TY - JOUR AB - Zygotic genome activation (ZGA) initiates regionalized transcription underlying distinct cellular identities. ZGA is dependent upon dynamic chromatin architecture sculpted by conserved DNA-binding proteins. However, the direct mechanistic link between the onset of ZGA and the tissue-specific transcription remains unclear. Here, we have addressed the involvement of chromatin organizer Satb2 in orchestrating both processes during zebrafish embryogenesis. Integrative analysis of transcriptome, genome-wide occupancy and chromatin accessibility reveals contrasting molecular activities of maternally deposited and zygotically synthesized Satb2. Maternal Satb2 prevents premature transcription of zygotic genes by influencing the interplay between the pluripotency factors. By contrast, zygotic Satb2 activates transcription of the same group of genes during neural crest development and organogenesis. Thus, our comparative analysis of maternal versus zygotic function of Satb2 underscores how these antithetical activities are temporally coordinated and functionally implemented highlighting the evolutionary implications of the biphasic and bimodal regulation of landmark developmental transitions by a single determinant. AU - Pradhan, Saurabh J. AU - Reddy, Puli Chandramouli AU - Smutny, Michael AU - Sharma, Ankita AU - Sako, Keisuke AU - Oak, Meghana S. AU - Shah, Rini AU - Pal, Mrinmoy AU - Deshpande, Ojas AU - Dsilva, Greg AU - Tang, Yin AU - Mishra, Rakesh AU - Deshpande, Girish AU - Giraldez, Antonio J. AU - Sonawane, Mahendra AU - Heisenberg, Carl-Philipp J AU - Galande, Sanjeev ID - 10202 IS - 1 JF - Nature Communications TI - Satb2 acts as a gatekeeper for major developmental transitions during early vertebrate embryogenesis VL - 12 ER - TY - JOUR AB - Understanding interactions between antibiotics used in combination is an important theme in microbiology. Using the interactions between the antifolate drug trimethoprim and the ribosome-targeting antibiotic erythromycin in Escherichia coli as a model, we applied a transcriptomic approach for dissecting interactions between two antibiotics with different modes of action. When trimethoprim and erythromycin were combined, the transcriptional response of genes from the sulfate reduction pathway deviated from the dominant effect of trimethoprim on the transcriptome. We successfully altered the drug interaction from additivity to suppression by increasing the sulfate level in the growth environment and identified sulfate reduction as an important metabolic determinant that shapes the interaction between the two drugs. Our work highlights the potential of using prioritization of gene expression patterns as a tool for identifying key metabolic determinants that shape drug-drug interactions. We further demonstrated that the sigma factor-binding protein gene crl shapes the interactions between the two antibiotics, which provides a rare example of how naturally occurring variations between strains of the same bacterial species can sometimes generate very different drug interactions. AU - Qi, Qin AU - Angermayr, S. Andreas AU - Bollenbach, Mark Tobias ID - 10271 JF - Frontiers in Microbiology KW - microbiology TI - Uncovering Key Metabolic Determinants of the Drug Interactions Between Trimethoprim and Erythromycin in Escherichia coli VL - 12 ER - TY - JOUR AB - We prove that any deterministic matrix is approximately the identity in the eigenbasis of a large random Wigner matrix with very high probability and with an optimal error inversely proportional to the square root of the dimension. Our theorem thus rigorously verifies the Eigenstate Thermalisation Hypothesis by Deutsch (Phys Rev A 43:2046–2049, 1991) for the simplest chaotic quantum system, the Wigner ensemble. In mathematical terms, we prove the strong form of Quantum Unique Ergodicity (QUE) with an optimal convergence rate for all eigenvectors simultaneously, generalizing previous probabilistic QUE results in Bourgade and Yau (Commun Math Phys 350:231–278, 2017) and Bourgade et al. (Commun Pure Appl Math 73:1526–1596, 2020). AU - Cipolloni, Giorgio AU - Erdös, László AU - Schröder, Dominik J ID - 10221 IS - 2 JF - Communications in Mathematical Physics SN - 0010-3616 TI - Eigenstate thermalization hypothesis for Wigner matrices VL - 388 ER - TY - JOUR AB - We investigate