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    Guidance of mesenchymal stem cells on fibronectin structured hydrogel films
    (San Francisco, California, US : PLOS, 2014) Kasten, Annika; Naser, Tamara; Brüllhoff, Kristina; Fiedler, Jörg; Müller, Petra; Möller, Martin; Rychly, Joachim; Groll, Jürgen; Brenner, Rolf E.; Engler, Adam J.
    Designing of implant surfaces using a suitable ligand for cell adhesion to stimulate specific biological responses of stem cells will boost the application of regenerative implants. For example, materials that facilitate rapid and guided migration of stem cells would promote tissue regeneration. When seeded on fibronectin (FN) that was homogeneously immmobilized to NCO-sP(EO-stat-PO), which otherwise prevents protein binding and cell adhesion, human mesenchymal stem cells (MSC) revealed a faster migration, increased spreading and a more rapid organization of different cellular components for cell adhesion on fibronectin than on a glass surface. To further explore, how a structural organization of FN controls the behavior of MSC, adhesive lines of FN with varying width between 10 µm and 80 µm and spacings between 5 µm and 20 µm that did not allow cell adhesion were generated. In dependance on both line width and gaps, cells formed adjacent cell contacts, were individually organized in lines, or bridged the lines. With decreasing sizes of FN lines, speed and directionality of cell migration increased, which correlated with organization of the actin cytoskeleton, size and shape of the nuclei as well as of focal adhesions. Together, defined FN lines and gaps enabled a fine tuning of the structural organization of cellular components and migration. Microstructured adhesive substrates can mimic the extracellular matrix in vivo and stimulate cellular mechanisms which play a role in tissue regeneration.
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    Improving Accuracy and Temporal Resolution of Learning Curve Estimation for within- and across-Session Analysis
    (San Francisco, California, US : PLOS, 2016) Deliano, Matthias; Tabelow, Karsten; König, Reinhard; Polzehl, Jörg
    Estimation of learning curves is ubiquitously based on proportions of correct responses within moving trial windows. Thereby, it is tacitly assumed that learning performance is constant within the moving windows, which, however, is often not the case. In the present study we demonstrate that violations of this assumption lead to systematic errors in the analysis of learning curves, and we explored the dependency of these errors on window size, different statistical models, and learning phase. To reduce these errors in the analysis of single-subject data as well as on the population level, we propose adequate statistical methods for the estimation of learning curves and the construction of confidence intervals, trial by trial. Applied to data from an avoidance learning experiment with rodents, these methods revealed performance changes occurring at multiple time scales within and across training sessions which were otherwise obscured in the conventional analysis. Our work shows that the proper assessment of the behavioral dynamics of learning at high temporal resolution can shed new light on specific learning processes, and, thus, allows to refine existing learning concepts. It further disambiguates the interpretation of neurophysiological signal changes recorded during training in relation to learning.
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    Distinguishing autocrine and paracrine signals in hematopoietic stem cell culture using a biofunctional microcavity platform
    ([London] : Macmillan Publishers Limited, part of Springer Nature, 2016) Müller, Eike; Wang, Weijia; Qiao, Wenlian; Bornhäuser, Martin; Zandstra, Peter W.; Werner, Carsten; Pompe, Tilo
    Homeostasis of hematopoietic stem cells (HSC) in the mammalian bone marrow stem cell niche is regulated by signals of the local microenvironment. Besides juxtacrine, endocrine and metabolic cues, paracrine and autocrine signals are involved in controlling quiescence, proliferation and differentiation of HSC with strong implications on expansion and differentiation ex vivo as well as in vivo transplantation. Towards this aim, a cell culture analysis on a polymer microcavity carrier platform was combined with a partial least square analysis of a mechanistic model of cell proliferation. We could demonstrate the discrimination of specific autocrine and paracrine signals from soluble factors as stimulating and inhibitory effectors in hematopoietic stem and progenitor cell culture. From that we hypothesize autocrine signals to be predominantly involved in maintaining the quiescent state of HSC in single-cell niches and advocate our analysis platform as an unprecedented option for untangling convoluted signaling mechanisms in complex cell systems being it of juxtacrine, paracrine or autocrine origin.
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    A systematic review of non-productivity-related animal-based indicators of heat stress resilience in dairy cattle
    (San Francisco, California, US : PLOS, 2018-11-1) Galán, Elena; Llonch, Pol; Villagrá, Arantxa; Levit, Harel; Pinto, Severino; del Prado, Agustín
    Introduction Projected temperature rise in the upcoming years due to climate change has increased interest in studying the effects of heat stress in dairy cows. Environmental indices are commonly used for detecting heat stress, but have been used mainly in studies focused on the productivity-related effects of heat stress. The welfare approach involves identifying physiological and behavioural measurements so as to start heat stress mitigation protocols before the appearance of impending severe health or production issues. Therefore, there is growing interest in studying the effects of heat stress on welfare. This systematic review seeks to summarise the animal-based responses to heat stress (physiological and behavioural, excluding productivity) that have been used in scientific literature. Methods Using systematic review guidelines set by PRISMA, research articles were identified, screened and summarised based on inclusion criteria for physiology and behaviour, excluding productivity, for animal-based resilience indicators. 129 published articles were reviewed to determine which animal-based indicators for heat stress were most frequently used in dairy cows. Results The articles considered report at least 212 different animal-based indicators that can be aggregated into body temperature, feeding, physiological response, resting, drinking, grazing and pasture-related behaviour, reactions to heat management and others. The most common physiological animal-based indicators are rectal temperature, respiration rate and dry matter intake, while the most common behavioural indicators are time spent lying, standing and feeding. Conclusion Although body temperature and respiration rate are the animal-based indicators most frequently used to assess heat stress in dairy cattle, when choosing an animal-based indicator for detecting heat stress using scientific literature to establish thresholds, characteristics that influence the scale of the response and the definition of heat stress must be taken into account, e.g. breed, lactation stage, milk yield, system type, climate region, bedding type, diet and cooling management strategies. © 2018 Galan∗E.∗Elena et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.