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Berlin Brandenburg

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  • 1
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 03 July 2012, Vol.109(27), pp.10990-5
    Description: Chemorepellants may play multiple roles in physiological and pathological processes. However, few endogenous chemorepellants have been identified, and how they function is unclear. We found that the autocrine signal AprA, which is produced by growing Dictyostelium discoideum cells and inhibits their proliferation, also functions as a chemorepellant. Wild-type cells at the edge of a colony show directed movement outward from the colony, whereas cells lacking AprA do not. Cells show directed movement away from a source of recombinant AprA and dialyzed conditioned media from wild-type cells, but not dialyzed conditioned media from aprA(-) cells. The secreted protein CfaD, the G protein Gα8, and the kinase QkgA are necessary for the chemorepellant activity of AprA as well as its proliferation-inhibiting activity, whereas the putative transcription factor BzpN is dispensable for the chemorepellant activity of AprA but necessary for inhibition of proliferation. Phospholipase C and PI3 kinases 1 and 2, which are necessary for the activity of at least one other chemorepellant in Dictyostelium, are not necessary for recombinant AprA chemorepellant activity. Starved cells are not repelled by recombinant AprA, suggesting that aggregation-phase cells are not sensitive to the chemorepellant effect. Cell tracking indicates that AprA affects the directional bias of cell movement, but not cell velocity or the persistence of cell movement. Together, our data indicate that the endogenous signal AprA acts as an autocrine chemorepellant for Dictyostelium cells.
    Keywords: Chemotaxis -- Physiology ; Dictyostelium -- Metabolism ; Protozoan Proteins -- Metabolism ; Signal Transduction -- Physiology
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 2
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 02 May 2017, Vol.114(18), pp.4649-4654
    Description: The capacity for representing and reasoning over sets of possibilities, or modal cognition, supports diverse kinds of high-level judgments: causal reasoning, moral judgment, language comprehension, and more. Prior research on modal cognition asks how humans explicitly and deliberatively reason about what is possible but has not investigated whether or how people have a default, implicit representation of which events are possible. We present three studies that characterize the role of implicit representations of possibility in cognition. Collectively, these studies differentiate explicit reasoning about possibilities from default implicit representations, demonstrate that human adults often default to treating immoral and irrational events as impossible, and provide a case study of high-level cognitive judgments relying on default implicit representations of possibility rather than explicit deliberation.
    Keywords: High-Level Cognition ; Modality ; Morality ; Norms ; Possibility ; Cognition ; Judgment ; Morals
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 3
    Language: English
    In: PLoS ONE, 01 January 2014, Vol.9(5), p.e96633
    Description: In Dictyostelium discoideum, the secreted proteins AprA and CfaD function as reporters of cell density and regulate cell number by inhibiting proliferation at high cell densities. AprA also functions to disperse groups of cells at high density by acting as a chemorepellent. However, the signal transduction pathways associated with AprA and CfaD are not clear, and little is known about how AprA affects the cytoskeleton to regulate cell movement. We found that the p21-activated kinase (PAK) family member PakD is required for both the proliferation-inhibiting activity of AprA and CfaD and the chemorepellent activity of AprA. Similar to cells lacking AprA or CfaD, cells lacking PakD proliferate to a higher cell density than wild-type cells. Recombinant AprA and CfaD inhibit the proliferation of wild-type cells but not cells lacking PakD. Like AprA and CfaD, PakD affects proliferation but does not significantly affect growth (the accumulation of mass) on a per-nucleus basis. In contrast to wild-type cells, cells lacking PakD are not repelled from a source of AprA, and colonies of cells lacking PakD expand at a slower rate than wild-type cells, indicating that PakD is required for AprA-mediated chemorepulsion. A PakD-GFP fusion protein localizes to an intracellular punctum that is not the nucleus or centrosome, and PakD-GFP is also occasionally observed at the rear cortex of moving cells. Vegetative cells lacking PakD show excessive actin-based filopodia-like structures, suggesting that PakD affects actin dynamics, consistent with previously characterized roles of PAK proteins in actin regulation. Together, our results implicate PakD in AprA/CfaD signaling and show that a PAK protein is required for proper chemorepulsive cell movement in Dictyostelium.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 4
