@article{14742,
  abstract     = {Chromosomal rearrangements (CRs) have been known since almost the beginning of genetics.
While an important role for CRs in speciation has been suggested, evidence primarily stems
from theoretical and empirical studies focusing on the microevolutionary level (i.e., on taxon
pairs where speciation is often incomplete). Although the role of CRs in eukaryotic speciation at
a macroevolutionary level has been supported by associations between species diversity and
rates of evolution of CRs across phylogenies, these findings are limited to a restricted range of
CRs and taxa. Now that more broadly applicable and precise CR detection approaches have
become available, we address the challenges in filling some of the conceptual and empirical
gaps between micro- and macroevolutionary studies on the role of CRs in speciation. We
synthesize what is known about the macroevolutionary impact of CRs and suggest new research avenues to overcome the pitfalls of previous studies to gain a more comprehensive understanding of the evolutionary significance of CRs in speciation across the tree of life.},
  author       = {Lucek, Kay and Giménez, Mabel D. and Joron, Mathieu and Rafajlović, Marina and Searle, Jeremy B. and Walden, Nora and Westram, Anja M and Faria, Rui},
  issn         = {1943-0264},
  journal      = {Cold Spring Harbor Perspectives in Biology},
  keywords     = {General Biochemistry, Genetics and Molecular Biology},
  number       = {11},
  publisher    = {Cold Spring Harbor Laboratory},
  title        = {{The impact of chromosomal rearrangements in speciation: From micro- to macroevolution}},
  doi          = {10.1101/cshperspect.a041447},
  volume       = {15},
  year         = {2023},
}

@article{14770,
  abstract     = {We developed LIONESS, a technology that leverages improvements to optical super-resolution microscopy and prior information on sample structure via machine learning to overcome the limitations (in 3D-resolution, signal-to-noise ratio and light exposure) of optical microscopy of living biological specimens. LIONESS enables dense reconstruction of living brain tissue and morphodynamics visualization at the nanoscale.},
  author       = {Danzl, Johann G and Velicky, Philipp},
  issn         = {1548-7105},
  journal      = {Nature Methods},
  keywords     = {Cell Biology, Molecular Biology, Biochemistry, Biotechnology},
  number       = {8},
  pages        = {1141--1142},
  publisher    = {Springer Nature},
  title        = {{LIONESS enables 4D nanoscale reconstruction of living brain tissue}},
  doi          = {10.1038/s41592-023-01937-5},
  volume       = {20},
  year         = {2023},
}

@article{14774,
  abstract     = {Morphogen gradients impart positional information to cells in a homogenous tissue field. Fgf8a, a highly conserved growth factor, has been proposed to act as a morphogen during zebrafish gastrulation. However, technical limitations have so far prevented direct visualization of the endogenous Fgf8a gradient and confirmation of its morphogenic activity. Here, we monitor Fgf8a propagation in the developing neural plate using a CRISPR/Cas9-mediated EGFP knock-in at the endogenous fgf8a locus. By combining sensitive imaging with single-molecule fluorescence correlation spectroscopy, we demonstrate that Fgf8a, which is produced at the embryonic margin, propagates by diffusion through the extracellular space and forms a graded distribution towards the animal pole. Overlaying the Fgf8a gradient curve with expression profiles of its downstream targets determines the precise input-output relationship of Fgf8a-mediated patterning. Manipulation of the extracellular Fgf8a levels alters the signaling outcome, thus establishing Fgf8a as a bona fide morphogen during zebrafish gastrulation. Furthermore, by hindering Fgf8a diffusion, we demonstrate that extracellular diffusion of the protein from the source is crucial for it to achieve its morphogenic potential.},
  author       = {Harish, Rohit K and Gupta, Mansi and Zöller, Daniela and Hartmann, Hella and Gheisari, Ali and Machate, Anja and Hans, Stefan and Brand, Michael},
  issn         = {1477-9129},
  journal      = {Development},
  keywords     = {Developmental Biology, Molecular Biology},
  number       = {19},
  publisher    = {The Company of Biologists},
  title        = {{Real-time monitoring of an endogenous Fgf8a gradient attests to its role as a morphogen during zebrafish gastrulation}},
  doi          = {10.1242/dev.201559},
  volume       = {150},
  year         = {2023},
}

