@article{10290,
  abstract     = {A precise quantitative description of the ultrastructural characteristics underlying biological mechanisms is often key to their understanding. This is particularly true for dynamic extra- and intracellular filamentous assemblies, playing a role in cell motility, cell integrity, cytokinesis, tissue formation and maintenance. For example, genetic manipulation or modulation of actin regulatory proteins frequently manifests in changes of the morphology, dynamics, and ultrastructural architecture of actin filament-rich cell peripheral structures, such as lamellipodia or filopodia. However, the observed ultrastructural effects often remain subtle and require sufficiently large datasets for appropriate quantitative analysis. The acquisition of such large datasets has been enabled by recent advances in high-throughput cryo-electron tomography (cryo-ET) methods. This also necessitates the development of complementary approaches to maximize the extraction of relevant biological information. We have developed a computational toolbox for the semi-automatic quantification of segmented and vectorized filamentous networks from pre-processed cryo-electron tomograms, facilitating the analysis and cross-comparison of multiple experimental conditions. GUI-based components simplify the processing of data and allow users to obtain a large number of ultrastructural parameters describing filamentous assemblies. We demonstrate the feasibility of this workflow by analyzing cryo-ET data of untreated and chemically perturbed branched actin filament networks and that of parallel actin filament arrays. In principle, the computational toolbox presented here is applicable for data analysis comprising any type of filaments in regular (i.e. parallel) or random arrangement. We show that it can ease the identification of key differences between experimental groups and facilitate the in-depth analysis of ultrastructural data in a time-efficient manner.},
  author       = {Dimchev, Georgi A and Amiri, Behnam and Fäßler, Florian and Falcke, Martin and Schur, Florian KM},
  issn         = {1047-8477},
  journal      = {Journal of Structural Biology},
  keywords     = {Structural Biology},
  number       = {4},
  publisher    = {Elsevier },
  title        = {{Computational toolbox for ultrastructural quantitative analysis of filament networks in cryo-ET data}},
  doi          = {10.1016/j.jsb.2021.107808},
  volume       = {213},
  year         = {2021},
}

@phdthesis{10293,
  abstract     = {Indirect reciprocity in evolutionary game theory is a prominent mechanism for explaining the evolution of cooperation among unrelated individuals. In contrast to direct reciprocity, which is based on individuals meeting repeatedly, and conditionally cooperating by using their own experiences, indirect reciprocity is based on individuals’ reputations. If a player helps another, this increases the helper’s public standing, benefitting them in the future. This lets cooperation in the population emerge without individuals having to meet more than once. While the two modes of reciprocity are intertwined, they are difficult to compare. Thus, they are usually studied in isolation. Direct reciprocity can maintain cooperation with simple strategies, and is robust against noise even when players do not remember more
than their partner’s last action. Meanwhile, indirect reciprocity requires its successful strategies, or social norms, to be more complex. Exhaustive search previously identified eight such norms, called the “leading eight”, which excel at maintaining cooperation. However, as the first result of this thesis, we show that the leading eight break down once we remove the fundamental assumption that information is synchronized and public, such that everyone agrees on reputations. Once we consider a more realistic scenario of imperfect information, where reputations are private, and individuals occasionally misinterpret or miss observations, the leading eight do not promote cooperation anymore. Instead, minor initial disagreements can proliferate, fragmenting populations into subgroups. In a next step, we consider ways to mitigate this issue. We first explore whether introducing “generosity” can stabilize cooperation when players use the leading eight strategies in noisy environments. This approach of modifying strategies to include probabilistic elements for coping with errors is known to work well in direct reciprocity. However, as we show here, it fails for the more complex norms of indirect reciprocity. Imperfect information still prevents cooperation from evolving. On the other hand, we succeeded to show in this thesis that modifying the leading eight to use “quantitative assessment”, i.e. tracking reputation scores on a scale beyond good and bad, and making overall judgments of others based on a threshold, is highly successful, even when noise increases in the environment. Cooperation can flourish when reputations
are more nuanced, and players have a broader understanding what it means to be “good.” Finally, we present a single theoretical framework that unites the two modes of reciprocity despite their differences. Within this framework, we identify a novel simple and successful strategy for indirect reciprocity, which can cope with noisy environments and has an analogue in direct reciprocity. We can also analyze decision making when different sources of information are available. Our results help highlight that for sustaining cooperation, already the most simple rules of reciprocity can be sufficient.},
  author       = {Schmid, Laura},
  issn         = {2663-337X},
  pages        = {171},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Evolution of cooperation via (in)direct reciprocity under imperfect information}},
  doi          = {10.15479/at:ista:10293},
  year         = {2021},
}

