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Chi Fung Willis Chow, Soumyadeep Ghosh, Anna Hadarovich, Agnes Toth-Petroczy
SHARK enables sensitive detection of evolutionary homologs and functional analogs in unalignable and disordered sequences.
Proc Natl Acad Sci U.S.A., 121(42) Art. No. e2401622121 (2024)
Open Access PubMed Source   

Intrinsically disordered regions (IDRs) are structurally flexible protein segments with regulatory functions in multiple contexts, such as in the assembly of biomolecular condensates. Since IDRs undergo more rapid evolution than ordered regions, identifying homology of such poorly conserved regions remains challenging for state-of-the-art alignment-based methods that rely on position-specific conservation of residues. Thus, systematic functional annotation and evolutionary analysis of IDRs have been limited, despite them comprising ~21% of proteins. To accurately assess homology between unalignable sequences, we developed an alignment-free sequence comparison algorithm, SHARK (Similarity/Homology Assessment by Relating K-mers). We trained SHARK-dive, a machine learning homology classifier, which achieved superior performance to standard alignment-based approaches in assessing evolutionary homology in unalignable sequences. Furthermore, it correctly identified dissimilar but functionally analogous IDRs in IDR-replacement experiments reported in the literature, whereas alignment-based tools were incapable of detecting such functional relationships. SHARK-dive not only predicts functionally similar IDRs at a proteome-wide scale but also identifies cryptic sequence properties and motifs that drive remote homology and analogy, thereby providing interpretable and experimentally verifiable hypotheses of the sequence determinants that underlie such relationships. SHARK-dive acts as an alternative to alignment to facilitate systematic analysis and functional annotation of the unalignable protein universe.
@article{Chow8819,
author={Chi Fung Willis Chow, Soumyadeep Ghosh, Anna Hadarovich, Agnes Toth-Petroczy},
title={SHARK enables sensitive detection of evolutionary homologs and functional analogs in unalignable and disordered sequences.},
journal ={Proceedings of the National Academy of Sciences of the United States of America},
volume={121},
issue ={42},
pages={null--null},
year=2024
}

Lennart J. Schulze, Sachin K. T. Veettil, Ivo F. Sbalzarini
A high-order fully Lagrangian particle level-set method for dynamic surfaces.
J Comput Phys, 515 Art. No. 113262 (2024)
Open Access   Source   

We present a fully Lagrangian particle level-set method based on high-order polynomial regression. This enables meshfree simulations of dynamic surfaces, relaxing the need for particle-mesh interpolation. Instead, we perform level-set redistancing directly on irregularly distributed particles by polynomial regression in a Newton-Lagrange basis on a set of unisolvent nodes. We demonstrate that the resulting particle closest-point (PCP) redistancing achieves high-order accuracy for 2D and 3D geometries discretized on irregular particle distributions and has better robustness against particle distortion than regression in a monomial basis. Further, we show convergence in classic level-set benchmark cases involving ill-conditioned particle distributions, and we present an example application to multi-phase flow problems involving oscillating and dividing droplets.
@article{Schulze8766,
author={Lennart J. Schulze, Sachin K. T. Veettil, Ivo F. Sbalzarini},
title={A high-order fully Lagrangian particle level-set method for dynamic surfaces.},
journal ={Journal of Computational Physics},
volume={515},
pages={null--null},
year=2024
}

Shanshan Xu, Maria E Gierisch, Enrica Barchi, Ina Poser, Simon Alberti, Florian A Salomons, Nico P Dantuma
Chemical inhibition of the integrated stress response impairs the ubiquitin-proteasome system.
Commun Biol, 7(1) Art. No. 1282 (2024)
Open Access PubMed Source   

Inhibitors of the integrated stress response (ISR) have been used to explore the potential beneficial effects of reducing the activation of this pathway in diseases. As the ISR is in essence a protective response, there is, however, a risk that inhibition may compromise the cell's ability to restore protein homeostasis. Here, we show that the experimental compound ISRIB impairs degradation of proteins by the ubiquitin-proteasome system (UPS) during proteotoxic stress in the cytosolic, but not nuclear, compartment. Accumulation of a UPS reporter substrate that is intercepted by ribosome quality control was comparable to the level observed after blocking the UPS with a proteasome inhibitor. Consistent with impairment of the cytosolic UPS, ISRIB treatment caused an accumulation of polyubiquitylated and detergent insoluble defective ribosome products (DRiPs) in the presence of puromycin. Our data suggest that the persistent protein translation during proteotoxic stress in the absence of a functional ISR increases the pool of DRiPs, thereby hindering the efficient clearance of cytosolic substrates by the UPS.
@article{Xu8822,
author={Shanshan Xu, Maria E Gierisch, Enrica Barchi, Ina Poser, Simon Alberti, Florian A Salomons, Nico P Dantuma},
title={Chemical inhibition of the integrated stress response impairs the ubiquitin-proteasome system.},
journal ={Communications biology},
volume={7},
issue ={1},
pages={null--null},
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, Art. No. doi: 10.1242/dev.202777 (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 (BC). 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 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. Time-course 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 increased intraluminal pressure caused similar transcriptional changes. These findings suggest that cell polarity and lumen morphogenesis feedback 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={},
pages={1--1},
year=2024
}

