295 research outputs found

    Between the cosmopolitan and the parochial: the immigrant gentrifier in Koreatown, Los Angeles

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    This paper questions the currently lopsided relationship between the cosmopolitan and the parochial, in which the former is favored both conceptually and empirically. In response, we propose a relational framework for bringing them into conversation, simultaneously recasting and re-animating longstanding debates via three framing devices – the process of relationality/territoriality, disposition, and spaces of encounter – embedded in and through the subject of the immigrant-gentrifier in Koreatown, Los Angeles, itself a novel category that has hitherto eluded systematic research. We present the results of 25 interviews of Korean immigrant-gentrifiers and 10 key informant interviews. The results constitute a parochial critique that emerges as a series of conflicted paradoxes but also productive tensions: between an ostensibly transnational process compromised by a profoundly homegrown, parochial set of investors and outlooks; between a set of dispositions that seek inner-city diversity and density, yet simultaneously sheltered from its spillover costs; and spaces of encounter marked by a gap between the promise of truly open spaces and the reality of guarded and self-segregated ones. Ultimately, this paper does double duty – conceptually rebalancing the cosmopolitan-parochial relationship, but in doing so empirically elevating the emergence of the understudied immigrant-gentrifier category

    Characteristics and Treatment Preferences of People with Symptoms of Posttraumatic Stress Disorder: An Internet Survey

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    Background: Although Posttraumatic Stress Disorder (PTSD) is a severe and disabling anxiety disorder, relatively few people with this condition access evidence-based care. Barriers to treatment are multiple and complex, but the emerging field of Internet therapy for PTSD may improve access to evidence-based treatment. However, little is known about the characteristics of people with PTSD who seek online treatment, or whether they perceive internet treatment as an acceptable treatment option. Methodology: An online survey was used to collect information about the demographic and symptom characteristics of individuals with elevated levels of PTSD symptoms, and this was compared to data from corresponding sample from a national survey. Previous treatment experiences, perceived barriers to treatment and treatment preferences for Internet therapy and face-to-face treatment were also compared. Principal Findings: High levels of PTSD symptoms were reported by survey respondents. Psychological distress and disability was greater than reported by individuals with PTSD from a national survey. Half of the sample reported not having received treatment for PTSD; however, 88% of those who reported receiving treatment stated they received an evidence-based treatment. Primary barriers to treatment included cost, poor awareness of service availability, lack of prior treatment response and not perceiving personal distress as severe enough to warrant treatment. Most survey respondents indicated they were willing to try Internet treatment for PTSD. Conclusions: The Internet sample was symptomatically severe and multiple barriers existed to treatment. Internet therapy is an acceptable option for the treatment of PTSD in an internet sample.6 page(s

    Engineering Orthogonal Polypeptide GalNAc-Transferase and UDP-Sugar Pairs

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    O-Linked α-N-acetylgalactosamine (O-GalNAc) glycans constitute a major part of the human glycome. They are difficult to study because of the complex interplay of 20 distinct glycosyltransferase isoenzymes that initiate this form of glycosylation, the polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts). Despite proven disease relevance, correlating the activity of individual GalNAc-Ts with biological function remains challenging due to a lack of tools to probe their substrate specificity in a complex biological environment. Here, we develop a “bump–hole” chemical reporter system for studying GalNAc-T activity in vitro. Individual GalNAc-Ts were rationally engineered to contain an enlarged active site (hole) and probed with a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs to identify enzyme–substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme–substrate pairs. The approach was applicable to multiple GalNAc-T isoenzymes, including GalNAc-T1 and -T2 that prefer nonglycosylated peptide substrates and GalNAcT-10 that prefers a preglycosylated peptide substrate. A detailed investigation of enzyme kinetics and specificities revealed the robustness of the approach to faithfully report on GalNAc-T activity and paves the way for studying substrate specificities in living systems

    The association of long-term outcome and biological sex in patients with acute heart failure from different geographic regions