@article{14776,
  abstract     = {Soluble chaperones residing in the endoplasmic reticulum (ER) play vitally important roles in folding and quality control of newly synthesized proteins that transiently pass through the ER en route to their final destinations. These soluble residents of the ER are themselves endowed with an ER retrieval signal that enables the cell to bring the escaped residents back from the Golgi. Here, by using purified proteins, we showed that Nicotiana tabacum phytaspase, a plant aspartate-specific protease, introduces two breaks at the C-terminus of the N. tabacum ER resident calreticulin-3. These cleavages resulted in removal of either a dipeptide or a hexapeptide from the C-terminus of calreticulin-3 encompassing part or all of the ER retrieval signal. Consistently, expression of the calreticulin-3 derivative mimicking the phytaspase cleavage product in Nicotiana benthamiana cells demonstrated loss of the ER accumulation of the protein. Notably, upon its escape from the ER, calreticulin-3 was further processed by an unknown protease(s) to generate the free N-terminal (N) domain of calreticulin-3, which was ultimately secreted into the apoplast. Our study thus identified a specific proteolytic enzyme capable of precise detachment of the ER retrieval signal from a plant ER resident protein, with implications for the further fate of the escaped resident.},
  author       = {Teplova, Anastasiia and Pigidanov, Artemii A. and Serebryakova, Marina V. and Golyshev, Sergei A. and Galiullina, Raisa A. and Chichkova, Nina V. and Vartapetian, Andrey B.},
  issn         = {1422-0067},
  journal      = {International Journal of Molecular Sciences},
  keywords     = {Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis},
  number       = {22},
  publisher    = {MDPI},
  title        = {{Phytaspase Is capable of detaching the endoplasmic reticulum retrieval signal from tobacco calreticulin-3}},
  doi          = {10.3390/ijms242216527},
  volume       = {24},
  year         = {2023},
}

@article{14781,
  abstract     = {Germ granules, condensates of phase-separated RNA and protein, are organelles that are essential for germline development in different organisms. The patterning of the granules and their relevance for germ cell fate are not fully understood. Combining three-dimensional in vivo structural and functional analyses, we study the dynamic spatial organization of molecules within zebrafish germ granules. We find that the localization of RNA molecules to the periphery of the granules, where ribosomes are localized, depends on translational activity at this location. In addition, we find that the vertebrate-specific Dead end (Dnd1) protein is essential for nanos3 RNA localization at the condensates’ periphery. Accordingly, in the absence of Dnd1, or when translation is inhibited, nanos3 RNA translocates into the granule interior, away from the ribosomes, a process that is correlated with the loss of germ cell fate. These findings highlight the relevance of sub-granule compartmentalization for post-transcriptional control and its importance for preserving germ cell totipotency.},
  author       = {Westerich, Kim Joana and Tarbashevich, Katsiaryna and Schick, Jan and Gupta, Antra and Zhu, Mingzhao and Hull, Kenneth and Romo, Daniel and Zeuschner, Dagmar and Goudarzi, Mohammad and Gross-Thebing, Theresa and Raz, Erez},
  issn         = {1534-5807},
  journal      = {Developmental Cell},
  keywords     = {Developmental Biology, Cell Biology, General Biochemistry, Genetics and Molecular Biology, Molecular Biology},
  number       = {17},
  pages        = {1578--1592.e5},
  publisher    = {Elsevier},
  title        = {{Spatial organization and function of RNA molecules within phase-separated condensates in zebrafish are controlled by Dnd1}},
  doi          = {10.1016/j.devcel.2023.06.009},
  volume       = {58},
  year         = {2023},
}

