Epigenetics of amphetamine-induced sensitization: HDAC5 expression and microRNA in neural remodeling

Background: Histone deacetylase (HDAC) activities modify chromatin structure and play a role in learning and memory during developmental processes. Studies of adult mice suggest HDACs are involved in neural network remodeling in brain repair, but its function in drug addiction is less understood. We aimed to examine in vivo HDAC5 expression in a preclinical model of amphetamine-induced sensitization (AIS) of behavior. We generated specific contrast agents to measure HDAC5 levels by in vivo molecular contrast-enhanced (MCE) magnetic resonance imaging (MRI) in amphetamine-naïve mice as well as in mice with AIS. To validate the MRI results we used ex vivo methods including in situ hybridization, RT-PCR, immunohistochemistry, and transmision electron microscopy. Methods: We compared the expression of HDAC5 mRNA in an acute exposure paradigm (in which animals experienced a single drug exposure [A1]) and in a chronic-abstinence-challenge paradigm (in which animals were exposed to the drug once every other day for seven doses, then underwent 2 weeks of abstinence followed by a challenge dose [A7WA]). Control groups for each of these exposure paradigms were given saline. To delineate how HDAC5 expression was related to AIS, we compared the expression of HDAC5 mRNA at sequences where no known microRNA (miR) binds (hdac5AS2) and at sequences where miR-2861 is known to bind (miD2861). We synthesized and labeled phosphorothioated oligonucleic acids (sODN) of hdac5AS2 or miD2861 linked to superparamagentic iron oxide nanoparticles (SPION), and generated HDAC5-specific contrast agents (30 ± 20 nm, diameter) for MCE MRI; the same sequences were used for primers for TaqMan® analysis (RT-qPCR) in ex vivo validation. In addition, we used subtraction R2* maps to identify regional HDAC5 expression. Results: Naïve C57black6 mice that experience acute exposure to amphetamine (4 mg/kg, by injection intraperitoneally) show expression of both total and phosphorylated (S259) HDAC5 antigens in GFAP+ and GFAP− cells, but the appearance of these cells was attenuated in the chronic paradigm. We found that MCE MRI reports HDAC5 mRNA with precision in physiological conditions because the HDAC5 mRNA copy number reported by TaqMan analysis was positively correlated (with a linear coefficient of 1.0) to the ΔR2* values (the frequency of signal reduction above background, 1/s) measured by MRI. We observed SPION-mid2861 as electron dense nanoparticles (EDNs) of less than 30 nm in the nucleus of the neurons, macrophages, and microglia, but not in glia and endothelia. We found no preferential distribution in any particular type of neural cells, but observed scattered EDNs of 60–150 nm (dia) in lysosomes. In the acute paradigm, mice pretreated with miD2861 (1.2 mmol/kg, i.p./icv) exhibited AIS similar to that exibited by mice in the chronic exposure group, which exhibited null response to mid2861 pretreatment. Moreover, SPION-miD2861 identified enhanced HDAC5 expression in the lateral septum and the striatum after amphetamine, where we found neurprogenitor cells coexpressing NeuN and GFAP. Conclusions: We conclude that miD2681 targets HDAC5 mRNA with precision similar to that of RT-PCR. Our MCE MRI detects RNA-bound nanoparticles (NPs) in vivo, and ex vivo validation methods confirm that EDNs do not accumulate in any particular cell type. As HDAC5 expression may help nullify AIS and identify progenitor cells, the precise delivery of miD2861 may serve as a vehicle for monitoring network remodeling with target specificity and signal sensitivity after drug exposure that identifies brain repair processes in adult animals. Electronic supplementary material The online version of this article (doi:10.1186/s12929-016-0294-8) contains supplementary material, which is available to authorized users

How quickly can anyons be braided? Or: How I learned to stop worrying about diabatic errors and love the anyon

