Nernst Effect and Anomalous Transport in Cuprates: A Preformed-Pair Alternative to the Vortex Scenario

We address those puzzling experiments in underdoped high $T_c$ superconductors which have been associated with normal state "vortices" and show these data can be understood as deriving from preformed pairs with onset temperature $T^* > T_c$. For uncorrelated bosons in small magnetic fields, and arbitrary $T^*/T_c$, we present the exact contribution to \textit{all} transport coefficients. In the overdoped regime our results reduce to those of standard fluctuation theories ($T^*\approx T_c$). Semi-quantitative agreement with Nernst, ac conductivity and diamagnetic measurements is quite reasonable.Comment: 9 pages, 4 figures; Title, abstract and contents modified, new references added, figures changed, one more figure added; to be published on PR

Biased signaling of lipids and allosteric actions of synthetic molecules for GPR119

AbstractGPR119 is a Gαs-coupled lipid-sensor in the gut, where it mediates release of incretin hormones from the enteroendocrine cells and in pancreatic α-cells, where it releases insulin. Naturally occurring lipids such as monoacylglycerols (MAGs) and N-acylethanolamines (NAEs), like oleoylethanolamide (OEA), activate GPR119, and multiple synthetic ligands have been described. Here, we extend the GPR119 signaling profile to Gαq and Gαi in addition to β-arrestin recruitment and the downstream transcription factors CRE (cAMP response element), SRE (serum response element) and NFAT (nuclear factor of activated T cells). The endogenous OEA and the synthetic AR231453 were full agonists in all pathways except for NFAT, where no ligand-modulation was observed. The potency of AR231453 varied <16-fold (EC50 from 6 to 95nM) across the different signaling pathways, whereas that of OEA varied >175-fold (from 85nM to 15μM) indicating a biased signaling for OEA. The degree of constitutive activity was 1–10%, 10–30% and 30–70% of OEA-induced Emax in Gαi, Gαq and Gαs-driven pathways, respectively. This coincided with the lowest and highest OEA potency observed in Gαi and Gαs-driven pathways, respectively. Incubation for 2h with the 2-MAG-lipase inhibitor JZL84 doubled the constitutive activity, indicating that endogenous lipids contribute to the apparent constitutive activity. Finally, besides being an agonist, AR231453 acted as a positive allosteric modulator of OEA and increased its potency by 54-fold at 100nM AR231453. Our studies uncovering broad and biased signaling, masked constitutive activity by endogenous MAGs, and ago-allosteric properties of synthetic ligands may explain why many GPR119 drug-discovery programs have failed so far

The pseudogap state in superconductors: Extended Hartree approach to time-dependent Ginzburg-Landau Theory

It is well known that conventional pairing fluctuation theory at the Hartree level leads to a normal state pseudogap in the fermionic spectrum. Our goal is to extend this Hartree approximated scheme to arrive at a generalized mean field theory of pseudogapped superconductors for all temperatures $T$. While an equivalent approach to the pseudogap has been derived elsewhere using a more formal Green's function decoupling scheme, in this paper we re-interpret this mean field theory and BCS theory as well, and demonstrate how they naturally relate to ideal Bose gas condensation. Here we recast the Hartree approximated Ginzburg-Landau self consistent equations in a T-matrix form. This recasting makes it possible to consider arbitrarily strong attractive coupling, where bosonic degrees of freedom appear at $T^*$ considerably above $T_c$. The implications for transport both above and below $T_c$ are discussed. Below $T_c$ we find two types of contributions. Those associated with fermionic excitations have the usual BCS functional form. That they depend on the magnitude of the excitation gap, nevertheless, leads to rather atypical transport properties in the strong coupling limit, where this gap (as distinct from the order parameter) is virtually $T$-independent. In addition, there are bosonic terms arising from non-condensed pairs whose transport properties are shown here to be reasonably well described by an effective time-dependent Ginzburg-Landau theory.Comment: 14 pages, 5 figures, REVTeX4, submitted to PRB; clarification of the diagrammatic technique added, one figure update

Critical fluctuation conductivity in layered superconductors in strong electric field

The paraconductivity, originating from critical superconducting order-parameter fluctuations in the vicinity of the critical temperature in a layered superconductor is calculated in the frame of the self-consistent Hartree approximation, for an arbitrarily strong electric field and zero magnetic field. The paraconductivity diverges less steep towards the critical temperature in the Hartree approximation than in the Gaussian one and it shows a distinctly enhanced variation with the electric field. Our results indicate that high electric fields can be effectively used to suppress order-parameter fluctuations in high-temperature superconductors.Comment: 11 pages, 2 figures, to be published in Phys. Rev.

