Innovating Pedagogy 2015: Open University Innovation Report 4

This series of reports explores new forms of teaching, learning and assessment for an interactive world, to guide teachers and policy makers in productive innovation. This fourth report proposes ten innovations that are already in currency but have not yet had a profound influence on education. To produce it, a group of academics at the Institute of Educational Technology in The Open University collaborated with researchers from the Center for Technology in Learning at SRI International. We proposed a long list of new educational terms, theories, and practices. We then pared these down to ten that have the potential to provoke major shifts in educational practice, particularly in post-school education. Lastly, we drew on published and unpublished writings to compile the ten sketches of new pedagogies that might transform education. These are summarised below in an approximate order of immediacy and timescale to widespread implementation

pH tolerances and regulatory abilities of freshwater and euryhaline Aedine mosquito larvae

The pH regulatory abilities of two members of the mosquito tribe Aedini, known to have dramatically different saline tolerances, are investigated. The freshwater mosquito Aedes aegypti and the euryhaline Ochlerotatus taeniorhynchus tolerate very similar pH ranges. Both species complete larval development in waters ranging from pH·4 to pH·11, but naïve larvae always die in water of pH·3 or 12. Across the pH range 4–11, the hemolymph pH of O. taeniorhynchus is maintained constant while that of A. aegypti varies by 0.1 pH units. The salt composition of the water (3.5·g·l–1 sea salt, 3.5·g·l–1 NaCl, or nominally salt-free) has no effect on the range of pH tolerated by A. aegypti. In both speies, the effects of pH on larval growth and development are minor in comparison with the influence of species and sex. Acclimation of A. aegypti to pH·4 or 11 increases survival times in pH·3 or 12, respectively, and allows a small percentage of larvae to pupate successfully at these extreme pH values. Such acclimation does not compromise survival at the other pH extreme. Key words: mosquito larvae, pH regulation, pH acclimation, life history, Aedes aegypti, Ochlerotatus taeniorhynchu

创新教学报告2015 —探索教学、学习与评价的新形式 [Innovating Pedagogy 2015]

本报告提出了在教学应用方面呈现端倪的“十大创新教学法”，包括跨界学习、论证学习、随机 学习、基于情境的学习、计算思维、利用远程实验室在科学实验中学习、具身学习、适应性教学、情绪分析 和隐性评价，预期这些方法有可能在教育实践中，尤其是在学校后继续教育中引发重大变革

Sirtuin 3 Downregulation in Mycobacterium tuberculosis-Infected Macrophages Reprograms Mitochondrial Metabolism and Promotes Cell Death

Mycobacterium tuberculosis induces metabolic reprogramming in macrophages like the Warburg effect. This enhances antimicrobial performance at the expense of increased inflammation, which may promote a pathogen-permissive host environment. Since the NAD(+)-dependent protein deacetylase Sirtuin 3 (SIRT3) is an important regulator of mitochondrial metabolism and cellular redox homeostasis, we hypothesized that SIRT3 modulation mediates M. tuberculosis-induced metabolic reprogramming. Infection of immortalized and primary murine macrophages resulted in reduced levels of SIRT3 mRNA and protein and perturbation of SIRT3-regulated enzymes in the tricarboxylic acid cycle, electron transport chain, and glycolytic pathway. These changes were associated with increased reactive oxygen species and reduced antioxidant scavenging, thereby triggering mitochondrial stress and macrophage cell death. Relevance to tuberculosis disease in vivo was indicated by greater bacterial burden and immune pathology in M. tuberculosis-infected Sirt3 (-/-) mice. CD11b(+) lung leukocytes isolated from infected Sirt3(-/-) mice showed decreased levels of enzymes involved in central mitochondrial metabolic pathways, along with increased reactive oxygen species. Bacterial burden was also greater in lungs of LysM(cre)Sirt3(L2/L2) mice, demonstrating the importance of macrophage-specific SIRT3 after infection. These results support the model of SIRT3 as a major upstream regulatory factor, leading to metabolic reprogramming in macrophages by M. tuberculosis IMPORTANCE Tuberculosis, the disease caused by the bacterium M. tuberculosis, remains one of the top 10 causes of death worldwide. Macrophages, the first cells to encounter M. tuberculosis and critical for defense against infection, are hijacked by M. tuberculosis as a protected growth niche. M. tuberculosis-infected macrophages undergo metabolic reprogramming where key mitochondrial pathways are modulated, but the mechanisms driving this metabolic shift is unknown. Our study demonstrates that M. tuberculosis downregulates Sirtuin 3 (SIRT3), an important regulator of mitochondrial metabolism, leading to SIRT3-dependent transcriptional downregulation of mitochondrial metabolic proteins, which is followed by oxidative stress and macrophage necrosis. This study identifies SIRT3 modulation as a key event in M. tuberculosis-induced metabolic reprograming in macrophages that defend against tuberculosis