    Language: English
    In: Catena, October 2018, Vol.169, pp.107-118
    Description: Relative sea-level rise (SLR) raises geomorphic base levels, displaces salt water and tidal or backwater effects inland, and changes the hydrology of aquatic and upland environments. On an all-other-things-being equal basis, we can predict some transitions associated with SLR. However, in real coastal landscapes, all other things are not equal. Factors other than sea-level influence geomorphic, hydrological, and ecological processes and controls, environmental interactions often complicate or obscure process-response relationships, and local disturbances may interrupt or overprint them. In this study relationships among coastal environments in North Carolina, USA were investigated as they respond to changes in multiple environmental gradients driven by relative sea level rise, to determine the extent to which the spatial complexity of landscape response can be explained by environmental gradients. Spatial adjacency graphs reflecting observed patterns of contiguity were derived empirically, and five key environmental gradients related to relative sea-level were identified (elevation, hydroperiod, salinity, vegetation, and process regime). The spectral radius of the spatial adjacency graph indicates a complex system that on the landscape level cannot be described or modeled based on linear gradients or successional relationships. Yet, spectral graph theory measures show that the complexity of the system can be fully explained, in the aggregate, by the five identified gradients, despite some redundancy of information therein. This indicates that coastal responses to SLR should be assessed based on multiscalar, nested environmental gradients rather than a single advancing front of change or linear sequence.
    Keywords: Sea-Level Rise ; Coastal Submergence ; Coastal Environments ; Spatial Adjacency Graph ; Complexity ; Sciences (General) ; Geography ; Geology
    ISSN: 0341-8162
    E-ISSN: 1872-6887
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  • 5
    Language: English
    In: Catena, December 2013, Vol.111, pp.98-103
    Description: The spatial pattern of soils and soil properties in soil landscapes is considered here as a function of (1) systematic variation along catenas or associated with spatial patterns of soil-forming factors; and (2) local pseudo-random variations associated with local disturbances or small, unobserved variations in soil-forming factors. The problem is approached at two study sites in the U.S. Atlantic Coastal Plain using algebraic graph theory and the spectral radius of the soil adjacency matrix as a measure of complexity. The matrix is constructed based on the observed spatial contiguity of soil taxa, and soil factor sequences (SFS) are defined for each site based on systematic soil variation associated with variations in parent material, topography, sandy surface thicknesses, and secondary podzolization. The spectral radii of the networks described by the adjacency graphs are compared to those associated with the maximum for a graph of the same size, and the maximum associated with control entirely by variations in soil forming factors. At the Clayroot study site, which is entirely cropland, complexity of the adjacency matrix is less than Λ, the maximum that could be accounted for by the four identified SFS, due to redundant information in the SFS. The Littlefield site, by contrast, has a spectral radius greater than Λ. Here, where about half the site is forested, the contingent variation is likely associated with effects of individual trees on soil morphology. The utility of the adjacency analysis is in identifying whether soil heterogeneity is likely associated with SFS or with contingent factors not captured in SFS.
