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Correction to: Oncogene https://doi.org/10.1038/onc.2011.368, Published online 22 Aug 2011 In the published version of this article, the images for cytoplasmic and nuclear FGF7 in MDA-MB-231 cells were duplicated and mistaken for total FGF7 in SKBR-3 and MDA-MB-231 cells.

Gamma-ray bursts are the strongest explosions in the Universe since the Big Bang, believed to be produced either in forming black holes at the end of massive star evolution or merging of compact objects. Spectral and timing properties of gamma-ray bursts suggest that the observed bright gamma-rays are produced in the most relativistic jets in the Universe; however, the physical properties, especially the structure and magnetic topologies in the jets are still not well known, despite several decades of studies. It is widely believed that precise measurements of the polarization properties of gamma-ray bursts should provide crucial information on the highly relativistic jets. As a result there have been many reports of gamma-ray burst polarization measurements with diverse results, see, however many such measurements suffered from substantial uncertainties, mostly systematic. After the first successful measurements by the GAP and COSI instruments, here we report a statistically meaningful sample of precise polarization measurements, obtained with the dedicated gamma-ray burst polarimeter, POLAR onboard China's Tiangong-2 spacelab. Our results suggest that the gamma-ray emission is at most polarized at a level lower than some popular models have predicted; although our results also show intrapulse evolution of the polarization angle. This indicates that the low polarization degrees could be due to an evolving polarization angle during a gamma-ray burst., 34 pages, 15 figures (16 pages and 3 figures without supplementary information). Accepted for publication in Nature Astronomy, http://dx.doi.org/10.1038/s41550-018-0664-0

Simple Summary Histones are also a common disease marker. After PAD4 mediated hypercitrullination extracellular H3Cit exhibits high toxicity contributing to tissue damage which, in cases of systemic inflammation, may lead to multiorgan failure and finally to death. We tested whether circulating histones rise in response to strenuous exercise. Herein, we have observed that circulating histones and PAD4 raised in response to exercise. Despite the parallel increase, no significant correlation between citrullinated histone and aggregation or cell-free nDNA was found. However, positive correlations of cf nDNA with aggregation and PAD4, lactate with aggregation, and lactate with citrullinated histone have been observed. Abstract Numerous studies have shown that cf nDNA significantly rises in stress caused by exercise. However, during nuclear decondensation, released DNA is followed by histones. Histones are also a common disease marker. After PAD4 mediated hypercitrullination extracellular H3Cit exhibits high toxicity contributing to tissue damage which, in cases of systemic inflammation, may lead to multiorgan failure and finally to death. We tested whether circulating histones rise in response to strenuous exercise. Eleven average-trained men performed three treadmill exercise tests to exhaustion at speed corresponding to 70% VO2max separated by 72 h of resting. Blood was collected before and just after each bout of exercise and plasma proteins were measured using enzyme-linked immunosorbent assay, whereas platelet activity was estimated with Light Transmission Aggregometry. Both, circulating histones and PAD4 raised in response to exercise. Plasma citrullinated histones increased from 3.1 ng/mL to 5.96 ng/mL (p = 0.0059), from 3.65 ng/mL to 6.37 ng/mL (p = 0.02), and from 3.86 ng/mL to 4.75 ng/mL (p = 0.033) after the first, second, and third treadmill run, respectively. However despite the parallel increase, no significant correlation between citrullinated histone and aggregation or cell-free nDNA was found. Furthermore, positive correlations of cf nDNA with aggregation and PAD4, lactate with aggregation, and lactate with citrullinated histone have been observed.

Strawberries can improve oxidants-antioxidants balance and reduce some cardiovascular risk factors in obese subjects. Paraoxonase-1 (PON-1) is a high-density lipoprotein-associated enzyme with antioxidant properties that can protect from coronary artery disease in humans. We examined the effect of strawberry consumption on plasma PON-1 activity and lipid profile in healthy nonobese subjects.Thirty-one subjects (body mass index [BMI] 24.4 ± 4.0 kg/m(2)) on their usual diet consumed 500 g of strawberry pulp daily for 30 days (first course) and after a 10-day washout the cycle was repeated (second course). Fasting blood and spot morning urine samples were collected before, during, and after each strawberry course (8 time points) for determination of paraoxonase and arylesterase PON-1 activities and lipid profile. Twenty subjects served as controls with respect to cholesterol and PON-1 activities changes over the study period.Strawberries decreased mean plasma paraoxonase PON-1 activity and this effect was more evident after the second course (by 11.6%, p0.05) than after the first course (5.4%, p = 0.06), whereas arylesterase activity was constant. Strawberries altered total cholesterol levels (p0.05) with a tendency to transiently decrease it (by 5.1%) only after 15 days of the first course. Triglycerides and high- and low-density lipoprotein cholesterol did not change in response to fruit consumption. No changes in PON-1 activities and lipid profile were noted in controls. Paraoxonase correlated with arylesterase activity (ƿ from 0.33 to 0.46 at the first 7 time points, p0.05). This association disappeared at the end of study (ƿ = 0.07) when the strongest inhibition of paraoxonase was noted.Supplementation of the usual diet with strawberries decreased paraoxonase PON-1 activity and did not improve lipid profiles in healthy nonobese subjects. Further studies are necessary to establish the clinical significance of paraoxonase suppression and to define a group of healthy subjects who can benefit from strawberry consumption with respect to cholesterol levels.

