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Benjamin Dalton, Ivo F. Sbalzarini, Itsuo Hanasaki
Fundamentals of the logarithmic measure for revealing multimodal diffusion.
Biophys J, 120(5) 829-843 (2021)
PubMed Source   

We develop a theoretical foundation for a time-series analysis method suitable for revealing the spectrum of diffusion coefficients in mixed Brownian systems, where no prior knowledge of particle distinction is required. This method is directly relevant for particle tracking in biological systems, where diffusion processes are often non-uniform. We transform Brownian data onto the logarithmic domain, where the coefficients for individual modes of diffusion appear as distinct spectral peaks in the probability density. We refer to the method as the logarithmic measure of diffusion, or simply as the logarithmic measure. We provide a general protocol for deriving analytical expressions for the probability densities on the logarithmic domain. The protocol is applicable for any number of spatial dimensions with any number of diffusive states. The analytical form can be fitted to data to reveal multiple diffusive modes. We validate the theoretical distributions and benchmark the accuracy and sensitivity of the method by extracting multi-modal diffusion coefficients from 2D Brownian simulations of poly-disperse filament bundles. Bundling the filaments allows us to control the system non-uniformity and hence quantify the sensitivity of the method. By exploiting the anisotropy of the simulated filaments, we generalize the logarithmic measure to rotational diffusion. By fitting the analytical forms to simulation data, we confirm the method's theoretical foundation. An error analysis in the single-mode regime shows that the proposed method is comparable in accuracy to the standard mean squared displacement approach for evaluating diffusion coefficients. For the case of multi-modal diffusion, we compare the logarithmic measure against other more sophisticated methods, showing that both model selectivity and extraction accuracy are comparable for small data sets. Therefore we suggest that the logarithmic measure, as a method for multi-modal diffusion coefficient extraction, is ideally suited for small data sets, a condition often confronted in the experimental context. Finally, we critically discuss the proposed benefits of the method and its information content.
@article{Dalton7880,
author={Benjamin Dalton, Ivo F. Sbalzarini, Itsuo Hanasaki},
title={Fundamentals of the logarithmic measure for revealing multimodal diffusion.},
journal ={Biophysical journal},
volume={120},
issue ={5},
pages={829--843},
year=2021
}

Felipe Mora-Bermúdez, Elena Taverna, Wieland Huttner
From stem and progenitor cells to neurons in the developing neocortex - key differences among hominids.
FEBS J, Art. No. doi: 10.1111/febs.15793 (2021)
PubMed Source   

Comparing the biology of humans to that of other primates, and notably other hominids, is a useful path to learn more about what makes us human. Some of the most interesting differences among hominids are closely related to brain development and function, for example behaviour and cognition. This makes it particularly interesting to compare the hominid neural cells of the neocortex, a part of the brain that plays central roles in those processes. However, well-preserved tissue from great apes is usually extremely difficult to obtain. A variety of new alternative tools, e.g. brain organoids, are now beginning to make it possible to search for such differences and analyse their potential biological and biomedical meaning. Here we present an overview of recent findings from comparisons of the neural stem and progenitor cells (NSPCs) and neurons of hominids. In addition to differences in proliferation and differentiation of NSPCs, and maturation of neurons, we highlight that the regulation of the timing of these processes is emerging as a general foundational difference in the development of the neocortex of hominids.
@article{Mora-Bermúdez7942,
author={Felipe Mora-Bermúdez, Elena Taverna, Wieland Huttner},
title={From stem and progenitor cells to neurons in the developing neocortex - key differences among hominids.},
journal ={The FEBS journal},
volume={},
pages={1--1},
year=2021
}

Lotta Hof, Till Moreth, Michael Koch, Tim Liebisch, Marina Kurtz, Julia Tarnick, Susanna M Lissek, Monique Ma Verstegen, Luc Jw van der Laan, Meritxell Huch, Franziska Matthäus, Ernst H K Stelzer, Francesco Pampaloni
Long-term live imaging and multiscale analysis identify heterogeneity and core principles of epithelial organoid morphogenesis.
BMC Biol, 19(1) Art. No. 37 (2021)
PubMed Source   

