1,200 research outputs found

    A Common Dominant TLR5 Stop Codon Polymorphism Abolishes Flagellin Signaling and Is Associated with Susceptibility to Legionnaires' Disease

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    Although Toll-like receptors (TLRs) are critical mediators of the immune response to pathogens, the influence of polymorphisms in this gene family on human susceptibility to infection is poorly understood. We demonstrated recently that TLR5 recognizes flagellin, a potent inflammatory stimulus present in the flagellar structure of many bacteria. Here, we show that a common stop codon polymorphism in the ligand-binding domain of TLR5 (TLR5392STOP) is unable to mediate flagellin signaling, acts in a dominant fashion, and is associated with susceptibility to pneumonia caused by Legionella pneumophila, a flagellated bacterium. We also show that flagellin is a principal stimulant of proinflammatory cytokine production in lung epithelial cells. Together, these observations suggest that TLR5392STOP increases human susceptibility to infection through an unusual dominant mechanism that compromises TLR5's essential role as a regulator of the lung epithelial innate immune response

    Timescales of Massive Human Entrainment

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    The past two decades have seen an upsurge of interest in the collective behaviors of complex systems composed of many agents entrained to each other and to external events. In this paper, we extend concepts of entrainment to the dynamics of human collective attention. We conducted a detailed investigation of the unfolding of human entrainment - as expressed by the content and patterns of hundreds of thousands of messages on Twitter - during the 2012 US presidential debates. By time locking these data sources, we quantify the impact of the unfolding debate on human attention. We show that collective social behavior covaries second-by-second to the interactional dynamics of the debates: A candidate speaking induces rapid increases in mentions of his name on social media and decreases in mentions of the other candidate. Moreover, interruptions by an interlocutor increase the attention received. We also highlight a distinct time scale for the impact of salient moments in the debate: Mentions in social media start within 5-10 seconds after the moment; peak at approximately one minute; and slowly decay in a consistent fashion across well-known events during the debates. Finally, we show that public attention after an initial burst slowly decays through the course of the debates. Thus we demonstrate that large-scale human entrainment may hold across a number of distinct scales, in an exquisitely time-locked fashion. The methods and results pave the way for careful study of the dynamics and mechanisms of large-scale human entrainment.Comment: 20 pages, 7 figures, 6 tables, 4 supplementary figures. 2nd version revised according to peer reviewers' comments: more detailed explanation of the methods, and grounding of the hypothese

    The Hip Spine Relationship—What We Know and What We Don’t: A Narrative Review

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    Background and Objective: The hip-spine syndrome was first described in 1983. The premise of the report was that the hip and spine are closely related and patients can easily have overlapping conditions and misdiagnoses. Since that time, there has been considerable advancement in our understanding of spinopelvic parameters and how degenerative disc disease can affect the pelvis and subsequently the acetabulum. Our objective is to provide an updated review on the relationship between hip and spine degeneration, how we define the relationship, and what steps should be taken when planning surgical intervention for these patients. Methods: A literature review was conducted via the PubMed database. Articles were screened based on their relevancy, recency, and quality of analysis. Search items included the following MeSH terms: “lumbar spine” with free text items: “hip, arthroplasty, parameters, spinopelvic, sagittal alignment, fusion, total hip arthroplasty, hip-spine syndrome, surgical complications, and dislocation”. Key Content and Findings: Novel spinopelvic parameters such as the combined sagittal index (CSI) may be useful in predicting complications in patients undergoing total hip arthroplasty. A reasonable approach may be to perform hip arthroplasty prior to a multilevel spinal fusion, especially when the fusion includes the pelvis. However, for patients with radiculopathy requiring a simpler one- or two-level spinal fusion, the spine may be safely addressed first to relieve the patient of radiculopathy prior to proceeding with a hip arthroplasty. Conclusions: New interpretations and applications of these parameters may decrease risk, prevent complications, and improve outcomes for patients who experience these associated, and often concurrent, pathologies

    Paxillin Dynamics Measured during Adhesion Assembly and Disassembly by Correlation Spectroscopy

