Journal of Contemporary Ethnography, Ahead of Print. Drawn from 18 months of ethnographic research with resettled refugees living in a mini enclave in one Canadian city, this article explores what ethnography offers research with resettled refugees. By interrogating the process of securing ethics approval from the Research Ethics Board (REB), I examine the figure of the refugee at the heart of liberal projects aimed at “saving” refugees. I demonstrate that the REB’s reluctance to approve this project stemmed not only from conventional bureaucratic overreach related to ethnographic research but also from an unexamined and problematic idea of what it means to be a refugee. I discuss the gaps between institutionally perceived forms of vulnerability and the actual vulnerabilities that shape life for refugee women. I argue that vulnerability and risk must be understood as contextual and contingent, rather than inherent. Second, I explore the implications of positioning refugees as always already vulnerable on research practice and the value that ethnography offers for overcoming these blind spots.
Creating artificial macromolecular transport systems that can support the movement of molecules along defined routes is a key goal of nanotechnology. Here, we report the bottom-up construction of a macromolecular transport system in which molecular pistons diffusively move through micrometer-long, hollow filaments. The pistons can cover micrometer distances in fractions of seconds. We build the system using multi-layer DNA origami and analyze the structures of the components using transmission electron microscopy. We study the motion of the pistons along the tubes using single-molecule fluorescence microscopy and perform Langevin simulations to reveal details of the free energy surface that directs the motions of the pistons. The tubular transport system achieves diffusivities and displacement ranges known from natural molecular motors and realizes mobility improvements over five orders of magnitude compared to previous artificial random walker designs. Electric fields can also be employed to actively pull the pistons along the filaments, thereby realizing a nanoscale electric rail system. Our system presents a platform for artificial motors that move autonomously driven by chemical fuels and for performing nanotribology studies, and it could form a basis for future molecular transportation networks.
Transfection is based on nonviral delivery of nucleic acids or proteins into cells. Viral approaches are being used; nevertheless, their translational capacity is nowadays decreasing due to persistent fear of their safety, therefore creating space for the field of nanotechnology. However, nanomedical approaches introducing static nanoparticles for the delivery of biologically active molecules are very likely to be overshadowed by the vast potential of nanorobotics. We hereby present a rapid nonviral transfection of protein into a difficult-to-transfect prostate cancer cell line facilitated by chemically powered rectangular virus-sized (68 nm × 33 nm) nanorobots. The enhanced diffusion of these biocompatible nanorobots is the key to their fast internalization into cells, happening in a matter of minutes and being up to 6-fold more efficient compared to static nanorobots in a nonfueled environment. The Au/Ag plasmonic nature of these nanorobots makes them simply traceable and allows for their detailed subcellular localization. Protein transfection mediated by such nanorobots is an important step forward, challenging the field of nanomedicine and having potential in future translational medical research.
Chemical biology tools to modulate protein levels in cells are critical to decipher complex biology. Targeted protein degradation offers the potential for rapid and dose-dependent protein depletion through the use of protein fusion tags toward which protein degraders have been established. Here, we present a newly developed protein degradation tag BRD4BD1L94V along with the corresponding cereblon (CRBN)-based heterobifunctional degrader based on a "bump-and-hole" approach. The resulting compound XY-06-007 shows a half-degradation concentration (DC50, 6 h) of 10 nM against BRD4BD1L94V with no degradation of off-targets, as assessed by whole proteome mass spectrometry, and demonstrates suitable pharmacokinetics for in vivo studies. We demonstrate that BRD4BD1L94V can be combined with the dTAG approach to achieve simultaneous degrader-mediated depletion of their respective protein fusions. This orthogonal system complements currently available protein degradation tags and enables investigation into the consequences resulting from rapid degradation of previously undruggable disease codependencies.
We sought to explore individuals’ motivations for using their direct-to-consumer genetic testing data to generate polygenic risk scores (PRSs) using a not-for-profit third-party tool, and to assess understanding of, and reaction to their results. Using a cross-sectional design, users of Impute.me who had already accessed PRS results were invited to complete an online questionnaire asking about demographics, motivations for seeking PRSs, understanding and interpretation of PRSs, and two validated scales regarding reactions to results—the Impact of Event Scale Revised (IES-R) and the Feelings About genomiC Testing Result (FACToR). Independent samples T-tests and ANOVA were used to explore associations between the variables. 227 individuals participated in the study. The most frequently reported motivation was general curiosity (98.2%). Only 25.6% of participants correctly answered all questions assessing understanding/interpretation of PRSs. Over half of participants (60.8%) experienced a negative reaction (upset, anxious, and/or sad on FACToR scale) after receiving their PRSs and 5.3% scored over the threshold for potential post-traumatic stress disorder on the IES-R. Lower understanding about PRS was associated with experiencing a negative psychological reaction (P values <0.001). Higher quality pre-test information, particularly to improve understanding, and manage expectations for PRS may be useful in limiting negative psychological reactions.
