155 research outputs found

    Tissue Microenvironments Define and Get Reinforced by Macrophage Phenotypes in Homeostasis or during Inflammation, Repair and Fibrosis

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    Current macrophage phenotype classifications are based on distinct in vitro culture conditions that do not adequately mirror complex tissue environments. In vivo monocyte progenitors populate all tissues for immune surveillance which supports the maintenance of homeostasis as well as regaining homeostasis after injury. Here we propose to classify macrophage phenotypes according to prototypical tissue environments, e.g. as they occur during homeostasis as well as during the different phases of (dermal) wound healing. In tissue necrosis and/or infection, damage- and/or pathogen-associated molecular patterns induce proinflammatory macrophages by Toll-like receptors or inflammasomes. Such classically activated macrophages contribute to further tissue inflammation and damage. Apoptotic cells and antiinflammatory cytokines dominate in postinflammatory tissues which induce macrophages to produce more antiinflammatory mediators. Similarly, tumor-associated macrophages also confer immunosuppression in tumor stroma. Insufficient parenchymal healing despite abundant growth factors pushes macrophages to gain a profibrotic phenotype and promote fibrocyte recruitment which both enforce tissue scarring. Ischemic scars are largely devoid of cytokines and growth factors so that fibrolytic macrophages that predominantly secrete proteases digest the excess extracellular matrix. Together, macrophages stabilize their surrounding tissue microenvironments by adapting different phenotypes as feed-forward mechanisms to maintain tissue homeostasis or regain it following injury. Furthermore, macrophage heterogeneity in healthy or injured tissues mirrors spatial and temporal differences in microenvironments during the various stages of tissue injury and repair. Copyright (C) 2012 S. Karger AG, Base

    A proposed potential role for increasing atmospheric CO2 as a promoter of weight gain and obesity

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    Human obesity has evolved into a global epidemic. Interestingly, a similar trend has been observed in many animal species, although diet composition, food availability and physical activity have essentially remained unchanged. This suggests a common factor—potentially an environmental factor affecting all species. Coinciding with the increase in obesity, atmospheric CO2 concentration has increased more than 40%. Furthermore, in modern societies, we spend more time indoors, where CO2 often reaches even higher concentrations. Increased CO2 concentration in inhaled air decreases the pH of blood, which in turn spills over to cerebrospinal fluids. Nerve cells in the hypothalamus that regulate appetite and wakefulness have been shown to be extremely sensitive to pH, doubling their activity if pH decreases by 0.1 units. We hypothesize that an increased acidic load from atmospheric CO2 may potentially lead to increased appetite and energy intake, and decreased energy expenditure, and thereby contribute to the current obesity epidemic

    The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

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    Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figuresMajor update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figuresThe preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess

    A computational pipeline to discover highly phylogenetically informative genes in sequenced genomes: application to Saccharomyces cerevisiae natural strains

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    The quest for genes representing genetic relationships of strains or individuals within populations and their evolutionary history is acquiring a novel dimension of complexity with the advancement of next-generation sequencing (NGS) technologies. In fact, sequencing an entire genome uncovers genetic variation in coding and non-coding regions and offers the possibility of studying Saccharomyces cerevisiae populations at the strain level. Nevertheless, the disadvantageous cost-benefit ratio (the amount of details disclosed by NGS against the time-expensive and expertise-demanding data assembly process) still precludes the application of these techniques to the routinely assignment of yeast strains, making the selection of the most reliable molecular markers greatly desirable. In this work we propose an original computational approach to discover genes that can be used as a descriptor of the population structure. We found 13 genes whose variability can be used to recapitulate the phylogeny obtained from genome-wide sequences. The same approach that we prove to be successful in yeasts can be generalized to any other population of individuals given the availability of high-quality genomic sequences and of a clear population structure to be targeted

    Patellofemoral pain syndrome (PFPS): a systematic review of anatomy and potential risk factors

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    Patellofemoral Pain Syndrome (PFPS), a common cause of anterior knee pain, is successfully treated in over 2/3 of patients through rehabilitation protocols designed to reduce pain and return function to the individual. Applying preventive medicine strategies, the majority of cases of PFPS may be avoided if a pre-diagnosis can be made by clinician or certified athletic trainer testing the current researched potential risk factors during a Preparticipation Screening Evaluation (PPSE). We provide a detailed and comprehensive review of the soft tissue, arterial system, and innervation to the patellofemoral joint in order to supply the clinician with the knowledge required to assess the anatomy and make recommendations to patients identified as potentially at risk. The purpose of this article is to review knee anatomy and the literature regarding potential risk factors associated with patellofemoral pain syndrome and prehabilitation strategies. A comprehensive review of knee anatomy will present the relationships of arterial collateralization, innervations, and soft tissue alignment to the possible multifactoral mechanism involved in PFPS, while attempting to advocate future use of different treatments aimed at non-soft tissue causes of PFPS