Organoids are morphologically heterogeneous three-dimensional cell culture systems and serve as an ideal model for understanding the principles of collective cell behaviour in mammalian organs during development, homeostasis, regeneration, and pathogenesis. To investigate the underlying cell organisation principles of organoids, we imaged hundreds of pancreas and cholangiocarcinoma organoids in parallel using light sheet and bright-field microscopy for up to 7 days.
@article{Hof7945,
author={Lotta Hof, Till Moreth, Michael Koch, Tim Liebisch, Marina Kurtz, Julia Tarnick, Susanna M Lissek, Monique Ma Verstegen, Luc Jw van der Laan, Meritxell Huch, Franziska Matthäus, Ernst H K Stelzer, Francesco Pampaloni},
title={Long-term live imaging and multiscale analysis identify heterogeneity and core principles of epithelial organoid morphogenesis.},
journal ={BMC biology},
volume={19},
issue ={1},
pages={null--null},
year=2021
}

Tingting Fu, Oskar Knittelfelder, Olivier Geffard, Yohann Clément, Eric Testet, Nicolas Elie, David Touboul, Khedidja Abbaci, Andrej Shevchenko, Jerome Lemoine, Arnaud Chaumot, Arnaud Salvador, Davide Degli-Esposti, Sophie Ayciriex
Shotgun lipidomics and mass spectrometry imaging unveil diversity and dynamics in Gammarus fossarum lipid composition.
iScience, 24(2) Art. No. 102115 (2021)
PubMed Source   

Sentinel species are playing an indispensable role in monitoring environmental pollution in aquatic ecosystems. Many pollutants found in water prove to be endocrine disrupting chemicals that could cause disruptions in lipid homeostasis in aquatic species. A comprehensive profiling of the lipidome of these species is thus an essential step toward understanding the mechanism of toxicity induced by pollutants. Both the composition and spatial distribution of lipids in freshwater crustacean Gammarus fossarum were extensively examined herein. The baseline lipidome of gammarids of different sex and reproductive stages was established by high throughput shotgun lipidomics. Spatial lipid mapping by high resolution mass spectrometry imaging led to the discovery of sulfate-based lipids in hepatopancreas and their accumulation in mature oocytes. A diverse and dynamic lipid composition in G. fossarum was uncovered, which deepens our understanding of the biochemical changes during development and which could serve as a reference for future ecotoxicological studies.
@article{Fu7939,
author={Tingting Fu, Oskar Knittelfelder, Olivier Geffard, Yohann Clément, Eric Testet, Nicolas Elie, David Touboul, Khedidja Abbaci, Andrej Shevchenko, Jerome Lemoine, Arnaud Chaumot, Arnaud Salvador, Davide Degli-Esposti, Sophie Ayciriex},
title={Shotgun lipidomics and mass spectrometry imaging unveil diversity and dynamics in Gammarus fossarum lipid composition.},
journal ={iScience},
volume={24},
issue ={2},
pages={null--null},
year=2021
}

Georg Krainer, Timothy J Welsh, Jerelle A Joseph, Jorge R Espinosa, Sina Wittmann, Ella de Csilléry, Akshay Sridhar, Zenon Toprakcioglu, Giedre Gudiškytė, Magdalena A Czekalska, William E Arter, Jordina Guillén-Boixet, Titus Franzmann, Seema Qamar, Peter St George-Hyslop, Anthony Hyman, Rosana Collepardo-Guevara, Simon Alberti, Tuomas P J Knowles
Reentrant liquid condensate phase of proteins is stabilized by hydrophobic and non-ionic interactions.
Nat Commun, 12(1) Art. No. 1085 (2021)
PubMed Source   

Liquid-liquid phase separation of proteins underpins the formation of membraneless compartments in living cells. Elucidating the molecular driving forces underlying protein phase transitions is therefore a key objective for understanding biological function and malfunction. Here we show that cellular proteins, which form condensates at low salt concentrations, including FUS, TDP-43, Brd4, Sox2, and Annexin A11, can reenter a phase-separated regime at high salt concentrations. By bringing together experiments and simulations, we demonstrate that this reentrant phase transition in the high-salt regime is driven by hydrophobic and non-ionic interactions, and is mechanistically distinct from the low-salt regime, where condensates are additionally stabilized by electrostatic forces. Our work thus sheds light on the cooperation of hydrophobic and non-ionic interactions as general driving forces in the condensation process, with important implications for aberrant function, druggability, and material properties of biomolecular condensates.
@article{Krainer7941,
author={Georg Krainer, Timothy J Welsh, Jerelle A Joseph, Jorge R Espinosa, Sina Wittmann, Ella de Csilléry, Akshay Sridhar, Zenon Toprakcioglu, Giedre Gudiškytė, Magdalena A Czekalska, William E Arter, Jordina Guillén-Boixet, Titus Franzmann, Seema Qamar, Peter St George-Hyslop, Anthony Hyman, Rosana Collepardo-Guevara, Simon Alberti, Tuomas P J Knowles},
title={Reentrant liquid condensate phase of proteins is stabilized by hydrophobic and non-ionic interactions.},
journal ={Nature communications},
volume={12},
issue ={1},
pages={null--null},
year=2021
}