Topological phases of matter are a potential platform for the storage and processing of quantum information with intrinsic error rates that decrease exponentially with inverse temperature and with the length scales of the system, such as the distance between quasiparticles. However, it is less well-understood how error rates depend on the speed with which non-Abelian quasiparticles are braided. In general, diabatic corrections to the holonomy or Berry's matrix vanish at least inversely with the length of time for the braid, with faster decay occurring as the time-dependence is made smoother. We show that such corrections will not affect quantum information encoded in topological degrees of freedom, unless they involve the creation of topologically nontrivial quasiparticles. Moreover, we show how measurements that detect unintentionally created quasiparticles can be used to control this source of error.Comment: 33 pages, 18 figures, version 3: extended results to general anyon braidin

Examining the Effects of Amino and Thiolate Ligands on the Reactivity and Selectivity of Palladium on Carbon in Hydrogenation Reactions

Heterogeneous catalysts are used widely by chemical and energy industries because they show high reactivity but often suffer from lack of selectivity. On the other hand, ligands are commonly used in homogeneous catalysts to control the reactivity and selectivity; however, the effects of the ligands on the steric and electronic properties of heterogeneous catalysts are less understood. We examine the effects of four different ligands: 1-adamantanethiol, 1-adamantylamine, 1-dodecanethiol, and 1-dodecylamine, for the commercial hydrogenation catalyst palladium on carbon. Hydrogenation reactions are used as a screening tool to see the behavior that the different catalysts exhibit in the presence of unsaturated functional groups. Specifically, we study the hydrogenation of alkynes, carbonyls, nitriles, and nitro functional groups as well as the reductive amination between an aldehyde and an amine. Trends across the reactions are observed and are related back to the properties of the different ligands. In the hydrogenation of diphenylacetylene, the catalyst with 4 equivalents of 1-adamantanethiol as the ligand with respect to palladium shows 73% selectivity towards the alkene product whereas the non-ligated palladium on carbon goes 100% to alkane. This shows how ligands can affect the selectivity of heterogeneous catalysts. As ligands effects are understood more thoroughly, more effective catalysts can be designed for industrial reactions

Securing Birth Certificate Documents with DNA Profiles

The birth certificate is a document used by a person to obtain identification and licensing documents throughout their lifetime. For identity verification, the birth certificate provides limited information to support a person’s claim of identity. Authentication to the birth certificate is strictly a matter of possession. DNA profiling is becoming a commodity analysis that can be done accurately in under two hours with little human intervention. The DNA profile is a superior biometric to add to a birth record because it is stable throughout a person’s life and beyond. Acceptability of universal DNA profiling will depend heavily on privacy and safety concerns. This paper uses the U.S. FBI CODIS profile as a basis to discuss the effectiveness of DNA profiling and to provide a practical basis for a discussion of potential privacy and authenticity controls. As is discussed, adopting DNA profiles to improve document security should be done cautiously

Pro-domain removal in ASP-2 and the cleavage of the amyloid precursor are influenced by pH

BACKGROUND: One of the signatures of Alzheimer's disease is the accumulation of aggregated amyloid protein, Aβ, in the brain. Aβ arises from cleavage of the Amyloid Precursor protein by β and γ secretases, which present attractive candidates for therapeutic targeting. Two β-secretase candidates, ASP-1 and ASP-2, were identified as aspartic proteases, both of which cleave the amyloid precursor at the β-site. These are produced as immature transmembrane proteins containing a pro-segment. RESULTS: ASP-2 expressed in HEK293-cells cleaved the Swedish mutant amyloid precursor at different β-sites at different pHs in vitro. Recent reports show that furin cleaves the pro-peptide of ASP-2, whereas ASP-1 undergoes auto-catalysis. We show that purified recombinant ASP-2 cleaves its own pro-peptide at ph 5 but not pH 8.5 as seen by mass spectrometry, electrophoresis and N-terminal sequencing. CONCLUSION: We suggest that ASP-2 processing as well as activity are influenced by pH, and hence the cellular localisation of the protein may have profound effects on the production of Aβ. These factors should be taken into consideration in the design of potential inhibitors for these enzymes

