306 research outputs found

    The Chicken Yolk Sac IgY Receptor, a Functional Equivalent of the Mammalian MHC-Related Fc Receptor, Is a Phospholipase A2 Receptor Homolog

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    AbstractIn mammals, IgG is transferred from mother to young by the MHC-related receptor FcRn, which binds IgG in acidic endosomes and releases it at basic pH into blood. Maternal IgY, the avian counterpart of IgG, is transferred to embryos across yolk sac membranes. We affinity-purified the chicken yolk sac IgY receptor (FcRY) and sequenced its gene. FcRY is unrelated to MHC molecules but is a homolog of the mammalian phospholipase A2 receptor. Analytical ultracentrifugation and truncation experiments suggest that FcRY forms a compact structure containing an IgY binding site at acidic pH but undergoes a conformational change at basic pH that disrupts the site. FcRY is thus unrelated to mammalian FcRn in both its structure and mechanism for pH-dependent binding, illustrating distinct routes utilized by evolution to transfer antibodies

    Quantum Control of the Hyperfine Spin of a Cs Atom Ensemble

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    We demonstrate quantum control of a large spin-angular momentum associated with the F=3 hyperfine ground state of 133Cs. A combination of time dependent magnetic fields and a static tensor light shift is used to implement near-optimal controls and map a fiducial state to a broad range of target states, with yields in the range 0.8-0.9. Squeezed states are produced also by an adiabatic scheme that is more robust against errors. Universal control facilitates the encoding and manipulation of qubits and qudits in atomic ground states, and may lead to improvement of some precision measurements.Comment: 4 pages, 4 figures (color

    The biomechanics and energetics of human running using an elastic knee exoskeleton

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    While the effects of series compliance on running biomechanics are well documented, the effects of parallel compliance are known only for the simpler case of hopping. As many practical exoskeletal and orthotic designs act in parallel with the leg, it is desirable to understand the effects of such an intervention. Spring-like forces offer a natural choice of perturbation for running, as they are both biologically motivated and energetically inexpensive to implement. To this end, we investigate the hypothesis that the addition of an external elastic element at the knee during the stance phase of running results in a reduction in knee extensor activation so that total joint quasi-stiffness is maintained. An exoskeletal knee brace consisting of an elastic element engaged by a clutch is used to provide this stance phase extensor torque. Motion capture of five subjects is used to investigate the consequences of running with this device. No significant change in leg stiffness or total knee stiffness is observed due to the activation of the clutched parallel knee spring. However, this pilot data suggests differing responses between casual runners and competitive long-distance runners, whose total knee torque is increased by the device. Such a relationship between past training and effective utilization of an external force is suggestive of limitations on the applicability of assistive devices

    Remote sensing continuity: a comparison of HTP platforms and potential challenges with field applications

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    In an era of climate change and increased environmental variability, breeders are looking for tools to maintain and increase genetic gain and overall efficiency. In recent years the field of high throughput phenotyping (HTP) has received increased attention as an option to meet this need. There are many platform options in HTP, but ground-based handheld and remote aerial systems are two popular options. While many HTP setups have similar specifications, it is not always clear if data from different systems can be treated interchangeably. In this research, we evaluated two handheld radiometer platforms, Cropscan MSR16R and Spectra Vista Corp (SVC) HR-1024i, as well as a UAS-based system with a Sentera Quad Multispectral Sensor. Each handheld radiometer was used for two years simultaneously with the unoccupied aircraft systems (UAS) in collecting winter wheat breeding trials between 2018-2021. Spectral reflectance indices (SRI) were calculated for each system. SRI heritability and correlation were analyzed in evaluating the platform and SRI usability for breeding applications. Correlations of SRIs were low against UAS SRI and grain yield while using the Cropscan system in 2018 and 2019. Dissimilarly, the SVC system in 2020 and 2021 produced moderate correlations across UAS SRI and grain yield. UAS SRI were consistently more heritable, with broad-sense heritability ranging from 0.58 to 0.80. Data standardization and collection windows are important to consider in ensuring reliable data. Furthermore, practical aspects and best practices for these HTP platforms, relative to applied breeding applications, are highlighted and discussed. The findings of this study can be a framework to build upon when considering the implementation of HTP technology in an applied breeding program

    Probing Within Partially Coherent Microcavity Frequency Combs via Optical Pulse Shaping

