Radioprotective and In-Vitro Cytotoxic Sapogenin from Euphorbia neriifolia (Euphorbiaceae) Leaf

Purpose: Euphorbia neriifolia Linn. (Euphorbiaceae) plant is traditionally used in the treatment of abdominal troubles, bronchitis, tumours,  leucoderma, piles, inflammation, and enlargement of spleen. The objective of this study was to evaluate the antioxidant and anticancer activities of a sapogenin isolate of this plant. Methods: Euphol was isolated as a major constituent from the triterpenoidal sapogenin fraction of E. neriifolia leaf. Its in-vitro antioxidant activity was evaluated by reducing power assay, 1,1 – diphenyl –2- picryl hydrazyl (DPPH) assay, as well as  hydroxyl radical and superoxide radical scavenging activities. Radioprotective activity was assessed against radiation-induced chromosomal aberrations and cytotoxicity on murine F1 B16 melanoma.Results: The sapogenin exerted moderate antioxidant activity with highly significant (p < 0.001) reduction of gamma radiation-induced chromosomal aberrations (33.5 % compared to 71.5 % for radiation treatment alone at 4 Gy). It also exhibited cytotoxic activity on melanoma cell lines (IC50 = 173.78 μg/ml). Conclusion: The sapogenin fraction showed antioxidant, radioprotective and cytotoxic activities. This study provides a scientific basis for the claimed traditional anticarcinogenic potentials of E. neriifolia.Keywords: Euphorbia neriifolia; Euphol; Sapogenin; Antioxidant; Radioprotective; Melanoma; Chromosomal aberratio

Protective effect of Euphorbia neriifolia saponin fraction on CCl4-induced acute hepatotoxicity

The present investigation aims at assessing the hepatoprotective effect of saponin fraction isolated from the leaf of Euphorbia neriifolia on CCl4-induced hepatotoxicity on rat. CCl4 (1.5 mg/kg, i.p) is a potent hepatotoxic agent, which induces peroxidative degeneration of membrane lipids causing hypoperfusion of the membrane. Cytosolic enzymes like SGPT, SGOT and ALP elevates in the blood and hepatic glutathione and SOD decreases. The hepatoprotection of triterpene was compared with silymerin, a well known standard hepatoprotectant. Euphol was isolated from E. neriifolia leaf total sapogenin fraction after separation and instrumentation.  Pretreatment with total saponin fraction (50, 125 and 175 mg/kg, p.o once a day for 4 days before CCl4 and  continued further for 3 days) attenuated the CCl4-induced acute increase in serum SGPT, SGOT and ALP  activities and considerably reduced the histopathological alterations. Further, saponin fraction reduced  thiopentone (4 mg/kg, i.p) induced sleeping time, suggesting the protection of liver metabolizing enzymes.  Saponin administration replenished the depleted hepatic GSH and SOD by improving the antioxidant status of  the liver. Saponin pretreatment improves bromsulphalein clearance and also increases the cellular viability.  These effects substantiate protection of cellular phospholipid from peroxidative damage induced by highly  reactive toxic intermediate radicals formed during biotransformation of CCl4.Key words: Euphorbia neriifolia, triterpenoidal saponin, euphol, β-amyrin, hepatoprotective

Structural basis for ligase-specific conjugation of linear ubiquitin chains by HOIP

Linear ubiquitin chains are important regulators of cellular signaling pathways that control innate immunity and inflammation through NF-κB activation and protection against TNFα-induced apoptosis(1-5). They are synthesized by HOIP, which belongs to the RBR (RING-between-RING) family of E3 ligases and is the catalytic component of LUBAC (linear ubiquitin chain assembly complex), a multi-subunit E3 ligase(6). RBR family members act as RING/HECT hybrids, employing RING1 to recognize ubiquitin-loaded E2 while a conserved cysteine in RING2 subsequently forms a thioester intermediate with the transferred or “donor” ubiquitin(7). Here we report the crystal structure of the catalytic core of HOIP in its apo form and in complex with ubiquitin. The C-terminal portion of HOIP adopts a novel fold that, together with a zinc finger, forms an ubiquitin-binding platform which orients the acceptor ubiquitin and positions its α-amino group for nucleophilic attack on the E3~ubiquitin thioester. The carboxy-terminal tail of a second ubiquitin molecule is located in close proximity to the catalytic cysteine providing a unique snapshot of the ubiquitin transfer complex containing both donor and acceptor ubiquitin. These interactions are required for activation of the NF-kB pathway in vivo and explain the determinants of linear ubiquitin chain specificity by LUBAC