@article{12114,
  abstract     = {Probing the dynamics of aromatic side chains provides important insights into the behavior of a protein because flips of aromatic rings in a protein’s hydrophobic core report on breathing motion involving a large part of the protein. Inherently invisible to crystallography, aromatic motions have been primarily studied by solution NMR. The question how packing of proteins in crystals affects ring flips has, thus, remained largely unexplored. Here we apply magic-angle spinning NMR, advanced phenylalanine 1H-13C/2H isotope labeling and MD simulation to a protein in three different crystal packing environments to shed light onto possible impact of packing on ring flips. The flips of the two Phe residues in ubiquitin, both surface exposed, appear remarkably conserved in the different crystal forms, even though the intermolecular packing is quite different: Phe4 flips on a ca. 10–20 ns time scale, and Phe45 are broadened in all crystals, presumably due to µs motion. Our findings suggest that intramolecular influences are more important for ring flips than intermolecular (packing) effects.},
  author       = {Gauto, Diego F. and Lebedenko, Olga O. and Becker, Lea Marie and Ayala, Isabel and Lichtenecker, Roman and Skrynnikov, Nikolai R. and Schanda, Paul},
  issn         = {2590-1524},
  journal      = {Journal of Structural Biology: X},
  keywords     = {Structural Biology},
  publisher    = {Elsevier},
  title        = {{Aromatic ring flips in differently packed ubiquitin protein crystals from MAS NMR and MD}},
  doi          = {10.1016/j.yjsbx.2022.100079},
  volume       = {7},
  year         = {2023},
}

@article{12152,
  abstract     = {ESCRT-III filaments are composite cytoskeletal polymers that can constrict and cut cell membranes from the inside of the membrane neck. Membrane-bound ESCRT-III filaments undergo a series of dramatic composition and geometry changes in the presence of an ATP-consuming Vps4 enzyme, which causes stepwise changes in the membrane morphology. We set out to understand the physical mechanisms involved in translating the changes in ESCRT-III polymer composition into membrane deformation. We have built a coarse-grained model in which ESCRT-III polymers of different geometries and mechanical properties are allowed to copolymerise and bind to a deformable membrane. By modelling ATP-driven stepwise depolymerisation of specific polymers, we identify mechanical regimes in which changes in filament composition trigger the associated membrane transition from a flat to a buckled state, and then to a tubule state that eventually undergoes scission to release a small cargo-loaded vesicle. We then characterise how the location and kinetics of polymer loss affects the extent of membrane deformation and the efficiency of membrane neck scission. Our results identify the near-minimal mechanical conditions for the operation of shape-shifting composite polymers that sever membrane necks.},
  author       = {Jiang, Xiuyun and Harker-Kirschneck, Lena and Vanhille-Campos, Christian Eduardo and Pfitzner, Anna-Katharina and Lominadze, Elene and Roux, Aurélien and Baum, Buzz and Šarić, Anđela},
  issn         = {1553-7358},
  journal      = {PLOS Computational Biology},
  keywords     = {Computational Theory and Mathematics, Cellular and Molecular Neuroscience, Genetics, Molecular Biology, Ecology, Modeling and Simulation, Ecology, Evolution, Behavior and Systematics},
  number       = {10},
  publisher    = {Public Library of Science},
  title        = {{Modelling membrane reshaping by staged polymerization of ESCRT-III filaments}},
  doi          = {10.1371/journal.pcbi.1010586},
  volume       = {18},
  year         = {2022},
}

@article{12156,
  abstract     = {Models of transcriptional regulation that assume equilibrium binding of transcription factors have been less successful at predicting gene expression from sequence in eukaryotes than in bacteria. This could be due to the non-equilibrium nature of eukaryotic regulation. Unfortunately, the space of possible non-equilibrium mechanisms is vast and predominantly uninteresting. The key question is therefore how this space can be navigated efficiently, to focus on mechanisms and models that are biologically relevant. In this review, we advocate for the normative role of theory—theory that prescribes rather than just describes—in providing such a focus. Theory should expand its remit beyond inferring mechanistic models from data, towards identifying non-equilibrium gene regulatory schemes that may have been evolutionarily selected, despite their energy consumption, because they are precise, reliable, fast, or otherwise outperform regulation at equilibrium. We illustrate our reasoning by toy examples for which we provide simulation code.},
  author       = {Zoller, Benjamin and Gregor, Thomas and Tkačik, Gašper},
  issn         = {2452-3100},
  journal      = {Current Opinion in Systems Biology},
  keywords     = {Applied Mathematics, Computer Science Applications, Drug Discovery, General Biochemistry, Genetics and Molecular Biology, Modeling and Simulation},
  number       = {9},
  publisher    = {Elsevier},
  title        = {{Eukaryotic gene regulation at equilibrium, or non?}},
  doi          = {10.1016/j.coisb.2022.100435},
  volume       = {31},
  year         = {2022},
}

