Possible modulation of dopaminergic neurotransmission function by acetyl-L-carnitine

Acetyl‐L‐Carnitine (ALC) has a putative neuroprotective effect being used in a variety of conditions. Nevertheless, the underlying molecular mechanisms, particularly regarding the induction of changes in neurotransmitter systems, are still not fully understood. We aim to contribute for the elucidation of the mechanisms by which ALC alters neurotransmitter release, using a cell line and an animal model of exposure to methamphetamine (METH). PC12 cells were incubated with several doses of ALC (0.01 to 1.0 mM) alone or in combination with METH 1.0 or 100 µM for 24h or 72h. When combined, ALC preceded METH administration in 30 minutes. Dopamine (DA) content was determined by high performance liquid chromatography. C57BL/6J mice were used for in vivo assays to assess DA striatal binding. Mice were divided into 4 groups, according to different treatments: group 1 (control), group 2 (ALC, 100 mg/kg), group 3 (METH, 10 mg/kg) and group 4 (ALC+METH). Images were acquired in a SPECT/CT scanner (NanoSPECT/CT, Mediso, Hungary) 70 minutes after 123I‐IBZM injection. Regions of interest were drawn in the striata and in the cerebellum to determine the striatal binding ratio. Increased intracellular levels of DA were observed in PC12 cells at 24h and 72h after the administration of ALC. Cells treated with METH 100 µM displayed decreased intracellular levels of DA. ALC prevented the METH‐induced decrease in DA concentration (p<0.0001). On the other hand, a single dose of 10 mg/kg of METH induced a decrease in striatal D2R binding ratios comparing to control group (between 20% and 30%). Interestingly, over time, ALC was able to reverse the decrease on the radiotracer binding induced by METH. The present study indicates a possible effect of ALC over METH‐induced DA release.info:eu-repo/semantics/publishedVersio

DNA methylation-associated colonic mucosal immune and defense responses in treatment-naïve pediatric ulcerative colitis

Inflammatory bowel diseases (IBD) are emerging globally, indicating that environmental factors may be important in their pathogenesis. Colonic mucosal epigenetic changes, such as DNA methylation, can occur in response to the environment and have been implicated in IBD pathology. However, mucosal DNA methylation has not been examined in treatment-naïve patients. We studied DNA methylation in untreated, left sided colonic biopsy specimens using the Infinium HumanMethylation450 BeadChip array. We analyzed 22 control (C) patients, 15 untreated Crohn’s disease (CD) patients, and 9 untreated ulcerative colitis (UC) patients from two cohorts. Samples obtained at the time of clinical remission from two of the treatment-naïve UC patients were also included into the analysis. UC-specific gene expression was interrogated in a subset of adjacent samples (5 C and 5 UC) using the Affymetrix GeneChip PrimeView Human Gene Expression Arrays. Only treatment-naïve UC separated from control. One-hundred-and-twenty genes with significant expression change in UC (> 2-fold, P &lt; 0.05) were associated with differentially methylated regions (DMRs). Epigenetically associated gene expression changes (including gene expression changes in the IFITM1, ITGB2, S100A9, SLPI, SAA1, and STAT3 genes) were linked to colonic mucosal immune and defense responses. These findings underscore the relationship between epigenetic changes and inflammation in pediatric treatment-naïve UC and may have potential etiologic, diagnostic, and therapeutic relevance for IBD

Precision atomic gravimeter based on Bragg diffraction

We present a precision gravimeter based on coherent Bragg diffraction of freely falling cold atoms. Traditionally, atomic gravimeters have used stimulated Raman transitions to separate clouds in momentum space by driving transitions between two internal atomic states. Bragg interferometers utilize only a single internal state, and can therefore be less susceptible to environmental perturbations. Here we show that atoms extracted from a magneto-optical trap using an accelerating optical lattice are a suitable source for a Bragg atom interferometer, allowing efficient beamsplitting and subsequent separation of momentum states for detection. Despite the inherently multi-state nature of atom diffraction, we are able to build a Mach-Zehnder interferometer using Bragg scattering which achieves a sensitivity to the gravitational acceleration of $\Delta g/g = 2.7\times10^{-9}$ with an integration time of 1000s. The device can also be converted to a gravity gradiometer by a simple modification of the light pulse sequence.Comment: 13 pages, 11 figure

Precise wavefunction engineering with magnetic resonance

Controlling quantum fluids at their fundamental length scale will yield superlative quantum simulators, precision sensors, and spintronic devices. This scale is typically below the optical diffraction limit, precluding precise wavefunction engineering using optical potentials alone. We present a protocol to rapidly control the phase and density of a quantum fluid down to the healing length scale using strong time-dependent coupling between internal states of the fluid in a magnetic field gradient. We demonstrate this protocol by simulating the creation of a single stationary soliton and double soliton states in a Bose-Einstein condensate with control over the individual soliton positions and trajectories, using experimentally feasible parameters. Such states are yet to be realized experimentally, and are a path towards engineering soliton gases and exotic topological excitations.Comment: 8+ pages, 3 figures; revised parameters and added section about optimisation of adiabatic, finite-duration pulses and analytic resolution limi