Combinatorial properties of triplet covers for binary trees

It is a classical result that an unrooted tree $T$ having positive real-valued edge lengths and no vertices of degree two can be reconstructed from the induced distance between each pair of leaves. Moreover, if each non-leaf vertex of $T$ has degree 3 then the number of distance values required is linear in the number of leaves. A canonical candidate for such a set of pairs of leaves in $T$ is the following: for each non-leaf vertex $v$, choose a leaf in each of the three components of $T-v$, group these three leaves into three pairs, and take the union of this set over all choices of $v$. This forms a so-called `triplet cover' for $T$. In the first part of this paper we answer an open question (from 2012) by showing that the induced leaf-to-leaf distances for any triplet cover for $T$ uniquely determine $T$ and its edge lengths. We then investigate the finer combinatorial properties of triplet covers. In particular, we describe the structure of triplet covers that satisfy one or more of the following properties of being minimal, `sparse', and `shellable'

Geometric inequalities from phase space translations

We establish a quantum version of the classical isoperimetric inequality relating the Fisher information and the entropy power of a quantum state. The key tool is a Fisher information inequality for a state which results from a certain convolution operation: the latter maps a classical probability distribution on phase space and a quantum state to a quantum state. We show that this inequality also gives rise to several related inequalities whose counterparts are well-known in the classical setting: in particular, it implies an entropy power inequality for the mentioned convolution operation as well as the isoperimetric inequality, and establishes concavity of the entropy power along trajectories of the quantum heat diffusion semigroup. As an application, we derive a Log-Sobolev inequality for the quantum Ornstein-Uhlenbeck semigroup, and argue that it implies fast convergence towards the fixed point for a large class of initial states.Comment: 37 pages; updated to match published versio

Reciprocal regulation of PKA and rac signaling

Activated G protein-coupled receptors (GPCRs) and receptor tyrosine kinases relay extracellular signals through spatial and temporal controlled kinase and GTPase entities. These enzymes are coordinated by multifunctional scaffolding proteins for precise intracellular signal processing. The cAMP-dependent protein kinase A (PKA) is the prime example for compartmentalized signal transmission downstream of distinct GPCRs. A-kinase anchoring proteins tether PKA to specific intracellular sites to ensure precision and directionality of PKA phosphorylation events. Here, we show that the Rho-GTPase Rac contains A-kinase anchoring protein properties and forms a dynamic cellular protein complex with PKA. The formation of this transient core complex depends on binary interactions with PKA subunits, cAMP levels and cellular GTP-loading accounting for bidirectional consequences on PKA and Rac downstream signaling. We show that GTP-Rac stabilizes the inactive PKA holoenzyme. However, β-adrenergic receptor-mediated activation of GTP-Rac–bound PKA routes signals to the Raf-Mek-Erk cascade, which is critically implicated in cell proliferation. We describe a further mechanism of how cAMP enhances nuclear Erk1/2 signaling: It emanates from transphosphorylation of p21-activated kinases in their evolutionary conserved kinase-activation loop through GTP-Rac compartmentalized PKA activities. Sole transphosphorylation of p21-activated kinases is not sufficient to activate Erk1/2. It requires complex formation of both kinases with GTP-Rac1 to unleash cAMP-PKA–boosted activation of Raf-Mek-Erk. Consequently GTP-Rac functions as a dual kinase-tuning scaffold that favors the PKA holoenzyme and contributes to potentiate Erk1/2 signaling. Our findings offer additional mechanistic insights how β-adrenergic receptor-controlled PKA activities enhance GTP-Rac–mediated activation of nuclear Erk1/2 signaling

TREM2 regulates microglial lipid droplet formation and represses post-ischemic brain injury

Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor protein predominantly expressed in microglia within the central nervous system (CNS). TREM2 regulates multiple microglial functions, including lipid metabolism, immune reaction, inflammation, and microglial phagocytosis. Recent studies have found that TREM2 is highly expressed in activated microglia after ischemic stroke. However, the role of TREM2 in the pathologic response after stroke remains unclear. Herein, TREM2-deficient microglia exhibit an impaired phagocytosis rate and cholesteryl ester (CE) accumulation, leading to lipid droplet formation and upregulation of Perilipin-2 (PLIN2) expression after hypoxia. Knockdown of TREM2 results in increased lipid synthesis (PLIN2, SOAT1) and decreased cholesterol clearance and lipid hydrolysis (LIPA, ApoE, ABCA1, NECH1, and NPC2), further impacting microglial phenotypes. In these lipid droplet-rich microglia, the TGF-β1/Smad2/3 signaling pathway is downregulated, driving microglia towards a pro-inflammatory phenotype. Meanwhile, in a neuron-microglia co-culture system under hypoxic conditions, we found that microglia lost their protective effect against neuronal injury and apoptosis when TREM2 was knocked down. Under in vivo conditions, TREM2 knockdown mice express lower TGF-β1 expression levels and a lower number of anti-inflammatory M2 phenotype microglia, resulting in increased cerebral infarct size, exacerbated neuronal apoptosis, and aggravated neuronal impairment. Our work suggests that TREM2 attenuates stroke-induced neuroinflammation by modulating the TGF-β1/Smad2/3 signaling pathway. TREM2 may play a direct role in the regulation of inflammation and also exert an influence on the post-ischemic inflammation and the stroke pathology progression via regulation of lipid metabolism processes. Thus, underscoring the therapeutic potential of TREM2 agonists in ischemic stroke and making TREM2 an attractive new clinical target for the treatment of ischemic stroke and other inflammation-related diseases.National Natural Science Foundation of China ; Science and Technology Commission of Shanghai Municipality ; China Scholarship Counci

Many-body Landau-Zener dynamics in coupled 1D Bose liquids

The Landau-Zener model of a quantum mechanical two-level system driven with a linearly time dependent detuning has served over decades as a textbook paradigm of quantum dynamics. In their seminal work [L. D. Landau, Physik. Z. Sowjet. 2, 46 (1932); C. Zener, Proc. Royal Soc. London 137, 696 (1932)], Landau and Zener derived a non-perturbative prediction for the transition probability between two states, which often serves as a reference point for the analysis of more complex systems. A particularly intriguing question is whether that framework can be extended to describe many-body quantum dynamics. Here we report an experimental and theoretical study of a system of ultracold atoms, offering a direct many-body generalization of the Landau-Zener problem. In a system of pairwise tunnel-coupled 1D Bose liquids we show how tuning the correlations of the 1D gases, the tunnel coupling between the tubes and the inter-tube interactions strongly modify the original Landau-Zener picture. The results are explained using a mean-field description of the inter-tube condensate wave-function, coupled to the low-energy phonons of the 1D Bose liquid.Comment: 13 pages, 10 figures

Light-field-driven electronics in the mid-infrared regime: Schottky rectification

The speed of an active electronic semiconductor device is limited by RC timescale, i.e., the time required for its charging and discharging. To circumvent this ubiquitous limitation of conventional electronics, we investigate diodes under intense mid-infrared light-field pulses. We choose epitaxial graphene on silicon carbide as a metal/semiconductor pair, acting as an ultrarobust and almost-transparent Schottky diode. The usually dominant forward direction is suppressed, but a characteristic signal occurs in reverse bias. For its theoretical description, we consider tunneling through the light-field–modulated Schottky barrier, complemented by a dynamical accumulation correction. On the basis only of the DC parametrization of the diode, the model provides a consistent and accurate description of the experimentally observed infrared phenomena. This allows the conclusion that cycle-by-cycle dynamics determines rectification. As the chosen materials have proven capabilities for transistors, circuits, and even a full logic, we see a way to establish light-field-driven electronics with rapidly increasing functionality

Thyroxine-thyroid hormone receptor interactions

ABSTRACTThyroid hormone (TH) actions are mediated by nuclear receptors (TRs α and β) that bind triiodothyronine (T3, 3,5,3′-triiodo-l-thyronine) with high affinity, and its precursor thyroxine (T4, 3,5,3′,5′-tetraiodo-l-thyronine) with lower affinity. T4 contains a bulky 5′ iodine group absent from T3. Because T3 is buried in the core of the ligand binding domain (LBD), we have predicted that TH analogues with 5′ substituents should fit poorly into the ligand binding pocket and perhaps behave as antagonists. We therefore examined how T4 affects TR activity and conformation. We obtained several lines of evidence (ligand dissociation kinetics, migration on hydrophobic interaction columns, and non-denaturing gels) that TR-T4 complexes adopt a conformation that differs from TR-T3 complexes in solution. Nonetheless, T4 behaves as an agonist in vitro (in effects on coregulator and DNA binding) and in cells, when conversion to T3 does not contribute to agonist activity. We determined x-ray crystal structures of the TRβ LBD in complex with T3 and T4 at 2.5-Å and 3.1-Å resolution. Comparison of the structures reveals that TRβ accommodates T4 through subtle alterations in the loop connecting helices 11 and 12 and amino acid side chains in the pocket, which, together, enlarge a niche that permits helix 12 to pack over the 5′ iodine and complete the coactivator binding surface. While T3 is the major active TH, our results suggest that T4 could activate nuclear TRs at appropriate concentrations. The ability of TR to adapt to the 5′ extension should be considered in TR ligand design