    Keywords: Soil Spatial Heterogeneity ; Soil-Forming Factors ; Soil Factor Sequences ; Adjacency Matrix ; Spectral Radius ; Soil Landscape Complexity ; Sciences (General) ; Geography ; Geology
    ISSN: 0341-8162
    E-ISSN: 1872-6887
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  • 6
    Language: English
    In: PLoS ONE, 01 January 2011, Vol.6(7), p.e21765
    Description: The secreted proteins AprA and CfaD function as autocrine signals that inhibit cell proliferation in Dictyostelium discoideum, thereby regulating cell numbers by a negative feedback mechanism. We report here that the putative basic leucine zipper transcription factor BzpN plays a role in the inhibition of proliferation by AprA and CfaD. Cells lacking BzpN proliferate more rapidly than wild-type cells but do not reach a higher stationary density. Recombinant AprA inhibits wild-type cell proliferation but does not inhibit the proliferation of cells lacking BzpN. Recombinant CfaD also inhibits wild-type cell proliferation, but promotes the proliferation of cells lacking BzpN. Overexpression of BzpN results in a reduced cell density at stationary phase, and this phenotype requires AprA, CfaD, and the kinase QkgA. Conditioned media from high-density cells stops the proliferation of wild-type but not bzpN(-) cells and induces a nuclear localization of a BzpN-GFP fusion protein, though this localization does not require AprA or CfaD. Together, the data suggest that BzpN is necessary for some but not all of the effects of AprA and CfaD, and that BzpN may function downstream of AprA and CfaD in a signal transduction pathway that inhibits proliferation.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 7
    Language: English
    In: Catena, June 2017, Vol.153, pp.168-181
    Description: State-and-transition models (STM) are used to describe, model, interpret, and predict when landscapes will undergo a qualitative state change. Although rangeland ecologists pioneered STMs, geomorphological STM-type models were developed prior to and independently of ecological STMs. This study categorized 47 geomorphological STMs according to whether they were: based on single or multiple study areas; primarily for description and interpretation or predictive and prescriptive use; explicitly concerned with complex system dynamics; and the role of biogeomorphic interactions in the model. Each STM was represented as a graph and the structure identified. Spectral radii were calculated to measure the complexity of each STM. Although STMs are associated with conceptual frameworks that recognize the possibility of nonequilibrium, alternative states, and path dependency, results show that an explicit concern with complexity does not necessarily lead to the identification of more states and transitions, or a more complex transition pattern. The purpose for which a STM was created, as well as the number of study sites it can be applied to, also had little bearing on the models' complexity. This review suggests that geomorphic STMs, rather than being used to fit explanations about landscape evolution into predefined theoretical categories, are veridical representations of empirical observations. Although STMs are particularly useful for grasping the biogeomorphological dynamics of landscapes, this review indicates their utility is not limited to biogeomorphology or to systems with a strong ecological imprint. Time scales involved in geomorphic change can make it difficult to observe a large number of states and transitions, which may constrain what types of STM structure can be identified, as the number of observed states and transitions required to develop particular graph structures varies widely.
    Keywords: State-and-Transition Models ; Geomorphic Systems ; Graph Theory ; Geomorphic Change ; Sciences (General) ; Geography ; Geology
    ISSN: 0341-8162
    E-ISSN: 1872-6887
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  • 8
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 15 March 2011, Vol.108(11), pp.4417-22
    Description: Based on our recent work with Haloferax volcanii, ubiquitin-like (Ubl) proteins (SAMP1 and SAMP2) are known to be covalently attached to proteins in archaea. Here, we investigated the enzymes required for the formation of these Ubl-protein conjugates (SAMPylation) and whether this system is linked to sulfur transfer. Markerless in-frame deletions were generated in H. volcanii target genes. The mutants were examined for: (i) the formation of Ubl protein conjugates, (ii) growth under various conditions, including those requiring the synthesis of the sulfur-containing molybdenum cofactor (MoCo), and (iii) the thiolation of tRNA. With this approach we found that UbaA of the E1/MoeB/ThiF superfamily was required for the formation of both SAMP1- and SAMP2-protein conjugates. In addition, UbaA, SAMP1, and MoaE (a homolog of the large subunit of molybdopterin synthase) were essential for MoCo-dependent dimethyl sulfoxide reductase activity, suggesting that these proteins function in MoCo-biosynthesis. UbaA and SAMP2 were also crucial for optimal growth at high temperature and the thiolation of tRNA. Based on these results, we propose a working model for archaea in which the E1-like UbaA can activate multiple Ubl SAMPs for protein conjugation as well as for sulfur transfer. In sulfur transfer, SAMP1 and SAMP2 appear specific for MoCo biosynthesis and the thiolation of tRNA, respectively. Overall, this study provides a fundamental insight into the diverse cellular functions of the Ubl system.
