertheless, fluorinated cation-disordered rock-salts still suffer from rapid material deterioration and low scalability which limit their practical applications. This mini-review highlights the key challenges for the commercialization of fluorinated cation-disordered rock-salts, discusses the underlying reasons behind material failure and proposes future development directions.

In this position paper, we introduce the concept of socioscientific capital (SSC) to denote students' resources that unequivocally play a part when students learn about and make decisions regarding socioscientific issues (SSIs). Students use a variety of resources when they engage with SSI. Our conceptualization of SSC expands on current conceptualizations to refer to resources related to both the scientific and the non-scientific aspects of SSI, including internal resources (personal experiences, values, attitudes, beliefs, knowledge, and skills), external resources (family, friends, communities, and media), and meta-level resources (dominant frames and cultures). Aiming to strengthen SSI education, we argue for taking into account how students' resources impact their SSI-related learning and decision-making. To this end, insight into students' SSC is needed and is imperative for teachers. By bringing together literature about SSI education and literature about students' resources, we provide a conceptual view on students' SSC and describe implications for SSI education.

The current study is about students' engagement with socioscientific issues (SSI). We explored the use of sources of knowledge about SSI and attitudes toward SSI among a sample of 1676 Dutch 8- to 16-year-old students. First, we developed a questionnaire that measured students' use of four sources of knowledge about SSI: Social Resources (online media use and talking with parents and friends), In-Class Resources (in-class talk and in-class offline media use), Visit Resources (visiting the zoo or a science museum with parents or school), and Offline Media Resources (engaging with issues or the news via books, magazines, newspapers, or TV). Second, we performed a latent profile analysis to explore students' patterns of use of these sources. This resulted in five profiles: Social Visitors (5.9%), Offline Media Consumers (10.6%), Media Discussers (14.3%), In-Class Users (21.0%), and Non-Users (48.3%). Third, we related these profiles to students' attitudes toward SSI, as measured with the Pupils' Attitudes toward Socioscientific Issues (PASSI) questionnaire. In line with the sources of knowledge profiles, the Non-Users felt and thought most negatively about engagement with SSI, while the Media Discussers showed the most positive attitudes. We believe that our exploration of the profiles adds to the discourse about students' socioscientific capital. Moreover, this study informs teachers about the resources that students may bring into the learning environment and their decision-making about SSI. The study concludes with practical suggestions about stimulating the use of sources of knowledge for certain groups of students and fostering positive attitudes toward engagement with SSI.

Development of optimal therapeutics for disease states that can be associated with increased membrane cholesterol requires better molecular understanding of lipid modulation of the drug target. Type 1 cholecystokinin receptor (CCK1R) agonist actions are affected by increased membrane cholesterol, enhancing ligand binding and reducing calcium signaling, while agonist actions of the closely related CCK2R are not. In this work, we identified a set of chimeric human CCK1R/CCK2R mutations that exchange the cholesterol sensitivity of these 2 receptors, providing powerful tools when expressed in CHO and HEK-293 model cell lines to explore mechanisms. Static, low energy, high-resolution structures of the mutant CCK1R constructs, stabilized in complex with G protein, were not substantially different, suggesting that alterations to receptor dynamics were key to altered function. We reveal that cholesterol-dependent dynamic changes in the conformation of the helical bundle of CCK receptors affects both ligand binding at the extracellular surface and G protein coupling at the cytosolic surface, as well as their interrelationships involved in stimulus-response coupling. This provides an ideal setting for potential allosteric modulators to correct the negative impact of membrane cholesterol on CCK1R.

Objective Skull base chordoma and chondrosarcoma are distinct sarcomas of the skull base but share significant therapeutic challenges due to their proximity to critical neurovascular structures, making surgical resection difficult. We sought to establish factors associated with outcome predictors in a national cohort of patients.Methods and analysis Data for all patients referred with a diagnosis of skull base chordoma or chondrosarcoma from April 2017 to December 2022 were obtained. We performed analyses of data pertaining to the first cohort of patients treated in the UK with proton beam therapy (PBT) to determine factors associated with obtaining gross total resection (GTR) and adequate clearance of the brainstem and optic apparatus.Results Of 230 patients with skull base chordoma or chondrosarcoma referred for PBT, 71% were accepted for PBT, with a wide regional variation between referring neurosurgical units (29%–93%). Of the first 75 consecutive patients treated with PBT, the only factor predictive of obtaining GTR was surgical resection at a unit with higher volumes of patients accepted for PBT (OR 1.32, 95% CI 1.11 to 1.63, p=0.004). Use of intraoperative MRI (OR 4.84, 95% CI 1.21 to 27.83, p=0.04) and resection at a higher volume unit (OR 1.29, 95% CI 1.07 to 1.64, p=0.013) were associated with increased rates of tumour clearance from the brainstem/optic apparatus.Conclusions Treatment at a higher volume centre was a key determinant of the optimal surgical outcome in this cohort. These data support the management of skull base chordomas and chondrosarcomas in higher volume centres where multidisciplinary experience can be accumulated.

