Carbon Dots based Tissue Equivalent Dosimeter as an Ionizing Radiation Sensor.

This work explores the potential of carbon dots as a fluorescent probe in the determination of heavy ions and as an electrochemical biosensor. It also discusses how carbon dots can be introduced into the Fricke solution to potentially serve as an ionizing radiation sensor. The study presents a novel tissue equivalent dosimeter carbon dots-based as an ionizing radiation sensor. The methodology for the synthesis of Nitrogen-doped Carbon Dots N-CDs and the characterization of the material are described. The results show that the N-CDs have a high sensitivity to ionizing radiation and can be used as a dosimeter for radiation detection. The study also discusses the limitations and challenges of using carbon dots as a dosimeter for ionizing radiation. Overall, this study provides valuable insights into the potential applications of carbon dots in different fields and highlights the importance of further research in this area.

Improvement of neutron sensitivity for lithium formate EPR dosemeters: a Monte Carlo analysis.

This work presents the computational analysis of the sensitivity improvements that could be achieved in lithium formate monohydrate (LFM) electron paramagnetic resonance (EPR) dosemeters exposed to neutron beams. Monte Carlo (MC) simulations were performed on LFM pellets exposed to neutron beams with different energy spectra at various depths inside a water phantom. Various computations were carried out by considering different enrichments of 6Li inside the LFM matrix as well as addition of different amounts of gadolinium oxide inside the pellet blend. The energy released per unit mass was calculated with the aim of predicting the increase in dose achievable by the addition of sensitizers inside the pellets. As expected, a larger amount of 6Li induces an increase of energy released because of the charged secondary particles (i.e. 3H ions and α-particles) produced after neutron capture. For small depths in water phantom and low-energy neutron spectra the dose increase due to 6Li enrichment is high (more than three orders of magnitude with respect to the case of with 7Li). In case of epithermal neutron beams the energy released in 6Li-enriched LFM compound is smaller but larger than in the case of fast neutron beams. On the other hand, the computational analysis evidenced that gadolinium is less effective than 6Li in improving neutron sensitivity of the LFM pellets. Discussion based on the features of MC transport code is provided. This result suggests that 6Li enrichment of LFM dosemeters would be more effective for neutron sensitivity improvement and these EPR dosemeters could be tested for dosimetric applications in Neutron Capture Therapy.

Perturbation of serine enantiomers homeostasis in the striatum of MPTP-lesioned monkeys and mice reflects the extent of dopaminergic midbrain degeneration.

Loss of dopaminergic midbrain neurons perturbs l-serine and d-serine homeostasis in the post-mortem caudate putamen (CPu) of Parkinson's disease (PD) patients. However, it is unclear whether the severity of dopaminergic nigrostriatal degeneration plays a role in deregulating serine enantiomers' metabolism. Here, through high-performance liquid chromatography (HPLC), we measured the levels of these amino acids in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys and MPTP-plus-probenecid (MPTPp)-treated mice to determine whether and how dopaminergic midbrain degeneration affects the levels of serine enantiomers in various basal ganglia subregions. In addition, in the same brain regions, we measured the levels of key neuroactive amino acids modulating glutamatergic neurotransmission, including l-glutamate, glycine, l-aspartate, d-aspartate, and their precursors l-glutamine, l-asparagine. In monkeys, MPTP treatment produced severe denervation of nigrostriatal dopaminergic fibers (⁓75%) and increased the levels of serine enantiomers in the rostral putamen (rPut), but not in the subthalamic nucleus, and the lateral and medial portion of the globus pallidus. Moreover, this neurotoxin significantly reduced the protein expression of the astrocytic serine transporter ASCT1 and the glycolytic enzyme GAPDH in the rPut of monkeys. Conversely, concentrations of d-serine and l-serine, as well as ASCT1 and GAPDH expression were unaffected in the striatum of MPTPp-treated mice, which showed only mild dopaminergic degeneration (⁓30%). These findings unveil a link between the severity of dopaminergic nigrostriatal degeneration and striatal serine enantiomers concentration, ASCT1 and GAPDH expression. We hypothesize that the up-regulation of d-serine and l-serine levels occurs as a secondary response within a homeostatic loop to support the metabolic and neurotransmission demands imposed by the degeneration of dopaminergic neurons.

