355 research outputs found

    Control of the Mitotic Cleavage Plane by Local Epithelial Topology

    Get PDF
    For nearly 150 years, it has been recognized that cell shape strongly influences the orientation of the mitotic cleavage plane (e.g. Hofmeister, 1863). However, we still understand little about the complex interplay between cell shape and cleavage plane orientation in epithelia, where polygonal cell geometries emerge from multiple factors, including cell packing, cell growth, and cell division itself. Here, using mechanical simulations, we show that the polygonal shapes of individual cells can systematically bias the long axis orientations of their adjacent mitotic neighbors. Strikingly, analysis of both animal epithelia and plant epidermis confirm a robust and nearly identical correlation between local cell topology and cleavage plane orientation in vivo. Using simple mathematics, we show that this effect derives from fundamental packing constraints. Our results suggest that local epithelial topology is a key determinant of cleavage plane orientation, and that cleavage plane bias may be a widespread property of polygonal cell sheets in plants and animals.Engineering and Applied Science

    Astro2020 Science White Paper: Triggered High-Priority Observations of Dynamic Solar System Phenomena

    Get PDF
    Unexpected dynamic phenomena have surprised solar system observers in the past and have led to important discoveries about solar system workings. Observations at the initial stages of these events provide crucial information on the physical processes at work. We advocate for long-term/permanent programs on ground-based and space-based telescopes of all sizes - including Extremely Large Telescopes (ELTs) - to conduct observations of high-priority dynamic phenomena, based on a predefined set of triggering conditions. These programs will ensure that the best initial dataset of the triggering event are taken; separate additional observing programs will be required to study the temporal evolution of these phenomena. While not a comprehensive list, the following are notional examples of phenomena that are rare, that cannot be anticipated, and that provide high-impact advances to our understandings of planetary processes. Examples include: new cryovolcanic eruptions or plumes on ocean worlds; impacts on Jupiter, Saturn, Uranus, or Neptune; extreme eruptions on Io; convective superstorms on Saturn, Uranus, or Neptune; collisions within the asteroid belt or other small-body populations; discovery of an interstellar object passing through our solar system (e.g. 'Oumuamua); and responses of planetary atmospheres to major solar flares or coronal mass ejections.Comment: Astro2020 white pape

    Increased fluid flow activity in shallow sediments at the 3 km Long Hugin Fracture in the central North Sea

    Get PDF
    The North Sea hosts a wide variety of seafloor seeps that may be important for transfer of chemical species, such as methane, from the Earth's interior to its exterior. Here we provide geochemical and geophysical evidence for fluid flow within shallow sediments at the recently discovered, 3-km long Hugin Fracture in the Central North Sea. Although venting of gas bubbles was not observed, concentrations of dissolved methane were significantly elevated (up to six-times background values) in the water column at various locations above the fracture, and microbial mats that form in the presence of methane were observed at the seafloor. Seismic amplitude anomalies revealed a bright spot at a fault bend that may be the source of the water column methane. Sediment porewaters recovered in close proximity to the Hugin Fracture indicate the presence of fluids from two different shallow (<500m) sources: (i) a reduced fluid characterized by elevated methane concentrations and/or high levels of dissolved sulfide (up to 6 mmol L−1), and (ii) a low-chlorinity fluid (Cl ∼305 mmol L−1) that has low levels of dissolved methane and/or sulfide. The area of the seafloor affected by the presence of methane-enriched fluids is similar to the footprint of seepage from other morphological features in the North Sea

    Mkk4 is a negative regulator of the transforming growth factor beta 1 signaling associated with atrial remodeling and arrhythmogenesis with age.

