An International Study in Competency Education: Postcards from Abroad

Acknowledging that national borders need not constrain our thinking, we have examined a selection of alternative academic cultures and, in some cases, specific schools, in search of solutions to common challenges we face when we consider reorganizing American schools. A wide range of interviews and e-mail exchanges with international researchers, government officials and school principals has informed this research, which was supplemented with a literature review scanning international reports and journal articles. Providing a comprehensive global inventory of competency-based education is not within the scope of this study, but we are confident that this is a representative sampling. The report that follows first reviews the definition of competency-based learning. A brief lesson in the international vocabulary of competency education is followed by a review of global trends that complement our own efforts to improve performance and increase equitable outcomes. Next, we share an overview of competency education against a backdrop of global education trends (as seen in the international PISA exams), before embarking on an abbreviated world tour. We pause in Finland, British Columbia (Canada), New Zealand and Scotland, with interludes in Sweden, England, Singapore and Shanghai, all of which have embraced practices that can inform the further development of competency education in the United States

Characterizing the Relationship Between Cell-Cycle Progression and a Transcriptional Oscillator

<p>The cell division cycle is the process in which the entirety of a cell's contents is duplicated completely and then equally segregated into two identical daughter cells. The order of the steps in the cell cycle must be followed with fidelity to guarantee two viable cells. Understanding the regulatory mechanisms that control cell-cycle events remains to be a fundamental question in cell biology. In this dissertation, I explore the mechanisms that coordinate and regulate cell-cycle progression in the budding yeast, Saccharomyces cerevisiae.</p><p>Cell-cycle events have been shown to be triggered by oscillations in the activity of cyclin dependent kinases (CDKs) when bound to cyclins. However, several studies have shown that some cell-cycle events, such as periodic transcription, can continue in the absence of CDK activity. How are periodic transcription and other cell-cycle events coupled to each other during a wild-type cell cycle? Currently, two models of cell-cycle regulation have been proposed. One model hypothesizes that oscillations in CDK activity controls the timing of cell-cycle events, including periodic transcription. The second model proposes that a transcription factor (TF) network oscillator controls the timing of cell-cycle events, via proper timing of gene expression, including cyclins. By measuring global gene expression dynamics in cells with persistent CDK activity, I show that periodic transcription continues. This result fits with the second model of cell-cycle regulation. Further, I show that during a wild-type cell cycle, checkpoints are responsible for arresting the bulk of periodic transcription. This finding adds a new layer of regulation to the second model, providing a mechanism that coordinates cell-cycle events with a TF network oscillator. Taken together, these data provide further insight into the regulation of the cell cycle.</p>Dissertatio

Exiting the Anthropocene : Achieving personal and planetary health in the 21st century

Planetary health provides a perspective of ecological interdependence that connects the health and vitality of individuals, communities, and Earth's natural systems. It includes the social, political, and economic ecosystems that influence both individuals and whole societies. In an era of interconnected grand challenges threatening health of all systems at all scales, planetary health provides a framework for cross-sectoral collaboration and unified systems approaches to solutions. The field of allergy is at the forefront of these efforts. Allergic conditions are a sentinel measure of environmental impact on human health in early life-illuminating how ecological changes affect immune development and predispose to a wider range of inflammatory noncommunicable diseases (NCDs). This shows how adverse macroscale ecology in the Anthropocene penetrates to the molecular level of personal and microscale ecology, including the microbial systems at the foundations of all ecosystems. It provides the basis for more integrated efforts to address widespread environmental degradation and adverse effects of maladaptive urbanization, food systems, lifestyle behaviors, and socioeconomic disadvantage. Nature-based solutions and efforts to improve nature-relatedness are crucial for restoring symbiosis, balance, and mutualism in every sense, recognizing that both personal lifestyle choices and collective structural actions are needed in tandem. Ultimately, meaningful ecological approaches will depend on placing greater emphasis on psychological and cultural dimensions such as mindfulness, values, and moral wisdom to ensure a sustainable and resilient future.Peer reviewe

Performance of the FOS and GHRS Pt/(Cr)-Ne Hollow-cathode Lamps after their Return from Space and Comparison with Archival Data

The Space Telescope European Coordinating Facility (ST-ECF) and National Institute of Standards and Technology (NIST) are collaborating to study hollow cathode calibration lamps as used onboard the Hubble Space Telescope (HST). As part of the STIS Calibration Enhancement (STIS-CE) Project we are trying to improve our understanding of the performance of hollow cathode lamps and the physical processes involved in their long term operation. The original flight lamps from the Faint Object Spectrograph (FOS) and the Goddard High Resolution Spectrograph (GHRS) are the only lamps that have ever been returned to Earth after extended operation in space. We have taken spectra of all four lamps using NIST s 10.7-m normal-incidence spectrograph and Fourier transform spectrometer (FTS) optimized for use in the ultraviolet (UV). These spectra, together with spectra archived from six years of on-orbit operations and pre-launch spectra, provide a unique data set - covering a period of about 20 years - for studying aging effects in these lamps. Our findings represent important lessons for the choice and design of calibration sources and their operation in future UV and optical spectrographs in space

Novel HIV-1 Knockdown Targets Identified by an Enriched Kinases/Phosphatases shRNA Library Using a Long-Term Iterative Screen in Jurkat T-Cells

