Genisa: A web-based interactive learning environment for teaching simulation modelling

Intelligent Tutoring Systems (ITS) provide students with adaptive instruction and can facilitate the acquisition of problem solving skills in an interactive environment. This paper discusses the role of pedagogical strategies that have been implemented to facilitate the development of simulation modelling knowledge. The learning environment integrates case-based reasoning with interactive tools to guide tutorial remediation. The evaluation of the system shows that the model for pedagogical activities is a useful method for providing efficient simulation modelling instruction

Reporting dose in complex self-management support interventions for long-term conditions: is it defined by researchers and received by participants? A systematic review

BACKGROUND: The minimum clinically effective dose, and whether this is received in randomised controlled trials (RCTs) of complex self-management interventions in long-term conditions (LTCs), can be unclear. The Template for Intervention Description and Replication (TIDieR) checklist states that dose should be clearly reported to ensure validity and reliable implementation. OBJECTIVES: To identify whether the expected minimum clinically effective dose, and the dose participants received is reported within research articles and if reporting has improved since the TIDieR checklist was published. METHODS: Four databases were systematically searched (MEDLINE, PsycINFO, AMED and CINAHL) to identify published reports between 2008 and 2022 for RCTs investigating complex self-management interventions in LTCs. Data on reporting of dose were extracted and synthesised from the eligible articles. RESULTS: 94 articles covering various LTCs including diabetes, stroke and arthritis were included. Most complex interventions involved behaviour change combined with education and/or exercise. The maximum dose was usually reported (n=90; 97.8%), but the expected minimum clinically effective dose and the dose received were reported in only 28 (30.4%) and 62 (67.4%) articles, respectively. Reporting of the expected minimum clinically effective dose and the dose participants received did not improve following the publication of the TIDieR checklist in 2014. CONCLUSIONS: Interpreting results and implementing effective complex self-management interventions is difficult when researchers' reporting of dose is not in line with guidelines. If trial findings indicate benefit from the intervention, clear reporting of dose ensures reliable implementation to standard care. If the results are non-significant, detailed reporting enables better interpretation of results, that is, differentiating between poor implementation and lack of effectiveness. This ensures quality of interventions and validity and generalisability of trial findings. Therefore, wider adoption of reporting the TIDieR checklist dose aspects is strongly recommended. Alternatively, customised guidelines for reporting dose in complex self-management interventions could be developed. PROSPERO REGISTRATION NUMBER: CRD42020180988

Reconstitution of T cell receptor signaling in ZAP-70-deficient cells by retroviral transduction of the ZAP-70 gene.

A variant of severe combined immunodeficiency syndrome (SCID) with a selective inability to produce CD8 single positive T cells and a signal transduction defect in peripheral CD4+ cells has recently been shown to be the result of mutations in the ZAP-70 gene. T cell receptor (TCR) signaling requires the association of the ZAP-70 protein tyrosine kinase with the TCR complex. Human T cell leukemia virus type I-transformed CD4+ T cell lines were established from ZAP-70-deficient patients and normal controls. ZAP-70 was expressed and appropriately phosphorylated in normal T cell lines after TCR engagement, but was not detected in T cell lines from ZAP-70-deficient patients. To determine whether signaling could be reconstituted, wild-type ZAP-70 was introduced into deficient cells with a ZAP-70 retroviral vector. High titer producer clones expressing ZAP-70 were generated in the Gibbon ape leukemia virus packaging line PG13. After transduction, ZAP-70 was detected at levels equivalent to those observed in normal cells, and was appropriately phosphorylated on tyrosine after receptor engagement. The kinase activity of ZAP-70 in the reconstituted cells was also appropriately upregulated by receptor aggregation. Moreover, normal and transduced cells, but not ZAP-70-deficient cells, were able to mobilize calcium after receptor ligation, indicating that proximal TCR signaling was reconstituted. These results indicate that this form of SCID may be corrected by gene therapy

Can patterns of chromosome inversions in Drosophila pseudoobscura predict polyandry across a geographical cline?

