@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{12225,
  abstract     = {In social networks, users often engage with like-minded peers. This selective exposure to opinions might result in echo chambers, i.e., political fragmentation and social polarization of user interactions. When echo chambers form, opinions have a bimodal distribution with two peaks on opposite sides. In certain issues, where either extreme positions contain a degree of misinformation, neutral consensus is preferable for promoting discourse. In this paper, we use an opinion dynamics model that naturally forms echo chambers in order to find a feedback mechanism that bridges these communities and leads to a neutral consensus. We introduce the <jats:italic>random dynamical nudge</jats:italic> (RDN), which presents each agent with input from a random selection of other agents’ opinions and does not require surveillance of every person’s opinions. Our computational results in two different models suggest that the RDN leads to a unimodal distribution of opinions centered around the neutral consensus. Furthermore, the RDN is effective both for preventing the formation of echo chambers and also for depolarizing existing echo chambers. Due to the simple and robust nature of the RDN, social media networks might be able to implement a version of this self-feedback mechanism, when appropriate, to prevent the segregation of online communities on complex social issues.},
  author       = {Currin, Christopher and Vera, Sebastián Vallejo and Khaledi-Nasab, Ali},
  issn         = {2045-2322},
  journal      = {Scientific Reports},
  keywords     = {Multidisciplinary},
  publisher    = {Springer Nature},
  title        = {{Depolarization of echo chambers by random dynamical nudge}},
  doi          = {10.1038/s41598-022-12494-w},
  volume       = {12},
  year         = {2022},
}

@article{12226,
  abstract     = {Background: Biases of DNA repair can shape the nucleotide landscape of genomes at evolutionary timescales. The molecular mechanisms of those biases are still poorly understood because it is difficult to isolate the contributions of DNA repair from those of DNA damage.

Results: Here, we develop a genome-wide assay whereby the same DNA lesion is repaired in different genomic contexts. We insert thousands of barcoded transposons carrying a reporter of DNA mismatch repair in the genome of mouse embryonic stem cells. Upon inducing a double-strand break between tandem repeats, a mismatch is generated if the break is repaired through single-strand annealing. The resolution of the mismatch showed a 60–80% bias in favor of the strand with the longest 3′ flap. The location of the lesion in the genome and the type of mismatch had little influence on the bias. Instead, we observe a complete reversal of the bias when the longest 3′ flap is moved to the opposite strand by changing the position of the double-strand break in the reporter.

Conclusions: These results suggest that the processing of the double-strand break has a major influence on the repair of mismatches during single-strand annealing.},
  author       = {Pokusaeva, Victoria and Diez, Aránzazu Rosado and Espinar, Lorena and Pérez, Albert Torelló and Filion, Guillaume J.},
  issn         = {1474-760X},
  journal      = {Genome Biology},
  publisher    = {Springer Nature},
  title        = {{Strand asymmetry influences mismatch resolution during single-strand annealing}},
  doi          = {10.1186/s13059-022-02665-3},
  volume       = {23},
  year         = {2022},
}

