The inflammatory cytokine IL-6 induces FRA1 deacetylation promoting colorectal cancer stem-like properties

Colorectal cancer (CRC) has long been known for its tight association with chronic inflammation, thought to play a key role in tumor onset and malignant progression through the modulation of cancer stemness. However, the underlying molecular and cellular mechanisms are still largely elusive. Here we show that the IL-6/STAT3 inflammatory signaling axis induces the deacetylation of FRA1 at the Lys-116 residue located within its DNA-binding domain. The HDAC6 deacetylase underlies this key modification leading to the increase of FRA1 transcriptional activity, the subsequent transactivation of NANOG expression, and the acquisition of stem-like cellular features. As validated in a large (n = 123) CRC cohort, IL-6 secretion was invariably accompanied by increased FRA1 deacetylation at K116 and an overall increase in its protein levels, coincident with malignant progression and poor prognosis. Of note, combined treatment with the conventional cytotoxic drug 5-FU together with Tubastatin A, a HDAC6-specific inhibitor, resulted in a significant in vivo synergistic inhibitory effect on tumor growth through suppression of CRC stemness. Our results reveal a novel transcriptional and posttranslational regulatory cross-talk between inflammation and stemness signaling pathways that underlie self-renewal and maintenance of CRC stem cells and promote their malignant behavior. Combinatorial treatment aimed at the core regulatory mechanisms downstream of IL-6 may offer a novel promising approach for CRC treatment

Tetracycline: production, waste treatment and environmental impact assessment

The frequent occurrence of pharmaceuticals in the aquatic environment requires an assessment of their environmental impact and their negative effects in humans. Among the drugs with high harmful potential to the environment are the antibiotics that reach the environment not only, as may be expected, through the effluents from chemical and pharmaceutical industries, but mainly through the sewage and livestock; because around 25 to 75% of the ingested drugs are excreted in unchanged form after the passage through the Gastro-Intestinal Tract. Tetracycline has high world consumption, representing a human consumption of about 23 kg/day in Brazil in 2007. At the moment, researches are being made to develop new tetracycline that incorporate heavy metals (Hg, Cd, Re, Pt, Pd) to their structures in order to increase their bactericidal effect. The conventional wastewater treatment plants are not able to degrade complex organic molecules to reduce their toxicity and improve their biodegradability. For this reason new technologies, i.e., the advanced oxidation processes, are being developed to handle this demand. The objectives of this study are to review the literature on the processes of obtaining tetracycline, presenting its waste treatment methods and evaluation of their environmental impact

First observation of a shape isomer and a low-lying strongly-coupled prolate band in neutron-deficient semi-magic 187Pb

Prompt and delayed γ-ray spectroscopy of the neutron-deficient, semi-magic isotope 187Pb has been performed using the recoil-decay and isomer-decay tagging techniques at the Argonne Gas-Filled Analyzer. A new 5.15(15)-μs isomeric state at only 308 keV above the spherical 3/2− ground state is identified and classified as a shape isomer. A strongly-coupled band is observed on top of the isomer, which is nearly identical to the one built on the prolate 7/2−[514] Nilsson state in the isotone 185Hg. Based on this similarity and on the result of the potential-energy surface calculations, the new isomer in 187Pb is proposed to originate from the same configuration. The retarded character of the 308-keV (7/2−)→3/2gs− transition with a deduced B(E2)=5.6(2)×10−4 W.u. can be well explained by the significant difference between the prolate parent and spherical daughter configurations, leading to the shape isomerism. The excitation energy of the isomer is surprisingly low, being roughly half of the excitation energies of the known 0+ intruder bandheads in the neighboring 186,188Pb isotopes. The combined results of the present work and the previous α-decay and laser spectroscopy studies present evidence for triple shape coexistence at low energy in the negative-parity configurations of 187Pb, which is well reproduced by the potential-energy surface calculations

What is the future for nuclear fission technology? A technical opinion from the Guest Editors of VSI NFT series and the Editor of the Journal Nuclear Engineering and Design

The Nuclear Fission Technology (NFT) series of Virtual Special Issues (VSIs) for the Journal Nuclear Engineering and Design (J NED) was proposed in 2023, including the request to potential authors of manuscript to address the following questions: o For how long will (water-cooling based) large size nuclear reactor survive? o Will water-technology based SMRs displace large reactors? o Will non-water-cooling technology SMRs and micro-reactors have an industrial deployment? o Will breeding technology, including thorium exploitation, have due relevance? o Will ‘nuclear infrastructure’ (fuel supply, financial framework, competence by regulators for new designs, waste management, etc.) remain or be sufficiently robust? Several dozen Guest Editors (GEs), i.e., the authors of the present document, managed the activity together with the Editor-in-Chief (EiC) of the journal. More than one thousand scientists contributed 470+ manuscripts, not evenly distributed among the geographical regions of the world and not necessarily addressing directly the bullet-questions, but certainly providing a view of current research being done. Key conclusions are as follows: (a) Large size reactors are necessary for a sustainable and safe exploitation of nuclear fission technology; (b) The burning of 233U (from thorium) and 239Pu (from uranium) is unavoidable, as well as recycling residual uranium currently part of waste; (c) Nuclear infrastructures in countries that currently use, or are entering the use of, fission energy for electricity production need a century planning; (d) The adoption of small reactors for commercial naval propulsion, hydrogen production and desalination is highly recommended

Open data from the third observing run of LIGO, Virgo, KAGRA, and GEO

The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in 2019 April and lasting six months, O3b starting in 2019 November and lasting five months, and O3GK starting in 2020 April and lasting two weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at https://gwosc.org. The main data set, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of binary black hole coalescences confidently observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include the effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that have already been identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total source-frame mass M > 70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz emitted gravitational-wave frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place a conservative upper limit for the merger rate density of high-mass binaries with eccentricities 0 < e ≤ 0.3 at 16.9 Gpc−3 yr−1 at the 90% confidence level

Resonant acceleration of electrons by intense circularly polarized Gaussian laser pulses

10.1017/S0263034608000086Laser and Particle Beams26151-59LPBE