Journal ArticleFemale multiple mating, known as polyandry, is ubiquitous and occurs in a wide variety of taxa. Polyandry varies greatly from species in which females mate with one or two males in their lifetime to species in which females may mate with several different males on the same day. As multiple mating by females is associated with costs, numerous hypotheses attempt to explain this phenomenon. One hypothesis not extensively explored is the possibility that polyandrous behavior is captured and "fixed" in populations via genetic processes that preserve the behavior independently of any adaptive benefit of polyandry. Here, we use female isolines derived from populations of Drosophila pseudoobscura from three locations in North America to examine whether different female remating levels are associated with patterns of chromosome inversions, which may explain patterns of polyandry across the geographic range. Populations differed with respect to the frequency of polyandry and the presence of inversion polymorphisms on the third chromosome. The population with the lowest level of female remating was the only one that was entirely comprised of homokaryotypic lines, but the small number of populations prevented us investigating this relationship further at a population level. However, we found no strong relationship between female remating levels and specific karyotypes of the various isolines.NER

Opposite environmental and genetic influences on body size in North American Drosophila pseudoobscura.

Journal ArticleResearch Support, Non-U.S. Gov'tBACKGROUND: Populations of a species often differ in key traits. However, it is rarely known whether these differences are associated with genetic variation and evolved differences between populations, or are instead simply a plastic response to environmental differences experienced by the populations. Here we examine the interplay of plasticity and direct genetic control by investigating temperature-size relationships in populations of Drosophila pseudoobscura from North America. We used 27 isolines from three populations and exposed them to four temperature regimes (16°C, 20°C, 23°C, 26°C) to examine environmental, genetic and genotype-by-environment sources of variance in wing size. RESULTS: By far the largest contribution to variation in wing size came from rearing temperature, with the largest flies emerging from the coolest temperatures. However, we also found a genetic signature that was counter to this pattern as flies originating from the northern, cooler population were consistently smaller than conspecifics from more southern, warmer populations when reared under the same laboratory conditions. CONCLUSIONS: We conclude that local selection on body size appears to be acting counter to the environmental effect of temperature. We find no evidence that local adaptation in phenotypic plasticity can explain this result, and suggest indirect selection on traits closely linked with body size, or patterns of chromosome inversion may instead be driving this relationship.NERCBBSR

A Case Study of Eukaryogenesis: The Evolution of Photoreception by Photolyase/Cryptochrome Proteins

Eukaryogenesis, the origin of the eukaryotes, is still poorly understood. Herein, we show how a detailed all-kingdom phylogenetic analysis overlaid with a map of key biochemical features can provide valuable clues. The photolyase/cryptochrome family of proteins are well known to repair DNA in response to potentially harmful effects of sunlight and to entrain circadian rhythms. Phylogenetic analysis of photolyase/cryptochrome protein sequences from a wide range of prokaryotes and eukaryotes points to a number of horizontal gene transfer events between ancestral bacteria and ancestral eukaryotes. Previous experimental research has characterised patterns of tryptophan residues in these proteins that are important for photoreception, specifically a tryptophan dyad, a canonical tryptophan triad, an alternative tryptophan triad, a tryptophan tetrad and an alternative tetrad. Our results suggest that the spread of the different triad and tetrad motifs across the kingdoms of life accompanied the putative horizontal gene transfers and is consistent with multiple bacterial contributions to eukaryogenesis

Cross modal perception of body size in domestic dogs (Canis familiaris)

While the perception of size-related acoustic variation in animal vocalisations is well documented, little attention has been given to how this information might be integrated with corresponding visual information. Using a cross-modal design, we tested the ability of domestic dogs to match growls resynthesised to be typical of either a large or a small dog to size- matched models. Subjects looked at the size-matched model significantly more often and for a significantly longer duration than at the incorrect model, showing that they have the ability to relate information about body size from the acoustic domain to the appropriate visual category. Our study suggests that the perceptual and cognitive mechanisms at the basis of size assessment in mammals have a multisensory nature, and calls for further investigations of the multimodal processing of size information across animal species

Topoisomer Differentiation of Molecular Knots by FTICR MS: Lessons from Class II Lasso Peptides