@article{12227,
  abstract     = {Polydicyclopentadiene (pDCPD), a thermoset with excellent mechanical properties, has enormous potential as a lightweight, tough, and stable matrix material owing to its highly cross-linked macromolecular network. This work describes generating pDCPD-based foams and hierarchically porous carbons derived therefrom by combining ring-opening metathesis polymerization (ROMP) of DCPD, high internal phase emulsions (HIPEs) as structural templates, and subsequent carbonization. The structure and function of the carbon foams were characterized and discussed in detail using scanning electron, transmission electron, or atomic force microscopy (SEM, TEM, AFM), electron energy-loss spectroscopy (TEM-EELS), N2 sorption, and analyses of electrical conductivity as well as mechanical properties. The resulting materials exhibited uniform, shape-retaining shrinkage of only ∼1/3 after carbonization. No structural failure was observed even when the pDCPD precursor foams were heated to 1400 °C. Instead, the high porosity, void size, and 3D interconnectivity were fully preserved, and the void diameters could be adjusted between 87 and 2.5 μm. Moreover, foams have a carbon content >97%, an electronic conductivity of up to 2800 S·m–1, a Young’s modulus of up to 2.1 GPa, and a specific surface area of up to 1200 m2·g–1. Surprisingly, the pDCPD foams were carbonized into shapes other than monoliths, such as 10’s of micron thick membranes or foamy coatings adhered to a metal foil or grid substrate. The latter coatings even adhere upon bending. Finally, as a use case, carbonized foams were applied as porous cathodes for Li–O2 batteries where the foams show a favorable combination of porosity, active surface area, and pore size for outstanding capacity.},
  author       = {Kovačič, Sebastijan and Schafzahl, Bettina and Matsko, Nadejda B. and Gruber, Katharina and Schmuck, Martin and Koller, Stefan and Freunberger, Stefan Alexander and Slugovc, Christian},
  issn         = {2574-0962},
  journal      = {ACS Applied Energy Materials},
  keywords     = {Electrical and Electronic Engineering, Materials Chemistry, Electrochemistry, Energy Engineering and Power Technology, Chemical Engineering (miscellaneous)},
  number       = {11},
  pages        = {14381--14390},
  publisher    = {American Chemical Society},
  title        = {{Carbon foams via ring-opening metathesis polymerization of emulsion templates: A facile method to make carbon current collectors for battery applications}},
  doi          = {10.1021/acsaem.2c02787},
  volume       = {5},
  year         = {2022},
}

@article{12228,
  abstract     = {The question of how RNA, as the principal carrier of genetic information evolved is fundamentally important for our understanding of the origin of life. The RNA molecule is far too complex to have formed in one evolutionary step, suggesting that ancestral proto-RNAs (first ancestor of RNA) may have existed, which evolved over time into the RNA of today. Here we show that isoxazole nucleosides, which are quickly formed from hydroxylamine, cyanoacetylene, urea and ribose, are plausible precursors for RNA. The isoxazole nucleoside can rearrange within an RNA-strand to give cytidine, which leads to an increase of pairing stability. If the proto-RNA contains a canonical seed-nucleoside with defined stereochemistry, the seed-nucleoside can control the configuration of the anomeric center that forms during the in-RNA transformation. The results demonstrate that RNA could have emerged from evolutionarily primitive precursor isoxazole ribosides after strand formation.},
  author       = {Xu, Felix and Crisp, Antony and Schinkel, Thea and Dubini, Romeo C. A. and Hübner, Sarah and Becker, Sidney and Schelter, Florian and Rovo, Petra and Carell, Thomas},
  issn         = {1521-3773},
  journal      = {Angewandte Chemie International Edition},
  keywords     = {General Chemistry, Catalysis},
  number       = {45},
  publisher    = {Wiley},
  title        = {{Isoxazole nucleosides as building blocks for a plausible proto‐RNA}},
  doi          = {10.1002/anie.202211945},
  volume       = {61},
  year         = {2022},
}

@inproceedings{12229,
  abstract     = {We present Bullshark, the first directed acyclic graph (DAG) based asynchronous Byzantine Atomic Broadcast protocol that is optimized for the common synchronous case. Like previous DAG-based BFT protocols [19, 25], Bullshark requires no extra communication to achieve consensus on top of building the DAG. That is, parties can totally order the vertices of the DAG by interpreting their local view of the DAG edges. Unlike other asynchronous DAG-based protocols, Bullshark provides a practical low latency fast-path that exploits synchronous periods and deprecates the need for notoriously complex view-change and view-synchronization mechanisms. Bullshark achieves this while maintaining all the desired properties of its predecessor DAG-Rider [25]. Namely, it has optimal amortized communication complexity, it provides fairness and asynchronous liveness, and safety is guaranteed even under a quantum adversary.

