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Melt Electrowriting of Scaffolds with a Porosity Gradient to Mimic the Matrix Structure of the Human Trabecular Meshwork
2022, Włodarczyk-Biegun, Małgorzata K., Villiou, Maria, Koch, Marcus, Muth, Christina, Wang, Peixi, Ott, Jenna, del Campo, Aranzazu
The permeability of the Human Trabecular Meshwork (HTM) regulates eye pressure via a porosity gradient across its thickness modulated by stacked layers of matrix fibrils and cells. Changes in HTM porosity are associated with increases in intraocular pressure and the progress of diseases like glaucoma. Engineered HTMs could help to understand the structure-function relation in natural tissues, and lead to new regenerative solutions. Here, melt electrowriting (MEW) is explored as a biofabrication technique to produce fibrillar, porous scaffolds that mimic the multilayer, gradient structure of native HTM. Poly(caprolactone) constructs with a height of 125-500 μm and fiber diameters of 10-12 μm are printed. Scaffolds with a tensile modulus between 5.6 and 13 MPa, and a static compression modulus in the range of 6-360 kPa are obtained by varying the scaffolds design, i.e., density and orientation of the fibers and number of stacked layers. Primary HTM cells attach to the scaffolds, proliferate, and form a confluent layer within 8-14 days, depending on the scaffold design. High cell viability and cell morphology close to that in the native tissue are observed. The present work demonstrates the utility of MEW to reconstruct complex morphological features of natural tissues.
Cascading Hazards in the Aftermath of Australia's 2019/2020 Black Summer Wildfires
2021, Kemter, M., Fischer, M., Luna, L.V., Schönfeldt, E., Vogel, J., Banerjee, A., Korup, O., Thonicke, K.
Following an unprecedented drought, Australia's 2019/2020 “Black Summer” fire season caused severe damage, gravely impacting both humans and ecosystems, and increasing susceptibility to other hazards. Heavy precipitation in early 2020 led to flooding and runoff that entrained ash and soil in burned areas, increasing sediment concentration in rivers, and reducing water quality. We exemplify this hazard cascade in a catchment in New South Wales by mapping burn severity, flood, and rainfall recurrence; estimating changes in soil erosion; and comparing them with river turbidity data. We show that following the extreme drought and wildfires, even moderate rain and floods led to undue increases in soil erosion and reductions in water quality. While natural risk analysis and planning commonly focuses on a single hazard, we emphasize the need to consider the entire hazard cascade, and highlight the impacts of ongoing climate change beyond its direct effect on wildfires.
Limiting global warming to 1.5 °C will lower increases in inequalities of four hazard indicators of climate change
2019, Shiogama, Hideo, Hasegawa, Tomoko, Fujimori, Shinichiro, Murakami, Daisuke, Takahashi, Kiyoshi, Tanaka, Katsumasa, Emori, Seita, Kubota, Izumi, Abe, Manabu, Imada, Yukiko, Watanabe, Masahiro, Mitchell, Daniel, Schaller, Nathalie, Sillmann, Jana, Fischer, Erich M., Scinocca, John F., Bethke, Ingo, Lierhammer, Ludwig, Takakura, Jun’ya, Trautmann, Tim, Döll, Petra, Ostberg, Sebastian, Müller Schmied, Hannes, Saeed, Fahad, Schleussner, Carl-Friedrich
Clarifying characteristics of hazards and risks of climate change at 2 °C and 1.5 °C global warming is important for understanding the implications of the Paris Agreement. We perform and analyze large ensembles of 2 °C and 1.5 °C warming simulations. In the 2 °C runs, we find substantial increases in extreme hot days, heavy rainfalls, high streamflow and labor capacity reduction related to heat stress. For example, about half of the world's population is projected to experience a present day 1-in-10 year hot day event every other year at 2 °C warming. The regions with relatively large increases of these four hazard indicators coincide with countries characterized by small CO2 emissions, low-income and high vulnerability. Limiting global warming to 1.5 °C, compared to 2 °C, is projected to lower increases in the four hazard indicators especially in those regions.
Quantifying the parameter dependent basin of the unsafe regime of asymmetric Lévy-noise-induced critical transitions
2021, Ma, Jinzhong, Xu, Yong, Li, Yongge, Tian, Ruilan, Ma, Shaojuan, Kurths, J.
In real systems, the unpredictable jump changes of the random environment can induce the critical transitions (CTs) between two non-adjacent states, which are more catastrophic. Taking an asymmetric Lévy-noise-induced tri-stable model with desirable, sub-desirable, and undesirable states as a prototype class of real systems, a prediction of the noise-induced CTs from the desirable state directly to the undesirable one is carried out. We first calculate the region that the current state of the given model is absorbed into the undesirable state based on the escape probability, which is named as the absorbed region. Then, a new concept of the parameter dependent basin of the unsafe regime (PDBUR) under the asymmetric Lévy noise is introduced. It is an efficient tool for approximately quantifying the ranges of the parameters, where the noise-induced CTs from the desirable state directly to the undesirable one may occur. More importantly, it may provide theoretical guidance for us to adopt some measures to avert a noise-induced catastrophic CT. © 2021, The Author(s).
