24 research outputs found
Diffusion and Current of Brownian Particles in Tilted Piecewise Linear Potentials: Amplification and Coherence
Overdamped motion of Brownian particles in tilted piecewise linear periodic
potentials is considered. Explicit algebraic expressions for the diffusion
coefficient, current, and coherence level of Brownian transport are derived.
Their dependencies on temperature, tilting force, and the shape of the
potential are analyzed. The necessary and sufficient conditions for the
non-monotonic behavior of the diffusion coefficient as a function of
temperature are determined. The diffusion coefficient and coherence level are
found to be extremely sensitive to the asymmetry of the potential. It is
established that at the values of the external force, for which the enhancement
of diffusion is most rapid, the level of coherence has a wide plateau at low
temperatures with the value of the Peclet factor 2. An interpretation of the
amplification of diffusion in comparison with free thermal diffusion in terms
of probability distribution is proposed.Comment: To appear in PR
Spatial Symmetry of Superconducting Gap in YBa2Cu3O7-\delta Obtained from Femtosecond Spectroscopy
The polarized femtosecond spectroscopies obtained from well characterized
(100) and (110) YBa2Cu3O7-\delta thin films are reported. This bulk-sensitive
spectroscopy, combining with the well-textured samples, serves as an effective
probe to quasiparticle relaxation dynamics in different crystalline
orientations. The significant anisotropy in both the magnitude of the
photoinduced transient reflectivity change and the characteristic relaxation
time indicates that the nature of the relaxation channel is intrinsically
different in various axes and planes. By the orientation-dependent analysis,
d-wave symmetry of the bulk-superconducting gap in cuprate superconductors
emerges naturally.Comment: 8 pages, 4 figures. To be published in Physical Review B, Rapid
Communication
Microanatomy of the Human Atherosclerotic Plaque by Single-Cell Transcriptomics
RATIONALE: Atherosclerotic lesions are known for their cellular heterogeneity, yet the molecular complexity within the cells of
human plaques has not been fully assessed.
OBJECTIVE: Using single-cell transcriptomics and chromatin accessibility, we gained a better understanding of the
pathophysiology underlying human atherosclerosis.
METHODS AND RESULTS: We performed single-cell RNA and single-cell ATAC sequencing on human carotid atherosclerotic
plaques to define the cells at play and determine their transcriptomic and epigenomic characteristics. We identified 14
distinct cell populations including endothelial cells, smooth muscle cells, mast cells, B cells, myeloid cells, and T cells and
identified multiple cellular activation states and suggested cellular interconversions. Within the endothelial cell population,
we defined subsets with angiogenic capacity plus clear signs of endothelial to mesenchymal transition. CD4+ and CD8+
T cells showed activation-based subclasses, each with a gradual decline from a cytotoxic to a more quiescent phenotype.
Myeloid cells included 2 populations of proinflammatory macrophages showing IL (interleukin) 1B or TNF (tumor necrosis
factor) expression as well as a foam cell-like population expressing TREM2 (triggering receptor expressed on myeloid
cells 2) and displaying a fibrosis-promoting phenotype. ATACseq data identified specific transcription factors associated
with the myeloid subpopulation and T cell cytokine profiles underlying mutual activation between both cell types. Finally,
cardiovascular disease susceptibility genes identified using public genome-wide association studies data were particularly
enriched in lesional macrophages, endothelial, and smooth muscle cells.
CONCLUSIONS: This study provides a transcriptome-based cellular landscape of human atherosclerotic plaques and highlights
cellular plasticity and intercellular communication at the site of disease. This detailed definition of cell communities at play
in atherosclerosis will facilitate cell-based mapping of novel interventional targets with direct functional relevance for the
treatment of human diseas
Amino Acid Availability Controls TRB3 Transcription in Liver through the GCN2/eIF2α/ATF4 Pathway
In mammals, plasma amino acid concentrations are markedly affected by dietary or pathological conditions. It has been well established that amino acids are involved in the control of gene expression. Up to now, all the information concerning the molecular mechanisms involved in the regulation of gene transcription by amino acid availability has been obtained in cultured cell lines. The present study aims to investigate the mechanisms involved in transcriptional activation of the TRB3 gene following amino acid limitation in mice liver. The results show that TRB3 is up-regulated in the liver of mice fed a leucine-deficient diet and that this induction is quickly reversible. Using transient transfection and chromatin immunoprecipitation approaches in hepatoma cells, we report the characterization of a functional Amino Acid Response Element (AARE) in the TRB3 promoter and the binding of ATF4, ATF2 and C/EBPβ to this AARE sequence. We also provide evidence that only the binding of ATF4 to the AARE plays a crucial role in the amino acid-regulated transcription of TRB3. In mouse liver, we demonstrate that the GCN2/eIF2α/ATF4 pathway is essential for the induction of the TRB3 gene transcription in response to a leucine-deficient diet. Therefore, this work establishes for the first time that the molecular mechanisms involved in the regulation of gene transcription by amino acid availability are functional in mouse liver
Trib3 is developmentally and nutritionally regulated in the brain but is dispensable for spatial memory, fear conditioning and sensing of amino acid-imbalanced diet.
Tribbles homolog 3 (TRIB3) is a mammalian pseudokinase that is induced in neuronal cell cultures in response to cell death-inducing stresses, including neurotrophic factor deprivation. TRIB3 is an inhibitor of activating transcription factor 4 (ATF4), the central transcriptional regulator in the eukaryotic translation initiation factor 2α (eIF2α) phosphorylation pathway that is involved in the cellular stress response and behavioral processes. In this article, we study the expression of Trib3 in the mouse brain, characterize the brain morphology of mice with a genetic ablation of Trib3 and investigate whether Trib3 deficiency alters eIF2α-dependent cognitive abilities. Our data show that the consumption of a leucine-deficient diet induces Trib3 expression in the anterior piriform cortex, the brain region responsible for detecting essential amino acid intake imbalance. However, the aversive response to leucine-devoid diet does not differ in Trib3 knockout and wild type mice. Trib3 deletion also does not affect long-term spatial memory and reversal learning in the Morris water maze and auditory or contextual fear conditioning. During embryonic development, Trib3 expression increases in the brain and persists in the early postnatal stadium. Neuroanatomical characterization of mice lacking Trib3 revealed enlarged lateral ventricles. Thus, although the absence of Trib3 does not alter the eIF2α pathway-dependent cognitive functions of several areas of the brain, including the hippocampus, amygdala and anterior piriform cortex, Trib3 may serve a role in other central nervous system processes and molecular pathways
The angiopoietin receptor Tie2 is atheroprotective in arterial endothelium
Leukocytes and resident cells in the arterial wall contribute to atherosclerosis, especially at sites of disturbed blood flow. Expression of endothelial Tie1 receptor tyrosine kinase is enhanced at these sites, and attenuation of its expression reduces atherosclerotic burden and decreases inflammation. However, Tie2 tyrosine kinase function in atherosclerosis is unknown. Here we provide genetic evidence from humans and from an atherosclerotic mouse model to show that TIE2 is associated with protection from coronary artery disease. We show that deletion of Tie2, or both Tie2 and Tie1, in the arterial endothelium promotes atherosclerosis by increasing Foxo1 nuclear localization, endothelial adhesion molecule expression and accumulation of immune cells. We also show that Tie2 is expressed in a subset of aortic fibroblasts, and its silencing in these cells increases expression of inflammation-related genes. Our findings indicate that unlike Tie1, the Tie2 receptor functions as the dominant endothelial angiopoietin receptor that protects from atherosclerosis.Peer reviewe