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Timon Beck, Lize-Mari van der Linden, Wade M Borcherds, Kyoohyun Kim, Raimund Schlüßler, Paul Müller, Titus Franzmann, Conrad Möckel, Ruchi Goswami, Mark Leaver, Tanja Mittag, Simon Alberti, Jochen Guck
Optical characterization of molecular interaction strength in protein condensates.
Mol Biol Cell, 35(12) Art. No. ar154 (2024)
Open Access PubMed Source   

Biomolecular condensates have been identified as a ubiquitous means of intracellular organization, exhibiting very diverse material properties. However, techniques to characterize these material properties and their underlying molecular interactions are scarce. Here, we introduce two optical techniques-Brillouin microscopy and quantitative phase imaging (QPI)-to address this scarcity. We establish Brillouin shift and linewidth as measures for average molecular interaction and dissipation strength, respectively, and we used QPI to obtain the protein concentration within the condensates. We monitored the response of condensates formed by fused in sarcoma (FUS) and by the low-complexity domain of hnRNPA1 (A1-LCD) to altering temperature and ion concentration. Conditions favoring phase separation increased Brillouin shift, linewidth, and protein concentration. In comparison to solidification by chemical cross-linking, the ion-dependent aging of FUS condensates had a small effect on the molecular interaction strength inside. Finally, we investigated how sequence variations of A1-LCD, that change the driving force for phase separation, alter the physical properties of the respective condensates. Our results provide a new experimental perspective on the material properties of protein condensates. Robust and quantitative experimental approaches such as the presented ones will be crucial for understanding how the physical properties of biological condensates determine their function and dysfunction.
@article{Beck8843,
author={Timon Beck, Lize-Mari van der Linden, Wade M Borcherds, Kyoohyun Kim, Raimund Schlüßler, Paul Müller, Titus Franzmann, Conrad Möckel, Ruchi Goswami, Mark Leaver, Tanja Mittag, Simon Alberti, Jochen Guck},
title={Optical characterization of molecular interaction strength in protein condensates.},
journal ={Molecular biology of the cell},
volume={35},
issue ={12},
pages={null--null},
year=2024
}

Tobias Grass, Zeynep Dokuzluoglu, Natalia Rodríguez-Muela
Neuromuscular Organoids to Study Spinal Cord Development and Disease.
Methods Mol Biol, Art. No. doi: 10.1007/7651_2024_574 (2024)
PubMed Source   

Many aspects of neurodegenerative disease pathology remain unresolved. Why do certain neuronal subpopulations acquire vulnerability to stress or mutations in ubiquitously expressed genes, while others remain resilient? Do these neurons harbor intrinsic marks that make them prone to degeneration? Do these diseases have a neurodevelopmental component? Lacking this fundamental knowledge hampers the discovery of efficacious treatments. While it is well established that human organoids enable the modeling of brain-related diseases, we still lack an organoid model that recapitulates the regionalization complexity and physiology of the spinal cord. Here, we describe an advanced experimental protocol to generate neuromuscular organoids composed of a wide rostro-caudal (RC) diversity of spinal motor neurons (spMNs) and mesodermal progenitor-derived muscle cells. This model therefore allows for the robust and reproducible study of neuromuscular unit development and disease.
@article{Grass8845,
author={Tobias Grass, Zeynep Dokuzluoglu, Natalia Rodríguez-Muela},
title={Neuromuscular Organoids to Study Spinal Cord Development and Disease.},
journal ={Methods in molecular biology (Clifton, N.J.)},
volume={},
pages={1--1},
year=2024
}

Xingyu Chen✳︎, Cristina Jiménez López✳︎, André Nadler#, Florian Stengel#
A photo-caged cross-linker for identifying protein-protein interactions.
Chembiochem, Art. No. e202400620 (2024)
Open Access PubMed Source   

Cross-linking mass spectrometry (XL-MS) has seen significant improvements which have enhanced its utility for studying protein-protein interactions (PPIs), primarily due to the emergence of novel crosslinkers and the development of streamlined analysis workflows. Nevertheless, poor membrane permeability and side reactions with water limit the extent of productive intracellular crosslinking events that can be achieved with current crosslinkers. To address these problems, we have synthesized a novel crosslinker with o-nitrobenzyl-based photoresponsive groups. These o-nitrobenzyl ester (o-NBE) groups enhance the stability and hydrophobic properties of the crosslinker and add the potential for temporal resolution, i.e. the ability to control the initiation of the crosslinking reaction. Upon exposure to UV light the resulting aldehyde product reacts with adjacent amino groups and subsequent reductive amination of the formed Schiff-bases yields stable secondary amine linkages. This controlled activation mechanism enables precise UV-triggered protein crosslinking. We demonstrate proof-of principle of our o-NBE cross-linker to reliably detect PPIs by XL-MS using a recombinant model protein. We also demonstrate its ability to enter intact Hela cells, thereby indicating its future potential as a useful tool to study PPIs within the cellular environment.
@article{Chen8848,
author={Xingyu Chen, Cristina Jiménez López, André Nadler, Florian Stengel},
title={A photo-caged cross-linker for identifying protein-protein interactions.},
journal ={Chembiochem : a European journal of chemical biology},
volume={},
pages={1--1},
year=2024
}

