1,589 research outputs found

    Long-Lasting Impairments in Quadriceps Mitochondrial Health, Muscle Size, and Phenotypic Composition Are Present After Non-Invasive Anterior Cruciate Ligament Injury

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    Introduction: Despite rigorous rehabilitation aimed at restoring muscle health, anterior cruciate ligament (ACL) injury is often hallmarked by significant long-term quadriceps muscle weakness. Derangements in mitochondrial function are a common feature of various atrophying conditions, yet it is unclear to what extent mitochondria are involved in the detrimental sequela of quadriceps dysfunction after ACL injury. Using a preclinical, non-invasive ACL injury rodent model, our objective was to explore the direct effect of an isolated ACL injury on mitochondrial function, muscle atrophy, and muscle phenotypic transitions. Methods: A total of 40 male and female, Long Evans rats (16-week-old) were exposed to non-invasive ACL injury, while 8 additional rats served as controls. Rats were euthanized at 3, 7, 14, 28, and 56 days after ACL injury, and vastus lateralis muscles were extracted to measure the mitochondrial respiratory control ratio (RCR; state 3 respiration/state 4 respiration), mitochondrial reactive oxygen species (ROS) production, fiber cross sectional area (CSA), and fiber phenotyping. Alterations in mitochondrial function and ROS production were detected using two-way (sex:group) analyses of variance. To determine if mitochondrial characteristics were related to fiber atrophy, individual linear mixed effect models were run by sex. Results: Mitochondria-derived ROS increased from days 7 to 56 after ACL injury (30–100%, P \u3c 0.05), concomitant with a twofold reduction in RCR (P \u3c 0.05). Post-injury, male rats displayed decreases in fiber CSA (days 7, 14, 56; P \u3c 0.05), loss of IIa fibers (day 7; P \u3c 0.05), and an increase in IIb fibers (day 7; P \u3c 0.05), while females displayed no changes in CSA or phenotyping (P \u3e 0.05). Males displayed a positive relationship between state 3 respiration and CSA at days 14 and 56 (P \u3c 0.05), while females only displayed a similar trend at day 14 (P = 0.05). Conclusion: Long-lasting impairments in quadriceps mitochondrial health are present after ACL injury and play a key role in the dysregulation of quadriceps muscle size and composition. Our preclinical data indicate that using mitoprotective therapies may be a potential therapeutic strategy to mitigate alterations in muscle size and characteristic after ACL injury

    Recommendations Supporting Development of Flight Deck DataComm Text and Graphic Display Evaluation Guidance

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    In the Next Generation Air Transportation System (NexGen), voice communications will become less frequent, and most communication will occur via data communications -- uplink messages (UM) (to pilot) and downlink messages (DM) and requests (to ATC). Clearances may include simple one-element clearances such as CLIMB TO [altitude] or complex clearances created by concatenating messages to create flight trajectories that include ATC-authorized route segments, altitudes, and at least one required time of arrival (RTA). Due to the complexity of clearances, aircraft and flight deck equipment manufacturers may seek approval for new and modified flight deck displays to more clearly depict clearances to the flight crew, likely using text and graphics. This research evaluated text and hybrid text and graphic concepts to develop human factors (HF) recommendations for specialists who participate in certification of new and modified flight deck DataComm displays, and as a potential update to AC 20-140, Guidelines for Design Approval of Aircraft Data Link Communication Systems Supporting Air Traffic Services (ATS)

    Seasonal prediction of bottom temperature on the Northeast U.S. Continental Shelf

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    © The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Chen, Z., Kwon, Y.-O., Chen, K., Fratantoni, P., Gawarkiewicz, G., Joyce, T. M., Miller, T. J., Nye, J. A., Saba, V. S., & Stock, B. C. Seasonal prediction of bottom temperature on the Northeast U.S. Continental Shelf. Journal of Geophysical Research: Oceans, 126(5), (2021): e2021JC017187, https://doi.org/10.1029/2021JC017187.The Northeast U.S. shelf (NES) is an oceanographically dynamic marine ecosystem and supports some of the most valuable demersal fisheries in the world. A reliable prediction of NES environmental variables, particularly ocean bottom temperature, could lead to a significant improvement in demersal fisheries management. However, the current generation of climate model-based seasonal-to-interannual predictions exhibits limited prediction skill in this continental shelf environment. Here, we have developed a hierarchy of statistical seasonal predictions for NES bottom temperatures using an eddy-resolving ocean reanalysis data set. A simple, damped local persistence prediction model produces significant skill for lead times up to ∼5 months in the Mid-Atlantic Bight and up to ∼10 months in the Gulf of Maine, although the prediction skill varies notably by season. Considering temperature from a nearby or upstream (i.e., more poleward) region as an additional predictor generally improves prediction skill, presumably as a result of advective processes. Large-scale atmospheric and oceanic indices, such as Gulf Stream path indices (GSIs) and the North Atlantic Oscillation Index, are also tested as predictors for NES bottom temperatures. Only the GSI constructed from temperature observed at 200 m depth significantly improves the prediction skill relative to local persistence. However, the prediction skill from this GSI is not larger than that gained using models incorporating nearby or upstream shelf/slope temperatures. Based on these results, a simplified statistical model has been developed, which can be tailored to fisheries management for the NES.This work was supported by NOAA's Climate Program Office's Modeling, Analysis, Predictions, and Projections (MAPP) Program (NA17OAR4310111, NA19OAR4320074), and Climate Program Office's Climate Variability and Predictability (CVP) Program (NA20OAR4310482). We acknowledge our participation in MAPP's Marine Prediction Task Force