@article{10299,
  abstract     = {Turbulence generally arises in shear flows if velocities and hence, inertial forces are sufficiently large. In striking contrast, viscoelastic fluids can exhibit disordered motion even at vanishing inertia. Intermediate between these cases, a state of chaotic motion, “elastoinertial turbulence” (EIT), has been observed in a narrow Reynolds number interval. We here determine the origin of EIT in experiments and show that characteristic EIT structures can be detected across an unexpectedly wide range of parameters. Close to onset, a pattern of chevron-shaped streaks emerges in qualitative agreement with linear and weakly nonlinear theory. However, in experiments, the dynamics remain weakly chaotic, and the instability can be traced to far lower Reynolds numbers than permitted by theory. For increasing inertia, the flow undergoes a transformation to a wall mode composed of inclined near-wall streaks and shear layers. This mode persists to what is known as the “maximum drag reduction limit,” and overall EIT is found to dominate viscoelastic flows across more than three orders of magnitude in Reynolds number.},
  author       = {Choueiri, George H and Lopez Alonso, Jose M and Varshney, Atul and Sankar, Sarath and Hof, Björn},
  issn         = {1091-6490},
  journal      = {Proceedings of the National Academy of Sciences},
  keywords     = {multidisciplinary, elastoinertial turbulence, viscoelastic flows, elastic instability, drag reduction},
  number       = {45},
  publisher    = {National Academy of Sciences},
  title        = {{Experimental observation of the origin and structure of elastoinertial turbulence}},
  doi          = {10.1073/pnas.2102350118},
  volume       = {118},
  year         = {2021},
}

@article{10301,
  abstract     = {De novo protein synthesis is required for synapse modifications underlying stable memory encoding. Yet neurons are highly compartmentalized cells and how protein synthesis can be regulated at the synapse level is unknown. Here, we characterize neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR activation and restricts the mTOR-dependent translation of specific activity-regulated mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent protein synthesis, and facilitates the consolidation of associative and spatial memories in mice. The memory enhancement becomes evident with light or spaced training, can be achieved by selectively deleting GluN3A from excitatory neurons during adulthood, and does not compromise other aspects of cognition such as memory flexibility or extinction. Our findings provide mechanistic insight into synaptic translational control and reveal a potentially selective target for cognitive enhancement.},
  author       = {Conde-Dusman, María J and Dey, Partha N and Elía-Zudaire, Óscar and Garcia Rabaneda, Luis E and García-Lira, Carmen and Grand, Teddy and Briz, Victor and Velasco, Eric R and Andero Galí, Raül and Niñerola, Sergio and Barco, Angel and Paoletti, Pierre and Wesseling, John F and Gardoni, Fabrizio and Tavalin, Steven J and Perez-Otaño, Isabel},
  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        = {{Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly}},
  doi          = {10.7554/elife.71575},
  volume       = {10},
  year         = {2021},
}

