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Natural infection with Plasmodium parasites, the causative agents of malaria, occurs via mosquito vectors. However, most of our knowledge of the immune response to the blood stages of Plasmodium is from infections initiated by injection of serially blood-passaged infected red blood cells, resulting in an incomplete life cycle in the mammalian host. Vector transmission of the rodent malaria parasite, Plasmodium chabaudi chabaudi AS has been shown to give rise to a more attenuated blood-stage infection in C57Bl/6J mice, when compared to infections initiated with serially blood-passaged P. chabaudi-infected red blood cells. In mouse models, the host immune response induced by parasites derived from natural mosquito transmission is likely to more closely resemble the immune responses to Plasmodium infections in humans. It is therefore important to determine how the host response differs between the two types of infections. As the spleen is considered to be a major contributor to the protective host response to P. chabaudi, we carried out a comparative transcriptomic analysis of the splenic response to recently mosquito-transmitted and serially blood-passaged parasites in C57Bl/6J mice. The attenuated infection arising from recently mosquito-transmitted parasites is characterised by an earlier and stronger myeloid- and IFNγ-related response. Analyses of spleen lysates from the two infections similarly showed stronger or earlier inflammatory cytokine and chemokine production in the recently mosquito-transmitted blood-stage infections. Furthermore, tissue macrophages, including red pulp macrophages, and IFNγ-signalling in myeloid cells, are required for the early control of P. chabaudi recently mosquito-transmitted parasites, thus contributing to the attenuation of mosquito-transmitted infections. The molecules responsible for this early activation response to recently-transmitted blood-stage parasites in mice would be important to identify, as they may help to elucidate the nature of the initial interactions between blood-stage parasites and the host immune system in naturally transmitted malaria.

Alternative splicing is widespread throughout eukaryotic genomes and greatly increases transcriptomic diversity. Many alternative isoforms have functional roles in developmental processes and are precisely temporally regulated. To facilitate the study of alternative splicing in a developmental context, we created MeDAS, a Metazoan Developmental Alternative Splicing database. MeDAS is an added-value resource that re-analyses publicly archived RNA-seq libraries to provide quantitative data on alternative splicing events as they vary across the time course of development. It has broad temporal and taxonomic scope and is intended to assist the user in identifying trends in alternative splicing throughout development. To create MeDAS, we re-analysed a curated set of 2232 Illumina polyA+ RNA-seq libraries that chart detailed time courses of embryonic and post-natal development across 18 species with a taxonomic range spanning the major metazoan lineages from Caenorhabditis elegans to human. MeDAS is freely available at https://das.chenlulab.com both as raw data tables and as an interactive browser allowing searches by species, tissue, or genomic feature (gene, transcript or exon ID and sequence). Results will provide details on alternative splicing events identified for the queried feature and can be visualised at the gene-, transcript- and exon-level as time courses of expression and inclusion levels, respectively.

Socioscientific issues (SSI) related teaching may positively influence students’ scientific epistemological beliefs (SEB). However, research is limited about elementary school students and the meth...

Modelling ability is one of the essential elements of the latest educational reforms, and Trends in International Mathematics and Science Study (TIMSS) is a curriculum-based assessment which allows...

Malaria is a devastating infectious disease and the immune response is complex and dynamic during a course of a malarial infection. Rodent malaria models allow detailed time-series studies of the host response in multiple organs. Here, we describe two comprehensive datasets containing host transcriptomic data from both the blood and spleen throughout an acute blood stage infection of virulent or avirulent Plasmodium chabaudi infection in C57BL/6 mice. The mRNA expression profiles were generated using Illumina BeadChip microarray. These datasets provide a groundwork for comprehensive and comparative studies on host gene expression in early, acute and recovering phases of a blood stage infection in both the blood and spleen, to explore the interaction between the two, and importantly to investigate whether these responses differ in virulent and avirulent infections., Measurement(s) transcriptome • gene expression • malaria Technology Type(s) Microarray Factor Type(s) blood versus spleen • virulent versus avirulent malaria infection Sample Characteristic - Organism Mus musculus Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.12619232

