First Directional Measurement of Sub-MeV Solar Neutrinos with Borexino.

We report the measurement of sub-MeV solar neutrinos through the use of their associated Cherenkov radiation, performed with the Borexino detector at the Laboratori Nazionali del Gran Sasso. The measurement is achieved using a novel technique that correlates individual photon hits of events to the known position of the Sun. In an energy window between 0.54 to 0.74 MeV, selected using the dominant scintillation light, we have measured 10 887_{-2103}^{+2386}(stat)±947(syst) (68% confidence interval) solar neutrinos out of 19 904 total events. This corresponds to a ^{7}Be neutrino interaction rate of 51.6_{-12.5}^{+13.9} counts/(day·100 ton), which is in agreement with the standard solar model predictions and the previous spectroscopic results of Borexino. The no-neutrino hypothesis can be excluded with >5σ confidence level. For the first time, we have demonstrated the possibility of utilizing the directional Cherenkov information for sub-MeV solar neutrinos, in a large-scale, high light yield liquid scintillator detector. This measurement provides an experimental proof of principle for future hybrid event reconstruction using both Cherenkov and scintillation signatures simultaneously.

Improved Measurement of Solar Neutrinos from the Carbon-Nitrogen-Oxygen Cycle by Borexino and Its Implications for the Standard Solar Model.

We present an improved measurement of the carbon-nitrogen-oxygen (CNO) solar neutrino interaction rate at Earth obtained with the complete Borexino Phase-III dataset. The measured rate, R_{CNO}=6.7_{-0.8}^{+2.0} counts/(day×100 tonnes), allows us to exclude the absence of the CNO signal with about 7σ C.L. The correspondent CNO neutrino flux is 6.6_{-0.9}^{+2.0}×10^{8} cm^{-2} s^{-1}, taking into account the neutrino flavor conversion. We use the new CNO measurement to evaluate the C and N abundances in the Sun with respect to the H abundance for the first time with solar neutrinos. Our result of N_{CN}=(5.78_{-1.00}^{+1.86})×10^{-4} displays a ∼2σ tension with the "low-metallicity" spectroscopic photospheric measurements. Furthermore, our result used together with the ^{7}Be and ^{8}B solar neutrino fluxes, also measured by Borexino, permits us to disfavor at 3.1σ C.L. the "low-metallicity" standard solar model B16-AGSS09met as an alternative to the "high-metallicity" standard solar model B16-GS98.

Unveiling resistome profiles in the sediments of an Antarctic volcanic island.

The Deception Island, located in Maritime Antarctica, is a volcanic island with geothermal activity and one of the most visited by tourists. However, the extent of the anthropogenic impact remains largely unknown and the factors shaping the resistance/tolerance mechanisms in the microbiomes from Whalers Bay ecosystems have never been investigated. In this context, this study aimed to reveal the resistome profiles of Whalers Bay sediments and correlate them with environmental factors. Samples were collected at four sites during the summer 2014/2015 along a transect of 27.5 m in the Whalers Bay sediments. DNA isolated from sediment samples was sequenced using the Illumina HiSeq platform. Bioinformatic analyses allowed the assembly of contigs and scaffolds, prediction of ORFs, and taxonomic and functional annotation using NCBI RefSeq database and KEGG orthology, respectively. Microorganisms belonging to the genera Psychrobacter, Flavobacterium and Polaromonas were shown to dominate all sites, representing 60% of taxonomic annotation. Arsenic (As), copper (Cu) and iron (Fe) were the most abundant metal resistance/tolerance types found in the microbiomes. Beta-lactam was the most common class related to antibiotics resistance/tolerance, corroborating with previous environmental resistome studies. The acridine class was the most abundant amongst the biocide resistance/tolerances, related to antiseptic compounds. Results gathered in this study reveal a repertoire of resistance/tolerance classes to antibiotics and biocides unusually found in Antarctica. However, given the volcanic nature (heavy metals-rich region) of Deception Island soils, this putative impact must be viewed with caution.

In vivo evidence that the cannabinoid receptor 2-63 RR variant is associated with the acquisition and/or expansion of HIV infection.

