“Science is not my thing”: Exploring deaf non-science majors’ science identities

Students who are deaf and hard-of-hearing are underrepresented in science majors, yet we know little about why. Students from other underrepresented groups in science—women and people of color—tend to highly value altruistic or communal career goals, while perceiving science as uncommunal. Research suggests that holding stereotypical conceptions about scientists and perceptions of science as uncommunal may strongly hinder recruitment into science majors. This study sought to explore the science identities of students who are deaf, hard-of-hearing, and hearing signers. The study focused on non-science majors in bilingual (American Sign Language and written English) biology laboratory courses. This study is the first step to understanding if stereotypes about scientists and perceptions of science as uncommunal disproportionately affect students who are deaf and hard-of-hearing. Findings suggest that students’ science identities are influenced by stereotypical portrayals of scientists and a preference for people-centered careers, specifically within the Deaf community. Applied research is needed to challenge stereotypes, and identify connections between science and the Deaf community, to support the growth of deaf and hard-of-hearing students’ science identities to increase participation in science careers

Structural Properties of Polyglutamine Aggregates Investigated via Molecular Dynamics Simulations

Polyglutamine (polyQ) beta-stranded aggregates constitute the hallmark of Huntington disease. The disease is fully penetrant when Q residues are more than 36-40 ("disease threshold"). Here, based on a molecular dynamics study on polyQ helical structures of different shapes and oligomeric states, we suggest that the stability of the aggregates increases with the number of monomers, while it is rather insensitive to the number of Qs in each monomer. However, the stability of the single monomer does depend on the number of side-chain intramolecular H-bonds, and therefore oil the number of Qs. If such number is lower than that of the disease threshold, the beta-stranded monomers are unstable and hence may aggregate with lower probability, consistently with experimental findings. Our results provide a possible interpretation of the apparent polyQ length dependent-toxicity, and they do not support the so-called "structural threshold hypothesis", which supposes a transition from random coil to a beta-sheet structure only above the disease threshold

Polyglutamine Induced Misfolding of Huntingtin Exon1 is Modulated by the Flanking Sequences

Polyglutamine (polyQ) expansion in exon1 (XN1) of the huntingtin protein is linked to Huntington's disease. When the number of glutamines exceeds a threshold of approximately 36–40 repeats, XN1 can readily form amyloid aggregates similar to those associated with disease. Many experiments suggest that misfolding of monomeric XN1 plays an important role in the length-dependent aggregation. Elucidating the misfolding of a XN1 monomer can help determine the molecular mechanism of XN1 aggregation and potentially help develop strategies to inhibit XN1 aggregation. The flanking sequences surrounding the polyQ region can play a critical role in determining the structural rearrangement and aggregation mechanism of XN1. Few experiments have studied XN1 in its entirety, with all flanking regions. To obtain structural insights into the misfolding of XN1 toward amyloid aggregation, we perform molecular dynamics simulations on monomeric XN1 with full flanking regions, a variant missing the polyproline regions, which are hypothesized to prevent aggregation, and an isolated polyQ peptide (Qn). For each of these three constructs, we study glutamine repeat lengths of 23, 36, 40 and 47. We find that polyQ peptides have a positive correlation between their probability to form a β-rich misfolded state and their expansion length. We also find that the flanking regions of XN1 affect its probability to^x_page_count=28 form a β-rich state compared to the isolated polyQ. Particularly, the polyproline regions form polyproline type II helices and decrease the probability of the polyQ region to form a β-rich state. Additionally, by lengthening polyQ, the first N-terminal 17 residues are more likely to adopt a β-sheet conformation rather than an α-helix conformation. Therefore, our molecular dynamics study provides a structural insight of XN1 misfolding and elucidates the possible role of the flanking sequences in XN1 aggregation

Are Long-Range Structural Correlations Behind the Aggregration Phenomena of Polyglutamine Diseases?

We have characterized the conformational ensembles of polyglutamine peptides of various lengths (ranging from to ), both with and without the presence of a C-terminal polyproline hexapeptide. For this, we used state-of-the-art molecular dynamics simulations combined with a novel statistical analysis to characterize the various properties of the backbone dihedral angles and secondary structural motifs of the glutamine residues. For (i.e., just above the pathological length for Huntington's disease), the equilibrium conformations of the monomer consist primarily of disordered, compact structures with non-negligible -helical and turn content. We also observed a relatively small population of extended structures suitable for forming aggregates including - and -strands, and - and -hairpins. Most importantly, for we find that there exists a long-range correlation (ranging for at least residues) among the backbone dihedral angles of the Q residues. For polyglutamine peptides below the pathological length, the population of the extended strands and hairpins is considerably smaller, and the correlations are short-range (at most residues apart). Adding a C-terminal hexaproline to suppresses both the population of these rare motifs and the long-range correlation of the dihedral angles. We argue that the long-range correlation of the polyglutamine homopeptide, along with the presence of these rare motifs, could be responsible for its aggregation phenomena