In order to show the practicality and simplicity of our approach, we also introduce a standalone partially synchronous version of Bullshark, which we evaluate against the state of the art. The implemented protocol is embarrassingly simple (200 LOC on top of an existing DAG-based mempool implementation). It is highly efficient, achieving for example, 125,000 transactions per second with a 2 seconds latency for a deployment of 50 parties. In the same setting, the state of the art pays a steep 50% latency increase as it optimizes for asynchrony.},
  author       = {Spiegelman, Alexander and Giridharan, Neil and Sonnino, Alberto and Kokoris Kogias, Eleftherios},
  booktitle    = {Proceedings of the 2022 ACM SIGSAC Conference on Computer and Communications Security},
  isbn         = {9781450394505},
  location     = {Los Angeles, CA, United States},
  pages        = {2705–2718},
  publisher    = {Association for Computing Machinery},
  title        = {{Bullshark: DAG BFT protocols made practical}},
  doi          = {10.1145/3548606.3559361},
  year         = {2022},
}

@article{12232,
  abstract     = {We derive a precise asymptotic formula for the density of the small singular values of the real Ginibre matrix ensemble shifted by a complex parameter z as the dimension tends to infinity. For z away from the real axis the formula coincides with that for the complex Ginibre ensemble we derived earlier in Cipolloni et al. (Prob Math Phys 1:101–146, 2020). On the level of the one-point function of the low lying singular values we thus confirm the transition from real to complex Ginibre ensembles as the shift parameter z becomes genuinely complex; the analogous phenomenon has been well known for eigenvalues. We use the superbosonization formula (Littelmann et al. in Comm Math Phys 283:343–395, 2008) in a regime where the main contribution comes from a three dimensional saddle manifold.},
  author       = {Cipolloni, Giorgio and Erdös, László and Schröder, Dominik J},
  issn         = {1424-0661},
  journal      = {Annales Henri Poincaré},
  keywords     = {Mathematical Physics, Nuclear and High Energy Physics, Statistical and Nonlinear Physics},
  number       = {11},
  pages        = {3981--4002},
  publisher    = {Springer Nature},
  title        = {{Density of small singular values of the shifted real Ginibre ensemble}},
  doi          = {10.1007/s00023-022-01188-8},
  volume       = {23},
  year         = {2022},
}

@article{12234,
  abstract     = {Hybrid speciation—the origin of new species resulting from the hybridization of genetically divergent lineages—was once considered rare, but genomic data suggest that it may occur more often than once thought. In this study, Noguerales and Ortego found genomic evidence supporting the hybrid origin of a grasshopper that is able to exploit a broader range of host plants than either of its putative parents.},
  author       = {Stankowski, Sean},
  issn         = {1558-5646},
  journal      = {Evolution},
  keywords     = {General Agricultural and Biological Sciences, Genetics, Ecology, Evolution, Behavior and Systematics},
  number       = {11},
  pages        = {2784--2785},
  publisher    = {Wiley},
  title        = {{Digest: On the origin of a possible hybrid species}},
  doi          = {10.1111/evo.14632},
  volume       = {76},
  year         = {2022},
}

@article{12235,
  abstract     = {Background: About 800 women die every day worldwide from pregnancy-related complications, including excessive blood loss, infections and high-blood pressure (World Health Organization, 2019). To improve screening for high-risk pregnancies, we set out to identify patterns of maternal hematological changes associated with future pregnancy complications.

Methods: Using mixed effects models, we established changes in 14 complete blood count (CBC) parameters for 1710 healthy pregnancies and compared them to measurements from 98 pregnancy-induced hypertension, 106 gestational diabetes and 339 postpartum hemorrhage cases.

Results: Results show interindividual variations, but good individual repeatability in CBC values during physiological pregnancies, allowing the identification of specific alterations in women with obstetric complications. For example, in women with uncomplicated pregnancies, haemoglobin count decreases of 0.12 g/L (95% CI −0.16, −0.09) significantly per gestation week (p value <.001). Interestingly, this decrease is three times more pronounced in women who will develop pregnancy-induced hypertension, with an additional decrease of 0.39 g/L (95% CI −0.51, −0.26). We also confirm that obstetric complications and white CBC predict the likelihood of giving birth earlier during pregnancy.

