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Long-lived cellular molecules in the brain
No full textIn long-lived mammals, including humans, brain cell homeostasis is critical for maintaining brain function throughout life. Most neurons are generated during development and must maintain their cellular identity and plasticity to preserve brain function. Although extensive studies indicate the importance of recycling and regenerating cellular molecules to maintain cellular homeostasis, recent evidence has shown that some proteins and RNAs do not turn over for months and even years. We propose that these long-lived cellular molecules may be the basis for maintaining brain function in the long term, but also a potential convergent target of brain aging. We highlight key discoveries and challenges, and propose potential directions to unravel the mystery of brain cell longevity
Single-molecule conductance through hybrid radially and linearly π-conjugated macromolecules reveals an unusual intramolecular π-interaction
No full textWe describe the design, synthesis, and single-molecule junction conductance of π-electron molecules bearing both radial and linear π-conjugation pathways, whereby cycloparaphenylene (CPP) radial cores are π-extended linearly with aryl alkyne substituents as models for previously reported CPP-arylene ethynylene conjugated polymers. Although radially and linearly conjugated molecules have been studied previously in isolation as junction-bridging molecular electronic units, this is the first study to examine molecules where both topologies are operative. Our results reveal that the presence of radial CPP components within the junction-spanning pathway leads to a reduction in the conductance of the backbone compared to model linear phenyl substituents. Through tight-binding and DFT-based calculations, we attribute this conductance change to intramolecular van der Waals (vdW) interactions between the CPP ring and the junction-spanning arylene-ethynylene molecular backbone. These interactions induce changes in the dihedral angles of the backbone, leading to a reduced overlap of π orbitals within the molecular junction
The actin cortex acts as a mechanical memory of morphology in confined migrating cells
No full textCell migration in narrow microenvironments occurs in numerous physiological processes. It involves successive cycles of confinement and release that drive important morphological changes. However, it remains unclear whether migrating cells can retain a memory of their past morphological states that could potentially facilitate their navigation through confined spaces. We demonstrate that local geometry governs a switch between two cell morphologies, thereby facilitating cell passage through long and narrow gaps. We combined cell migration assays on standardized microsystems with biophysical modelling and biochemical perturbations to show that migrating cells have a long-term memory of past confinement events. The morphological cell states correlate across transitions through actin cortex remodelling. These findings indicate that mechanical memory in migrating cells plays an active role in their migratory potential in confined environments
Interior rotation modelling of the β Cep pulsator HD 192575 including multiplet asymmetries
No full textContext. Rotation plays an important role in stellar evolution. However, the mechanisms behind the transport of angular momentum in stars at various stages of their evolution are not well understood. To improve our understanding of these processes, it is necessary to measure and validate the internal rotation profiles of stars across different stages of evolution and mass regimes.
Aims. Our aim is to constrain the internal rotation profile of the 12-M⊙ β Cep pulsator HD 192575 from the observed pulsational multiplets and the asymmetries of their component frequencies.
Methods. We updated the forward asteroseismic modelling of HD 192575 based on new TESS observations. We inverted the rotation profile from the symmetric part of the splittings and computed the multiplet asymmetries due to the Coriolis force and stellar deformation, which we treated perturbatively. We compared the computed asymmetries with the observed asymmetries.
Results. Our new forward asteroseismic modelling is in agreement with previous results but with increased uncertainties, partially due to increased frequency precision, which required us to relax certain constraints. Ambiguity in the mode identification is the main source of the uncertainty, which also affects the inferred rotation profiles. Almost all acceptable rotation profiles occur in the regime below 0.4 d−1 and favour weak radial differential rotation, with a ratio of core to envelope rotation of less than 2. We find that the quality of the match between the observed and theoretically predicted mode asymmetries is strongly dependent on the mode identification and the internal structure of the star.
Conclusions. Our results offer the first detailed rotation inversion for a β Cep pulsator. They show that the rotation profile and the mode asymmetries provide a valuable tool for further constraining the evolutionary properties of HD 192575, and in particular the details of angular momentum transport in massive stars
Mechanistic adaptation of the metazoan RabGEFs Mon1-Ccz1 and Fuzzy-Inturned
No full textRab GTPases organize intracellular trafficking and provide identity to organelles. Their spatiotemporal activation by guanine nucleotide exchange factors (GEFs) is tightly controlled to ensure fidelity. Our structural and functional comparison of the tri-longin domain RabGEFs Mon1-Ccz1 and Fuzzy-Inturned reveals the molecular basis for their target specificity. Both complexes rely on a conserved sequence motif of their substrate GTPases for the catalytic mechanism, while secondary interactions allow discrimination between targets. We also find that dimeric Mon1-Ccz1 from fungi and the metazoan homologs with the additional third subunit RMC1/Bulli bind membranes through electrostatic interactions via distinct interfaces. Protein-lipid interaction studies and functional characterization in flies reveal an essential function of RMC1/Bulli as mediator of GEF complex membrane recruitment. In the case of Fuzzy-Inturned, reconstitution experiments demonstrate that the BAR (Bin-Amphiphysin-Rvs) domain protein CiBAR1 can support membrane recruitment of the GEF. Collectively, our study demonstrates the molecular basis for the adaptation of TLD-RabGEFs to different cellular functions
Armadillo repeat only proteins are required for the function of plant CNGC channels