Interactive engagement in Introductory Physics at UFJF

In this paper we describe a series of changes to the teaching method of an undergraduate introductory physics course for physics majors at the Federal University of Juiz de Fora. The aim of the method is to foster interactive engagement. We analyze the effectiveness of instruction by measuring the normalized gain g for the Force Concept Inventory and compare it to previous semesters. We show an increase in g compared to traditional teaching methods.Neste trabalho descrevemos uma série de modificações no ensino de Física I para alunos do curso de Física da UFJF. Estas modificações introduziram um ambiente de engajamento interativo. Analisamos o sucesso do método aplicando o Force Concept Inventory e mostramos uma melhora do desempenho dos alunos, se comparados aos desempenhos típicos dos alunos em métodos convencionais

Efferocytosis is an innate antibacterial mechanism

Mycobacterium tuberculosis persists within macrophages in an arrested phagosome and depends upon necrosis to elude immunity and disseminate. Although apoptosis of M. tuberculosis-infected macrophages is associated with reduced bacterial growth, the bacteria are relatively resistant to other forms of death, leaving the mechanism underlying this observation unresolved. We find that after apoptosis, M. tuberculosis-infected macrophages are rapidly taken up by uninfected macrophages through efferocytosis, a dedicated apoptotic cell engulfment process. Efferocytosis of M. tuberculosis sequestered within an apoptotic macrophage further compartmentalizes the bacterium and delivers it along with the apoptotic cell debris to the lysosomal compartment. M. tuberculosis is killed only after efferocytosis, indicating that apoptosis itself is not intrinsically bactericidal but requires subsequent phagocytic uptake and lysosomal fusion of the apoptotic body harboring the bacterium. While efferocytosis is recognized as a constitutive housekeeping function of macrophages, these data indicate that it can also function as an antimicrobial effector mechanism.Behar, Fortune, and Remold labs for reagents, helpful discussion, and insights. TIM4-blocking antibodies were a generous gift of Vijay Kuchroo. Members of the Harvard Electron Microscopy Core Facility helped in the preparation, staining, and operation of the electron microscope. The Small Animal Biocontainment (ABC) Suite is supported by CFAR 5P30AI060354. T.R.R and S.M.F were supported by CFAR 5P30AI060354, DP2-0d001378, and T32-AI07387. C.N.A. is the recipient of a fellowship from FCT. S.M.B and H.G.R. were supported by R56AI084161 and R01AI072143

Evolution of Highly Polymorphic T Cell Populations in Siblings with the Wiskott-Aldrich Syndrome