Homeostasis of serine enantiomers is disrupted in the post-mortem caudate putamen and cerebrospinal fluid of living Parkinson's disease patients.

L-serine generated in astrocytes plays a pivotal role in modulating essential neurometabolic processes, while its enantiomer, D-serine, specifically regulates NMDA receptor (NMDAR) signalling. Despite their physiological relevance in modulating cerebral activity, serine enantiomers metabolism in Parkinson's disease (PD) remains elusive. Using High-Performance Liquid Chromatography (HPLC), we measured D- and L-serine levels along with other amino acids known to modulate NMDAR function, such as L-glutamate, L-aspartate, D-aspartate, and glycine, in the post-mortem caudate putamen (CPu) and superior frontal gyrus (SFG) of PD patients. Moreover, we examined these amino acids in the cerebrospinal fluid (CSF) of de novo living PD, Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) patients versus subjects with other neurological disorders (OND), used as control. We found higher D-serine and L-serine levels in the CPu of PD patients but not in the SFG, a cerebral region that, in contrast to the CPu, is not innervated by nigral dopaminergic terminals. We also highlighted a significant elevation of both serine enantiomers in the CSF samples from PD but not in those of AD and ALS patients, compared with control subjects. By contrast, none or only minor changes were found in the amount of other NMDAR modulating amino acids. Our findings identify D-serine and L-serine level upregulation as a biochemical signature associated with nigrostriatal dopaminergic degeneration in PD.

Nusinersen mitigates neuroinflammation in severe spinal muscular atrophy patients.

BACKGROUND: Neuroinflammation contributes to the onset and progression of neurodegenerative diseases, but has not been specifically investigated in patients affected by severe and milder forms of spinal muscular atrophy (SMA). METHODS: In this two-center retrospective study, we investigated signatures of neuroinflammation in forty-eight pediatric male and female SMA1 (n = 18), male and female SMA2 (n = 19), and female SMA3 (n = 11) patients, as well as in a limited number of male and female non-neurological control subjects (n = 4). We employed a Bio-Plex multiplex system based on xMAP technology and performed targeted quantitative analysis of a wide range of pro- and anti-inflammatory cytokines (chemokines, interferons, interleukins, lymphokines and tumor necrosis factors) and neurotrophic factors in the cerebrospinal fluid (CSF) of the study cohort before and after Nusinersen treatment at loading and maintenance stages. RESULTS: We find a significant increase in the levels of several pro-inflammatory cytokines (IL-6, IFN-γ, TNF-α, IL-2, IL-8, IL-12, IL-17, MIP-1α, MCP-1, and Eotaxin) and neurotrophic factors (PDGF-BB and VEGF) in the CSF of SMA1 patients relative to SMA2 and SMA3 individuals, who display levels in the range of controls. We also find that treatment with Nusinersen significantly reduces the CSF levels of some but not all of these neuroinflammatory molecules in SMA1 patients. Conversely, Nusinersen increases the CSF levels of proinflammatory G-CSF, IL-8, MCP-1, MIP-1α, and MIP-1ß in SMA2 patients and decreases those of anti-inflammatory IL-1ra in SMA3 patients. CONCLUSIONS: These findings highlight signatures of neuroinflammation that are specifically associated with severe SMA and the neuro-immunomodulatory effects of Nusinersen therapy.

Spinal muscular atrophy (SMA) is an inherited disorder which leads to muscle weakening. Three therapies have recently been developed, including Nusinersen. However, the effect of SMA on the immune system and how this could be affected by Nusinersen is unknown. The immune system protects the body from infection and, in some disorders, misfunctions and damages the body in the absence of infection. Here, we analyze components of the immune system in body fluids from SMA patients before and after treatment with Nusinersen. The immune system was found to be more active in patients with more severe disease. Treatment with Nusinersen reduced the levels of some, but not all of these, components of the immune system. Thus, treatments that impact the immune system might improve symptoms in patients with SMA.

