67 research outputs found

    Benefits of a College STEM Faculty Development Initiative: Instructors Report Increased and Sustained Implementation of Research-Based Instructional Strategies

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    The Summer Institutes on Scientific Teaching (SI) is a faculty development workshop in which science, technology, engineering, and mathematics (STEM) instructors, particularly from biology, are trained in the Scientific Teaching (ST) pedagogy. While participants have generally reported positive experiences, we aimed to assess how the SI affected participants’ teaching practices. Building on a previously developed taxonomy of ST practices, we surveyed SI participants from the 2004–2014 SI classes regarding specific ST practices. Participants’ self-reported use and implementation of ST practices increased immediately after SI attendance as well as over a longer time frame, suggesting that implementation persisted and even increased with time. However, instructors reported implementation gains for some practices more than others. The practices with the highest gains were engaging students in their own learning, using learning goals in course design, employing formative assessment, developing overarching course learning goals, representing science as a process, and facilitating group discussion activities. We propose that the ST practices showing the greatest gains may serve as beneficial focal points for professional development programs, while practices with smaller gains may require modified dissemination approaches or support structures

    Effects of the small molecule SIRT1 activator, SRT2104 on arterial stiffness in otherwise healthy cigarette smokers and subjects with type 2 diabetes mellitus

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    Objective: Arterial stiffness increases with age, and is associated with adverse cardiovascular outcome including increased mortality. The effect of the oral small molecule SIRT1 activator, SRT2104, on arterial stiffness was examined in otherwise healthy cigarette smokers and participants with type 2 diabetes mellitus. Methods: 24 otherwise healthy cigarette smokers and 15 people with stable type 2 diabetes were randomised in a double-blind placebo-controlled crossover trial and received 28 days of oral SRT2104 (2.0 g/day) or matched placebo. Blood pressure was measured using non-invasive oscillatory sphygmomanometry. Pulse wave analysis and velocity were measured using applanation tonometry at baseline and the end of each treatment period. Owing to the small sample size and similar trends for both groups, data for the two groups were pooled (post hoc analysis). Results: Compared to placebo, treatment with SRT2104 was associated with a significant reduction in augmentation pressure (p=0.0273) and a trend towards improvement in the augmentation index and corrected augmentation index (p>0.05 for both). However, no changes were observed in pulse wave velocity and time to wave reflection (p>0.05). Systolic and diastolic blood pressures remained unchanged throughout the study. Treatment by cohort interaction was not significant for any of the pulse wave parameters, suggesting that the response to SRT2104 in otherwise healthy smokers and people with diabetes was consistent. Conclusions: SRT2104 may improve measures of arterial stiffness in otherwise healthy cigarette smokers and in participants with type 2 diabetes. Definitive conclusions are not possible given the small sample size and exploratory nature of this analysis. Trial registration number: NCT01031108

    Cardiovascular effects of a novel SIRT1 activator, SRT2104, in otherwise healthy cigarette smokers

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    Background: We examined the effect of the oral SIRT1 activator SRT2104 on cardiovascular function in otherwise healthy cigarette smokers. Methods and Results: Twenty‐four otherwise healthy cigarette smokers participated in a randomized double‐blind, placebo‐controlled crossover trial and received 28 days of oral SRT2104 (2.0 g/day) or matched placebo. Plasma SRT2104 concentrations, serum lipid profile, plasma fibrinolytic factors, and markers of platelet and monocyte activation were measured at baseline and at the end of each treatment period together with an assessment of forearm blood flow during intra‐arterial bradykinin, acetylcholine, and sodium nitroprusside infusions. Three hours postdose, mean plasma SRT2104 concentration was 1328±748 ng/mL after 28 days of active treatment. Compared with placebo, serum lipid profile improved during SRT2104 administration, with reductions in serum total cholesterol (−11.6±20 versus 6±21 mg/dL), low‐density lipoprotein cholesterol (−10±17 versus 3±21 mg/dL), and triglyceride (−39.8±77 versus 13.3±57 mg/dL) concentrations (P<0.05 for all). All vasodilators produced a dose‐dependent increase in blood flow (P<0.0001) that was similar during each treatment period (P>0.05 for all). No significant differences in fibrinolytic or blood flow parameters were observed between placebo and SRT2014. Conclusions: SRT2104 appears to be safe and well tolerated and associated with an improved lipid profile without demonstrable differences in vascular or platelet function in otherwise healthy cigarette smokers