the Fröhlich polaron model on a three-dimensional torus, and give a proof of the second-order quantum corrections to its ground-state energy in the strong-coupling limit. Compared to previous work in the confined case, the translational symmetry (and its breaking in the Pekar approximation) makes the analysis substantially more challenging. AU - Feliciangeli, Dario AU - Seiringer, Robert ID - 10224 IS - 3 JF - Archive for Rational Mechanics and Analysis SN - 0003-9527 TI - The strongly coupled polaron on the torus: Quantum corrections to the Pekar asymptotics VL - 242 ER - TY - JOUR AB - Mutations affecting mTOR or RAS signaling underlie defined syndromes (the so-called mTORopathies and RASopathies) with high risk for Autism Spectrum Disorder (ASD). These syndromes show a broad variety of somatic phenotypes including cancers, skin abnormalities, heart disease and facial dysmorphisms. Less well studied are the neuropsychiatric symptoms such as ASD. Here, we assess the relevance of these signalopathies in ASD reviewing genetic, human cell model, rodent studies and clinical trials. We conclude that signalopathies have an increased liability for ASD and that, in particular, ASD individuals with dysmorphic features and intellectual disability (ID) have a higher chance for disruptive mutations in RAS- and mTOR-related genes. Studies on rodent and human cell models confirm aberrant neuronal development as the underlying pathology. Human studies further suggest that multiple hits are necessary to induce the respective phenotypes. Recent clinical trials do only report improvements for comorbid conditions such as epilepsy or cancer but not for behavioral aspects. Animal models show that treatment during early development can rescue behavioral phenotypes. Taken together, we suggest investigating the differential roles of mTOR and RAS signaling in both human and rodent models, and to test drug treatment both during and after neuronal development in the available model systems AU - Vasic, Verica AU - Jones, Mattson S.O. AU - Haslinger, Denise AU - Knaus, Lisa AU - Schmeisser, Michael J. AU - Novarino, Gaia AU - Chiocchetti, Andreas G. ID - 10281 IS - 11 JF - Genes TI - Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment VL - 12 ER - TY - JOUR AB - Advanced transcriptome sequencing has revealed that the majority of eukaryotic genes undergo alternative splicing (AS). Nonetheless, little effort has been dedicated to investigating the functional relevance of particular splicing events, even those in the key developmental and hormonal regulators. Combining approaches of genetics, biochemistry and advanced confocal microscopy, we describe the impact of alternative splicing on the PIN7 gene in the model plant Arabidopsis thaliana. PIN7 encodes a polarly localized transporter for the phytohormone auxin and produces two evolutionarily conserved transcripts, PIN7a and PIN7b. PIN7a and PIN7b, differing in a four amino acid stretch, exhibit almost identical expression patterns and subcellular localization. We reveal that they are closely associated and mutually influence each other's mobility within the plasma membrane. Phenotypic complementation tests indicate that the functional contribution of PIN7b per se is minor, but it markedly reduces the prominent PIN7a activity, which is required for correct seedling apical hook formation and auxin-mediated tropic responses. Our results establish alternative splicing of the PIN family as a conserved, functionally relevant mechanism, revealing an additional regulatory level of auxin-mediated plant development. AU - Kashkan, Ivan AU - Hrtyan, Mónika AU - Retzer, Katarzyna AU - Humpolíčková, Jana AU - Jayasree, Aswathy AU - Filepová, Roberta AU - Vondráková, Zuzana AU - Simon, Sibu AU - Rombaut, Debbie AU - Jacobs, Thomas B. AU - Frilander, Mikko J. AU - Hejátko, Jan AU - Friml, Jiří AU - Petrášek, Jan AU - Růžička, Kamil ID - 10282 JF - New Phytologist SN - 0028-646X TI - Mutually opposing activity of PIN7 splicing isoforms is required for auxin-mediated tropic responses in Arabidopsis thaliana VL - 233 ER - TY - JOUR AB - We study conditions under which a finite simplicial complex K can be mapped to ℝd without higher-multiplicity intersections. An almost r-embedding is a map f: K → ℝd such that the images of any r pairwise disjoint simplices of K