Investigative activities for statistics learning with 1st grade Portuguese students

The relevance of data exploration in mathematics programmes at all levels of education led us to develop a learning experience with 1st grade students with the aim of investigating the contribution of investigative activities in the learning of statistics. To achieve this objective, the following research questions were outlined: How do students implement investigative activities when learning statistics? What difficulties do students have in carrying out investigative activities when learning statistics? Adopting a qualitative and interpretative approach, data were collected through students’ written records, the reflections of the teacher, and a written test applied before and after the learning experience. The results obtained suggest that students were able to carry out investigative activities when learning statistics although with some weaknesses, namely defining the topic and research questions, and analysing the data due to the greater complexity of the research proposed by them. Students were able to formulate conclusions, although in some groups the conclusions were underdeveloped. Students were most confident in data collection, organization, and representation activities, with limitations typical of their young age (e.g., written communication). Students also showed difficulties in managing group work and knowledge of statistics, notably concerning strategies of data organization and representation and statistical measures

Fidelity of Phenylalanyl-tRNA Synthetase in Binding the Natural Amino Acids

Aminoacyl-tRNA synthetases guard the fidelity of cognate amino acid incorporation during protein biosynthesis; for example, phenylalanyl-tRNA synthetase (PheRS) activates and transfers only Phe to its tRNA. Since we are interested in using a computational protocol to identify nonnatural amino acids that are incorporated by wild-type PheRS, it is critical to understand the fidelity of PheRS in binding the 20 natural amino acids. To this end, HierDock, a computational protocol for predicting binding sites and relative binding affinities, was used for testing the natural amino acids in PheRS. Scanning the entire ligand-accessible protein surface for the best binding region, we find that HierDock correctly identifies the active site of Phe in PheRS and predicts Phe within 0.61 Å RMSD of the crystal structure. HierDock also successfully shows PheRS discriminates for Phe, as the noncognate amino acids bind less favorably in the binding site of Phe. However, we find that Met, Cys, and Tyr bind competitively but at positions distant from the Phe binding site. This result corroborates in vitro measurements of aminoacyl adenylate formation, which show Met competes with Phe at the amino acid binding stage. We predict that the binding site of Met would not activate PheRS, as the noncognate amino acid cannot establish suitable hydrogen bonds with the PheRS reaction center. These results validate the use of HierDock in predicting the binding sites of the cognate amino acids in PheRS. The HierDock procedure calculates the discrimination of aminoacyl-tRNA synthetases at the stage of binding the cognate amino acid and offers a molecular level understanding of the mistakes made in protein biosynthesis that are not readily uncovered through experiments. This technique is also useful for predicting the binding of a selected nonnatural amino acid analogue, thereby indicating whether the molecule would be incorporated into a wild-type aminoacyl-tRNA synthetase

Test of the Binding Threshold Hypothesis for olfactory receptors: Explanation of the differential binding of ketones to the mouse and human orthologs of olfactory receptor 912-93

We tested the Binding Threshold Hypothesis (BTH) for activation of olfactory receptors (ORs): To activate an OR, the odorant must bind to the OR with binding energy above some threshold value. The olfactory receptor (OR) 912‐93 is known experimentally to be activated by ketones in mouse, but is inactive to ketones in human, despite an amino acid sequence identity of ∼66%. To investigate the origins of this difference, we used the MembStruk first‐principles method to predict the tertiary structure of the mouse OR 912‐93 (mOR912‐93), and the HierDock first‐principles method to predict the binding site for ketones to this receptor. We found that the strong binding of ketones to mOR912‐93 is dominated by a hydrogen bond of the ketone carbonyl group to Ser105. All ketones predicted to have a binding energy stronger than E_(BindThresh) = 26 kcal/mol were observed experimentally to activate this OR, while the two ketones predicted to bind more weakly do not. In addition, we predict that 2‐undecanone and 2‐dodecanone both bind sufficiently strongly to activate mOR912‐93. A similar binding site for ketones was predicted in hOR912‐93, but the binding is much weaker because the human ortholog has a Gly at the position of Ser105. We predict that mutating this Gly to Ser in human should lead to activation of hOR912‐93 by these ketones. Experimental substantiations of the above predictions would provide further tests of the validity of the BTH, our predicted 3D structures, and our predicted binding sites for these ORs