@phdthesis{10303,
  abstract     = {Nitrogen is an essential macronutrient determining plant growth, development and affecting agricultural productivity. Root, as a hub that perceives and integrates local and systemic signals on the plant’s external and endogenous nitrogen resources, communicates with other plant organs to consolidate their physiology and development in accordance with actual nitrogen balance. Over the last years, numerous studies demonstrated that these comprehensive developmental adaptations rely on the interaction between pathways controlling nitrogen homeostasis and hormonal networks acting globally in the plant body. However, molecular insights into how the information about the nitrogen status is translated through hormonal pathways into specific developmental output are lacking. In my work, I addressed so far poorly understood mechanisms underlying root-to-shoot communication that lead to a rapid re-adjustment of shoot growth and development after nitrate provision. Applying a combination of molecular, cell, and developmental biology approaches, genetics and grafting experiments as well as hormonal analytics, I identified and characterized an unknown molecular framework orchestrating shoot development with a root nitrate sensory system. },
  author       = {Abualia, Rashed},
  issn         = {2663-337X},
  pages        = {139},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Role of hormones in nitrate regulated growth}},
  doi          = {10.15479/at:ista:10303},
  year         = {2021},
}

@phdthesis{10307,
  abstract     = {Bacteria-host interactions represent a continuous trade-off between benefit and risk. Thus, the host immune response is faced with a non-trivial problem – accommodate beneficial commensals and remove harmful pathogens. This is especially difficult as molecular patterns, such as lipopolysaccharide or specific surface organelles such as pili, are conserved in both, commensal and pathogenic bacteria. Type 1 pili, tightly regulated by phase variation, are considered an important virulence factor of pathogenic bacteria as they facilitate invasion into host cells. While invasion represents a de facto passive mechanism for pathogens to escape the host immune response, we demonstrate a fundamental role of type 1 pili as active modulators of the innate and adaptive immune response.},
  author       = {Tomasek, Kathrin},
  issn         = {2663-337X},
  pages        = {73},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Pathogenic Escherichia coli hijack the host immune response}},
  doi          = {10.15479/at:ista:10307},
  year         = {2021},
}

@article{10310,
  abstract     = {A high-resolution structure of trimeric cyanobacterial Photosystem I (PSI) from Thermosynechococcus elongatus was reported as the first atomic model of PSI almost 20 years ago. However, the monomeric PSI structure has not yet been reported despite long-standing interest in its structure and extensive spectroscopic characterization of the loss of red chlorophylls upon monomerization. Here, we describe the structure of monomeric PSI from Thermosynechococcus elongatus BP-1. Comparison with the trimer structure gave detailed insights into monomerization-induced changes in both the central trimerization domain and the peripheral regions of the complex. Monomerization-induced loss of red chlorophylls is assigned to a cluster of chlorophylls adjacent to PsaX. Based on our findings, we propose a role of PsaX in the stabilization of red chlorophylls and that lipids of the surrounding membrane present a major source of thermal energy for uphill excitation energy transfer from red chlorophylls to P700.},
  author       = {Çoruh, Mehmet Orkun and Frank, Anna and Tanaka, Hideaki and Kawamoto, Akihiro and El-Mohsnawy, Eithar and Kato, Takayuki and Namba, Keiichi and Gerle, Christoph and Nowaczyk, Marc M. and Kurisu, Genji},
  issn         = {2399-3642},
  journal      = {Communications Biology},
  keywords     = {general agricultural and biological Sciences, general biochemistry, genetics and molecular biology, medicine (miscellaneous)},
  number       = {1},
  publisher    = {Springer },
  title        = {{Cryo-EM structure of a functional monomeric Photosystem I from Thermosynechococcus elongatus reveals red chlorophyll cluster}},
  doi          = {10.1038/s42003-021-01808-9},
  volume       = {4},
  year         = {2021},
}

@unpublished{10316,
  abstract     = {A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on dendritic cells as a previously undescribed binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of pathogenic bacteria to CD14 lead to reduced dendritic cell migration and blunted expression of co-stimulatory molecules, both rate-limiting factors of T cell activation. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease.},
  author       = {Tomasek, Kathrin and Leithner, Alexander F and Glatzová, Ivana and Lukesch, Michael S. and Guet, Calin C and Sixt, Michael K},
  booktitle    = {bioRxiv},
  publisher    = {Cold Spring Harbor Laboratory},
  title        = {{Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14}},
  doi          = {10.1101/2021.10.18.464770},
  year         = {2021},
}