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    Aims: Recent data from national registries suggest that acute heart failure (AHF) outcomes might vary in men and women, however, it is not known whether this observation is universal. The aim of this study was to evaluate the association of biological sex and 1-year all-cause mortality in patients with AHF in various regions of the world. Methods and results: We analysed several AHF cohorts including GREAT registry (22 523 patients, mostly from Europe and Asia) and OPTIMIZE-HF (26 376 patients from the USA). Clinical characteristics and medication use at discharge were collected. Hazard ratios (HRs) for 1-year mortality according to biological sex were calculated using a Cox proportional hazards regression model with adjustment for baseline characteristics (e.g. age, comorbidities, clinical and laboratory parameters at admission, left ventricular ejection fraction). In the GREAT registry, women had a lower risk of death in the year following AHF [HR 0.86 (0.79-0.94), P < 0.001 after adjustment]. This was mostly driven by northeast Asia [n = 9135, HR 0.76 (0.67-0.87), P < 0.001], while no significant differences were seen in other countries. In the OPTIMIZE-HF registry, women also had a lower risk of 1-year death [HR 0.93 (0.89-0.97), P < 0.001]. In the GREAT registry, women were less often prescribed with a combination of angiotensin-converting enzyme inhibitors and beta-blockers at discharge (50% vs. 57%, P = 0.001). Conclusion: Globally women with AHF have a lower 1-year mortality and less evidenced-based treatment than men. Differences among countries need further investigation. Our findings merit consideration when designing future global clinical trials in AHF

    Submucosal Gland Myoepithelial Cells Are Reserve Stem Cells That Can Regenerate Mouse Tracheal Epithelium

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    The mouse trachea is thought to contain two distinct stem cell compartments that contribute to airway repair-basal cells in the surface airway epithelium (SAE) and an unknown submucosal gland (SMG) cell type. Whether a lineage relationship exists between these two stem cell compartments remains unclear. Using lineage tracing of glandular myoepithelial cells (MECs), we demonstrate that MECs can give rise to seven cell types of the SAE and SMGs following severe airway injury. MECs progressively adopted a basal cell phenotype on the SAE and established lasting progenitors capable of further regeneration following reinjury. MECs activate Wnt-regulated transcription factors (Lef-1/TCF7) following injury and Lef-1 induction in cultured MECs promoted transition to a basal cell phenotype. Surprisingly, dose-dependent MEC conditional activation of Lef-1 in vivo promoted self-limited airway regeneration in the absence of injury. Thus, modulating the Lef-1 transcriptional program in MEC-derived progenitors may have regenerative medicine applications for lung diseases

    Engineering Orthogonal Polypeptide GalNAc-Transferase and UDP-Sugar Pairs

    Get PDF
    O-Linked α-N-acetylgalactosamine (O-GalNAc) glycans constitute a major part of the human glycome. They are difficult to study because of the complex interplay of 20 distinct glycosyltransferase isoenzymes that initiate this form of glycosylation, the polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts). Despite proven disease relevance, correlating the activity of individual GalNAc-Ts with biological function remains challenging due to a lack of tools to probe their substrate specificity in a complex biological environment. Here, we develop a “bump–hole” chemical reporter system for studying GalNAc-T activity in vitro. Individual GalNAc-Ts were rationally engineered to contain an enlarged active site (hole) and probed with a newly synthesized collection of 20 (bumped) uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) analogs to identify enzyme–substrate pairs that retain peptide specificities but are otherwise completely orthogonal to native enzyme–substrate pairs. The approach was applicable to multiple GalNAc-T isoenzymes, including GalNAc-T1 and -T2 that prefer nonglycosylated peptide substrates and GalNAcT-10 that prefers a preglycosylated peptide substrate. A detailed investigation of enzyme kinetics and specificities revealed the robustness of the approach to faithfully report on GalNAc-T activity and paves the way for studying substrate specificities in living systems

    Methodological consensus on clinical proton MRS of the brain: Review and recommendations

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    © 2019 International Society for Magnetic Resonance in Medicine Proton MRS (1H MRS) provides noninvasive, quantitative metabolite profiles of tissue and has been shown to aid the clinical management of several brain diseases. Although most modern clinical MR scanners support MRS capabilities, routine use is largely restricted to specialized centers with good access to MR research support. Widespread adoption has been slow for several reasons, and technical challenges toward obtaining reliable good-quality results have been identified as a contributing factor. Considerable progress has been made by the research community to address many of these challenges, and in this paper a consensus is presented on deficiencies in widely available MRS methodology and validated improvements that are currently in routine use at several clinical research institutions. In particular, the localization error for the PRESS localization sequence was found to be unacceptably high at 3 T, and use of the semi-adiabatic localization by adiabatic selective refocusing sequence is a recommended solution. Incorporation of simulated metabolite basis sets into analysis routines is recommended for reliably capturing the full spectral detail available from short TE acquisitions. In addition, the importance of achieving a highly homogenous static magnetic field (B0) in the acquisition region is emphasized, and the limitations of current methods and hardware are discussed. Most recommendations require only software improvements, greatly enhancing the capabilities of clinical MRS on existing hardware. Implementation of these recommendations should strengthen current clinical applications and advance progress toward developing and validating new MRS biomarkers for clinical use
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