Strawberries can augment plasma antioxidant activity, but this may be confounded by selection of methods, time of blood sampling and concomitant dietary restrictions. We examined the effect of strawberry consumption on ferric reducing ability (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (DPPH-test) of native and non-urate plasma in healthy subjects on their usual diet. Eleven subjects consumed strawberries (500 g daily) for 9 days. Fasting and 3-h postprandial plasma and 24-h urine collection were obtained before, during and after strawberry course for FRAP, DPPH-test and polyphenols determination. Fifteen subjects served as a control in respect to plasma antioxidant activity changes and effect of 300 mg of oral ascorbate. First, 5th and 9th strawberry dose increased 3-h postprandial DPPH-test by 17.4, 17.6 and 12.6%, and FRAP by 15.5, 25.6 and 21.4% in comparison to fasting values in non-urate plasma (p

POLAR is a compact space-borne detector designed to perform reliable measurements of the polarization for transient sources like Gamma-Ray Bursts in the energy range 50-500keV. The instrument works based on the Compton Scattering principle with the plastic scintillators as the main detection material along with the multi-anode photomultiplier tube. POLAR has been launched successfully onboard the Chinese space laboratory TG-2 on 15th September, 2016. In order to reliably reconstruct the polarization information a highly detailed understanding of the instrument is required for both data analysis and Monte Carlo studies. For this purpose a full study of the in-orbit performance was performed in order to obtain the instrument calibration parameters such as noise, pedestal, gain nonlinearity of the electronics, threshold, crosstalk and gain, as well as the effect of temperature on the above parameters. Furthermore the relationship between gain and high voltage of the multi-anode photomultiplier tube has been studied and the errors on all measurement values are presented. Finally the typical systematic error on polarization measurements of Gamma-Ray Bursts due to the measurement error of the calibration parameters are estimated using Monte Carlo simulations., Comment: 43 pages, 30 figures, 1 table; Preprint accepted by NIMA

In-depth studies of solar flares emissions and energy releases include analyses of polarization data. Polarization gives clear information about mechanisms and processes leading to electron acceleration and photon production. Despite of many past attempts, the key energy range of hard X-rays was only rarely explored and results were inconclusive. To large extend it was due to greater instrumental complications. Currently several novel polarimeters are either to be employed or under constructions for both balloon and satellite based observations. The novel hard X-ray polarimeter POLAR is an instrument developed by a collaboration between Switzerland, China and Poland. It is primarily designed for high accuracy polarization measurements from the prompt photon emissions of the gamma-ray bursts. The satellite orientation and instrument pointing direction make it also capable for precise measurements of polarization in solar flares. The instrument should fly in near future onboard of the Chinese Space Station TG2.

Objective The oxidative burst of the host cells associated with bacterial pathogen infection contributes to the destruction of periodontal tissue. The present study investigates the effect of docosahexaenoic acid (DHA) on human gingival fibroblast (HGF) viability and ROS generation. Methods The cell viability by MTT assay, ROS level using H 2 DCF-DA probe, and protein thiol content were measured in HGFs after 24 h preincubation with different concentrations of DHA followed by treatment with H 2 O 2 . The cell death rate was determined by Annexin V/propidium iodide staining, and mitochondrial membrane potential (Δ Ψm ) was examined by MitoTracker Red probe in H 2 O 2 - and butyric acid-treated HGFs. The fatty acid composition of plasma membranes after incubation with DHA was determined by gas chromatography mass spectrometry. Results DHA preincubation in a dose-dependent manner increased the viability of HGFs exposed to H 2 O 2 and decreased ROS generation compared to the control cells. In HGFs preincubated with 30 μM DHA, the Δ Ψm significantly increased in both H 2 O 2 - and butyric acid-treated cells. Moreover, incubation with DHA preserved the protein thiol level as effectively as N-acetylcysteine. Application of 50 μM DHA increased the quantity of viable cells, decreased the number of necrotic cells after H 2 O 2 treatment, and protected HGFs from apoptosis induced by butyric acid. DHA in the plasma membranes of these HGFs represented about 6% of the total amount of fatty acids. Conclusions These results demonstrate that enrichment of HGFs with DHA reduces ROS generation and enhances the mitochondrial membrane potential protecting the fibroblasts against cytotoxic factors.