Molecular mechanisms underlying differential odor responses of a mouse olfactory receptor

The prevailing paradigm for G protein-coupled receptors is that each receptor is narrowly tuned to its ligand and closely related agonists. An outstanding problem is whether this paradigm applies to olfactory receptor (ORs), which is the largest gene family in the genome, in which each of 1,000 different G protein-coupled receptors is believed to interact with a range of different odor molecules from the many thousands that comprise “odor space.” Insights into how these interactions occur are essential for understanding the sense of smell. Key questions are: (i) Is there a binding pocket? (ii) Which amino acid residues in the binding pocket contribute to peak affinities? (iii) How do affinities change with changes in agonist structure? To approach these questions, we have combined single-cell PCR results [Malnic, B., Hirono, J., Sato, T. & Buck, L. B. (1999) Cell 96, 713–723] and well-established molecular dynamics methods to model the structure of a specific OR (OR S25) and its interactions with 24 odor compounds. This receptor structure not only points to a likely odor-binding site but also independently predicts the two compounds that experimentally best activate OR S25. The results provide a mechanistic model for olfactory transduction at the molecular level and show how the basic G protein-coupled receptor template is adapted for encoding the enormous odor space. This combined approach can significantly enhance the identification of ligands for the many members of the OR family and also may shed light on other protein families that exhibit broad specificities, such as chemokine receptors and P450 oxidases

A Search for FeH in Hot-Jupiter Atmospheres with High-Dispersion Spectroscopy

Most of the molecules detected thus far in exoplanet atmospheres, such as water and CO, are present for a large range of pressures and temperatures. In contrast, metal hydrides exist in much more specific regimes of parameter space, and so can be used as probes of atmospheric conditions. Iron hydride (FeH) is a dominant source of opacity in low-mass stars and brown dwarfs, and evidence for its existence in exoplanets has recently been observed at low resolution. We performed a systematic search of archival CARMENES near-infrared data for signatures of FeH during transits of 12 exoplanets. These planets span a large range of equilibrium temperatures (600 $\lesssim T_{eq} \lesssim$ 4000K) and surface gravities (2.5 $\lesssim \mathrm{log} g \lesssim$ 3.5). We did not find a statistically significant FeH signal in any of the atmospheres, but obtained potential low-confidence signals (SNR$\sim$3) in two planets, WASP-33b and MASCARA-2b. Previous modeling of exoplanet atmospheres indicate that the highest volume mixing ratios (VMRs) of 10$^{-7}$ to 10$^{-9}$ are expected for temperatures between 1800 and 3000K and log $g \gtrsim3$. The two planets for which we find low-confidence signals are in the regime where strong FeH absorption is expected. We performed injection and recovery tests for each planet and determined that FeH would be detected in every planet for VMRs $\geq 10^{-6}$, and could be detected in some planets for VMRs as low as 10$^{-9.5}$. Additional observations are necessary to conclusively detect FeH and assess its role in the temperature structures of hot Jupiter atmospheres.Comment: Accepted to AAS journal

Responsible Research and Innovation in Science Education: the IRRESISTIBLE Project

The EU funded IRRESISTIBLE-project (Project Coordinator: Jan Apotheker, University of Groningen, Netherlands) develop activities designed to foster the involvement of high school and elementary students and the public in Responsible Research and Innovation (RRI). In the project, awareness about RRI is raised in two ways: increasing content knowledge about research by bringing topics of cutting edge research into the program; fostering a discussion among the students on RRI issues about the topics that are introduced. Responsible Research and Innovation focuses on six key issues: Engagement, Gender equality, Science education, Ethics, including societal relevance and acceptability of research and innovation outcomes , Open access, Governance. The project combines formal and informal teaching to familiarize schoolchildren with science. Sixteen partners in ten countries are involved and coordinated by Science LinX. Each participants will establish a community of learners (CoL). The communities include school teachers together with university experts in the field of science communication and science centre staff. Each CoL will develop materials that the teachers will use at their own schools and students will develop an exhibit for a science centre in their own country. Once they have completed their teaching module, the teachers will each train five colleagues, in using the developed modules from the first year. Ultimately, this project will train almost ten thousand pupils to consider the social impact of scientific research

