There is a short gamma-ray burst prompt phase at the beginning of each long one

We compare the prompt intrinsic spectral properties of a sample of short Gamma--ray Burst (GRB) with the first 0.3 seconds (rest frame) of long GRBs observed by Fermi/GBM. We find that short GRBs and the first part of long GRBs lie on the same E_p--E_iso correlation, that is parallel to the relation for the time averaged spectra of long GRBs. Moreover, they are indistinguishable in the E_p--L_iso plane. This suggests that the emission mechanism is the same for short and for the beginning of long events, and both short and long GRBs are very similar phenomena, occurring on different timescales. If the central engine of a long GRB would stop after ~0.3 * (1+z) seconds the resulting event would be spectrally indistinguishable from a short GRB.Comment: 14 pages, 6 figures, MNRAS accepte

Transcription Impacts the Efficiency of mRNA Translation via Co-transcriptional N6-adenosine Methylation

Transcription and translation are two main pillars of gene expression. Due to the different timings, spots of action, and mechanisms of regulation, these processes are mainly regarded as distinct and generally uncoupled, despite serving a common purpose. Here, we sought for a possible connection between transcription and translation. Employing an unbiased screen of multiple human promoters, we identified a positive effect of TATA box on translation and a general coupling between mRNA expression and translational efficiency. Using a CRISPR-Cas9-mediated approach, genome-wide analyses, and in vitro experiments, we show that the rate of transcription regulates the efficiency of translation. Furthermore, we demonstrate that m6A modification of mRNAs is co-transcriptional and depends upon the dynamics of the transcribing RNAPII. Suboptimal transcription rates lead to elevated m6A content, which may result in reduced translation. This study uncovers a general and widespread link between transcription and translation that is governed by epigenetic modification of mRNAs

Palmitoylethanolamide Counteracts Enteric Inflammation and Bowel Motor Dysfunctions in a Mouse Model of Alzheimer’s Disease

Palmitoylethanolamide (PEA), an endogenous lipid mediator, is emerging as a promising pharmacological agent in multiple neurodegenerative disorders for its anti-inflammatory and neuroprotective properties. However, its effects on enteric inflammation and colonic dysmotility associated with Alzheimer’s disease (AD) are lacking. This study was designed to investigate the beneficial effect of PEA administration in counteracting the enteric inflammation and relieving the bowel motor dysfunctions in an AD mouse model, SAMP8 mice. In addition, the ability of PEA in modulating the activation of enteric glial cells (EGCs), pivotally involved in the pathophysiology of bowel dysfunctions associated with inflammatory conditions, has also been examined. SAMP8 mice at 4 months of age were treated orally with PEA (5 mg/kg/day) for 2 months. SAMR1 animals were employed as controls. At the end of treatment, parameters dealing with colonic motility, inflammation, barrier integrity and AD protein accumulation were evaluated. The effect of PEA on EGCs was tested in cultured cells treated with lipopolysaccharide (LPS) plus β-amyloid 1–42 (Aβ). SAMP8 treated with PEA displayed: 1) an improvement of in vitro colonic motor activity, citrate synthase activity and intestinal epithelial barrier integrity and 2) a decrease in colonic Aβ and α-synuclein (α-syn) accumulation, S100-β expression as well as enteric IL-1β and circulating LPS levels, as compared with untreated SAMP8 mice. In EGCs, treatment with PEA counteracted the increment of S100-β, TLR-4, NF-κB p65 and IL-1β release induced by LPS and Aβ. These results suggest that PEA, under a condition of cognitive decline, prevents the enteric glial hyperactivation, reduces AD protein accumulation and counteracts the onset and progression of colonic inflammatory condition, as well as relieves intestinal motor dysfunctions and improves the intestinal epithelial barrier integrity. Therefore, PEA represents a viable approach for the management of the enteric inflammation and motor contractile abnormalities associated with AD

The spectroscopic follow-up of the QUBRICS bright quasar survey

We present the results of the spectroscopic follow up of the QUBRICS survey. The selection method is based on a machine learning approach applied to photometric catalogs, covering an area of $\sim$ 12,400 deg$^2$ in the Southern Hemisphere. The spectroscopic observations started in 2018 and identified 55 new, high-redshift (z>=2.5), bright (i<=18) QSOs, with the catalog published in late 2019. Here we report the current status of the survey, bringing the total number of bright QSOs at z<=2.5 identified by QUBRICS to 224. The success rate of the QUBRICS selection method, in its most recent training, is estimated to be 68%. The predominant contaminant turns out to be lower-z QSOs at z<2.5. This survey provides a unique sample of bright QSOs at high-z available for a number of cosmological investigations. In particular, carrying out the redshift drift measurements (Sandage Test) in the Southern Hemisphere, using the HIRES spectrograph at the 39m ELT, appears to be possible with less than 2500 hours of observations spread over 30 targets in 25 years.Comment: Accepted for publication in ApJS, 24 pages, 8 figures, 4 table

Dietary Supplementation with the Probiotic SF68 Reinforces Intestinal Epithelial Barrier in Obese Mice by Improving Butyrate Bioavailability