do not have a common point. We show that if r is not a prime power and d ≥ 2r + 1, then there is a counterexample to the topological Tverberg conjecture, i.e., there is an almost r-embedding of the (d +1)(r − 1)-simplex in ℝd. This improves on previous constructions of counterexamples (for d ≥ 3r) based on a series of papers by M. Özaydin, M. Gromov, P. Blagojević, F. Frick, G. Ziegler, and the second and fourth present authors. The counterexamples are obtained by proving the following algebraic criterion in codimension 2: If r ≥ 3 and if K is a finite 2(r − 1)-complex, then there exists an almost r-embedding K → ℝ2r if and only if there exists a general position PL map f: K → ℝ2r such that the algebraic intersection number of the f-images of any r pairwise disjoint simplices of K is zero. This result can be restated in terms of a cohomological obstruction and extends an analogous codimension 3 criterion by the second and fourth authors. As another application, we classify ornaments f: S3 ⊔ S3 ⊔ S3 → ℝ5 up to ornament concordance. It follows from work of M. Freedman, V. Krushkal and P. Teichner that the analogous criterion for r = 2 is false. We prove a lemma on singular higher-dimensional Borromean rings, yielding an elementary proof of the counterexample. AU - Avvakumov, Sergey AU - Mabillard, Isaac AU - Skopenkov, Arkadiy B. AU - Wagner, Uli ID - 10220 JF - Israel Journal of Mathematics SN - 0021-2172 TI - Eliminating higher-multiplicity intersections. III. Codimension 2 VL - 245 ER - TY - GEN AB - Infections early in life can have enduring effects on an organism’s development and immunity. In this study, we show that this equally applies to developing “superorganisms” – incipient social insect colonies. When we exposed newly mated Lasius niger ant queens to a low pathogen dose, their colonies grew more slowly than controls before winter, but reached similar sizes afterwards. Independent of exposure, queen hibernation survival improved when the ratio of pupae to workers was small. Queens that reared fewer pupae before worker emergence exhibited lower pathogen levels, indicating that high brood rearing efforts interfere with the ability of the queen’s immune system to suppress pathogen proliferation. Early-life queen pathogen-exposure also improved the immunocompetence of her worker offspring, as demonstrated by challenging the workers to the same pathogen a year later. Transgenerational transfer of the queen’s pathogen experience to her workforce can hence durably reduce the disease susceptibility of the whole superorganism. AU - Casillas Perez, Barbara E AU - Pull, Christopher AU - Naiser, Filip AU - Naderlinger, Elisabeth AU - Matas, Jiri AU - Cremer, Sylvia ID - 13061 TI - Early queen infection shapes developmental dynamics and induces long-term disease protection in incipient ant colonies ER - TY - JOUR AB - 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. AU - Conde-Dusman, María J AU - Dey, Partha N AU - Elía-Zudaire, Óscar AU - Garcia Rabaneda, Luis E AU - García-Lira, Carmen AU - Grand, Teddy AU - Briz, Victor AU - Velasco, Eric R AU - Andero Galí, Raül AU - Niñerola, Sergio AU - Barco, Angel AU - Paoletti, Pierre AU - Wesseling, John F AU - Gardoni, Fabrizio AU - Tavalin, Steven J AU - Perez-Otaño, Isabel ID - 10301 JF - eLife KW - general immunology and microbiology KW - general biochemistry KW - genetics and molecular biology KW - general medicine KW - general neuroscience SN - 2050-084X TI - Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly VL - 10 ER - TY - JOUR AB - During the past decade, the scientific community and outside observers have noted a concerning lack of rigor and transparency in preclinical research that led to talk of a “reproducibility crisis” in the life sciences (Baker, 2016; Bespalov & Steckler, 2018; Heddleston et al, 2021). Various measures have been proposed to address the problem: from better training of scientists to more oversight to expanded publishing practices such as preregistration of studies. The recently published EQIPD (Enhancing Quality in Preclinical Data) System is, to date, the largest initiative that aims to establish a systematic approach for increasing the robustness and reliability of biomedical research (Bespalov et al, 2021). However, promoting a cultural change in research practices warrants a broad