Berry fruits rich in anthocyanins have antioxidant and anti-inflammatory properties. Blood phagocytes are an important source of oxidants that contribute to inflammatory response and oxidative stress. We examined the effect of sour cherry consumption on luminol-enhanced whole blood chemiluminescence (LBCL) reflecting oxidants generation by circulating phagocytes in healthy subjects.Thirty-four and 29 healthy subjects (on a regular diet) consumed 500 g of sour cherries containing 346.5 mg of total anthocyanins or 500 g of anthocyanin-free apples everyday (between 1100 and 1400 hours) for 30 days. Twenty-four volunteers without any dietary intervention served as the control with respect to LBCL changes over the study period. Fasting blood and spot morning urine samples were collected before and after the fruit courses and after the 10-day wash-out period to measure resting and agonist (fMLP)-induced LBCL, blood cell count, concentration of various phenolics, and plasma antioxidant activity.Sour cherries inhibited (p0.05) median resting LBCL (by 29.5% and 33.7%) and fMLP-LBCL (by 24.7% and 32.3%) after 30-day consumption and after 10-day wash-out, respectively. No changes in LBCL were noted in the apple consumers and controls. Increased urinary levels of chlorogenic, 4-hydroxyhippuric, and 3-hydroxyhippuric acids occasionally correlated negatively with resting and fMLP-LBCL in sour cherry consumers. Other measured variables did not change in all groups over the study period.The inhibition of resting and agonist-induced LBCL suggests that regular sour cherry consumption may suppress the formation of reactive oxygen species by circulating phagocytes and decrease the risk of systemic imbalance between oxidants and antioxidants. This may be attributed to the anthocyanins in sour cherry and be one of mechanisms of the health-promoting effects of consumption of anthocyanin-rich fruits.

POLAR is a new satellite-born detector aiming to measure the polarization of an unprecedented number of Gamma-Ray Bursts in the 50-500 keV energy range. The instrument, launched on-board the Tiangong-2 Chinese Space lab on the 15th of September 2016, is designed to measure the polarization of the hard X-ray flux by measuring the distribution of the azimuthal scattering angles of the incoming photons. A detailed understanding of the polarimeter and specifically of the systematic effects induced by the instrument's non-uniformity are required for this purpose. In order to study the instrument's response to polarization, POLAR underwent a beam test at the European Synchrotron Radiation Facility in France. In this paper both the beam test and the instrument performance will be described. This is followed by an overview of the Monte Carlo simulation tools developed for the instrument. Finally a comparison of the measured and simulated instrument performance will be provided and the instrument response to polarization will be presented., Preprint Accepted for Publication in Nuclear Instruments and Methods in Physics Research A

The polarimetric data taken together with lightcurve and spectral data may provide a powerful probe of the nature of sources and emission mechanisms of Gamma-ray Bursts (GRBs). We would like to know if most of the GRBs are strongly polarized. There were several reports of detections of linear polarization but more accurate observational data and the statistical study are still needed. The POLAR experiment is a space-born polarimeter designed for measurement of γ-ray in the energy range 50-500 keV. The detector was mounted onto the Chinese Tiangong 2 space station in 2016. The preflight status of the POLAR experiment has been presented in the talk.

The POLAR detector is a space based Gamma Ray Burst (GRB) polarimeter with a wide field of view, which covers almost half the sky. The instrument uses Compton scattering of gamma rays on a plastic scintillator hodoscope to measure the polarization of the incoming photons. The instrument has been successfully launched on board of the Chinese space laboratory Tiangong 2 on September 15, 2016. The construction of the instrument components is described in this article. Details are provided on problems encountered during the construction phase and their solutions. Initial performance of the instrument in orbit is as expected from ground tests and Monte Carlo simulation.