    Climate Process Team on internal wave–driven ocean mixing

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    Author Posting. © American Meteorological Society, 2017. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Bulletin of the American Meteorological Society 98 (2017): 2429-2454, doi:10.1175/BAMS-D-16-0030.1.Diapycnal mixing plays a primary role in the thermodynamic balance of the ocean and, consequently, in oceanic heat and carbon uptake and storage. Though observed mixing rates are on average consistent with values required by inverse models, recent attention has focused on the dramatic spatial variability, spanning several orders of magnitude, of mixing rates in both the upper and deep ocean. Away from ocean boundaries, the spatiotemporal patterns of mixing are largely driven by the geography of generation, propagation, and dissipation of internal waves, which supply much of the power for turbulent mixing. Over the last 5 years and under the auspices of U.S. Climate Variability and Predictability Program (CLIVAR), a National Science Foundation (NSF)- and National Oceanic and Atmospheric Administration (NOAA)-supported Climate Process Team has been engaged in developing, implementing, and testing dynamics-based parameterizations for internal wave–driven turbulent mixing in global ocean models. The work has primarily focused on turbulence 1) near sites of internal tide generation, 2) in the upper ocean related to wind-generated near inertial motions, 3) due to internal lee waves generated by low-frequency mesoscale flows over topography, and 4) at ocean margins. Here, we review recent progress, describe the tools developed, and discuss future directions.We are grateful to U.S. CLIVAR for their leadership in instigating and facilitating the Climate Process Team program. We are indebted to NSF and NOAA for sponsoring the CPT series.2018-06-0

    Climate Process Team on Internal-Wave Driven Ocean Mixing

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    Diapycnal mixing plays a primary role in the thermodynamic balance of the ocean, and consequently, in oceanic heat and carbon uptake and storage. Though observed mixing rates are on average consistent with values required by inverse models, recent attention has focused on the dramatic spatial variability, spanning several orders of magnitude, of mixing rates in both the upper and deep ocean. Climate models have been shown to be very sensitive not only to the overall level but to the detailed distribution of mixing; sub-grid-scale parameterizations based on accurate physical processes will allow model forecasts to evolve with a changing climate. Spatio-temporal patterns of mixing are largely driven by the geography of generation, propagation and destruction of internal waves, which are thought to supply much of the power for turbulent mixing. Over the last five years and under the auspices of US CLIVAR, a NSF and NOAA supported Climate Process Team has been engaged in developing, implementing and testing dynamics-base parameterizations for internal-wave driven turbulent mixing in global ocean models. The work has primarily focused on turbulence 1) near sites of internal tide generation, 2) in the upper ocean related to wind-generated near inertial motions, 3) due to internal lee waves generated by low-frequency mesoscale flows over topography, and 4) at ocean margins. Here we review recent progress, describe the tools developed, and discuss future directions

    Structural Elucidation and Functional Characterization of the Hyaloperonospora arabidopsidis Effector Protein ATR13

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    The oomycete Hyaloperonospora arabidopsidis (Hpa) is the causal agent of downy mildew on the model plant Arabidopsis thaliana and has been adapted as a model system to investigate pathogen virulence strategies and plant disease resistance mechanisms. Recognition of Hpa infection occurs when plant resistance proteins (R-genes) detect the presence or activity of pathogen-derived protein effectors delivered to the plant host. This study examines the Hpa effector ATR13 Emco5 and its recognition by RPP13-Nd, the cognate R-gene that triggers programmed cell death (HR) in the presence of recognized ATR13 variants. Herein, we use NMR to solve the backbone structure of ATR13 Emco5, revealing both a helical domain and a disordered internal loop. Additionally, we use site-directed and random mutagenesis to identify several amino acid residues involved in the recognition response conferred by RPP13-Nd. Using our structure as a scaffold, we map these residues to one of two surface-exposed patches of residues under diversifying selection. Exploring possible roles of the disordered region within the ATR13 structure, we perform domain swapping experiments and identify a peptide sequence involved in nucleolar localization. We conclude that ATR13 is a highly dynamic protein with no clear structural homologues that contains two surface-exposed patches of polymorphism, only one of which is involved in RPP13-Nd recognition specificity

    De Novo Transcriptome Sequencing in Anopheles funestus Using Illumina RNA-Seq Technology