Cytogenetic effects of ß-particles in Allium cepa cells used as a biological indicator for radiation damages.

Analysis of cytogenetics effects of ionizing radiation for flora and fauna is essential to determine the impact on these communities and may produce an efficient warning system to avoid harm to human health. Onion (Allium cepa) is a well-established in vivo standard model, and it is widely used in cytogenetics studies for different environmental pollutants. In this work, onion roots were exposed to 0.04-1.44 Gy of ß-particles from a 90Sr/90Y source. We investigated the capacity of brief external exposures to ß-particles on inducing cytogenetic damages in root meristematic cells of onion aiming to verify if onion can be used as a radiation-sensitive cytogenetic bioindicator. A nonlinear increase in the frequencies of chromosomal aberrations and cells with micronuclei was observed. Onion roots exposed to doses 0.13 Gy or higher of ß-particles showed a significant difference (p<0.05) in these frequencies when compared to the unirradiated group. The frequencies of these endpoints showed to be suitable to assess the difference in the dose of beta radiation received from 0.36 Gy. Our research shows the potential of using cytogenetic effects in Allium cepa cells as a biological indicator for a first screening of genotoxic damages induced by brief external exposures to ß-particles.

Effects of Ionizing Radiation on Flora Ten Years after the Fukushima Dai-ichi Disaster.

The aim of this work is to analyze the effects of ionizing radiation and radionuclides (like 137Cs) in several higher plants located around the Fukushima Dai-ichi Nuclear Power Plant (FNPP), evaluating both their adaptive processes and evolution. After the FNPP accident in March 2011 much attention was focused to the biological consequences of ionizing radiation and radionuclides released in the area surrounding the nuclear plant. This unexpected mishap led to the emission of radionuclides in aerosol and gaseous forms from the power plant, which contaminated a large area, including wild forest, cities, farmlands, mountains, and the sea, causing serious problems. Large quantities of 131I, 137Cs, and 134Cs were detected in the fallout. People were evacuated but the flora continued to be affected by the radiation exposure and by the radioactive dusts' fallout. The response of biota to FNPP irradiation was a complex interaction among radiation dose, dose rate, temporal and spatial variation, varying radiation sensitivities of the different plants' species, and indirect effects from other events. The repeated ionizing radiations, acute or chronic, guarantee an adaptation of the plant species, demonstrating a radio-resistance. Consequently, ionizing radiation affects the genetic structure, especially during chronic irradiation, reducing genetic variability. This reduction is associated with the different susceptibility of plant species to chronic stress. This would confirm the adaptive theory associated with this phenomenon. The effects that ionizing radiation has on different life forms are examined in this review using the FNPP disaster as a case study focusing the attention ten years after the accident.

Hydrogels for Three-Dimensional Ionizing-Radiation Dosimetry.

Radiation-sensitive gels are among the most recent and promising developments for radiation therapy (RT) dosimetry. RT dosimetry has the twofold goal of ensuring the quality of the treatment and the radiation protection of the patient. Benchmark dosimetry for acceptance testing and commissioning of RT systems is still based on ionization chambers. However, even the smallest chambers cannot resolve the steep dose gradients of up to 30-50% per mm generated with the most advanced techniques. While a multitude of systems based, e.g., on luminescence, silicon diodes and radiochromic materials have been developed, they do not allow the truly continuous 3D dose measurements offered by radiation-sensitive gels. The gels are tissue equivalent, so they also serve as phantoms, and their response is largely independent of radiation quality and dose rate. Some of them are infused with ferrous sulfate and rely on the radiation-induced oxidation of ferrous ions to ferric ions (Fricke-gels). Other formulations consist of monomers dispersed in a gelatinous medium (Polyacrylamide gels) and rely on radiation-induced polymerization, which creates a stable polymer structure. In both gel types, irradiation causes changes in proton relaxation rates that are proportional to locally absorbed dose and can be imaged using magnetic resonance imaging (MRI). Changes in color and/or opacification of the gels also occur upon irradiation, allowing the use of optical tomography techniques. In this work, we review both Fricke and polyacrylamide gels with emphasis on their chemical and physical properties and on their applications for radiation dosimetry.

