A complex network of many interacting mechanisms orchestrates immune and inflammatory responses. Among these, the cation channels of the transient receptor potential (TRP) family expressed by ...resident tissue cells, inflammatory and immune cells and distinct subsets of primary sensory neurons, have emerged as a novel and interrelated system to detect and respond to harmful agents. TRP channels, by means of their direct effect on the intracellular levels of cations and/or through the indirect modulation of a large series of intracellular pathways, orchestrate a range of cellular processes, such as cytokine production, cell differentiation and cytotoxicity. The contribution of TRP channels to the transition of inflammation and immune responses from a defensive early response to a chronic and pathological condition is also emerging as a possible underlying mechanism in various diseases. This review discusses the roles of TRP channels in inflammatory and immune cell function and provides an overview of the effects of inflammatory and immune TRP channels on the pathogenesis of human diseases.
Why do we observe increasing rates of new cancer cases? Is the increasing burden of cancer mainly the outcome of higher life expectancy and better life conditions brought about by economic ...development? To what extent do environmental degradation and changes in life-styles play a relevant role? To answer these questions, we empirically assessed the relationship between per capita income and new cancer cases (incidence) by using cross-sectional data from 122 countries.
We found that the incidence rate of all-sites cancer increases linearly with per capita income, even after controlling for population ageing, improvement in cancer detection, and omitted spatially correlated variables. If higher incidence rates in developed countries were merely due to those factors, and not also to life-styles and environmental degradation, we would have found a flat or even an inverted-U pattern between per capita income and cancer incidence.
The regression analysis was applied also to the eight most common site-specific cancers. This confirmed the existing evidence on the different patterns in rich and poor countries, explained the pattern of the estimated relationship for aggregate cancers, and gave some other interesting insights.
•New cancer cases increase with p.c. income in a cross-section of 122 countries.•Improved detection potential and a longer life alone cannot explain this evidence.•Bad life-styles and environmental degradation play a relevant role.
Abstract
Eukaryotic cells recognize intracellular pathogens through pattern recognition receptors, including sensors of aberrant nucleic acid structures. Sensors of double-stranded RNA (dsRNA) are ...known to detect replication intermediates of RNA viruses. It has long been suggested that annealing of mRNA from symmetrical transcription of both top and bottom strands of DNA virus genomes can produce dsRNA during infection. Supporting this hypothesis, nearly all DNA viruses encode inhibitors of dsRNA-recognition pathways. However, direct evidence that DNA viruses produce dsRNA is lacking. Contrary to dogma, we show that the nuclear-replicating DNA virus adenovirus (AdV) does not produce detectable levels of dsRNA during infection. In contrast, abundant dsRNA is detected within the nucleus of cells infected with AdV mutants defective for viral RNA processing. In the presence of nuclear dsRNA, the cytoplasmic dsRNA sensor PKR is relocalized and activated within the nucleus. Accumulation of viral dsRNA occurs in the late phase of infection, when unspliced viral transcripts form intron/exon base pairs between top and bottom strand transcripts. We propose that DNA viruses actively limit dsRNA formation by promoting efficient splicing and mRNA processing, thus avoiding detection and restriction by host innate immune sensors of pathogenic nucleic acids.
Graphical Abstract
Graphical Abstract
Inefficient splicing of overlapping viral transcripts can lead to intermolecular dsRNA formation. During wildtype virus infection the presence of the E1B55K/E4orf6 viral hijacked ubiquitin ligase leads to the ubiquitination of cellular RNA binding proteins (RBPs) RALY and hnRNPC, which precludes their binding to viral RNA. In the presence of RALY and hnRNPC viral transcripts are poorly spliced, leading to the formation of dsRNA between the exonic regions of viral RNAs to the intronic regions of transcripts derived from the opposing strand. After these dsRNA molecules form, a fraction of the cytoplasmic dsRNA-sensor PKR translocates into the nucleus, where it co-localizes with viral dsRNA and is activated by auto-phosphorylation.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed over 6 million individuals worldwide and continues to spread in countries where vaccines are not yet widely available or its ...citizens are hesitant to become vaccinated. Therefore, it is critical to unravel the molecular mechanisms that allow SARS-CoV-2 and other coronaviruses to infect and overtake the host machinery of human cells. Coronavirus replication triggers endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR), a key host cell pathway widely believed to be essential for viral replication. We examined the master UPR sensor IRE1α kinase/RNase and its downstream transcription factor effector XBP1s, which is processed through an IRE1α-mediated mRNA splicing event, in human lung-derived cells infected with betacoronaviruses. We found that human respiratory coronavirus OC43 (HCoV-OC43), Middle East respiratory syndrome coronavirus (MERS-CoV), and murine coronavirus (MHV) all induce ER stress and strongly trigger the kinase and RNase activities of IRE1α as well as XBP1 splicing. In contrast, SARS-CoV-2 only partially activates IRE1α through autophosphorylation, but its RNase activity fails to splice XBP1. Moreover, while IRE1α was dispensable for replication in human cells for all coronaviruses tested, it was required for maximal expression of genes associated with several key cellular functions, including the interferon signaling pathway, during SARS-CoV-2 infection. Our data suggest that SARS-CoV-2 actively inhibits the RNase of autophosphorylated IRE1α, perhaps as a strategy to eliminate detection by the host immune system.