Hematopoietic stem cells (HSCs) lie at the top of the differentiation hierarchy. Although HSC and their immediate downstream, multipotent progenitors (MPP) have full multilineage differentiation capacity, only long-term (LT-) HSC has the capacity of long-term self-renewal. The heterogeneity within the HSC population is gradually acknowledged with the development of single-cell RNA sequencing and lineage tracing technologies. Transcriptional and post-transcriptional regulations play important roles in controlling the differentiation and self-renewal capacity within HSC population. Here we report a dataset comprising short- and long-read RNA sequencing for mouse long- and short-term HSC and MPP at bulk and single-cell levels. We demonstrate that integrating short- and long-read sequencing can facilitate the identification and quantification of known and unannotated isoforms. Thus, this dataset provides a groundwork for comprehensive and comparative studies on transcriptional diversity and heterogeneity within different HSC cell types., Measurement(s)short term hematopoietic stem cell • long term hematopoietic stem cell • multipotent stem cellTechnology Type(s)RNA sequencingFactor Type(s)read lengthSample Characteristic - OrganismMus musculus Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.16759069

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(1) Background: Due to the high proportion of disadvantaged students in a rural school in Taiwan and the gap between students’ concepts and practices of environmental protection and sustainable energy, four science and mathematics teachers in this school planned an engineering-centred PjBL of sustainable energy curriculum in a Makers Club to enhance students’ creativity, engineering technical skills, practices of environmental protection and sustainable energy, and learning attitudes, (2) Methods: This study is a four-year action research. Teachers and students initiated the idea from rebuilding an old fan in a classroom, (3) Results: The students in the Makers Club improved their engineering technical skills and created various green-power generation devices (evolved from a ventilation ball generator, hydropower, ocean current power generators to tiny, 3D-printing wind power generators). They turned environmental protection and sustainable energy concepts into actions during practices and won awards from science and engineering fairs every year. This creative and supportive atmosphere spread from the club to the whole school and improved the students’ practices of environmental protection and learning attitudes after long-term implementation, (4) Conclusions: The design principles of the engineering-centred PjBL of sustainable energy curriculum played a critical role and were outlined at the end of the study.

We aimed to identify long non-coding RNAs (lncRNAs) aberrantly expressed in peripheral blood mononuclear cells (PBMCs) triggered by active tuberculosis (ATB), latent tuberculosis infection (LTBI), and healthy controls (HC). We examined lncRNAs expression in PBMCs isolated from children with ATB and LTBI, and from HC using RNA sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to explore the biological processes and signaling pathways of aberrantly expressed mRNAs. A total of 348 and 205 lncRNAs were differentially expressed in the ATB and LTBI groups, respectively, compared to the HC group. Compared to the LTBI group, 125 lncRNAs were differentially expressed in the ATB group. Compared to the HC group, 2317 mRNAs were differentially expressed in the ATB group, and 1093 mRNAs were differentially expressed in the LTBI group. Compared to the LTBI group, 2328 mRNAs were differentially expressed in the ATB group. The upregulated mRNAs were mainly enriched in neutrophil activation, neutrophil-mediated biological processes, and positive regulation of immune response in tuberculosis (TB), whereas the downregulated mRNAs were enriched in signaling pathways and structural processes, such as the Wnt signaling pathway and rDNA heterochromatin assembly. This is the first study on the differential expression of lncRNAs in PBMCs of children with TB. We identified significant differences in the expression profiles of lncRNAs and mRNAs in the PBMCs of children with ATB, LTBI, and HC, which has important implications for exploring lncRNAs as novel biomarkers for the diagnosis of TB. In addition, further experimental identification and validation of lncRNA roles could help elucidate the underlying mechanisms of Mycobacterium tuberculosis infection in children.

Research on the understanding of the nature of models and modeling processes in science education have received a lot of attention in science education. In this article, we make five claims about the research on modeling competence in science education. The five claims are (1) the development of modeling competence in practice is essential to scientific literacy for twenty-first century citizens, (2) further research is needed to build a holistic and theoretical understanding of models and modeling knowledge (MMingK), (3) providing a modeling-based scaffolding framework for meaningful and active authentic learning is to enhance student’s engagement of scientific practice, (4) appropriate formative assessment instruments and evaluation rubrics to assess students’ modeling processes and products within the context of modeling practice should be developed, and (5) research on learning progression in modeling competence needs to be intertwined with MMingK and modeling practice. Implications for student learning and teacher professional development will be drawn from existing literature.

