@article{11713, abstract = {Objective: MazF is a sequence-specific endoribonuclease-toxin of the MazEF toxin–antitoxin system. MazF cleaves single-stranded ribonucleic acid (RNA) regions at adenine–cytosine–adenine (ACA) sequences in the bacterium Escherichia coli. The MazEF system has been used in various biotechnology and synthetic biology applications. In this study, we infer how ectopic mazF overexpression affects production of heterologous proteins. To this end, we quantified the levels of fluorescent proteins expressed in E. coli from reporters translated from the ACA-containing or ACA-less messenger RNAs (mRNAs). Additionally, we addressed the impact of the 5′-untranslated region of these reporter mRNAs under the same conditions by comparing expression from mRNAs that comprise (canonical mRNA) or lack this region (leaderless mRNA). Results: Flow cytometry analysis indicates that during mazF overexpression, fluorescent proteins are translated from the canonical as well as leaderless mRNAs. Our analysis further indicates that longer mazF overexpression generally increases the concentration of fluorescent proteins translated from ACA-less mRNAs, however it also substantially increases bacterial population heterogeneity. Finally, our results suggest that the strength and duration of mazF overexpression should be optimized for each experimental setup, to maximize the heterologous protein production and minimize the amount of phenotypic heterogeneity in bacterial populations, which is unfavorable in biotechnological processes.}, author = {Nikolic, Nela and Sauert, Martina and Albanese, Tanino G. and Moll, Isabella}, issn = {1756-0500}, journal = {BMC Research Notes}, keywords = {General Biochemistry, Genetics and Molecular Biology, General Medicine}, publisher = {Springer Nature}, title = {{Quantifying heterologous gene expression during ectopic MazF production in Escherichia coli}}, doi = {10.1186/s13104-022-06061-9}, volume = {15}, year = {2022}, } @article{13347, abstract = {Confining molecules within well-defined nanosized spaces can profoundly alter their physicochemical characteristics. For example, the controlled aggregation of chromophores into discrete oligomers has been shown to tune their optical properties whereas encapsulation of reactive species within molecular hosts can increase their stability. The resazurin/resorufin pair has been widely used for detecting redox processes in biological settings; yet, how tight confinement affects the properties of these two dyes remains to be explored. Here, we show that a flexible PdII6L4 coordination cage can efficiently encapsulate both resorufin and resazurin in the form of dimers, dramatically modulating their optical properties. Furthermore, binding within the cage significantly decreases the reduction rate of resazurin to resorufin, and the rate of the subsequent reduction of resorufin to dihydroresorufin. During our studies, we also found that upon dilution, the PdII6L4 cage disassembles to afford PdII2L2 species, which lacks the ability to form inclusion complexes – a process that can be reversed upon the addition of the strongly binding resorufin/resazurin guests. We expect that the herein disclosed ability of a water-soluble cage to reversibly modulate the optical and chemical properties of a molecular redox probe will expand the versatility of synthetic fluorescent probes in biologically relevant environments.}, author = {Yanshyna, Oksana and Białek, Michał J. and Chashchikhin, Oleg V. and Klajn, Rafal}, issn = {2399-3669}, journal = {Communications Chemistry}, keywords = {Materials Chemistry, Biochemistry, Environmental Chemistry, General Chemistry}, publisher = {Springer Nature}, title = {{Encapsulation within a coordination cage modulates the reactivity of redox-active dyes}}, doi = {10.1038/s42004-022-00658-8}, volume = {5}, year = {2022}, } @article{13348, abstract = {Molecular confinement effects can profoundly alter the physicochemical properties of the confined species. A plethora of organic molecules were encapsulated within the cavities of supramolecular hosts, and the impact of the cavity size and polarity was widely investigated. However, the extent to which the properties of the confined guests can be affected by the symmetry of the cage─which dictates the shape of the cavity─remains to be understood. Here we show that cage symmetry has a dramatic effect on the equilibrium between two isomers of the encapsulated spiropyran guests. Working with two Pd-based coordination cages featuring similarly sized but differently shaped hydrophobic cavities, we found a highly selective stabilization of the isomer whose shape matches that of the cavity of the cage. A Td-symmetric cage stabilized the spiropyrans’ colorless form and rendered them photochemically inert. In contrast, a D2h-symmetric cage favored the colored isomer, while maintaining reversible photoswitching between the two states of the encapsulated spiropyrans. We also show that the switching kinetics strongly depend on the substitution pattern on the spiropyran scaffold. This finding was used to fabricate a time-sensitive information storage medium with tunable lifetimes of the encoded messages.