@article{10321,
  abstract     = {Mosaic analysis with double markers (MADM) technology enables the generation of genetic mosaic tissue in mice. MADM enables concomitant fluorescent cell labeling and introduction of a mutation of a gene of interest with single-cell resolution. This protocol highlights major steps for the generation of genetic mosaic tissue and the isolation and processing of respective tissues for downstream histological analysis. For complete details on the use and execution of this protocol, please refer to Contreras et al. (2021).},
  author       = {Amberg, Nicole and Hippenmeyer, Simon},
  issn         = {2666-1667},
  journal      = {STAR Protocols},
  number       = {4},
  publisher    = {Cell Press},
  title        = {{Genetic mosaic dissection of candidate genes in mice using mosaic analysis with double markers}},
  doi          = {10.1016/j.xpro.2021.100939},
  volume       = {2},
  year         = {2021},
}

@article{10322,
  abstract     = {To survive elevated temperatures, ectotherms adjust the fluidity of membranes by fine-tuning lipid desaturation levels in a process previously described to be cell autonomous. We have discovered that, in Caenorhabditis elegans, neuronal heat shock factor 1 (HSF-1), the conserved master regulator of the heat shock response (HSR), causes extensive fat remodeling in peripheral tissues. These changes include a decrease in fat desaturase and acid lipase expression in the intestine and a global shift in the saturation levels of plasma membrane’s phospholipids. The observed remodeling of plasma membrane is in line with ectothermic adaptive responses and gives worms a cumulative advantage to warm temperatures. We have determined that at least 6 TAX-2/TAX-4 cyclic guanosine monophosphate (cGMP) gated channel expressing sensory neurons, and transforming growth factor ß (TGF-β)/bone morphogenetic protein (BMP) are required for signaling across tissues to modulate fat desaturation. We also find neuronal hsf-1 is not only sufficient but also partially necessary to control the fat remodeling response and for survival at warm temperatures. This is the first study to show that a thermostat-based mechanism can cell nonautonomously coordinate membrane saturation and composition across tissues in a multicellular animal.},
  author       = {Chauve, Laetitia and Hodge, Francesca and Murdoch, Sharlene and Masoudzadeh, Fatemah and Mann, Harry Jack and Lopez-Clavijo, Andrea and Okkenhaug, Hanneke and West, Greg and Sousa, Bebiana C. and Segonds-Pichon, Anne and Li, Cheryl and Wingett, Steven and Kienberger, Hermine and Kleigrewe, Karin and De Bono, Mario and Wakelam, Michael and Casanueva, Olivia},
  issn         = {1545-7885},
  journal      = {PLoS Biology},
  number       = {11},
  publisher    = {Public Library of Science},
  title        = {{Neuronal HSF-1 coordinates the propagation of fat desaturation across tissues to enable adaptation to high temperatures in C. elegans}},
  doi          = {10.1371/journal.pbio.3001431},
  volume       = {19},
  year         = {2021},
}