Srustidhar Das✳︎, S Martina Parigi✳︎, Xinxin Luo✳︎, Jennifer Fransson, Bianca C Kern, Ali Okhovat, Oscar E Diaz, Chiara Sorini, Paulo Czarnewski, Anna T Webb, Rodrigo A Morales, Sacha Lebon, Gustavo Monasterio, Francisca Castillo, Kumar P Tripathi, Ning He, Penelope Pelczar, Nicola Schaltenberg, Marjorie De la Fuente, Francisco López-Köstner, Susanne Nylén, Hjalte List Larsen, Raoul Kuiper, Per Antonson, Marcela A Hermoso, Samuel Huber, Moshe Biton, Sandra Scharaw, Jan-Åke Gustafsson, Pekka Katajisto, Eduardo J Villablanca
Liver X receptor unlinks intestinal regeneration and tumorigenesis.
Nature, Art. No. doi: 10.1038/s41586-024-08247-6 (2024)
Open Access PubMed Source   

Uncontrolled regeneration leads to neoplastic transformation1-3. The intestinal epithelium requires precise regulation during continuous homeostatic and damage-induced tissue renewal to prevent neoplastic transformation, suggesting that pathways unlinking tumour growth from regenerative processes must exist. Here, by mining RNA-sequencing datasets from two intestinal damage models4,5 and using pharmacological, transcriptomics and genetic tools, we identified liver X receptor (LXR) pathway activation as a tissue adaptation to damage that reciprocally regulates intestinal regeneration and tumorigenesis. Using single-cell RNA sequencing, intestinal organoids, and gain- and loss-of-function experiments, we demonstrate that LXR activation in intestinal epithelial cells induces amphiregulin (Areg), enhancing regenerative responses. This response is coordinated by the LXR-ligand-producing enzyme CYP27A1, which was upregulated in damaged intestinal crypt niches. Deletion of Cyp27a1 impaired intestinal regeneration, which was rescued by exogenous LXR agonists. Notably, in tumour models, Cyp27a1 deficiency led to increased tumour growth, whereas LXR activation elicited anti-tumour responses dependent on adaptive immunity. Consistently, human colorectal cancer specimens exhibited reduced levels of CYP27A1, LXR target genes, and B and CD8 T cell gene signatures. We therefore identify an epithelial adaptation mechanism to damage, whereby LXR functions as a rheostat, promoting tissue repair while limiting tumorigenesis.
@article{Das8847,
author={Srustidhar Das, S Martina Parigi, Xinxin Luo, Jennifer Fransson, Bianca C Kern, Ali Okhovat, Oscar E Diaz, Chiara Sorini, Paulo Czarnewski, Anna T Webb, Rodrigo A Morales, Sacha Lebon, Gustavo Monasterio, Francisca Castillo, Kumar P Tripathi, Ning He, Penelope Pelczar, Nicola Schaltenberg, Marjorie De la Fuente, Francisco López-Köstner, Susanne Nylén, Hjalte List Larsen, Raoul Kuiper, Per Antonson, Marcela A Hermoso, Samuel Huber, Moshe Biton, Sandra Scharaw, Jan-Åke Gustafsson, Pekka Katajisto, Eduardo J Villablanca},
title={Liver X receptor unlinks intestinal regeneration and tumorigenesis.},
journal ={Nature},
volume={},
pages={1--1},
year=2024
}

Mehrez Gammoudi, Isabel L. Dittmann, Johannes Girstmair, Pavel Tomançak, Bernhard Egger, Veronica N. Bulnes
A new Phrikoceros species (Polycladida: Cotylea) from Ghar El Melh lagoon (Tunisia) with some remarks on the morphology of the genera Phrikoceros and Thytthosoceros.
Biologia, Art. No. doi: 10.1007/s11756-024-01818-y (2024)
Source   

