Toll-like receptor-mediated signaling cascade as a regulator of the inflammation network during alcoholic liver disease

Chronic abuse of alcohol leads to various histological abnormalities in the liver. These are conditions collectively known as alcoholic liver disease (ALD). Currently, ALD is considered to be one of the major causes of death worldwide. An impaired intestinal barrier with related endotoxemia is among the various pathogenetic factors. This is mainly characterized by circulating levels of lipopolysaccharide (LPS), considered critical for the onset of intra-hepatic inflammation. This in turn promotes hepatocellular damage and fibrosis in ALD. Elevated levels of LPS exert their effects by binding to Toll-like receptors (TLRs) which are expressed by all liver-resident cells. The activation of TLR signaling triggers an overproduction and release of some cytokines, which promote an autocatalytic cascade of other proinflammatory signals. In this review, we provide an overview of the mechanisms that sustain LPS-mediated activation of TLR signaling, reporting current experimental and clinical evidence of its role during inflammation in ALD

Dynamical Comptonization in spherical flows: black hole accretion and stellar winds

The transport of photons in steady, spherical, scattering flows is investigated. The moment equations are solved analytically for accretion onto a Schwarzschild black hole, taking into full account relativistic effects. We show that the emergent radiation spectrum is a power law at high frequencies with a spectral index smaller (harder spectrum) than in the non--relativistic case. Radiative transfer in an expanding envelope is also analyzed. We find that adiabatic expansion produces a drift of injected monochromatic photons towards lower frequencies and the formation of a power--law, low--energy tail with spectral index $-3$.Comment: 11 pages with 3 ps figures, MNRAS to appea

ADAR enzyme and miRNA story: A nucleotide that can make the difference

Adenosine deaminase acting on RNA (ADAR) enzymes convert adenosine (A) to inosine (I) in double-stranded (ds) RNAs. Since Inosine is read as Guanosine, the biological consequence of ADAR enzyme activity is an A/G conversion within RNA molecules. A-to-I editing events can occur on both coding and non-coding RNAs, including microRNAs (miRNAs), which are small regulatory RNAs of ~20-23 nucleotides that regulate several cell processes by annealing to target mRNAs and inhibiting their translation. Both miRNA precursors and mature miRNAs undergo A-to-I RNA editing, affecting the miRNA maturation process and activity. ADARs can also edit 3' UTR of mRNAs, further increasing the interplay between mRNA targets and miRNAs. In this review, we provide a general overview of the ADAR enzymes and their mechanisms of action as well as miRNA processing and function. We then review the more recent findings about the impact of ADAR-mediated activity on the miRNA pathway in terms of biogenesis, target recognition, and gene expression regulation

An unified timing and spectral model for the Anomalous X-ray Pulsars XTE J1810-197 and CXOU J164710.2-455216

Anomalous X-ray pulsars (AXPs) and soft gamma repeaters (SGRs) are two small classes of X-ray sources strongly suspected to host a magnetar, i.e. an ultra-magnetized neutron star with $B\approx 10^14-10^15 G. Many SGRs/AXPs are known to be variable, and recently the existence of genuinely "transient" magnetars was discovered. Here we present a comprehensive study of the pulse profile and spectral evolution of the two transient AXPs (TAXPs) XTE J1810-197 and CXOU J164710.2-455216. Our analysis was carried out in the framework of the twisted magnetosphere model for magnetar emission. Starting from 3D Monte Carlo simulations of the emerging spectrum, we produced a large database of synthetic pulse profiles which was fitted to observed lightcurves in different spectral bands and at different epochs. This allowed us to derive the physical parameters of the model and their evolution with time, together with the geometry of the two sources, i.e. the inclination of the line-of-sight and of the magnetic axis with respect to the rotation axis. We then fitted the (phase-averaged) spectra of the two TAXPs at different epochs using a model similar to that used to calculate the pulse profiles ntzang in XSPEC) freezing all parameters to the values obtained from the timing analysis, and leaving only the normalization free to vary. This provided acceptable fits to XMM-Newton data in all the observations we analyzed. Our results support a picture in which a limited portion of the star surface close to one of the magnetic poles is heated at the outburst onset. The subsequent evolution is driven both by the cooling/varying size of the heated cap and by a progressive untwisting of the magnetosphere.Comment: 15 pages, 12 figures, accepted for publication in Ap

Bifidobacteria and lactobacilli in the gut microbiome of children with non-alcoholic fatty liver disease: which strains act as health players?

Introduction: Non-alcoholic fatty liver disease (NAFLD), considered the leading cause of chronic liver disease in children, can often progress from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH). It is clear that obesity is one of the main risk factors involved in NAFLD pathogenesis, even if specific mechanisms have yet to be elucidated. We investigated the distribution of intestinal bifidobacteria and lactobacilli in the stools of four groups of children: obese, obese with NAFL, obese with NASH, and healthy, age-matched controls (CTRLs). Material and methods: Sixty-one obese, NAFL and NASH children and 54 CTRLs were enrolled in the study. Anthropometric and metabolic parameters were measured for all subjects. All children with suspected NASH underwent liver biopsy. Bifidobacteria and lactobacilli were analysed in children’s faecal samples, during a broader, 16S rRNA-based pyrosequencing analysis of the gut microbiome. Results: Three Bifidobacterium spp. (Bifidobacterium longum, Bifidobacterium bifidum, and Bifidobacterium adolescentis) and five Lactobacillus spp. (L. zeae, L. vaginalis, L. brevis, L. ruminis, and L. mucosae) frequently recurred in metagenomic analyses. Lactobacillus spp. increased in NAFL, NASH, or obese children compared to CTRLs. Particularly, L. mucosae was significantly higher in obese (p = 0.02426), NAFLD (p = 0.01313) and NASH (p = 0.01079) than in CTRLs. In contrast, Bifidobacterium spp. were more abundant in CTRLs, suggesting a protective and beneficial role of these microorganisms against the aforementioned diseases. Conclusions: Bifidobacteria seem to have a protective role against the development of NAFLD and obesity, highlighting their possible use in developing novel, targeted and effective probiotics

