355 research outputs found

    Nebraska’s Natural Resource District System: Collaborative Approaches to Adaptive Groundwater Quality Governance

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    Nonpoint source pollution of groundwater by nitrates from agricultural activity is a persistent problem for which developing effective policy approaches has proven difficult. There is little empirical information on forms of governance or regime attributes that effectively and sustainably address agricultural nonpoint source pollution of groundwater. Nebraska’s Natural Resource District (NRD) system is a rare example of a groundwater governance regime that is putting programmes in place that are likely to generate sustainable groundwater quality outcomes. We focus on three groundwater nitrate management programmes in the state that collectively represent the broader NRD system. The research shows that four elements of Nebraska’s groundwater governance regime are fundamental to its success in addressing groundwater nitrates: 1) the local nature of governance, which builds trust among stakeholders; 2) the significant authority granted to the local districts by the state, allowing for the development of locally tailored solutions; 3) the collaborative governance approach, which allows potential scale imbalances to be overcome; and 4) the taxing authority granted to NRDs, which enables them to fund locally tailored management solutions. We find that these aspects of the NRD system have created conditions that enable adaptive, collaborative governance that positions the state well to address emerging groundwater quality challenges. We present aspects of the governance regime that are generalisable to other American states as efforts to address nitrate pollution in groundwater increase

    The extracellular matrix of the spleen as a potential organizer of immune cell compartments

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    Until recently little information was available on the molecular details of the extracellular matrix (ECM) of secondary lymphoid tissues. There is now growing evidence that these ECMs are unique structures, combining characteristics of basement membranes and interstitial or fibrillar matrices, resulting in scaffolds that are strong and highly flexible and, in certain secondary lymphoid compartments, also forming conduit networks for rapid fluid transport. This review will address the structural characteristics of the ECM of the murine spleen and its potential role as an organizer of immune cell compartments, with reference to the lymph node where relevant

    Preparation of individual magnetic sub-levels of <sup>4</sup>He(2<sup>3</sup>S<sub>1</sub>) in a supersonic beam using laser optical pumping and magnetic hexapole focusing

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    We compare two different experimental techniques for the magnetic-sub-level preparation of metastable 4He in the 23S1 level in a supersonic beam, namely, magnetic hexapole focusing and optical pumping by laser radiation. At a beam velocity of v = 830 m/s, we deduce from a comparison with a particle trajectory simulation that up to 99% of the metastable atoms are in the MJ″ = +1 sub-level after magnetic hexapole focusing. Using laser optical pumping via the 23P2–23S1 transition, we achieve a maximum efficiency of 94% ± 3% for the population of the MJ″ = +1 sub-level. For the first time, we show that laser optical pumping via the 23P1–23S1 transition can be used to selectively populate each of the three MJ″ sub-levels (MJ″ = −1, 0, +1). We also find that laser optical pumping leads to higher absolute atom numbers in specific MJ″ sub-levels than magnetic hexapole focusing

    Mediat. Inflamm.

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    There is increasing evidence that proteasomes have a biological role in the extracellular alveolar space, but inflammation could change their composition. We tested whether immunoproteasome protein-containing subpopulations are present in the alveolar space of patients with lung inflammation evoking the acute respiratory distress syndrome (ARDS). Bronchoalveolar lavage (BAL) supernatants and cell pellet lysate from ARDS patients (n = 28) and healthy subjects (n = 10) were analyzed for the presence of immunoproteasome proteins (LMP2 and LMP7) and proteasome subtypes by western blot, chromatographic purification, and 2D-dimensional gelelectrophoresis. In all ARDS patients but not in healthy subjects LMP7 and LMP2 were observed in BAL supernatants. Proteasomes purified from pooled ARDS BAL supernatant showed an altered enzyme activity ratio. Chromatography revealed a distinct pattern with 7 proteasome subtype peaks in BAL supernatant of ARDS patients that differed from healthy subjects. Total proteasome concentration in BAL supernatant was increased in ARDS (971 ng/mL perpendicular to 1116 versus 59 perpendicular to 25; P < 0.001), and all fluorogenic substrates were hydrolyzed, albeit to a lesser extent, with inhibition by epoxomicin (P = 0.0001). Thus, we identified for the first time immunoproteasome proteins and a distinct proteasomal subtype pattern in the alveolar space of ARDS patients, presumably in response to inflammation