HIV-1 is a complex retrovirus that uses host machinery to promote its replication. Understanding cellular proteins involved in the multistep process of HIV-1 infection may result in the discovery of more adapted and effective therapeutic targets. Kinases and phosphatases are a druggable class of proteins critically involved in regulation of signal pathways of eukaryotic cells. Here, we focused on the discovery of kinases and phosphatases that are essential for HIV-1 replication but dispensable for cell viability. We performed an iterative screen in Jurkat T-cells with a short-hairpin-RNA (shRNA) library highly enriched for human kinases and phosphatases. We identified 14 new proteins essential for HIV-1 replication that do not affect cell viability. These proteins are described to be involved in MAPK, JNK and ERK pathways, vesicular traffic and DNA repair. Moreover, we show that the proteins under study are important in an early step of HIV-1 infection before viral integration, whereas some of them affect viral transcription/translation. This study brings new insights for the complex interplay of HIV-1/host cell and opens new possibilities for antiviral strategies

Science Priorities for the Extraction of the Solid MSR Samples from their Sample Tubes NASA-ESA Mars Rock Team

editorial reviewedPreservation of the chemical and structural integrity of samples that will be brought back from Mars is paramount to achieving the scientific objectives of MSR. Given our knowledge of the nature of the samples retrieved at Jezero by Perseverance, at least two options need to be tested for opening the sample tubes: (1) One or two radial cuts at the end of the tube to slide the sample out. (2) Two radial cuts at the ends of the tube and two longitudinal cuts to lift the upper half of the tube and access the sample. Strategy 1 will likely minimize contamination but incurs the risk of affecting the physical integrity of weakly consolidated samples. Strategy 2 will be optimal for preserving the physical integrity of the samples but increases the risk of contamination and mishandling of the sample as more manipulations and additional equipment will be needed. A flexible approach to opening the sample tubes is therefore required, and several options need to be available, depending on the nature of the rock samples returned. Both opening strategies 1 and 2 may need to be available when the samples are returned to handle different sample types (e.g., loosely bound sediments vs. indurated magmatic rocks). This question should be revisited after engineering tests are performed on analogue samples. The MSR sample tubes will have to be opened under stringent BSL4 conditions and this aspect needs to be integrated into the planning

Caveolin contributes to the modulation of basal and β-adrenoceptor stimulated function of the adult rat ventricular myocyte by simvastatin: A novel pleiotropic effect

The number of people taking statins is increasing across the globe, highlighting the Importance of fully understanding statins effects on the cardiovascular system. The beneficial impact of statins extends well beyond regression of atherosclerosis to include direct effects on tissues of the cardiovascular system (pleiotropic effects). Pleiotropic effects on the cardiac myocyte are often overlooked. Here we consider the contribution of the caveolin protein, whose expression and cellular distribution is dependent on cholesterol, to statin effects on the cardiac myocyte. Caveolin is a structural and regulatory component of caveolae, and is a key regulator of cardiac contractile function and adrenergic responsiveness. We employed an experimental model in which inhibition of myocyte HMG CoA reductase could be studied in the absence of paracrine influences from non-myocyte cells. Adult rat ventricular myocytes were treated with 10 μM simvastatin for 2 days. Simvastatin treatment reduced myocyte cholesterol, caveolin 3 and caveolar density. Negative inotropic and positive lusitropic effects (with corresponding changes in [Ca2]¡) were seen in statin-treated cells. Simvastatin significantly potentiated the inotropic response to β2-, but not β1-, adrenoceptor stimulation. Under conditions of β2-adrenoceptor stimulation, phosphorylation of phospholamban at Ser16and troponin I at Ser23/24was enhanced with statin treatment. Simvastatin increased NO production without significant effects on eNOS expression or phosphorylation (Ser1177), consistent with the reduced expression of caveolin 3, its constitutive Inhibitor. In conclusion, statin treatment can reduce caveolin 3 expression, with functional consequences consistent with the known role of caveolae in the cardiac cell. These data are likely to be of significance, particularly during the early phases of statin treatment, and in patients with heart failure who have altered ß-adrenoceptor signalling. In addition, as caveolin is ubiquitously expressed and has myriad tissue-specific functions, the impact of statin-dependent changes in caveolin is likely to have many other functional sequelae

Finished Genome of the Fungal Wheat Pathogen Mycosphaerella graminicola Reveals Dispensome Structure, Chromosome Plasticity, and Stealth Pathogenesis.

The plant-pathogenic fungus Mycosphaerella graminicola (asexual stage: Septoria tritici) causes septoria tritici blotch, a disease that greatly reduces the yield and quality of wheat. This disease is economically important in most wheat-growing areas worldwide and threatens global food production. Control of the disease has been hampered by a limited understanding of the genetic and biochemical bases of pathogenicity, including mechanisms of infection and of resistance in the host. Unlike most other plant pathogens, M. graminicola has a long latent period during which it evades host defenses. Although this type of stealth pathogenicity occurs commonly in Mycosphaerella and other Dothideomycetes, the largest class of plant-pathogenic fungi, its genetic basis is not known. To address this problem, the genome of M. graminicolawas sequenced completely. The finished genome contains 21 chromosomes, eight of which could be lost with no visible effect on the fungus and thus are dispensable. This eight-chromosome dispensome is dynamic in field and progeny isolates, is different from the core genome in gene and repeat content, and appears to have originated by ancient horizontal transfer from an unknown donor. Synteny plots of the M. graminicola chromosomes versus those of the only other sequenced Dothideomycete, Stagonospora nodorum, revealed conservation of gene content but not order or orientation, suggesting a high rate of intra-chromosomal rearrangement in one or both species. This observed “mesosynteny” is very different from synteny seen between other organisms. A surprising feature of the M. graminicolagenome compared to other sequenced plant pathogens was that it contained very few genes for enzymes that break down plant cell walls, which was more similar to endophytes than to pathogens. The stealth pathogenesis of M. graminicola probably involves degradation of proteins rather than carbohydrates to evade host defenses during the biotrophic stage of infection and may have evolved from endophytic ancestors

Identification of functional elements and regulatory circuits by Drosophila modENCODE

To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation