2020, Bakalis, Serafim, Valdramidis, Vasilis P., Argyropoulos, Dimitrios, Ahrne, Lilia, Chen, Jianshe, Cullen, P.J., Cummins, Enda, Datta, Ashim K., Emmanouilidis, Christos, Foster, Tim, Fryer, Peter J., Gouseti, Ourania, Hospido, Almudena, Knoerzer, Kai, LeBail, Alain, Marangoni, Alejandro G., Rao, Pingfan, Schlüter, Oliver K., Taoukis, Petros, Xanthakis, Epameinondas, Van Impe, Jan F.M.

[no abstract available]

2020, Kässner F., Kirstein A., Händel N., Schmid G.L., Landgraf K., Berthold A., Tannert A., Schaefer M., Wabitsch M., Kiess W., Körner A., Garten A.

Few human cell strains are suitable and readily available as in vitro adipocyte models. We used resected lipoma tissue from a patient with germline phosphatase and tensin homolog (PTEN) haploinsufficiency to establish a preadipocyte cell strain termed LipPD1 and aimed to characterize cellular functions and signalling pathway alterations in comparison to the established adipocyte model Simpson-Golabi-Behmel-Syndrome (SGBS) and to primary stromal-vascular fraction cells. We found that both cellular life span and the capacity for adipocyte differentiation as well as adipocyte-specific functions were preserved in LipPD1 and comparable to SGBS adipocytes. Basal and growth factor-stimulated activation of the PI3 K/AKT signalling pathway was increased in LipPD1 preadipocytes, corresponding to reduced PTEN levels in comparison to SGBS cells. Altogether, LipPD1 cells are a novel primary cell model with a defined genetic lesion suitable for the study of adipocyte biology. © 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

2020, Khan, E.S., Sankaran, S., Llontop, L., Del Campo, A.

Background: Collagen is a structural protein that provides mechanical stability and defined architectures to skin. In collagen-based skin disorders this stability is lost, either due to mutations in collagens or in the chaperones involved in collagen assembly. This leads to chronic wounds, skin fragility, and blistering. Existing approaches to treat such conditions rely on administration of small molecules to simulate collagen production, like 4-phenylbutyrate (4-PBA) or growth factors like TGF-β. However, these molecules are not specific for collagen synthesis, and result in unsolicited side effects. Hsp47 is a collagen-specific chaperone with a major role in collagen biosynthesis. Expression levels of Hsp47 correlate with collagen deposition. This article explores the stimulation of collagen deposition by exogenously supplied Hsp47 (collagen specific chaperone) to skin cells, including specific collagen subtypes quantification. Results: Here we quantify the collagen deposition level and the types of deposited collagens after Hsp47 stimulation in different in vitro cultures of cells from human skin tissue (fibroblasts NHDF, keratinocytes HaCat and endothelial cells HDMEC) and mouse fibroblasts (L929 and MEF). We find upregulated deposition of fibrillar collagen subtypes I, III and V after Hsp47 delivery. Network collagen IV deposition was enhanced in HaCat and HDMECs, while fibril-associated collagen XII was not affected by the increased intracellular Hsp47 levels. The deposition levels of fibrillar collagen were cell-dependent i.e. Hsp47-stimulated fibroblasts deposited significantly higher amount of fibrillar collagen than Hsp47-stimulated HaCat and HDMECs. Conclusions: A 3-fold enhancement of collagen deposition was observed in fibroblasts upon repeated dosage of Hsp47 within the first 6 days of culture. Our results provide fundamental understanding towards the idea of using Hsp47 as therapeutic protein to treat collagen disorders.

2020, Bodirsky, Benjamin Leon, Dietrich, Jan Philipp, Martinelli, Eleonora, Stenstad, Antonia, Pradhan, Prajal, Gabrysch, Sabine, Mishra, Abhijeet, Weindl, Isabelle, Le Mouël, Chantal, Rolinski, Susanne, Baumstark, Lavinia, Wang, Xiaoxi, Waid, Jillian L., Lotze-Campen, Hermann, Popp, Alexander

