Gut colonization by Proteobacteria alters host metabolism and modulates cocaine neurobehavioral responses

Gut-microbiota membership is associated with diverse neuropsychological outcomes, including substance use disorders (SUDs). Here, we use mice colonized with Citrobacter rodentium or the human γ-Proteobacteria commensal Escherichia coli HS as a model to examine the mechanistic interactions between gut microbes and host responses to cocaine. We find that cocaine exposure increases intestinal norepinephrine levels that are sensed through the bacterial adrenergic receptor QseC to promote intestinal colonization of γ-Proteobacteria. Colonized mice show enhanced host cocaine-induced behaviors. The neuroactive metabolite glycine, a bacterial nitrogen source, is depleted in the gut and cerebrospinal fluid of colonized mice. Systemic glycine repletion reversed, and γ-Proteobacteria mutated for glycine uptake did not alter the host response to cocaine. γ-Proteobacteria modulated glycine levels are linked to cocaine-induced transcriptional plasticity in the nucleus accumbens through glutamatergic transmission. The mechanism outline here could potentially be exploited to modulate reward-related brain circuits that contribute to SUDs.Fil: Cuesta, Santiago. University of Texas. Southwestern Medical Center; Estados UnidosFil: Burdisso, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Segev, Amir. University Of Texas Southwestern Medical School,; Estados Unidos. University of Texas; Estados UnidosFil: Kourrich, Saïd. Université du Québec a Montreal; CanadáFil: Sperandio, Vanessa. University of Texas. Southwestern Medical Center; Estados Unido

Quantum \v{C}erenkov Radiation: Spectral Cutoffs and the Role of Spin and Orbital Angular Momentum

We show that the well-known \v{C}erenkov Effect contains new phenomena arising from the quantum nature of charged particles. The \v{C}erenkov transition amplitudes allow coupling between the charged particle and the emitted photon through their orbital angular momentum (OAM) and spin, by scattering into preferred angles and polarizations. Importantly, the spectral response reveals a discontinuity immediately below a frequency cutoff that can occur in the optical region. Specifically, with proper shaping of electron beams (ebeams), we predict that the traditional \v{C}erenkov radiation angle splits into two distinctive cones of photonic shockwaves. One of the shockwaves can move along a backward cone, otherwise considered impossible for \v{C}erenkov radiation in ordinary matter. Our findings are observable for ebeams with realistic parameters, offering new applications including novel quantum optics sources, and open a new realm for \v{C}erenkov detectors involving the spin and orbital angular momentum of charged particles.Comment: 27 pages, 3 figure

The P4 promoter of the parvovirus minute virus of mice is developmentally regulated in transgenic P4-LacZ mice

AbstractActivation of the minute virus of mice (MVM) P4 promoter is a key step in the life cycle of the virus and is completely dependent on host transcription factors. Since transcription-factor composition varies widely in different cell types, there is the possibility that only some cell types in the host organism have the capacity to initiate expression from the P4 promoter and therefore that the promoter may be a factor in determining the tropism of MVM. In this study, the ability of various cell types to activate P4, independent of the other virus–host interactions, was examined in transgenic mouse lines bearing a β-galactosidase reporter sequence driven by the P4 promoter. It was found that lacZ was expressed during embryogenesis and in the adult in a cell-type-specific and differentiation-dependent pattern. The data are consistent with cell-type and stage-specific activation of the P4 promoter having a role in determining the host cell-type range of MVM. The ability of some parvoviruses to replicate in, and kill oncogenically transformed cells, and to destroy induced tumors in laboratory animals is the basis of recent approaches to use MVM-based vectors in cancer gene therapy. Since these vectors rely on the activation of the P4 promoter by the target tissues, understanding the promoter dependence on cell-type and differentiation status is important for their design and potential use

