Stress-induced reinstatement of nicotine preference requires dynorphin/kappa opioid activity in the basolateral amygdala

UNLABELLED: The dynorphin (DYN)/kappa-opioid receptor (KOR) system plays a conserved role in stress-induced reinstatement of drug seeking for prototypical substances of abuse. Due to nicotine\u27s high propensity for stress-induced relapse, we hypothesized that stress would induce reinstatement of nicotine seeking-like behavior in a KOR-dependent manner. Using a conditioned place preference (CPP) reinstatement procedure in mice, we show that both foot-shock stress and the pharmacological stressor yohimbine (2 mg/kg, i.p.) induce reinstatement of nicotine CPP in a norbinaltorphimine (norBNI, a KOR antagonist)-sensitive manner, indicating that KOR activity is necessary for stress-induced nicotine CPP reinstatement. After reinstatement testing, we visualized robust c-fos expression in the basolateral amygdala (BLA), which was reduced in mice pretreated with norBNI. We then used several distinct but complementary approaches of locally disrupting BLA KOR activity to assess the role of KORs and KOR-coupled intracellular signaling cascades on reinstatement of nicotine CPP. norBNI injected locally into the BLA prevented yohimbine-induced nicotine CPP reinstatement without affecting CPP acquisition. Similarly, selective deletion of BLA KORs in KOR conditional knock-out mice prevented foot-shock-induced CPP reinstatement. Together, these findings strongly implicate BLA KORs in stress-induced nicotine seeking-like behavior. In addition, we found that chemogenetic activation of Gαi signaling within CaMKIIα BLA neurons was sufficient to induce nicotine CPP reinstatement, identifying an anatomically specific intracellular mechanism by which stress leads to reinstatement. Considered together, our findings suggest that activation of the DYN/KOR system and Gαi signaling within the BLA is both necessary and sufficient to produce reinstatement of nicotine preference. SIGNIFICANCE STATEMENT: Considering the major impact of nicotine use on human health, understanding the mechanisms by which stress triggers reinstatement of drug-seeking behaviors is particularly pertinent to nicotine. The dynorphin (DYN)/kappa-opioid receptor (KOR) system has been implicated in stress-induced reinstatement of drug seeking for other commonly abused drugs. However, the specific role, brain region, and mechanisms that this system plays in reinstatement of nicotine seeking has not been characterized. Here, we report region-specific engagement of the DYN/KOR system and subsequent activation of inhibitory (Gi-linked) intracellular signaling pathways within the basolateral amygdala during stress-induced reinstatement of nicotine preference. We show that the DYN/KOR system is necessary to produce this behavioral state. This work may provide novel insight for the development of therapeutic approaches to prevent stress-related nicotine relapse

p-GaAs nanowire MESFETs with near-thermal limit gating

Difficulties in obtaining high-performance p-type transistors and gate insulator charge-trapping effects present two major challenges for III-V complementary metal-oxide semiconductor (CMOS) electronics. We report a p-GaAs nanowire metal-semiconductor field-effect transistor (MESFET) that eliminates the need for a gate insulator by exploiting the Schottky barrier at the metal-GaAs interface. Our device beats the best-performing p-GaSb nanowire metal-oxide-semiconductor field effect transistor (MOSFET), giving a typical sub-threshold swing of 62 mV/dec, within 4% of the thermal limit, on-off ratio $\sim 10^{5}$, on-resistance ~700 k$\Omega$, contact resistance ~30 k$\Omega$, peak transconductance 1.2 $\mu$S/$\mu$m and high-fidelity ac operation at frequencies up to 10 kHz. The device consists of a GaAs nanowire with an undoped core and heavily Be-doped shell. We carefully etch back the nanowire at the gate locations to obtain Schottky-barrier insulated gates whilst leaving the doped shell intact at the contacts to obtain low contact resistance. Our device opens a path to all-GaAs nanowire MESFET complementary circuits with simplified fabrication and improved performance

Transport and Strong-Correlation Phenomena in Carbon Nanotube Quantum Dots in a Magnetic Field

Transport through carbon nanotube (CNT) quantum dots (QDs) in a magnetic field is discussed. The evolution of the system from the ultraviolet to the infrared is analyzed; the strongly correlated (SC) states arising in the infrared are investigated. Experimental consequences of the physics are presented -- the SC states arising at various fillings are shown to be drastically different, with distinct signatures in the conductance and, in particular, the noise. Besides CNT QDs, our results are also relevant to double QD systems.Comment: 5 pages, 5 figure

Parity lifetime of bound states in a proximitized semiconductor nanowire

Quasiparticle excitations can compromise the performance of superconducting devices, causing high frequency dissipation, decoherence in Josephson qubits, and braiding errors in proposed Majorana-based topological quantum computers. Quasiparticle dynamics have been studied in detail in metallic superconductors but remain relatively unexplored in semiconductor-superconductor structures, which are now being intensely pursued in the context of topological superconductivity. To this end, we introduce a new physical system comprised of a gate-confined semiconductor nanowire with an epitaxially grown superconductor layer, yielding an isolated, proximitized nanowire segment. We identify Andreev-like bound states in the semiconductor via bias spectroscopy, determine the characteristic temperatures and magnetic fields for quasiparticle excitations, and extract a parity lifetime (poisoning time) of the bound state in the semiconductor exceeding 10 ms.Comment: text and supplementary information combine

Social Participation in Relation to Technology Use and Social Deprivation: A Mixed Methods Study Among Older People with and without Dementia