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    Recent investigations of microcavity frequency combs based on cascaded four-wave mixing have revealed a link between the evolution of the optical spectrum and the observed temporal coherence. Here we study a silicon nitride microresonator for which the initial four-wave mixing sidebands are spaced by multiple free spectral ranges (FSRs) from the pump, then fill in to yield a comb with single FSR spacing, resulting in partial coherence. By using a pulse shaper to select and manipulate the phase of various subsets of spectral lines, we are able to probe the structure of the coherence within the partially coherent comb. Our data demonstrate strong variation in the degree of mutual coherence between different groups of lines and provide support for a simple model of partially coherent comb formation

    Structural basis for concerted recruitment and activation of IRF-3 by innate immune adaptor proteins

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    Type I IFNs are key cytokines mediating innate antiviral immunity. cGMP-AMP synthase, ritinoic acid-inducible protein 1 (RIG-I)–like receptors, and Toll-like receptors recognize microbial double-stranded (ds)DNA, dsRNA, and LPS to induce the expression of type I IFNs. These signaling pathways converge at the recruitment and activation of the transcription factor IRF-3 (IFN regulatory factor 3). The adaptor proteins STING (stimulator of IFN genes), MAVS (mitochondrial antiviral signaling), and TRIF (TIR domain-containing adaptor inducing IFN-β) mediate the recruitment of IRF-3 through a conserved pLxIS motif. Here we show that the pLxIS motif of phosphorylated STING, MAVS, and TRIF binds to IRF-3 in a similar manner, whereas residues upstream of the motif confer specificity. The structure of the IRF-3 phosphomimetic mutant S386/396E bound to the cAMP response element binding protein (CREB)-binding protein reveals that the pLxIS motif also mediates IRF-3 dimerization and activation. Moreover, rotavirus NSP1 (nonstructural protein 1) employs a pLxIS motif to target IRF-3 for degradation, but phosphorylation of NSP1 is not required for its activity. These results suggest a concerted mechanism for the recruitment and activation of IRF-3 that can be subverted by viral proteins to evade innate immune responses

    An in vitro proof-of-principle study of sonobactericide

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    Infective endocarditis (IE) is associated with high morbidity and mortality rates. The predominant bacteria causing IE is Staphylococcus aureus (S. aureus), which can bind to existing thrombi on heart valves and generate vegetations (biofilms). In this in vitro flow study, we evaluated sonobactericide as a novel strategy to treat IE, using ultrasound and an ultrasound contrast agent with or without other therapeutics. We developed a model of IE biofilm using human whole-blood clots infected with patient-derived S. aureus (infected clots). Histology and live-cell imaging revealed a biofilm layer of fibrin-embedded living Staphylococci around a dense erythrocyte core. Infected clots were treated under flow for 30 minutes and degradation was assessed by time-lapse microscopy imaging. Treatments consisted of either continuous plasma flow alone or with different combinations of therapeutics: oxacillin (antibiotic), recombinant tissue plasminogen activator (rt-PA; thrombolytic), intermittent continuous-wave low-frequency ultrasound (120-kHz, 0.44 MPa peak-to-peak pressure), and an ultrasound contrast agent (Definity). Infected clots exposed to the combination of oxacillin, rt-PA, ultrasound, and Definity achieved 99.3 ± 1.7% loss, which was greater than the other treatment arms. Effluent size measurements suggested low likelihood of emboli formation. These results support the continued investigation of sonobactericide as a therapeutic strategy for IE

    A human cancer-predisposing polymorphism in Cdc25A is embryonic lethal in the mouse and promotes ASK-1 mediated apoptosis

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    <p>Abstract</p> <p>Background</p> <p>Failure to regulate the levels of Cdc25A phosphatase during the cell cycle or during a checkpoint response causes bypass of DNA damage and replication checkpoints resulting in genomic instability and cancer. During G1 and S and in cellular response to DNA damage, Cdc25A is targeted for degradation through the Skp1-cullin-β-TrCP (SCF<sup>β-TrCP</sup>) complex. This complex binds to the Cdc25A DSG motif which contains serine residues at positions 82 and 88. Phosphorylation of one or both residues is necessary for the binding and degradation to occur.</p> <p>Results</p> <p>We now show that mutation of serine 88 to phenylalanine, which is a cancer-predisposing polymorphic variant in humans, leads to early embryonic lethality in mice. The mutant protein retains its phosphatase activity both <it>in vitro </it>and in cultured cells. It fails to interact with the apoptosis signal-regulating kinase 1 (ASK1), however, and therefore does not suppress ASK1-mediated apoptosis.</p> <p>Conclusions</p> <p>These data suggest that the DSG motif, in addition to its function in Cdc25A-mediated degradation, plays a role in cell survival during early embyogenesis through suppression of ASK1-mediated apoptosis.</p
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