@article{12157,
  abstract     = {Polygenic adaptation is thought to be ubiquitous, yet remains poorly understood. Here, we model this process analytically, in the plausible setting of a highly polygenic, quantitative trait that experiences a sudden shift in the fitness optimum. We show how the mean phenotype changes over time, depending on the effect sizes of loci that contribute to variance in the trait, and characterize the allele dynamics at these loci. Notably, we describe the two phases of the allele dynamics: The first is a rapid phase, in which directional selection introduces small frequency differences between alleles whose effects are aligned with or opposed to the shift, ultimately leading to small differences in their probability of fixation during a second, longer phase, governed by stabilizing selection. As we discuss, key results should hold in more general settings and have important implications for efforts to identify the genetic basis of adaptation in humans and other species.},
  author       = {Hayward, Laura and Sella, Guy},
  issn         = {2050-084X},
  journal      = {eLife},
  keywords     = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience},
  publisher    = {eLife Sciences Publications},
  title        = {{Polygenic adaptation after a sudden change in environment}},
  doi          = {10.7554/elife.66697},
  volume       = {11},
  year         = {2022},
}

@article{12208,
  abstract     = {The inadequate understanding of the mechanisms that reversibly convert molecular sulfur (S) into lithium sulfide (Li<jats:sub>2</jats:sub>S) via soluble polysulfides (PSs) formation impedes the development of high-performance lithium-sulfur (Li-S) batteries with non-aqueous electrolyte solutions. Here, we use operando small and wide angle X-ray scattering and operando small angle neutron scattering (SANS) measurements to track the nucleation, growth and dissolution of solid deposits from atomic to sub-micron scales during real-time Li-S cell operation. In particular, stochastic modelling based on the SANS data allows quantifying the nanoscale phase evolution during battery cycling. We show that next to nano-crystalline Li<jats:sub>2</jats:sub>S the deposit comprises solid short-chain PSs particles. The analysis of the experimental data suggests that initially, Li<jats:sub>2</jats:sub>S<jats:sub>2</jats:sub> precipitates from the solution and then is partially converted via solid-state electroreduction to Li<jats:sub>2</jats:sub>S. We further demonstrate that mass transport, rather than electron transport through a thin passivating film, limits the discharge capacity and rate performance in Li-S cells.},
  author       = {Prehal, Christian and von Mentlen, Jean-Marc and Drvarič Talian, Sara and Vizintin, Alen and Dominko, Robert and Amenitsch, Heinz and Porcar, Lionel and Freunberger, Stefan Alexander and Wood, Vanessa},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  keywords     = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary},
  publisher    = {Springer Nature},
  title        = {{On the nanoscale structural evolution of solid discharge products in lithium-sulfur batteries using operando scattering}},
  doi          = {10.1038/s41467-022-33931-4},
  volume       = {13},
  year         = {2022},
}

