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Gasdermin-D (GSDMD) is the ultimate effector of pyroptosis, a form of programmed cell death associated with pathogen invasion and inflammation. After proteolytic cleavage by caspases activated by the inflammasome, the GSDMD N-terminal domain (GSDMDNT) assembles on the inner leaflet of the plasma membrane and induces the formation of large membrane pores. We use atomistic molecular dynamics simulations to study GSDMDNT monomers, oligomers, and rings in an asymmetric plasma membrane mimetic. We identify distinct interaction motifs of GSDMDNT with phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) and phosphatidylserine (PS) head-groups and describe differential lipid binding between the pore and prepore conformations. Oligomers are stabilized by shared lipid binding sites between neighboring monomers acting akin to double-sided tape. We show that already small GSDMDNT oligomers form stable, water-filled and ion-conducting membrane pores bounded by curled beta-sheets. In large-scale simulations, we resolve the process of pore formation by lipid detachment from GSDMDNT arcs and lipid efflux from partial rings. We find that that high-order GSDMDNT oligomers can crack under the line tension of 86 pN created by an open membrane edge to form the slit pores or closed GSDMDNT rings seen in experiment. Our simulations provide a detailed view of key steps in GSDMDNT-induced plasma membrane pore formation, including sublytic pores that explain nonselective ion flux during early pyroptosis.
Cryo electron tomography (cryo-ET) combined with subtomogram averaging (StA) enables structural determination of macromolecules in their native context. A few structures were reported by StA at resolution higher than 4.5 Å, however all of these are from viral structural proteins or vesicle coats. Reaching high resolution for a broader range of samples is uncommon due to beam-induced sample drift, poor signal-to-noise ratio (SNR) of images, challenges in CTF correction, limited number of particles. Here we propose a strategy to address these issues, which consists of a tomographic data collection scheme and a processing workflow. Tilt series are collected with higher electron dose at zero-degree tilt in order to increase SNR. Next, after performing StA conventionally, we extract 2D projections of the particles of interest from the higher SNR images and use the single particle analysis tools to refine the particle alignment and generate a reconstruction. We benchmarked our proposed hybrid StA (hStA) workflow and improved the resolution for tobacco mosaic virus from 7.2 to 5.2 Å and the resolution for the ion channel RyR1 in crowded native membranes from 12.9 to 9.1 Å. We demonstrate that hStA can improve the resolution obtained by conventional StA and promises to be a useful tool for StA projects aiming at subnanometer resolution or higher.
We present a RQMD calculation of antiproton yields and their momentum distribution in Ne + NaF collisions at 2 GeV/u. The antiprotons can be produced below threshold due to multi-step excitations for which meson-baryon interactions play a considerable role. In this system the annihilation probability for an initially produced antiproton is predicted to be about 65%.
The firing pattern of ventral midbrain dopamine neurons is controlled by afferent and intrinsic activity to generate prediction error signals that are essential for reward-based learning. Given the absence of intracellular in vivo recordings in the last three decades, the subthreshold membrane potential events that cause changes in dopamine neuron firing patterns remain unknown. By establishing stable in vivo whole-cell recordings of >100 spontaneously active midbrain dopamine neurons in anaesthetized mice, we identified the repertoire of subthreshold membrane potential signatures associated with distinct in vivo firing patterns. We demonstrate that dopamine neuron in vivo activity deviates from a single spike pacemaker pattern by eliciting transient increases in firing rate generated by at least two diametrically opposing biophysical mechanisms: a transient depolarization resulting in high frequency plateau bursts associated with a reactive, depolarizing shift in action potential threshold; and a prolonged hyperpolarization preceding slower rebound bursts characterized by a predictive, hyperpolarizing shift in action potential threshold. Our findings therefore illustrate a framework for the biophysical implementation of prediction error and sensory cue coding in dopamine neurons by tuning action potential threshold dynamics.
Results from various theoretical approaches and ideas presented at this exciting meeting (summary talk at the 5th International Conference on Physics and Astrophysics of Quark Gluon Plasma (ICPAQGP - 2005)) are reviewed. I also point towards future directions, in particular hydrodynamic behaviour induced by jets traveling through the quark-gluon plasma, which might be worth looking at in more detail.
