Publications by authors named "G Björn Stark"

1,093 Publications

  • Page 1 of 1

Evaluation of a Novel Thiol-Norbornene-Functionalized Gelatin Hydrogel for Bioprinting of Mesenchymal Stem Cells.

Int J Mol Sci 2022 Jul 19;23(14). Epub 2022 Jul 19.

Department of Plastic and Hand Surgery, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany.

Three-dimensional bioprinting can be considered as an advancement of the classical tissue engineering concept. For bioprinting, cells have to be dispersed in hydrogels. Recently, a novel semi-synthetic thiolene hydrogel system based on norbornene-functionalized gelatin (GelNB) and thiolated gelatin (GelS) was described that resulted in the photoclick hydrogel GelNB/GelS. In this study, we evaluated the printability and biocompatibility of this hydrogel system towards adipose-tissue-derived mesenchymal stem cells (ASCs). GelNB/GelS was synthesized with three different crosslinking densities (low, medium and high), resulting in different mechanical properties with moduli of elasticity between 206 Pa and 1383 Pa. These hydrogels were tested for their biocompatibility towards ASCs in terms of their viability, proliferation and differentiation. The extrusion-based bioprinting of ASCs in GelNB/GelS-high was performed to manufacture three-dimensional cubic constructs. All three hydrogels supported the viability, proliferation and chondrogenic differentiation of ASCs to a similar extent. The adipogenic differentiation of ASCs was better supported by the softer hydrogel (GelNB/GelS-low), whereas the osteogenic differentiation was more pronounced in the harder hydrogel (GelNB/GelS-high), indicating that the differentiation fate of ASCs can be influenced via the adaption of the mechanical properties of the GelNB/GelS system. After the ex vivo chondrogenic differentiation and subcutaneous implantation of the bioprinted construct into immunocompromised mice, the production of negatively charged sulfated proteoglycans could be observed with only minimal inflammatory signs in the implanted material. Our results indicate that the GelNB/GelS hydrogels are very well suited for the bioprinting of ASCs and may represent attractive hydrogels for subsequent in vivo tissue engineering applications.
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http://dx.doi.org/10.3390/ijms23147939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321464PMC
July 2022

Rocks and Vegetation Cover Improve Body Condition of Desert Lizards During Both Summer and Winter.

Integr Comp Biol 2022 Jul 1. Epub 2022 Jul 1.

School of Zoology, Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 6997801, Israel.

Microhabitats provide ecological and physiological benefits to animals, sheltering them from predation and extreme temperatures and offering an additional supply of water and food. However, most studies have assumed no energetic costs of searching for microhabitats or moving between them, or considered how the availability of microhabitats may affect the energy reserves of animals and how such effects may differ between seasons. To fill these gaps, we studied how the body condition of lizards is affected by microhabitat availability in the extreme environment of the Judean Desert. In particular, we quantified how vegetation and rock cover in the vicinity of these lizards affect their body condition during summer and winter. First, we used aerial imagery to map the vegetation/rock cover at two study sites. Next, we collected 68 adult lizards and examined how their body condition varies across seasons and availability of vegetation and rock cover. In addition, we examined how vegetation and rock cover may differ in their effective distance (i.e, the distance that best explains body condition of lizards). We found that lizards body condition was better if they were collected closer to a higher availability of vegetation or rocks. However, while close proximity (within 10 m) was the best predictor for the positive effect of rocks, a greater distance (up to 90 m) was the best predictor for the effect of the vegetation cover. Moreover, the positive effect of vegetation was 12-fold higher than the effect of rocks. Interestingly, although the lizards' body condition during winter was poorer than during summer, the positive effects of rock and vegetation cover remained constant between the seasons. This similarity of benefits across seasons suggests that shaded microhabitats have important additional ecological roles regardless of climate, and that they may provide thermoregulatory benefits in winter too. We also found a synergic effect of vegetation and rock cover on the lizards' body condition, suggesting that their roles are complementary rather than overlapping. Our research has revealed the importance of shade- and shelter-providing microhabitats in both summer and winter. We suggest that proximity to microhabitat diversity may contribute to better body condition in lizards; or, alternatively, facilitates competition and attracts lizards with better body condition. Comprehending the complex interactions between animals and different microhabitats is critical for developing better conservation plans, understanding the risks of climate change, and suggesting mitigation strategies.
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http://dx.doi.org/10.1093/icb/icac104DOI Listing
July 2022

H3K9 methylation drives resistance to androgen receptor-antagonist therapy in prostate cancer.

Proc Natl Acad Sci U S A 2022 05 18;119(21):e2114324119. Epub 2022 May 18.

Genitourinary Malignancies Research Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195.