Cerebrospinal fluid and serum d-serine concentrations are unaltered across the whole clinical spectrum of Alzheimer's disease.

The diagnosis of Alzheimer's disease (AD) relies on the presence of amyloidosis and tauopathy, as reflected in cerebrospinal fluid (CSF), independently from the clinical stage. Recently, CSF d-serine has been proposed as a possible new AD biomarker, reflecting dysfunctional activation of neuronal glutamatergic N-methyl-d-aspartate receptor (NMDAR). In this study, we measured blood serum and CSF concentration of two NMDAR modulators, such as d-serine and d-aspartate, in a cohort of drug-free subjects encompassing the whole AD clinical spectrum. In addition, we also analyzed d-serine levels in a cohort of post-mortem AD and control cortex samples. We reported unaltered serum and CSF concentrations of d-serine and d-aspartate in AD patients both during the AD progression and compared to non-demented controls. Accordingly, no correlation was detected between serum or CSF d-serine content and mini-mental state examination or Clinical Dementia Rating. Similarly, cortical d-serine levels were also unaltered in post-mortem samples of AD patients. Overall, our results failed to confirm previous findings indicating the CSF d-serine as a novel biomarker for AD.

Adaptation to ionizing radiation of higher plants: From environmental radioactivity to chernobyl disaster.

The purpose of this work is to highlight the effects of ionizing radiation on the genetic material in higher plants by assessing both adaptive processes as well as the evolution of plant species. The effects that the ionizing radiation has on greenery following a nuclear accident, was examined by taking the Chernobyl Nuclear Power Plant disaster as a case study. The genetic and evolutionary effects that ionizing radiation had on plants after the Chernobyl accident were highlighted. The response of biota to Chernobyl irradiation was a complex interaction among radiation dose, dose rate, temporal and spatial variation, varying radiation sensitivities of the different plants' species, and indirect effects from other events. Ionizing radiation causes water radiolysis, generating highly reactive oxygen species (ROS). ROS induce the rapid activation of detoxifying enzymes. DeoxyriboNucleic Acid (DNA) is the object of an attack by both, the hydroxyl ions and the radiation itself, thus triggering a mechanism both direct and indirect. The effects on DNA are harmful to the organism and the long-term development of the species. Dose-dependent aberrations in chromosomes are often observed after irradiation. Although multiple DNA repair mechanisms exist, double-strand breaks (DSBs or DNA-DSBs) are often subject to errors. Plants DSBs repair mechanisms mainly involve homologous and non-homologous dependent systems, the latter especially causing a loss of genetic information. Repeated ionizing radiation (acute or chronic) ensures that plants adapt, demonstrating radioresistance. An adaptive response has been suggested for this phenomenon. As a result, ionizing radiation influences the genetic structure, especially during chronic irradiation, reducing genetic variability. This reduction may be associated with the fact that particular plant species are more subject to chronic stress, confirming the adaptive theory. Therefore, the genomic effects of ionizing radiation demonstrate their likely involvement in the evolution of plant species.

Enhancing Radiation Detection by Drones through Numerical Fluid Dynamics Simulations.

This study addresses the optimization of the location of a radioactive-particle sensor on a drone. Based on the analysis of the physical process and of the boundary conditions introduced in the model, computational fluid dynamics simulations were performed to analyze how the turbulence caused by drone propellers may influence the response of the sensors. Our initial focus was the detection of a small amount of radioactivity, such as that associated with a release of medical waste. Drones equipped with selective low-cost sensors could be quickly sent to dangerous areas that first responders might not have access to and be able to assess the level of danger in a few seconds, providing details about the source terms to Radiological-Nuclear (RN) advisors and decision-makers. Our ultimate application is the simulation of complex scenarios where fluid-dynamic instabilities are combined with elevated levels of radioactivity, as was the case during the Chernobyl and Fukushima nuclear power plant accidents. In similar circumstances, accurate mapping of the radioactive plume would provide invaluable input-data for the mathematical models that can predict the dispersion of radioactivity in time and space. This information could be used as input for predictive models and decision support systems (DSS) to get a full situational awareness. In particular, these models may be used either to guide the safe intervention of first responders or the later need to evacuate affected regions.

