Xenobiotic-induced activation of human aryl hydrocarbon receptor target genes in Drosophila is mediated by the epigenetic chromatin modifiers

Aryl hydrocarbon receptor (AHR) is the key transcription factor that controls animal development and various adaptive processes. The AHR\u27s target genes are involved in biodegradation of endogenous and exogenous toxins, regulation of immune response, organogenesis, and neurogenesis. Ligand binding is important for the activation of the AHR signaling pathway. Invertebrate AHR homologs are activated by endogenous ligands whereas vertebrate AHR can be activated by both endogenous and exogenous ligands (xenobiotics). Several studies using mammalian cultured cells have demonstrated that transcription of the AHR target genes can be activated by exogenous AHR ligands, but little is known about the effects of AHR in a living organism. Here, we examined the effects of human AHR and its ligands using transgenic Drosophila lines with an inducible human AhR gene. We found that exogenous AHR ligands can increase as well as decrease the transcription levels of the AHR target genes, including genes that control proliferation, motility, polarization, and programmed cell death. This suggests that AHR activation may affect the expression of gene networks that could be critical for cancer progression and metastasis. Importantly, we found that AHR target genes are also controlled by the enzymes that modify chromatin structure, in particular components of the epigenetic Polycomb Repressive complexes 1 and 2. Since exogenous AHR ligands (alternatively - xenobiotics) and small molecule inhibitors of epigenetic modifiers are often used as pharmaceutical anticancer drugs, our findings may have significant implications in designing new combinations of therapeutic treatments for oncological diseases. © Akishina et al

Sparkling extreme-ultraviolet bright dots observed with Hi-C

Observing the Sun at high time and spatial scales is a step toward understanding the finest and fundamental scales of heating events in the solar corona. The high-resolution coronal (Hi-C) instrument has provided the highest spatial and temporal resolution images of the solar corona in the EUV wavelength range to date. Hi-C observed an active region on 2012 July 11 that exhibits several interesting features in the EUV line at 193 Å. One of them is the existence of short, small brightenings "sparkling" at the edge of the active region; we call these EUV bright dots (EBDs). Individual EBDs have a characteristic duration of 25 s with a characteristic length of 680 km. These brightenings are not fully resolved by the SDO/AIA instrument at the same wavelength; however, they can be identified with respect to the Hi-C location of the EBDs. In addition, EBDs are seen in other chromospheric/coronal channels of SDO/AIA, which suggests a temperature between 0.5 and 1.5 MK. Based on their frequency in the Hi-C time series, we define four different categories of EBDs: single peak, double peak, long duration, and bursty. Based on a potential field extrapolation from an SDO/HMI magnetogram, the EBDs appear at the footpoints of large-scale, trans-equatorial coronal loops. The Hi-C observations provide the first evidence of small-scale EUV heating events at the base of these coronal loops, which have a free magnetic energy of the order of 1026 erg. © 2014. The American Astronomical Society. All rights reserved

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

The Status of Humoral Immunity to Parvovirus B19 in Population of Certain Geographical Regions

Introduction. In a number of countries, including Russia, there is no systematic registration and reporting of parvovirus infection cases; the extent of its spread can be estimated by using humoral immunity rates.Purpose of the study: Assessment of seroprevalence of parvovirus B19 (B19V) in different age groups of population of Russia, Central Asia, and West Africa.Materials and methods. A total of 1,732 blood serum samples from residents of St. Petersburg and Nur-Sultan, migrant workers from Uzbekistan and Tajikistan, residents of the Republic of Guinea were studied for IgG antibodies to B19V.Results. The highest seroprevalence rates were identified in St. Petersburg and Nur-Sultan (62–65%); the lowest rates were registered among migrant workers from Uzbekistan and Tajikistan (47%). The results for the Republic of Guinea showed a B19V seroprevalence rate of 53%. It was found that there is an increasing trend of seropositivity with age; the percentage of seropositive individuals clearly increases in older age groups: up to 55% — among migrant workers from Central Asia and residents of the Republic of Guinea; up to 80–85% — among residents of St. Petersburg and Nur-Sultan.Discussion. The obtained results confirm the worldwide occurrence of parvovirus infection. People susceptible to infection can cause infection spreading in high-risk groups — among pregnant women, immunodeficient patients, blood product recipients, and cancer patients

Soliton Molecules in Self-Mode-Locked Ring-Cavity Er/Yb Double-Clad Fiber Laser

In this paper, generation of soliton molecules by a self-mode-locked Er/Yb double clad fiber laser is experimentally demonstrated. The optical spectrum of the bound solitons exhibits eight well defined peaks at similar to 1563 nm with high modulation depth. The corresponding autocorrelation measurement shows a fundamental trace with several narrow peaks, suggesting the presence of bound solitons. The obtained results demonstrate the reliability of our simple laser configuration for the formation of more robust soliton molecules as the pump power is increased. The soliton molecules exhibit repetition rate of 19.54 MHz and average power of 1.2 W, achieved with a pump power of similar to 4.8 W

The Space Weather and Ultraviolet Solar Variability (SWUSV) Microsatellite Mission

International audienceWe present the ambitions of the SWUSV (Space Weather and Ultraviolet Solar Variability) Microsatellite Mission that encompasses three major scientific objectives: (1) Space Weather including the prediction and detection of major eruptions and coronal mass ejections (Lyman-Alpha and Herzberg continuum imaging); (2) solar forcing on the climate through radiation and their interactions with the local stratosphere (UV spectral irradiance from 180 to 400 nm by bands of 20 nm, plus Lyman-Alpha and the CN bandhead); (3) simultaneous radiative budget of the Earth, UV to IR, with an accuracy better than 1% in differential. The paper briefly outlines the mission and describes the five proposed instruments of the model payload: SUAVE (Solar Ultraviolet Advanced Variability Experiment), an optimized telescope for FUV (Lyman-Alpha) and MUV (200-220 nm Herzberg continuum) imaging (sources of variability); UPR (Ultraviolet Passband Radiometers), with 64 UV filter radiometers; a vector magnetometer; thermal plasma measurements and Langmuir probes; and a total and spectral solar irradiance and Earth radiative budget ensemble (SERB, Solar irradiance & Earth Radiative Budget). SWUSV is proposed as a small mission to CNES and to ESA for a possible flight as early as 2017-2018

Ash2 acts as an Ecdysone Receptor coactivator by stabilizing the histone methyltransferase Trr.

The molting hormone ecdysone triggers chromatin changes via histone modifica- tions that are important for gene regulation. On hormone activation, the ecdysone receptor (EcR) binds to the SET domain-containing histone H3 methyltransferase trithorax-related protein (Trr). Methylation of histone H3 at lysine 4 (H3K4me), which is associated with tran- scriptional activation, requires several cofactors, including Ash2. We find that ash2 mutants have severe defects in pupariation and metamorphosis due to a lack of activation of ecdy- sone-responsive genes. This transcriptional defect is caused by the absence of the H3K4me3 marks set by Trr in these genes. We present evidence that Ash2 interacts with Trr and is re- quired for its stabilization. Thus we propose that Ash2 functions together with Trr as an ecdysone receptor coactivator

The Space Weather & Ultraviolet Solar Variability Microsatellite Mission (SWUSV)

International audienceWe present a summary of the scientific objectives, payload and mission profile of the Space Weather & Ultraviolet Solar Variability Microsatellite Mission (SWUSV) proposed to CNES and ESA (small mission)