@article{10323,
  abstract     = {Molecular chaperones are central to cellular protein homeostasis. Dynamic disorder is a key feature of the complexes of molecular chaperones and their client proteins, and it facilitates the client release towards a folded state or the handover to downstream components. The dynamic nature also implies that a given chaperone can interact with many different client proteins, based on physico-chemical sequence properties rather than on structural complementarity of their (folded) 3D structure. Yet, the balance between this promiscuity and some degree of client specificity is poorly understood. Here, we review recent atomic-level descriptions of chaperones with client proteins, including chaperones in complex with intrinsically disordered proteins, with membrane-protein precursors, or partially folded client proteins. We focus hereby on chaperone-client interactions that are independent of ATP. The picture emerging from these studies highlights the importance of dynamics in these complexes, whereby several interaction types, not only hydrophobic ones, contribute to the complex formation. We discuss these features of chaperone-client complexes and possible factors that may contribute to this balance of promiscuity and specificity.},
  author       = {Sučec, Iva and Bersch, Beate and Schanda, Paul},
  issn         = {2296-889X},
  journal      = {Frontiers in Molecular Biosciences},
  publisher    = {Frontiers},
  title        = {{How do chaperones bind (partly) unfolded client proteins?}},
  doi          = {10.3389/fmolb.2021.762005},
  volume       = {8},
  year         = {2021},
}

@inproceedings{10324,
  abstract     = {Off-chain protocols (channels) are a promising solution to the scalability and privacy challenges of blockchain payments. Current proposals, however, require synchrony assumptions to preserve the safety of a channel, leaking to an adversary the exact amount of time needed to control the network for a successful attack. In this paper, we introduce Brick, the first payment channel that remains secure under network asynchrony and concurrently provides correct incentives. The core idea is to incorporate the conflict resolution process within the channel by introducing a rational committee of external parties, called wardens. Hence, if a party wants to close a channel unilaterally, it can only get the committee’s approval for the last valid state. Additionally, Brick provides sub-second latency because it does not employ heavy-weight consensus. Instead, Brick uses consistent broadcast to announce updates and close the channel, a light-weight abstraction that is powerful enough to preserve safety and liveness to any rational parties. We formally define and prove for Brick the properties a payment channel construction should fulfill. We also design incentives for Brick such that honest and rational behavior aligns. Finally, we provide a reference implementation of the smart contracts in Solidity.},
  author       = {Avarikioti, Zeta and Kokoris Kogias, Eleftherios and Wattenhofer, Roger and Zindros, Dionysis},
  booktitle    = {25th International Conference on Financial Cryptography and Data Security},
  isbn         = {9-783-6626-4330-3},
  issn         = {1611-3349},
  location     = {Virtual},
  pages        = {209--230},
  publisher    = {Springer Nature},
  title        = {{Brick: Asynchronous incentive-compatible payment channels}},
  doi          = {10.1007/978-3-662-64331-0_11},
  volume       = {12675 },
  year         = {2021},
}

@inproceedings{10325,
  abstract     = {Since the inception of Bitcoin, a plethora of distributed ledgers differing in design and purpose has been created. While by design, blockchains provide no means to securely communicate with external systems, numerous attempts towards trustless cross-chain communication have been proposed over the years. Today, cross-chain communication (CCC) plays a fundamental role in cryptocurrency exchanges, scalability efforts via sharding, extension of existing systems through sidechains, and bootstrapping of new blockchains. Unfortunately, existing proposals are designed ad-hoc for specific use-cases, making it hard to gain confidence in their correctness and composability. We provide the first systematic exposition of cross-chain communication protocols. We formalize the underlying research problem and show that CCC is impossible without a trusted third party, contrary to common beliefs in the blockchain community. With this result in mind, we develop a framework to design new and evaluate existing CCC protocols, focusing on the inherent trust assumptions thereof, and derive a classification covering the field of cross-chain communication to date. We conclude by discussing open challenges for CCC research and the implications of interoperability on the security and privacy of blockchains.},
  author       = {Zamyatin, Alexei and Al-Bassam, Mustafa and Zindros, Dionysis and Kokoris Kogias, Eleftherios and Moreno-Sanchez, Pedro and Kiayias, Aggelos and Knottenbelt, William J.},
  booktitle    = {25th International Conference on Financial Cryptography and Data Security},
  isbn         = {9-783-6626-4330-3},
  issn         = {1611-3349},
  location     = {Virtual},
  pages        = {3--36},
  publisher    = {Springer Nature},
  title        = {{SoK: Communication across distributed ledgers}},
  doi          = {10.1007/978-3-662-64331-0_1},
  volume       = {12675 },
  year         = {2021},
}

