INVESTIGATING HOW TIMING OF CASE STUDY PRESENTATION ON HUNTINGTON DISEASE INFLUENCES CONSTRUCTION OF ARGUMENT WARRANT WHILE LEARNING THE CENTRAL DOGMA OF MOLECULAR BIOLOGY

A common belief among pre-medical and medical students is that biochemistry is not relevant to practicing medicine. Among topics commonly taught in biochemistry, courses include the Central Dogma of Molecular Biology, which is among the most critical science topics taught to medical students by biochemistry educators. Perceived irrelevance among students may be due to common curricular trends in biochemistry education. Many biochemistry courses are found at Research I (R1) universities that teach biochemistry using traditional lectures with little evidence of supporting learning with real-world applications. Instructors commonly assume that students can make realworld connections independently during lecture courses, but it is difficult for students to establish such connections unless explicit examples are available. The objective of this dissertation is to find how the timing of a medical case study presentation can support learning the Central Dogma of Molecular Biology among undergraduate learners. Specifically, the dissertation seeks to identify how real-world learning situations can support students’ reasoning skills while constructing scientific arguments. This dissertation utilized a mixed-methods approach to analyze learning outcomes and reasoning during argument construction in an advanced genetics course at an R1 university that utilizes case studies. A published medical case reported on the diagnosis of Huntington Disease in a child was provided to students (n=19). Students were able to select if they wanted to review the case study before or during class. The CBL+ group reviewed the case study before class, and the CBL- group was presented the case study during class. Overall, there was no significant difference in preand posttest scores using the Central Dogma Concept Inventory and self-efficacy between CBL+ and CBL- groups. However, learning gains were present in additional open-response tasks added to the pre- and post- tests. Students demonstrated foundational knowledge about the Central Dogma of Molecular Biology, and it appears that foundational knowledge remained consistent, but the CBL+ group began to develop a deeper understanding. The case study appeared to support both groups in applying the Central Dogma to real-world scenarios, but similar to trends in establishing foundational knowledge, the CBL+ group began to demonstrate deeper learning. Students’ small group discussion and written pre- and post- test responses were analyzed to observe argumentation. The CBL+ group tended to construct complete arguments on their posttest responses, with a noticeable increase of argument warrants compared to the CBL- group, in addition to more detailed supporting arguments. While argumentation was less frequently observed during small group discussion, no instances of argumentation were observed in the CBL- small group discussion. When students were asked to apply the Central Dogma of Molecular Biology to Huntington Disease, many students demonstrated increased understanding. Students in the CBL+ group demonstrated increased instances on argument construction and reasoning. In contrast, the CBL- group experienced minimal student interaction. Case studies appear to support student learning, but the timing of case study presentation influences argument construction and learning interactions among peers

Comparison of Destructive Wind Forces of Hurricane Irma and Other Hurricanes Impacting NASA Kennedy Space Center, 2004-2017

Hurricane Irma produced sustained hurricane force winds (lowest altitude occurrence at 54-ft) resulting in facility damage at Kennedy Space Center (KSC) on September 10-11, 2017. Irma's large destructive wind footprint also caused significant wind damage across the adjacent communities within Brevard County. Wind damage was augmented by frequent gusts of higher magnitude, along with several embedded tornadoes. Hurricanes have previously impacted and produced significant wind damage to infrastructure at KSC as a result of kinetic energy dissipated, in part, through contact with man-made structures. This paper is intended to provide information specific to the destructive force of Hurricane Irma's sustained winds and previous hurricanes of 2004, 2005 and 2016 as calculated from sustained 10 meters per second wind speeds measured from wind towers at KSC for the onset and cessation of destructive forces. Other factors such as pre-existing condition of impacted infrastructure, upstream structures causing turbulent wind patterns, and associated severe convective weather, are contributing factors but are not analyzed here

The Phenotypic Effects of Royal Jelly on Wild-Type \u3cem\u3eD. melanogaster\u3c/em\u3e Are Strain-Specific