The nutrition transition transforms food systems globally and shapes public health and environmental change. Here we provide a global forward-looking assessment of a continued nutrition transition and its interlinked symptoms in respect to food consumption. These symptoms range from underweight and unbalanced diets to obesity, food waste and environmental pressure. We find that by 2050, 45% (39–52%) of the world population will be overweight and 16% (13–20%) obese, compared to 29% and 9% in 2010 respectively. The prevalence of underweight approximately halves but absolute numbers stagnate at 0.4–0.7 billion. Aligned, dietary composition shifts towards animal-source foods and empty calories, while the consumption of vegetables, fruits and nuts increases insufficiently. Population growth, ageing, increasing body mass and more wasteful consumption patterns are jointly pushing global food demand from 30 to 45 (43–47) Exajoules. Our comprehensive open dataset and model provides the interfaces necessary for integrated studies of global health, food systems, and environmental change. Achieving zero hunger, healthy diets, and a food demand compatible with environmental boundaries necessitates a coordinated redirection of the nutrition transition. Reducing household waste, animal-source foods, and overweight could synergistically address multiple symptoms at once, while eliminating underweight would not substantially increase food demand.

2020, Weinberg, F., Han, M.K.L., Dahmke, I.N., Campo, A.D., de Jonge, N.

Excess presence of the human epidermal growth factor receptor 2 (HER2) as well as of the focal adhesion protein complexes are associated with increased proliferation, migratory, and invasive behavior of cancer cells. A cross-regulation between HER2 and integrin signaling pathways has been found, but the exact mechanism remains elusive. Here, we investigated whether HER2 colocalizes with focal adhesion complexes on breast cancer cells overexpressing HER2. For this purpose, vinculin or talin green fluorescent protein (GFP) fusion proteins, both key constituents of focal adhesions, were expressed in breast cancer cells. HER2 was either extracellularly or intracellularly labeled with fluorescent quantum dots nanoparticles (QDs). The cell-substrate interface was analyzed at the location of the focal adhesions by means of total internal reflection fluorescent microscopy or correlative fluorescence- and scanning transmission electron microscopy. Expression of HER2 at the cell-substrate interface was only observed upon intracellular labeling, and was heterogeneous with both HER2-enriched and -low regions. In contrast to an expected enrichment of HER2 at focal adhesions, an anti-correlated expression pattern was observed for talin and HER2. Our findings suggest a spatial anti-correlation between HER2 and focal adhesion complexes for adherent cells.

2020, Gorzkiewicz, Michal, Konopka, Malgorzata, Janaszewska, Anna, Tarasenko, Irina I., Sheveleva, Nadezhda N., Gajek, Arkadiusz, Neelov, Igor M., Klajnert-Maculewicz, Barbara

In order to enhance intracellular uptake and accumulation of therapeutic nucleic acids for improved gene therapy methods, numerous delivery vectors have been elaborated. Based on their origin, gene carriers are generally classified as viral or non-viral vectors. Due to their significantly reduced immunogenicity and highly optimized methods of synthesis, nanoparticles (especially those imitating natural biomolecules) constitute a promising alternative for virus-based delivery devices. Thus, we set out to develop innovative peptide dendrimers for clinical application as transfection agents and gene carriers. In the present work we describe the synthesis of two novel lysine-based dendritic macromolecules (D3K2 and D3G2) and their initial characterization for cytotoxicity/genotoxicity and transfection potential in two human cell line models: cervix adenocarcinoma (HeLa) and microvascular endothelial (HMEC-1). This approach allowed us to identify more cationic D3K2 as potent delivery agent, being able to increase intracellular accumulation of large nucleic acid molecules such as plasmids. Moreover, the dendrimers exhibited specific cytotoxicity towards cancer cell line without showing significant toxic effects on normal cells. These observations are promising prognosis for future clinical application of this type of nanoparticles. © 2019 The Authors

2020, Kiefer, R., Jurisic, M., Dahlem, C., Koch, M., Schmitt, M.J., Kiemer, A.K., Schneider, M., Breinig, F.

Nanoparticles (NPs) are able to deliver a variety of substances into eukaryotic cells. However, their usage is often hampered by a lack of specificity, leading to the undesired uptake of NPs by virtually all cell types. In contrast to this, yeast is known to be specifically taken up into immune cells after entering the body. Therefore, we investigated the interaction of biodegradable surface-modified poly(lactic-co-glycolic acid) (PLGA) particles with yeast cells to overcome the unspecificity of the particulate carriers. Cells of different Saccharomyces cerevisiae strains were characterized regarding their interaction with PLGA-NPs under isotonic and hypotonic conditions. The particles were shown to efficiently interact with yeast cells leading to stable NP/yeast-complexes allowing to associate or even internalize compounds. Notably, applying those complexes to a coculture model of HeLa cells and macrophages, the macrophages were specifically targeted. This novel nano-in-micro carrier system suggests itself as a promising tool for the delivery of biologically active agents into phagocytic cells combining specificity and efficiency.