Dimitri Eigel, Romy Schuster, Max J Männel, Julian Thiele, Martyna J Panasiuk, Laura C Andreae, Carmine Varricchio, Andrea Brancale, Petra B Welzel, Wieland Huttner, Carsten Werner, Ben Newland, Katherine S. Long
Sulfonated cryogel scaffolds for focal delivery in ex-vivo brain tissue cultures.
Biomaterials, 271 Art. No. 120712 (2021)
PubMed Source   

The human brain has unique features that are difficult to study in animal models, including the mechanisms underlying neurodevelopmental and psychiatric disorders. Despite recent advances in human primary brain tissue culture systems, the use of these models to elucidate cellular disease mechanisms remains limited. A major reason for this is the lack of tools available to precisely manipulate a specific area of the tissue in a reproducible manner. Here we report an easy-to-use tool for site-specific manipulation of human brain tissue in culture. We show that line-shaped cryogel scaffolds synthesized with precise microscale dimensions allow the targeted delivery of a reagent to a specific region of human brain tissue in culture. 3-sulfopropyl acrylate (SPA) was incorporated into the cryogel network to yield a negative surface charge for the reversible binding of molecular cargo. The fluorescent dyes BODIPY and DiI were used as model cargos to show that placement of dye loaded scaffolds onto brain tissue in culture resulted in controlled delivery without a burst release, and labelling of specific regions without tissue damage. We further show that cryogels can deliver tetrodotoxin to tissue, inhibiting neuronal function in a reversible manner. The robust nature and precise dimensions of the cryogel resulted in a user-friendly and reproducible tool to manipulate primary human tissue cultures. These easy-to-use cryogels offer an innovate approach for more complex manipulations of ex-vivo tissue.
@article{Eigel7943,
author={Dimitri Eigel, Romy Schuster, Max J Männel, Julian Thiele, Martyna J Panasiuk, Laura C Andreae, Carmine Varricchio, Andrea Brancale, Petra B Welzel, Wieland Huttner, Carsten Werner, Ben Newland, Katherine S. Long},
title={Sulfonated cryogel scaffolds for focal delivery in ex-vivo brain tissue cultures.},
journal ={Biomaterials},
volume={271},
pages={null--null},
year=2021
}

Christoph Heier, Oskar Knittelfelder, Harald F Hofbauer, Wolfgang Mende, Ingrid Pörnbacher, Laura Schiller, Gabriele Schoiswohl, Hao Xie, Sebastian Grönke, Andrej Shevchenko, Ronald P Kühnlein
Hormone-sensitive lipase couples intergenerational sterol metabolism to reproductive success.
Elife, 10 Art. No. e63252 (2021)
PubMed Source   

Triacylglycerol (TG) and steryl ester (SE) lipid storage is a universal strategy to maintain organismal energy and membrane homeostasis. Cycles of building and mobilizing storage fat are fundamental in (re)distributing lipid substrates between tissues or to progress ontogenetic transitions. In this study we show that Hormone-sensitive lipase (Hsl) specifically controls SE mobilization to initiate intergenerational sterol transfer in Drosophila melanogaster. Tissue-autonomous Hsl functions in the maternal fat body and germline coordinately prevent adult SE overstorage and maximize sterol allocation to embryos. While Hsl-deficiency is largely dispensable for normal development on sterol-rich diets, animals depend on adipocyte Hsl for optimal fecundity when dietary sterol becomes limiting. Notably, accumulation of SE but not of TG is a characteristic of Hsl-deficient cells across phyla including murine white adipocytes. In summary, we identified Hsl as an ancestral regulator of SE degradation, which improves intergenerational sterol transfer and reproductive success in flies.
@article{Heier7935,
author={Christoph Heier, Oskar Knittelfelder, Harald F Hofbauer, Wolfgang Mende, Ingrid Pörnbacher, Laura Schiller, Gabriele Schoiswohl, Hao Xie, Sebastian Grönke, Andrej Shevchenko, Ronald P Kühnlein},
title={Hormone-sensitive lipase couples intergenerational sterol metabolism to reproductive success.},
journal ={eLife},
volume={10},
pages={1--1},
year=2021
}

