Neuronal nicotinic receptors (NAChRs) form a heterogeneous family of ion channels that are differently expressed in many regions of the central nervous system (CNS) and peripheral nervous system. ...These different receptor subtypes, which have characteristic pharmacological and biophysical properties, have a pentameric structure consisting of the homomeric or heteromeric combination of 12 different subunits (alpha2-alpha10, beta2-beta4). By responding to the endogenous neurotransmitter acetylcholine, NAChRs contribute to a wide range of brain activities and influence a number of physiological functions. Furthermore, it is becoming evident that the perturbation of cholinergic nicotinic neurotransmission can lead to various diseases involving nAChR dysfunction during development, adulthood and ageing. In recent years, it has been discovered that NAChRs are present in a number of non-neuronal cells where they play a significant functional role and are the pathogenetic targets in several diseases. NAChRs are also the target of natural ligands and toxins including nicotine (Nic), the most widespread drug of abuse. This review will attempt to survey the major achievements reached in the study of the structure and function of NAChRs by examining their regional and cellular localisation and the molecular basis of their functional diversity mainly in pharmacological and biochemical terms. The recent availability of mice with the genetic ablation of single or double nicotinic subunits or point mutations have shed light on the role of nAChRs in major physiological functions, and we will here discuss recent data relating to their behavioural phenotypes. Finally, the role of NAChRs in disease will be considered in some details.
The R&D project COSINUS (Cryogenic Observatory for SIgnatures seen in Next-generation Underground Searches) aims to develop a cryogenic scintillating calorimeter using an undoped NaI-crystal as ...target for direct dark matter search. Dark matter particles interacting with the detector material generate both a phonon signal and scintillation light. While the phonon signal provides a precise determination of the deposited energy, the simultaneously measured scintillation light allows for particle identification on an event-by-event basis, a powerful tool to study material-dependent interactions, and to suppress backgrounds. Using the same target material as the DAMA/LIBRA collaboration, the COSINUS technique may offer a unique possibility to investigate and contribute information to the presently controversial situation in the dark matter sector. We report on the dedicated design planned for the NaI proof-of-principle detector and the objectives of using this detection technique in the light of direct dark matter detection.
The signal digitization for CROSS, a bolometric experiment for the search of neutrinoless double beta decay at LSC—Canfranc Underground Laboratory, will be based on a custom solution comprised of an ...analog-to-digital board interfaced to an Altera Cyclone V FPGA module. Each analog-to-digital board hosts 12 channels that allow data digitization up to 25 ksps per channel and an effective resolution of 21 bits at the typical sample rate required by the experiment (5 ksps). The board also allows to digitally select the cutoff frequency of the anti-aliasing filter with 10 bit resolution from 24 Hz up to 2.5 kHz, as required by fast scintillating bolometers. The FPGA is responsible for the synchronization of the analog-to-digital boards and for the data transfer to the storage, using UDP protocol on a standard Ethernet interface. Each FPGA can manage the data coming from eight boards (96 channels), allowing an excellent scalability. In this contribution, we will present a complete overview of the system and a detailed characterization of the system performance.
Background model of the CUPID-0 experiment Azzolini, O.; Beeman, J. W.; Bellini, F. ...
The European physical journal. C, Particles and fields,
07/2019, Volume:
79, Issue:
7
Journal Article
Peer reviewed
Open access
CUPID-0 is the first large mass array of enriched Zn
82
Se scintillating low temperature calorimeters, operated at LNGS since 2017. During its first scientific runs, CUPID-0 collected an exposure of ...9.95 kg year. Thanks to the excellent rejection of
α
particles, we attained the lowest background ever measured with thermal detectors in the energy region where we search for the signature of
82
Se
neutrinoless double beta decay. In this work we develop a model to reconstruct the CUPID-0 background over the whole energy range of experimental data. We identify the background sources exploiting their distinctive signatures and we assess their extremely low contribution down to
∼
10
-
4
counts/(keV kg year) in the region of interest for
82
Se
neutrinoless double beta decay search. This result represents a crucial step towards the comprehension of the background in experiments based on scintillating calorimeters and in next generation projects such as CUPID.