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    Paxillin is an adaptor molecule involved in the assembly of focal adhesions. Using different fluorescence fluctuation approaches, we established that paxillin-EGFP is dynamic on many timescales within the cell, ranging from milliseconds to seconds. In the cytoplasmic regions, far from adhesions, paxillin is uniformly distributed and freely diffusing as a monomer, as determined by single-point fluctuation correlation spectroscopy and photon-counting histogram analysis. Near adhesions, paxillin dynamics are reduced drastically, presumably due to binding to protein partners within the adhesions. The photon-counting histogram analysis of the fluctuation amplitudes reveals that this binding equilibrium in new or assembling adhesions is due to paxillin monomers binding to quasi-immobile structures, whereas in disassembling adhesions or regions of adhesions, the equilibrium is due to exchange of large aggregates. Scanning fluctuation correlation spectroscopy and raster-scan image correlation spectroscopy analysis of laser confocal images show that the environments within adhesions are heterogeneous. Relatively large adhesions appear to slide transversally due to a treadmilling mechanism through the addition of monomeric paxillin at one side and removal of relatively large aggregates of proteins from the retracting edge. Total internal reflection microscopy performed with a fast acquisition EM-CCD camera completes the overall dynamic picture and adds details of the heterogeneous dynamics across single adhesions and simultaneous bursts of activity at many adhesions across the cell

    Sloan Digital Sky Survey Imaging of Low Galactic Latitude Fields: Technical Summary and Data Release

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    The Sloan Digital Sky Survey (SDSS) mosaic camera and telescope have obtained five-band optical-wavelength imaging near the Galactic plane outside of the nominal survey boundaries. These additional data were obtained during commissioning and subsequent testing of the SDSS observing system, and they provide unique wide-area imaging data in regions of high obscuration and star formation, including numerous young stellar objects, Herbig-Haro objects and young star clusters. Because these data are outside the Survey regions in the Galactic caps, they are not part of the standard SDSS data releases. This paper presents imaging data for 832 square degrees of sky (including repeats), in the star-forming regions of Orion, Taurus, and Cygnus. About 470 square degrees are now released to the public, with the remainder to follow at the time of SDSS Data Release 4. The public data in Orion include the star-forming region NGC 2068/NGC 2071/HH24 and a large part of Barnard's loop.Comment: 31 pages, 9 figures (3 missing to save space), accepted by AJ, in press, see http://photo.astro.princeton.edu/oriondatarelease for data and paper with all figure

    A Comparison of Radiographic Alignment between Bilateral and Unilateral Interbody Cages in Patients Undergoing Transforaminal Lumbar Interbody Fusion

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    Study Design Retrospective cohort study. Purpose: To compare radiographic outcomes between unilateral and bilateral cage placement in transforaminal lumbar interbody fusions (TLIF) and to determine if the rate of fusion at the 1-year postoperative point was different in patients who received bilateral versus unilateral cages. Overview of Literature There is no clear evidence to dictate whether bilateral or unilateral cages promote superior radiographic or surgical outcomes in TLIF. Methods: Patients \u3e18 years old who underwent primary one- or two-level TLIFs at our institution were identified and propensity-matched in a 3:1 fashion (unilateral:bilateral). Patient demographics, surgical characteristics, and radiographic outcomes, including vertebral endplate obliquity, segmental lordosis, subsidence, and fusion status, were compared between groups. Results: Of the 184 patients included, 46 received bilateral cages. Bilateral cage placement was associated with greater subsidence (1.06±1.25 mm vs. 0.59±1.16 mm, p=0.028) and enhanced restoration of segmental lordosis (5.74°±14.1° vs. −1.57°±10.9°, p=0.002) at the 1-year postoperative point, while unilateral cage placement was associated with an increased correction of endplate obliquity (−2.02°±4.42° vs. 0.24°±2.81°, p\u3c0.001). Bilateral cage placement was significantly associated with radiographic fusion on bivariate analysis (89.1% vs. 70.3%, p=0.018) and significantly predicted radiographic fusion on multivariable regression analysis (estimate, 1.35; odds ratio, 3.87; 95% confidence interval, 1.51–12.05; p=0.010). Conclusions: Bilateral interbody cage placement in TLIF procedures was associated with restoration of lumbar lordosis and increased fusion rates. However, endplate obliquity correction was significantly greater for patients who received a unilateral cage
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