Conclusion: We provide a comprehensive description of the associations between haematological changes through pregnancy and three major obstetric complications to support strategies for prevention, early-diagnosis and maternal care.},
  author       = {Patxot, Marion and Stojanov, Miloš and Ojavee, Sven Erik and Gobert, Rosanna Pescini and Kutalik, Zoltán and Gavillet, Mathilde and Baud, David and Robinson, Matthew Richard},
  issn         = {1600-0609},
  journal      = {European Journal of Haematology},
  keywords     = {Hematology, General Medicine},
  number       = {5},
  pages        = {566--575},
  publisher    = {Wiley},
  title        = {{Haematological changes from conception to childbirth: An indicator of major pregnancy complications}},
  doi          = {10.1111/ejh.13844},
  volume       = {109},
  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{12243,
  abstract     = {We consider the eigenvalues of a large dimensional real or complex Ginibre matrix in the region of the complex plane where their real parts reach their maximum value. This maximum follows the Gumbel distribution and that these extreme eigenvalues form a Poisson point process as the dimension asymptotically tends to infinity. In the complex case, these facts have already been established by Bender [Probab. Theory Relat. Fields 147, 241 (2010)] and in the real case by Akemann and Phillips [J. Stat. Phys. 155, 421 (2014)] even for the more general elliptic ensemble with a sophisticated saddle point analysis. The purpose of this article is to give a very short direct proof in the Ginibre case with an effective error term. Moreover, our estimates on the correlation kernel in this regime serve as a key input for accurately locating [Formula: see text] for any large matrix X with i.i.d. entries in the companion paper [G. Cipolloni et al., arXiv:2206.04448 (2022)]. },
  author       = {Cipolloni, Giorgio and Erdös, László and Schröder, Dominik J and Xu, Yuanyuan},
  issn         = {1089-7658},
  journal      = {Journal of Mathematical Physics},
  keywords     = {Mathematical Physics, Statistical and Nonlinear Physics},
  number       = {10},
  publisher    = {AIP Publishing},
  title        = {{Directional extremal statistics for Ginibre eigenvalues}},
  doi          = {10.1063/5.0104290},
  volume       = {63},
  year         = {2022},
}

@article{12246,
  abstract     = {The Lieb–Oxford inequality provides a lower bound on the Coulomb energy of a classical system of N identical charges only in terms of their one-particle density. We prove here a new estimate on the best constant in this inequality. Numerical evaluation provides the value 1.58, which is a significant improvement to the previously known value 1.64. The best constant has recently been shown to be larger than 1.44. In a second part, we prove that the constant can be reduced to 1.25 when the inequality is restricted to Hartree–Fock states. This is the first proof that the exchange term is always much lower than the full indirect Coulomb energy.},
  author       = {Lewin, Mathieu and Lieb, Elliott H. and Seiringer, Robert},
  issn         = {1573-0530},
  journal      = {Letters in Mathematical Physics},
  keywords     = {Mathematical Physics, Statistical and Nonlinear Physics},
  number       = {5},
  publisher    = {Springer Nature},
  title        = {{Improved Lieb–Oxford bound on the indirect and exchange energies}},
  doi          = {10.1007/s11005-022-01584-5},
  volume       = {112},
  year         = {2022},
}

@article{12247,
  abstract     = {Chromosomal inversions have been shown to play a major role in a local adaptation by suppressing recombination between alternative arrangements and maintaining beneficial allele combinations. However, so far, their importance relative to the remaining genome remains largely unknown. Understanding the genetic architecture of adaptation requires better estimates of how loci of different effect sizes contribute to phenotypic variation. Here, we used three Swedish islands where the marine snail Littorina saxatilis has repeatedly evolved into two distinct ecotypes along a habitat transition. We estimated the contribution of inversion polymorphisms to phenotypic divergence while controlling for polygenic effects in the remaining genome using a quantitative genetics framework. We confirmed the importance of inversions but showed that contributions of loci outside inversions are of similar magnitude, with variable proportions dependent on the trait and the population. Some inversions showed consistent effects across all sites, whereas others exhibited site-specific effects, indicating that the genomic basis for replicated phenotypic divergence is only partly shared. The contributions of sexual dimorphism as well as environmental factors to phenotypic variation were significant but minor compared to inversions and polygenic background. Overall, this integrated approach provides insight into the multiple mechanisms contributing to parallel phenotypic divergence.},
  author       = {Koch, Eva L. and Ravinet, Mark and Westram, Anja M and Johannesson, Kerstin and Butlin, Roger K.},
  issn         = {1558-5646},
  journal      = {Evolution},
  keywords     = {General Agricultural and Biological Sciences, Genetics, Ecology, Evolution, Behavior and Systematics},
  number       = {10},
  pages        = {2332--2346},
  publisher    = {Wiley},
  title        = {{Genetic architecture of repeated phenotypic divergence in Littorina saxatilis evolution}},
  doi          = {10.1111/evo.14602},
  volume       = {76},
  year         = {2022},
}