OBJECTIVES: The aim of the study was to investigate whether the rs35761398 variants of the cannabinoid receptor 2 (CB2) gene may influence the acquisition of HIV infection and the clinical presentation of HIV/hepatitis C virus (HCV) coinfection. METHODS: We compared 166 HIV/HCV-coinfected patients with 186 HCV-monoinfected patients, all with biopsy-proven chronic hepatitis (using the Ishak scoring system), naïve for anti-HCV treatment and tested for the CB2 rs35761398 polymorphism (using the TaqMan assay). RESULTS: The HIV/HCV-coinfected patients were more frequently male (P < 0.002), were younger (P < 0.001), and had lower median BMI (P < 0.001) and HCV RNA (P < 0.05) and higher median aspartate aminotransferase (AST; P < 0.001), alanine aminotransferase (ALT; P < 0.001) and gamma glutamyl transferase (GGT; P < 0.001) levels than the HCV-monoinfected patients. The CB2 RR variant predominated in HIV/HCV-coinfected patients (45.8% vs. 31.2% in HCV-monoinfected patients; P < 0.001) and the CB2 QR variant in HCV-monoinfected patients (57.5% vs. 38.6% in HIV/HCV-coinfected patients; P < 0.00001), and the CB2 QQ variant was equally distributed. Focusing on patients with the CB2 QQ variant, the 26 HIV/HCV-coinfected patients, compared with the 21 HCV-monoinfected patients, showed less severe liver necroinflammation [lower histological activity index (HAI)] (P < 0.05). Of the patients with the CB2 RR variant, the 76 HIV/HCV-coinfected patients, compared with the 58 HCV-monoinfected patients, were more frequently male (P < 0.05), were younger (P < 0.001), and had a lower median body mass index (BMI; P < 0.001), a higher median AST level (P < 0.001), a higher mean HAI score (P < 0.05) and a higher rate of cases with severe steatosis (P = 0.05). In an analysis of variance (anova) of HCV/HIV-coinfected and HCV-monoinfected patient data, those with the CB2 RR variant (P = 0.003) and of male sex (P = 0.002) were more prevalent in the HCV/HIV-coinfected group. CONCLUSIONS: There is the suggestion of a positive effect of the CB2 RR variant on HIV acquisition and/or spread, which is in accordance with previous in vitro observations.

Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor.

The endogenous fatty acid amide palmitoylethanolamide (PEA) has been shown to exert anti-inflammatory actions mainly through inhibition of the release of pro-inflammatory molecules from mast cells, monocytes and macrophages. Indirect activation of the endocannabinoid (eCB) system is among the several mechanisms of action that have been proposed to underlie the different effects of PEA in vivo. In this study, we used cultured rat microglia and human macrophages to evaluate whether PEA affects eCB signaling. PEA was found to increase CB2 mRNA and protein expression through peroxisome proliferator-activated receptor-α (PPAR-α) activation. This novel gene regulation mechanism was demonstrated through: (i) pharmacological PPAR-α manipulation, (ii) PPAR-α mRNA silencing, (iii) chromatin immunoprecipitation. Moreover, exposure to PEA induced morphological changes associated with a reactive microglial phenotype, including increased phagocytosis and migratory activity. Our findings suggest indirect regulation of microglial CB2R expression as a new possible mechanism underlying the effects of PEA. PEA can be explored as a useful tool for preventing/treating the symptoms associated with neuroinflammation in CNS disorders.

Test of Electric Charge Conservation with Borexino.

Borexino is a liquid scintillation detector located deep underground at the Laboratori Nazionali del Gran Sasso (LNGS, Italy). Thanks to the unmatched radio purity of the scintillator, and to the well understood detector response at low energy, a new limit on the stability of the electron for decay into a neutrino and a single monoenergetic photon was obtained. This new bound, τ≥6.6×10^{28} yr at 90% C.L., is 2 orders of magnitude better than the previous limit.

Association between cannabinoid receptor type 2 Q63R variant and oligo/polyarticular juvenile idiopathic arthritis.

OBJECTIVES: To investigate whether the functional variant Q63R of the cannabinoid 2 (CB2) receptor is associated with susceptibility to oligo/poly-articular juvenile idiopathic arthritis (JIA) and with its clinical features. METHOD: A total of 171 Italian children with oligoarticular/rheumatoid factor negative poly-articular JIA and 600 healthy controls were enrolled in the study and genotyped. RESULTS: A significant difference in genotype distribution of the CB2 Q63R variant (CNR2 rs35761398) between oligo/poly-articular JIA patients and controls was found (p = 0.001). The R63 variant was associated with increased rates of relapse (p = 0.0001). CONCLUSIONS: This study indicates that the CB2 receptor contributes to susceptibility to oligo/polyarticular JIA and to the severity of its clinical course.