The role for royal jelly (RJ) in promoting caste differentiation of honeybee larvae into queens rather than workers is well characterized. A recent study demonstrated that this poorly understood complex nutrition drives strikingly similar phenotypic effects in Drosophila melanogaster, such as increased body size and reduced developmental time, making possible the use of D. melanogaster as a model system for the genetic analysis of the cellular mechanisms underlying RJ and caste differentiation. We demonstrate here that RJ increases the body size of some wild-type strains of D. melanogaster but not others, and report significant delays in developmental time in all flies reared on RJ. These findings suggest that cryptic genetic variation may be a factor in the D. melanogaster response to RJ, and should be considered when attempting to elucidate response mechanisms to environmental changes in non-honeybee species

Sulfur degassing at Erta Ale (Ethiopia) and Masaya (Nicaragua) volcanoes: Implications for degassing processes and oxygen fugacities of basaltic systems

We investigate the relationship between sulfur and oxygen fugacity at Erta Ale and Masaya volcanoes. Oxygen fugacity was assessed utilizing Fe3+/∑Fe and major element compositions measured in olivine‐hosted melt inclusions and matrix glasses. Erta Ale melts have Fe3+/∑Fe of 0.15–0.16, reflecting fO2 of ΔQFM 0.0 ± 0.3, which is indistinguishable from fO2 calculated from CO2/CO ratios in high‐temperature gases. Masaya is more oxidized at ΔQFM +1.7 ± 0.4, typical of arc settings. Sulfur isotope compositions of gases and scoria at Erta Ale (δ34Sgas − 0.5‰; δ34Sscoria + 0.9‰) and Masaya (δ34Sgas + 4.8‰; δ34Sscoria + 7.4‰) reflect distinct sulfur sources, as well as isotopic fractionation during degassing (equilibrium and kinetic fractionation effects). Sulfur speciation in melts plays an important role in isotope fractionation during degassing and S6+/∑S is 0.67 in Masaya melt inclusions. No change is observed in Fe3+/∑Fe or S6+/∑S with extent of S degassing at Erta Ale, indicating negligible effect on fO2, and further suggesting that H2S is the dominant gas species exsolved from the S2−‐rich melt (i.e., no redistribution of electrons). High SO2/H2S observed in Erta Ale gas emissions is due to gas re‐equilibration at low pressure and fixed fO2. Sulfur budget considerations indicate that the majority of S injected into the systems is emitted as gas, which is therefore representative of the magmatic S isotope composition. The composition of the Masaya gas plume (+4.8‰) cannot be explained by fractionation effects but rather reflects recycling of high δ34S oxidized sulfur through the subduction zone

Lysosomal Dysfunction Promotes Cleavage and Neurotoxicity of Tau In Vivo

Article Number: e1001026Peer reviewe

Argonaute Utilization for miRNA Silencing Is Determined by Phosphorylation-Dependent Recruitment of LIM-Domain-Containing Proteins

As core components of the microRNA-induced silencing complex (miRISC), Argonaute (AGO) proteins interact with TNRC6 proteins, recruiting other effectors of translational repression/mRNA destabilization. Here, we show that LIMD1 coordinates the assembly of an AGO-TNRC6 containing miRISC complex by binding both proteins simultaneously at distinct interfaces. Phosphorylation of AGO2 at Ser 387 by Akt3 induces LIMD1 binding, which in turn enables AGO2 to interact with TNRC6A and downstream effector DDX6. Conservation of this serine in AGO1 and 4 indicates this mechanism may be a fundamental requirement for AGO function and miRISC assembly. Upon CRISPR-Cas9-mediated knockout of LIMD1, AGO2 miRNA-silencing function is lost and miRNA silencing becomes dependent on a complex formed by AGO3 and the LIMD1 family member WTIP. The switch to AGO3 utilization occurs due to the presence of a glutamic acid residue (E390) on the interaction interface, which allows AGO3 to bind to LIMD1, AJUBA, and WTIP irrespective of Akt signaling

Border collapse and boundary maintenance: militarisation and the micro-geographies of violence in Israel–Palestine