This study explored how a 2-year, maker-centered science, technology, engineering, and mathematics (STEM) project-based learning (M-STEM-PjBL) curriculum aimed at leading students to be makers changed students, science teachers, and a rural middle school in Taiwan, where teachers were stressed due to the low birth rate and low grades in the Comprehensive Assessment Program for Junior High School Students (CAP). This practical action research study utilized data collected from 24 students in a maker class, their peers, 4 teachers, and administrative documents related to school enrollment and student competitions’ records. Results showed that teachers had shifted their teaching from being teacher-centered to student-centered. The students who participated in the M-STEM-PjBL curriculum actively assisted peer learning and initiated active teacher–student interactions. Both teacher and student participants improved their practical skills during the process. Students in the maker science class had more positive attitudes toward science and science learning and changed their peers’ attitudes in the regular science class. The problematic rate of not meeting the required standard in the science subtest of the CAP was reduced from 36 to 26%. Moreover, student participants’ products recommended to the county or national level competitions frequently won awards. Student participants’ creativity and the science teachers’ teaching efforts were recognized in the media. Parent endorsement of the school was increased, the threat of losing students to other schools was decreased, and the crisis of cutting the number of classes was reduced.

In the field of science education, laboratory learning environment has gained renewed interest in the recent decade. This study aimed to investigate the relationships among students’ conceptions of science laboratory learning, perceptions of the science laboratory learning environment, and their academic self-efficacy in science learning by adopting the structural equation modeling (SEM) technique. A total of 513 senior high school students (262 females) in Taiwan were invited to participate in this survey study. Three instruments were adapted and implemented to investigate the aim of the study (i.e. the conceptions of science laboratory learning questionnaire, the science laboratory environment inventory, and the academic self-efficacy in science learning questionnaire). The results indicated that the students’ conceptions of science laboratory learning made a significant contribution to their perceptions of the science laboratory environment, which consequently fostered their science learning self-efficacy. More specifically, students with conceptions of science laboratory learning as reviewing their prior learning profiles tended to highlight the “student cohesiveness,” “integration,” and “material environment” aspects of the laboratory environment. Moreover, students who held personal ideas of science laboratory learning as acquiring manipulative skills tended to perceive actual science laboratory environments as much more open-ended and to attain advanced academic science learning self-efficacy. In addition, those students who viewed laboratory learning as achieving in-depth understanding, and who perceived that laboratory activities are guided by clear rules, were prone to express a stronger sense of academic self-efficacy. Based on the results, practical implications and suggestions for future research are discussed.

The SARS-CoV-2 virus, the causative agent of COVID-19, is undergoing constant mutation. Here, we utilized an integrative approach combining epidemiology, virus genome sequencing, clinical phenotyping, and experimental validation to locate mutations of clinical importance. We identified 35 recurrent variants, some of which are associated with clinical phenotypes related to severity. One variant, containing a deletion in the Nsp1-coding region (Δ500-532), was found in more than 20% of our sequenced samples and associates with higher RT-PCR cycle thresholds and lower serum IFN-β levels of infected patients. Deletion variants in this locus were found in 37 countries worldwide, and viruses isolated from clinical samples or engineered by reverse genetics with related deletions in Nsp1 also induce lower IFN-β responses in infected Calu-3 cells. Taken together, our virologic surveillance characterizes recurrent genetic diversity and identified mutations in Nsp1 of biological and clinical importance, which collectively may aid molecular diagnostics and drug design., Graphical Abstract, Bringing together epidemiological, genetic, and clinical data, Lin et al. identify viral mutations that associate with clinical phenotypes. The 500-532 locus in the Nsp1 coding region is a deletion hotspot in the SARS-CoV-2 genome, and deletion variants lead to lower IFN-I response. Prevalence of 500-532 deletion variants is accumulating worldwide.