The discovery of superconductivity in layered vanadium-based kagome metals AV3Sb5 (A: K, Rb, Cs) has added a new family of materials to the growing class of possible unconventional superconductors. However, the nature of the superconducting pairing in these materials remains elusive. We present a microscopic theoretical study of the leading superconducting instabilities on the kagome lattice based on spin- and charge-fluctuation mediated Cooper pairing. The applied methodology includes effects of both on-site and nearest-neighbor repulsive Coulomb interactions. Near the upper van Hove filling -- relevant for the AV3Sb5 materials -- we find a rich phase diagram with several pairing symmetries being nearly degenerate. In particular, while a substantial fraction of the phase diagram is occupied by a spin-singlet order parameter transforming as a two-dimensional irreducible representation of the point group, several nodal spin-triplet pairing states remain competitive. We compute the band and interaction parameter-dependence of the hierarchy of the leading superconducting instabilities, and determine the detailed momentum dependence of the resulting preferred gap structures. Crucially, for moderate values of the interaction parameters, the individual pairing states depend strongly on momentum and exhibit multiple nodes on the Fermi surface. We discuss the properties of these superconducting gap structures in light of recent experimental developments of the AV3Sb5 materials.
We reexamine the scenario of homogeneous nucleation of the quark-gluon plasma produced in ultra-relativistic heavy ion collisions. A generalization of the standard nucleation theory to rapidly expanding system is proposed. The nucleation rate is derived via the new scaling parameter Z. It is shown that the size distribution of hadronic clusters plays an important role in the dynamics of the phase transition. The longitudinally expanding system is supercooled to about 3 6%, then it is reheated, and the hadronization is completed within 6 10 fm/c, i.e. 5 10 times faster than it was estimated earlier, in a strongly nonequilibrium way. PACS: 12.38.Mh; 12.39.Ba; 25.75.-q; 64.60.Qb
Communication sounds are ubiquitous in the animal kingdom, where they play a role in advertising physiological states and/or socio-contextual scenarios. Distress sounds, for example, are typically uttered in distressful scenarios such as agonistic interactions. Here, we report on the occurrence of superfast temporal periodicities in distress calls emitted by bats (species Carollia perspicillata). Distress vocalizations uttered by this bat species are temporally modulated at frequencies close to 1.7 kHz, that is, ∼17 times faster than modulation rates observed in human screams. Fast temporal periodicities are represented in the bats’ brain by means of frequency following responses, and temporally periodic sounds are more effective in boosting the heart rate of awake bats than their demodulated versions. Altogether, our data suggest that bats, an animal group classically regarded as ultrasonic, can exploit the low frequency portion of the soundscape during distress calling to create spectro-temporally complex, arousing sounds.
Effective knowledge communication presupposes common ground (Clark & Brennan, 1991) that needs to be established and maintained. This is particularly difficult in remote communication as well as in non-interactive settings, because the speaker cannot use gestures or mimic and has to tailor his utterances to the addressee without receiving feedback. In these situations, the speaker may achieve mutual understanding for example by adopting the addressee’s perspective. We present a study conducted to test the impact of instructions that support and hinder individual problem solving and knowledge communication. We used a picture-sorting task requiring individual cognitive processes of feature search (Treisman & Gelade, 1980) in addition to referential communication. As our study focused on the design of utterances, all participants assumed the role of speaker. Participants were told that their descriptions would be recorded and then listened to later on by a participant in the role of addressee. Eight sets of pictures were used, which varied on two dimensions: the individual cognitive demands of detecting the relevant features (varied as between-subject factor) and the communicative demands (varied as within-subject factor). A further between-subject factor was the type of instructions: The participants received either a collaboration script as supporting instructions, or time pressure was applied to induce stress, or else they were given no additional instructions (control group). We used the speakers’ verbal utterances to examine the quality of the speakers’ descriptions. For both dimensions of difficulty, we found the expected effects. In the conditions with a collaboration script, there were fewer irrelevant features mentioned and fewer features were described with delay. In the conditions with time pressure, there were fewer irrelevant features described, but the number of correctly described pictures was impaired through the fact that relevant features were also neglected. Under time pressure, speakers tended to provide ambiguous descriptions regarding the frame of reference.