Antiandrogen strategies remain the prostate cancer treatment backbone, but drug resistance develops. We show that androgen blockade in prostate cancer leads to derepression of retroelements (REs) followed by a double-stranded RNA (dsRNA)-stimulated interferon response that blocks tumor growth. A forward genetic approach identified H3K9 trimethylation (H3K9me3) as an essential epigenetic adaptation to antiandrogens, which enabled transcriptional silencing of REs that otherwise stimulate interferon signaling and glucocorticoid receptor expression. Elevated expression of terminal H3K9me3 writers was associated with poor patient hormonal therapy outcomes. Forced expression of H3K9me3 writers conferred resistance, whereas inhibiting H3K9-trimethylation writers and readers restored RE expression, blocking antiandrogen resistance. Our work reveals a drug resistance axis that integrates multiple cellular signaling elements and identifies potential pharmacologic vulnerabilities.
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http://dx.doi.org/10.1073/pnas.2114324119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9173765PMC
May 2022

Large and expensive brain comes with a short lifespan: The relationship between brain size and longevity among fish taxa.

Authors:
Gavin Stark

J Fish Biol 2022 Jul 11;101(1):92-99. Epub 2022 May 11.

School of Zoology, Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.

Vertebrates show substantial interspecific variation in brain size in relation to body mass. It has long been recognized that the evolution of large brains is associated with both costs and benefits, and it is their net benefit which should be favoured by natural selection. On one hand, the substantial energetic cost imposed by the maintenance of neural tissue is expected to compromise the energetic budget of organisms with large brains and their investment in other critical organs (expensive brain framework, EBF) or important physiological process, such as somatic maintenance and repair, thus accelerating ageing that shortens lifespan, as predicted by the disposable soma theory (DST). However, selection towards larger brain size can provide cognitive benefits (e.g., high behavioural flexibility) that may mitigate extrinsic mortality pressures, and thus may indirectly select for slower ageing that prolongs lifespan, as predicted by the cognitive buffer hypothesis (CBH). The relationship between longevity and brain size has been investigated to date only among terrestrial vertebrates, although the same selective forces acting on those species may also affect vertebrates living in aquatic habitats, such as fish. Thus, whether this evolutionary trade-off for brain size and longevity exists on a large scale among fish clades remains to be addressed. In this study, using a global dataset of 407 fish species, I undertook the first phylogenetic test of the brain size/longevity relationship in aquatic vertebrate species. The study revealed a negative relationship between brain size and longevity among cartilaginous fish confirming EBF and DST. However, no pattern emerged among bony fish species. Among sharks and rays, the high metabolic cost of producing neural tissue transcends the cognitive benefits of evolving a larger brain. Consequently, my findings suggest that the cost of maintaining brain tissue is relatively higher in ectothermic species than in endothermic ones.
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http://dx.doi.org/10.1111/jfb.15074DOI Listing
July 2022

Fast and efficient CRISPR-mediated genome editing in Aureobasidium using Cas9 ribonucleoproteins.

J Biotechnol 2022 May 7;350:11-16. Epub 2022 Apr 7.

Institute of Chemical, Environmental and Bioscience Engineering, TU Wien, Gumpendorfer Strasse 1a, 1060 Wien, Austria. Electronic address:

Species of the genus Aureobasidium are ubiquitous, polyextremotolerant, "yeast-like" ascomycetes used for the industrial production of pullulan and other products and as biocontrol agents in agriculture. Their application potential and wide-spread occurrence make Aureobasidium spp. interesting study objects. The availability of a fast and efficient genome editing method is an obvious advantage for future basic and applied research on Aureobasidium. In this study, we describe the development of a CRISPR/Cas9-based genome editing method using ribonucleoproteins (RNPs) in A. pullulans and A. melanogenum. We demonstrate that this method can be used for single and multiplex genome editing using only RNPs by targeting URA3 (encoding for orotidine-5'-phosphate decarboxylase), ADE2 (encoding for phosphoribosylaminoimidazole carboxylase) and ARG4 (encoding for argininosuccinate lyase). We demonstrate the applicability of Trichoderma reesei pyr4 and Aspergillus fumigatus pyrG to complement the URA3 deficiency. Further, we show that using RNPs improves the homologous recombination rate and 20 bp long homologous flanks are sufficient. Therefore, the repair cassettes can be constructed by a single PCR, abolishing the need for laborious and time-consuming cloning, which is necessary for previously described methods for CRISPR-mediated genome editing in these fungi. The here presented method allows fast and efficient genome editing for gene deletions, modifications, and insertions in Auresobasidium with a minimized risk of off-target effects.
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http://dx.doi.org/10.1016/j.jbiotec.2022.03.017DOI Listing
May 2022
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