The impact of the CB2-63 polymorphism on the histological presentation of chronic hepatitis B.

The impact of the cannabinoid receptor 2 (CB2) rs35761398 polymorphism on chronic hepatitis B (CHB) was evaluated in 106 consecutive biopsy-proven CHB patients naive for antiviral therapy. A histological activity index (HAI) > 8 (Ishak scoring) was more frequent in patients with CB2-63 RR than in those with CB2-63 QR or QQ (37% vs. 16.7%, p < 0.05). The logistic regression analysis identified CB2-63 RR (p < 0.05) and a fibrosis score >3 (p < 0.005) as independently associated with an HAI >8. The observation that the CB2-63 RR variant is an independent predictor of extensive necroinflammation opens up new prospects in the study of CHB.

Lifetimes of (214)Po and (212)Po measured with Counting Test Facility at Gran Sasso National Laboratory.

The decays of (214)Po into (210)Pb and of (212)Po into (208)Pb tagged by the previous decays from (214)Bi and (212)Bi have been studied inserting quartz vials inside the Counting Test Facility (CTF) at the underground laboratory in Gran Sasso (LNGS). We find that the mean lifetime of (214)Po is (236.00 ± 0.42(stat) ± 0.15(syst)) µs and that of (212)Po is (425.1 ± 0.9(stat) ± 1.2(syst)) ns. Our results are compatible with previous measurements, have a much better signal to background ratio, and reduce the overall uncertainties.

The A1 adenosine receptor as a new player in microglia physiology.

The purinergic system is highly involved in the regulation of microglial physiological processes. In addition to the accepted roles for the P2 X4,7 and P2 Y12 receptors activated by adenosine triphosphate (ATP) and adenosine diphosphate, respectively, recent evidence suggests a role for the adenosine A2A receptor in microglial cytoskeletal rearrangements. However, the expression and function of adenosine A1 receptor (A1AR) in microglia is still unclear. Several reports have demonstrated possible expression of A1AR in microglia, but a new study has refuted such evidence. In this study, we investigated the presence and function of A1AR in microglia using biomolecular techniques, live microscopy, live calcium imaging, and in vivo electrophysiological approaches. The aim of this study was to clarify the expression of A1AR in microglia and to highlight its possible roles. We found that microglia express A1AR and that it is highly upregulated upon ATP treatment. Moreover, we observed that selective stimulation of A1AR inhibits the morphological activation of microglia, possibly by suppressing the Ca(2+) influx induced by ATP treatment. Finally, we recorded the spontaneous and evoked activity of spinal nociceptive-specific neuron before and after application of resting or ATP-treated microglia, with or without preincubation with a selective A1AR agonist. We found that the microglial cells, pretreated with the A1AR agonist, exhibit lower capability to facilitate the nociceptive neurons, as compared with the cells treated with ATP alone.

The genetic ablation or pharmacological inhibition of TRPV1 signalling is beneficial for the restoration of quiescent osteoclast activity in ovariectomized mice.

BACKGROUND AND PURPOSE: Osteoporosis is a condition characterized by a decrease in bone density, which decreases its strength and results in fragile bones. The endocannabinoid/endovanilloid system has been shown to be involved in the regulation of skeletal remodelling. The aim of this study was to investigate the possible modulation of bone mass mediated by the transient receptor potential vanilloid type 1 channel (TRPV1) in vivo and in vitro. EXPERIMENTAL APPROACH: A multidisciplinary approach, including biomolecular, biochemical and morphological analysis, was used to investigate the involvement of TRPV1 in changes in bone density in vivo and osteoclast activity in vitro, in wild-type and Trpv1(-/-) mice, that had undergone ovariectomy or had a sham operation. KEY RESULTS: Genetic deletion of Trpv1 as well as pharmacological inhibition/desensitization of TRPV1 signalling dramatically reduced the osteoclast activity in vitro and prevented the ovariectomy-induced bone loss in vivo, whereas the expression of cannabinoid type 2 (CB2 ) receptors was increased. CONCLUSIONS AND IMPLICATIONS: These findings highlight the pivotal role TRPV1 channels play in bone resorption and suggest a possible cross-talk between TRPV1 and CB2 receptors. Based on these results, hybrid compounds acting on both TRPV1 and CB2 receptors in an opposite manner could provide a future pharmacological tool for the treatment of diseases associated with disturbances in the bone remodelling process.

