École des Neurosciences de Paris

Abstract Lipid droplets (LDs) are the major sites of lipid and energy homeostasis. However, few LD biogenesis proteins have been identified. Here, usingChlamydomonasas a model, we show that ABHD1, a member of the α/β hydrolase domain-containing protein family, is a novel type of LD-associated protein which stimulates LD formation through two distinct actions on the LD surface, one enzymatic and the other structural. ABHD1 was localized to LD surface inChlamydomonascells. The knockout mutants contained similar amounts of triacylglycerols (TAG) but their LDs showed an increased content in lyso- derivatives of the betaine lipid diacylglyceryl-N,N,N-trimethylhomoserine (DGTS). Over-expression ofABHD1in Chlamydomonas induced LD formation and boosted TAG content, suggesting a key role in LD biogenesis. The purified recombinant ABHD1 protein hydrolyzed lyso-DGTS, producing a free fatty acid and a glyceryltrimethylhomoserine moiety. In vitro experiments using droplet- embedded vesicles showed that ABHD1 promoted LD emergence. Taken together, these results identify ABHD1 as a new player in LD formation by its lipase activity on lyso-DGTS and by its distinct biophysical property. This study further suggests that lipases targeted to LDs and able to act on their polar lipid coat may be interesting tools to promote LD assembly in eukaryotic cells.Significant statementLipid droplets are subcellular organelles specialized for triacylglycerol storage. Their dynamic turnover is key to managing energy homeostasis in response to cell cycle states and environmental cues. To gain insights into LD biogenesis, we characterized a putative α/β- hydrolase (ABHD1) in the model algaeChlamydomonas reinhardtiiand show it is located at the LD surface. We found that ABHD1 overexpression promotes LD formation and acts as a lipase mainly on lyso derivatives of the betaine lipid diacylglyceryl-N,N,N-trimethylhomoserine (DGTS), the major lipid constituent of the LD hemi-membrane. We also show that ABHD1 has a remarkable biophysical property favoring LD budding. This work thus identifies a novel type of lipase acting on betaine lipid and provides a first example of a protein with a dual function nvolved in LD formation.

This data includes the sample velocity fields and also the meshmask.nc file to run the ARIANE Lagrangian tool and some sample trajectories simulated based on the flow fields.

Boolean programs with multiple recursive threads can be captured as pushdown automata with multiple stacks. This model is Turing complete, and hence, one is often interested in analyzing a restricted class that still captures useful behaviors. In this paper, we propose a new class of bounded under approximations for multi-pushdown systems, which subsumes most existing classes. We develop an efficient algorithm for solving the under-approximate reachability problem, which is based on efficient fix-point computations. We implement it in our tool BHIM and illustrate its applicability by generating a set of relevant benchmarks and examining its performance. As an additional takeaway, BHIM solves the binary reachability problem in pushdown automata. To show the versatility of our approach, we then extend our algorithm to the timed setting and provide the first implementation that can handle timed multi-pushdown automata with closed guards.

<p>Mesoporous materials suffer from limitations including poor crystallinity and hydrolytic stability, lack of chemical diversity, insufficient pore accessibility, complex synthesis and toxicity issues. Here the association of non-toxic Zr-oxo clusters and feedstock isophthalic acid (IPA) via a Homometallic-Multicluster-Dot strategy results in a robust crystalline mesoporous MOF, denoted as MIP-206, that overcomes the aforementioned limitations. MIP-206, built up from an unprecedented combination of Zr<sub>6</sub> and Zr<sub>12</sub> oxo-cluster inorganic building units into a single structure, exhibits accessible meso-channels of ca. 2.6 nm and displays excellent chemical stability under different hydrolytic and harsh conditions. Owing to the abundant variety of functionalized IPA linkers, the chemical environment of MIP-206 can be easily tuned without hampering pore accessibility due to its large pore windows. As a result, MIP-206 loaded with palladium nanoparticles acts as an efficient and durable catalyst for the dehydrogenation of formic acid under mild conditions, outperforming benchmark mesoporous materials. This paves the way towards the utilization of MIP-206 as a robust mesoporous platform for a wide range of potential applications.</p>

Abstract Existence of solutions to a non‐local Cahn‐Hilliard model with degenerate mobility is considered. The PDE is written as a gradient flow with respect to the L2‐Wasserstein metric for two components that are coupled by an incompressibility constraint. Approximating solutions are constructed by means of an implicit discretization in time and variational methods.

We present a group signature scheme, based on the hardness of lattice problems, whose outputs are more than an order of magnitude smaller than the currently most efficient schemes in the literature. Since lattice-based schemes are also usually non-trivial to efficiently implement, we additionally provide the first experimental implementation of lattice-based group signatures demonstrating that our construction is indeed practical -- all operations take less than half a second on a standard laptop. A key component of our construction is a new zero-knowledge proof system for proving that a committed value belongs to a particular set of small size. The sets for which our proofs are applicable are exactly those that contain elements that remain stable under Galois automorphisms of the underlying cyclotomic number field of our lattice-based protocol. We believe that these proofs will find applications in other settings as well. The motivation of the new zero-knowledge proof in our construction is to allow the efficient use of the selectively-secure signature scheme (i.e. a signature scheme in which the adversary declares the forgery message before seeing the public key) of Agrawal et al. (Eurocrypt 2010) in constructions of lattice-based group signatures and other privacy protocols. For selectively-secure schemes to be meaningfully converted to standard signature schemes, it is crucial that the size of the message space is not too large. Using our zero-knowledge proofs, we can strategically pick small sets for which we can provide efficient zero-knowledge proofs of membership.

Abstract Working memory and conscious perception are thought to share similar brain mechanisms, yet recent reports of non-conscious working memory challenge this view. Combining visual masking with magnetoencephalography, we demonstrate the reality of non-conscious working memory and dissect its neural mechanisms. In a spatial delayed-response task, participants reported the location of a subjectively unseen target above chance-level after a long delay. Conscious perception and conscious working memory were characterized by similar signatures: a sustained desynchronization in the alpha/beta band over frontal cortex, and a decodable representation of target location in posterior sensors. During non-conscious working memory, such activity vanished. Our findings contradict models that identify working memory with sustained neural firing, but are compatible with recent proposals of ‘activity-silent’ working memory. We present a theoretical framework and simulations showing how slowly decaying synaptic changes allow cell assemblies to go dormant during the delay, yet be retrieved above chance-level after several seconds.

We obtain a necessary and sufficient condition of existence of a K{\"a}hler-Einstein metric on a $G\times G$-equivariant Fano compactification of a complex connected reductive group $G$ in terms of the associated polytope. This condition is not equivalent to the vanishing of the Futaki invariant. The proof relies on the continuity method and its translation into a real Monge-Amp{\`e}re equation, using the invariance under the action of a maximal compact subgroup $K\times K$.

One main challenge of the theory of computational effects is to understand how to combine various notions of effects in a meaningful way. Here, we study the particular case of the local state monad, which we would like to express as the result of combining together a family of global state monads parametrized by the number of available registers. To that purpose, we develop a notion of indexed monad which refines and generalizes Power's recent notion of indexed Lawvere theory. One main achievement of the paper is to integrate the block structure necessary to encode allocation as part of the resulting notion of indexed state monad. We then explain how to recover the local state monad from the functorial data provided by our notion of indexed state monad. This reconstruction is based on the guiding idea that an algebra of the indexed state monad should be defined as a section of a 2-categorical notion of fibration associated to the indexed state monad by a Grothendieck construction.