Learning to Teach Argumentation: Research and development in the science classroom

The research reported in this study focuses on an investigation into the teaching of argumentation in secondary science classrooms. Over a one-year period, a group of 12 teachers from schools in the greater London area attended a series of workshops to develop materials and strategies to support the teaching of argumentation in scientific contexts. Data were collected at the beginning and end of the year by audio and video recording lessons where the teachers attempted to implement argumentation. To assess the quality of argumentation, analytical tools derived from Toulmin's argument pattern (TAP) were developed and applied to classroom transcripts. Analysis shows there was development in teachers' use of argumentation across the year. Results indicate that the pattern of use of argumentation is teacher-specific, as is the nature of change. To inform future professional development programmes, transcripts of five teachers, three showing a significant change and two no change, were analysed in more detail to identify features of teachers' oral contributions that facilitated and supported argumentation. The analysis showed that all teachers attempted to encourage a variety of processes involved in argumentation and that the teachers whose lessons included the highest quality of argumentation (TAP analysis) also encouraged higher order processes in their teaching. The analysis of teachers' facilitation of argumentation has helped to guide the development of in-service materials and to identify the barriers to learning in the professional development of less experienced teachers

Sensitive detection of glucagon aggregation using amyloid fibril‐specific antibodies

Sensitive detection of protein aggregates is important for evaluating the quality of biopharmaceuticals and detecting misfolded proteins in several neurodegenerative diseases. However, it is challenging to detect extremely low concentrations (20 times more sensitive than detection using a conventional, amyloid‐specific fluorescent dye (Thioflavin T). We expect that this type of sensitive immunoassay can be readily integrated into the drug development process to improve the generation of safe and potent peptide therapeutics.Sensitive detection of protein aggregates is important for evaluating the quality of biopharmaceuticals and detecting misfolded proteins in several neurodegenerative diseases. However, it is challenging to detect extremely low concentrations (20 times more sensitive than conventional methods for detecting glucagon fibrils.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150615/1/bit26994_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150615/2/bit26994.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150615/3/bit26994-sup-0001-Supporting_Information__submission_.pd

Ryanodine receptor and FK506 binding protein 1 in the Atlantic killifish (Fundulus heteroclitus) : a phylogenetic and population-based comparison

Author Posting. © The Author(s), 2017. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Aquatic Toxicology 192 (2017): 105-115, doi:10.1016/j.aquatox.2017.09.002.Non-dioxin-like polychlorinated biphenyls (NDL PCBs) activate ryanodine receptors (RyR), microsomal Ca2+ channels of broad significance. Teleost fish may be important models for NDL PCB neurotoxicity, and we used sequencing databases to characterize teleost RyR and FK506 binding protein 12 or 12.6 kDa (genes FKBP1A; FKBP1B), which promote NDL PCB-triggered Ca2+ dysregulation. Particular focus was placed on describing genes in the Atlantic killifish (Fundulus heteroclitus) genome and searching available RNA-sequencing datasets for single nucleotide variants (SNV) between PCB tolerant killifish from New Bedford Harbor (NBH) versus sensitive killifish from Scorton Creek (SC), MA. Consistent with the teleost whole genome duplication (tWGD), killifish have six RyR genes, corresponding to a and b paralogs of mammalian RyR1, 2 and 3. The presence of six RyR genes was consistent in all teleosts investigated including zebrafish. Killifish have four FKBP1; one FKBP1b and three FKBP1a named FKBP1aa, FKBP1ab, likely from the tWGD and a single gene duplicate FKBP1a3 suggested to have arisen in Atherinomorphae. The RyR and FKBP1 genes displayed tissue and developmental stage-specific mRNA expression, and the previously uncharacterized RyR3, herein named RyR3b, and all FKBP1 genes were prominent in brain. We identified a SNV in RyR3b encoding missense mutation E1458D. In NBH killifish, 57% were heterozygous and 28% were homozygous for this SNV, whereas almost all SC killifish (94%) lacked the variant (n≥39 per population). The outlined sequence differences between mammalian and teleost RyR and FKBP1 together with outlined population differences in SNV frequency may contribute to our understanding of NDL PCB neurotoxicity.This research was supported by the KC Donnelly Research Externship made possible by the National Institute of Environmental Health Sciences’ Superfund Research Program (EBH) and the Superfund Research Programs at UC Davis (INP and EBH; P42ES004699) and Boston University (JJS, JVG, MEH, SIK; P42ES007381). Additional support was provided by the National Institute of Health (INP; R01 ES014901; and P01 AR052354) and by National Science Foundation collaborative research grants (MEH and SIK; DEB-1265282 and DEB-1120263). This research was also supported in part by an appointment (to BC) with the Postdoctoral Research Program at the U.S. Environmental Protection (US EPA) Office of Research and Development administered by the Oak Ridge Institute for Science and Education (ORISE) through Interagency Agreement No. DW92429801 between the U.S. Department of Energy and the US EPA