2020, Liu, Zhu, Ciais, Philippe, Deng, Zhu, Lei, Ruixue, Davis, Steven J., Feng, Sha, Zheng, Bo, Cui, Duo, Dou, Xinyu, Zhu, Biqing, Guo, Rui, Ke, Piyu, Sun, Taochun, Lu, Chenxi, He, Pan, Wang, Yuan, Yue, Xu, Wang, Yilong, Lei, Yadong, Zhou, Hao, Cai, Zhaonan, Wu, Yuhui, Guo, Runtao, Han, Tingxuan, Xue, Jinjun, Boucher, Olivier, Boucher, Eulalie, Chevallier, Frédéric, Tanaka, Katsumasa, Wei, Yiming, Zhong, Haiwang, Kang, Chongqing, Zhang, Ning, Chen, Bin, Xi, Fengming, Liu, Miaomiao, Bréon, François-Marie, Lu, Yonglong, Zhang, Qiang, Guan, Dabo, Gong, Peng, Kammen, Daniel M., He, Kebin, Schellnhuber, Hans Joachim

The COVID-19 pandemic is impacting human activities, and in turn energy use and carbon dioxide (CO2) emissions. Here we present daily estimates of country-level CO2 emissions for different sectors based on near-real-time activity data. The key result is an abrupt 8.8% decrease in global CO2 emissions (−1551 Mt CO2) in the first half of 2020 compared to the same period in 2019. The magnitude of this decrease is larger than during previous economic downturns or World War II. The timing of emissions decreases corresponds to lockdown measures in each country. By July 1st, the pandemic’s effects on global emissions diminished as lockdown restrictions relaxed and some economic activities restarted, especially in China and several European countries, but substantial differences persist between countries, with continuing emission declines in the U.S. where coronavirus cases are still increasing substantially.

2020, Clauder, Franziska, Zitzmann, Franziska D., Friebe, Sabrina, Mayr, Stefan G., Robitzki, Andrea A., Beck-Sickinger, Annette G.

Insufficient endothelialization of cardiovascular devices is a high-risk factor for implant failure. Presentation of extracellular matrix (ECM)-derived coatings is a well-known strategy to improve implant integration. However, the complexity of the system is challenging and strategies for applying multifunctionality are required. Here, we engineered mussel-derived surface-binding peptides equipped with integrin (c[RGDfK]) and proteoglycan binding sites (FHRRIKA) for enhanced endothelialization. Surface-binding properties of the platform containing l-3,4-dihydroxyphenylalanine (DOPA) residues were confirmed for hydrophilized polycaprolactone-co-lactide scaffolds as well as for glass and polystyrene. Further, heparin and the heparin-binding angiogenic factors VEGF, FGF-2 and CXCL12 were immobilized onto the peptide in a modular assembly. Presentation of bioactive peptides greatly enhanced human umbilical vein endothelial cell (HUVEC) adhesion and survival under static and fluidic conditions. In subsequent investigations, peptide-heparin-complexes loaded with CXCL12 or VEGF had an additional increasing effect on cell viability, differentiation and migration. Finally, hemocompatibility of the coatings was ensured. This study demonstrates that coatings combining adhesion peptides, glycosaminoglycans and modulators are a versatile tool to convey ECM-inspired multifunctionality to biomaterials and efficiently promote their integration. © 2020 The Royal Society of Chemistry.

2020, Wiedermann, Marc, Smith, E. Keith, Heitzig, Jobst, Donges, Jonathan F.

Social tipping, where minorities trigger larger populations to engage in collective action, has been suggested as one key aspect in addressing contemporary global challenges. Here, we refine Granovetter’s widely acknowledged theoretical threshold model of collective behavior as a numerical modelling tool for understanding social tipping processes and resolve issues that so far have hindered such applications. Based on real-world observations and social movement theory, we group the population into certain or potential actors, such that – in contrast to its original formulation – the model predicts non-trivial final shares of acting individuals. Then, we use a network cascade model to explain and analytically derive that previously hypothesized broad threshold distributions emerge if individuals become active via social interaction. Thus, through intuitive parameters and low dimensionality our refined model is adaptable to explain the likelihood of engaging in collective behavior where social-tipping-like processes emerge as saddle-node bifurcations and hysteresis. © 2020, The Author(s).