Optimization of oncological ¹8F-FDG PET/CT imaging based on a multiparameter analysis.

PURPOSE: This paper describes a method to achieve consistent clinical image quality in (18)F-FDG scans accounting for patient habitus, dose regimen, image acquisition, and processing techniques. METHODS: Oncological PET/CT scan data for 58 subjects were evaluated retrospectively to derive analytical curves that predict image quality. Patient noise equivalent count rate and coefficient of variation (CV) were used as metrics in their analysis. Optimized acquisition protocols were identified and prospectively applied to 179 subjects. RESULTS: The adoption of different schemes for three body mass ranges (<60 kg, 60-90 kg, >90 kg) allows improved image quality with both point spread function and ordered-subsets expectation maximization-3D reconstruction methods. The application of this methodology showed that CV improved significantly (p < 0.0001) in clinical practice. CONCLUSIONS: Consistent oncological PET/CT image quality on a high-performance scanner was achieved from an analysis of the relations existing between dose regimen, patient habitus, acquisition, and processing techniques. The proposed methodology may be used by PET/CT centers to develop protocols to standardize PET/CT imaging procedures and achieve better patient management and cost-effective operations.

Rhes influences striatal cAMP/PKA-dependent signaling and synaptic plasticity in a gender-sensitive fashion.

Mechanisms of gender-specific synaptic plasticity in the striatum, a brain region that controls motor, cognitive and psychiatric functions, remain unclear. Here we report that Rhes, a GTPase enriched in medium spiny neurons (MSNs) of striatum, alters the striatal cAMP/PKA signaling cascade in a gender-specific manner. While Rhes knockout (KO) male mice, compared to wild-type (WT) mice, had a significant basal increase of cAMP/PKA signaling pathway, the Rhes KO females exhibited a much stronger response of this pathway, selectively under the conditions of dopamine/adenosine-related drug challenge. Corticostriatal LTP defects are exclusively found in A2AR/D2R-expressing MSNs of KO females, compared to KO males, an effect that is abolished by PKA inhibitors but not by the removal of circulating estrogens. This suggests that the synaptic alterations found in KO females could be triggered by an aberrant A2AR/cAMP/PKA activity, but not due to estrogen-mediated effect. Consistent with increased cAMP signaling, D1R-mediated motor stimulation, haloperidol-induced catalepsy and caffeine-evoked hyper-activity are robustly enhanced in Rhes KO females compared to mutant males. Thus Rhes, a thyroid hormone-target gene, plays a relevant role in gender-specific synaptic and behavioral responses.

Evaluation of air photoactivation at linear accelerators for radiotherapy.

High-energy x-rays produced by radiotherapy accelerators operating at potentials above 10 MV may activate the air via (γ, n) reactions with both oxygen and nitrogen. While the activation products are relatively short-lived, personnel entering the accelerator room may inhale some radioactive air, which warrants internal dosimetry assessments. This work illustrates a method based on the use of ammonium nitrate solutions for the evaluation of photon-induced air activation and for the estimate of internal doses to radiotherapy personnel. Air activation and internal dosimetry assessments based on our method are presented for some widespread radiotherapy linear accelerator models. Our results indicate that the equivalent dose to the lungs of radiotherapy personnel is negligible for beam energies below 18 MeV.

Characterization of a low-cost PIN photodiode for dosimetry in diagnostic radiology.