Temperature changes and the ATP concentration of the soil microbial biomass

Two soils from temperate sites (UK; arable and grassland) were incubated aerobically at 0, 5, 15 or 258C for up to 23 days. During this period both soils were analysed for soil microbial biomass carbon (biomass C) and adenosine 5' triphosphate contents (ATP). Biomass C did not change signi\uaecantly in either soil at any temperature throughout, except during days 0 to 1 in the grassland soil. Soil ATP contents increased slowly throughout the 23 days of incubation, from 2.2 to a maximum of 3.1 nmol ATP g \uff1 soil in the arable soil (a 40% increase) and from 6.2 to a maximum of 11.2 nmol ATP g \uff1 soil in the grassland soil (an increase of 81%), both at 258C. Since biomass C did not change either with increasing temperature or increasing time of incubation, it was concluded that an increase in ATP was either due to an increase in adenylate energy charge or de novo synthesis of ATP, or both. During the incubation, biomass ATP concentrations ranged from about 5 to 12 mmol ATP g \uff1 biomass C but trends between biomass ATP and incubation temperatures were not very obvious until about day 13. On day 23, biomass ATP concentrations were positively and linearly related to temperature: (mmol ATP g \uff1 biomass C = 6.9820.35 + 0.13420.023 T0 (r 2 = 0.77) with no signi\uaecant di erence in the slope between the grassland and arable soils. At 258C the biomass ATP concentration was 10.3 mmol g \uff1 biomass C, remarkably close to many other published values. It was concluded that, although the biomass increased its ATP concentration in response to increasing temperature, the increase was comparatively small. Also, at all temperatures tested, the biomass maintained its ATP concentration within the range commonly reported for micro-organisms growing expontentially in vitro. This is despite the fact that the biomass normally exhibits other features more typical of a ``resting'' or dormant population 0 a paradox which still is not resolved

Correlation of Ac-impedance and in situ X-ray spectra of LiCoO2

In-situ X-ray and AC-impedance spectra have been obtained simultaneously during the deintercalation of lithium from LiCoO2 using a specially designed electrochemical cell. The AC-dispersions have been correlated with the cell parameters obtained from the X-ray spectra. The correlation confirms previous hypothesis on the interpretation of the AC-dispersions in terms of an equivalent circuit comprising an element that relates the change of the intrinsic electronic conductivity, occurring at the early stages of deintercalation, to the semiconductor to metal transition caused by the change of the cell parameters

Vibrational Stabilization of Cluster Synchronization in Oscillator Networks

Cluster synchronization is of paramount importance for the normal functioning of numerous technological and natural systems. Deviations from normal cluster synchronization patterns are closely associated with various malfunctions, such as neurological disorders in the brain. Therefore, it is crucial to restore normal system functions by stabilizing the appropriate cluster synchronization patterns. Most existing studies focus on designing controllers based on state measurements to achieve system stabilization. However, in many real-world scenarios, measuring system states, such as neuronal activity in the brain, poses significant challenges, rendering the stabilization of such systems difficult. To overcome this challenge, in this paper, we employ an open-loop control strategy, vibrational control, which does not requires any state measurements. We establish some sufficient conditions under which vibrational inputs stabilize cluster synchronization. Further, we provide a tractable approach to design vibrational control. Finally, numerical experiments are conducted to demonstrate our theoretical findings.Comment: Submitted to Open Journal of Control System

Immune checkpoint inhibitors in pre-treated gastric cancer patients: Results from a literature-based meta-analysis

Immunotherapy has recently changed the treatment of several cancers. We performed a literature-based meta-analysis of randomised controlled trials to assess the efficacy of the novel immune checkpoint inhibitors (ICIs) in metastatic gastric cancer. The main outcome was overall survival. Based on age (cut-off agreed at 65 years), tumour location (gastric vs. gastro-oesophageal junction), programmed death-ligand 1 (PD-L1) status, sex and Eastern Cooperative Oncology Group (ECOG) status (1 vs. 0), we scheduled a subgroup analysis for the overall survival. Three studies were included in the analysis for a total of 1456 cases (811 cases were in the experimental group and 645 cases in the control group). The pooled analysis showed improved overall survival in the experimental arm in the absence of statistical significance (hazard ratio (HR) = 0.87, 95% CI: 0.64\u20131.18; p = 0.37). The subgroup of patients with PD-L1-positive tumours (HR = 0.82 vs. 1.04) and gastro-oesophageal junction cancer (HR = 0.82 vs. 1.04) showed a statistically significant advantage of overall survival. This study supports the efficacy of immune checkpoint inhibitors in the subgroup of patients with metastatic gastric cancer with PD-L1-positive and gastro-oesophageal junction tumour location. Future studies are needed with the aim of identifying reliable predictive biomarkers of ICI efficacy