@article{12217,
  abstract     = {The development dynamics and self-organization of glandular branched epithelia is of utmost importance for our understanding of diverse processes ranging from normal tissue growth to the growth of cancerous tissues. Using single primary murine pancreatic ductal adenocarcinoma (PDAC) cells embedded in a collagen matrix and adapted media supplementation, we generate organoids that self-organize into highly branched structures displaying a seamless lumen connecting terminal end buds, replicating in vivo PDAC architecture. We identify distinct morphogenesis phases, each characterized by a unique pattern of cell invasion, matrix deformation, protein expression, and respective molecular dependencies. We propose a minimal theoretical model of a branching and proliferating tissue, capturing the dynamics of the first phases. Observing the interaction of morphogenesis, mechanical environment and gene expression in vitro sets a benchmark for the understanding of self-organization processes governing complex organoid structure formation processes and branching morphogenesis.},
  author       = {Randriamanantsoa, S. and Papargyriou, A. and Maurer, H. C. and Peschke, K. and Schuster, M. and Zecchin, G. and Steiger, K. and Öllinger, R. and Saur, D. and Scheel, C. and Rad, R. and Hannezo, Edouard B and Reichert, M. and Bausch, A. R.},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  keywords     = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary},
  publisher    = {Springer Nature},
  title        = {{Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids}},
  doi          = {10.1038/s41467-022-32806-y},
  volume       = {13},
  year         = {2022},
}

@article{12224,
  abstract     = {Muskelin (Mkln1) is implicated in neuronal function, regulating plasma membrane receptor trafficking. However, its influence on intrinsic brain activity and corresponding behavioral processes remains unclear. Here we show that murine <jats:italic>Mkln1</jats:italic> knockout causes non-habituating locomotor activity, increased exploratory drive, and decreased locomotor response to amphetamine. Muskelin deficiency impairs social novelty detection while promoting the retention of spatial reference memory and fear extinction recall. This is strongly mirrored in either weaker or stronger resting-state functional connectivity between critical circuits mediating locomotor exploration and cognition. We show that <jats:italic>Mkln1</jats:italic> deletion alters dendrite branching and spine structure, coinciding with enhanced AMPAR-mediated synaptic transmission but selective impairment in synaptic potentiation maintenance. We identify muskelin at excitatory synapses and highlight its role in regulating dendritic spine actin stability. Our findings point to aberrant spine actin modulation and changes in glutamatergic synaptic function as critical mechanisms that contribute to the neurobehavioral phenotype arising from <jats:italic>Mkln1</jats:italic> ablation.},
  author       = {Muhia, Mary W and YuanXiang, PingAn and Sedlacik, Jan and Schwarz, Jürgen R. and Heisler, Frank F. and Gromova, Kira V. and Thies, Edda and Breiden, Petra and Pechmann, Yvonne and Kreutz, Michael R. and Kneussel, Matthias},
  issn         = {2399-3642},
  journal      = {Communications Biology},
  keywords     = {General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology, Medicine (miscellaneous)},
  publisher    = {Springer Nature},
  title        = {{Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes}},
  doi          = {10.1038/s42003-022-03446-1},
  volume       = {5},
  year         = {2022},
}

@article{12231,
  abstract     = {Ventral tail bending, which is transient but pronounced, is found in many chordate embryos and constitutes an interesting model of how tissue interactions control embryo shape. Here, we identify one key upstream regulator of ventral tail bending in embryos of the ascidian Ciona. We show that during the early tailbud stages, ventral epidermal cells exhibit a boat-shaped morphology (boat cell) with a narrow apical surface where phosphorylated myosin light chain (pMLC) accumulates. We further show that interfering with the function of the BMP ligand Admp led to pMLC localizing to the basal instead of the apical side of ventral epidermal cells and a reduced number of boat cells. Finally, we show that cutting ventral epidermal midline cells at their apex using an ultraviolet laser relaxed ventral tail bending. Based on these results, we propose a previously unreported function for Admp in localizing pMLC to the apical side of ventral epidermal cells, which causes the tail to bend ventrally by resisting antero-posterior notochord extension at the ventral side of the tail.},
  author       = {Kogure, Yuki S. and Muraoka, Hiromochi and Koizumi, Wataru C. and Gelin-alessi, Raphaël and Godard, Benoit G and Oka, Kotaro and Heisenberg, Carl-Philipp J and Hotta, Kohji},
  issn         = {1477-9129},
  journal      = {Development},
  keywords     = {Developmental Biology, Molecular Biology},
  number       = {21},
  publisher    = {The Company of Biologists},
  title        = {{Admp regulates tail bending by controlling ventral epidermal cell polarity via phosphorylated myosin localization in Ciona}},
  doi          = {10.1242/dev.200215},
  volume       = {149},
  year         = {2022},
}