Population level evolutionary processes can occur within a single organism when the germ line contains a mutation that confers a cost at the level of the cell. Here we describe how multiple compensatory mutations arose through a within-individual evolutionary process in two brothers with the immune deficiency Wiskott-Aldrich Syndrome (WAS). As a result, both brothers have T lymphocyte populations that are highly polymorphic at the locus of the germ line defect, and no single allele achieves fixation. WASP, the gene product affected in this disease, is specific to white blood cells where it is responsible for regulating actin cytoskeleton dynamics in a wide range of cellular responses. The brothers inherited a rare allele predicted to result in truncated WASP lacking the carboxy-terminal VCA domains, the region that directly catalyzes actin filament generation. Although the brothers' T cell populations are highly polymorphic, all share a corrective effect relative to the inherited allele in that they restore the VCA domain. This indicates massive selection against the truncated germ line allele. No single somatic allele becomes fixed in the circulating T cell population of either brother, indicating that a regulated step in maturation of the affected cell lineage is severely compromised by the germ line allele. Based on the finding of multiple somatic mutations, the known maturation pathway for T-lineage cells and the known defects of T cells and precursor thymocytes in mice with truncated WASP, we hypothesize that the presence of truncated WASP (WASPΔVCA) confers an extreme disadvantage in early developing thymocytes, above and beyond the known cost of absence of full-length WASP, and that the disadvantage likely occurs through dominant negative competition of WASPΔVCA with N-WASP, a protein that otherwise partially compensates for WASP absence in developing thymocytes

Effect of Host Species on the Distribution of Mutational Fitness Effects for an RNA Virus

Knowledge about the distribution of mutational fitness effects (DMFE) is essential for many evolutionary models. In recent years, the properties of the DMFE have been carefully described for some microorganisms. In most cases, however, this information has been obtained only for a single environment, and very few studies have explored the effect that environmental variation may have on the DMFE. Environmental effects are particularly relevant for the evolution of multi-host parasites and thus for the emergence of new pathogens. Here we characterize the DMFE for a collection of twenty single-nucleotide substitution mutants of Tobacco etch potyvirus (TEV) across a set of eight host environments. Five of these host species were naturally infected by TEV, all belonging to family Solanaceae, whereas the other three were partially susceptible hosts belonging to three other plant families. First, we found a significant virus genotype-by-host species interaction, which was sustained by differences in genetic variance for fitness and the pleiotropic effect of mutations among hosts. Second, we found that the DMFEs were markedly different between Solanaceae and non-Solanaceae hosts. Exposure of TEV genotypes to non-Solanaceae hosts led to a large reduction of mean viral fitness, while the variance remained constant and skewness increased towards the right tail. Within the Solanaceae hosts, the distribution contained an excess of deleterious mutations, whereas for the non-Solanaceae the fraction of beneficial mutations was significantly larger. All together, this result suggests that TEV may easily broaden its host range and improve fitness in new hosts, and that knowledge about the DMFE in the natural host does not allow for making predictions about its properties in an alternative host

On the Accessibility of Adaptive Phenotypes of a Bacterial Metabolic Network

The mechanisms by which adaptive phenotypes spread within an evolving population after their emergence are understood fairly well. Much less is known about the factors that influence the evolutionary accessibility of such phenotypes, a pre-requisite for their emergence in a population. Here, we investigate the influence of environmental quality on the accessibility of adaptive phenotypes of Escherichia coli's central metabolic network. We used an established flux-balance model of metabolism as the basis for a genotype-phenotype map (GPM). We quantified the effects of seven qualitatively different environments (corresponding to both carbohydrate and gluconeogenic metabolic substrates) on the structure of this GPM. We found that the GPM has a more rugged structure in qualitatively poorer environments, suggesting that adaptive phenotypes could be intrinsically less accessible in such environments. Nevertheless, on average ∼74% of the genotype can be altered by neutral drift, in the environment where the GPM is most rugged; this could allow evolving populations to circumvent such ruggedness. Furthermore, we found that the normalized mutual information (NMI) of genotype differences relative to phenotype differences, which measures the GPM's capacity to transmit information about phenotype differences, is positively correlated with (simulation-based) estimates of the accessibility of adaptive phenotypes in different environments. These results are consistent with the predictions of a simple analytic theory that makes explicit the relationship between the NMI and the speed of adaptation. The results suggest an intuitive information-theoretic principle for evolutionary adaptation; adaptation could be faster in environments where the GPM has a greater capacity to transmit information about phenotype differences. More generally, our results provide insight into fundamental environment-specific differences in the accessibility of adaptive phenotypes, and they suggest opportunities for research at the interface between information theory and evolutionary biology