}, author = {Wang, Jinhua and Avram, Liat and Diskin-Posner, Yael and Białek, Michał J. and Stawski, Wojciech and Feller, Moran and Klajn, Rafal}, issn = {1520-5126}, journal = {Journal of the American Chemical Society}, keywords = {Colloid and Surface Chemistry, Biochemistry, General Chemistry, Catalysis}, number = {46}, pages = {21244--21254}, publisher = {American Chemical Society}, title = {{Altering the properties of spiropyran switches using coordination cages with different symmetries}}, doi = {10.1021/jacs.2c08901}, volume = {144}, year = {2022}, } @article{13350, abstract = {Confinement within molecular cages can dramatically modify the physicochemical properties of the encapsulated guest molecules, but such host-guest complexes have mainly been studied in a static context. Combining confinement effects with fast guest exchange kinetics could pave the way toward stimuli-responsive supramolecular systems—and ultimately materials—whose desired properties could be tailored “on demand” rapidly and reversibly. Here, we demonstrate rapid guest exchange between inclusion complexes of an open-window coordination cage that can simultaneously accommodate two guest molecules. Working with two types of guests, anthracene derivatives and BODIPY dyes, we show that the former can substantially modify the optical properties of the latter upon noncovalent heterodimer formation. We also studied the light-induced covalent dimerization of encapsulated anthracenes and found large effects of confinement on reaction rates. By coupling the photodimerization with the rapid guest exchange, we developed a new way to modulate fluorescence using external irradiation.}, author = {Gemen, Julius and Białek, Michał J. and Kazes, Miri and Shimon, Linda J.W. and Feller, Moran and Semenov, Sergey N. and Diskin-Posner, Yael and Oron, Dan and Klajn, Rafal}, issn = {2451-9294}, journal = {Chem}, keywords = {Materials Chemistry, Biochemistry (medical), General Chemical Engineering, Environmental Chemistry, Biochemistry, General Chemistry}, number = {9}, pages = {2362--2379}, publisher = {Elsevier}, title = {{Ternary host-guest complexes with rapid exchange kinetics and photoswitchable fluorescence}}, doi = {10.1016/j.chempr.2022.05.008}, volume = {8}, year = {2022}, } @article{13351, abstract = {Molecular recognition is at the heart of the noncovalent synthesis of supramolecular assemblies and, at higher length scales, supramolecular materials. In a recent publication in Nature, Stoddart and co-workers demonstrate that the formation of host-guest complexes can be catalyzed by one of the simplest possible catalysts: the electron.}, author = {Gemen, Julius and Klajn, Rafal}, issn = {2451-9294}, journal = {Chem}, keywords = {Materials Chemistry, Biochemistry (medical), General Chemical Engineering, Environmental Chemistry, Biochemistry, General Chemistry}, number = {5}, pages = {1183--1186}, publisher = {Elsevier}, title = {{Electron catalysis expands the supramolecular chemist’s toolbox}}, doi = {10.1016/j.chempr.2022.04.022}, volume = {8}, year = {2022}, } @article{11951, abstract = {The mammalian hippocampal formation (HF) plays a key role in several higher brain functions, such as spatial coding, learning and memory. Its simple circuit architecture is often viewed as a trisynaptic loop, processing input originating from the superficial layers of the entorhinal cortex (EC) and sending it back to its deeper layers. Here, we show that excitatory neurons in layer 6b of the mouse EC project to all sub-regions comprising the HF and receive input from the CA1, thalamus and claustrum. Furthermore, their output is characterized by unique slow-decaying excitatory postsynaptic currents capable of driving plateau-like potentials in their postsynaptic targets. Optogenetic inhibition of the EC-6b pathway affects spatial coding in CA1 pyramidal neurons, while cell ablation impairs not only acquisition of new spatial memories, but also degradation of previously acquired ones. Our results provide evidence of a functional role for cortical layer 6b neurons in the adult brain.