ABSTRACT The closest radio galaxies; Centaurus A (Cen A), M87, and NGC 1275, have been detected from radio wavelengths to TeV γ-rays, and also studied as high-energy neutrino and ultra-high-energy ...cosmic-ray (UHECR) potential emitters. Their spectral energy distributions (SEDs) show a double-peak feature, which is explained by a synchrotron self-Compton (SSC) model. However, TeV γ-ray measured spectra could suggest that very-high-energy γ-rays might have a hadronic origin. We introduce a lepto-hadronic model to describe the broadband SED; from radio to sub-GeV photons as synchrotron SSC emission and TeV γ-ray photons as neutral pion decay resulting from pγ interactions occurring close to the core. These photo-hadronic interactions take place when Fermi-accelerated protons interact with the seed photons around synchrotron SSC peaks. Obtaining a good description of the TeV γ-ray fluxes, first, we compute neutrino fluxes and events expected in the IceCube detector and, second, we estimate UHECR fluxes and the event rate expected in Telescope Array, Pierre Auger, and HiRes observatories. Within this scenario, we show that the expected high-energy neutrinos cannot explain the astrophysical flux observed by IceCube, and the connection with UHECRs observed by Auger experiment around Cen A might be possible only considering a heavy nuclei composition in the observed events.
One form of liver steatosis, namely Non-Alcoholic Fatty Liver Disease (NAFLD), is a worrisome health problem worldwide characterized by intrahepatic triacylglycerol (TG) overaccumulation. NAFLD is a ...common feature of metabolic syndrome being often associated with obesity, dyslipidemia and diabetes and mostly closely linked to insulin resistance. The mechanism of NAFLD pathogenesis is object of intense investigation especially regarding complex systems ultimately resulting in excessive TG deposition in hepatocytes. However, scarce is the attention about the relevance of hepatic import of glycerol, the other primary source (as glycerol-3-phosphate) of increased TG in hepatocytes. Obese leptin-deficient (ob/ob) mice, an animal model of NAFLD, were used to evaluate the functional involvement of Aquaporin-9 (AQP9), the major pathway of liver glycerol entry, in hepatosteatosis. By RT-PCR and qPCR, the level of Aqp9 mRNA in the liver of starved obese mice was comparable with the corresponding control lean littermates. By immunoblotting, the AQP9 protein at the hepatocyte sinusoidal plasma membrane of obese mice was markedly lower (33%) than lean mice, a finding fully confirmed by immunohistochemistry. By stopped-flow light scattering, the liver glycerol permeability of ob/ob mice was significantly lower (53%) than lean mice, a finding consistent with both the observed down-regulation of AQP9 protein and increased level of plasma glycerol characterizing obese mice. In summary, our results suggest implication of AQP9 in liver steatosis. The reduction of hepatocyte AQP9 and, consequently, glycerol permeability might be a defensive mechanism to counteract further fat infiltration in liver parenchyma.
The time–energy information of ultrashort X-ray free-electron laser pulses generated by the Linac Coherent Light Source is measured with attosecond resolution via angular streaking of neon 1s ...photoelectrons. The X-ray pulses promote electrons from the neon core level into an ionization continuum, where they are dressed with the electric field of a circularly polarized infrared laser. This induces characteristic modulations of the resulting photoelectron energy and angular distribution. From these modulations we recover the single-shot attosecond intensity structure and chirp of arbitrary X-ray pulses based on self-amplified spontaneous emission, which have eluded direct measurement so far. We characterize individual attosecond pulses, including their instantaneous frequency, and identify double pulses with well-defined delays and spectral properties, thus paving the way for X-ray pump/X-ray probe attosecond free-electron laser science.
The X-ray free-electron laser has opened a new era for photon science, improving the X-ray brightness by ten orders of magnitude over previously available sources. Similar to an optical laser, the ...spectral and temporal structure of the radiation pulses can be tailored to the specific needs of many experiments by accurately manipulating the lasing medium, that is, the electron beam. Here we report the generation of mJ-level two-colour hard X-ray pulses of few femtoseconds duration with an XFEL driven by twin electron bunches at the Linac Coherent Light Source. This performance represents an improvement of over an order of magnitude in peak power over state-of-the-art two-colour XFELs. The unprecedented intensity and temporal coherence of this new two-colour X-ray free-electron laser enable an entirely new set of scientific applications, ranging from X-ray pump/X-ray probe experiments to the imaging of complex biological samples with multiple wavelength anomalous dispersion.
Reactive oxygen species (ROS) are produced as a result of aerobic metabolism and as by-products through numerous physiological and biochemical processes. While ROS-dependent modifications are ...fundamental in transducing intracellular signals controlling pleiotropic functions, imbalanced ROS can cause oxidative damage, eventually leading to many chronic diseases. Moreover, increased ROS and reduced nitric oxide (NO) bioavailability are main key factors in dysfunctions underlying aging, frailty, hypertension, and atherosclerosis. Extensive investigation aims to elucidate the beneficial effects of ROS and NO, providing novel insights into the current medical treatment of oxidative stress-related diseases of high epidemiological impact. This review focuses on emerging topics encompassing the functional involvement of aquaporin channel proteins (AQPs) and membrane transport systems, also allowing permeation of NO and hydrogen peroxide, a major ROS, in oxidative stress physiology and pathophysiology. The most recent advances regarding the modulation exerted by food phytocompounds with antioxidant action on AQPs are also reviewed.