Lasso peptides constitute a class of bioactive peptides sharing a knotted structure where the C-terminal tail of the peptide is threaded through and trapped within an N-terminalmacrolactamring. The structural characterization of lasso structures and differentiation from their unthreaded topoisomers is not trivial and generally requires the use of complementary biochemical and spectroscopic methods. Here we investigated two antimicrobial peptides belonging to the class II lasso peptide family and their corresponding unthreaded topoisomers: microcin J25 (MccJ25), which is known to yield two-peptide product ions specific of the lasso structure under collisioninduced dissociation (CID), and capistruin, for which CID does not permit to unambiguously assign the lasso structure. The two pairs of topoisomers were analyzed by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR MS) upon CID, infrared multiple photon dissociation (IRMPD), and electron capture dissociation (ECD). CID and ECDspectra clearly permitted to differentiate MccJ25 from its non-lasso topoisomer MccJ25-Icm, while for capistruin, only ECD was informative and showed different extent of hydrogen migration (formation of c\bullet/z from c/z\bullet) for the threaded and unthreaded topoisomers. The ECD spectra of the triply-charged MccJ25 and MccJ25-lcm showed a series of radical b-type product ions {\eth}b0In{\TH}. We proposed that these ions are specific of cyclic-branched peptides and result from a dual c/z\bullet and y/b dissociation, in the ring and in the tail, respectively. This work shows the potentiality of ECD for structural characterization of peptide topoisomers, as well as the effect of conformation on hydrogen migration subsequent to electron capture

Causes of Higher Climate Sensitivity in CMIP6 Models

Equilibrium climate sensitivity, the global surface temperature response to CO urn:x-wiley:grl:media:grl60047:grl60047-math-0001 doubling, has been persistently uncertain. Recent consensus places it likely within 1.5–4.5 K. Global climate models (GCMs), which attempt to represent all relevant physical processes, provide the most direct means of estimating climate sensitivity via CO urn:x-wiley:grl:media:grl60047:grl60047-math-0002 quadrupling experiments. Here we show that the closely related effective climate sensitivity has increased substantially in Coupled Model Intercomparison Project phase 6 (CMIP6), with values spanning 1.8–5.6 K across 27 GCMs and exceeding 4.5 K in 10 of them. This (statistically insignificant) increase is primarily due to stronger positive cloud feedbacks from decreasing extratropical low cloud coverage and albedo. Both of these are tied to the physical representation of clouds which in CMIP6 models lead to weaker responses of extratropical low cloud cover and water content to unforced variations in surface temperature. Establishing the plausibility of these higher sensitivity models is imperative given their implied societal ramifications

18F-FDG PET/MRI for staging and interim response assessment in pediatric and adolescent Hodgkin lymphoma: a prospective study with 18F-FDG PET/CT as reference standard

Rationale: Treatment regimens for pediatric Hodgkin's lymphoma (HL) depend on accurate staging and treatment response assessment, based on accurate disease distribution and metabolic activity depiction. With the aim of radiation dose reduction, we compared the diagnostic performance of 18F-FDG PET/MR to a 18F-FDG PET/CT reference standard for staging and response assessment. Methods: Twenty-four patients (mean age 15.4 years, range 8-19.5 years) with histologically proven HL were prospectively and consecutively recruited in 2015 and 2016, undergoing both 18F-FDG PET/CT and 18F-FDG PET/MRI at initial staging (N n = 24) and at response assessment (N n = 21). Diagnostic accuracy of 18F-FDG PET/MRI for both nodal and extra-nodal disease was compared to 18F-FDG PET/CT, which was considered as the reference standard. Discrepancies were retrospectively classified as perceptual or technical errors and 18F-FDG PET/MRI and 18F-FDG PET/CT were corrected by removing perceptual error. Agreement with Ann-Arbor staging and Deauville grading was also assessed. Results: For nodal and extranodal sites combined, corrected staging 18F-FDG PET/MRI sensitivity was 100% (95% confidence interval (CI) 96.7%-100%), specificity 99.5% (95%CI 98.3%-99.9%). Corrected response assessment 18F-FDG PET/MRI sensitivity was 83.3% (95%CI 36.5%-99.1%), specificity 100% (95%CI 99.2%-100%). Modified Ann-Arbor staging agreement between F18-FDG PET/CT and 18F-FDG PET/MRI was perfect (k = 1.0, P = 0.000). Deauville grading agreement between 18F-FDG PET/MRI and 18F-FDG PET/CT was excellent (k = 0.835, P = 0.000). Conclusion:18F-FDG PET/MRI is a promising alternative to 18F-FDG PET/CT for staging and response assessment in children with Hodgkin lymphoma