Gonzalo Alvarez Viar, Nikolai Klena, Fabrizio Martino, Adrian Pascal Nievergelt, Davide Bolognini, Paola Capasso, Gaia Pigino
Protofilament-specific nanopatterns of tubulin post-translational modifications regulate the mechanics of ciliary beating.
Curr Biol, 34(19) 4464-4475 (2024)
Open Access PubMed Source   

Controlling ciliary beating is essential for motility and signaling in eukaryotes. This process relies on the regulation of various axonemal proteins that assemble in stereotyped patterns onto individual microtubules of the ciliary structure. Additionally, each axonemal protein interacts exclusively with determined tubulin protofilaments of the neighboring microtubule to carry out its function. While it is known that tubulin post-translational modifications (PTMs) are important for proper ciliary motility, the mode and extent to which they contribute to these interactions remain poorly understood. Currently, the prevailing understanding is that PTMs can confer functional specialization at the level of individual microtubules. However, this paradigm falls short of explaining how the tubulin code can manage the complexity of the axonemal structure where functional interactions happen in defined patterns at the sub-microtubular scale. Here, we combine immuno-cryo-electron tomography (cryo-ET), expansion microscopy, and mutant analysis to show that, in motile cilia, tubulin glycylation and polyglutamylation form mutually exclusive protofilament-specific nanopatterns at a sub-microtubular scale. These nanopatterns are consistent with the distributions of axonemal dyneins and nexin-dynein regulatory complexes, respectively, and are indispensable for their regulation during ciliary beating. Our findings offer a new paradigm for understanding how different tubulin PTMs, such as glycylation, glutamylation, acetylation, tyrosination, and detyrosination, can coexist within the ciliary structure and specialize individual protofilaments for the regulation of diverse protein complexes. The identification of a ciliary tubulin nanocode by cryo-ET suggests the need for high-resolution studies to better understand the molecular role of PTMs in other cellular compartments beyond the cilium.
@article{Viar8798,
author={Gonzalo Alvarez Viar, Nikolai Klena, Fabrizio Martino, Adrian Pascal Nievergelt, Davide Bolognini, Paola Capasso, Gaia Pigino},
title={Protofilament-specific nanopatterns of tubulin post-translational modifications regulate the mechanics of ciliary beating.},
journal ={Current biology : CB},
volume={34},
issue ={19},
pages={4464--4475},
year=2024
}

Alfonso Martinez Arias, Nicolas Rivron, Naomi Moris, Patrick P L Tam, Cantas Alev, Jianping Fu, Anna-Katerina Hadjantonakis, Jacob H Hanna, Gabriella Minchiotti, Olivier Pourquie, Guojun Sheng, Liliana Solnica Krezel, Jesse V Veenvliet, Aryeh Warmflash
Criteria for the standardization of stem-cell-based embryo models.
Nat Cell Biol, 26(10) 1625-1628 (2024)
PubMed Source  

@article{Arias8797,
author={Alfonso Martinez Arias, Nicolas Rivron, Naomi Moris, Patrick P L Tam, Cantas Alev, Jianping Fu, Anna-Katerina Hadjantonakis, Jacob H Hanna, Gabriella Minchiotti, Olivier Pourquie, Guojun Sheng, Liliana Solnica Krezel, Jesse V Veenvliet, Aryeh Warmflash},
title={Criteria for the standardization of stem-cell-based embryo models.},
journal ={Nature cell biology},
volume={26},
issue ={10},
pages={1625--1628},
year=2024
}

David Thomas Gonzales, Naresh Yandrapalli, Tom Robinson, Christoph Zechner#, T-Y Dora Tang#
Correction to "Cell-Free Gene Expression Dynamics in Synthetic Cell Populations".
ACS Synth Biol, Art. No. doi: 10.1021/acssynbio.4c00583 (2024)
Open Access PubMed Source  

@article{Gonzales8811,
author={David Thomas Gonzales, Naresh Yandrapalli, Tom Robinson, Christoph Zechner, T-Y Dora Tang},
title={Correction to "Cell-Free Gene Expression Dynamics in Synthetic Cell Populations".},
journal ={ACS synthetic biology},
volume={},
pages={1--1},
year=2024
}