Regular strawberry consumption augmented plasma antioxidant activity and decreased lipid peroxidation suggests preventive potential of these fruits against oxidative stress-dependent disorders. Blood phagocytes are important source of oxidants that may contribute to systemic oxidative stress. We examined the effect of strawberry consumption on the luminol enhanced whole blood chemiluminescence (LBCL) reflecting oxidants generation by circulating phagocytes in healthy subjects.Thirty-one healthy subjects (being on their usual diet) consumed 500 g of strawberry pulp daily (between 11.00-14.00) for 30 days (1st strawberry course) and after 10 day wash-out the cycle was repeated (2nd strawberry course). Fasting blood and spot morning urine samples were collected before and after each strawberry course for measuring resting and agonist (fMLP)-induced LBCL, various phenolics and plasma antioxidant activity. Twenty subjects served as a control in respect to LBCL changes over the study period.Strawberry consumption decreased median resting LBCL and this effect was more evident after the 1st course (by 38.2%, p0.05) than after the the 2nd one (18.7%), while fMLP-induced LBCL was constant. No changes in LBCL were noted in controls. Strawberries increased fasting plasma levels of caffeic acid and homovanillic acid as well as urolithin A and 4-hydroxyhippuric acid in spot urine. Plasma antioxidant activity and the number of circulating phagocytes did not change over the study period. Resting LBCL correlated positively with the number of circulating polymorphonuclear leukocytes at all occasions and negative correlation with plasma 4-hydroxyhippuric acid was noted especially after the first strawberry course (r = -0.46, p0.05).The decrease in resting LBCL suggests that regular strawberry consumption may suppress baseline formation of oxidants by circulating phagocytes. This may decrease the risk of systemic imbalance between oxidants and anti-oxidants and be one of mechanisms of health-promoting effect of these fruits consumption.

Onconase (ONC) and R-Amphinase (R-AM) are enzymes with anti-tumor activity, belonging to pancreatic ribonuclease A family, received from eggs collected from frog Rana pipiens. Both proteins can induce death of some types of neoplastic cells by inhibition of protein synthesis, cell growth and proliferation. The aim of this study was to assess the cytotoxicity of R-AM, used alone or in combination with one of the most active anti-leukemic drug, doxorubicin (DOX), on diffuse large B-cell lymphoma (DLBCL)-derived cell line, Toledo. We found high cytotoxic activity of R-AM against DLBCL cells as well as influence on expression of several apoptosis-regulating proteins. Moreover, we observed increase in proapoptotic activity after combination of R-AM and DOX, compared with both drugs used alone. These results may justify further studies on interactions of R-AM with other drugs active in DLBCL.

Senescence induction contributes to cancer therapy responses and is crucial for p53-mediated tumor suppression. However, whether p53 inactivation actively suppresses senescence induction has been unclear. Here, we show that E2F1 overexpression, due to p53 or p21 inactivation, promotes expression of human oncoprotein CIP2A, which in turn, by inhibiting PP2A activity, increases stabilizing serine 364 phosphorylation of E2F1. Several lines of evidence show that increased activity of E2F1-CIP2A feedback renders breast cancer cells resistant to senescence induction. Importantly, mammary tumorigenesis is impaired in a CIP2A-deficient mouse model, and CIP2A-deficient tumors display markers of senescence induction. Moreover, high CIP2A expression predicts for poor prognosis in a subgroup of patients with breast cancer treated with senescence-inducing chemotherapy. Together, these results implicate the E2F1-CIP2A feedback loop as a key determinant of breast cancer cell sensitivity to senescence induction. This feedback loop also constitutes a promising prosenescence target for therapy of cancers with an inactivated p53–p21 pathway. Significance: It has been recently realized that most currently used chemotherapies exert their therapeutic effect at least partly by induction of terminal cell arrest, senescence. However, the mechanisms by which cell-intrinsic senescence sensitivity is determined are poorly understood. Results of this study identify the E2F1-CIP2A positive feedback loop as a key determinant of breast cancer cell sensitivity to senescence and growth arrest induction. Our data also indicate that this newly characterized interplay between 2 frequently overexpressed oncoproteins constitutes a promising prosenescence target for therapy of cancers with inactivated p53 and p21. Finally, these results may also facilitate novel stratification strategies for selection of patients to receive senescence-inducing cancer therapies. Cancer Discov; 3(2); 182–97. ©2013 AACR. This article is highlighted in the In This Issue feature, p. 125

Molecular dynamics (MD) simulation combined with inelastic neutron scattering can provide information about the thermal dynamics of proteins, especially the low-frequency vibrational modes responsible for large movement of some parts of protein molecules. We performed several 30-ns MD simulations of cytochrome c (Cyt c) in a water box for temperatures ranging from 110 to 300 K and compared the results with those from experimental inelastic neutron scattering. The low-frequency vibrational modes were obtained via dynamic structure factors, S(Q, ω), obtained both from inelastic neutron scattering experiments and calculated from MD simulations for Cyt c in the same range of temperatures. The well known thermal transition in structural movements of Cyt c is clearly seen in MD simulations; it is, however, confined to unstructured fragments of loops Ω1 and Ω2; movement of structured loop Ω3 and both helical ends of the protein is resistant to thermal disturbance. Calculated and experimental S(Q, ω) plots are in qualitative agreement for low temperatures whereas above 200 K a boson peak vanishes from the calculated plots. This may be a result of loss of crystal structure by the protein-water system compared with the protein crystal.