A commercial silicon PIN-photodiode was tested and characterized as ionizing radiation detector for radiological applications. A current-to-voltage amplification stage was designed and realized in order to acquire the photodiode signal in current mode. The system was tested with clinical beams routinely used for radiography and mammography. A Monte Carlo simulation of the detector was performed with the MCNPX code in order to model and fully understand, in particular, the impact of the sensor casing on the low energy response of the device. A reproducible output linearity was found over the dose range 0.03-4.5 mGy of great clinical relevance. The system sensitivity was found to be stable at 0.2 V s Gy(-1) for effective X-ray energies between 17 and 40 keV. The batch-to-batch reproducibility of the diodes was also experimentally investigated for two different batches of 14 diodes each. An inter-comparison with dosimeters routinely used in medical physics (i.e. Barracuda MPD RTI) showed a linear correlation between PIN-photodiode readout and absorbed dose measured with Barracuda, in the range of doses received by mammography and radiology patients.

Using SUV as a guide to 18F-FDG dose reduction.

UNLABELLED: This article explores how one can lower the injected (18)F-FDG dose while maintaining validity in comparing standardized uptake values (SUVs) between studies. Variations of the SUV within each lesion were examined at different acquisition times. METHODS: Our protocol was approved by either the Human Investigation Committee or the Institutional Review Board. All 120 PET datasets were acquired continuously for 180 s per bed position in list mode and were reconstructed to obtain 30-, 60-, 90-, 120-, 150-, and 180-s-per-bed-position PET images with registration to a single set of nondiagnostic CT images. Qualitative assessment of the images was performed separately for correlation. The SUV measurements of each lesion were computed and normalized to the 180-s acquisition values to create a stabilization factor. These stabilization factors were used to demonstrate a predictable trend of stabilization over time. The variances of the stabilization factors over the entire dataset, composed of several tumor types over a range of sizes, were compared for each time point with the corresponding 150-s time point using a 2-sided F test, which has similar values to the 180-s time point. RESULTS: The variance of the data decreased with increasing acquisition time and with increasing dose but leveled off for sufficiently long acquisitions. CONCLUSION: Through the statistical analysis of SUVs for increasing acquisition times and visual evaluation of the plots, we developed and hereby propose an algorithm that can be used to seek the maximum reduction in administered (18)F-FDG dose while preserving the validity of SUV comparisons.

Role of aberrant striatal dopamine D1 receptor/cAMP/protein kinase A/DARPP32 signaling in the paradoxical calming effect of amphetamine.

Attention deficit/hyperactivity disorder (ADHD) is characterized by inattention, impulsivity, and motor hyperactivity. Several lines of research support a crucial role for the dopamine transporter (DAT) gene in this psychiatric disease. Consistently, the most commonly prescribed medications in ADHD treatment are stimulant drugs, known to preferentially act on DAT. Recently, a knock-in mouse [DAT-cocaine insensitive (DAT-CI)] has been generated carrying a cocaine-insensitive DAT that is functional but with reduced dopamine uptake function. DAT-CI mutants display enhanced striatal extracellular dopamine levels and basal motor hyperactivity. Herein, we showed that DAT-CI animals present higher striatal dopamine turnover, altered basal phosphorylation state of dopamine and cAMP-regulated phosphoprotein 32 kDa (DARPP32) at Thr75 residue, but preserved D(2) receptor (D(2)R) function. However, although we demonstrated that striatal D(1) receptor (D(1)R) is physiologically responsive under basal conditions, its stimulus-induced activation strikingly resulted in paradoxical electrophysiological, behavioral, and biochemical responses. Indeed, in DAT-CI animals, (1) striatal LTP was completely disrupted, (2) R-(+)-6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF 81297) treatment induced paradoxical motor calming effects, and (3) SKF 81297 administration failed to increase cAMP/protein kinase A (PKA)/DARPP32 signaling. Such biochemical alteration selectively affected dopamine D(1)Rs since haloperidol, by blocking the tonic inhibition of D(2)R, unmasked a normal activation of striatal adenosine A(2A) receptor-mediated cAMP/PKA/DARPP32 cascade in mutants. Most importantly, our studies highlighted that amphetamine, nomifensine, and bupropion, through increased striatal dopaminergic transmission, are able to revert motor hyperactivity of DAT-CI animals. Overall, our results suggest that the paradoxical motor calming effect induced by these drugs in DAT-CI mutants depends on selective aberrant phasic activation of D(1)R/cAMP/PKA/DARPP32 signaling in response to increased striatal extracellular dopamine levels.