Scope: Modifications in intestinal microbiota and its metabolites, the short-chain fatty acids (SCFA) are main factors altering intestinal epithelial barrier integrity and eliciting the onset of a meta-inflammation observed in obesity. The present study is aimed at evaluating the efficacy of Enterococcus faecium (SF68) administration in counteracting the impairment of gut barrier and enteric inflammation in a model of diet-induced obesity, characterizing the molecular mechanisms underlying such beneficial effects. Methods and Results: Male C57BL/6J mice, fed with standard diet (SD) or high-fat diet (HFD), are treated with SF68 (108&nbsp;CFU&nbsp;day−1). After 8&nbsp;weeks, plasma interleukin (IL)-1β and lipopolysaccharide binding protein (LBP) are measured, analysis of fecal microbiota composition and butyrate content as well as intestinal malondialdehyde, myeloperoxidase, mucins, tight junction protein, and butyrate transporter expression are investigated. After 8&nbsp;weeks, SF68 administration counteracts the body weight gain in HFD mice, reducing plasma IL-1β and LBP. In parallel, SF68 treatment acts against the intestinal inflammation in HFD-fed animals and improves the intestinal barrier integrity and functionality in obese mice via the increase in tight junction protein and intestinal butyrate transporter (sodium-coupled monocarboxylate transporter 1) expression. Conclusions: Supplementation with SF68 reduces intestinal inflammation and reinforces the enteric epithelial barrier in obese mice, improving the transport and utilization of butyrate

Comparing the spectral lag of short and long gamma-ray bursts and its relation with the luminosity

We investigated the rest frame spectral lags of two complete samples of bright long (50) and short (6) gamma-ray bursts (GRB) detected by Swift. We analysed the Swift/BAT data through a discrete cross-correlation function (CCF) fitted with an asymmetric Gaussian function to estimate the lag and the associated uncertainty. We find that half of the long GRBs have a positive lag and half a lag consistent with zero. All short GRBs have lags consistent with zero. The distributions of the spectral lags for short and long GRBs have different average values. Limited by the small number of short GRBs, we cannot exclude at more than 2 sigma significance level that the two distributions of lags are drawn from the same parent population. If we consider the entire sample of long GRBs, we do not find evidence for a lag-luminosity correlation, rather the lag-luminosity plane appears filled on the left hand side, thus suggesting that the lag-luminosity correlation could be a boundary. Short GRBs are consistent with the long ones in the lag-luminosity plane.Comment: 11 pages, 6 figures, 2 tables, accepted for publication in MNRA

New Visions on Natural Products and Cancer Therapy: Autophagy and Related Regulatory Pathways

Macroautophagy (autophagy) has been a highly conserved process throughout evolution and allows cells to degrade aggregated/misfolded proteins, dysfunctional or superfluous organelles and damaged macromolecules, in order to recycle them for biosynthetic and/or energetic purposes to preserve cellular homeostasis and health. Changes in autophagy are indeed correlated with several pathological disorders such as neurodegenerative and cardiovascular diseases, infections, cancer and inflammatory diseases. Conversely, autophagy controls both apoptosis and the unfolded protein response (UPR) in the cells. Therefore, any changes in the autophagy pathway will affect both the UPR and apoptosis. Recent evidence has shown that several natural products can modulate (induce or inhibit) the autophagy pathway. Natural products may target different regulatory components of the autophagy pathway, including specific kinases or phosphatases. In this review, we evaluated ~100 natural compounds and plant species and their impact on different types of cancers via the autophagy pathway. We also discuss the impact of these compounds on the UPR and apoptosis via the autophagy pathway. A multitude of preclinical findings have shown the function of botanicals in regulating cell autophagy and its potential impact on cancer therapy; however, the number of related clinical trials to date remains low. In this regard, further pre-clinical and clinical studies are warranted to better clarify the utility of natural compounds and their modulatory effects on autophagy, as fine-tuning of autophagy could be translated into therapeutic applications for several cancers

Cinnamides Target Leishmania amazonensis Arginase Selectively

Caffeic acid and related natural compounds were previously described as Leishmania amazonensis arginase (L-ARG) inhibitors, and against the whole parasite in vitro. In this study, we tested cinnamides that were previously synthesized to target human arginase. The compound caffeic acid phenethyl amide (CAPA), a weak inhibitor of human arginase (IC50 = 60.3 ± 7.8 μM) was found to have 9-fold more potency against L-ARG (IC50 = 6.9 ± 0.7 μM). The other compounds that did not inhibit human arginase were characterized as L-ARG, showing an IC50 between 1.3-17.8 μM, and where the most active was compound 15 (IC50 = 1.3 ± 0.1 μM). All compounds were also tested against L. amazonensis promastigotes, and only the compound CAPA showed an inhibitory activity (IC50 = 80 μM). In addition, in an attempt to gain an insight into the mechanism of competitive L-ARG inhibitors, and their selectivity over mammalian enzymes, we performed an extensive computational investigation, to provide the basis for the selective inhibition of L-ARG for this series of compounds. In conclusion, our results indicated that the compounds based on cinnamoyl or 3,4-hydroxy cinnamoyl moiety could be a promising starting point for the design of potential antileishmanial drugs based on selective L-ARG inhibitors