We propose a framework of individual problem-solving and communicative demands (IproCo) that bridges the gap between models from cognitive psychology and communication pragmatics. Furthermore, we present two experiments conducted to identify factors influencing the demands and to test possibilities for support. The experiments employed a remote collaborative picture-sorting task with concrete and abstract pictures and applied non-interactive conditions compared to interactive conditions. In a first experiment, the influence of the postulated demands on collaboration process and outcome was analysed, and the impact of shared applications was tested. In a second experiment, we evaluated instructional support measures consisting of model collaboration and a collaboration script. The collaboration process showed benefits of the support but the outcome did not. However, the support measures fostered the collaboration process even in the particularly difficult conditions with non-interactive communication. We discuss the impact of the IproCo framework and apply it to other tasks.
We address the production of black holes at LHC in space times with compactified space-like large extra dimensions (LXD). Final state black hole production leads to suppression of high-PT jets, i.e. a sharp cut-o in (pp!jet+X). This signal is compared to the jet plus missing energy signature due to graviton production in the final state as proposed by the ATLAS collaboration. Time evolution and lifetimes of the newly created black holes are calculated based on the micro- canonical formalism. It is demonstrated that previous lifetime estimates of micro black holes have been dramatically underestimated. The creation of a large number of quasi-stable black holes is predicted with life times of hundred fm/c at LHC. Medium modifications of the black holes evaporation rate due to the quark gluon plasma in relativistic heavy ion collisions as well as provided by the cosmic fluid in the early universe are studied
A model for the production of quarkonium states in the midrapidity region at RHIC and LHC energy range is presented which explores well understood properties of QCD only. An increase of the quarkonium hadronisation time with the initial energy leads to a gradual change of the most important phenomena from fixed target- to collider-energies. We evaluate nuclear e ects in the quarkonium production due to medium modification of the momentum distribution of the heavy quarks produced in the hard interactions, i.e. due to the broadening of the transverse momentum distribution. Other nuclear effects, i.e. nuclear shadowing and parton energy loss, are also evaluated.
The production yield of the Λ(1520) baryon resonance is measured at mid-rapidity in Pb-Pb collisions at sNN−−−√ = 2.76 TeV with the ALICE detector at the LHC. The measurement is performed in the Λ(1520)→pK− (and charge conjugate) hadronic decay channel as a function of the transverse momentum (pT) and collision centrality. The pT-integrated production rate of Λ(1520) relative to Λ in central collisions is suppressed by about a factor of 2 with respect to peripheral collisions. This is the first observation of the suppression of a baryonic resonance at LHC and the first evidence of Λ(1520) suppression in heavy-ion collisions. The measured Λ(1520)/Λ ratio in central collisions is smaller than the value predicted by the statistical hadronisation model calculations. The shape of the measured pT distribution and the centrality dependence of the suppression are reproduced by the EPOS3 Monte Carlo event generator. The measurement adds further support to the formation of a dense hadronic phase in the final stages of the evolution of the fireball created in heavy-ion collisions, lasting long enough to cause a significant reduction in the observable yield of short-lived resonances.
The production yield of the Λ(1520) baryon resonance is measured at mid-rapidity in Pb-Pb collisions at sNN−−−√ = 2.76 TeV with the ALICE detector at the LHC. The measurement is performed in the Λ(1520)→pK− (and charge conjugate) hadronic decay channel as a function of the transverse momentum (pT) and collision centrality. The pT-integrated production rate of Λ(1520) relative to Λ in central collisions is suppressed by about a factor of 2 with respect to peripheral collisions. This is the first observation of the suppression of a baryonic resonance at the LHC and the first 3σ evidence of Λ(1520) suppression within a single collision system. The measured Λ(1520)/Λ ratio in central collisions is smaller than the value predicted by the statistical hadronisation model calculations. The shape of the measured pT distribution and the centrality dependence of the suppression are reproduced by the EPOS3 Monte Carlo event generator. The measurement adds further support to the formation of a dense hadronic phase in the final stages of the evolution of the fireball created in heavy-ion collisions, lasting long enough to cause a significant reduction in the observable yield of short-lived resonances.