Dopamine D2 receptor dysfunction is rescued by adenosine A2A receptor antagonism in a model of DYT1 dystonia.

DYT1 dystonia is an inherited disease linked to mutation in the TOR1A gene encoding for the protein torsinA. Although the mechanism by which this genetic alteration leads to dystonia is unclear, multiple lines of clinical evidence suggest a link between dystonia and a reduced dopamine D2 receptor (D2R) availability. Based on this evidence, herein we carried out a comprehensive analysis of electrophysiological, behavioral and signaling correlates of D2R transmission in transgenic mice with the DYT1 dystonia mutation. Electrophysiological recordings from nigral dopaminergic neurons showed a normal responsiveness to D2-autoreceptor function. Conversely, postsynaptic D2R function in hMT mice was impaired, as suggested by the inability of a D2R agonist to re-establish normal corticostriatal synaptic plasticity and supported by the reduced sensitivity to haloperidol-induced catalepsy. Although an in situ hybridization analysis showed normal D1R and D2R mRNA expression levels in the striata of hMT mice, we found a significant decrease of D2R protein, coupled to a reduced ability of D2Rs to activate their cognate Go/i proteins. Of relevance, we found that pharmacological blockade of adenosine A2A receptors (A2ARs) fully restored the impairment of synaptic plasticity observed in hMT mice. Together, our findings demonstrate an important link between torsinA mutation and D2R dysfunction and suggest that A2AR antagonism is able to counteract the deficit in D2R-mediated transmission observed in mutant mice, opening new perspectives for the treatment of this movement disorder.

The GTP-binding protein Rhes modulates dopamine signalling in striatal medium spiny neurons.

Rhes is a small GTP-binding protein prominently localized in the striatum. Previous findings obtained in cell culture systems demonstrated an involvement of Rhes in cAMP/PKA signalling pathway, at a level proximal to the activation of heterotrimeric G-protein complex. However, its role in the striatum has been, so far, only supposed. Here we studied the involvement of Rhes in dopaminergic signalling, by employing mice with a null mutation in the Rhes gene. We demonstrated that the absence of Rhes modulates cAMP/PKA signalling in both striatopallidal and striatonigral projection neurons by increasing Golf protein levels and, in turn, influencing motor responses challenged by dopaminergic agonist/antagonist. Interestingly, we also show that Rhes is required for a correct dopamine-mediated GTP binding, a function mainly associated to stimulation of dopamine D2 receptors. Altogether, our results indicate that Rhes is an important modulator of dopaminergic transmission in the striatum.

Some developments in neutron and charged particle dosimetry.

There is an increasing need for dosimetry of neutrons and charged particles. Increasing exposure levels are reported in the nuclear industry, deriving from more frequent in-service entries at commercial nuclear power plants, and from increased plant decommissioning and refurbishment activities. Another need stems from the compliance with requirements of the regulations and standards. The European Council directive 96/29 requires dosimetric precautions if the effective dose exceeds 1 mSv a(-1). On average, aircrew members exceed this value. Further, there is a trend of increasing use of charged particles in radiotherapy. The present situation is that we have reasonably good photon dosemeters, but neutron and charged particle dosemeters are still in need of improvements. This work highlights some of the developments in this field. It is mainly concentrated on some developments in passive dosimetry, in particular thermally and optically stimulated luminescent detectors, indicating the direction of ongoing research. It shows that passive dosemeters are still a very active field. Active dosemeters will not be discussed with the exception of new developments in microdosimetric measurements [new types of tissue equivalent proportional counters (TEPCs)]. The TEPC is unique in its ability to provide a simultaneous determination of neutron / charged particle / gamma ray doses, or dose equivalents using a single detector.