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.
The systems approach has been used to evaluate higher education and explores inputs, transformation process, and outputs of a system that is also influenced by environmental factors such as COVID-19. ...The COVID-19 pandemic shifted many college students to different learning modes, changing their university experience. This study evaluated dietetics students' education experiences and characteristics in the latter period (spring 2022) of the COVID-19 pandemic using the systems approach.
Researchers developed and distributed an electronic survey to all 215 US-based Didactic Program in Dietetics (DPD) directors during March to May 2022 to forward to their students. Researchers calculated descriptive statistics for variables related to inputs, transformation process, and outputs in the systems approach.
Respondents (n = 341) represented 51 DPDs in 31 states in the United States. Overall, DPD students (88.5%) were mostly or very satisfied with their choice of majoring in dietetics. Most (84.0%) planned to earn the RDN credential. Nearly half (46.9%) of DPD students were somewhat or extremely concerned about their readiness to continue their dietetics education path due to the pandemic-related learning conditions. Most students (43.6%) reported dissatisfaction with asynchronous remote instruction in laboratory courses. DPD students' GPAs remained consistent within the range of 3.75-4.0 from Fall 2019 (43.2%) to Spring 2022 (44.5%). The most important expectations of professors moving forward were to communicate effectively (97.3%), employ cultural humility (93.8%), eliminate discrimination in the classroom (93.6%), provide lecture slides (89.7%), and be flexible and accommodating (88.7%).
DPD students emerged from COVID-19 with new perspectives and expectations for their university learning experience. Future research should explore the perspectives of DI directors, preceptors, and employers of COVID-19 era DPD graduates.
The purinergic system is highly involved in the regulation of microglial physiological processes. In addition to the accepted roles for the P2X4,7 and P2Y12 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 Ca2+ 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. GLIA 2014;62:122–132
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.
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•Soil samples characterized by a high concentration of Co, Fe, Mn and Pb.•The genera Psychrobacter and Polaromonas dominated the microbial community.•Transposases were one of the highly abundant protein families.•A wide variety of resistance/tolerance genes and mechanisms was found.•Resistance to compounds unusually found in Antarctica suggests anthropogenic impact.
Context:
Obesity is associated with a low-grade inflammatory state and adipocyte (ADP) hyperplasia/hypertrophy. Obesity inhibits the “browning” of white adipose tissue. Cannabinoid receptor 2 (CB2) ...agonists reduce food intake and induce antiobesity effect in mice. A common missense CB2 variant, Q63R, causes CB2-reduced function.
Objective:
To evaluate the influence of CB2 receptor on the modulation of childhood obesity and of ADP activity and morphology.
Design:
CB2-Q63R variant was analyzed in obese Italian children. The effects of an inflammatory stimulus and those of drugs selectively acting on CB2 were investigated on in vitro ADPs obtained from mesenchymal stem cells of adult healthy donors or from sc adipose biopsies of adult nonobese and obese subjects.
Setting:
Department of Women, Child and General and Specialist Surgery of the Second University of Naples.
Patients or Other Participants:
A total of 501 obese Italian children (age 11 ± 2.75). Twelve healthy bone marrow donors (age 36.5 ± 15); and 17 subjects, 7 lean (age 42 ± 10) and 10 obese (age 37.8 ± 12) underwent sc adipose tissue biopsies.
Main Outcome Measures:
Effects of CB2 stimulation on adipokine, perilipin, and uncoupling protein-1 expression.
Results:
The less-functional CB2-R63 variant was significantly associated with a high z-score body mass index. CB2 blockade with AM630 reverse agonist increased inflammatory adipokine release and fat storage and reduced browning. CB2 stimulation with JWH-133 agonist reversed all of the obesity-related effects.
Conclusion:
CB2 receptor is a novel pharmacological target that should be considered for obesity.
Adipocyte cultures obtained from adipose biopsies of non-obese and obese subjects and treated with drugs acting on CB2 receptor revealed that CB2 stimulation inhibits inflammation and fat storage and induces browning.
Neutrino Oscillations Bellini, G.; Ludhova, L.; Ranucci, G. ...
Advances in High Energy Physics,
01/2014, Letnik:
2014
Journal Article
Recenzirano
Odprti dostop
In the last decades, a very important breakthrough has been brought about in the elementary particle physics by the discovery of the phenomenon of the neutrino oscillations, which has shown neutrino ...properties beyond the Standard Model. But a full understanding of the various aspects of the neutrino oscillations is far to be achieved. In this paper the theoretical background of the neutrino oscillation phenomenon is described, referring in particular to the paradigmatic models. Then the various techniques and detectors which studied neutrinos from different sources are discussed, starting from the pioneering ones up to the detectors still in operation and to those in preparation. The physics results are finally presented adopting the same research path which has been crossed by this long saga. The problems not yet fixed in this field are discussed, together with the perspectives of their solutions in the near future.
Abstract
Cosmogenic radio-nuclei are an important source of background for low-energy neutrino experiments. In Borexino, cosmogenic
$$^{11}$$
11
C decays outnumber solar
pep
and CNO neutrino events ...by about ten to one. In order to extract the flux of these two neutrino species, a highly efficient identification of this background is mandatory. We present here the details of the most consolidated strategy, used throughout Borexino solar neutrino measurements. It hinges upon finding the space-time correlations between
$$^{11}$$
11
C decays, the preceding parent muons and the accompanying neutrons. This article describes the working principles and evaluates the performance of this Three-Fold Coincidence (TFC) technique in its two current implementations: a hard-cut and a likelihood-based approach. Both show stable performances throughout Borexino Phases II (2012–2016) and III (2016–2020) data sets, with a
$$^{11}$$
11
C tagging efficiency of
$$\sim 90$$
∼
90
% and
$$\sim $$
∼
63–66 % of the exposure surviving the tagging. We present also a novel technique that targets specifically
$$^{11}$$
11
C produced in high-multiplicity during major spallation events. Such
$$^{11}$$
11
C appear as a
burst
of events, whose space-time correlation can be exploited. Burst identification can be combined with the TFC to obtain about the same tagging efficiency of
$$\sim 90\%$$
∼
90
%
but with a higher fraction of the exposure surviving, in the range of
$$\sim $$
∼
66–68 %.
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.
Linked Articles
This article is part of a themed section on the pharmacology of TRP channels. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐10
Abstract 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).
We report on the search for anti-neutrinos of yet unknown origin with the Borexino detector at the Laboratori Nazionali del Gran Sasso. In particular, a hypothetical anti-neutrino flux from the Sun ...is investigated. Anti-neutrinos are detected through the neutron inverse β decay reaction in a large liquid organic scintillator target. We set a new upper limit for a hypothetical solar ν¯e flux of 760 cm−2s−1, obtained assuming an undistorted solar 8B energy spectrum. This corresponds to a limit on the transition probability of solar neutrinos to anti-neutrinos of 1.3×10−4 (90% C.L.) for Eν¯>1.8 MeV, covering the entire 8B spectrum. Best differential limits on anti-neutrino fluxes from unknown sources are also obtained between the detection energy threshold of 1.8 MeV and 17.8 MeV with more than 2 years of data.
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