Realities of mobile learning technologies in foreign language classes

While it is common to assume that our current undergraduates are digital native who are naturally proficient and expect the use of technology, the research base that supports those assumptions is limited. This is especially true of students in foreign language classes. Much of the national research that has been conducted has not focused on specific subsets of students. It is important to address this paucity of research, as instructors, textbook publishers, and other stakeholders must make informed decisions regarding the design and development of curriculum and instructional materials. This article reports a study conducted in exploration of the ownership and use of mobile devices by students in foreign language courses. The study used survey methodology and focus group protocols to investigate what technological devices students have and use for personal and academic activities. Salient findings include the reaffirmation of the need to maintain appropriate pedagogy in light of the latest and greatest technological developments, distinctions between the use of technology for content consumption versus content production, and a distinct preference for a separation between personal and academic activities among digital natives

Evidence of Environmental Quenching at Redshift z ~ 2

We report evidence of environmental quenching among galaxies at redshift ~ 2, namely the probability that a galaxy quenches its star formation activity is enhanced in the regions of space in proximity of other quenched, more massive galaxies. The effect is observed as strong clustering of quiescent galaxies around quiescent galaxies on angular scales \theta < 20 arcsec, corresponding to a proper(comoving) scale of 168 (502) kpc at z = 2. The effect is observed only for quiescent galaxies around other quiescent galaxies; the probability to find star-forming galaxies around quiescent or around star-forming ones is consistent with the clustering strength of galaxies of the same mass and at the same redshift, as observed in dedicated studies of galaxy clustering. The effect is mass dependent in the sense that the quenching probability is stronger for galaxies of smaller mass ($\rm{M_*<10^{10} Msun}$) than for more massive ones, i.e. it follows the opposite trend with mass relative to gravitational galaxy clustering. The spatial scale where the effect is observed suggests these environments are massive halos, in which case the observed effect would likely be satellite quenching. The effect is also redshift dependent in that the clustering strength of quiescent galaxies around other quiescent galaxies at z = 1.6 is ~ 1.7 times larger than that of the galaxies with the same stellar mass at z = 2.6. This redshift dependence allows for a crude estimate of the time scale of environmental quenching of low-mass galaxies, which is in the range 1.5 - 4 Gyr, in broad agreement with other estimates and with our ideas on satellite quenching.Comment: 12 pages, 9 figures, Accepted for publication in Ap

Do They Pursue the Same? A Cross-culture Research on Career Anchor of IT/IS Personnel

While career anchor has been mainly studied in US society; this study extends research to Chinese cultural context to investigate the implications of career anchor in terms of job/career satisfaction and subsequent turnover intention among information technology/information systems (IT/IS) personnel in Taiwan and United Arab Emirates (UAE) societies. Chinese guanxi culture could be plays key roles in shaping career anchor and in affecting employees\u27 assessing their job/career and turnover decision. A survey study will be used for conducted to validate the hypotheses and compare the different with Taiwan and UAE two societies

Method Validation of Functional Magnetic Resonance Imaging and Electrophysiological Recording to Investigate Mechanisms of Vagus Nerve

Vagus nerve stimulation (VNS) is used clinically to treat epilepsy and depression, but its mechanism of action is unknown. Useful techniques to study this are functional magnetic resonance imaging (fMRI) and the local field potential (LFP). fMRI relies on oxygen use in the brain to show areas where neurons are active. The LFP is an electrical signal created by neuron action potentials and other current moving across cell membranes. The most information can be gained when the two methods are used simultaneously, however, this is difficult to do. This study seeks to validate the technique of fMRI-LFP as applied to study the mechanism of VNS. The rat is used as an animal model. Previously collected data is analyzed to determine effects of stimulation on respiration, since this will affect oxygen levels in the blood. Recording electrodes of different materials are tested to find the artifact size created in an MRI environment. Iridium electrodes were found to have the smallest artifact and therefore the best performance. It is unclear whether the stimulation used affects respiration, so a simultaneous fMRI-LFP experiment is needed to interpret fMR images. More work needs to be done before fMRI-LFP recordings can be taken during VNS