    Keywords: Archaeal Proteins -- Metabolism ; Haloferax Volcanii -- Metabolism ; Sulfur -- Metabolism ; Ubiquitin-Activating Enzymes -- Metabolism ; Ubiquitins -- Metabolism
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 9
    Language: English
    In: PLoS ONE, 01 January 2014, Vol.9(6), p.e99463
    Description: BACKGROUND:Alcohol misuse is common in people attending emergency departments (EDs) and there is some evidence of efficacy of alcohol screening and brief interventions (SBI). This study investigated the effectiveness of SBI approaches of different intensities delivered by ED staff in nine typical EDs in England: the SIPS ED trial. METHODS AND FINDINGS:Pragmatic multicentre cluster randomized controlled trial of SBI for hazardous and harmful drinkers presenting to ED. Nine EDs were randomized to three conditions: a patient information leaflet (PIL), 5 minutes of brief advice (BA), and referral to an alcohol health worker who provided 20 minutes of brief lifestyle counseling (BLC). The primary outcome measure was the Alcohol Use Disorders Identification Test (AUDIT) status at 6 months. Of 5899 patients aged 18 or more presenting to EDs, 3737 (63·3%) were eligible to participate and 1497 (40·1%) screened positive for hazardous or harmful drinking, of whom 1204 (80·4%) gave consent to participate in the trial. Follow up rates were 72% (n = 863) at six, and 67% (n = 810) at 12 months. There was no evidence of any differences between intervention conditions for AUDIT status or any other outcome measures at months 6 or 12 in an intention to treat analysis. At month 6, compared to the PIL group, the odds ratio of being AUDIT negative for brief advice was 1·103 (95% CI 0·328 to 3·715). The odds ratio comparing BLC to PIL was 1·247 (95% CI 0·315 to 4·939). A per protocol analysis confirmed these findings. CONCLUSIONS:SBI is difficult to implement in typical EDs. The results do not support widespread implementation of alcohol SBI in ED beyond screening followed by simple clinical feedback and alcohol information, which is likely to be easier and less expensive to implement than more complex interventions. TRIAL REGISTRATION:Current Controlled Trials ISRCTN 93681536.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 10
    Language: English
    In: PLoS ONE, 01 January 2013, Vol.8(4), p.e59348
    Description: The preclinical model of bleomycin-induced lung fibrosis, used to investigate mechanisms related to idiopathic pulmonary fibrosis (IPF), has incorrectly predicted efficacy for several candidate compounds suggesting that it may be of limited value. As an attempt to improve the predictive nature of this model, integrative bioinformatic approaches were used to compare molecular alterations in the lungs of bleomycin-treated mice and patients with IPF. Using gene set enrichment analysis we show for the first time that genes differentially expressed during the fibrotic phase of the single challenge bleomycin model were significantly enriched in the expression profiles of IPF patients. The genes that contributed most to the enrichment were largely involved in mitosis, growth factor, and matrix signaling. Interestingly, these same mitotic processes were increased in the expression profiles of fibroblasts isolated from rapidly progressing, but not slowly progressing, IPF patients relative to control subjects. The data also indicated that TGFβ was not the sole mediator responsible for the changes observed in this model since the ALK-5 inhibitor SB525334 effectively attenuated some but not all of the fibrosis associated with this model. Although some would suggest that repetitive bleomycin injuries may more effectively model IPF-like changes, our data do not support this conclusion. Together, these data highlight that a single bleomycin instillation effectively replicates several of the specific pathogenic molecular changes associated with IPF, and may be best used as a model for patients with active disease.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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