Determining crystal structures through crowdsourcing and coursework

We show here that computer game players can build high-quality crystal structures. Introduction of a new feature into the computer game Foldit allows players to build and real-space refine structures into electron density maps. To assess the usefulness of this feature, we held a crystallographic model-building competition between trained crystallographers, undergraduate students, Foldit players and automatic model-building algorithms. After removal of disordered residues, a team of Foldit players achieved the most accurate structure. Analysing the target protein of the competition, YPL067C, uncovered a new family of histidine triad proteins apparently involved in the prevention of amyloid toxicity. From this study, we conclude that crystallographers can utilize crowdsourcing to interpret electron density information and to produce structure solutions of the highest quality

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Measuring and manipulating epistemological beliefs in early childhood education students

Engendering sophisticated epistemological beliefs (beliefs about knowing and learning) in student teachers is a critical function of higher education. We report the preliminary results of a collaborative teaching unit and study examining the development of epistemological beliefs among early childhood pre-service teachers (N = 65). The program was unique in that it promoted sophisticated beliefs through explicit reflection on both personal epistemology and content related to research methods. Explicit reflection on the nature of beliefs about knowing and learning has been shown to impact on the development of students’ personal epistemology. In this study, such reflection took place through tutorial discussions, practicum reflections and students interviewing critical friends about epistemological beliefs. Personal epistemology was also developed through a focus on research methods as the content of the course, which provided students with a first-hand experience of using evidenced-based knowledge – a key component of sophisticated personal epistemologies. Students were both the subject of, and joint researchers in the study. The program taught, and the study utilized, quantitative and qualitative research methods. Changes in epistemological beliefs were assessed pre- and post-test using Schommer’s epistemological questionnaire. The results demonstrate the utility of explicit reflection and genuine experience in research pedagogy in developing sophisticated epistemological beliefs

Moral and social development : teachers’ knowledge of learning and teaching strategies in the early years

The intention of the analysis in this paper was to determine, from interviews with eleven early years’ teachers, what knowledge guided their teaching of moral behaviour. Six of the teachers defined moral behaviour in terms of social conventions only. Children’s learning was attributed by five of the teachers to incidental/contextual issues. Nine of the teachers used discussion of issues, in various contexts, as a way of teaching about social and moral issues. The majority of the teachers (n=7) gave the source of their knowledge of pedagogy as practical as opposed to theoretically informed. There was no clear relationship between their definitions, understanding of children’s learning, pedagogy or source of knowledge. Most of the teachers were using discussion, negotiation and reflection to develop the children’s moral and social behaviour. This is probably effective; however, it suggests a strong need for teaching of moral development to be given more prominence and addressed directly in in-service courses so that teachers are clear about their intentions and the most effective ways of achieving them

An investigation of core beliefs about knowing and peripheral beliefs about learning and teaching in pre-service teacher education students: Implementing a teaching program to develop epistemological beliefs

Research related to epistemological beliefs or beliefs about knowing and learning has offered insight into promoting effective learning (Hofer, 1994; Schommer, 1990, 1993a, 1993b ). A teaching program designed to foster the development of more sophisticated epistemological beliefs was implemented with 29 pre-service graduate teacher education students at the Queensland University of Technology, Brisbane, Australia. As part of the year-long teaching program, students were required to reflect in journal entries on both the content of an educational psychology unit and their epistemological beliefs. The students engaged in this teaching program (henceforth known as the research group) were interviewed in relation to their beliefs about knowing, learning and teaching at the beginning (Time 1) and conclusion (Time 2) of the teaching program. Students in a comparison group, which comprised another educational psychology tutorial group for which the inquirer was responsible, were not exposed to the teaching program that was implemented with the research group. Therefore, students in the comparison group were not encouraged to reflect on their epistemological beliefs, but were engaged in large and small group tutorial discussions in relation to the educational psychology content. They were asked to complete written statements about their beliefs about knowing, learning and teaching at the beginning (Time 1) and end (Time 2) of the year-long unit. Schommer's (1988, 1990) epistemological beliefs questionnaire, the Study Process Questionnaire (SPQ) (Biggs, 1987) and the Conceptions of Learning Inventory (COLI) (Purdie & Hattie, 1997) were administered to both the comparison and research groups at Time 1 and Time 2. These questionnaires measured beliefs about knowing, approaches to learning and conceptions of learning respectively. The results of both the qualitative and quantitative data analysis indicated that the group of students engaged in the teaching program experienced more growth in sophisticated beliefs about knowing, and to a lesser extent, beliefs about learning and teaching. Furthermore, there appeared to be a relationship between core beliefs about knowing and peripheral beliefs about learning and teaching in the research group. For example, all students who described at least some sophisticated core beliefs about knowing also reported sophisticated beliefs about learning and teaching. Both the success of the teaching program and the perceived consistency between core and peripheral epistemological beliefs have implications for how teacher educators develop relational learning environments

