Aboriginal Fractions: Enumerating Identity in Taiwan

Notions of identity in Taiwan are configured in relation to numbers. I examine the polyvalent capacities of enumerative technologies in both the production of ethnic identities and claims to polit- ical representation and justice. By critically historicizing the manner in which Aborigines in Taiwan have been, and continue to be, constructed as objects and subjects of scientific knowledge production through technologies of measuring, I examine the genetic claim made by some Taiwanese to be ‘‘fractionally’’ Aboriginal. Numbers and techniques of measuring are used ostensibly to know the Aborigines, but they are also used to construct a genetically unique Taiwanese identity and to incor- porate the Aborigines within projects of democratic governance. Technologies of enumeration thus serve within multiple, and sometimes contradictory, projects of representation and knowledge production

From the ECM to the Cytoskeleton and Back: How Integrins Orchestrate T Cell Action

T lymphocytes constitute a highly dynamic tissue type. During the course of their lives, they travel through a variety of physiological environments and experience a multitude of interactions with extracellular matrix components and other cells. In order to do this, they must receive many environmental cues, and translate these signals into the appropriate biological actions. Particularly dramatic are the cytoskeletal shape changes a T cell must undergo during the processes of leaving the bloodstream, migrating through tissues, and encountering antigen. In this review, we highlight the role of integrins in providing a link between the extracellular environment and cytoskeletal regulation and how these receptors help to orchestrate T cell migration and antigen recognition

Two conserved domains in PCIF1 mediate interaction with pancreatic transcription factor PDX-1

AbstractPCIF1 is a TRAF and POZ domain containing nuclear factor that interacts with and inhibits transactivation of pancreatic homeodomain transcription factor PDX-1. Here, we demonstrate interaction of endogenous PDX-1 and PCIF1 in MIN6 insulinoma cells. Within PCIF1, the TRAF and POZ domains are both required for physical and functional interaction with the C-terminus of PDX-1, whereas the C-terminal domain of PCIF1 directs its nuclear localization. A human PDX-1 mutation associated with diabetes, E224K, disrupts the ability of PCIF1 to inhibit PDX-1 transactivation, suggesting that the interaction between PDX-1 and PCIF1 is required for normal glucose homeostasis. Inhibition of transactivation occurs by a mechanism distinct from the classical role of POZ domains to recruit co-repressors and histone deacetylases. Understanding the functional roles of PCIF1 domains may have application to therapeutic β-cell replacement strategies involving PDX-1 for the treatment of diabetes

Association of Health Literacy and Provider Education with Knowledge of Breast and Cervical Cancer Screening in an Underserved Female Population

https://digitalcommons.unmc.edu/emet_posters/1028/thumbnail.jp

Evaluating the in-situ effectiveness of indoor environment guidelines on occupant satisfaction

Post occupancy evaluation (POE) studies typically use a combination of occupant questionnaires and physical measurements of various aspects of the indoor environment to assess building performance. These physical measurements are often compared against published reference limits to evaluate compliance and satisfactory performance. This study investigates whether indoor environment conditions compatible with published indoor environment quality (IEQ) standards and guidelines are predictive of occupant satisfaction. Data used in this study were collected as part of two large building evaluation field studies conducted in the past eight years. Occupant questionnaire and physical measurement data from 11 office buildings across North America were used (N=194). Inputs for the analyses were demographic factors and workstation characteristics, as well as aspects of the measured physical indoor environment. Outcome variables were various measures of environmental satisfaction (i.e. lighting, acoustics/privacy, and ventilation/temperature). The results of this study suggest that occupants had higher satisfaction with lighting when measured desktop illuminance levels were within IESNA RP-1-12 (2012) recommendations. Measured sound levels and thermal conditions within reference limits did not correlate to higher occupant satisfaction in their respective categories

The alternatively spliced fibronectin CS1 isoform regulates IL-17A levels and mechanical allodynia after peripheral nerve injury.