Mental disorders are increasingly understood as involving complex alterations of self that emerge from dynamical interactions of constituent elements, including cognitive, bodily, affective, social, narrative, cultural and normative aspects and processes. An account of self that supports this view is the pattern theory of self (PTS). The PTS is a non-reductive account of the self, consistent with both embodied-enactive cognition and phenomenological psychopathology; it foregrounds the multi-dimensionality of subjects, stressing situated embodiment and intersubjective processes in the formation of the self-pattern. Indications in the literature already demonstrate the viability of the PTS for formulating an alternative methodology to better understand the lived experience of those suffering mental disorders and to guide mental health research more generally. This article develops a flexible methodological framework that front-loads the self-pattern into a minimally structured phenomenological interview. We call this framework ‘Examination of Self Patterns’ (ESP). The ESP is unconstrained by internalist or externalist assumptions about mind and is flexibly guided by person-specific interpretations rather than pre-determined diagnostic categories. We suggest this approach is advantageous for tackling the inherent complexity of mental health, the clinical protocols and the requirements of research.

While the ubiquity and importance of narratives for human adaptation is widely recognized, there is no integrative framework for understanding the roles of narrative in human adaptation. Research has identified several cognitive and social functions of narratives that are conducive to well-being and adaptation as well as to coordinated social practices and enculturation. In this paper, we characterize the cognitive and social functions of narratives in terms of active inference, to support the claim that one of the main adaptive functions of narrative is to generate more useful (i.e., accurate, parsimonious) predictions for the individual, as well as to coordinate group action (over multiple timescales) through shared predictions about collective behavior. Active inference is a theory that depicts the fundamental tendency of living organisms to adapt by proactively inferring the causes of their sensations (including their own actions). We review narrative research on identity, event segmentation, episodic memory, future projections, storytelling practices, enculturation, and master narratives. We show how this research dovetails with the active inference framework and propose an account of the cognitive and social functions of narrative that emphasizes that narratives are for the future—even when they are focused on recollecting or recounting the past. Understanding narratives as cognitive and cultural tools for mutual prediction in social contexts can guide research on narrative in adaptive behavior and psychopathology, based on a parsimonious mechanistic model of some of the basic adaptive functions of narrative.

Morphological and molecular phylogenetic evidence indicate that Eleutherostylis Burret (Malvaceae, Grewioideae), a monotypic genus described from New Guinea, is best considered a synonym of Grewia L., a species-rich genus widespread across the Paleotropics and found in Africa, Arabia, Asia, Australia and the western Pacific. A new combination, based on E. renistipulata Burret, G. renistipulata (Burret) Dorr, comb. nov., is proposed. Original material of the basionym could not be located and a neotype is designated. A lectotype is designated for G. morotaiensis Kosterm., a synonym of G. renistipulata.

Background: Older adults in residential aged care facilities (RACFs) experience disproportionate levels of poor oral health relative to other groups in the general population, affecting their physical and mental wellbeing. The Oral Health Assessment Tool (OHAT) is a validated and widely used dental assessment tool; however, recent systematic reviews have identified shortcomings with respect to its measurement properties. Objective: The objective of this protocol is to provide a detailed overview of a multidisciplinary qualitative study that aims to (a) co-design and develop a modified OHAT for RACFs and (b) inform the development of an OHAT training package and implementation strategies. Methods: This study will utilize a co-design methodology with aged care residents, caregivers, staff members, and health professionals. The co-design workshops will: (1) investigate the barriers to and enablers of optimal oral healthcare in RACFs; and (2) co-design a modified version of the Oral Health Assessment Tool and a referral to treatment pathway that is appropriate for use in RACFs. The co-design workshops will facilitate group discussion and involve interactive activities using, for example, mind mapping and Sticky Notes. Qualitative data (transcripts and artefacts from co-design activities) will be analyzed in NVivo using an inductive codebook thematic analysis, specifically a template analysis. Conclusion: The findings of this study will inform a modified OHAT (M-OHAT), as well as future study phases regarding training and implementation strategies. It is expected that the M-OHAT will have enhanced usability and relevance to RACFs, facilitating the identification of poor oral health and timely referral to dental treatment.

Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects.

Abstract We investigated the effect of femtosecond (fs) laser ablation of enamel and dentin for different pulse wavelengths: infrared (1030 nm), green (515 nm), and ultra-violet (343 nm) and for different pulse separations to determine the optimal irradiation conditions for the precise removal of dental hard tissues with the absence of structural and compositional damage. The ablation rates and efficiencies were established for all three laser wavelengths for both enamel and dentin at room temperature without using any irrigation or cooling system, and the surfaces were assessed with optical and scanning electron microscopy, optical profilometry, and Raman spectroscopy. We demonstrated that 515 nm fs irradiation provides the highest rate and efficiency for ablation, followed by infrared. Finally, we explored the temperature variations inside the dental pulp during the laser procedures for all three wavelengths and showed that the maximum increase at the optimum conditions for both infrared and green irradiations was 5.5 °C, within the acceptable limit of temperature increase during conventional dental treatments. Ultra-violet irradiation significantly increased the internal temperature of the teeth, well above the acceptable limit, and caused severe damage to tooth structures. Thus, ultra-violet is not a compatible laser wavelength for femtosecond teeth ablation.