Takashi Namba, Wieland Huttner
What Makes Us Human: Insights from the Evolution and Development of the Human Neocortex.
Annu Rev Cell Dev Biol, 40(1) 427-452 (2024)
Open Access PubMed Source   

"What makes us human?" is a central question of many research fields, notably anthropology. In this review, we focus on the development of the human neocortex, the part of the brain with a key role in cognition, to gain neurobiological insight toward answering this question. We first discuss cortical stem and progenitor cells and human-specific genes that affect their behavior. We thus aim to understand the molecular foundation of the expansion of the neocortex that occurred in the course of human evolution, as this expansion is generally thought to provide a basis for our unique cognitive abilities. We then review the emerging evidence pointing to differences in the development of the neocortex between present-day humans and Neanderthals, our closest relatives. Finally, we discuss human-specific genes that have been implicated in neuronal circuitry and offer a perspective for future studies addressing the question of what makes us human.
@article{Namba8810,
author={Takashi Namba, Wieland Huttner},
title={What Makes Us Human: Insights from the Evolution and Development of the Human Neocortex.},
journal ={Annual review of cell and developmental biology},
volume={40},
issue ={1},
pages={427--452},
year=2024
}

Manfred Schartl#, Joost M Woltering, Iker Irisarri, Kang Du, Susanne Kneitz, Martin Pippel, Thomas Brown, Paolo Franchini, Jing Li, Ming Li, Mateus Adolfi, Sylke Winkler, Josane de Freitas Sousa, Zhuoxin Chen, Sandra Jacinto, Evgeny Z Kvon, Luis Rogério Correa de Oliveira, Erika Monteiro, Danielson Baia Amaral, Thorsten Burmester, Domitille Chalopin, Alexander Suh, Eugene W Myers, Oleg Simakov, Igor Schneider, Axel Meyer#
The genomes of all lungfish inform on genome expansion and tetrapod evolution.
Nature, 634(8032) 96-103 (2024)
PubMed Source   

The genomes of living lungfishes can inform on the molecular-developmental basis of the Devonian sarcopterygian fish-tetrapod transition. We de novo sequenced the genomes of the African (Protopterus annectens) and South American lungfishes (Lepidosiren paradoxa). The Lepidosiren genome (about 91 Gb, roughly 30 times the human genome) is the largest animal genome sequenced so far and more than twice the size of the Australian (Neoceratodus forsteri)1 and African2 lungfishes owing to enlarged intergenic regions and introns with high repeat content (about 90%). All lungfish genomes continue to expand as some transposable elements (TEs) are still active today. In particular, Lepidosiren's genome grew extremely fast during the past 100 million years (Myr), adding the equivalent of one human genome every 10 Myr. This massive genome expansion seems to be related to a reduction of PIWI-interacting RNAs and C2H2 zinc-finger and Krüppel-associated box (KRAB)-domain protein genes that suppress TE expansions. Although TE abundance facilitates chromosomal rearrangements, lungfish chromosomes still conservatively reflect the ur-tetrapod karyotype. Neoceratodus' limb-like fins still resemble those of their extinct relatives and remained phenotypically static for about 100 Myr. We show that the secondary loss of limb-like appendages in the Lepidosiren-Protopterus ancestor was probably due to loss of sonic hedgehog limb-specific enhancers.
@article{Schartl8782,
author={Manfred Schartl, Joost M Woltering, Iker Irisarri, Kang Du, Susanne Kneitz, Martin Pippel, Thomas Brown, Paolo Franchini, Jing Li, Ming Li, Mateus Adolfi, Sylke Winkler, Josane de Freitas Sousa, Zhuoxin Chen, Sandra Jacinto, Evgeny Z Kvon, Luis Rogério Correa de Oliveira, Erika Monteiro, Danielson Baia Amaral, Thorsten Burmester, Domitille Chalopin, Alexander Suh, Eugene W Myers, Oleg Simakov, Igor Schneider, Axel Meyer},
title={The genomes of all lungfish inform on genome expansion and tetrapod evolution.},
journal ={Nature},
volume={634},
issue ={8032},
pages={96--103},
year=2024
}

Alexandra Schauer, Jesse V Veenvliet
Retinoid-enhanced human gastruloids.
Nat Cell Biol, 26(10) 1634-1636 (2024)
PubMed Source  

@article{Schauer8820,
author={Alexandra Schauer, Jesse V Veenvliet},
title={Retinoid-enhanced human gastruloids.},
journal ={Nature cell biology},
volume={26},
issue ={10},
pages={1634--1636},
year=2024
}
✳︎ joint first authors, # joint corresponding authors
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