Cortical Plasticity Induced by Transcranial Magnetic Stimulation during Wakefulness Affects Electroencephalogram Activity during Sleep

BACKGROUND:Sleep electroencephalogram (EEG) brain oscillations in the low-frequency range show local signs of homeostatic regulation after learning. Such increases and decreases of slow wave activity are limited to the cortical regions involved in specific task performance during wakefulness. Here, we test the hypothesis that reorganization of motor cortex produced by long-term potentiation (LTP) affects EEG activity of this brain area during subsequent sleep. METHODOLOGY/PRINCIPAL FINDINGS:By pairing median nerve stimulation with transcranial magnetic stimulation over the contralateral motor cortex, one can potentiate the motor output, which is presumed to reflect plasticity of the neural circuitry. This paired associative stimulation increases M1 cortical excitability at interstimulus intervals of 25 ms. We compared the scalp distribution of sleep EEG power following paired associative stimulation at 25 ms to that following a control paradigm with 50 ms intervals. It is shown that the experimental manipulation by paired associative stimulation at 25 ms induces a 48% increase in amplitude of motor evoked potentials. This LTP-like potentiation, induced during waking, affects delta and theta EEG power in both REM and non-REM sleep, measured during the following night. Slow-wave activity increases in some frontal and prefrontal derivations and decreases at sites neighboring and contralateral to the stimulated motor cortex. The magnitude of increased amplitudes of motor evoked potentials by the paired associative stimulation at 25 ms predicts enhancements of slow-wave activity in prefrontal regions. CONCLUSIONS/SIGNIFICANCE:An LTP-like paradigm, presumably inducing increased synaptic strength, leads to changes in local sleep regulation, as indexed by EEG slow-wave activity. Enhancement and depression of slow-wave activity are interpreted in terms of a simultaneous activation of both excitatory and inhibitory circuits consequent to the paired associative stimulation at 25 ms

Preconditioned extracellular vesicles from hypoxic microglia reduce poststroke AQP4 depolarization, disturbed cerebrospinal fluid flow, astrogliosis, and neuroinflammation

Background: Stroke stimulates reactive astrogliosis, aquaporin 4 (AQP4) depolarization and neuroinflammation. Preconditioned extracellular vesicles (EVs) from microglia exposed to hypoxia, in turn, reduce poststroke brain injury. Nevertheless, the underlying mechanisms of such effects are elusive, especially with regards to inflammation, AQP4 polarization, and cerebrospinal fluid (CSF) flow. Methods: Primary microglia and astrocytes were exposed to oxygen-glucose deprivation (OGD) injury. For analyzing the role of AQP4 expression patterns under hypoxic conditions, a co-culture model of astrocytes and microglia was established. Further studies applied a stroke model, where some mice also received an intracisternal tracer infusion of rhodamine B. As such, these in vivo studies involved the analysis of AQP4 polarization, CSF flow, astrogliosis, and neuroinflammation as well as ischemia-induced brain injury. Results: Preconditioned EVs decreased periinfarct AQP4 depolarization, brain edema, astrogliosis, and inflammation in stroke mice. Likewise, EVs promoted postischemic CSF flow and cerebral blood perfusion, and neurological recovery. Under in vitro conditions, hypoxia stimulated M2 microglia polarization, whereas EVs augmented M2 microglia polarization and repressed M1 microglia polarization even further. In line with this, astrocytes displayed upregulated AQP4 clustering and proinflammatory cytokine levels when exposed to OGD, which was reversed by preconditioned EVs. Reduced AQP4 depolarization due to EVs, however, was not a consequence of unspecific inflammatory regulation, since LPS-induced inflammation in co-culture models of astrocytes and microglia did not result in altered AQP4 expression patterns in astrocytes. Conclusions: These findings show that hypoxic microglia may participate in protecting against stroke-induced brain damage by regulating poststroke inflammation, astrogliosis, AQP4 depolarization, and CSF flow due to EV release

Early onset of ground-state deformation in the neutron-deficient polonium isotopes

In-source resonant ionization laser spectroscopy of the even-$A$ polonium isotopes $^{192-210,216,218}$Po has been performed using the $6p^37s$ $^5S_2$ to $6p^37p$ $^5P_2$ ($\lambda=843.38$ nm) transition in the polonium atom (Po-I) at the CERN ISOLDE facility. The comparison of the measured isotope shifts in $^{200-210}$Po with a previous data set allows to test for the first time recent large-scale atomic calculations that are essential to extract the changes in the mean-square charge radius of the atomic nucleus. When going to lighter masses, a surprisingly large and early departure from sphericity is observed, which is only partly reproduced by Beyond Mean Field calculations.Comment: As submitted to PR