Microscopic theory of the pseudogap and Peierls transition in quasi-one-dimensional materials

The problem of deriving from microscopic theory a Ginzburg-Landau free energy functional to describe the Peierls or charge-density-wave transition in quasi-one-dimensional materials is considered. Particular attention is given to how the thermal lattice motion affects the electronic states. Near the transition temperature the thermal lattice motion produces a pseudogap in the density of states at the Fermi level. Perturbation theory diverges and the traditional quasi-particle or Fermi liquid picture breaks down. The pseudogap causes a significant modification of the coefficients in the Ginzburg-Landau functional from their values in the rigid lattice approximation, which neglects the effect of the thermal lattice motion. To appear in Physical Review B.Comment: 21 pages, RevTeX, 5 figures in uuencoded compressed tar fil

Original Article

Objective: Glucagon is well known to regulate blood glucose but may be equally important for amino acid metabolism. Plasma levels of amino acids are regulated by glucagon-dependent mechanism(s), while amino acids stimulate glucagon secretion from alpha cells, completing the recently described liver-alpha cell axis. The mechanisms underlying the cycle and the possible impact of hepatic steatosis are unclear. Methods: We assessed amino acid clearance in vivo in mice treated with a glucagon receptor antagonist (GRA), transgenic mice with 95% reduction in alpha cells, and mice with hepatic steatosis. In addition, we evaluated urea formation in primary hepatocytes from ob/ob mice and humans, and we studied acute metabolic effects of glucagon in perfused rat livers. We also performed RNA sequencing on livers from glucagon receptor knock-out mice and mice with hepatic steatosis. Finally, we measured individual plasma amino acids and glucagon in healthy controls and in two independent cohorts of patients with biopsy-verified non-alcoholic fatty liver disease (NAFLD). Results: Amino acid clearance was reduced in mice treated with GRA and mice lacking endogenous glucagon (loss of alpha cells) concomitantly with reduced production of urea. Glucagon administration markedly changed the secretion of rat liver metabolites and within minutes increased urea formation in mice, in perfused rat liver, and in primary human hepatocytes. Transcriptomic analyses revealed that three genes responsible for amino acid catabolism (Cps1, Slc7a2, and Slc38a2) were downregulated both in mice with hepatic steatosis and in mice with deletion of the glucagon receptor. Cultured ob/ob hepatocytes produced less urea upon stimulation with mixed amino acids, and amino acid clearance was lower in mice with hepatic steatosis. Glucagon-induced ureagenesis was impaired in perfused rat livers with hepatic steatosis. Patients with NAFLD had hyperglucagonemia and increased levels of glucagonotropic amino acids, including alanine in particular. Both glucagon and alanine levels were reduced after diet-induced reduction in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR, a marker of hepatic steatosis). Conclusions: Glucagon regulates amino acid metabolism both non-transcriptionally and transcriptionally. Hepatic steatosis may impair glucagon-dependent enhancement of amino acid catabolism. (C) 2020 The Author(s). Published by Elsevier GmbH

Acquisition of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) carriage after exposure to systemic antimicrobials during travel: systematic review and meta-analysis

BACKGROUND: International travel is an important risk factor for colonization with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). Antimicrobial use during travel likely amplifies this risk, yet to what extent, and whether it varies by antimicrobial class, has not been established. METHODS: We conducted a systematic review that included prospective cohorts reporting both receipt of systemic antimicrobials and acquired ESBL-PE isolated from stool or rectum during international travel. We performed a random effects meta-analysis to estimate odds of acquiring ESBL-PE due to antimicrobials during travel, overall and by antimicrobial class. RESULTS: Fifteen studies were included. The study population was mainly female travellers from high income countries recruited primarily from travel clinics. Participants travelled most frequently to Asia and Africa with 10% reporting antimicrobial use during travel. The combined odds ratio (OR) for ESBL-PE acquisition during travel was 2.37 for antimicrobial use overall (95% confidence interval [CI], 1.69 to 3.33), but there was substantial heterogeneity between studies. Fluoroquinolones were the antibiotic class associated with the highest combined OR of ESBL-PE acquisition, compared to no antimicrobial use (OR 4.68, 95% CI, 2.34 to 9.37). CONCLUSIONS: The risk of ESBL-PE colonization during travel is increased substantially with exposure to antimicrobials, especially fluoroquinolones. While a small proportion of colonized individuals will develop a resistant infection, there remains the potential for onward spread among returning travellers. Public health efforts to decrease inappropriate antimicrobial usage during travel are warranted