SARS-CoV-2 is the third lethal respiratory coronavirus, after MERS-CoV and SARS-CoV, to emerge this century, causing millions of deaths worldwide. Other common coronaviruses such as HCoV-OC43 cause less severe respiratory disease. Thus, it is imperative to understand the similarities and differences among these viruses in how each interacts with host cells. We focused here on the inositol-requiring enzyme 1α (IRE1α) pathway, part of the host unfolded protein response to virus-induced stress. We found that while MERS-CoV and HCoV-OC43 fully activate the IRE1α kinase and RNase activities, SARS-CoV-2 only partially activates IRE1α, promoting its kinase activity but not RNase activity. Based on IRE1α-dependent gene expression changes during infection, we propose that SARS-CoV-2 prevents IRE1α RNase activation as a strategy to limit detection by the host immune system.
The DArk Matter Particle Explorer (DAMPE) is a space-based particle detector launched in a sun-synchronous orbit on December 17, 2015 from the Jiuquan Satellite Launch Center, in China. The main ...goals of the DAMPE mission include the study of the electron–positron energy spectrum, the study of galactic cosmic rays, gamma-ray astronomy, and indirect dark matter searches. Among its subdetectors, the deep BGO calorimeter makes DAMPE able to measure the cosmic-ray electrons and positrons (CRE) spectrum up to 10 TeV and cosmic-ray nuclei (CR) spectra up to 100 TeV, with unprecedented energy resolution. This high-energy region is important in order to search for possible nearby CRE sources, for dark matter signatures, and to have a better understanding of CR acceleration and propagation mechanisms inside the Galaxy. A break at about 1 TeV was clearly evidenced by DAMPE in the CRE energy spectrum. Moreover, DAMPE precise measurements of CR protons and helium spectra, confirmed the hardening at few hundreds GeV
and revealed a spectral softening at about 14 and 30 TeV for
and He, respectively, suggesting a rigidity dependent mechanism. About 250 gamma ray sources were detected and identified. Spectral analyses on medium and heavy mass nuclei are currently ongoing. The main results of the mission will be presented, along with ongoing activities.
Background and Aims
Governo all'uso toscano (GUT) is a traditional winemaking practice where withered grapes are added to a freshly fermented wine. This results in a second alcoholic fermentation and ...a distinctive wine, in which there is renewed interest. Grape withering is problematic for winemakers, however, both in terms of cost and risks. It is therefore important to determine the minimum amount of withered grapes needed to typify the wine in order to minimise risks and costs.
Methods and Results
During the trials, Sangiovese grapes were withered for 2 months in a dedicated room, a ‘fruttaio’, with a resulting mass loss of about 40%. Afterwards, withered grapes (5–20% berry mass/wine mass) were added to a Control wine to reproduce the GUT procedure. The GUT technique significantly changed the chemical profile of the wines. Ethanol, colour intensity and hue increased, while acidity decreased. Malolactic fermentation occurred simultaneously with the second alcoholic fermentation in all GUT wines, but not in the Control wines. The GUT practice significantly changed the volatile profile, including the concentration of several primary grape compounds, such as aromatic alcohols, C6 compounds and terpenoids, and of several fermentation compounds.
Conclusion
Under the experimental conditions, the optimal amount of withered grapes added to the base wine was 5%.