Gelation kinetics of thiol-methylsulfone (MS) hydrogel formulations for 3D cell culture
2022, de Miguel-Jiménez, Adrián, Ebeling, Bastian, Paez, Julieta I., Fink-Straube, Claudia, Pearson, Samuel, del Campo, Aranzazu
Crosslinking chemistries that allow hydrogel formation within minutes are essential to achieve homogeneous networks and cell distributions in 3D cell culture. Thiol-methylsulfone (MS) crosslinking chemistry offers minutes-scale gelation under near-physiological conditions showing many desirable attributes for 3D cell encapsulation. Here we investigate the gelation kinetics and mechanical properties of PEG-based hydrogels formed by thiol-tetrazole methylsulfone (TzMS) crosslinking as a function of buffer, crosslinker structure, and degree of TzMS functionalization. Appropriate buffer selection ensured constant pH throughout crosslinking. The formulation containing cell adhesive ligand RGD and enzymatically-degradable peptide VPM gelled in ca. 4 min at pH 7.5, and stiffness could be increased from hundreds of Pascals to > 1 kPa by using excess VPM. The gelation times and stiffnesses for these hydrogels are highly suitable for 3D cell encapsulations, and pave the way for reliable 3D cell culture workflows in pipetting robots.
The Berlin principles on one health - Bridging global health and conservation
2020, Gruetzmacher, Kim, Karesh, William B., Amuasi, John H., Arshad, Adnan, Farlow, Andrew, Gabrysch, Sabine, Jetzkowitz, Jens, Lieberman, Susan, Palmer, Clare, Winkler, Andrea S., Walzer, Chris
For over 15-years, proponents of the One Health approach have worked to consistently interweave components that should never have been separated and now more than ever need to be re-connected: the health of humans, non-human animals, and ecosystems. We have failed to heed the warning signs. A One Health approach is paramount in directing our future health in this acutely and irrevocably changed world. COVID-19 has shown us the exorbitant cost of inaction. The time to act is now. © 2020
The First Report of mcr-1-Carrying Escherichia coli Originating from Animals in Serbia
2021, Mišić, Dušan, Kiskaroly, Ferenc, Szostak, Michael P., Cabal, Adriana, Ruppitsch, Werner, Bernreiter-Hofer, Tanja, Milovanovic, Viktoria, Feßler, Andrea T., Allerberger, Franz, Spergser, Joachim, Müller, Elke, Schwarz, Stefan, Braun, Sascha D., Monecke, Stefan, Ehricht, Ralf, Korus, Maciej, Benković, Damir, Korzeniowska, Malgorzata, Loncaric, Igor
The aim of this study was continuous monitoring of the presence of mcr-1 to mcr-5 genes in Enterobacterales isolated from cattle, pigs, and domestic poultry at intensive breeding facilities in Northern Vojvodina, Serbia, from 1 January 1 to 1 October 2020. Out of 2167 examined samples, mcr-1 was observed in five E. coli isolates originating from healthy turkeys. Four isolates belonged to the phylogenetic group B1, and one isolate to the phylogenetic group A. Detected E. coli serogenotypes (somatic O and flagellar H antigens) were O8:H25 and O29:H25. Core-genome multi-locus sequence typing (cgMLST) revealed three ST58 isolates clustering together in Clonal Complex (CC) 155 and two singletons of ST641-CC86 and ST410-CC23, respectively. Clonotyping revealed CH4-32 (n = 3), CH6-53 (n = 1) and CH4-24 (n = 1). In all isolates, the mcr-1 gene was located on a large IncX4 replicon type plasmid. Eight virulence-associated genes (VAGs) typical of avian pathogenic E. coli (APEC) (fyuA, fimH, hlyF, iss, ompT, sitA, traT, iroN) were detected in four isolates. These isolates were investigated for susceptibility to four biocides and revealed MIC values of 0.125% for glutardialdehyde, of 0.00003-0.00006% for chlorohexidine, of 4-6% for isopropanol and of 0.001-0.002% for benzalkonium chloride. All obtained MIC values of the tested biocides were comparable to the reference strain, with no indication of possible resistance. This is the first report of mcr-1.1-carrying E. coli from Serbia. Although only samples from turkeys were mcr-positive in this study, continuous monitoring of livestock samples is advised to prevent a spill-over from animals to humans.
Redox-triggerable Luciferin-Bioinspired Hydrogels as Injectable and Cell-encapsulating Matrices
2022, Jin, Minye, Gläser, Alisa, Paez, Julieta I.
Over the past few decades there has been a great interest in developing smart hydrogels that are stimuli-responsive, due to their ability to respond to variations caused by external stimuli. These materials are exploited for biomedical applications such as biosensors, injectable scaffolds, drug delivery and tissue engineering. Recently, our group reported firefly-inspired hydrogel matrices for 3D cell culture. This platform exhibited certain advantages like rapid gelation rate and tunability of mechanical and biological properties. However, this firstly reported system did not allow for fine control of the gelation onset because the crosslinking reaction started as soon as the two precursors were mixed. Moreover, one of its precursors demonstrated poor storage stability in aqueous solution. These limitations restrict its application as injectable matrices. In this article, we endow the luciferin-inspired hydrogels with redox-triggering capability, to overcome the limitations of the previous system and to widen its application range. We achieve this goal by introducing protected macromers as hydrogel polymeric precursors that can be activated in the presence of a mild reductant, to trigger gel formation in situ with high degree of control. We demonstrate that the regulation of intrinsic (e.g., structure of protecting group, reductant type) and extrinsic (e.g., pH, temperature) parameters of the triggering reaction can be used to modulate key materials properties. This novel upgraded redox-triggerable system enables precise control over gelation onset and kinetics, thus facilitating its utilization as injectable hydrogel without negatively impacting its cytocompatibility. Our findings expand the current toolkit of chemically-based stimuli-responsive hydrogels.