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

A structure-based proposal for the catalytic mechanism of the bacterial acid phosphatase AphA belonging to the DDDD superfamily of phosphohydrolases

The Escherichia coli gene aphA codes for a periplasmic acid phosphatase called AphA, belonging to class B bacterial phosphatases, which is part of the DDDD superfamily of phosphohydrolases. After our first report about its crystal structure, we have started a series of crystallographic studies aimed at understanding of the catalytic mechanism of the enzyme. Here, we report three crystal structures of the AphA enzyme in complex with the hydrolysis products of nucleoside monophosphate substrates and a fourth with a proposed intermediate analogue that appears to be covalently bound to the enzyme. Comparison with the native enzyme structure and with the available X-ray structures of different phosphatases provides clues about the enzyme chemistry and allows us to propose a catalytic mechanism for AphA, and to discuss it with respect to the mechanism of other bacterial and human phosphatases. (c) 2005 Elsevier Ltd. All rights reserved

SARS-CoV-2 Mproinhibition by a zinc ion: structural features and hints for drug design

The first structure of the SARS-CoV-2 main protease in complex with an isolated zinc ion provides solid ground for the design of potent and selective metal-conjugated inhibitors

Cytogenetic study in therapy-related myelodysplastic syndromes (t-MDS) and acute non-lymphocytic leukaemia (t-ANLL).

A cytogenetic study was performed in 27 patients suspected of t-MDS or t-ANLL. In 12 patients the diagnosis of t-MDS or t-ANLL was confirmed by morphological, cytochemical and immunophenotypical analysis. The cases were classified as RA (one), RAEB (four), CMML (two), ANLL (five). They had received chemotherapy and/or RT for Hodgkin's disease (eight cases), solid tumours (three cases) and multiple myeloma (one case). Clonal chromosome abnormalities were found in bone marrow or peripheral blood cells in all the 12 cases. Five patients had a clonal abnormality of chromosome no. 5 (monosomy, deletions, translocation and inversion of 5q). The critical region on chromosome no. 5 comprised bands q12-q34. Monosomy and deletion of chromosome 7q was observed in the other two patients. In the six remaining patients various karyotypic patterns were observed including a t(4;11) (q21;q23) in one case, monosomies (four cases) and trisomies (one case) of different chromosomes. In the other 15 cases, the presence of a normal karyotype together with the morphological and immunophenotypical characterisation was consistent with a diagnosis of non-neoplastic specimens

Choreography, controversy and child sex abuse: Theoretical reflections on a cultural criminological analysis of dance in a pop music video

This article was inspired by the controversy over claims of ‘pedophilia!!!!’ undertones and the ‘triggering’ of memories of childhood sexual abuse in some viewers by the dance performance featured in the music video for Sia’s ‘Elastic Heart’ (2015). The case is presented for acknowledging the hidden and/or overlooked presence of dance in social scientific theory and cultural studies and how these can enhance and advance cultural criminological research. Examples of how these insights have been used within other disciplinary frameworks to analyse and address child sex crime and sexual trauma are provided, and the argument is made that popular cultural texts such as dance in pop music videos should be regarded as significant in analysing and tracing public perceptions and epistemologies of crimes such as child sex abuse

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

Spectroscopy of QUBRICS quasar candidates: 1672 new redshifts and a golden sample for the Sandage test of the redshift drift

The QUBRICS (QUasars as BRIght beacons for Cosmology in the Southern hemisphere) survey aims at constructing a sample of the brightest quasars with z∼> 2.5, observable with facilities in the Southern Hemisphere. QUBRICS makes use of the available optical and IR wide-field surveys in the South and of Machine Learning techniques to produce thousands of bright quasar candidates of which only a few hundred have been confirmed with follow-up spectroscopy. Taking advantage of the recent Gaia Data Release 3, which contains 220 million low-resolution spectra, and of a newly developed spectral energy distribution fitting technique, designed to combine the photometric information with the Gaia spectroscopy, it has been possible to measure 1672 new secure redshifts of QUBRICS candidates, with a typical uncertainty of σz = 0.02. This significant progress of QUBRICS brings it closer to (one of) its primary goals: providing a sample of bright quasars at redshift 2.5 < z < 5 to perform the Sandage test of the cosmological redshift drift. A Golden Sample of seven quasars is presented that makes it possible to carry out this experiment in about 1500 h of observation in 25 yr, using the ANDES spectrograph at the 39m ELT, a significant improvement with respect to previous estimates

Enhancing the pharmacodynamic profile of a class of selective COX-2 inhibiting nitric oxide donors

We report herein the development, synthesis, physicochemical and pharmacological characterization of a novel class of pharmacodynamic hybrids that selectively inhibit cyclooxygenase-2 (COX-2) isoform and present suitable nitric oxide releasing properties. The replacement of the ester moiety with the amide group gave access to in vivo more stable and active derivatives that highlighted outstanding pharmacological properties. In particular, the glycine derivative proved to be extremely active in suppressing hyperalgesia and edema. © 2013 Elsevier Ltd. All rights reserved