Comparative analysis of homology models of the Ah receptor ligand binding domain: Verification of structure-function predictions by site-directed mutagenesis of a nonfunctional receptor

The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that mediates the biological and toxic effects of a wide variety of structurally diverse chemicals, including the toxic environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). While significant interspecies differences in AHR ligand binding specificity, selectivity, and response have been observed, the structural determinants responsible for those differences have not been determined, and homology models of the AHR ligand-binding domain (LBD) are available for only a few species. Here we describe the development and comparative analysis of homology models of the LBD of 16 AHRs from 12 mammalian and nonmammalian species and identify the specific residues contained within their ligand binding cavities. The ligand-binding cavity of the fish AHR exhibits differences from those of mammalian and avian AHRs, suggesting a slightly different TCDD binding mode. Comparison of the internal cavity in the LBD model of zebrafish (zf) AHR2, which binds TCDD with high affinity, to that of zfAHR1a, which does not bind TCDD, revealed that the latter has a dramatically shortened binding cavity due to the side chains of three residues (Tyr296, Thr386, and His388) that reduce the amount of internal space available to TCDD. Mutagenesis of two of these residues in zfAHR1a to those present in zfAHR2 (Y296H and T386A) restored the ability of zfAHR1a to bind TCDD and to exhibit TCDD-dependent binding to DNA. These results demonstrate the importance of these two amino acids and highlight the predictive potential of comparative analysis of homology models from diverse species. The availability of these AHR LBD homology models will facilitate in-depth comparative studies of AHR ligand binding and ligand-dependent AHR activation and provide a novel avenue for examining species-specific differences in AHR responsiveness. © 2013 American Chemical Society

Vitamin K Antagonists, Non-Vitamin K Antagonist Oral Anticoagulants, and Vascular Calcification in Patients with Atrial Fibrillation

Background  Vitamin K antagonists (VKAs) are associated with coronary artery calcification in low-risk populations, but their effect on calcification of large arteries remains uncertain. The effect of non-vitamin K antagonist oral anticoagulants (NOACs) on vascular calcification is unknown. We investigated the influence of use of VKA and NOAC on calcification of the aorta and aortic valve. Methods  In patients with atrial fibrillation without a history of major adverse cardiac or cerebrovascular events who underwent computed tomographic angiography, the presence of ascending aorta calcification (AsAC), descending aorta calcification (DAC), and aortic valve calcification (AVC) was determined. Confounders for VKA/NOAC treatment were identified and propensity score adjusted logistic regression explored the association between treatment and calcification (Agatston score > 0). AsAC, DAC, and AVC differences were assessed in propensity score-matched groups. Results  Of 236 patients (33% female, age: 58 ± 9 years), 71 (30%) used VKA (median duration: 122 weeks) and 79 (34%) used NOAC (median duration: 16 weeks). Propensity score-adjusted logistic regression revealed that use of VKA was significantly associated with AsAC (odds ratio [OR]: 2.31; 95% confidence interval [CI]: 1.16-4.59; p  = 0.017) and DAC (OR: 2.38; 95% CI: 1.22-4.67; p  = 0.012) and a trend in AVC (OR: 1.92; 95% CI: 0.98-3.80; p  = 0.059) compared with non-anticoagulation. This association was absent in NOAC versus non-anticoagulant (AsAC OR: 0.51; 95% CI: 0.21-1.21; p  = 0.127; DAC OR: 0.80; 95% CI: 0.36-1.76; p  = 0.577; AVC OR: 0.62; 95% CI: 0.27-1.40; p  = 0.248). A total of 178 patients were propensity score matched in three pairwise comparisons. Again, use of VKA was associated with DAC ( p  = 0.043) and a trend toward more AsAC ( p  = 0.059), while use of NOAC was not (AsAC p  = 0.264; DAC p  = 0.154; AVC p  = 0.280). Conclusion  This cross-sectional study shows that use of VKA seems to contribute to vascular calcification. The calcification effect was not observed in NOAC users

The landscape of extreme genomic variation in the highly adaptable Atlantic killifish