    The Effect of Sensory Uncertainty Due to Amblyopia (Lazy Eye) on the Planning and Execution of Visually-Guided 3D Reaching Movements

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    Background: Impairment of spatiotemporal visual processing in amblyopia has been studied extensively, but its effects on visuomotor tasks have rarely been examined. Here, we investigate how visual deficits in amblyopia affect motor planning and online control of visually-guided, unconstrained reaching movements. Methods: Thirteen patients with mild amblyopia, 13 with severe amblyopia and 13 visually-normal participants were recruited. Participants reached and touched a visual target during binocular and monocular viewing. Motor planning was assessed by examining spatial variability of the trajectory at 50–100 ms after movement onset. Online control was assessed by examining the endpoint variability and by calculating the coefficient of determination (R 2) which correlates the spatial position of the limb during the movement to endpoint position. Results: Patients with amblyopia had reduced precision of the motor plan in all viewing conditions as evidenced by increased variability of the reach early in the trajectory. Endpoint precision was comparable between patients with mild amblyopia and control participants. Patients with severe amblyopia had reduced endpoint precision along azimuth and elevation during amblyopic eye viewing only, and along the depth axis in all viewing conditions. In addition, they had significantly higher R 2 values at 70 % of movement time along the elevation and depth axes during amblyopic eye viewing. Conclusion: Sensory uncertainty due to amblyopia leads to reduced precision of the motor plan. The ability to implemen

    Age and task difficulty differences in dual tasking using circle tracing and serial subtraction tasks

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    YesThe aim of this study was to investigate age-related differences in dual task performance by using an upper limb proprioceptive task. Twenty-eight younger (18–30 years) and 28 older (>60 years) healthy adults performed circle tracing and serial subtraction tasks separately and concurrently. The tasks had two levels of difficulty: easy and hard. The circle tracing task included direct (easy) and indirect (hard) visual feedback conditions, and it was paired with serial subtraction by twos (easy) or threes (hard). We found that older adults were significantly slower than younger adults across all conditions and had significantly greater dual task costs when they performed circle tracing with easy serial subtraction. Higher levels of task difficulty were associated with slower speed in both groups. We found no age differences in accuracy. Participants either traded speed for accuracy or accuracy for speed regardless of age group. Overall, the findings suggest that speed and accuracy may be affected differently during dual tasking. In addition, older adults may rely more extensively on proprioceptive feedback to guide upper limb movement compared with younger adults.Financial support for this study was obtained from the School of Psychology and Psychiatry, Monash University

    Scintillation light detection in the 6-m drift-length ProtoDUNE Dual Phase liquid argon TPC

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    DUNE is a dual-site experiment for long-baseline neutrino oscillation studies, neutrino astrophysics and nucleon decay searches. ProtoDUNE Dual Phase (DP) is a 6  ×  6  ×  6 m 3 liquid argon time-projection-chamber (LArTPC) that recorded cosmic-muon data at the CERN Neutrino Platform in 2019-2020 as a prototype of the DUNE Far Detector. Charged particles propagating through the LArTPC produce ionization and scintillation light. The scintillation light signal in these detectors can provide the trigger for non-beam events. In addition, it adds precise timing capabilities and improves the calorimetry measurements. In ProtoDUNE-DP, scintillation and electroluminescence light produced by cosmic muons in the LArTPC is collected by photomultiplier tubes placed up to 7 m away from the ionizing track. In this paper, the ProtoDUNE-DP photon detection system performance is evaluated with a particular focus on the different wavelength shifters, such as PEN and TPB, and the use of Xe-doped LAr, considering its future use in giant LArTPCs. The scintillation light production and propagation processes are analyzed and a comparison of simulation to data is performed, improving understanding of the liquid argon properties

    Supernova neutrino burst detection with the Deep Underground Neutrino Experiment

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    The Deep Underground Neutrino Experiment (DUNE), a 40-kton underground liquid argon time projection chamber experiment, will be sensitive to the electron-neutrino flavor component of the burst of neutrinos expected from the next Galactic core-collapse supernova. Such an observation will bring unique insight into the astrophysics of core collapse as well as into the properties of neutrinos. The general capabilities of DUNE for neutrino detection in the relevant few- to few-tens-of-MeV neutrino energy range will be described. As an example, DUNE's ability to constrain the νe spectral parameters of the neutrino burst will be considered
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