@article{12251,
  abstract     = {Amyloid formation is linked to devastating neurodegenerative diseases, motivating detailed studies of the mechanisms of amyloid formation. For Aβ, the peptide associated with Alzheimer’s disease, the mechanism and rate of aggregation have been established for a range of variants and conditions <jats:italic>in vitro</jats:italic> and in bodily fluids. A key outstanding question is how the relative stabilities of monomers, fibrils and intermediates affect each step in the fibril formation process. By monitoring the kinetics of aggregation of Aβ42, in the presence of urea or guanidinium hydrochloride (GuHCl), we here determine the rates of the underlying microscopic steps and establish the importance of changes in relative stability induced by the presence of denaturant for each individual step. Denaturants shift the equilibrium towards the unfolded state of each species. We find that a non-ionic denaturant, urea, reduces the overall aggregation rate, and that the effect on nucleation is stronger than the effect on elongation. Urea reduces the rate of secondary nucleation by decreasing the coverage of fibril surfaces and the rate of nucleus formation. It also reduces the rate of primary nucleation, increasing its reaction order. The ionic denaturant, GuHCl, accelerates the aggregation at low denaturant concentrations and decelerates the aggregation at high denaturant concentrations. Below approximately 0.25 M GuHCl, the screening of repulsive electrostatic interactions between peptides by the charged denaturant dominates, leading to an increased aggregation rate. At higher GuHCl concentrations, the electrostatic repulsion is completely screened, and the denaturing effect dominates. The results illustrate how the differential effects of denaturants on stability of monomer, oligomer and fibril translate to differential effects on microscopic steps, with the rate of nucleation being most strongly reduced.},
  author       = {Weiffert, Tanja and Meisl, Georg and Curk, Samo and Cukalevski, Risto and Šarić, Anđela and Knowles, Tuomas P. J. and Linse, Sara},
  issn         = {1662-453X},
  journal      = {Frontiers in Neuroscience},
  keywords     = {General Neuroscience},
  publisher    = {Frontiers Media},
  title        = {{Influence of denaturants on amyloid β42 aggregation kinetics}},
  doi          = {10.3389/fnins.2022.943355},
  volume       = {16},
  year         = {2022},
}