Abstract
Seed harvesting from wild plant populations is key for ecological restoration, but may threaten the persistence of source populations. Consequently, several countries have set guidelines limiting the proportions of harvestable seeds. However, these guidelines are so far inconsistent, and they lack a solid empirical basis. Here, we use high-resolution data from 298 plant species to model the demographic consequences of seed harvesting. We find that the current guidelines do not protect populations of annuals and short-lived perennials, while they are overly restrictive for long-lived plants. We show that the maximum possible fraction of seed production – what can be harvested without compromising the long-term persistence of populations – is strongly related to the generation time of the target species. When harvesting every year, this safe seed fraction ranges from 80% in long-lived species to 2% in most annuals. Less frequent seed harvesting substantially increases the safe seed fraction: In the most vulnerable annual species, it is safe to harvest 5%, 10% or 30% of population seed production when harvesting every two, five or ten years, respectively. Our results provide a quantitative basis for seed harvesting legislations worldwide, based on species’ generation time and harvesting regime.
Significance The UN Decade on Ecosystem Restoration, 2021-2030, foresees upscaling restoration, and the demand for native seed is skyrocketing. Seeds for restoring native vegetation are often harvested in wild, but too intensive harvest can threaten the donor populations. Existing guidelines that set limits to wild seed harvest are mostly based on expert opinions, yet they commonly lack empirical basis and vary among regions in one order of magnitude. We show that the current guidelines urgently need to be reformulated, because they are overly restrictive in long-lived species, while they do not protect annual plants from extinction. Using matrix population models of nearly 300 plant species, we provide a quantitative basis for a new seed harvesting legislation world-wide.
Seed harvesting from wild plant populations is key for ecological restoration, but may threaten the persistence of source populations. Consequently, several countries have set guidelines limiting the proportions of harvestable seeds. Here, we use high-resolution data from 298 plant species to model the demographic consequences of seed harvesting. We find that the current guidelines only protect some species, but are insufficient or overly restrictive for others. We show that the maximum possible fraction of seed harvesting is strongly associated with harvesting frequency and generation time of the target species, ranging from 100% in long-lived species to <1% in the most annuals. Our results provide quantitative basis to guide seed harvesting legislation based on species’ generation time and harvesting regime.
Antimicrobial resistance is a major threat to global health and food security today. Scheduling cycling therapies by targeting phenotypic states associated to specific mutations can help us to eradicate pathogenic variants in chronic infections. In this paper, we introduce a logistic switching model in order to abstract mutation networks of collateral resistance. We found particular conditions for which unstable zero-equilibrium of the logistic maps can be stabilized through a switching signal. That is, persistent populations can be eradicated through tailored switching regimens.
Starting from an optimal-control formulation, the switching policies show their potential in the stabilization of the zero-equilibrium for dynamics governed by logistic maps. However, employing such switching strategies, deserve a specific characterization in terms of limit behaviour. Ultimately, we use evolutionary and control algorithms to find either optimal and sub-optimal switching policies. Simulations results show the applicability of Parrondo’s Paradox to design cycling therapies against drug resistance.
We use the topological heavy fermion (THF) model and its Kondo Lattice (KL) formulation to study the symmetric Kondo state in twisted bilayer graphene. Via a large-N approximation, we find a symmetric Kondo (SK) state in KL mode at fillings ν=0,±1,±2. In the SK state, all symmetries are preserved and the local moments are Kondo screened by the conduction electrons. At the mean-field level of the THF model at ν=0,±1,±2,±3, we also find a similar symmetric state. We study the stability of the symmetric state by comparing its energy with the ordered states and find the ordered states to have lower energy. However, moving away from integer fillings by doping holes to the light bands, we find the energy difference is reduced, which suggests the loss of ordering and a tendency towards Kondo screening. In order to include many-body effects beyond the mean-field approximation, we perform dynamical mean-field theory (DMFT) calculations on the THF model. We find the spin susceptibility follows a Curie behavior at ν=0,±1,±2 down to ∼2K where the onset of screening of the local moment becomes visible. This hints to very low Kondo temperatures at these fillings, in agreement with the outcome of our mean-field calculations. At non-integer filling ν=±0.5,±0.8,±1.2 DMFT shows deviations from a 1/T-susceptibility at much higher temperatures, suggesting a more effective screening of local moments with doping. Finally, we study the effect of a C3z-rotational-symmetry-breaking strain via mean-field approaches and find that a symmetric phase (that only breaks C3z symmetry) can be stabilized at sufficiently large strain at ν=0,±1,±2. Our results suggest that a symmetric Kondo phase is strongly suppressed at integer fillings, but could be stabilized either at non-integer fillings or by applying strain.
Symmetrie
(1997)