@article{10326,
  abstract     = {Strigolactones (SLs) are carotenoid-derived plant hormones that control shoot branching and communications between host plants and symbiotic fungi or root parasitic plants. Extensive studies have identified the key components participating in SL biosynthesis and signalling, whereas the catabolism or deactivation of endogenous SLs in planta remains largely unknown. Here, we report that the Arabidopsis carboxylesterase 15 (AtCXE15) and its orthologues function as efficient hydrolases of SLs. We show that overexpression of AtCXE15 promotes shoot branching by dampening SL-inhibited axillary bud outgrowth. We further demonstrate that AtCXE15 could bind and efficiently hydrolyse SLs both in vitro and in planta. We also provide evidence that AtCXE15 is capable of catalysing hydrolysis of diverse SL analogues and that such CXE15-dependent catabolism of SLs is evolutionarily conserved in seed plants. These results disclose a catalytic mechanism underlying homoeostatic regulation of SLs in plants, which also provides a rational approach to spatial-temporally manipulate the endogenous SLs and thus architecture of crops and ornamental plants.},
  author       = {Xu, Enjun and Chai, Liang and Zhang, Shiqi and Yu, Ruixue and Zhang, Xixi and Xu, Chongyi and Hu, Yuxin},
  issn         = {2055-0278},
  journal      = {Nature Plants},
  pages        = {1495–1504 },
  publisher    = {Springer Nature},
  title        = {{Catabolism of strigolactones by a carboxylesterase}},
  doi          = {10.1038/s41477-021-01011-y},
  volume       = {7},
  year         = {2021},
}

@article{10327,
  abstract     = {Composite materials offer numerous advantages in a wide range of applications, including thermoelectrics. Here, semiconductor–metal composites are produced by just blending nanoparticles of a sulfide semiconductor obtained in aqueous solution and at room temperature with a metallic Cu powder. The obtained blend is annealed in a reducing atmosphere and afterward consolidated into dense polycrystalline pellets through spark plasma sintering (SPS). We observe that, during the annealing process, the presence of metallic copper activates a partial reduction of the PbS, resulting in the formation of PbS–Pb–CuxS composites. The presence of metallic lead during the SPS process habilitates the liquid-phase sintering of the composite. Besides, by comparing the transport properties of PbS, the PbS–Pb–CuxS composites, and PbS–CuxS composites obtained by blending PbS and CuxS nanoparticles, we demonstrate that the presence of metallic lead decisively contributes to a strong increase of the charge carrier concentration through spillover of charge carriers enabled by the low work function of lead. The increase in charge carrier concentration translates into much higher electrical conductivities and moderately lower Seebeck coefficients. These properties translate into power factors up to 2.1 mW m–1 K–2 at ambient temperature, well above those of PbS and PbS + CuxS. Additionally, the presence of multiple phases in the final composite results in a notable decrease in the lattice thermal conductivity. Overall, the introduction of metallic copper in the initial blend results in a significant improvement of the thermoelectric performance of PbS, reaching a dimensionless thermoelectric figure of merit ZT = 1.1 at 750 K, which represents about a 400% increase over bare PbS. Besides, an average ZTave = 0.72 in the temperature range 320–773 K is demonstrated.},
  author       = {Li, Mengyao and Liu, Yu and Zhang, Yu and Han, Xu and Xiao, Ke and Nabahat, Mehran and Arbiol, Jordi and Llorca, Jordi and Ibáñez, Maria and Cabot, Andreu},
  issn         = {1944-8252},
  journal      = {ACS Applied Materials and Interfaces},
  keywords     = {CuxS, PbS, energy conversion, nanocomposite, nanoparticle, solution synthesis, thermoelectric},
  number       = {43},
  pages        = {51373–51382},
  publisher    = {American Chemical Society },
  title        = {{PbS–Pb–CuxS composites for thermoelectric application}},
  doi          = {10.1021/acsami.1c15609},
  volume       = {13},
  year         = {2021},
}