Frontal sinus mucocele with intracranial and intraorbital extension

ABSTRACT Introduction: Frontal sinus mucoceles can present with a multitude of different symptoms including ophthalmic disturbances. Even benign, they have a tendency to expand by eroding the surrounding bony walls that displaces and destroys structures by pressure and bony resorption. Case report: A 32-year-old man with diplopia, proptosis of the right eye and headache was presented. The diagnosis was frontal sinus mucocele with intracranial and intraorbital extension. Possible clinical manifestations of mucoceles, diagnostic imaging techniques and treatment used are discussed. Conclusion: Frontal mucoceles are benign and curable, early recognition and management of them is of paramount importance, because they can cause local, orbital or intracranial complications

Frontal sinus mucocele with intracranial and intraorbital extension

ABSTRACT Introduction: Frontal sinus mucoceles can present with a multitude of different symptoms including ophthalmic disturbances. Even benign, they have a tendency to expand by eroding the surrounding bony walls that displaces and destroys structures by pressure and bony resorption. Case report: A 32-year-old man with diplopia, proptosis of the right eye and headache was presented. The diagnosis was frontal sinus mucocele with intracranial and intraorbital extension. Possible clinical manifestations of mucoceles, diagnostic imaging techniques and treatment used are discussed. Conclusion: Frontal mucoceles are benign and curable, early recognition and management of them is of paramount importance, because they can cause local, orbital or intracranial complications

Functional variants of human papillomavirus type 16 demonstrate host genome integration and transcriptional alterations corresponding to their unique cancer epidemiology

BACKGROUND: Human papillomaviruses (HPVs) are a worldwide burden as they are a widespread group of tumour viruses in humans. Having a tropism for mucosal tissues, high-risk HPVs are detected in nearly all cervical cancers. HPV16 is the most common high-risk type but not all women infected with high-risk HPV develop a malignant tumour. Likely relevant, HPV genomes are polymorphic and some HPV16 single nucleotide polymorphisms (SNPs) are under evolutionary constraint instigating variable oncogenicity and immunogenicity in the infected host. RESULTS: To investigate the tumourigenicity of two common HPV16 variants, we used our recently developed, three-dimensional organotypic model reminiscent of the natural HPV infectious cycle and conducted various “omics” and bioinformatics approaches. Based on epidemiological studies we chose to examine the HPV16 Asian-American (AA) and HPV16 European Prototype (EP) variants. They differ by three non-synonymous SNPs in the transforming and virus-encoded E6 oncogene where AAE6 is classified as a high- and EPE6 as a low-risk variant. Remarkably, the high-risk AAE6 variant genome integrated into the host DNA, while the low-risk EPE6 variant genome remained episomal as evidenced by highly sensitive Capt-HPV sequencing. RNA-seq experiments showed that the truncated form of AAE6, integrated in chromosome 5q32, produced a local gene over-expression and a large variety of viral-human fusion transcripts, including long distance spliced transcripts. In addition, differential enrichment of host cell pathways was observed between both HPV16 E6 variant-containing epithelia. Finally, in the high-risk variant, we detected a molecular signature of host chromosomal instability, a common property of cancer cells. CONCLUSIONS: We show how naturally occurring SNPs in the HPV16 E6 oncogene cause significant changes in the outcome of HPV infections and subsequent viral and host transcriptome alterations prone to drive carcinogenesis. Host genome instability is closely linked to viral integration into the host genome of HPV-infected cells, which is a key phenomenon for malignant cellular transformation and the reason for uncontrolled E6 oncogene expression. In particular, the finding of variant-specific integration potential represents a new paradigm in HPV variant biology. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3203-3) contains supplementary material, which is available to authorized users