    Rapid leukocyte migration by integrin-independent flowing and squeezing

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    All metazoan cells carry transmembrane receptors of the integrin family, which couple the contractile force of the actomyosin cytoskeleton to the extracellular environment. In agreement with this principle, rapidly migrating leukocytes use integrin-mediated adhesion when moving over two-dimensional surfaces. As migration on two-dimensional substrates naturally overemphasizes the role of adhesion, the contribution of integrins during three-dimensional movement of leukocytes within tissues has remained controversial. We studied the interplay between adhesive, contractile and protrusive forces during interstitial leukocyte chemotaxis in vivo and in vitro. We ablated all integrin heterodimers from murine leukocytes, and show here that functional integrins do not contribute to migration in three-dimensional environments. Instead, these cells migrate by the sole force of actin-network expansion, which promotes protrusive flowing of the leading edge. Myosin II-dependent contraction is only required on passage through narrow gaps, where a squeezing contraction of the trailing edge propels the rigid nucleus

    Actin Flows Mediate a Universal Coupling between Cell Speed and Cell Persistence

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    Cell movement has essential functions in development, immunity, and cancer. Various cell migration patterns have been reported, but no general rule has emerged so far. Here, we show on the basis of experimental data in vitro and in vivo that cell persistence, which quantifies the straightness of trajectories, is robustly coupled to cell migration speed. We suggest that this universal coupling constitutes a generic law of cell migration, which originates in the advection of polarity cues by an actin cytoskeleton undergoing flows at the cellular scale. Our analysis relies on a theoretical model that we validate by measuring the persistence of cells upon modulation of actin flow speeds and upon optogenetic manipulation of the binding of an actin regulator to actin filaments. Beyond the quantitative prediction of the coupling, the model yields a generic phase diagram of cellular trajectories, which recapitulates the full range of observed migration patterns

    Phytohormone cytokinin guides microtubule dynamics during cell progression from proliferative to differentiated stage

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    Cell production and differentiation for the acquisition of specific functions are key features of living systems. The dynamic network of cellular microtubules provides the necessary platform to accommodate processes associated with the transition of cells through the individual phases of cytogenesis. Here, we show that the plant hormone cytokinin fine‐tunes the activity of the microtubular cytoskeleton during cell differentiation and counteracts microtubular rearrangements driven by the hormone auxin. The endogenous upward gradient of cytokinin activity along the longitudinal growth axis in Arabidopsis thaliana roots correlates with robust rearrangements of the microtubule cytoskeleton in epidermal cells progressing from the proliferative to the differentiation stage. Controlled increases in cytokinin activity result in premature re‐organization of the microtubule network from transversal to an oblique disposition in cells prior to their differentiation, whereas attenuated hormone perception delays cytoskeleton conversion into a configuration typical for differentiated cells. Intriguingly, cytokinin can interfere with microtubules also in animal cells, such as leukocytes, suggesting that a cytokinin‐sensitive control pathway for the microtubular cytoskeleton may be at least partially conserved between plant and animal cells

    Partial loss of actin nucleator actin-related protein 2/3 activity triggers blebbing in primary T lymphocytes

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    T lymphocytes utilize amoeboid migration to navigate effectively within complex microenvironments. The precise rearrangement of the actin cytoskeleton required for cellular forward propulsion is mediated by actin regulators, including the actin‐related protein 2/3 (Arp2/3) complex, a macromolecular machine that nucleates branched actin filaments at the leading edge. The consequences of modulating Arp2/3 activity on the biophysical properties of the actomyosin cortex and downstream T cell function are incompletely understood. We report that even a moderate decrease of Arp3 levels in T cells profoundly affects actin cortex integrity. Reduction in total F‐actin content leads to reduced cortical tension and disrupted lamellipodia formation. Instead, in Arp3‐knockdown cells, the motility mode is dominated by blebbing migration characterized by transient, balloon‐like protrusions at the leading edge. Although this migration mode seems to be compatible with interstitial migration in three‐dimensional environments, diminished locomotion kinetics and impaired cytotoxicity interfere with optimal T cell function. These findings define the importance of finely tuned, Arp2/3‐dependent mechanophysical membrane integrity in cytotoxic effector T lymphocyte activities
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