First evidence of pep solar neutrinos by direct detection in Borexino.

We observed, for the first time, solar neutrinos in the 1.0-1.5 MeV energy range. We determined the rate of pep solar neutrino interactions in Borexino to be 3.1±0.6{stat}±0.3{syst} counts/(day·100 ton). Assuming the pep neutrino flux predicted by the standard solar model, we obtained a constraint on the CNO solar neutrino interaction rate of <7.9 counts/(day·100 ton) (95% C.L.). The absence of the solar neutrino signal is disfavored at 99.97% C.L., while the absence of the pep signal is disfavored at 98% C.L. The necessary sensitivity was achieved by adopting data analysis techniques for the rejection of cosmogenic {11}C, the dominant background in the 1-2 MeV region. Assuming the Mikheyev-Smirnov-Wolfenstein large mixing angle solution to solar neutrino oscillations, these values correspond to solar neutrino fluxes of (1.6±0.3)×10{8} cm{-2} s^{-1} and <7.7×10{8} cm{-2} s{-1} (95% C.L.), respectively, in agreement with both the high and low metallicity standard solar models. These results represent the first direct evidence of the pep neutrino signal and the strongest constraint of the CNO solar neutrino flux to date.

Precision measurement of the (7)Be solar neutrino interaction rate in Borexino.

The rate of neutrino-electron elastic scattering interactions from 862 keV (7)Be solar neutrinos in Borexino is determined to be 46.0±1.5(stat)(-1.6)(+1.5)(syst) counts/(day·100 ton). This corresponds to a ν(e)-equivalent (7)Be solar neutrino flux of (3.10±0.15)×10(9) cm(-2) s(-1) and, under the assumption of ν(e) transition to other active neutrino flavours, yields an electron neutrino survival probability of 0.51±0.07 at 862 keV. The no flavor change hypothesis is ruled out at 5.0 σ. A global solar neutrino analysis with free fluxes determines Φ(pp)=6.06(-0.06)(+0.02)×10(10) cm(-2) s(-1) and Φ(CNO)<1.3×10(9) cm(-2) s(-1) (95% C.L.). These results significantly improve the precision with which the Mikheyev-Smirnov-Wolfenstein large mixing angle neutrino oscillation model is experimentally tested at low energy.

Two-dimensional strain in Takotsubo cardiomyopathy.

This report presents the late follow-up of a case of Takotsubo cardiomyopathy with good clinical outcome and improved left ventricular global systolic function. However, there was persistence of significant regional longitudinal systolic dysfunction evaluated using a new echocardiographic technique (speckle tracking), with corresponding measures of strain (S) and strain rate (SR). We emphasize the importance of this new method to monitoring this cardiomyopathy, since it identifies patients with persistent systolic dysfunction who will possibly benefit from maintenance of clinical therapy.

Strain bidimensional na cardiopatia de Takotsubo / Two-dimensional strain in Takotsubo cardiomyopathy

Este relato apresenta o seguimento tardio de um caso de cardiomiopatia de Takotsubo com boa evolução clínica e melhora da função sistólica global ventricular esquerda. Contudo, observou-se persistência de significativa disfunção sistólica regional longitudinal que foi avaliada por meio de nova técnica ecocardiográfica (speckle tracking), com as medidas do strain (S) e strain rate (SR) correspondentes. Ressaltamos a importância desse novo método para o acompanhamento dessa cardiopatia, pois permite identificar os pacientes que persistem com disfunção sistólica e que possivelmente serão beneficiados com a manutenção da terapêutica clínica.

This report presents the late follow-up of a case of Takotsubo cardiomyopathy with good clinical outcome and improved left ventricular global systolic function. However, there was persistence of significant regional longitudinal systolic dysfunction evaluated using a new echocardiographic technique (speckle tracking), with corresponding measures of strain (S) and strain rate (SR). We emphasize the importance of this new method to monitoring this cardiomyopathy, since it identifies patients with persistent systolic dysfunction who will possibly benefit from maintenance of clinical therapy.

The endovanilloid/endocannabinoid system in human osteoclasts: possible involvement in bone formation and resorption.

