13,864 research outputs found

    \u3cem\u3eChlamydomonas\u3c/em\u3e mutants display reversible deficiencies in flagellar beating and axonemal assembly

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    Axonemal complexes in flagella are largely prepackaged in the cell body. As such, one mutation often results in the absence of the co-assembled components and permanent motility deficiencies. For example, a Chlamydomonas mutant defective in RSP4 in the radial spoke (RS), which is critical for bend propagation, has paralyzed flagella that also lack the paralogue RSP6 and three additional RS proteins. Intriguingly, recent studies showed that several mutant strains contain a mixed population of swimmers and paralyzed cells despite their identical genetic background. Here we report a cause underlying these variations. Two new mutants lacking RSP6 swim processively and other components appear normally assembled in early log phase indicating that, unlike RSP4, this paralogue is dispensable. However, swimmers cannot maintain the typical helical trajectory and reactivated cell models tend to spin. Interestingly the motile fraction and the spokehead content dwindle during stationary phase. These results suggest that (1) intact RS is critical for maintaining the rhythm of oscillatory beating and thus the helical trajectory; (2) assembly of the axonemal complex with subtle defects is less efficient and the inefficiency is accentuated in compromised conditions, leading to reversible dyskinesia. Consistently, several organisms only possess one RSP4/6 gene. Gene duplication in Chlamydomonas enhances RS assembly to maintain optimal motility in various environments

    Constitutively active transforming growth factor β receptor 1 in the mouse ovary promotes tumorigenesis

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    Despite the well-established tumor suppressive role of TGFβ proteins, depletion of key TGFβ signaling components in the mouse ovary does not induce a growth advantage. To define the role of TGFβ signaling in ovarian tumorigenesis, we created a mouse model expressing a constitutively active TGFβ receptor 1 (TGFBR1) in ovarian somatic cells using conditional gain-of-function approach. Remarkably, these mice developed ovarian sex cord-stromal tumors with complete penetrance, leading to reproductive failure and mortality. The tumors expressed multiple granulosa cell markers and caused elevated serum inhibin and estradiol levels, reminiscent of granulosa cell tumors. Consistent with the tumorigenic effect, overactivation of TGFBR1 altered tumor microenvironment by promoting angiogenesis and enhanced ovarian cell proliferation, accompanied by impaired cell differentiation and dysregulated expression of critical genes in ovarian function. By further exploiting complementary genetic models, we substantiated our finding that constitutively active TGFBR1 is a potent oncogenic switch in mouse granulosa cells. In summary, overactivation of TGFBR1 drives gonadal tumor development. The TGFBR1 constitutively active mouse model phenocopies a number of morphological, hormonal, and molecular features of human granulosa cell tumors and are potentially valuable for preclinical testing of targeted therapies to treat granulosa cell tumors, a class of poorly defined ovarian malignancies

    Dimeric heat shock protein 40 binds radial spokes for generating coupled power strokes and recovery strokes of 9 + 2 flagella

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    T-shape radial spokes regulate flagellar beating. However, the precise function and molecular mechanism of these spokes remain unclear. Interestingly, Chlamydomonas reinhardtii flagella lacking a dimeric heat shock protein (HSP) 40 at the spokehead–spokestalk juncture appear normal in length and composition but twitch actively while cells jiggle without procession, resembling a central pair (CP) mutant. HSP40− cells begin swimming upon electroporation with recombinant HSP40. Surprisingly, the rescue doesn't require the signature DnaJ domain. Furthermore, the His-Pro-Asp tripeptide that is essential for stimulating HSP70 adenosine triphosphatase diverges in candidate orthologues, including human DnaJB13. Video microscopy reveals hesitance in bend initiation and propagation as well as irregular stalling and stroke switching despite fairly normal waveform. The in vivo evidence suggests that the evolutionarily conserved HSP40 specifically transforms multiple spoke proteins into stable conformation capable of mechanically coupling the CP with dynein motors. This enables 9 + 2 cilia and flagella to bend and switch to generate alternate power strokes and recovery strokes

    A direct method for analyzing the nonlinear vehicle–structure interaction

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    This article presents an accurate, efficient and stable algorithm to analyze the nonlinear vertical vehicle-structure interaction. The governing equilibrium equations of the vehicle and structure are complemented with additional constraint equations that relate the displacements of the vehicle with the corresponding displacements of the structure. These equations form a single system, with displacements and contact forces as unknowns, that is solved using an optimized block factorization algorithm. Due to the nonlinear nature of contact, an incremental formulation based on the Newton method is adopted. The vehicles, track and structure are modeled using finite elements to take into account all the significant deformations. The numerical example presented clearly demonstrates the accuracy and computational efficiency of the proposed method

