Indigenous (Mis)Representation: Implications for the MMIWG2S Epidemic

In the United States and Canada, Native women, girls, and two-spirit people are stolen and killed at a disproportionate rate. Despite their pleas for justice, non-indigenous media are reluctant to give Indigenous voices a platform to incite change. Critically, the crisis of Missing and Murdered Indigenous Women, Girls, and Two-Spirit People (MMIWG2S) is not endemic to North America, but permeates through aboriginal life on every continent as a tool of settler colonialism. Existing literature on the topic of MMIWG2S has traced the roots of the crisis to settler colonialism and to non-Indigenous popular culture, but there is a gap in knowledge about how these two phenomena reinforce one another. After all, colonialism is an ongoing process. Our research question addresses this gap by asking: how does settler colonialism inform the portrayal of Indigenous women in popular culture today and perpetuate the disproportionate rates of violence that contribute to the MMIWG2S epidemic? We find that popular culture intentionally fetishizes and misrepresents Indigenous women and girls, through the folklorized narrative of Pocahontas, for example, so as to reinforce ideologies of conquest and colonization that are embedded in the American ethos. While American media is consumed on a global scale, colonized media representations of Indigenous people are not specific to the American experience, and are present in settler colonial states across the globe including Canada and Australia. Taught to children at a young age, these sexualized, gendered, and racialized narratives contribute to settler attempts at erasure of Native people across the globe.To rectify this, our capstone group devised a two-part project. First, we collaborated with the Big Sky Institute to organize and promote the Native Filmmaker Initiative feature of their documentary film festival and host a panel discussion after the showing. Additionally, we sold raffle tickets and donated proceeds to Missoula Project Beacon and an MMIP direct services organization. Second, using perspective and knowledge gained from organizing the panel discussion and speaking with Indigenous filmmakers, educators, and activists, we created and shared a media literacy toolkit designed to help high school educators encourage critical thinking about misrepresentations of Indigenous life in popular culture. It is our hope that this toolkit will transcend the boundaries of the Missoula community and uplift Indigenous voices on a global scale

Inducing chromosome pairing through premature condensation: analysis of wheat interspecific hybrids

At the onset of meiosis, chromosomes first decondense and then condense as the process of recognition and intimate pairing occurs between homologous chromosomes. We show here that okadaic acid, a drug known to induce chromosome condensation, can be introduced into wheat interspecific hybrids prior to meiosis to induce chromosome pairing. This pairing occurs in the presence of the Ph1 locus, which usually suppresses pairing of related chromosomes and which we show here delays condensation. Thus the timing of chromosome condensation during the onset of meiosis is an important factor in controlling chromosome pairing

An Indocyanine Green-Based Nanoprobe for In Vivo Detection of Cellular Senescence

There is an urgent need to improve conventional cancer-treatments by preventing detrimental side effects, cancer recurrence and metastases. Recent studies have shown that presence of senescent cells in tissues treated with chemo- or radiotherapy can be used to predict the effectiveness of cancer treatment. However, although the accumulation of senescent cells is one of the hallmarks of cancer, surprisingly little progress has been made in development of strategies for their detection in vivo. To address a lack of detection tools, we developed a biocompatible, injectable organic nanoprobe (NanoJagg), which is selectively taken up by senescent cells and accumulates in the lysosomes. The NanoJagg probe is obtained by self-assembly of indocyanine green (ICG) dimers using a scalable manufacturing process and characterized by a unique spectral signature suitable for both photoacoustic tomography (PAT) and fluorescence imaging. In vitro, ex vivo and in vivo studies all indicate that NanoJaggs are a clinically translatable probe for detection of senescence and their PAT signal makes them suitable for longitudinal monitoring of the senescence burden in solid tumors after chemotherapy or radiotherapy.</p

An Indocyanine Green-Based Nanoprobe for In Vivo Detection of Cellular Senescence

There is an urgent need to improve conventional cancer-treatments by preventing detrimental side effects, cancer recurrence and metastases. Recent studies have shown that presence of senescent cells in tissues treated with chemo- or radiotherapy can be used to predict the effectiveness of cancer treatment. However, although the accumulation of senescent cells is one of the hallmarks of cancer, surprisingly little progress has been made in development of strategies for their detection in vivo. To address a lack of detection tools, we developed a biocompatible, injectable organic nanoprobe (NanoJagg), which is selectively taken up by senescent cells and accumulates in the lysosomes. The NanoJagg probe is obtained by self-assembly of indocyanine green (ICG) dimers using a scalable manufacturing process and characterized by a unique spectral signature suitable for both photoacoustic tomography (PAT) and fluorescence imaging. In vitro, ex vivo and in vivo studies all indicate that NanoJaggs are a clinically translatable probe for detection of senescence and their PAT signal makes them suitable for longitudinal monitoring of the senescence burden in solid tumors after chemotherapy or radiotherapy.</p

A deep learning model to generate synthetic CT for prostate MR-only radiotherapy dose planning: a multicenter study