Pregnant women are generally more susceptible to viral infection. Although the impact of SARS-CoV-2 in pregnancy remains to be determined, evidence indicates that the risk factors for severe COVID-19 are similar in pregnancy to the general population. Here we systemically analyzed the clinical characteristics of pregnant and non-pregnant female COVID-19 patients who were hospitalized during the same period and found that pregnant patients developed marked lymphopenia and higher inflammation evident by higher C-reactive protein and IL-6. To elucidate the pathways that might contribute to immunopathology or protective immunity against COVID-19 during pregnancy, we applied single-cell mRNA sequencing to profile peripheral blood mononuclear cells from four pregnant and six non-pregnant female patients after recovery along with four pregnant and three non-pregnant healthy donors. We found normal clonal expansion of T cells in the pregnant patients, heightened activation and chemotaxis in NK, NKT, and MAIT cells, and differential interferon responses in the monocyte compartment. Our data present a unique feature in both innate and adaptive immune responses in pregnant patients recovered from COVID-19.

Alternative polyadenylation increases transcript diversities at the 3’ end, regulating biological processes including cell differentiation, embryonic development and cancer progression. Here, we present a Bayesian method SCAPE, which enables de novo identification and quantification of polyadenylation (pA) sites at single-cell level by utilizing insert size information. We demonstrated its accuracy and robustness and identified 31 558 sites from 36 mouse organs, 43.8% (13 807) of which were novel. We illustrated that APA isoforms were associated with miRNAs binding and regulated in tissue-, cell type-and tumor-specific manners where no difference was found at gene expression level, providing an extra layer of information for cell clustering. Furthermore, we found genome-wide dynamic changes of APA usage during erythropoiesis and induced pluripotent stem cell (iPSC) differentiation, suggesting APA contributes to the functional flexibility and diversity of single cells. We expect SCAPE to aid the analyses of cellular dynamics and diversities in health and disease.

Both poly(A) enrichment and ribosomal RNA depletion are commonly used for RNA sequencing. Either has its advantages and disadvantages that may lead to biases in the downstream analyses. To better access these effects, we carried out both ribosomal RNA-depleted and poly(A)-selected RNA-seq for CD4+ T naive cells isolated from 40 healthy individuals from the Blueprint Project. For these 40 individuals, the genomic and epigenetic data were also available. This dataset offers a unique opportunity to understand how library construction influences differential gene expression, alternative splicing and molecular QTL (quantitative loci) analyses for human primary cells., Measurement(s) RNA • gene expression Technology Type(s) RNA-seq of coding RNA • RNA-seq of total RNA • bioinformatics analysis Factor Type(s) gene expression level quantification • ribosomal RNA-depleted and poly(A)-selected RNA-seq • type of human primary cells Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.12932711

The cell permeable small fluorescent organic molecules possessing RNA-specific binding property were synthesized for the study of structural influence on two determining factors of binding affinity and specificity. Similar investigations are scarce in the field of RNA-specific binding ligand development based on a systematic structural change of small molecules. The newly developed and structurally simple ligands show much higher RNA-binding affinity (equilibrium binding constant: PI1, K = 4.50 × 105 M−1; PI2, K = 4.48 × 105 M−1) than that of a well-studied RNA-selective dye E36 (K = 0.89 × 105 M−1) by the introduction of an aminoethylpiperidine group on the quinolinium scaffold. In addition, the in vivo study of live cell imaging (human prostate cancer cells) indicated that these small molecules are able to provide strong interaction signals when binding with RNA in the region of nucleolus and cytoplasm. The interaction specificity of the molecule towards RNA is found much higher than other types of nucleic acids, which was further supported by the digest tests with ribonuclease (RNase). The experimental results of the present study not only provide important cues on the fluorescent signaling, binding affinity, and specificity advancement with the small RNA-specific binding ligands through structurally refinement of molecular scaffolds, but also give complementary information in searching lead ligands for targeting RNA sequence using high-throughput compound screening techniques and molecular modeling studies.