We describe Phrikoceros jannetae sp. n., a new cotylean polyclad species from Ghar El Melh lagoon, a natural seawater lagoon situated in the north of Tunisia. The new species is characterized by the dorsal translucent white to brownish dorsal surface, with black round dots, red microdots, white blotches arranged as discrete lateral streaks, a mid-dorsal darker band and an interrupted slender black rim. We provide some insights into the biology of this species including the plastic tentacle configuration and the variability of body form and outline within the same specimen. Phrikoceros jannetae sp. n. was found among tunicates of the species Ciona intestinalis.
@article{Gammoudi8860,
author={Mehrez Gammoudi, Isabel L. Dittmann, Johannes Girstmair, Pavel Tomançak, Bernhard Egger, Veronica N. Bulnes},
title={A new Phrikoceros species (Polycladida: Cotylea) from Ghar El Melh lagoon (Tunisia) with some remarks on the morphology of the genera Phrikoceros and Thytthosoceros.},
journal ={Biologia},
volume={},
pages={1--1},
year=2024
}

Maarten P Bebelman✳︎, Lenka Belicova✳︎, Elzbieta Gralinska, Tobias Jumel, Aparajita Lahree, Sarah Sommer, Andrej Shevchenko, Timofei Zatsepin, Yannis Kalaidzidis, Martin Vingron, Marino Zerial
Hepatocyte differentiation requires anisotropic expansion of bile canaliculi.
Development, 151(22) Art. No. dev202777 (2024)
Open Access PubMed Source   

During liver development, bipotential progenitor cells called hepatoblasts differentiate into hepatocytes or cholangiocytes. Hepatocyte differentiation is uniquely associated with multi-axial polarity, enabling the anisotropic expansion of apical lumina between adjacent cells and formation of a three-dimensional network of bile canaliculi. Cholangiocytes, the cells forming the bile ducts, exhibit the vectorial polarity characteristic of epithelial cells. Whether cell polarization feeds back on the gene regulatory pathways governing hepatoblast differentiation is unknown. Here, we used primary mouse hepatoblasts to investigate the contribution of anisotropic apical expansion to hepatocyte differentiation. Silencing of the small GTPase Rab35 caused isotropic lumen expansion and formation of multicellular cysts with the vectorial polarity of cholangiocytes. Gene expression profiling revealed that these cells express reduced levels of hepatocyte markers and upregulate genes associated with cholangiocyte identity. Timecourse RNA sequencing demonstrated that loss of lumen anisotropy precedes these transcriptional changes. Independent alterations in apical lumen morphology induced either by modulation of the subapical actomyosin cortex or by increased intraluminal pressure caused similar transcriptional changes. These findings suggest that cell polarity and lumen morphogenesis feed back to hepatoblast-to-hepatocyte differentiation.
@article{Bebelman8817,
author={Maarten P Bebelman, Lenka Belicova, Elzbieta Gralinska, Tobias Jumel, Aparajita Lahree, Sarah Sommer, Andrej Shevchenko, Timofei Zatsepin, Yannis Kalaidzidis, Martin Vingron, Marino Zerial},
title={Hepatocyte differentiation requires anisotropic expansion of bile canaliculi.},
journal ={Development (Cambridge, England)},
volume={151},
issue ={22},
pages={null--null},
year=2024
}

A Sophie Brumm, Afshan McCarthy, Claudia Gerri, Todd Fallesen, Laura Woods, Riley McMahon, Athanasios Papathanasiou, Kay Elder, Phil Snell, Leila Christie, Patricia Garcia, Valerie Shaikly, Mohamed Taranissi, Paul Serhal, Rabi A Odia, Mina Vasilic, Anna Osnato, Peter J Rugg-Gunn, Ludovic Vallier, Caroline S Hill, Kathy K Niakan
Initiation and maintenance of the pluripotent epiblast in pre-implantation human development is independent of NODAL signaling.
Dev Cell, 60 Art. No. doi: 10.1016/j.devcel.2024.10.020 (2024)
Open Access PubMed Source   

The human blastocyst contains the pluripotent epiblast from which human embryonic stem cells (hESCs) can be derived. ACTIVIN/NODAL signaling maintains expression of the transcription factor NANOG and in vitro propagation of hESCs. It is unknown whether this reflects a functional requirement for epiblast development in human embryos. Here, we characterized NODAL signaling activity during pre-implantation human development. We showed that NANOG is an early molecular marker restricted to the nascent human pluripotent epiblast and was initiated prior to the onset of NODAL signaling. We further demonstrated that expression of pluripotency-associated transcription factors NANOG, SOX2, OCT4, and KLF17 were maintained in the epiblast in the absence of NODAL signaling activity. Genome-wide transcriptional analysis showed that NODAL signaling inhibition did not decrease NANOG transcription or impact the wider pluripotency-associated gene regulatory network. These data suggest differences in the signaling requirements regulating pluripotency in the pre-implantation human epiblast compared with existing hESC culture.
@article{Brumm8846,
author={A Sophie Brumm, Afshan McCarthy, Claudia Gerri, Todd Fallesen, Laura Woods, Riley McMahon, Athanasios Papathanasiou, Kay Elder, Phil Snell, Leila Christie, Patricia Garcia, Valerie Shaikly, Mohamed Taranissi, Paul Serhal, Rabi A Odia, Mina Vasilic, Anna Osnato, Peter J Rugg-Gunn, Ludovic Vallier, Caroline S Hill, Kathy K Niakan},
title={Initiation and maintenance of the pluripotent epiblast in pre-implantation human development is independent of NODAL signaling.},
journal ={Developmental cell},
volume={60},
pages={1--1},
year=2024
}

David Beers, Heather Harrington, Jacob Leygonie, Uzu Lim, Theran Louis
Fibers of point cloud persistence.
arXiv, Art. No. 2411.08201 (2024)
Open Access   Source Full Text   

Persistent homology (PH) studies the topology of data across multiple scales by building nested collections of topological spaces called filtrations, computing homology and returning an algebraic object that can be vizualised as a barcode--a multiset of intervals. The barcode is stable and interpretable, leading to applications within mathematics and data science. We study the spaces of point clouds with the same barcode by connecting persistence with real algebraic geometry and rigidity theory. Utilizing a semi-algebraic setup of point cloud persistence, we give lower and upper bounds on its dimension and provide combinatorial conditions in terms of the local and global rigidity properties of graphs associated with point clouds and filtrations. We prove that for generic point clouds in ℝᵈ (d≥2), a point cloud is identifiable up to isometry from its VR persistence if the associated graph is globally rigid, and locally identifiable up to isometry from its Čech persistence if the associated hypergraph is rigid.
@article{Beers8864,
author={David Beers, Heather Harrington, Jacob Leygonie, Uzu Lim, Theran Louis},
title={Fibers of point cloud persistence.},
journal ={arXiv},
volume={},
pages={1--1},
year=2024
}

Isaac Justice, Petra Kiesel, Nataliya Safronova, Alexander von Appen, James P Saenz
A tuneable minimal cell membrane reveals that two lipid species suffice for life.
Nat Commun, 15(1) Art. No. 9679 (2024)
Open Access PubMed Source Full Text   

All cells are encapsulated by a lipid membrane that facilitates their interactions with the environment. How cells manage diverse mixtures of lipids, which dictate membrane property and function, is experimentally challenging to address. Here, we present an approach to tune and minimize membrane lipid composition in the bacterium Mycoplasma mycoides and its derived 'minimal cell' (JCVI-Syn3A), revealing that a two-component lipidome can support life. Systematic reintroduction of phospholipids with different features demonstrates that acyl chain diversity is more important for growth than head group diversity. By tuning lipid chirality, we explore the lipid divide between Archaea and the rest of life, showing that ancestral lipidomes could have been heterochiral. However, in these simple organisms, heterochirality leads to impaired cellular fitness. Thus, our approach offers a tunable minimal membrane system to explore the fundamental lipidomic requirements for life, thereby extending the concept of minimal life from the genome to the lipidome.
@article{Justice8844,
author={Isaac Justice, Petra Kiesel, Nataliya Safronova, Alexander von Appen, James P Saenz},
title={A tuneable minimal cell membrane reveals that two lipid species suffice for life.},
journal ={Nature communications},
volume={15},
issue ={1},
pages={null--null},
year=2024
}

Johannes Pahlke, Ivo F. Sbalzarini
Proven Distributed Memory Parallelization of Particle Methods
ACM Trans. Parallel Comput., 11(4) Art. No. 17 (2024)
Open Access   Source   

We provide a mathematically proven parallelization scheme for particle methods on distributed-memory computer systems. Particle methods are a versatile and widely used class of algorithms for computer simulations and numerical predictions in various applications, ranging from continuum fluid dynamics to discrete granular flows and molecular dynamics simulations. Particle methods naturally lend themselves to implementation on parallel computing systems. So far, however, a mathematical proof of correctness and equivalence to sequential implementations has only been available for shared-memory parallelism. Here, we leverage a formal definition of the algorithmic class of particle methods to provide a proven parallelization scheme for distributed-memory computers. We prove that thus parallelized particle methods on distributed-memory computers are formally equivalent to their sequential counterpart for a well-defined class of particle methods, and we provide analytical expressions for the speedup and scalability bounds of this class of algorithms in function of their parameters. The parallelization scheme analyzed here is the basis of many real-world software designs for parallel particle methods. The present analysis is, therefore, of direct relevance to existing and new parallel implementations of particle methods and places them on solid theoretical grounds, rationalizing best practices and providing useful scalability and speedup bounds for benchmarking.
@article{Pahlke8842,
author={Johannes Pahlke, Ivo F. Sbalzarini},
title={Proven Distributed Memory Parallelization of Particle Methods},
journal ={ACM Transactions on Parallel Computing},
volume={11},
issue ={4},
pages={null--null},
year=2024
}
✳︎ joint first authors, # joint corresponding authors
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