Tobias Pietzsch, Lorenzo Duso, Christoph Zechner
Compartor: A toolbox for the automatic generation of moment equations for dynamic compartment populations.
Bioinformatics, Art. No. doi: 10.1093/bioinformatics/btab058 (2021)
PubMed Source   

Many biochemical processes in living organisms take place inside compartments that can interact with each other and remodel over time. In a recent work (Duso and Zechner, 2020), we have shown how the stochastic dynamics of a compartmentalized biochemical system can be effectively studied using moment equations. With this technique, the time evolution of a compartment population is summarized using a finite number of ordinary differential equations, which can be analyzed very efficiently. However, the derivation of moment equations by hand can become time-consuming for systems comprising multiple reactants and interactions. Here we present Compartor, a toolbox that automatically generates the moment equations associated with a user-defined compartmentalized system. Through the moment equation method, Compartor renders the analysis of stochastic population models accessible to a broader scientific community.
@article{Pietzsch7933,
author={Tobias Pietzsch, Lorenzo Duso, Christoph Zechner},
title={Compartor: A toolbox for the automatic generation of moment equations for dynamic compartment populations.},
journal ={Bioinformatics (Oxford, England)},
volume={},
pages={1--1},
year=2021
}

Veronica Diez, Sofia Traikov, Kathrin Schmeisser, Akshay Kumar Das Adhikari, Teymuras V. Kurzchalia
Glycolate combats massive oxidative stress by restoring redox potential in Caenorhabditis elegans.
Commun Biol, 4(1) Art. No. 151 (2021)
PubMed Source   

Upon exposure to excessive reactive oxygen species (ROS), organismal survival depends on the strength of the endogenous antioxidant defense barriers that prevent mitochondrial and cellular deterioration. Previously, we showed that glycolic acid can restore the mitochondrial membrane potential of C. elegans treated with paraquat, an oxidant that produces superoxide and other ROS species, including hydrogen peroxide. Here, we demonstrate that glycolate fully suppresses the deleterious effects of peroxide on mitochondrial activity and growth in worms. This endogenous compound acts by entering serine/glycine metabolism. In this way, conversion of glycolate into glycine and serine ameliorates the drastically decreased NADPH/NADP+ and GSH/GSSG ratios induced by H2O2 treatment. Our results reveal the central role of serine/glycine metabolism as a major provider of reducing equivalents to maintain cellular antioxidant systems and the fundamental function of glycolate as a natural antioxidant that improves cell fitness and survival.
@article{Diez7934,
author={Veronica Diez, Sofia Traikov, Kathrin Schmeisser, Akshay Kumar Das Adhikari, Teymuras V. Kurzchalia},
title={Glycolate combats massive oxidative stress by restoring redox potential in Caenorhabditis elegans.},
journal ={Communications biology},
volume={4},
issue ={1},
pages={null--null},
year=2021
}

Anders S Hansen, Christoph Zechner
Promoters adopt distinct dynamic manifestations depending on transcription factor context.
Mol Syst Biol, 17(2) Art. No. e9821 (2021)
PubMed Source   

Cells respond to external signals and stresses by activating transcription factors (TF), which induce gene expression changes. Prior work suggests that signal-specific gene expression changes are partly achieved because different gene promoters exhibit distinct induction dynamics in response to the same TF input signal. Here, using high-throughput quantitative single-cell measurements and a novel statistical method, we systematically analyzed transcriptional responses to a large number of dynamic TF inputs. In particular, we quantified the scaling behavior among different transcriptional features extracted from the measured trajectories such as the gene activation delay or duration of promoter activity. Surprisingly, we found that even the same gene promoter can exhibit qualitatively distinct induction and scaling behaviors when exposed to different dynamic TF contexts. While it was previously known that promoters fall into distinct classes, here we show that the same promoter can switch between different classes depending on context. Thus, promoters can adopt context-dependent "manifestations". Our analysis suggests that the full complexity of signal processing by genetic circuits may be significantly underestimated when studied in only specific contexts.
@article{Hansen7940,
author={Anders S Hansen, Christoph Zechner},
title={Promoters adopt distinct dynamic manifestations depending on transcription factor context.},
journal ={Molecular systems biology},
volume={17},
issue ={2},
pages={null--null},
year=2021
}