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Drawing upon subaltern geopolitics and feminist geography, this article explores how militarisation shapes micro-geographies of violence and occupation in Israel–Palestine. While accounts of spectacular and large-scale political violence dominate popular imaginaries and academic analyses in/of the region, a shift to the micro-scale foregrounds the relationship between power, politics and space at the level of everyday life. In the context of Israel–Palestine, micro-geographies have revealed dynamic strategies for ‘getting by’ or ‘dealing with’ the occupation, as practiced by Palestinian populations in the face of spatialised violence. However, this article considers how Jewish Israelis actively shape the spatial micro-politics of power within and along the borders of the Israeli state. Based on 12 months of ethnographic research in Tel Aviv and West Jerusalem during 2010–2011, an analysis of everyday narratives illustrates how relations of violence, occupation and domination rely upon gendered dynamics of border collapse and boundary maintenance. Here, the borders between home front and battlefield break down at the same time as communal boundaries are reproduced, generating conditions of ‘total militarism’ wherein military interests and agendas are both actively and passively diffused. Through gendering the militarised micro-geographies of violence among Jewish Israelis, this article reveals how individuals construct, navigate and regulate the everyday spaces of occupation, detailing more precisely how macro political power endures.This work was supported by the SOAS, University of London; University of London Central Research Fund

A Common Allele in FGF21 Associated with Sugar Intake Is Associated with Body Shape, Lower Total Body-Fat Percentage, and Higher Blood Pressure

Summary: Fibroblast growth factor 21 (FGF21) is a hormone that has insulin-sensitizing properties. Some trials of FGF21 analogs show weight loss and lipid-lowering effects. Recent studies have shown that a common allele in the FGF21 gene alters the balance of macronutrients consumed, but there was little evidence of an effect on metabolic traits. We studied a common FGF21 allele (A:rs838133) in 451,099 people from the UK Biobank study, aiming to use the human allele to inform potential adverse and beneficial effects of targeting FGF21. We replicated the association between the A allele and higher percentage carbohydrate intake. We then showed that this allele is more strongly associated with higher blood pressure and waist-hip ratio, despite an association with lower total body-fat percentage, than it is with BMI or type 2 diabetes. These human phenotypes of variation in the FGF21 gene will inform research into FGF21’s mechanisms and therapeutic potential. : Drugs targeting the hormone FGF21 may have beneficial health effects. Variations in human DNA in the FGF21 gene provide an indication of what those effects may be. Here, we show that variation in the FGF21 gene is associated with higher blood pressure and altered body shape, despite lower total body-fat percentage. Keywords: FGF21, BMI, waist-hip ratio, blood pressure, body fat, allele, genetic variant, UK Bioban

A HIF-LIMD1 negative feedback mechanism mitigates the pro-tumorigenic effects of hypoxia

The adaptive cellular response to low oxygen tensions is mediated by the hypoxia inducible factors (HIFs), a family of heterodimeric transcription factors composed of HIF-α and β subunits. Prolonged HIF expression is a key contributor to cellular transformation, tumourigenesis and metastasis. As such, HIF degradation under hypoxic conditions is an essential homeostatic and tumour suppressive mechanism. LIMD1 complexes with PHD2 and VHL in physiological oxygen levels (normoxia) to facilitate proteasomal degradation of the HIF-α subunit. Here, we identify LIMD1 as a HIF-1 target gene, which mediates a previously uncharacterised, negative regulatory feedback mechanism for hypoxic HIF-α degradation by modulating PHD2-LIMD1- VHL complex formation. Hypoxic induction of LIMD1 expression results in increased HIF-α protein degradation, inhibiting HIF-1 target-gene expression, tumour growth and vascularisation. Furthermore, we report that copy number variation at the LIMD1 locus occurs in 47.1% of lung adenocarcinoma patients, correlates with enhanced expression of a HIF target gene signature and is a negative prognostic indicator. Taken together, our data open a new field of research into the aetiology, diagnosis and prognosis of LIMD1-negative lung cancers