@article{10337,
  abstract     = {The T cell receptor (TCR) pathway receives, processes, and amplifies the signal from pathogenic antigens to the activation of T cells. Although major components in this pathway have been identified, the knowledge on how individual components cooperate to effectively transduce signals remains limited. Phase separation emerges as a biophysical principle in organizing signaling molecules into liquid-like condensates. Here, we report that phospholipase Cγ1 (PLCγ1) promotes phase separation of LAT, a key adaptor protein in the TCR pathway. PLCγ1 directly cross-links LAT through its two SH2 domains. PLCγ1 also protects LAT from dephosphorylation by the phosphatase CD45 and promotes LAT-dependent ERK activation and SLP76 phosphorylation. Intriguingly, a nonmonotonic effect of PLCγ1 on LAT clustering was discovered. Computer simulations, based on patchy particles, revealed how the cluster size is regulated by protein compositions. Together, these results define a critical function of PLCγ1 in promoting phase separation of the LAT complex and TCR signal transduction.},
  author       = {Zeng, Longhui and Palaia, Ivan and Šarić, Anđela and Su, Xiaolei},
  issn         = {1540-8140},
  journal      = {Journal of Cell Biology},
  keywords     = {cell biology},
  number       = {6},
  publisher    = {Rockefeller University Press},
  title        = {{PLCγ1 promotes phase separation of T cell signaling components}},
  doi          = {10.1083/jcb.202009154},
  volume       = {220},
  year         = {2021},
}

@article{10338,
  abstract     = {In the nuclear pore complex, intrinsically disordered proteins (FG Nups), along with their interactions with more globular proteins called nuclear transport receptors (NTRs), are vital to the selectivity of transport into and out of the cell nucleus. Although such interactions can be modeled at different levels of coarse graining, in vitro experimental data have been quantitatively described by minimal models that describe FG Nups as cohesive homogeneous polymers and NTRs as uniformly cohesive spheres, in which the heterogeneous effects have been smeared out. By definition, these minimal models do not account for the explicit heterogeneities in FG Nup sequences, essentially a string of cohesive and noncohesive polymer units, and at the NTR surface. Here, we develop computational and analytical models that do take into account such heterogeneity in a minimal fashion and compare them with experimental data on single-molecule interactions between FG Nups and NTRs. Overall, we find that the heterogeneous nature of FG Nups and NTRs does play a role in determining equilibrium binding properties but is of much greater significance when it comes to unbinding and binding kinetics. Using our models, we predict how binding equilibria and kinetics depend on the distribution of cohesive blocks in the FG Nup sequences and of the binding pockets at the NTR surface, with multivalency playing a key role. Finally, we observe that single-molecule binding kinetics has a rather minor influence on the diffusion of NTRs in polymer melts consisting of FG-Nup-like sequences.},
  author       = {Davis, Luke K. and Šarić, Anđela and Hoogenboom, Bart W. and Zilman, Anton},
  issn         = {0006-3495},
  journal      = {Biophysical Journal},
  keywords     = {biophysics},
  number       = {9},
  pages        = {1565--1577},
  publisher    = {Elsevier},
  title        = {{Physical modeling of multivalent interactions in the nuclear pore complex}},
  doi          = {10.1016/j.bpj.2021.01.039},
  volume       = {120},
  year         = {2021},
}