Knowing and Learning in Teacher Education: A Theoretical Framework of Core and Peripheral Beliefs in Application

The study to be reported here extends the current understanding of epistemological beliefs by taking into account another set of beliefs related to learning that have often been overlooked. This study, basing on empirical data collected via semi-structured interviews from 29 student teachers in Australia, examines how core beliefs about knowing are related to peripheral beliefs about learning. A theoretical framework is developed for considering these beliefs about knowing in relation to beliefs about learning as an overall set of epistemological beliefs - such links between the developmental epistemological beliefs and student learning research have not been made in the literature to date. As a group, it is found, students’ beliefs about knowing ranged from a focus on knowledge as absolute and received to a view that knowledge was constructed and reasoned. The categories related to learning reflected a range of beliefs from reproductive through to more transformative beliefs about learning. A relationship was noted between the more sophisticated beliefs about knowing and transformative beliefs about learning. Implications are discussed

An investigation of teacher education students’ epistemological beliefs: Developing a relational model of teaching

A teaching program based on relational pedagogy (Baxter Magolda, 1993a) was implemented to foster the development of epistemological beliefs in 29 pre-service teacher education students at a large metropolitan university in Australia. Epistemological beliefs are those personally held beliefs about the nature and structure of knowing. The students were interviewed in relation to their epistemological beliefs at the beginning (Time 1) and conclusion (Time 2) of the teaching program. The results of the qualitative data analysis indicated that students described more sophisticated relational epistemological beliefs over time. This finding is important given that teachers with relativistic epistemological beliefs are more likely to conceive of teaching as a transformative (constructivist) rather than transmissive. The perceived success of the teaching program has implications for the development of a relational teaching model in teacher education courses

An investigation of pre-service teacher's knowledge about learning

Twenty-nine student teachers from a large metropolitan university in Queensland, Australia were interviewed at the beginning (Time 1) and end (Time 2) of a year-long graduate diploma in education to investigate the nature of their knowledge about learning and changes in such knowledge over the year. At Time 1 and Time 2 most students thought learning should be meaningful and preferred to use transformative learning approaches. However, students indicated a willingness to engage in reproductive approaches to learning if the content to be learned was uninteresting, workloads were high, or assessment was examination-focussed. The results also indicated that while many students did not experience significant changes in their knowledge about learning over the year, they believed that transformative learning had become more of a focus for them. Investigating student teachers’ knowledge about learning has implications for effective learning in teacher education programs

Cross-cultural early childhood teaching experiences : \ud impacting Hong Kong teachers’ beliefs about children’ learning

Twenty-one in-service early childhood teachers participated in a teaching practicum in Australia as part of the final year of a Bachelor of Arts in Hong Kong. Teachers spent two weeks visiting a university and early childhood settings in Australia. The university based component of the program included workshops and discussions with lecturing staff located in both the Australian and Hong Kong universities. Teachers were asked to complete written statements about "What is children’s learning?" before and after their practicum experience. An inductive analysis of students’ written statements and practicum evaluations revealed an increase in qualitative beliefs about children’s learning over the two-week period. Implications for teacher education programs are discussed

Evolution de la morphologie du pollen chez les Angiospermes (sélection naturelle et/ou contraintes développementales?)