}, author = {Ben Simon, Yoav and Käfer, Karola and Velicky, Philipp and Csicsvari, Jozsef L and Danzl, Johann G and Jonas, Peter M}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary}, publisher = {Springer Nature}, title = {{A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory}}, doi = {10.1038/s41467-022-32559-8}, volume = {13}, year = {2022}, } @article{12051, abstract = {Transcription of the ribosomal RNA precursor by RNA polymerase (Pol) I is a major determinant of cellular growth, and dysregulation is observed in many cancer types. Here, we present the purification of human Pol I from cells carrying a genomic GFP fusion on the largest subunit allowing the structural and functional analysis of the enzyme across species. In contrast to yeast, human Pol I carries a single-subunit stalk, and in vitro transcription indicates a reduced proofreading activity. Determination of the human Pol I cryo-EM reconstruction in a close-to-native state rationalizes the effects of disease-associated mutations and uncovers an additional domain that is built into the sequence of Pol I subunit RPA1. This “dock II” domain resembles a truncated HMG box incapable of DNA binding which may serve as a downstream transcription factor–binding platform in metazoans. Biochemical analysis, in situ modelling, and ChIP data indicate that Topoisomerase 2a can be recruited to Pol I via the domain and cooperates with the HMG box domain–containing factor UBF. These adaptations of the metazoan Pol I transcription system may allow efficient release of positive DNA supercoils accumulating downstream of the transcription bubble.}, author = {Daiß, Julia L and Pilsl, Michael and Straub, Kristina and Bleckmann, Andrea and Höcherl, Mona and Heiss, Florian B and Abascal-Palacios, Guillermo and Ramsay, Ewan P and Tluckova, Katarina and Mars, Jean-Clement and Fürtges, Torben and Bruckmann, Astrid and Rudack, Till and Bernecky, Carrie A and Lamour, Valérie and Panov, Konstantin and Vannini, Alessandro and Moss, Tom and Engel, Christoph}, issn = {2575-1077}, journal = {Life Science Alliance}, keywords = {Health, Toxicology and Mutagenesis, Plant Science, Biochemistry, Genetics and Molecular Biology (miscellaneous), Ecology}, number = {11}, publisher = {Life Science Alliance}, title = {{The human RNA polymerase I structure reveals an HMG-like docking domain specific to metazoans}}, doi = {10.26508/lsa.202201568}, volume = {5}, year = {2022}, } @article{12117, abstract = {To understand how potential gene manipulations affect in vitro microglia, we provide a set of short protocols to evaluate microglia identity and function. We detail steps for immunostaining to determine microglia identity. We describe three functional assays for microglia: phagocytosis, calcium response following ATP stimulation, and cytokine expression upon inflammatory stimuli. We apply these protocols to human induced-pluripotent-stem-cell (hiPSC)-derived microglia, but they can be also applied to other in vitro microglial models including primary mouse microglia. For complete details on the use and execution of this protocol, please refer to Bartalska et al. (2022).1}, author = {Hübschmann, Verena and Korkut, Medina and Siegert, Sandra}, issn = {2666-1667}, journal = {STAR Protocols}, keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Neuroscience}, number = {4}, publisher = {Elsevier}, title = {{Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay}}, doi = {10.1016/j.xpro.2022.101866}, volume = {3}, year = {2022}, } @article{12120, abstract = {Plant root architecture flexibly adapts to changing nitrate (NO3−) availability in the soil; however, the underlying molecular mechanism of this adaptive development remains under-studied. To explore the regulation of NO3−-mediated root growth, we screened for low-nitrate-resistant mutant (lonr) and identified mutants that were defective in the NAC transcription factor NAC075 (lonr1) as being less sensitive to low NO3− in terms of primary root growth. We show that NAC075 is a mobile transcription factor relocating from the root stele tissues to the endodermis based on NO3− availability. Under low-NO3− availability, the kinase CBL-interacting protein kinase 1 (CIPK1) is activated, and it phosphorylates NAC075, restricting its movement from the stele, which leads to the transcriptional regulation of downstream target WRKY53, consequently leading to adapted root architecture. Our work thus identifies an adaptive mechanism involving translocation of transcription factor based on nutrient availability and leading to cell-specific reprogramming of plant root growth.}, author = {Xiao, Huixin and Hu, Yumei and Wang, Yaping and Cheng, Jinkui and Wang, Jinyi and Chen, Guojingwei and Li, Qian and Wang, Shuwei and Wang, Yalu and Wang, Shao-Shuai and Wang, Yi and Xuan, Wei and Li, Zhen and Guo, Yan and Gong, Zhizhong and Friml, Jiří and Zhang, Jing}, issn = {1534-5807}, journal = {Developmental Cell}, keywords = {Developmental Biology, Cell Biology, General Biochemistry, Genetics and Molecular Biology, Molecular Biology}, number = {23}, pages = {2638--2651.e6}, publisher = {Elsevier}, title = {{Nitrate availability controls translocation of the transcription factor NAC075 for cell-type-specific reprogramming of root growth}}, doi = {10.1016/j.devcel.2022.11.006}, volume = {57}, year = {2022}, } @article{12130, abstract = {Germline determination is essential for species survival and evolution in multicellular organisms. In most flowering plants, formation of the female germline is initiated with specification of one megaspore mother cell (MMC) in each ovule; however, the molecular mechanism underlying this key event remains unclear. Here we report that spatially restricted auxin signaling promotes MMC fate in Arabidopsis. Our results show that the microRNA160 (miR160) targeted gene ARF17 (AUXIN RESPONSE FACTOR17) is required for promoting MMC specification by genetically interacting with the SPL/NZZ (SPOROCYTELESS/NOZZLE) gene. Alterations of auxin signaling cause formation of supernumerary MMCs in an ARF17- and SPL/NZZ-dependent manner. Furthermore, miR160 and ARF17 are indispensable for attaining a normal auxin maximum at the ovule apex via modulating the expression domain of PIN1 (PIN-FORMED1) auxin transporter. Our findings elucidate the mechanism by which auxin signaling promotes the acquisition of female germline cell fate in plants.}, author = {Huang, Jian and Zhao, Lei and Malik, Shikha and Gentile, Benjamin R. and Xiong, Va and Arazi, Tzahi and Owen, Heather A. and Friml, Jiří and Zhao, Dazhong}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary}, publisher = {Springer Nature}, title = {{Specification of female germline by microRNA orchestrated auxin signaling in Arabidopsis}}, doi = {10.1038/s41467-022-34723-6}, volume = {13}, 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 (Li2S) 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 Li2S the deposit comprises solid short-chain PSs particles. The analysis of the experimental data suggests that initially, Li2S2 precipitates from the solution and then is partially converted via solid-state electroreduction to Li2S. 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 Mkln1 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 Mkln1 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 Mkln1 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{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{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{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}, } @article{12288, abstract = {To understand the function of neuronal circuits, it is crucial to disentangle the connectivity patterns within the network. However, most tools currently used to explore connectivity have low throughput, low selectivity, or limited accessibility. Here, we report the development of an improved packaging system for the production of the highly neurotropic RVdGenvA-CVS-N2c rabies viral vectors, yielding titers orders of magnitude higher with no background contamination, at a fraction of the production time, while preserving the efficiency of transsynaptic labeling. Along with the production pipeline, we developed suites of ‘starter’ AAV and bicistronic RVdG-CVS-N2c vectors, enabling retrograde labeling from a wide range of neuronal populations, tailored for diverse experimental requirements. We demonstrate the power and flexibility of the new system by uncovering hidden local and distal inhibitory connections in the mouse hippocampal formation and by imaging the functional properties of a cortical microcircuit across weeks. Our novel production pipeline provides a convenient approach to generate new rabies vectors, while our toolkit flexibly and efficiently expands the current capacity to label, manipulate and image the neuronal activity of interconnected neuronal circuits in vitro and in vivo.}, author = {Sumser, Anton L and Jösch, Maximilian A and Jonas, Peter M and Ben Simon, Yoav}, 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 = {{Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling}}, doi = {10.7554/elife.79848}, volume = {11}, year = {2022}, } @article{12670, abstract = {DNA methylation plays essential homeostatic functions in eukaryotic genomes. In animals, DNA methylation is also developmentally regulated and, in turn, regulates development. In the past two decades, huge research effort has endorsed the understanding that DNA methylation plays a similar role in plant development, especially during sexual reproduction. The power of whole-genome sequencing and cell isolation techniques, as well as bioinformatics tools, have enabled recent studies to reveal dynamic changes in DNA methylation during germline development. Furthermore, the combination of these technological advances with genetics, developmental biology and cell biology tools has revealed functional methylation reprogramming events that control gene and transposon activities in flowering plant germlines. In this review, we discuss the major advances in our knowledge of DNA methylation dynamics during male and female germline development in flowering plants.}, author = {He, Shengbo and Feng, Xiaoqi}, issn = {1744-7909}, journal = {Journal of Integrative Plant Biology}, keywords = {Plant Science, General Biochemistry, Genetics and Molecular Biology, Biochemistry}, number = {12}, pages = {2240--2251}, publisher = {Wiley}, title = {{DNA methylation dynamics during germline development}}, doi = {10.1111/jipb.13422}, volume = {64}, year = {2022}, }