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    BACKGROUND: Anopheles funestus is one of the primary vectors of human malaria, which causes a million deaths each year in sub-Saharan Africa. Few scientific resources are available to facilitate studies of this mosquito species and relatively little is known about its basic biology and evolution, making development and implementation of novel disease control efforts more difficult. The An. funestus genome has not been sequenced, so in order to facilitate genome-scale experimental biology, we have sequenced the adult female transcriptome of An. funestus from a newly founded colony in Burkina Faso, West Africa, using the Illumina GAIIx next generation sequencing platform. METHODOLOGY/PRINCIPAL FINDINGS: We assembled short Illumina reads de novo using a novel approach involving iterative de novo assemblies and "target-based" contig clustering. We then selected a conservative set of 15,527 contigs through comparisons to four Dipteran transcriptomes as well as multiple functional and conserved protein domain databases. Comparison to the Anopheles gambiae immune system identified 339 contigs as putative immune genes, thus identifying a large portion of the immune system that can form the basis for subsequent studies of this important malaria vector. We identified 5,434 1:1 orthologues between An. funestus and An. gambiae and found that among these 1:1 orthologues, the protein sequence of those with putative immune function were significantly more diverged than the transcriptome as a whole. Short read alignments to the contig set revealed almost 367,000 genetic polymorphisms segregating in the An. funestus colony and demonstrated the utility of the assembled transcriptome for use in RNA-seq based measurements of gene expression. CONCLUSIONS/SIGNIFICANCE: We developed a pipeline that makes de novo transcriptome sequencing possible in virtually any organism at a very reasonable cost ($6,300 in sequencing costs in our case). We anticipate that our approach could be used to develop genomic resources in a diversity of systems for which full genome sequence is currently unavailable. Our An. funestus contig set and analytical results provide a valuable resource for future studies in this non-model, but epidemiologically critical, vector insect

    EXD2 governs germ stem cell homeostasis and lifespan by promoting mitoribosome integrity and translation

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    Mitochondria are subcellular organelles critical for meeting the bioenergetic and biosynthetic needs of the cell. Mitochondrial function relies on genes and RNA species encoded both in the nucleus and mitochondria, as well as their coordinated translation, import and respiratory complex assembly. Here we describe the characterization of exonuclease domain like 2 (EXD2), a nuclear encoded gene that we show is targeted to the mitochondria and prevents the aberrant association of mRNAs with the mitochondrial ribosome. The loss of EXD2 resulted in defective mitochondrial translation, impaired respiration, reduced ATP production, increased reactive oxygen species and widespread metabolic abnormalities. Depletion of EXD2/CG6744 in D.melanogaster caused developmental delays and premature female germline stem cell attrition, reduced fecundity and a dramatic extension of lifespan that could be reversed with an anti-oxidant diet. Our results define a conserved role for EXD2 in mitochondrial translation that influences development and aging

    Comparative and Functional Genomics of Rhodococcus opacus PD630 for Biofuels Development

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    The Actinomycetales bacteria Rhodococcus opacus PD630 and Rhodococcus jostii RHA1 bioconvert a diverse range of organic substrates through lipid biosynthesis into large quantities of energy-rich triacylglycerols (TAGs). To describe the genetic basis of the Rhodococcus oleaginous metabolism, we sequenced and performed comparative analysis of the 9.27 Mb R. opacus PD630 genome. Metabolic-reconstruction assigned 2017 enzymatic reactions to the 8632 R. opacus PD630 genes we identified. Of these, 261 genes were implicated in the R. opacus PD630 TAGs cycle by metabolic reconstruction and gene family analysis. Rhodococcus synthesizes uncommon straight-chain odd-carbon fatty acids in high abundance and stores them as TAGs. We have identified these to be pentadecanoic, heptadecanoic, and cis-heptadecenoic acids. To identify bioconversion pathways, we screened R. opacus PD630, R. jostii RHA1, Ralstonia eutropha H16, and C. glutamicum 13032 for growth on 190 compounds. The results of the catabolic screen, phylogenetic analysis of the TAGs cycle enzymes, and metabolic product characterizations were integrated into a working model of prokaryotic oleaginy.Cambridge-MIT InstituteMassachusetts Institute of Technology. (Seed Grant program)Shell Oil CompanyNational Institute of Allergy and Infectious Diseases (U.S.)United States. National Institutes of HealthNational Institutes of Health. Department of Health and Human Services (Contract No. HHSN272200900006C
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