Neuronal nicotinic receptors (nAChRs) are a heterogeneous family of ion channels differently expressed in the nervous system where, by responding to the endogenous neurotransmitter acetylcholine, ...they contribute to a wide range of brain activities and influence a number of physiological functions. Over recent years, the application of newly developed molecular and cellular biological techniques has made it possible to correlate the subunit composition of nAChRs with specific nicotine-elicited behaviours, and refine some of the in vivo physiological functions of nAChR subtypes. The major new findings are the widespread expression of nAChRs, outside the nervous system, their specific and complex organisation, and their relevance to normal brain function. Moreover, the combination of clinical and basic research has better defined the involvement of nAChRs in a growing number of nervous pathologies other than degenerative diseases. However, there are still only a limited number of nicotinic-specific drugs and, although some nicotinic agonists have an interesting pharmacology, their clinical use is limited by undesirable side effects. Some selective nicotinic ligands have recently been developed and used to explore the complexity of nAChR subtype structure and function in the expectation that they will become rational therapeutic alternatives in a number of neurodegenerative, neuropsychiatric and neurological disorders. In this review, we will discuss the molecular basis of brain nAChR structural and functional diversity mainly in pharmacological and biochemical terms, and summarise current knowledge concerning the newly discovered drugs used to classify the numerous receptor subtypes and treat the brain diseases in which nAChRs are involved.
A
bstract
Neutrinoless double-beta decay is a key process in particle physics. Its experimental investigation is the only viable method that can establish the Majorana nature of neutrinos, providing ...at the same time a sensitive inclusive test of lepton number violation. CROSS (Cryogenic Rare-event Observatory with Surface Sensitivity) aims at developing and testing a new bolometric technology to be applied to future large-scale experiments searching for neutrinoless double-beta decay of the promising nuclei
100
Mo and
130
Te. The limiting factor in large-scale bolometric searches for this rare process is the background induced by surface radioactive contamination, as shown by the results of the CUORE experiment. The basic concept of CROSS consists of rejecting this challenging background component by pulse-shape discrimination, assisted by a proper coating of the faces of the crystal containing the isotope of interest and serving as energy absorber of the bolometric detector. In this paper, we demonstrate that ultra-pure superconductive Al films deposited on the crystal surfaces act successfully as pulse-shape modifiers, both with fast and slow phonon sensors. Rejection factors higher than 99.9% of
α
surface radioactivity have been demonstrated in a series of prototypes based on crystals of Li
2
MoO
4
and TeO
2
. We have also shown that point-like energy depositions can be identified up to a distance of
∼
1 mm from the coated surface. The present program envisions an intermediate experiment to be installed underground in the Canfranc laboratory (Spain) in a CROSS-dedicated facility. This experiment, comprising
∼
3
×
10
25
nuclei of
100
Mo, will be a general test of the CROSS technology as well as a worldwide competitive search for neutrinoless double-beta decay, with sensitivity to the effective Majorana mass down to 70 meV in the most favorable conditions.
We present the performances of two 92% enriched 130TeO2 crystals operated as thermal bolometers in view of a next generation experiment to search for neutrinoless double beta decay of 130Te. The ...crystals, 435 g each, show an energy resolution, evaluated at the 2615 keV γ-line of 208Tl, of 6.5 and 4.3 keV FWHM. The only observable internal radioactive contamination arises from 238U (15 and 8 μBq/kg, respectively). The internal activity of the most problematic nuclei for neutrinoless double beta decay, 226Ra and 228Th, are both evaluated as <3.1 μBq/kg for one crystal and <2.3 μBq/kg for the second. Thanks to the readout of the weak Cherenkov light emitted by β/γ particles by means of Neganov–Luke bolometric light detectors we were able to perform an event-by-event identification of β/γ events with a 95% acceptance level, while establishing a rejection factor of 98.21% and 99.99% for α particles.
Abstract Nicotine is the primary addictive substance in tobacco smoke and electronic cigarette (e-cig) vapour. Methodological limitations have made it difficult to compare the role of the nicotine ...and non-nicotine constituents of tobacco smoke. The aim of this study was to compare the effects of traditional cigarette smoke and e-cig vapour containing the same amount of nicotine in male BALB/c mice exposed to the smoke of 21 cigarettes or e-cig vapour containing 16.8 mg of nicotine delivered by means of a mechanical ventilator for three 30-min sessions/day for seven weeks. One hour after the last session, half of the animals were sacrificed for neurochemical analysis, and the others underwent mecamylamine-precipitated or spontaneous withdrawal for the purposes of behavioural analysis. Chronic intermittent non-contingent, second-hand exposure to cigarette smoke or e-cig vapour led to similar brain cotinine and nicotine levels, similar urine cotinine levels and the similar up-regulation of α4β2 nicotinic acetylcholine receptors in different brain areas, but had different effects on body weight, food intake, and the signs of mecamylamine-precipitated and spontaneous withdrawal episodic memory and emotional responses. The findings of this study demonstrate for the first time that e-cig vapour induces addiction-related neurochemical, physiological and behavioural alterations. The fact that inhaled cigarette smoke and e-cig vapour have partially different dependence-related effects indicates that compounds other than nicotine contribute to tobacco dependence.
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