Nano-sized SQUID-on-tip for scanning probe microscopy

We present a SQUID of novel design, which is fabricated on the tip of a pulled quartz tube in a simple 3-step evaporation process without need for any additional processing, patterning, or lithography. The resulting devices have SQUID loops with typical diameters in the range 75–300 nm. They operate in magnetic fields up to 0.6 T and have flux sensitivity of 1.8 μΦ0/Hz1/2 and magnetic field sensitivity of 10−7 T/Hz1/2, which corresponds to a spin sensitivity of 65 μB/Hz1/2 for aluminum SQUIDs. The shape of the tip and the small area of the SQUID loop, together with its high sensitivity, make our device an excellent tool for scanning SQUID microscopy: With the SQUID-on-tip glued to a tine of a quartz tuning fork, we have succeeded in obtaining magnetic images of a patterned niobium film and of vortices in a superconducting film in a magnetic field.Physic

Apelin Enhances Directed Cardiac Differentiation of Mouse and Human Embryonic Stem Cells

Apelin is a peptide ligand for an orphan G-protein coupled receptor (APJ receptor) and serves as a critical gradient for migration of mesodermal cells fated to contribute to the myocardial lineage. The present study was designed to establish a robust cardiac differentiation protocol, specifically, to evaluate the effect of apelin on directed differentiation of mouse and human embryonic stem cells (mESCs and hESCs) into cardiac lineage. Different concentrations of apelin (50, 100, 500 nM) were evaluated to determine its differentiation potential. The optimized dose of apelin was then combined with mesodermal differentiation factors, including BMP-4, activin-A, and bFGF, in a developmentally specific temporal sequence to examine the synergistic effects on cardiac differentiation. Cellular, molecular, and physiologic characteristics of the apelin-induced contractile embryoid bodies (EBs) were analyzed. It was found that 100 nM apelin resulted in highest percentage of contractile EB for mESCs while 500 nM had the highest effects on hESCs. Functionally, the contractile frequency of mESCs-derived EBs (mEBs) responded appropriately to increasing concentration of isoprenaline and diltiazem. Positive phenotype of cardiac specific markers was confirmed in the apelin-treated groups. The protocol, consisting of apelin and mesodermal differentiation factors, induced contractility in significantly higher percentage of hESC-derived EBs (hEBs), up-regulated cardiac-specific genes and cell surface markers, and increased the contractile force. In conclusion, we have demonstrated that the treatment of apelin enhanced cardiac differentiation of mouse and human ESCs and exhibited synergistic effects with mesodermal differentiation factors

Stress Hormones Receptors in the Amygdala Mediate the Effects of Stress on the Consolidation, but Not the Retrieval, of a Non Aversive Spatial Task

This study examined the effects of the arousal level of the rat and exposure to a behavioral stressor on acquisition, consolidation and retrieval of a non-aversive hippocampal-dependent learning paradigm, the object location task. Learning was tested under two arousal conditions: no previous habituation to the experimental context (high novelty stress/arousal level) or extensive prior habituation (reduced novelty stress/arousal level). Results indicated that in the habituated rats, exposure to an out-of-context stressor (i.e, elevated platform stress) impaired consolidation and retrieval, but not acquisition, of the task. Non-habituated animals under both stressed and control conditions did not show retention of the task. In habituated rats, RU-486 (10 ng/side), a glucocorticoid receptor (GR) antagonist, or propranolol (0.75 µg/side), a beta-adrenergic antagonist, injected into the basolateral amygdala (BLA), prevented the impairing effects of the stressor on consolidation, but not on retrieval. The CB1/CB2 receptor agonist WIN55,212-2 (WIN, 5 µg/side) microinjected into the BLA did not prevent the effects of stress on either consolidation or retrieval. Taken together the results suggest that: (i) GR and β-adrenergic receptors in the BLA mediate the impairing effects of stress on the consolidation, but not the retrieval, of a neutral, non-aversive hippocampal-dependent task, (ii) the impairing effects of stress on hippocampal consolidation and retrieval are mediated by different neural mechanisms (i.e., different neurotransmitters or different brain areas), and (iii) the effects of stress on memory depend on the interaction between several main factors such as the stage of memory processing under investigation, the animal's level of arousal and the nature of the task (neutral or aversive)

Long-Term Relationships between Synaptic Tenacity, Synaptic Remodeling, and Network Activity

Long term time-lapse imaging reveals that individual synapses undergo significant structural remodeling not only when driven by activity, but also when network activity is absent, raising questions about how reliably individual synapses maintain connections