TY - JOUR AB - How tissues acquire complex shapes is a fundamental question in biology and regenerative medicine. Zebrafish semicircular canals form from invaginations in the otic epithelium (buds) that extend and fuse to form the hubs of each canal. We find that conventional actomyosin-driven behaviors are not required. Instead, local secretion of hyaluronan, made by the enzymes uridine 5′-diphosphate dehydrogenase (ugdh) and hyaluronan synthase 3 (has3), drives canal morphogenesis. Charged hyaluronate polymers osmotically swell with water and generate isotropic extracellular pressure to deform the overlying epithelium into buds. The mechanical anisotropy needed to shape buds into tubes is conferred by a polarized distribution of actomyosin and E-cadherin-rich membrane tethers, which we term cytocinches. Most work on tissue morphogenesis ascribes actomyosin contractility as the driving force, while the extracellular matrix shapes tissues through differential stiffness. Our work inverts this expectation. Hyaluronate pressure shaped by anisotropic tissue stiffness may be a widespread mechanism for powering morphological change in organogenesis and tissue engineering. AU - Munjal, Akankshi AU - Hannezo, Edouard B AU - Tsai, Tony Y.C. AU - Mitchison, Timothy J. AU - Megason, Sean G. ID - 10573 IS - 26 JF - Cell SN - 0092-8674 TI - Extracellular hyaluronate pressure shaped by cellular tethers drives tissue morphogenesis VL - 184 ER - TY - JOUR AB - In two-player games on graphs, the players move a token through a graph to produce an infinite path, which determines the winner of the game. Such games are central in formal methods since they model the interaction between a non-terminating system and its environment. In bidding games the players bid for the right to move the token: in each round, the players simultaneously submit bids, and the higher bidder moves the token and pays the other player. Bidding games are known to have a clean and elegant mathematical structure that relies on the ability of the players to submit arbitrarily small bids. Many applications, however, require a fixed granularity for the bids, which can represent, for example, the monetary value expressed in cents. We study, for the first time, the combination of discrete-bidding and infinite-duration games. Our most important result proves that these games form a large determined subclass of concurrent games, where determinacy is the strong property that there always exists exactly one player who can guarantee winning the game. In particular, we show that, in contrast to non-discrete bidding games, the mechanism with which tied bids are resolved plays an important role in discrete-bidding games. We study several natural tie-breaking mechanisms and show that, while some do not admit determinacy, most natural mechanisms imply determinacy for every pair of initial budgets. AU - Aghajohari, Milad AU - Avni, Guy AU - Henzinger, Thomas A ID - 10674 IS - 1 JF - Logical Methods in Computer Science KW - computer science KW - computer science and game theory KW - logic in computer science TI - Determinacy in discrete-bidding infinite-duration games VL - 17 ER - TY - CONF AB - We study Multi-party computation (MPC) in the setting of subversion, where the adversary tampers with the machines of honest parties. Our goal is to construct actively secure MPC protocols where parties are corrupted adaptively by an adversary (as in the standard adaptive security setting), and in addition, honest parties’ machines are compromised. The idea of reverse firewalls (RF) was introduced at EUROCRYPT’15 by Mironov and Stephens-Davidowitz as an approach to protecting protocols against corruption of honest parties’ devices. Intuitively, an RF for a party P is an external entity that sits between P and the outside world and whose scope is to sanitize P ’s incoming and outgoing messages in the face of subversion of their computer. Mironov and Stephens-Davidowitz constructed a protocol for passively-secure two-party computation. At CRYPTO’20, Chakraborty, Dziembowski and Nielsen constructed a protocol for secure computation with firewalls that improved on this result, both by extending it to multi-party computation protocol, and considering active security in the presence of static corruptions. In this paper, we initiate the study of RF for MPC in the adaptive setting. We put forward a definition for adaptively secure MPC in the reverse firewall setting, explore relationships among the security notions, and then construct reverse firewalls for MPC in this stronger setting of adaptive security. We also resolve the open question of Chakraborty, Dziembowski and Nielsen by removing the need for a trusted setup in constructing RF for MPC. Towards this end, we construct reverse firewalls for adaptively secure augmented coin tossing and adaptively secure zero-knowledge protocols and obtain a constant round adaptively secure MPC protocol in the reverse firewall setting without setup. Along the way, we propose a new multi-party adaptively secure coin tossing protocol in the plain model, that is of independent interest. AU - Chakraborty, Suvradip AU - Ganesh, Chaya AU - Pancholi, Mahak AU - Sarkar, Pratik ID - 10609 SN - 0302-9743 T2 - 27th International Conference on the Theory and Application of Cryptology and Information Security TI - Reverse firewalls for adaptively secure MPC without setup VL - 13091 ER - TY - JOUR AB - Cell division orientation is thought to result from a competition between cell geometry and polarity domains controlling the position of the mitotic spindle during mitosis. Depending on the level of cell shape anisotropy or the strength of the polarity domain, one dominates the other and determines the orientation of the spindle. Whether and how such competition is also at work to determine unequal cell division (UCD), producing daughter cells of different size, remains unclear. Here, we show that cell geometry and polarity domains cooperate, rather than compete, in positioning the cleavage plane during UCDs in early ascidian embryos. We found that the UCDs and their orientation at the ascidian third cleavage rely on the spindle tilting in an anisotropic cell shape, and cortical polarity domains exerting different effects on spindle astral microtubules. By systematically varying mitotic cell shape, we could modulate the effect of attractive and repulsive polarity domains and consequently generate predicted daughter cell size asymmetries and position. We therefore propose that the spindle position during UCD is set by the combined activities of cell geometry and polarity domains, where cell geometry modulates the effect of cortical polarity domain(s). AU - Godard, Benoit G AU - Dumollard, Remi AU - Heisenberg, Carl-Philipp J AU - Mcdougall, Alex ID - 10606 JF - eLife TI - Combined effect of cell geometry and polarity domains determines the orientation of unequal division VL - 10 ER - TY - JOUR AB - The evidence linking innate immunity mechanisms and neurodegenerative diseases is growing, but the specific mechanisms are incompletely understood. Experimental data suggest that microglial TLR4 mediates the uptake and clearance of α-synuclein also termed synucleinophagy. The accumulation of misfolded α-synuclein throughout the brain is central to Parkinson's disease (PD). The distribution and progression of the pathology is often attributed to the propagation of α-synuclein. Here, we apply a classical α-synuclein propagation model of prodromal PD in wild type and TLR4 deficient mice to study the role of TLR4 in the progression of the disease. Our data suggest that TLR4 deficiency facilitates the α-synuclein seed spreading associated with reduced lysosomal activity of microglia. Three months after seed inoculation, more pronounced proteinase K-resistant α-synuclein inclusion pathology is observed in mice with TLR4 deficiency. The facilitated propagation of α-synuclein is associated with early loss of dopamine transporter (DAT) signal in the striatum and loss of dopaminergic neurons in substantia nigra pars compacta of TLR4 deficient mice. These new results support TLR4 signaling as a putative target for disease modification to slow the progression of PD and related disorders. AU - Venezia, Serena AU - Kaufmann, Walter AU - Wenning, Gregor K. AU - Stefanova, Nadia ID - 10607 JF - Parkinsonism & Related Disorders SN - 1353-8020 TI - Toll-like receptor 4 deficiency facilitates α-synuclein propagation and neurodegeneration in a mouse model of prodromal Parkinson's disease VL - 91 ER -