A Story of Bodying In Science Education

In poetic dialogue with BecomingAlivewithinScienceEducation(Research):ThinkingwithLifeHistory(ies),BodiesandStickiness, stories of bodying and body(ies) of work are playfully explored

Autocrine Activation of the MET Receptor Tyrosine Kinase in Acute Myeloid Leukemia

Although the treatment of acute myeloid leukemia (AML) has improved significantly, more than half of all patients develop disease that is refractory to intensive chemotherapy. Functional genomics approaches offer a means to discover specific molecules mediating aberrant growth and survival of cancer cells. Thus, using a loss-of-function RNA interference genomic screen, we identified aberrant expression of the hepatocyte growth factor (HGF) as a critical factor in AML pathogenesis. We found HGF expression leading to autocrine activation of its receptor tyrosine kinase, MET, in nearly half of the AML cell lines and clinical samples studied. Genetic depletion of HGF or MET potently inhibited the growth and survival of HGF-expressing AML cells. However, leukemic cells treated with the specific MET kinase inhibitor crizotinib developed resistance due to compensatory upregulation of HGF expression, leading to restoration of MET signaling. In cases of AML where MET is coactivated with other tyrosine kinases, such as fibroblast growth factor receptor 1 (FGFR1), concomitant inhibition of FGFR1 and MET blocked compensatory HGF upregulation, resulting in sustained logarithmic cell kill both in vitro and in xenograft models in vivo. Our results demonstrate widespread dependence of AML cells on autocrine activation of MET, as well as the importance of compensatory upregulation of HGF expression in maintaining leukemogenic signaling by this receptor. We anticipate that these findings will lead to the design of additional strategies to block adaptive cellular responses that drive compensatory ligand expression as an essential component of the targeted inhibition of oncogenic receptors in human cancers

Narrative approach to understand people's comprehension of acquaintance rape: The role of Sex Role Stereotyping

One of the most unreported crimes is acquaintance rape. This may be the result of people's understanding of what rape is because of their rape script and their stereotypes of victim characteristics. These judgements may be moderated by sex role stereotyping (SRS). We utilised a narrative approach to understand low and high SRS participants' rape scripts. Young-adult participants described what they believed a typical rape was, followed by describing an acquaintance rape and then what they believed the stereotypical victim of each crime would be. A narrative analysis was conducted on the data. We found that the blitz script is still held by 44% of low SRS and 47% of high SRS people despite 90% of rapes being committed by an acquaintance. While acquaintance rape scripts existed, the emotional imagery and content of these depended on participants level of SRS. Stereotypical victim characteristics also depended on SRS: those with high SRS were more likely to endorse rape myth ideals in describing victims than those with low SRS. These results have implications for educating people about what rape is so that victims might feel more confident in reporting rape

Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin

Recent genomic analyses of pathologically-defined tumor types identify “within-a-tissue” disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head & neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multi-platform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All datasets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies

Growing Pains: The Entanglement of Emotion, Vulnerability, Voice, Ethics, and Power in Becoming a Qualitative to Post-Qualitative Researcher in a “Rational” World

In this paper I share my exploratory, reflective, and reflexive lived experiences in becoming a qualitative, and bending toward post-qualitative researcher within the heavily cognitive and rational world of science education research and academia in general. My process of becoming is an emotional one, as I learn about the deep entanglement of emotions, vulnerability, and voice as they relate to important ethical and political moments within my own context and the various contexts of my research participants. The process of becoming is made more complex, but nonetheless valuable, through my awkward challenges to existing power structures and dominant epistemologies. Gathering initial support through journaling and responding to others’ journals within a feminist reflexivity group, I document my intersubjective and reflective growth through three empowerment-focused research projects: YPAR and photovoice with ELL students, exploring the identities of science teachers who privilege student voice, and YPAR with young girls who have experienced trauma. I offer no easy solutions or a definitive how-to guide, but rather an opportunity to peek inside the complexities of my intensely emotional journey of becoming a reflexive qualitative researcher within a culture of rationality

Autocrine activation of the MET receptor tyrosine kinase in acute myeloid leukemia

Although the treatment of acute myeloid leukemia (AML) has improved substantially in the past three decades, more than half of all patients develop disease that is refractory to intensive chemotherapy(1,2). Functional genomics approaches offer a means to discover specific molecules mediating the aberrant growth and survival of cancer cells(3-8). Thus, using a loss-of-function RNA interference genomic screen, we identified the aberrant expression of hepatocyte growth factor (HGF) as a crucial element in AML pathogenesis. We found HGF expression leading to autocrine activation of its receptor tyrosine kinase, MET, in nearly half of the AML cell lines and clinical samples we studied. Genetic depletion of HGF or MET potently inhibited the growth and survival of HGF-expressing AML cells. However, leukemic cells treated with the specific MET kinase inhibitor crizotinib developed resistance resulting from compensatory upregulation of HGF expression, leading to the restoration of MET signaling. In cases of AML where MET is coactivated with other tyrosine kinases, such as fibroblast growth factor receptor 1 (FGFR1)(9), concomitant inhibition of FGFR1 and MET blocked this compensatory HGF upregulation, resulting in sustained logarithmic cell killing both in vitro and in xenograft models in vivo. Our results show a widespread dependence of AML cells on autocrine activation of MET, as well as the key role of compensatory upregulation of HGF expression in maintaining leukemogenic signaling by this receptor. We anticipate that these findings will lead to the design of additional strategies to block adaptive cellular responses that drive compensatory ligand expression as an essential component of the targeted inhibition of oncogenic receptors in human cancers

Female and male serins ( Serinus serinus ) respond differently to derived song traits

Abstract We tested if male or female behavior towards manipulated song indicates intra- or inter-sexual selection of two characteristics of serin song that are extreme and evolutionarily derived in this species: high frequency and fast syllable rate. In a first experiment, we monitored vocal responses and attendance to song playbacks. Female behavior indicated a preference for high-frequency song and suggested an aggressive function for fast syllable rates, as fast songs inhibited vocal response. Males did not show discrimination of frequency or syllable rate with this experimental design. The second experiment used a simple approach/no approach design, and in this experiment, males showed stronger discrimination between stimuli than did females. Therefore, sex differences in discrimination appear not to result from differences in perceptual abilities but from differences in the context of stimulus presentation. The second experiment also supported a role of song frequency in female choice, as the effect of frequency was limited to females: males did not respond differently to song frequency and approached high-frequency songs less than females did. Results of this experiment also supported an aggressive function for fast syllable rates, as the effect of fast songs did extend to male behavior. Taken together, our results indicate that the high frequency and fast syllable rate of serin song cannot result from a single selection process: while high frequency may have evolved by inter-sexual selection, syllable rate provokes a pattern of response that is more consistent with intra-sexual selection