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Genome Biology and Evolution 9 (2017): 659-676, doi:10.1093/gbe/evx023.Understanding and predicting the fate of populations in changing environments require knowledge about the mechanisms that support phenotypic plasticity and the adaptive value and evolutionary fate of genetic variation within populations. Atlantic killifish (Fundulus heteroclitus) exhibit extensive phenotypic plasticity that supports large population sizes in highly fluctuating estuarine environments. Populations have also evolved diverse local adaptations. To yield insights into the genomic variation that supports their adaptability, we sequenced a reference genome and 48 additional whole genomes from a wild population. Evolution of genes associated with cell cycle regulation and apoptosis is accelerated along the killifish lineage, which is likely tied to adaptations for life in highly variable estuarine environments. Genome-wide standing genetic variation, including nucleotide diversity and copy number variation, is extremely high. The highest diversity genes are those associated with immune function and olfaction, whereas genes under greatest evolutionary constraint are those associated with neurological, developmental, and cytoskeletal functions. Reduced genetic variation is detected for tight junction proteins, which in killifish regulate paracellular permeability that supports their extreme physiological flexibility. Low-diversity genes engage in more regulatory interactions than high-diversity genes, consistent with the influence of pleiotropic constraint on molecular evolution. High genetic variation is crucial for continued persistence of species given the pace of contemporary environmental change. Killifish populations harbor among the highest levels of nucleotide diversity yet reported for a vertebrate species, and thus may serve as a useful model system for studying evolutionary potential in variable and changing environments.This work was primarily supported by a grant from the National Science Foundation (collaborative research grants DEB-1265282, DEB-1120512, DEB-1120013, DEB-1120263, DEB-1120333, DEB-1120398 to J.K.C., D.L.C., M.E.H., S.I.K., M.F.O., J.R.S., W.W., and A.W.). Further support was provided by the National Institute of Environmental Health Sciences (1R01ES021934-01 to A.W., P42ES7373 to T.H.H., P42ES007381 to M.E.H., and R01ES019324 to J.R.S.), the National Institute of General Medical Sciences (P20GM103423 and P20GM104318 to B.L.K.), and the National Science Foundation (DBI-0640462 and XSEDE-MCB100147 to D.G.)

Non-invasive ventilation in patients with an altered level of consciousness. A clinical review and practical insights

Non-invasive ventilation has gained an increasingly pivotal role in the treatment of acute hypoxemic and/or hypercapnic respira-tory failure and offers multiple advantages over invasive mechanical ventilation. Some of these advantages include the preserva-tion of airway defense mechanisms, a reduced need for sedation, and an avoidance of complications related to endotracheal intubation.Despite its advantages, non-invasive ventilation has some contraindications that include, among them, severe encephalopathy. In this review article, the rationale, evidence, and drawbacks of the use of noninvasive ventilation in the context of hypercapnic and non-hypercapnic patients with an altered level of consciousness are analyzed

Brain function assessment in different conscious states

Background: The study of brain functioning is a major challenge in neuroscience fields as human brain has a dynamic and ever changing information processing. Case is worsened with conditions where brain undergoes major changes in so-called different conscious states. Even though the exact definition of consciousness is a hard one, there are certain conditions where the descriptions have reached a consensus. The sleep and the anesthesia are different conditions which are separable from each other and also from wakefulness. The aim of our group has been to tackle the issue of brain functioning with setting up similar research conditions for these three conscious states.Methods: In order to achieve this goal we have designed an auditory stimulation battery with changing conditions to be recorded during a 40 channel EEG polygraph (Nuamps) session. The stimuli (modified mismatch, auditory evoked etc.) have been administered both in the operation room and the sleep lab via Embedded Interactive Stimulus Unit which was developed in our lab. The overall study has provided some results for three domains of consciousness. In order to be able to monitor the changes we have incorporated Bispectral Index Monitoring to both sleep and anesthesia conditions.Results: The first stage results have provided a basic understanding in these altered states such that auditory stimuli have been successfully processed in both light and deep sleep stages. The anesthesia provides a sudden change in brain responsiveness; therefore a dosage dependent anesthetic administration has proved to be useful. The auditory processing was exemplified targeting N1 wave, with a thorough analysis from spectrogram to sLORETA. The frequency components were observed to be shifting throughout the stages. The propofol administration and the deeper sleep stages both resulted in the decreasing of N1 component. The sLORETA revealed similar activity at BA7 in sleep (BIS 70) and target propofol concentration of 1.2 μg/mL.Conclusions: The current study utilized similar stimulation and recording system and incorporated BIS dependent values to validate a common approach to sleep and anesthesia. Accordingly the brain has a complex behavior pattern, dynamically changing its responsiveness in accordance with stimulations and states. © 2010 Ozgoren et al; licensee BioMed Central Ltd