    Performance characteristics of eight estradiol immunoassays

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    Journal ArticleMeasurement of estradiol is useful in assisted reproduction, evaluation of infertility, menopause, and male feminization. The analytic performance of 8 estradiol immunoassays was evaluated. The imprecision and accuracy of the Access, ADVIA Centaur, ARCHITECT i2000, AutoDELFIA, Elecsys 2010, IMMULITE 2000, and Vitros ECi estradiol assays (see text for proprietary information) were evaluated by using an isotope dilution-gas chromatography-mass spectrometry (ID-GC-MS) reference method. The coefficient of variation (CV) ranged from 6.9% on the Elecsys 2010 to 42.6% on the ADVIA Centaur at an estradiol concentration of 18 pg/mL (66 pmol/L), with the ARCHITECT i2000 assay in development and the Vitros ECi having a CV below 10% at this estradiol concentration. Agreement between the automated assays and ID-GC-MS was variable, with slopes ranging from 0.87 to 1.20. The Access, ARCHITECT i2000 in development, and the IMMULITE 2000 were the most accurate, with slopes of 0.99, 0.98, and 1.03, respectively. These findings indicate that the ARCHITECT i2000 estradiol assay in development had the best precision and accuracy of the assays evaluated for measurement of serum estradiol concentrations

    A new method to prevent degradation of lithium–oxygen batteries: reduction of superoxide by viologen

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    Lithium–oxygen battery development is hampered by degradation reactions initiated by superoxide, which is formed in the pathway of oxygen reduction to peroxide. This work demonstrates that the superoxide lifetime is drastically decreased upon addition of ethyl viologen, which catalyses the reduction of superoxide to peroxide

    Cobra for white mold suppression

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    Many fields planted to soybeans this year had white mold problems in 1996, thus providing inoculum for infestations during the current season. Growers are looking for ways to manage white mold problems and one strategy may be to use a herbicide. Cobra (lactofen) has recently received a supplemental label for suppression of soybean white mold. In this article, we address questions related to using Cobra for white mold suppression

    Examining the Externalities of Highway Capacity Expansions in California: An Analysis of Land Use and Land Cover (LULC) Using Remote Sensing Technology

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    There are over 590,000 bridges dispersed across the roadway network that stretches across the United States alone. Each bridge with a length of 20 feet or greater must be inspected at least once every 24 months, according to the Federal Highway Act (FHWA) of 1968. This research developed an artificial intelligence (AI)-based framework for bridge and road inspection using drones with multiple sensors collecting capabilities. It is not sufficient to conduct inspections of bridges and roads using cameras alone, so the research team utilized an infrared (IR) camera along with a high-resolution optical camera. In many instances, the IR camera can provide more details to the interior structural damages of a bridge or a road surface than an optical camera, which is more suitable for inspecting damages on the surface of a bridge or a road. In addition, the drone inspection system is equipped with a minicomputer that runs Machine Learning algorithms. These algorithms enable autonomous drone navigation, image capture of the bridge or road structure, and analysis of the images. Whenever any damage is detected, the location coordinates are saved. Thus, the drone can self-operate and carry out the inspection process using advanced AI algorithms developed by the research team. The experimental results reveal the system can detect potholes with an average accuracy of 84.62% using the visible light camera and 95.12% using a thermal camera. This developed bridge and road inspection framework can save time, money, and lives by automating and having drones conduct major inspection operations in place of humans

    Nonthermal ice nucleation observed at distorted contact lines of supercooled water drops

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    Ice nucleation is the crucial step for ice formation in atmospheric clouds and therefore underlies climatologically relevant precipitation and radiative properties. Progress has been made in understanding the roles of temperature, supersaturation, and material properties, but an explanation for the efficient ice nucleation occurring when a particle contacts a supercooled water drop has been elusive for over half a century. Here, we explore ice nucleation initiated at constant temperature and observe that mechanical agitation induces freezing of supercooled water drops at distorted contact lines. Results show that symmetric motion of supercooled water on a vertically oscillating substrate does not freeze, no matter how we agitate it. However, when the moving contact line is distorted with the help of trace amounts of oil or inhomogeneous pinning on the substrate, freezing can occur at temperatures much higher than in a static droplet, equivalent to ∼1010 increase in nucleation rate. Several possible mechanisms are proposed to explain the observations. One plausible explanation among them, decreased pressure due to interface curvature, is explored theoretically and compared with the observational results quasiquantitatively. Indeed, the observed freezing-temperature increase scales with contact line speed in a manner consistent with the pressure hypothesis. Whatever the mechanism, the experiments demonstrate a strong preference for ice nucleation at three-phase contact lines compared to the two-phase interface, and they also show that movement and distortion of the contact line are necessary contributions to stimulating the nucleation process
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