@article{10339,
  abstract     = {We study the effects of osmotic shocks on lipid vesicles via coarse-grained molecular dynamics simulations by explicitly considering the solute in the system. We find that depending on their nature (hypo- or hypertonic) such shocks can lead to bursting events or engulfing of external material into inner compartments, among other morphology transformations. We characterize the dynamics of these processes and observe a separation of time scales between the osmotic shock absorption and the shape relaxation. Our work consequently provides an insight into the dynamics of compartmentalization in vesicular systems as a result of osmotic shocks, which can be of interest in the context of early proto-cell development and proto-cell compartmentalisation.},
  author       = {Vanhille-Campos, Christian and Šarić, Anđela},
  issn         = {1744-6848},
  journal      = {Soft Matter},
  keywords     = {condensed matter physics, general chemistry},
  number       = {14},
  pages        = {3798--3806},
  publisher    = {Royal Society of Chemistry},
  title        = {{Modelling the dynamics of vesicle reshaping and scission under osmotic shocks}},
  doi          = {10.1039/d0sm02012e},
  volume       = {17},
  year         = {2021},
}

@article{10340,
  abstract     = {The cell membrane is an inhomogeneous system composed of phospholipids, sterols, carbohydrates, and proteins that can be directly attached to underlying cytoskeleton. The protein linkers between the membrane and the cytoskeleton are believed to have a profound effect on the mechanical properties of the cell membrane and its ability to reshape. Here, we investigate the role of membrane-cortex linkers on the extrusion of membrane tubes using computer simulations and experiments. In simulations, we find that the force for tube extrusion has a nonlinear dependence on the density of membrane-cortex attachments: at a range of low and intermediate linker densities, the force is not significantly influenced by the presence of the membrane-cortex attachments and resembles that of the bare membrane. For large concentrations of linkers, however, the force substantially increases compared with the bare membrane. In both cases, the linkers provided membrane tubes with increased stability against coalescence. We then pulled tubes from HEK cells using optical tweezers for varying expression levels of the membrane-cortex attachment protein Ezrin. In line with simulations, we observed that overexpression of Ezrin led to an increased extrusion force, while Ezrin depletion had a negligible effect on the force. Our results shed light on the importance of local protein rearrangements for membrane reshaping at nanoscopic scales.},
  author       = {Paraschiv, Alexandru and Lagny, Thibaut J. and Campos, Christian Vanhille and Coudrier, Evelyne and Bassereau, Patricia and Šarić, Anđela},
  issn         = {0006-3495},
  journal      = {Biophysical Journal},
  keywords     = {biophysics},
  number       = {4},
  pages        = {598--606},
  publisher    = {Cell Press},
  title        = {{Influence of membrane-cortex linkers on the extrusion of membrane tubes}},
  doi          = {10.1016/j.bpj.2020.12.028},
  volume       = {120},
  year         = {2021},
}

@article{10363,
  abstract     = {Erythropoietin enhances oxygen delivery and reduces hypoxia-induced cell death, but its pro-thrombotic activity is problematic for use of erythropoietin in treating hypoxia. We constructed a fusion protein that stimulates red blood cell production and neuroprotection without triggering platelet production, a marker for thrombosis. The protein consists of an anti-glycophorin A nanobody and an erythropoietin mutant (L108A). The mutation reduces activation of erythropoietin receptor homodimers that induce erythropoiesis and thrombosis, but maintains the tissue-protective signaling. The binding of the nanobody element to glycophorin A rescues homodimeric erythropoietin receptor activation on red blood cell precursors. In a cell proliferation assay, the fusion protein is active at 10−14 M, allowing an estimate of the number of receptor–ligand complexes needed for signaling. This fusion protein stimulates erythroid cell proliferation in vitro and in mice, and shows neuroprotective activity in vitro. Our erythropoietin fusion protein presents a novel molecule for treating hypoxia.},
  author       = {Lee, Jungmin and Vernet, Andyna and Gruber, Nathalie and Kready, Kasia M. and Burrill, Devin R. and Way, Jeffrey C. and Silver, Pamela A.},
  issn         = {1741-0134},
  journal      = {Protein Engineering, Design and Selection},
  publisher    = {Oxford University Press},
  title        = {{Rational engineering of an erythropoietin fusion protein to treat hypoxia}},
  doi          = {10.1093/protein/gzab025},
  volume       = {34},
  year         = {2021},
}