adoption of the Quality System and its underlying philosophy. It is here that academic Core Facilities (CF), research service providers at universities and research institutions, can make a difference. It is fair to assume that a significant fraction of published data originated from experiments that were designed, run, or analyzed in CFs. These academic services play an important role in the research ecosystem by offering access to cutting-edge equipment and by developing and testing novel techniques and methods that impact research in the academic and private sectors alike (Bikovski et al, 2020). Equipment and infrastructure are not the only value: CFs employ competent personnel with profound knowledge and practical experience of the specific field of interest: animal behavior, imaging, crystallography, genomics, and so on. Thus, CFs are optimally positioned to address concerns about the quality and robustness of preclinical research. AU - Restivo, Leonardo AU - Gerlach, Björn AU - Tsoory, Michael AU - Bikovski, Lior AU - Badurek, Sylvia AU - Pitzer, Claudia AU - Kos-Braun, Isabelle C. AU - Mausset-Bonnefont, Anne Laure Mj AU - Ward, Jonathan AU - Schunn, Michael AU - Noldus, Lucas P.J.J. AU - Bespalov, Anton AU - Voikar, Vootele ID - 10283 JF - EMBO Reports SN - 1469-221X TI - Towards best practices in research: Role of academic core facilities VL - 22 ER - TY - JOUR AB - 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. AU - Çoruh, Mehmet Orkun AU - Frank, Anna AU - Tanaka, Hideaki AU - Kawamoto, Akihiro AU - El-Mohsnawy, Eithar AU - Kato, Takayuki AU - Namba, Keiichi AU - Gerle, Christoph AU - Nowaczyk, Marc M. AU - Kurisu, Genji ID - 10310 IS - 1 JF - Communications Biology KW - general agricultural and biological Sciences KW - general biochemistry KW - genetics and molecular biology KW - medicine (miscellaneous) SN - 2399-3642 TI - Cryo-EM structure of a functional monomeric Photosystem I from Thermosynechococcus elongatus reveals red chlorophyll cluster VL - 4 ER - TY - JOUR AB - Plants develop new organs to adjust their bodies to dynamic changes in the environment. How independent organs achieve anisotropic shapes and polarities is poorly understood. To address this question, we constructed a mechano-biochemical model for Arabidopsis root meristem growth that integrates biologically plausible principles. Computer model simulations demonstrate how differential growth of neighboring tissues results in the initial symmetry-breaking leading to anisotropic root growth. Furthermore, the root growth feeds back on a polar transport network of the growth regulator auxin. Model, predictions are in close agreement with in vivo patterns of anisotropic growth, auxin distribution, and cell polarity, as well as several root phenotypes caused by chemical, mechanical, or genetic perturbations. Our study demonstrates that the combination of tissue mechanics and polar auxin transport organizes anisotropic root growth and cell polarities during organ outgrowth. Therefore, a mobile auxin signal transported through immobile cells drives polarity and growth mechanics to coordinate complex organ development. AU - Marconi, Marco AU - Gallemi, Marçal AU - Benková, Eva AU - Wabnik, Krzysztof ID - 10270 JF - eLife SN - 2050-084X TI - A coupled mechano-biochemical model for cell polarity guided anisotropic root growth VL - 10 ER - TY - JOUR AB - 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. AU - Choueiri, George H AU - Lopez Alonso, Jose M AU - Varshney, Atul AU - Sankar, Sarath AU - Hof, Björn ID - 10299 IS - 45 JF - Proceedings of the National Academy of Sciences KW - multidisciplinary KW - elastoinertial turbulence KW - viscoelastic flows KW - elastic instability KW - drag reduction SN - 0027-8424 TI - Experimental observation of the origin and structure of elastoinertial turbulence VL - 118 ER - TY - JOUR AB - Machines enabled the Industrial Revolution and are central to modern technological progress: A machine’s parts transmit forces, motion, and energy to one another in a predetermined manner. Today’s engineering frontier, building artificial micromachines that emulate the biological machinery of living organisms, requires faithful assembly and energy consumption at the microscale. Here, we demonstrate the programmable assembly of active particles into autonomous metamachines