Many of the ligands for Toll-like receptors (TLRs) are unique to microorganisms, such that receptor activation unequivocally indicates the presence of something foreign. However, a subset of TLRs recognizes nucleic acids, which are present in both the host and foreign microorganisms. This specificity enables broad recognition by virtue of the ubiquity of nucleic acids but also introduces the possibility of self-recognition and autoinflammatory or autoimmune disease. Defining the regulatory mechanisms required to ensure proper discrimination between foreign and self-nucleic acids by TLRs is an area of intense research. Progress over the past decade has revealed a complex array of regulatory mechanisms that ensure maintenance of this delicate balance. These regulatory mechanisms can be divided into a conceptual framework with four categories: compartmentalization, ligand availability, receptor expression and signal transduction. In this Review, we discuss our current understanding of each of these layers of regulation.
Stroke, Ahead of Print. Primary care teams provide the majority of poststroke care. When optimally configured, these teams provide patient centered care to prevent recurrent stroke, maximize function, prevent late complications, and optimize quality of life. Patient centered primary care after stroke begins with establishing the foundation for poststroke management while engaging caregivers and family members in support of the patient. Screening for complications (eg, depression, cognitive impairment, and fall risk) and unmet needs is both a short term and long term component of poststroke care. Patients with ongoing functional impairments may benefit from referral to appropriate services. Ongoing care consists of managing risk factors such as high blood pressure, atrial fibrillation, diabetes, carotid stenosis, and dyslipidemia. Recommendations to reduce risk of recurrent stroke also include lifestyle modifications such as healthy diet and exercise. At the system level, primary care practices can use quality improvement strategies and available resources to enhance the delivery of evidence based care and optimize outcomes.
Using a mouse model in which early life antibiotics enhance T1D, Zhang et al. show that subsequent maternal cecal microbiota transfer reduces illness. The restorative effects on the intestinal microbiome and metabolism, ileal wall gene expression and regulation, and innate and adaptive immune effectors suggest a gut microbiota regulated T1D protective mechanism.
Assemblies of racemic β‐sheet‐forming peptides have attracted attention for biomedical applications because racemic forms of peptides can self‐associate more avidly than do single enantiomers. In 1953, Pauling and Corey proposed "rippled β‐sheet" modes of H‐bond‐mediated interstrand assembly for alternating L‐ and D‐peptide strands; this structural hypothesis was complementary to their proposal of "pleated β‐sheet" assembly for L‐peptides. Although no high‐resolution structure has been reported for a rippled β‐sheet, there is strong evidence for the occurrence of rippled β‐sheets in racemic peptide assemblies. Here we compare propensities of peptide diastereomers in aqueous solution to form a minimum increment of β‐sheet in which two antiparallel strands associate. β‐Hairpin folding is observed for homochiral peptides with aligned nonpolar side chains, but no β‐hairpin population can be detected for diastereomers in which one strand contains L residues and the other contains D residues. These observations suggest that rippled β‐sheet assemblies are stabilized by interactions between β‐sheet layers rather than interactions within these layers.
New Media & Society, Ahead of Print. This article develops the concept of “identity propaganda,” or narratives that strategically target and exploit identity based differences in accord with pre existing power structures to maintain hegemonic social orders. In proposing and developing the concept of identity propaganda, we especially aim to help researchers find new insights into their data on misinformation, disinformation, and propaganda by outlining a framework for unpacking layers of historical power relations embedded in the content they analyze. We focus on three forms of identity propaganda: othering narratives that alienate and marginalize non white or non dominant groups; essentializing narratives that create generalizing tropes of marginalized groups; and authenticating narratives that call upon people to prove or undermine their claims to be part of certain groups. We demonstrate the utility of this framework through our analysis of identity propaganda around Vice President Kamala Harris during the 2020 US presidential election.
In 2019, China emerged prominently on NATO’s agenda, growing more prominent ever since. What accounts for this phenomenon? Is it best explained by Chinese behaviour, changing perceptions of its behaviour, or by an internal Alliance snowball effect resulting from the desire to appear dynamic and relevant, particularly following the Trump administration’s prioritization of China over Russia as the United States’ principal security challenge? To help answer this question, this article provides an historic overview of NATO’s policy approaches towards China. Contrary to the belief of many officials and commentators, China is not a new topic for the Alliance. In fact, China has regularly featured in NATO policies since the early Cold War, alternating between adversary to ally and back again. This article argues that despite recently prioritizing China in its discourse, the historical record provides ample reasons to cast doubt on any expectations this will lead to major substantive changes in NATO’s diplomacy or military posture.
The nuclear receptor FXR lowers hepatic triglycerides to protect against the onset of NAFLD. Clifford et al. demonstrate that activation of FXR decreases hepatic triglycerides through two distinct mechanisms. First, via bile acid dependent decreases in intestinal lipid absorption and second, through selective changes in lipogenesis.