We investigate the emergence of a time crystal (TC) in a driven dissipative many-body spin array. In this system the interplay between incoherent spin pumping and collective emission stabilizes a synchronized non-equilibrium steady state which in the thermodynamic limit features a self-generated time-periodic pattern imposed by collective elastic interactions. In contrast to prior realizations where the time symmetry is already broken by an external drive, here it is only spontaneously broken by the elastic exchange interactions and manifest in the two-time correlation spectrum. Employing a combination of exact numerical calculations and a second-order cumulant expansion, we investigate the impact of many-body correlations on the TC formation and establish a connection between the regime where it is stable and where the system features a slow growth rate of the mutual information. This observation allows us to conclude that the TC studied here is an emergent semi-classical out-of-equilibrium state of matter. We also confirm the rigidity of the TC to single-particle dephasing. Finally, we discuss an experimental implementation using long lived dipoles in an optical cavity.

BackgroundClaudins are transmembrane proteins expressed in tight junctions that prevent paracellular transport of extracellular fluid and a variety of other substances. However, the expression profile of Claudin-6 (Cldn6) in the developing lung has not been characterized.Methods and resultsCldn6 expression was determined during important periods of lung organogenesis by microarray analysis, qPCR and immunofluorescence. Expression patterns were confirmed to peak at E12.5 and diminish as lung development progressed. Immunofluorescence revealed that Cldn6 was detected in cells that also express TTF-1 and FoxA2, two critical transcriptional regulators of pulmonary branching morphogenesis. Cldn6 was also observed in cells that express Sox2 and Sox9, factors that influence cell differentiation in the proximal and distal lung, respectively. In order to assess transcriptional control of Cldn6, 0.5, 1.0, and 2.0-kb of the proximal murine Cldn6 promoter was ligated into a luciferase reporter and co-transfected with expression vectors for TTF-1 or two of its important transcriptional co-regulators, FoxA2 and Gata-6. In almost every instance, TTF-1, FoxA2, and Gata-6 activated gene transcription in cell lines characteristic of proximal airway epithelium (Beas2B) and distal alveolar epithelium (A-549).ConclusionsThese data revealed for the first time that Cldn6 might be an important tight junctional component expressed by pulmonary epithelium during lung organogenesis. Furthermore, Cldn6-mediated aspects of cell differentiation may describe mechanisms of lung perturbation coincident with impaired cell junctions and abnormal membrane permeability.

Manganese exposure produces Parkinson's-like neurologic symptoms, suggesting a selective dysregulation of dopamine transmission. It is unknown, however, how manganese accumulates in dopaminergic brain regions or how it regulates the activity of dopamine neurons. Our in vivo studies in male C57BLJ mice suggest that manganese accumulates in dopamine neurons of the VTA and substantia nigra via nifedipine-sensitive Ca 21 channels. Manganese produces a Ca 21 channel-mediated current, which increases neurotransmitter release and rhythmic firing activity of dopamine neurons. These increases are prevented by blockade of Ca 21 channels and depend on downstream recruitment of Ca 21 -activated potassium channels to the plasma membrane. These findings demonstrate the mechanism of manganese-induced dysfunction of dopamine neurons, and reveal a potential therapeutic target to attenuate manganese-induced impairment of dopamine transmission.

Skeletal muscle represents the largest pool of body zinc, however, little is known about muscle zinc homeostasis or muscle-specific zinc functions. Zip14 (Slc39a14) was the most highly expressed zinc transporter in skeletal muscle of mice in response to LPS-induced inflammation. We compared metabolic parameters of skeletal muscle from global Zip14 knockout (KO) and wild-type mice (WT). At basal steady state Zip14 Ko mice exhibited a phenotype that included muscle wasting and metabolic endotoxemia. Microarray and qpcR analysis of gastrocnemius muscle RnA revealed that ablation of Zip14 produced increased muscle p-Mef2c, Hspb7 and miR-675-5p expression and increased p38 activation. chip assays showed enhanced binding of nf-κβ to the Mef2c promoter. in contrast, LpSinduced systemic inflammation enhanced Zip14-dependent zinc uptake by muscle, increased expression of Atrogin1 and MuRF1 and markedly reduced MyoD. these signatures of muscle atrophy and cachexia were not influenced by Zip14 ablation, however. LpS-induced miR-675-3p and-5p expression was Zip14-dependent. Collectively, these results with an integrative model are consistent with a Zip14 function in skeletal muscle at steady state that supports myogenesis through suppression of metabolic endotoxemia and that Zip14 ablation coincides with sustained activity of phosphorylated components of signaling pathways including p-Mef2c, which causes Hspb7-dependent muscle wasting.