Significance of the Study
The study described the oenological effects of GUT and the optimisation of the amount of withered grapes required to make a wine with this characteristic winemaking practice clearly recognisable.
An original computer program was set up to predict and control olive paste malaxation in the range of temperature between 22 and 37 °C under exposure to air. The program consisted of four sections to ...solve the our previous literature time-temperature kinetics. It was able to predict both the apparent oil extraction yield and the relative variation of 3,4 DHPEA-EDA and sum of verbascoside diastereoisomers contents in steady and unsteady-conditions; it was also able to determine optimal malaxation time-temperature conditions to maximize the oil extraction yield and minimize the oxidative degradation of phenolic compounds. Simulation examples were carried out to test prediction potentiality. The malaxation treatments at low temperatures appeared preferable, since they seemed to be unaffected by time-temperature profiles under unsteady-state conditions. However, it seemed more difficult to identify optimal time-temperature conditions at a low temperature than at a high temperature in some operating states.
•An original computer program was written to optimize olive paste malaxation under exposure to air.•Simulation examples were carried out to predict oil yield and damage to phenols.•Malaxation at low temperature and intermediate time appeared preferable.•Some operating states appeared critical to identify optimal conditions.
An original kinetic study of the transformation phenomena of phenolic compounds in olive paste was carried out at different malaxation time-temperature conditions under exposure to air, using Abencor ...lab equipment to process olives (Frantoio cv) of a known degree of ripeness.
Empirical kinetic models and the relevant apparent kinetic constants were determined for the following significant indices: total phenolic compound content in waste water samples using the Folin-Ciocalteu method; verbascoside and β-OH-verbascoside contents in olive paste samples using HPLC; and 3,4-DHPEA-EDA contents in olive oil samples using HPLC. Two opposite phenolic compound transformation phenomena were proposed to explain the kinetic models: (i) enzymatic oxidative damage of phenolic compounds; (ii) physical and enzymatic release of phenolic compounds from cellular tissues. It was possible to propose a reference optimization chart to predict “selective” time-temperature conditions to maximize the apparent EVOO extraction yield while minimizing the degradation phenomena of phenolic compounds during malaxation.
•An original experimental approach was used to study olive paste malaxation.•A time-temperature kinetic study was applied to predict malaxation phenomena.•Indices were selected to monitor oxidative damage to phenolic compounds.•A reference synoptic chart was proposed to optimize malaxation.
An original kinetic study of both oil coalescence phenomena and potential extra virgin olive oil extraction yield (i.e. apparent Extractability Index) was carried out at different malaxation ...time-temperature conditions using Abencor lab equipment to process olives (Frantoio cv) of a known degree of ripeness.
The apparent Extractability Index was modelled at every malaxation temperature by pseudo first-order kinetics, where the yield rate constant was temperature dependent following the Arrhenius equation (k0 = 7.50 107 min−1; Ea = 54512 J/mol). Oil droplet coalescence, which was expressed as a relative variation in the percentage of oil droplets with a diameter of >30 μm, proved to be an time-dependent phenomenon only; the pseudo zero-order kinetics modelling was statistically significant, where the coalescence rate constant was equal to 0.033 min−1. The above kinetics were applied in order to propose a synoptic chart to predict the potential effect of malaxation in isothermal conditions on EVOO extraction yield.
•An original experimental approach was used to study olive paste malaxation.•A time-temperature kinetic study was applied to predict malaxation phenomena.•An apparent Extractability Index and oil droplet coalescence phenomena were considered.•A synoptic chart was proposed to predict the potential effect of malaxation on yield.•Phenomena that condition oil extraction yield changed as a function of temperature.
Plastic scintillators are widely used for anti-coincidence systems and for the identification of charged cosmic-ray nuclei in satellite experiments. For this reason, a plastic scintillator detector ...(PSD) should have a high detection efficiency for charged cosmic rays and a very good capability of measuring charges. We implemented a full and customizable simulation tool to investigate the performance of a PSD coupled to Silicon Photomultipliers. The overall performance of the detector is studied by tracking optical photons produced inside the scintillator. The simulation will be used for the design of a PSD for future space experiments, such as HERD, AMEGO, e-Astrogam. In this work we investigated in detail the effect of Birks’ saturation in the discrimination of charged ions up to iron nuclei. We will show the comparison between simulations and measurements conducted on prototype scintillator tiles.
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