    Barriers to HIV Testing Within a Sample of Spanish-speaking Latinx Gay, Bisexual, and Other Men Who Have Sex with Men: Implications for HIV Prevention and Care

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    Gay, bisexual, and other men who have sex with men (GBMSM) have higher rates of HIV infection compared to the general population in the United States, and the infection rate is growing among Latinx GBMSM, compared to a decline in most other demographic subgroups. Uptake of pre-exposure prophylaxis (PrEP), a biomedical strategy designed to reduce HIV transmission, is very low among Latinx GBMSM. HIV testing is a critical first step in the HIV prevention and care continua. We analyzed data from a community-based sample of Latinx GBMSM in the southeastern United States to identify the most common HIV testing barriers and the factors associated with barriers. The five most commonly reported HIV testing barriers included not knowing where to get tested, not having health insurance, fear of being HIV positive, practicing safer sex and perceiving not needing to be tested, and not being recommended to get tested. Using multivariable logistic regression modeling, speaking only Spanish, being unemployed, and adhering to traditional notions of masculinity were associated with increased barriers to HIV testing. We recommend that interventions to increase HIV testing among Latinx GBMSM be provided in Spanish and use culturally congruent messaging, be accessible to those who are unemployed, and incorporate positive risk-reducing aspects of masculinity

    Accessory Genome Dynamics and Structural Variation of Shigella from Persistent Infections

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    Shigellosis is a diarrheal disease caused mainly by Shigella flexneri and Shigella sonnei Infection is thought to be largely self-limiting, with short- to medium-term and serotype-specific immunity provided following clearance. However, cases of men who have sex with men (MSM)-associated shigellosis have been reported where Shigella of the same serotype were serially sampled from individuals between 1 and 1,862 days apart, possibly due to persistent carriage or reinfection with the same serotype. Here, we investigate the accessory genome dynamics of MSM-associated S. flexneri and S. sonnei isolates serially sampled from individual patients at various days apart to shed light on the adaptation of these important pathogens during infection. We find that pairs likely associated with persistent infection/carriage and with a smaller single nucleotide polymorphism (SNP) distance, demonstrated significantly less variation in accessory genome content than pairs likely associated with reinfection, and with a greater SNP distance. We observed antimicrobial resistance acquisition during Shigella carriage, including the gain of an extended-spectrum beta-lactamase gene during carriage. Finally, we explored large chromosomal structural variations and rearrangements in seven (five chronic and two reinfection associated) pairs of S. flexneri 3a isolates from an MSM-associated epidemic sublineage, which revealed variations at several common regions across isolate pairs, mediated by insertion sequence elements and comprising a distinct predicted functional profile. This study provides insight on the variation of accessory genome dynamics and large structural genomic changes in Shigella during persistent infection/carriage. In addition, we have also created a complete reference genome and biobanked isolate of the globally important pathogen, S. flexneri 3a.IMPORTANCE Shigella spp. are Gram-negative bacteria that are the etiological agent of shigellosis, the second most common cause of diarrheal illness among children under the age of five in low-income countries. In high-income countries, shigellosis is also a sexually transmissible disease among men who have sex with men. Within the latter setting, we have captured prolonged and/or recurrent infection with shigellae of the same serotype, challenging the belief that Shigella infection is short lived and providing an early opportunity to study the evolution of the pathogen over the course of infection. Using this recently emerged transmission scenario, we comprehensively characterize the genomic changes that occur over the course of individual infection with Shigella and uncover a distinct functional profile of variable genomic regions, findings that have relevance for other Enterobacteriaceae