BackgroundMechanical pain hypersensitivity associated with physical trauma to peripheral nerve depends on T-helper (Th) cells expressing the algesic cytokine, interleukin (IL)-17A. Fibronectin (FN) isoform alternatively spliced within the IIICS region encoding the 25-residue-long connecting segment 1 (CS1) regulates T cell recruitment to the sites of inflammation. Herein, we analyzed the role of CS1-containing FN (FN-CS1) in IL-17A expression and pain after peripheral nerve damage.MethodsMass spectrometry, immunoblotting, and FN-CS1-specific immunofluorescence analyses were employed to examine FN expression after chronic constriction injury (CCI) in rat sciatic nerves. The acute intra-sciatic nerve injection of the synthetic CS1 peptide (a competitive inhibitor of the FN-CS1/α4 integrin binding) was used to elucidate the functional significance of FN-CS1 in mechanical and thermal pain hypersensitivity and IL-17A expression (by quantitative Taqman RT-PCR) after CCI. The CS1 peptide effects were analyzed in cultured primary Schwann cells, the major source of FN-CS1 in CCI nerves.ResultsFollowing CCI, FN expression in sciatic nerve increased with the dominant FN-CS1 deposition in endothelial cells, Schwann cells, and macrophages. Acute CS1 therapy attenuated mechanical allodynia (pain from innocuous stimulation) but not thermal hyperalgesia and reduced the levels of IL-17A expression in the injured nerve. CS1 peptide inhibited the LPS- or starvation-stimulated activation of the stress ERK/MAPK pathway in cultured Schwann cells.ConclusionsAfter physical trauma to the peripheral nerve, FN-CS1 contributes to mechanical pain hypersensitivity by increasing the number of IL-17A-expressing (presumably, Th17) cells. CS1 peptide therapy can be developed for pharmacological control of neuropathic pain

Isomeric triazines exhibit unique profiles of bioorthogonal reactivity.

Expanding the scope of bioorthogonal reactivity requires access to new and mutually compatible reagents. We report here that 1,2,4-triazines can be tuned to exhibit unique reaction profiles with biocompatible strained alkenes and alkynes. Computational analyses were used to identify candidate orthogonal reactions, and the predictions were experimentally verified. Notably, 5-substituted triazines, unlike their 6-substituted counterparts, undergo rapid [4 + 2] cycloadditions with a sterically encumbered strained alkyne. This unique, sterically controlled reactivity was exploited for dual bioorthogonal labeling. Mutually orthogonal triazines and cycloaddition chemistries will enable new multi-component imaging applications

A preexisting rare PIK3CA e545k subpopulation confers clinical resistance to MEK plus CDK4/6 inhibition in NRAS melanoma and is dependent on S6K1 signaling

Combined MEK and CDK4/6 inhibition (MEKi + CDK4i) has shown promising clinical outcomes in patients with NRAS- mutant melanoma. Here, we interrogated longitudinal biopsies from a patient who initially responded to MEKi + CDK4i therapy but subsequently developed resistance. Whole-exome sequencing and functional validation identified an acquired PIK3CA E545K mutation as conferring drug resistance. We demonstrate that PIK3CA E545K preexisted in a rare subpopulation that was missed by both clinical and research testing, but was revealed upon multiregion sampling due to PIK3CA E545K being nonuniformly distributed. This resistant population rapidly expanded after the initiation of MEKi + CDK4i therapy and persisted in all successive samples even after immune checkpoint therapy and distant metastasis. Functional studies identified activated S6K1 as both a key marker and specific therapeutic vulnerability downstream of PIK3CA E545K -induced resistance. These results demonstrate that difficult-to-detect preexisting resistance mutations may exist more often than previously appreciated and also posit S6K1 as a common downstream therapeutic nexus for the MAPK, CDK4/6, and PI3K pathways. SIGNIFICANCE: We report the first characterization of clinical acquired resistance to MEKi + CDK4i, identifying a rare preexisting PIK3CA E545K subpopulation that expands upon therapy and exhibits drug resistance. We suggest that single-region pretreatment biopsy is insufficient to detect rare, spatially segregated drug-resistant subclones. Inhibition of S6K1 is able to resensitize PIK3CA E545K -expressing NRAS-mutant melanoma cells to MEKi + CDK4i. © 2018 AAC