Social participation is a modifiable determinant for health and wellbeing among older people; however, social participation is increasingly dependent on technology use. This study investigated social participation in relation to Everyday Technology use and social deprivation of the living environment, among older people with and without dementia in the United Kingdom. Sixty-four people with dementia and sixty-four people without dementia were interviewed using standardized questionnaires: The Participation in ACTivities and Places OUTside Home Questionnaire and Everyday Technology Use Questionnaire. A mixed methods approach integrated statistical analyses and content analysis of free-text responses, through data visualizations. Small, statistically significant associations were found between social participation and Everyday Technology use outside home, for participants with dementia (Rs = 0.247; p = 0.049) and without dementia (Rs = 0.343; p = 0.006). A small, statistically significant association was identified between social participation and social deprivation in the living environment, among only participants with dementia (Rs = 0.267, p = 0.033). The content analysis and graphical joint display revealed motivators, considerations that require extra attention, and strategies for managing social participation. The results underline how Everyday Technology use can be assistive to social participation but also the need to consider social deprivation of the living environment, especially among people with dementia

Interference effects in electronic transport through metallic single-wall carbon nanotubes

In a recent paper Liang {\it et al.} [Nature {\bf 411}, 665 (2001)] showed experimentally, that metallic nanotubes, strongly coupled to external electrodes, may act as coherent molecular waveguides for electronic transport. The experimental results were supported by theoretical analysis based on the scattering matrix approach. In this paper we analyze theoretically this problem using a real-space approach, which makes it possible to control quality of interface contacts. Electronic structure of the nanotube is taken into account within the tight-binding model. External electrodes and the central part (sample) are assumed to be made of carbon nanotubes, while the contacts between electrodes and the sample are modeled by appropriate on-site (diagonal) and hopping (off-diagonal) parameters. Conductance is calculated by the Green function technique combined with the Landauer formalism. In the plots displaying conductance {\it vs.} bias and gate voltages, we have found typical diamond structure patterns, similar to those observed experimentally. In certain cases, however, we have found new features in the patterns, like a double-diamond sub-structure.Comment: 15 pages, 4 figures. To apear in Phys. Rev.

Maternal nutrient restriction in Guinea pigs leads to fetal growth restriction with evidence for chronic hypoxia

BackgroundWe determined whether maternal nutrient restriction (MNR) in Guinea pigs leading to fetal growth restriction (FGR) impacts markers for tissue hypoxia, implicating a mechanistic role for chronic hypoxia.MethodsGuinea pigs were fed ad libitum (Control) or 70% of the control diet before pregnancy, switching to 90% at mid-pregnancy (MNR). Near term, hypoxyprobe-1 (HP-1), a marker of tissue hypoxia, was injected into pregnant sows. Fetuses were then necropsied and liver, kidney, and placental tissues were processed for erythropoietin (EPO), EPO-receptor (EPOR), and vascular endothelial growth factor (VEGF) protein levels, and for HP-1 immunoreactivity (IR).ResultsFGR-MNR fetuses were 36% smaller with asymmetrical growth restriction compared to controls. EPO and VEGF protein levels were increased in the female FGR-MNR fetuses, providing support for hypoxic stimulus and linkage to increased erythropoiesis, but not in the male FGR-MNR fetuses, possibly reflecting a weaker link between oxygenation and erythropoiesis. HP-1 IR was increased in the liver and kidneys of both male and female FGR-MNR fetuses as an index of local tissue hypoxia, but with no changes in the placenta.ConclusionChronic hypoxia is likely to be an important signaling mechanism for the decreased fetal growth seen with maternal undernutrition and appears to be post-placental in nature

A large community outbreak of waterborne giardiasis- delayed detection in a non-endemic urban area

BACKGROUND: Giardia is not endemic in Norway, and more than 90% of reported cases acquire the infection abroad. In late October 2004, an increase in laboratory confirmed cases of giardiasis was reported in the city of Bergen. An investigation was started to determine the source and extent of the outbreak in order to implement control measures. METHODS: Cases were identified through the laboratory conducting giardia diagnostics in the area. All laboratory-confirmed cases were mapped based on address of residence, and attack rates and relative risks were calculated for each water supply zone. A case control study was conducted among people living in the central area of Bergen using age- and sex matched controls randomly selected from the population register. RESULTS: The outbreak investigation showed that the outbreak started in late August and peaked in early October. A total of 1300 laboratory-confirmed cases were reported. Data from the Norwegian Prescription Database gave an estimate of 2500 cases treated for giardiasis probably linked to the outbreak. There was a predominance of women aged 20–29 years, with few children or elderly. The risk of infection for persons receiving water from the water supply serving Bergen city centre was significantly higher than for those receiving water from other supplies. Leaking sewage pipes combined with insufficient water treatment was the likely cause of the outbreak. CONCLUSION: Late detection contributed to the large public health impact of this outbreak. Passive surveillance of laboratory-confirmed cases is not sufficient for timely detection of outbreaks with non-endemic infections

Active cooling control of the CLEO detector using a hydrocarbon coolant farm

We describe a novel approach to particle-detector cooling in which a modular farm of active coolant-control platforms provides independent and regulated heat removal from four recently upgraded subsystems of the CLEO detector: the ring-imaging Cherenkov detector, the drift chamber, the silicon vertex detector, and the beryllium beam pipe. We report on several aspects of the system: the suitability of using the aliphatic-hydrocarbon solvent PF(TM)-200IG as a heat-transfer fluid, the sensor elements and the mechanical design of the farm platforms, a control system that is founded upon a commercial programmable logic controller employed in industrial process-control applications, and a diagnostic system based on virtual instrumentation. We summarize the system's performance and point out the potential application of the design to future high-energy physics apparatus.Comment: 21 pages, LaTeX, 5 PostScript figures; version accepted for publication in Nuclear Instruments and Methods in Physics Research