Influenza virus infection causes 3-5 million cases of severe illness and 250,000-500,000 deaths worldwide annually. Although pneumonia is the most common complication associated with influenza, there ...are several reports demonstrating increased risk for cardiovascular diseases. Several clinical case reports, as well as both prospective and retrospective studies, have shown that influenza can trigger cardiovascular events including myocardial infarction (MI), myocarditis, ventricular arrhythmia, and heart failure. A recent study has demonstrated that influenza-infected patients are at highest risk of having MI during the first seven days of diagnosis. Influenza virus infection induces a variety of pro-inflammatory cytokines and chemokines and recruitment of immune cells as part of the host immune response. Understanding the cellular and molecular mechanisms involved in influenza-associated cardiovascular diseases will help to improve treatment plans. This review discusses the direct and indirect effects of influenza virus infection on triggering cardiovascular events. Further, we discussed the similarities and differences in epidemiological and pathogenic mechanisms involved in cardiovascular events associated with coronavirus disease 2019 (COVID-19) compared to influenza infection.
Cholesterol, via sterol regulatory element-binding protein (SREBP) transcription factors, activates or represses genes involved in its hepatic biosynthetic pathway, and also modulates the expression ...of hepatocyte mitochondrial aquaporin-8 (mtAQP8), a channel that can function as peroxiporin by facilitating the transmembrane diffusion of H2O2. Here we tested the hypothesis that mtAQP8 is involved in the SREBP-mediated regulation of hepatocyte cholesterol biosynthesis. Using human hepatocyte-derived Huh-7 cells and primary rat hepatocytes, we found that mtAQP8 knockdown significantly downregulated de novo cholesterol synthesis as well as protein expressions of SREBP-2 and its target gene, a rate-limiting enzyme in cholesterol synthesis 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR). In contrast, adenovirus-mediated human AQP8 mitochondrial expression significantly increased de novo cholesterol synthesis and protein expressions of SREBP-2 and HMGCR. In mtAQP8-overexpressed hepatocytes, mitochondrial H2O2 release was found to be increased; and a mitochondria-targeted antioxidant prevented the upregulation of mitochondrial H2O2 release and that of cholesterol synthesis. Our results suggest that peroxiporin mtAQP8 plays a role in the SREBP-controlled hepatocyte cholesterogenesis, a finding that might be relevant to cholesterol-related metabolic disorders.
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•mtAQP8 knockdown downregulates SREBP-controlled hepatocyte cholesterogenesis.•mtAQP8 overexpression upregulates SREBP-controlled hepatocyte cholesterogenesis.•mitochondria-derived H2O2 mediates mtAQP8-modulated cholesterol synthesis.
The adenoviral gene transfer of human aquaporin‐1 (hAQP1) water channels to the liver of 17α‐ethinylestradiol‐induced cholestatic rats improves bile flow, in part by enhancing canalicular ...hAQP1‐mediated osmotic water secretion. To gain insight into the mechanisms of 17α‐ethinylestradiol cholestasis improvement, we studied the biliary output of bile salts (BS) and the functional expression of the canalicular BS export pump (BSEP; ABCB11). Adenovector encoding hAQP1 (AdhAQP1) or control vector was administered by retrograde intrabiliary infusion. AdhAQP1‐transduced cholestatic rats increased the biliary output of major endogenous BS (50%‐80%, P < 0.05) as well as that of taurocholate administered in choleretic or trace radiolabel amounts (around 60%, P < 0.05). Moreover, liver transduction with AdhAQP1 normalized serum BS levels, otherwise markedly elevated in cholestatic animals. AdhAQP1 treatment was unable to improve BSEP protein expression in cholestasis; however, its transport activity, assessed by adenosine triphosphate‐dependent taurocholate transport in canalicular membrane vesicles, was induced by 90% (P < 0.05). AdhAQP1 administration in noncholestatic rats induced no significant changes in either biliary BS output or BSEP activity. Canalicular BSEP, mostly present in raft (high cholesterol) microdomains in control rats, was largely found in nonraft (low cholesterol) microdomains in cholestasis. Considering that BSEP activity directly depends on canalicular membrane cholesterol content, decreased BSEP presence in rafts may contribute to BSEP activity decline in 17α‐ethinylestradiol cholestasis. In AdhAQP1‐transduced cholestatic rats, BSEP showed a canalicular microdomain distribution similar to that of control rats, which provides an explanation for the improved BSEP activity. Conclusion: Hepatocyte canalicular expression of hAQP1 through adenoviral gene transfer promotes biliary BS output by modulating BSEP activity in estrogen‐induced cholestasis, a novel finding that might help us to better understand and treat cholestatic disorders. (Hepatology 2016;64:535‐548)
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