Recent studies suggest a role for the endocannabinoid/endovanilloid anandamide in the regulation of bone resorption/formation balance in mice. Here, we examined the co-expression of the transient receptor potential vanilloid type 1 (TRPV1) and the cannabinoid CB1/CB2 receptors together with N-acylphosphatidylethanolamine-hydrolizing phospholipase D (NAPE-PLD) and fatty acid amide hydrolase (FAAH), the two enzymes responsible of the synthesis and catabolism of anandamide respectively, in human osteoclasts. Co-expression of TRPV1, CB1/CB2, NAPE-PLD and FAAH was found in both human osteoclast cultures and in native osteoclasts from human bone biopsies. Moreover, agonist-evoked calcium entry indicated that the TRPV1 receptor is functionally active in vitro. Consistently, biomolecular and functional experiments showed that resiniferatoxin (RTX), a selective TRPV1 receptor agonist, increased the expression and the activity of TRAP and cathepsin K, two specific osteoclast biomarkers. The evidence that cannabinoid and vanilloid receptors are co-expressed in human osteoclasts suggests that they might cross-talk to modulate the intrinsic balance of bone mineralization and resorption by different actions of anandamide through TRPV1 and cannabinoid receptors. The presence of the endocannabinoid/endovanilloid proteins in human osteoclasts will likely have implications for the management of bone demineralization associated syndrome (i. e. osteoporosis).

Direct measurement of the 7Be solar neutrino flux with 192 days of borexino data.

We report the direct measurement of the 7Be solar neutrino signal rate performed with the Borexino detector at the Laboratori Nazionali del Gran Sasso. The interaction rate of the 0.862 MeV 7Be neutrinos is 49+/-3stat+/-4syst counts/(day.100 ton). The hypothesis of no oscillation for 7Be solar neutrinos is inconsistent with our measurement at the 4sigma C.L. Our result is the first direct measurement of the survival probability for solar nu(e) in the transition region between matter-enhanced and vacuum-driven oscillations. The measurement improves the experimental determination of the flux of 7Be, pp, and CNO solar nu(e), and the limit on the effective neutrino magnetic moment using solar neutrinos.

Rizatriptan does not change cerebral blood flow velocity during migraine attacks.

Rizatriptan represents a major advance in the treatment of migraine attack: inhibition of peripheral trigeminal nerve and constriction of intracranial extracerebral blood vessels have been proposed as its main antimigraine mechanisms of action. Although many studies may suggest that rizatriptan causes highly selective vasoconstriction within intracranial extracerebral vessels (i.e., meningeal arteries), no literature data are available to date on possible cerebral hemodynamic changes in humans after treatment with rizatriptan. The aim of this study was to evaluate the effect of rizatriptan on cerebral blood flow velocity performing transcranial Doppler during spontaneous attacks of migraine without aura. Fourteen patients suffering from migraine without aura were monitored to evaluate mean flow velocity changes on both middle cerebral arteries during migraine attack 30 min before and 120 min after oral administration of rizatriptan 10mg. Monitoring was repeated for 30 min during the pain-free period. All patients turned out to be drug responders and no significant mean flow velocity changes were observed between the pain-free period and pre-treatment phase; besides no significant difference in mean flow velocity value have been detected between the periods after the drug administration during the attack versus both pre-treatment period and pain-free phase. These findings indicate that the antimigraine action of rizatriptan is not associated with clear intracranial cerebral hemodynamic changes and may support its cerebrovascular safety.

Environmental factors and Parkinson's disease: a case-control study in the Tuscany region of Italy.

To date the aetiology of Parkinson's disease (PD) is unknown although both genetic susceptibility and environmental factors appear to play an important role in the development of the disease. Recent data have also indicated that chronic exposure to a common pesticide can reproduce the neurochemical, behavioral and neuropathological features of PD. The epidemiological studies previously carried on the prevalence of PD in population exposed to environmental factors have produced controversial results, probably because of different trial design and different analysis methods. A case-control retrospective study was conducted in a well-defined geographic area in Tuscany-Italy with the aim to identify environmental factors possibly related to PD. No significant difference between PD patients and control subjects was observed in time spent in rural or industrial residence, in well water drinking and in the exposure to herbicides and pesticides. A significant difference between patients with PD and controls was reported for cigarette smoking, controls resulting more likely cigarette smokers in comparison with PD patients. The present findings support the view of a protective effect of cigarette smoking and do not show any significant association between environmental factors and the risk of development of PD.