    Get PDF
    BACKGROUND: Atrial fibrillation (AF), often associated with structural, fibrotic change in cardiac tissues involving regulatory signaling mediators, becomes increasingly common with age. In the present study, we explored the role of mitogen-activated protein kinase kinase 4 (Mkk4), a critical component of the stress-activated mitogen-activated protein kinase family, in age-associated AF. METHODS AND RESULTS: We developed a novel mouse model with a selective inactivation of atrial cardiomyocyte Mkk4 (Mkk4(ACKO)). We characterized and compared electrophysiological, histological, and molecular features of young (3- to 4-month), adult (6-month), and old (1-year) Mkk4(ACKO) mice with age-matched control littermates (Mkk4(F/F)). Aging Mkk4(ACKO) mice were more susceptible to atrial tachyarrhythmias than the corresponding Mkk4(F/F) mice, showing characteristic slow and dispersed atrial conduction, for which modeling studies demonstrated potential arrhythmic effects. These differences paralleled increased interstitial fibrosis, upregulated transforming growth factor beta 1 (TGF-β1) signaling and dysregulation of matrix metalloproteinases in Mkk4(ACKO), compared to Mkk4(F/F), atria. Mkk4 inactivation increased the sensitivity of cultured cardiomyocytes to angiotensin II-induced activation of TGF-β1 signaling. This, in turn, enhanced expression of profibrotic molecules in cultured cardiac fibroblasts, suggesting cross-talk between these two cell types in profibrotic signaling. Finally, human atrial tissues in AF showed a Mkk4 downregulation associated with increased production of profibrotic molecules, compared to findings in tissue from control subjects in sinus rhythm. CONCLUSIONS: These findings together demonstrate, for the first time, that Mkk4 is a negative regulator of the TGF-β1 signaling associated with atrial remodeling and arrhythmogenesis with age, establishing Mkk4 as a new potential therapeutic target for treating AF

    Solar system Deep Time-Surveys of atmospheres, surfaces, and rings

    Get PDF
    Imaging and resolved spectroscopy reveal varying environmental conditions in our dynamic solar system. Many key advances have focused on how these conditions change over time. Observatory-level commitments to conduct annual observations of solar system bodies would establish a long-term legacy chronicling the evolution of dynamic planetary atmospheres, surfaces, and rings. Science investigations will use these temporal datasets to address potential biosignatures, circulation and evolution of atmospheres from the edge of the habitable zone to the ice giants, orbital dynamics and planetary seismology with ring systems, exchange between components in the planetary system, and the migration and processing of volatiles on icy bodies, including Ocean Worlds. The common factor among these diverse investigations is the need for a very long campaign duration, and temporal sampling at an annual cadence.Comment: 10 pages, 4 figures: submitted for Astro2020 White Pape

    Low concentrations of nitric oxide delay the differentiation of embryonic stem cells and promote their survival

    Get PDF
    Nitric oxide (NO) is an intracellular messenger in several cell systems, but its contribution to embryonic stem cell (ESC) biology has not been characterized. Exposure of ESCs to low concentrations (2–20 μM) of the NO donor diethylenetriamine NO adduct confers protection from apoptosis elicited by leukaemia inhibitory factor (LIF) withdrawal. NO blocked caspase 3 activation, PARP degradation, downregulation of the pro-apoptotic genes Casp7, Casp9, Bax and Bak1 and upregulation of the anti-apoptotic genes Bcl-2 111, Bcl-2 and Birc6. These effects were also observed in cells overexpressing eNOS. Exposure of LIF-deprived mESCs to low NO prevented the loss of expression of self-renewal genes (Oct4, Nanog and Sox2) and the SSEA marker. Moreover, NO blocked the differentiation process promoted by the absence of LIF and bFGF in mouse and human ESCs. NO treatment decreased the expression of differentiation markers, such as Brachyury, Gata6 and Gata4. Constitutive overexpression of eNOS in cells exposed to LIF deprivation maintained the expression of self-renewal markers, whereas the differentiation genes were repressed. These effects were reversed by addition of the NOS inhibitor L-NMMA. Altogether, the data suggest that low NO has a role in the regulation of ESC differentiation by delaying the entry into differentiation, arresting the loss of self-renewal markers and promoting cell survival by inhibiting apoptosis
    corecore