using optical templates. Metamachines, or machines made of machines, are stable, mobile and autonomous architectures, whose dynamics stems from the geometry. We use the interplay between anisotropic force generation of the active colloids with the control of their orientation by local geometry. This allows autonomous reprogramming of active particles of the metamachines to achieve multiple functions. It permits the modular assembly of metamachines by fusion, reconfiguration of metamachines and, we anticipate, a shift in focus of self-assembly towards active matter and reprogrammable materials. AU - Aubret, Antoine AU - Martinet, Quentin AU - Palacci, Jérémie A ID - 10280 IS - 1 JF - Nature Communications TI - Metamachines of pluripotent colloids VL - 12 ER - TY - JOUR AB - 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. AU - Chauve, Laetitia AU - Hodge, Francesca AU - Murdoch, Sharlene AU - Masoudzadeh, Fatemah AU - Mann, Harry Jack AU - Lopez-Clavijo, Andrea AU - Okkenhaug, Hanneke AU - West, Greg AU - Sousa, Bebiana C. AU - Segonds-Pichon, Anne AU - Li, Cheryl AU - Wingett, Steven AU - Kienberger, Hermine AU - Kleigrewe, Karin AU - De Bono, Mario AU - Wakelam, Michael AU - Casanueva, Olivia ID - 10322 IS - 11 JF - PLoS Biology SN - 1544-9173 TI - Neuronal HSF-1 coordinates the propagation of fat desaturation across tissues to enable adaptation to high temperatures in C. elegans VL - 19 ER - TY - JOUR AB - Consider a random set of points on the unit sphere in ℝd, which can be either uniformly sampled or a Poisson point process. Its convex hull is a random inscribed polytope, whose boundary approximates the sphere. We focus on the case d = 3, for which there are elementary proofs and fascinating formulas for metric properties. In particular, we study the fraction of acute facets, the expected intrinsic volumes, the total edge length, and the distance to a fixed point. Finally we generalize the results to the ellipsoid with homeoid density. AU - Akopyan, Arseniy AU - Edelsbrunner, Herbert AU - Nikitenko, Anton ID - 10222 JF - Experimental Mathematics SN - 1058-6458 TI - The beauty of random polytopes inscribed in the 2-sphere ER - TY - JOUR AB - 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. AU - Sučec, Iva AU - Bersch, Beate AU - Schanda, Paul ID - 10323 JF - Frontiers in Molecular Biosciences TI - How do chaperones bind (partly) unfolded client proteins? VL - 8 ER - TY - JOUR AB - 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. AU - Xu, Enjun AU - Chai, Liang AU - Zhang, Shiqi AU - Yu, Ruixue AU - Zhang, Xixi AU - Xu, Chongyi AU - Hu, Yuxin ID - 10326 JF - Nature Plants TI - Catabolism of strigolactones by a carboxylesterase VL - 7 ER - TY - GEN AB - 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 remodelling 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 remodelling 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 six TAX-2/TAX-4 cGMP gated channel expressing sensory neurons and TGF-β/BMP are required for signalling across tissues to modulate fat desaturation. We also find neuronal hsf-1 is not only sufficient but also partially necessary to control the fat remodelling response and for survival at warm temperatures. This is the first study to show that a thermostat-based mechanism can cell non-autonomously coordinate membrane saturation and composition across tissues in a multicellular animal. AU - Chauve, Laetitia AU - Hodge, Francesca AU - Murdoch, Sharlene AU - Masoudzadeh, Fatemah AU - Mann, Harry-Jack AU - Lopez-Clavijo, Andrea AU - Okkenhaug, Hanneke AU - West, Greg AU - Sousa, Bebiana C. AU - Segonds-Pichon, Anne AU - Li, Cheryl AU - Wingett, Steven AU - Kienberger, Hermine AU - Kleigrewe, Karin AU - de Bono, Mario AU - Wakelam, Michael AU - Casanueva, Olivia ID - 13069 TI - Neuronal HSF-1 coordinates the propagation of fat desaturation across tissues to enable adaptation to high temperatures in C. elegans ER - TY - CONF AB - 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. AU - Zamyatin, Alexei AU - Al-Bassam, Mustafa AU - Zindros, Dionysis AU - Kokoris Kogias, Eleftherios AU - Moreno-Sanchez, Pedro AU - Kiayias, Aggelos AU - Knottenbelt, William J. ID - 10325 SN - 0302-9743 T2 - 25th International Conference on Financial Cryptography and Data Security TI - SoK: Communication across distributed ledgers VL - 12675 ER -