IntroductionFor radiotherapy based solely on magnetic resonance imaging (MRI), generating synthetic computed tomography scans (sCT) from MRI is essential for dose calculation. The use of deep learning (DL) methods to generate sCT from MRI has shown encouraging results if the MRI images used for training the deep learning network and the MRI images for sCT generation come from the same MRI device. The objective of this study was to create and evaluate a generic DL model capable of generating sCTs from various MRI devices for prostate radiotherapyMaterials and methodsIn total, 90 patients from three centers (30 CT-MR prostate pairs/center) underwent treatment using volumetric modulated arc therapy for prostate cancer (PCa) (60 Gy in 20 fractions). T2 MRI images were acquired in addition to computed tomography (CT) images for treatment planning. The DL model was a 2D supervised conditional generative adversarial network (Pix2Pix). Patient images underwent preprocessing steps, including nonrigid registration. Seven different supervised models were trained, incorporating patients from one, two, or three centers. Each model was trained on 24 CT-MR prostate pairs. A generic model was trained using patients from all three centers. To compare sCT and CT, the mean absolute error in Hounsfield units was calculated for the entire pelvis, prostate, bladder, rectum, and bones. For dose analysis, mean dose differences of D99% for CTV, V95% for PTV, Dmax for rectum and bladder, and 3D gamma analysis (local, 1%/1 mm) were calculated from CT and sCT. Furthermore, Wilcoxon tests were performed to compare the image and dose results obtained with the generic model to those with the other trained models.ResultsConsidering the image results for the entire pelvis, when the data used for the test comes from the same center as the data used for training, the results were not significantly different from the generic model. Absolute dose differences were less than 1 Gy for the CTV D99% for every trained model and center. The gamma analysis results showed nonsignificant differences between the generic and monocentric models.ConclusionThe accuracy of sCT, in terms of image and dose, is equivalent to whether MRI images are generated using the generic model or the monocentric model. The generic model, using only eight MRI-CT pairs per center, offers robust sCT generation, facilitating PCa MRI-only radiotherapy for routine clinical use

Targeting of the Arpc3 actin nucleation factor by miR-29a/b regulates dendritic spine morphology

Regulation of Arpc3 by miRNA alters dendritic spine morphology

Ethics, politics and embodied imagination in crafting scientific knowledge

This article explores ‘research-as-craft’ as a sensitizing concept for disclosing the presence of ethics and politics, as well as embodiment and imagination, in the doing and representation of scientific activity. Routinely unnoticed, marginalized or suppressed in methodology sections of articles and methodology textbooks, research-as-craft gestures towards messy, tacit, uncertain, yet rarely thematized, practices that are central to getting science done. To acknowledge and address the significance of research-as-craft in knowledge production, we show how it relates to three forms of reflexivity – constitutive, epistemic and disruptive. Through this we demonstrate the craftiness that is required when struggling with the indeterminacy that is endemic to the production and communication of scientific knowledge. By showing how empirical situations require imaginative interpretation by embodied researchers, we argue that our conception of research-as-craft facilitates appreciation of scientific inquiry as an indexical activity that involves the crafted object and the researcher in an ethico-political process of co-constituting knowledge

HIF-1 Modulates Dietary Restriction-Mediated Lifespan Extension via IRE-1 in Caenorhabditis elegans

Dietary restriction (DR) extends lifespan in various species and also slows the onset of age-related diseases. Previous studies from flies and yeast have demonstrated that the target of rapamycin (TOR) pathway is essential for longevity phenotypes resulting from DR. TOR is a conserved protein kinase that regulates growth and metabolism in response to nutrients and growth factors. While some of the downstream targets of TOR have been implicated in regulating lifespan, it is still unclear whether additional targets of this pathway also modulate lifespan. It has been shown that the hypoxia inducible factor-1 (HIF-1) is one of the targets of the TOR pathway in mammalian cells. HIF-1 is a transcription factor complex that plays key roles in oxygen homeostasis, tumor formation, glucose metabolism, cell survival, and inflammatory response. Here, we describe a novel role for HIF-1 in modulating lifespan extension by DR in Caenorhabditis elegans. We find that HIF-1 deficiency results in extended lifespan, which overlaps with that by inhibition of the RSKS-1/S6 kinase, a key component of the TOR pathway. Using a modified DR method based on variation of bacterial food concentrations on solid agar plates, we find that HIF-1 modulates longevity in a nutrient-dependent manner. The hif-1 loss-of-function mutant extends lifespan under rich nutrient conditions but fails to show lifespan extension under DR. Conversely, a mutation in egl-9, which increases HIF-1 activity, diminishes the lifespan extension under DR. This deficiency is rescued by tissue-specific expression of egl-9 in specific neurons and muscles. Increased lifespan by hif-1 or DR is dependent on the endoplasmic reticulum (ER) stress regulator inositol-requiring protein-1 (IRE-1) and is associated with lower levels of ER stress. Therefore, our results demonstrate a tissue-specific role for HIF-1 in the lifespan extension by DR involving the IRE-1 ER stress pathway