@article{12238,
  abstract     = {Upon the initiation of collective cell migration, the cells at the free edge are specified as leader cells; however, the mechanism underlying the leader cell specification remains elusive. Here, we show that lamellipodial extension after the release from mechanical confinement causes sustained extracellular signal-regulated kinase (ERK) activation and underlies the leader cell specification. Live-imaging of Madin-Darby canine kidney (MDCK) cells and mouse epidermis through the use of Förster resonance energy transfer (FRET)-based biosensors showed that leader cells exhibit sustained ERK activation in a hepatocyte growth factor (HGF)-dependent manner. Meanwhile, follower cells exhibit oscillatory ERK activation waves in an epidermal growth factor (EGF) signaling-dependent manner. Lamellipodial extension at the free edge increases the cellular sensitivity to HGF. The HGF-dependent ERK activation, in turn, promotes lamellipodial extension, thereby forming a positive feedback loop between cell extension and ERK activation and specifying the cells at the free edge as the leader cells. Our findings show that the integration of physical and biochemical cues underlies the leader cell specification during collective cell migration.},
  author       = {Hino, Naoya and Matsuda, Kimiya and Jikko, Yuya and Maryu, Gembu and Sakai, Katsuya and Imamura, Ryu and Tsukiji, Shinya and Aoki, Kazuhiro and Terai, Kenta and Hirashima, Tsuyoshi and Trepat, Xavier and Matsuda, Michiyuki},
  issn         = {1534-5807},
  journal      = {Developmental Cell},
  keywords     = {Developmental Biology, Cell Biology, General Biochemistry, Genetics and Molecular Biology, Molecular Biology},
  number       = {19},
  pages        = {2290--2304.e7},
  publisher    = {Elsevier},
  title        = {{A feedback loop between lamellipodial extension and HGF-ERK signaling specifies leader cells during collective cell migration}},
  doi          = {10.1016/j.devcel.2022.09.003},
  volume       = {57},
  year         = {2022},
}

@article{12239,
  abstract     = {Biological systems are the sum of their dynamic three-dimensional (3D) parts. Therefore, it is critical to study biological structures in 3D and at high resolution to gain insights into their physiological functions. Electron microscopy of metal replicas of unroofed cells and isolated organelles has been a key technique to visualize intracellular structures at nanometer resolution. However, many of these methods require specialized equipment and personnel to complete them. Here, we present novel accessible methods to analyze biological structures in unroofed cells and biochemically isolated organelles in 3D and at nanometer resolution, focusing on Arabidopsis clathrin-coated vesicles (CCVs). While CCVs are essential trafficking organelles, their detailed structural information is lacking due to their poor preservation when observed via classical electron microscopy protocols experiments. First, we establish a method to visualize CCVs in unroofed cells using scanning transmission electron microscopy tomography, providing sufficient resolution to define the clathrin coat arrangements. Critically, the samples are prepared directly on electron microscopy grids, removing the requirement to use extremely corrosive acids, thereby enabling the use of this method in any electron microscopy lab. Secondly, we demonstrate that this standardized sample preparation allows the direct comparison of isolated CCV samples with those visualized in cells. Finally, to facilitate the high-throughput and robust screening of metal replicated samples, we provide a deep learning analysis method to screen the “pseudo 3D” morphologies of CCVs imaged with 2D modalities. Collectively, our work establishes accessible ways to examine the 3D structure of biological samples and provide novel insights into the structure of plant CCVs.},
  author       = {Johnson, Alexander J and Kaufmann, Walter and Sommer, Christoph M and Costanzo, Tommaso and Dahhan, Dana A. and Bednarek, Sebastian Y. and Friml, Jiří},
  issn         = {1674-2052},
  journal      = {Molecular Plant},
  keywords     = {Plant Science, Molecular Biology},
  number       = {10},
  pages        = {1533--1542},
  publisher    = {Elsevier},
  title        = {{Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution}},
  doi          = {10.1016/j.molp.2022.09.003},
  volume       = {15},
  year         = {2022},
}