@article{12252,
  abstract     = {The COVID−19 pandemic not only resulted in a global crisis, but also accelerated vaccine development and antibody discovery. Herein we report a synthetic humanized VHH library development pipeline for nanomolar-range affinity VHH binders to SARS-CoV-2 variants of concern (VoC) receptor binding domains (RBD) isolation. Trinucleotide-based randomization of CDRs by Kunkel mutagenesis with the subsequent rolling-cycle amplification resulted in more than 10<jats:sup>11</jats:sup> diverse phage display library in a manageable for a single person number of electroporation reactions. We identified a number of nanomolar-range affinity VHH binders to SARS-CoV-2 variants of concern (VoC) receptor binding domains (RBD) by screening a novel synthetic humanized antibody library. In order to explore the most robust and fast method for affinity improvement, we performed affinity maturation by CDR1 and CDR2 shuffling and avidity engineering by multivalent trimeric VHH fusion protein construction. As a result, H7-Fc and G12x3-Fc binders were developed with the affinities in nM and pM range respectively. Importantly, these affinities are weakly influenced by most of SARS-CoV-2 VoC mutations and they retain moderate binding to BA.4\5. The plaque reduction neutralization test (PRNT) resulted in IC50 = 100 ng\ml and 9.6 ng\ml for H7-Fc and G12x3-Fc antibodies, respectively, for the emerging Omicron BA.1 variant. Therefore, these VHH could expand the present landscape of SARS-CoV-2 neutralization binders with the therapeutic potential for present and future SARS-CoV-2 variants.},
  author       = {Dormeshkin, Dmitri and Shapira, Michail and Dubovik, Simon and Kavaleuski, Anton and Katsin, Mikalai and Migas, Alexandr and Meleshko, Alexander and Semyonov, Sergei},
  issn         = {1664-3224},
  journal      = {Frontiers in Immunology},
  keywords     = {Immunology, Immunology and Allergy, COVID-19, SARS-CoV-2, synthetic library, RBD, neutralization nanobody, VHH},
  publisher    = {Frontiers Media},
  title        = {{Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library}},
  doi          = {10.3389/fimmu.2022.965446},
  volume       = {13},
  year         = {2022},
}

@article{12253,
  abstract     = {The sculpting of germ layers during gastrulation relies on the coordinated migration of progenitor cells, yet the cues controlling these long-range directed movements remain largely unknown. While directional migration often relies on a chemokine gradient generated from a localized source, we find that zebrafish ventrolateral mesoderm is guided by a self-generated gradient of the initially uniformly expressed and secreted protein Toddler/ELABELA/Apela. We show that the Apelin receptor, which is specifically expressed in mesodermal cells, has a dual role during gastrulation, acting as a scavenger receptor to generate a Toddler gradient, and as a chemokine receptor to sense this guidance cue. Thus, we uncover a single receptor–based self-generated gradient as the enigmatic guidance cue that can robustly steer the directional migration of mesoderm through the complex and continuously changing environment of the gastrulating embryo.},
  author       = {Stock, Jessica and Kazmar, Tomas and Schlumm, Friederike and Hannezo, Edouard B and Pauli, Andrea},
  issn         = {2375-2548},
  journal      = {Science Advances},
  number       = {37},
  publisher    = {American Association for the Advancement of Science},
  title        = {{A self-generated Toddler gradient guides mesodermal cell migration}},
  doi          = {10.1126/sciadv.add2488},
  volume       = {8},
  year         = {2022},
}

@article{12259,
  abstract     = {Theoretical foundations of chaos have been predominantly laid out for finite-dimensional dynamical systems, such as the three-body problem in classical mechanics and the Lorenz model in dissipative systems. In contrast, many real-world chaotic phenomena, e.g., weather, arise in systems with many (formally infinite) degrees of freedom, which limits direct quantitative analysis of such systems using chaos theory. In the present work, we demonstrate that the hydrodynamic pilot-wave systems offer a bridge between low- and high-dimensional chaotic phenomena by allowing for a systematic study of how the former connects to the latter. Specifically, we present experimental results, which show the formation of low-dimensional chaotic attractors upon destabilization of regular dynamics and a final transition to high-dimensional chaos via the merging of distinct chaotic regions through a crisis bifurcation. Moreover, we show that the post-crisis dynamics of the system can be rationalized as consecutive scatterings from the nonattracting chaotic sets with lifetimes following exponential distributions. },
  author       = {Choueiri, George H and Suri, Balachandra and Merrin, Jack and Serbyn, Maksym and Hof, Björn and Budanur, Nazmi B},
  issn         = {1089-7682},
  journal      = {Chaos: An Interdisciplinary Journal of Nonlinear Science},
  keywords     = {Applied Mathematics, General Physics and Astronomy, Mathematical Physics, Statistical and Nonlinear Physics},
  number       = {9},
  publisher    = {AIP Publishing},
  title        = {{Crises and chaotic scattering in hydrodynamic pilot-wave experiments}},
  doi          = {10.1063/5.0102904},
  volume       = {32},
  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},
}