    A New Era in Extragalactic Background Light Measurements: The Cosmic History of Accretion, Nucleosynthesis and Reionization

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    (Brief Summary) What is the total radiative content of the Universe since the epoch of recombination? The extragalactic background light (EBL) spectrum captures the redshifted energy released from the first stellar objects, protogalaxies, and galaxies throughout cosmic history. Yet, we have not determined the brightness of the extragalactic sky from UV/optical to far-infrared wavelengths with sufficient accuracy to establish the radiative content of the Universe to better than an order of magnitude. Among many science topics, an accurate measurement of the EBL spectrum from optical to far-IR wavelengths, will address: What is the total energy released by stellar nucleosynthesis over cosmic history? Was significant energy released by non-stellar processes? Is there a diffuse component to the EBL anywhere from optical to sub-millimeter? When did first stars appear and how luminous was the reionization epoch? Absolute optical to mid-IR EBL spectrum to an astrophysically interesting accuracy can be established by wide field imagingat a distance of 5 AU or above the ecliptic plane where the zodiacal foreground is reduced by more than two orders of magnitude.Comment: 7 pages; Science White Paper for the US Astro 2010-2020 Decadal Survey. If interested in further community-wide efforts on this topic please contact the first autho

    Signatures of minor mergers in the Milky Way disc I: The SEGUE stellar sample

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    It is now known that minor mergers are capable of creating structure in the phase-space distribution of their host galaxy's disc. In order to search for such imprints in the Milky Way, we analyse the SEGUE F/G-dwarf and the Schuster et al. (2006) stellar samples. We find similar features in these two completely independent stellar samples, consistent with the predictions of a Milky Way minor-merger event. We next apply the same analyses to high-resolution, idealised N-body simulations of the interaction between the Sagittarius dwarf galaxy and the Milky Way. The energy distributions of stellar particle samples in small spatial regions in the host disc reveal strong variations of structure with position. We find good matches to the observations for models with a mass of Sagittarius' dark matter halo progenitor 1011\lessapprox 10^{11} M_{\odot}. Thus, we show that this kind of analysis could be used to provide unprecedentedly tight constraints on Sagittarius' orbital parameters, as well as place a lower limit on its mass.Comment: 14 pages, 9 figures, 2 tables. Revised to reflect accepted versio

    Global population structure and genotyping framework for genomic surveillance of the major dysentery pathogen, Shigella sonnei.

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    Shigella sonnei is the most common agent of shigellosis in high-income countries, and causes a significant disease burden in low- and middle-income countries. Antimicrobial resistance is increasingly common in all settings. Whole genome sequencing (WGS) is increasingly utilised for S. sonnei outbreak investigation and surveillance, but comparison of data between studies and labs is challenging. Here, we present a genomic framework and genotyping scheme for S. sonnei to efficiently identify genotype and resistance determinants from WGS data. The scheme is implemented in the software package Mykrobe and tested on thousands of genomes. Applying this approach to analyse >4,000 S. sonnei isolates sequenced in public health labs in three countries identified several common genotypes associated with increased rates of ciprofloxacin resistance and azithromycin resistance, confirming intercontinental spread of highly-resistant S. sonnei clones and demonstrating the genomic framework can facilitate monitoring the spread of resistant clones, including those that have recently emerged, at local and global scales

    Near-Infrared Imaging Polarimetry of Inner Region of GG Tau A Disk

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    By performing non-masked polarization imaging with Subaru/HiCIAO, polarized scattered light from the inner region of the disk around the GG Tau A system was successfully detected in the HH band with a spatial resolution of approximately 0.07\arcsec, revealing the complicated inner disk structures around this young binary. This paper reports the observation of an arc-like structure to the north of GG Tau Ab and part of a circumstellar structure that is noticeable around GG Tau Aa extending to a distance of approximately 28 AU from the primary star. The speckle noise around GG Tau Ab constrains its disk radius to <13 AU. Based on the size of the circumbinary ring and the circumstellar disk around GG Tau Aa, the semi-major axis of the binary's orbit is likely to be 62 AU. A comparison of the present observations with previous ALMA and near-infrared (NIR) H2_2 emission observations suggests that the north arc could be part of a large streamer flowing from the circumbinary ring to sustain the circumstellar disks. According to the previous studies, the circumstellar disk around GG Tau Aa has enough mass and can sustain itself for a duration sufficient for planet formation; thus, our study indicates that planets can form within close (separation \lesssim 100 AU) young binary systems.Comment: Accepted for publication in AJ, 12 pages, 5 figure
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