La sélection naturelle est considérée comme une des forces responsables de l'évolution adaptative des organismes en général, et de leur morphologie en particulier. Depuis une trentaine d'années, un débat a lieu sur la question de savoir si chaque caractéristique doit être considérée comme le résultat d'une adaptation orchestrée par la sélection naturelle. Les caractéristiques biologiques des organismes peuvent en effet n'être que le résultat de contraintes de leur développement, soit du fait de leur histoire (contraintes phylogénétiques), soit du fait de contraintes structurelles (contraintes formelles). Afin d'étudier l'influence respective de la sélection naturelle, optimisant les phénotypes, et des contraintes développementales, limitant les phénotypes offrant prise à la sélection, nous avons choisi comme organisme modèle le grain de pollen, et nous avons centré notre étude sur le type apertural, qui est le nombre, la forme et la disposition des apertures (zones amincies de la paroi du grain de pollen impliquées dans la résistance à la dessiccation et dans la germination du tube pollinique). L'étude de la microsporogénèse montre que le type apertural des grains de pollen est déterminé précocément au cours de ce processus, et que des facteurs clés y exercent une influence fondamentale (type de cytocinèse, mode de formation des parois callosiques, forme des tétrades contenant les microsporocytes, et localisation des apertures au sein de la tétrade). Cette thèse comporte deux parties: i) l'étude fine de la variation du développement au cours de la microsporogénèse en liaison avec le type apertural, chez les Asparagales (ordre caractérisé par la présence de plusieurs types aperturaux); ii) l'influence de la sélection naturelle, étudiée par une analyse de paternité chez le frêne commun (Fraxinus excelsior), qui produit deux types aperturaux en proportions variables. L'influence de la proportion des différents types aperturaux sur le succès reproducteur a été testée. Les résultats montrent que la microsporogénèse est variable et diversifiée chez les Asparagales. En dépit de la variation rencontrée, qui serait susceptible de permettre la formation de types aperturaux variés, le type apertural monosulqué est produit de façon majoritaire chez cet ordre. On observe de nombreuses modifications du développement qui ont pour conséquence de canaliser la microsporogénèse vers la production de cette morphologie de pollen. Ceci indique un avantage sélectif important pour ce type apertural. Une des étapes de la microsporogénèse possède une des caractéristiques d'une contrainte évolutive liée au développement: la formation des parois. Cependant, cette contrainte évolutive d'origine développementale ne semble pas affecter l'évolution du type apertural, puisque qu'il existe de nombreuses voies alternatives pour produire du pollen monosulqué. Des études directes de l'avantage du type apertural monosulqué, ainsi que des conditions écologiques nécessaires aux transitions vers d'autres types aperturaux, sont nécessaires pour confirmer ces observations indirectes de l'influence de la sélection naturelle. L'analyse de paternité chez le frêne ne nous a pas permis de mettre en évidence d'influence significative du type apertural sur le succès reproducteur, pour des raisons méthodologiques (discutées dans le manuscrit).Natural selection is considered as one of the main evolutionary forces responsible for adaptive evolution in organisms in general, and for their morphology in particular. Since three decades, a debate rages about whether each trait of an organism should be considered as the result of an adaptation due to natural selection. Traits of organisms can actually be the result of developmental constraints, either because of their natural history (phylogenetic constraints) or because of structural constraints (formal constraints). In order to investigate the relative importance of natural selection, that optimizes phenotypes, and developmental constraints, that limit phenotypes available to selection, we chose pollen grains as model organisms and we centred our study on aperture type, which is defined as the number, the shape and position of apertures (thinned area on pollen grain wall that serve for desiccation resistance and pollen tube germination). Previous studies on microsporogenesis showed that aperture type is determined early during this process and that key steps do have a dramatic influence on this character (cytokinesis type, intersporal wall formation, tetrad shape, and position of apertures within tetrads). This document has two parts: i) A fine scale study of developmental variation during microsporogenesis and its link with aperture type in Asparagales (an order characterized by several different aperture types); ii) The influence of natural selection, investigated with a paternity analysis in the common ash (Fraxinus excelsior), a tree that produces two main aperture types in variable proportions. The influence of pollen morphs ratio on male reproductive success was tested. Results show that microsporogenesis is variable and diverse in Asparagales. Despite such variation that would lead to diverse aperture types monosulcate pollen is mainly produced in this order. We observe numerous modifications of development which canalize microsporogenesis into producing such pollen morphology. This implies an important selective advantage of this aperture type. One step of microsporogenesis possesses a characteristic of evolutionary constraint linked to development: the formation of the intersporal wall. However, this developmental constraint does not affect aperture type evolution, since several alternative pathways leading to monosulcate pollen exist. Direct studies of advantages of monosulcate pollen, and of ecological conditions responsible for transition to other morphologies are needed to confirm these indirect observations of natural selection. Paternity analysis did not provide evidence for a significant influence of aperture type ratio on male reproductive success for methodological reasons (discussed in the manuscript).ORSAY-PARIS 11-BU Sciences (914712101) / SudocPARIS-Museum Hist.Naturelle (751052304) / SudocSudocFranceF