No full textPlant cells respond to a wide range of stimuli through intracellular calcium (Ca2+) signaling. Cyclic nucleotide-gated channels (CNGCs) are a major class of plant Ca2+ channels, with 20 homologs in Arabidopsis. These tetrameric plasma membrane proteins act downstream of diverse signals, such as phytohormones, extracellular damage, cell wall integrity or temperature. Here, we identify a class of plant-specific proteins, Armadillo Repeat Only (ARO), as essential regulators of possibly all plant CNGCs. Abrogation of functional sporophytic AROs results in a phenotypic pattern strongly reminiscent of CNGC dysfunction, including defects in root gravitropism, root hair growth and morphology, stomatal movement, and responses to extracellular ATP and the phytohormone auxin. aro2/3/4 mutants are fully resistant to the toxic effects caused by overexpression of CNGCs. AROs colocalize and physically interact with multiple CNGCs and modulate CNGC-dependent currents in Xenopus oocytes. Structural modeling and site-directed mutagenesis reveal AROs tetramer formation surrounding the CNGC channel, interacting via its IQ domain. Taken together, plant CNGC channels don’t act alone, but in a larger complex - channelosome, first of a kind in plants
Efficient contractions of dynamic graphs - with applications
No full textA non-trivial minimum cut (NMC) sparsifier is a multigraph Ĝ that preserves all non-trivial minimum cuts of a given undirected graph G. We introduce a flexible data structure for fully dynamic graphs that can efficiently provide an NMC sparsifier upon request at any point during the sequence of updates. We employ simple dynamic forest data structures to achieve a fast from-scratch construction of the sparsifier at query time. Based on the strength of the adversary and desired type of time bounds, the data structure comes with different guarantees. Specifically, let G be a fully dynamic simple graph with n vertices and minimum degree δ. Then our data structure supports an insertion/deletion of an edge to/from G in n^o(1) worst-case time. Furthermore, upon request, it can return w.h.p. an NMC sparsifier of G that has O(n/δ) vertices and O(n) edges, in Ô(n) time. The probabilistic guarantees hold against an adaptive adversary. Alternatively, the update and query times can be improved to Õ(1) and Õ(n) respectively, if amortized-time guarantees are sufficient, or if the adversary is oblivious. Throughout the paper, we use Õ to hide polylogarithmic factors and Ô to hide subpolynomial (i.e., n^o(1)) factors.
We discuss two applications of our new data structure. First, it can be used to efficiently report a cactus representation of all minimum cuts of a fully dynamic simple graph. Building this cactus for the NMC sparsifier instead of the original graph allows for a construction time that is sublinear in the number of edges. Against an adaptive adversary, we can with high probability output the cactus representation in worst-case Ô(n) time. Second, our data structure allows us to efficiently compute the maximal k-edge-connected subgraphs of undirected simple graphs, by repeatedly applying a minimum cut algorithm on the NMC sparsifier. Specifically, we can compute with high probability the maximal k-edge-connected subgraphs of a simple graph with n vertices and m edges in Õ(m+n²/k) time. This improves the best known time bounds for k = Ω(n^{1/8}) and naturally extends to the case of fully dynamic graphs
Quantifying the seasonal dynamics of a transitional ice cliff-pond system on a debris-covered glacier
No full textIce cliffs and supraglacial ponds are key drivers of mass loss on debris-covered glaciers. However, the relationship between melt ponds and adjacent ice cliffs has not been fully explored. We investigated the seasonal drainage patterns of a melt pond on the debris-covered Zhuxi Glacier in southeast Tibet and estimated the mass loss of its adjacent ice cliff during 2023-2024. Using hourly time-lapse photogrammetry we built a series of high-resolution point clouds to quantify the evolution of the ice cliff-pond system. Our findings indicate that subaerial melting and undercutting were the primary mechanisms of ice cliff mass loss during summer. In winter when the pond water level dropped, ice cliff calving became the dominant mode of ice loss. As the water level rose in spring, calving and subaerial melting occurred simultaneously and ice loss from calving accounted for approximately 19.5 % of total ice loss from February to July 2024. Our results reveal the transitional state of this ice cliff-pond system, exhibiting characteristics of both melt hotspots and lake-terminating calving fronts, and highlight the interplay between seasonal drainage-refill pond and differing modes of ice loss on adjacent ice cliff. Future research should focus on additional high-resolution monitoring of similar systems and incorporation of ice cliff-pond dynamics in glacier-scale numerical models
Bridging solution and solid-state mechanism: Confined quasi-solid-state conversion in Li–S batteries
No full text“Quasi-solid-state” conversion mechanisms using sparingly solvating electrolytes (SPSEs) bridge the gap between traditional solid–liquid–solid and solid-state sulfur conversion in lithium–sulfur (Li–S) batteries. Although these terms are commonly used, their precise distinctions and impacts on key performance metrics, such as rate capability, energy density, and capacity fading, remain poorly understood. In this work, we employ operando small- and wide-angle X-ray scattering alongside cryogenic transmission electron microscopy (cryo-TEM) to compare Li–S batteries in sparingly solvating and solvating ether-based electrolytes. We find that, unlike solvating electrolytes, SPSEs lead to an extended presence of lithium sulfide during cycling, coexisting with sulfur at a 50% state of charge and beyond. In the charged state, solid sulfur is present in its amorphous form inside the carbon black nanopores. These findings indicate that the limited solubility confines polysulfides in regions near the carbon surface, where these polysulfides enable conversion between the coexisting solid discharge and charge product
Heat flow, log-concavity, and Lipschitz transport maps
No full textIn this paper we derive estimates for the Hessian of the logarithm (log-Hessian) for solutions to the heat equation. For initial data in the form of log-Lipschitz perturbation of strongly log-concave measures, the log-Hessian admits an explicit, uniform (in space) lower bound. This yields a new estimate for the Lipschitz constant of a transport map pushing forward the standard Gaussian to a measure in this class. On the other hand, we show that assuming only fast decay of the tails of the initial datum does not suffice to guarantee uniform log-Hessian upper bounds