This work receives funding from the Wellcome Trust (WT102907) and the Francis Crick Institute (FC 10101), which receives its funding from the UK Medical Research Council, Cancer Research UK, and the Wellcome Trust, UK. Although the spleen is broadly accepted as the major lymphoid organ involved in generating immune responses to the erythrocytic stages of the malaria parasite, Plasmodium, human splenic tissue is not readily available in most cases. As a result, most studies of malaria in humans rely on peripheral blood to assess cellular immune responses to malaria. The suitability of peripheral blood as a proxy for splenic immune responses is however unknown. Here, we have simultaneously analysed the transcriptomes of whole blood and spleen over 12 days of erythrocytic stage Plasmodium chabaudi infection in C57BL/6 mice. Using both unsupervised and directed approaches, we compared gene expression between blood and spleen over the course of infection. Taking advantage of publicly available datasets, we used machine learning approaches to infer cell proportions and cell-specific gene expression signatures from our whole tissue transcriptome data. Our findings demonstrate that spleen and blood are quite dissimilar, sharing only a small amount of transcriptional information between them, with transcriptional differences in both cellular composition and transcriptional activity. These results suggest that while blood transcriptome data may be useful in defining surrogate markers of protection and pathology, they should not be used to predict specific immune responses occurring in lymphoid organs. Publisher PDF

Understanding how immune challenges elicit different responses is critical for diagnosing and deciphering immune regulation. Using a modular strategy to interpret the complex transcriptional host response in mouse models of infection and inflammation, we show a breadth of immune responses in the lung. Lung immune signatures are dominated by either IFN-γ and IFN-inducible, IL-17-induced neutrophil- or allergy-associated gene expression. Type I IFN and IFN-γ-inducible, but not IL-17- or allergy-associated signatures, are preserved in the blood. While IL-17-associated genes identified in lung are detected in blood, the allergy signature is only detectable in blood CD4+ effector cells. Type I IFN-inducible genes are abrogated in the absence of IFN-γ signaling and decrease in the absence of IFNAR signaling, both independently contributing to the regulation of granulocyte responses and pathology during Toxoplasma gondii infection. Our framework provides an ideal tool for comparative analyses of transcriptional signatures contributing to protection or pathogenesis in disease., The authors present an extensive profile of host transcriptional respones to a diverse group of pathogens and allergens. In doing so, they identify TH1, type I IFN, TH17, and TH2 responses, that underlie each immune response in both the blood and lung, which represents a global profile of host-pathogen immune responses.

To address the changing needs of the labour market better, higher education institutions have increasingly aimed to enhance their teaching quality and the learning experiences of their students. Therefore, a key concept of the missions of contemporary educational institutions is to improve students’ employability after graduation. Although extensive initiatives have been undertaken, educational mismatch remains intensely debated and may seriously challenge the greater use of limited human resources in Taiwan. In this study, a vocational-oriented department (baking) of a local well-known university was chosen for a case study. A holistic approach from student admission to entry in the labour market is adopted to analyse student learning, teaching, curriculum planning, and structural and enterprise demands to estimate the extent to which these graduates fit the requirement of employers. Research findings indicate multiple gaps in skill formation, intended labour needs, and career ladders. These gaps...

This study adopted a quasi-experimental design with follow-up interview to develop a computer-based two-tier assessment (CBA) regarding the science topic of electric circuits and to evaluate the diagnostic power of the assessment. Three assessment formats (i.e., paper-and-pencil, static computer-based, and dynamic computer-based tests) using two-tier items were conducted on Grade 4 (n = 90) and Grade 5 (n = 86) students, respectively. One-way ANCOVA was conducted to investigate whether the different assessment formats affected these students’ posttest scores on both the phenomenon and reason tiers, and confidence rating for an answer was assessed to diagnose the nature of students’ responses (i.e., scientific answer, guessing, alternative conceptions, or knowledge deficiency). Follow-up interview was adopted to explore whether and how the various CBA representations influenced both graders’ responses. Results showed that the CBA, in particular the dynamic representation format, allowed students who lacked prior knowledge (Grade 4) to easily understand the question stems. The various CBA representations also potentially encouraged students who already had learning experience (Grade 5) to enhance the metacognitive judgment of their responses. Therefore, CBA could reduce students’ use of test-taking strategies and provide better diagnostic power for a two-tier instrument than the traditional paper-based version.