@article{12245,
  abstract     = {MicroRNAs (miRs) have an important role in tuning dynamic gene expression. However, the mechanism by which they are quantitatively controlled is unknown. We show that the amount of mature miR-9, a key regulator of neuronal development, increases during zebrafish neurogenesis in a sharp stepwise manner. We characterize the spatiotemporal profile of seven distinct microRNA primary transcripts (pri-mir)-9s that produce the same mature miR-9 and show that they are sequentially expressed during hindbrain neurogenesis. Expression of late-onset pri-mir-9-1 is added on to, rather than replacing, the expression of early onset pri-mir-9-4 and -9-5 in single cells. CRISPR/Cas9 mutation of the late-onset pri-mir-9-1 prevents the developmental increase of mature miR-9, reduces late neuronal differentiation and fails to downregulate Her6 at late stages. Mathematical modelling shows that an adaptive network containing Her6 is insensitive to linear increases in miR-9 but responds to stepwise increases of miR-9. We suggest that a sharp stepwise increase of mature miR-9 is created by sequential and additive temporal activation of distinct loci. This may be a strategy to overcome adaptation and facilitate a transition of Her6 to a new dynamic regime or steady state.},
  author       = {Soto, Ximena and Burton, Joshua and Manning, Cerys S. and Minchington, Thomas and Lea, Robert and Lee, Jessica and Kursawe, Jochen and Rattray, Magnus and Papalopulu, Nancy},
  issn         = {1477-9129},
  journal      = {Development},
  keywords     = {Developmental Biology, Molecular Biology},
  number       = {19},
  publisher    = {The Company of Biologists},
  title        = {{Sequential and additive expression of miR-9 precursors control timing of neurogenesis}},
  doi          = {10.1242/dev.200474},
  volume       = {149},
  year         = {2022},
}

@article{12261,
  abstract     = {Dose–response relationships are a general concept for quantitatively describing biological systems across multiple scales, from the molecular to the whole-cell level. A clinically relevant example is the bacterial growth response to antibiotics, which is routinely characterized by dose–response curves. The shape of the dose–response curve varies drastically between antibiotics and plays a key role in treatment, drug interactions, and resistance evolution. However, the mechanisms shaping the dose–response curve remain largely unclear. Here, we show in Escherichia coli that the distinctively shallow dose–response curve of the antibiotic trimethoprim is caused by a negative growth-mediated feedback loop: Trimethoprim slows growth, which in turn weakens the effect of this antibiotic. At the molecular level, this feedback is caused by the upregulation of the drug target dihydrofolate reductase (FolA/DHFR). We show that this upregulation is not a specific response to trimethoprim but follows a universal trend line that depends primarily on the growth rate, irrespective of its cause. Rewiring the feedback loop alters the dose–response curve in a predictable manner, which we corroborate using a mathematical model of cellular resource allocation and growth. Our results indicate that growth-mediated feedback loops may shape drug responses more generally and could be exploited to design evolutionary traps that enable selection against drug resistance.},
  author       = {Angermayr, Andreas and Pang, Tin Yau and Chevereau, Guillaume and Mitosch, Karin and Lercher, Martin J and Bollenbach, Mark Tobias},
  issn         = {1744-4292},
  journal      = {Molecular Systems Biology},
  keywords     = {Applied Mathematics, Computational Theory and Mathematics, General Agricultural and Biological Sciences, General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, Information Systems},
  number       = {9},
  publisher    = {Embo Press},
  title        = {{Growth‐mediated negative feedback shapes quantitative antibiotic response}},
  doi          = {10.15252/msb.202110490},
  volume       = {18},
  year         = {2022},
}