Intensive induction chemotherapy using anthracycline and cytarabine backbone is considered the most effective upfront therapy in physically fit older patients with acute myeloid leukemia (AML). However, outcomes of the standard induction in elderly AML are inferior to those observed in younger patients and they are still unsatisfactory. As addition of cladribine to the standard induction therapy is known to improve outcome in younger AML patients, the present randomized phase II study compares efficacy and toxicity of the DAC (daunorubicin plus cytarabine plus cladribine) regimen with the standard DA (daunorubicin plus cytarabine) regimen in the newly diagnosed AML patients over 60 years of age. A total of 171 patients were enrolled in the study (DA, 86; DAC, 85). A trend towards higher complete remission (CR) was observed in the DAC arm compared to the DA arm (44% vs 34%; p=0.19), which did not lead to improved median overall survival (OS), which in the case of the DAC group was 8.6 months compared to in 9.1 months in the DA group (p=0.64). However, DAC appeared to be superior in the group of patients aged 60-65 (CR rate: DAC 51% vs. DA 29%; p=0.02). What is more, a subgroup of patients, with good and intermediate karyotypes, benefited from addition of cladribine also in terms of overall survival (p=0.02). No differences in hematological and non-hematological toxicity between the DA and DAC regimens were observed. This article is protected by copyright. All rights reserved.

The Gamma-ray Burst Polarimeter-POLAR is a highly sensitive detector which is dedicated to the measurement of GRB’s polarization with a large effective detection area and a large field of view (FOV). The optimized performance of POLAR will contribute to the capture and measurement of the transient sources like GRBs and Solar Flares. The detection energy range of POLAR is 50 keV ~ 500 keV, and mainly dominated by the Compton scattering effect. POLAR consists of 25 detector modular units (DMUs), and each DMU is composed of low Z material Plastic Scintillators (PS), multi-anode photomultipliers (MAPMT) and multi-channel ASIC Front-end Electronics (FEE). POLAR experiment is an international collaboration project involving China, Switzerland and Poland, and is expected to be launched in September in 2016 onboard the Chinese space laboratory “Tiangong-2 (TG-2)”. With the efforts from the collaborations, POLAR has experienced the Demonstration Model (DM) phase, Engineering and Qualification Model (EQM) phase, Qualification Model (QM) phase, and now a full Flight Model (FM) of POLAR has been constructed. The FM of POLAR has passed the environmental acceptance tests (thermal cycling, vibration, shock and thermal vacuum tests) and experienced the calibration tests with both radioactive sources and 100% polarized Gamma-Ray beam at ESRF after its construction. The design of POLAR, Monte-Carlo simulation analysis, as well as the performance test results will all be introduced in this paper.

Gamma-ray polarimetry is a new powerful tool to study the processes responsible for the emission from astrophysical sources and the environments in which this emission takes place. Few successful polarimetric measurements have however been performed thus far in the gamma-ray energy band due to the difficulties involved. POLAR is a dedicated polarimeter designed to perform high precision measurements of the polarization of the emission from gamma-ray burst in the 50-500 keV energy range. This new polarimeter is expected to detect approximately 50 gamma-ray bursts per year while performing high precision polarization measurements on approximately 10 bursts per year. The instrument was launched into lower earth orbit as part of the second Chinese space lab, the Tiangong-2, on September 15th 2016 and has been taking data successfully since being switched on one week after. The instrument uses a segmented scintillator array consisting of 1600 plastic scintillator bars, read out by 25 flat-panel multi-anode photomultipliers, to measure the Compton scattering angles of incoming photons. The small segmentation and relatively large uniform effective area allow the instrument to measure the polarization of a large number of transient events, such as gamma-ray bursts, with an unprecedented precision during its two year life-time. The final flight model underwent detailed calibration prior to launch as well as intensive space qualification tests, a summary of which will be presented in this paper. The instrument design will be discussed first followed by an overview of the on-ground tests, finally the in-orbit behavior as measured during the first weeks of the mission will be presented.