We review studies measuring people's perceptions of technology learning environments.A framework conceptualizing technology learning environments (TSLEs) is proposed.It includes six dimensions: technical, content, cognitive, metacognitive, social, & affective.The studies considered more the technical, cognitive and social dimensions.The results provide insights into an overview of the instruments used for TSLEs. In this study we reviewed 22 studies on developing instruments that measure teachers', students' and adult students' perceptions of learning environments enhanced by a certain type of technology. We conducted a review of all the instruments to propose a new framework conceptualizing technology-supported learning environments (TSLEs) for future instructional designs, and research on learning environments. This framework was also confirmed with the literature on learning theories. The framework consists of six dimensions: technical, content, cognitive, metacognitive, social, and affective. We found that the studies took more into consideration the technical, cognitive and social dimensions, and less the content, metacognitive, and affective dimensions. Moreover, usability in the technical dimension, relevance in the content dimension, inquiry learning in the cognitive dimension, student autonomy in the metacognitive dimension, and teacher support in the social dimension are the salient features most often investigated in TSLEs. The results provide insights into an overview of the instruments used for TSLEs, implications for the instructional design of TSLEs, and trends in the current and future research on perceptions of TSLEs.

Objectives Plasmodium berghei ANKA infection in mice is a model for human cerebral malaria, the most severe complication of Plasmodium falciparum infection. Responses of brain microglia have been little investigated, and may contribute to the pathogenesis of cerebral malaria. We showed previously that microglia are activated in P. berghei infections, and that Type 1-Interferon signaling is important for activation. This dataset compares transcriptomic profiles of brain microglia of infected mice in the presence and absence of Type 1 interferon signaling, with the aim of identifying genes in microglia in this pathway during experimental cerebral malaria. Data description We documented global gene expression from microglial RNA from uninfected and P berghei-infected wild-type C57BL/6 and IFNA Receptor Knock-out mice using Illumina Beadarrays. Principal component analysis showed 4 groups of samples corresponding to naïve wild-type, naïve IFNA Receptor knock-out, infected wild-type, and IFNA Receptor knock-out mice. Differentially-expressed genes of microglia from the two groups of infected mice are documented. Gene set enrichment analysis showing the top 500 genes assigned to Reactome pathways from infected IFNA Receptor knock-out versus naïve, and infected WT versus naïve has been generated. These data will be useful for those interested in microglia cells, and in experimental cerebral malaria.

In this study, we propose a novel iterative refinement approach to predict the popularity score of the social media meta-data effectively. With the rapid growth of the social media on the Internet, how to adequately forecast the view count or popularity becomes more important. Conventionally, the ensemble approach such as random forest regression achieves high and stable performance on various prediction tasks. However, most of the regression methods may not precisely predict the extreme high or low values. To address this issue, we first predict the initial popularity score and retrieve their residues. In order to correctly compensate those extreme values, we adopt an ensemble regressor to compensate the residues to further improve the prediction performance. Comprehensive experiments are conducted to demonstrate the proposed iterative refinement approach outperforms the state-of-the-art regression approach., Comment: 5 pages, ACM Multimedia Conference 2018

Holding scientific conceptions and having the ability to accurately predict students’ preconceptions are a prerequisite for science teachers to design appropriate constructivist-oriented learning experiences. This study explored the types and sources of students’ preconceptions of electric circuits. First, 438 grade 3 (9 years old) students were surveyed about their pre-instructional ideas on electric circuits and where they developed these ideas. Then, 76 elementary school teachers with master’s degrees in science education were selected and their content knowledge of electric circuits was documented. Next, they were asked to make predictions about the kind of preconceptions most grade 3 students would have about electric circuits and the most dominant source of these preconceptions. The results revealed that these skilled teachers held scientific conceptions for most of the questions surveyed; however, they inaccurately predicted the types and sources of the students’ prominent alternative preconceptions. Specifically, they underestimated the possibility of students holding scientific concepts and neglected the effect of students’ intuition on their conceptions. Implications for teaching and teacher education are discussed.