@article{12262,
  abstract     = {The AAA-ATPase Drg1 is a key factor in eukaryotic ribosome biogenesis that initiates cytoplasmic maturation of the large ribosomal subunit. Drg1 releases the shuttling maturation factor Rlp24 from pre-60S particles shortly after nuclear export, a strict requirement for downstream maturation. The molecular mechanism of release remained elusive. Here, we report a series of cryo-EM structures that captured the extraction of Rlp24 from pre-60S particles by Saccharomyces cerevisiae Drg1. These structures reveal that Arx1 and the eukaryote-specific rRNA expansion segment ES27 form a joint docking platform that positions Drg1 for efficient extraction of Rlp24 from the pre-ribosome. The tips of the Drg1 N domains thereby guide the Rlp24 C terminus into the central pore of the Drg1 hexamer, enabling extraction by a hand-over-hand translocation mechanism. Our results uncover substrate recognition and processing by Drg1 step by step and provide a comprehensive mechanistic picture of the conserved modus operandi of AAA-ATPases.},
  author       = {Prattes, Michael and Grishkovskaya, Irina and Hodirnau, Victor-Valentin and Hetzmannseder, Christina and Zisser, Gertrude and Sailer, Carolin and Kargas, Vasileios and Loibl, Mathias and Gerhalter, Magdalena and Kofler, Lisa and Warren, Alan J. and Stengel, Florian and Haselbach, David and Bergler, Helmut},
  issn         = {1545-9985},
  journal      = {Nature Structural & Molecular Biology},
  keywords     = {Molecular Biology, Structural Biology},
  number       = {9},
  pages        = {942--953},
  publisher    = {Springer Nature},
  title        = {{Visualizing maturation factor extraction from the nascent ribosome by the AAA-ATPase Drg1}},
  doi          = {10.1038/s41594-022-00832-5},
  volume       = {29},
  year         = {2022},
}

@article{12272,
  abstract     = {Reading, interpreting and crawling along gradients of chemotactic cues is one of the most complex questions in cell biology. In this issue, Georgantzoglou et al. (2022. J. Cell. Biol.https://doi.org/10.1083/jcb.202103207) use in vivo models to map the temporal sequence of how neutrophils respond to an acutely arising gradient of chemoattractant.},
  author       = {Stopp, Julian A and Sixt, Michael K},
  issn         = {1540-8140},
  journal      = {Journal of Cell Biology},
  keywords     = {Cell Biology},
  number       = {8},
  publisher    = {Rockefeller University Press},
  title        = {{Plan your trip before you leave: The neutrophils’ search-and-run journey}},
  doi          = {10.1083/jcb.202206127},
  volume       = {221},
  year         = {2022},
}

@article{12275,
  abstract     = {N-glycans are molecularly diverse sugars borne by over 70% of proteins transiting the secretory pathway and have been implicated in protein folding, stability, and localization. Mutations in genes important for N-glycosylation result in congenital disorders of glycosylation that are often associated with intellectual disability. Here, we show that structurally distinct N-glycans regulate an extracellular protein complex involved in the patterning of somatosensory dendrites in Caenorhabditis elegans. Specifically, aman-2/Golgi alpha-mannosidase II, a conserved key enzyme in the biosynthesis of specific N-glycans, regulates the activity of the Menorin adhesion complex without obviously affecting the protein stability and localization of its components. AMAN-2 functions cell-autonomously to allow for decoration of the neuronal transmembrane receptor DMA-1/LRR-TM with the correct set of high-mannose/hybrid/paucimannose N-glycans. Moreover, distinct types of N-glycans on specific N-glycosylation sites regulate DMA-1/LRR-TM receptor function, which, together with three other extracellular proteins, forms the Menorin adhesion complex. In summary, specific N-glycan structures regulate dendrite patterning by coordinating the activity of an extracellular adhesion complex, suggesting that the molecular diversity of N-glycans can contribute to developmental specificity in the nervous system.},
  author       = {Rahman, Maisha and Ramirez, Nelson and Diaz‐Balzac, Carlos A and Bülow, Hannes E},
  issn         = {1469-3178},
  journal      = {EMBO Reports},
  keywords     = {Genetics, Molecular Biology, Biochemistry},
  number       = {7},
  publisher    = {Embo Press},
  title        = {{Specific N-glycans regulate an extracellular adhesion complex during somatosensory dendrite patterning}},
  doi          = {10.15252/embr.202154163},
  volume       = {23},
  year         = {2022},
}