Discovery of coherent pulsations from the Ultraluminous X-ray Source NGC 7793 P13

We report the detection of coherent pulsations from the ultraluminous X-ray source (ULX) NGC 7793 P13. The ≈0.42 s nearly sinusoidal pulsations were initially discovered in broadband X-ray observations using XMM-Newton and NuSTAR taken in 2016. We subsequently also found pulsations in archival XMM-Newton data taken in 2013 and 2014. The significant (≫5σ) detection of coherent pulsations demonstrates that the compact object in P13 is a neutron star, and given the observed peak luminosity of ≈10⁴⁰ erg s⁻¹ (assuming isotropy), it is well above the Eddington limit for a 1.4 M⨀ accretor. This makes P13 the second ULX known to be powered by an accreting neutron star. The pulse period varies between epochs, with a slow but persistent spin-up over the 2013–2016 period. This spin-up indicates a magnetic field of B ≈ 1.5 × 10¹² G, typical of many Galactic accreting pulsars. The most likely explanation for the extreme luminosity is a high degree of beaming; however, this is difficult to reconcile with the sinusoidal pulse profile.We would like the thank the referee for the helpful comments. M.J.M. acknowledges support from an STFC Ernest Rutherford fellowship and D.B. acknowledges financial support from the French Space Agency (CNES). This research has made use of data obtained with NuSTAR, a project led by Caltech, funded by NASA and managed by NASA/JPL, and has utilized the nustardas software package, jointly developed by the ASDC (Italy) and Caltech (USA). This research has also made use of data obtained with XMM-Newton, an ESA science mission with instruments and contributions directly funded by ESA Member States. This work made use of data supplied by the UK Swift Science Data Centre at the University of Leicester, and also made use of the XRT Data Analysis Software (XRTDAS) developed under the responsibility of the ASI Science Data Center (ASDC), Italy. This research has made use of a collection of ISIS functions (ISISscripts) provided by ECAP/Remeis observatory and MIT (http://www.sternwarte.uni-erlangen.de/isis/). Facilities: NuSTAR - The NuSTAR (Nuclear Spectroscopic Telescope Array) mission, XMM - , Swift -

The Broadband Spectral Variability of Holmberg IX X-1

We present results from four new broadband X-ray observations of the extreme ultraluminous X-ray source Holmberg IX X-1 (L$_{x}$ > 10$^{40}$ erg s$^{-1}$), performed by $\textit{Suzaku}$ and $\textit{Nu}$STAR in coordination. Combined with the archival data, we now have broadband observations of this remarkable source from six separate epochs. Two of these new observations probe lower fluxes than seen previously, allowing us to extend our knowledge of the broadband spectral variability exhibited. The spectra are well fit by two thermal blackbody components that dominate the emission below 10 keV, as well as a steep ($\Gamma$ $\sim$ 3.5) power-law tail that dominates above ~15 keV. Remarkably, while the 0.3–10.0 keV flux varies by a factor of ~3 between all these epochs, the 15–40 keV flux varies by only ~20%. Although the spectral variability is strongest in the ~1–10 keV band, both of the thermal components are required to vary when all epochs are considered. We also revisit the search for iron absorption features by leveraging the high-energy NuSTAR data to improve our sensitivity to extreme velocity outflows in light of the ultra-fast outflow recently detected in NGC 1313 X-1. Iron absorption from a similar outflow along our line of sight can be ruled out in this case. We discuss these results in the context of super-Eddington accretion models that invoke a funnel-like geometry for the inner flow, and propose a scenario in which we have an almost face-on view of a funnel that expands to larger radii with increasing flux, resulting in an increasing degree of geometrical collimation for the emission from intermediate-temperature regions.D.J.W. and M.J.M. acknowledge support from STFC through Ernest Rutherford fellowships, A.C.F. acknowledges support from ERC Advanced Grant 340442, and D.B. acknowledges financial support from the French Space Agency (CNES). This research has made use of data obtained with NuSTAR, a project led by Caltech, funded by NASA and managed by NASA/JPL, and has utilized the NUSTARDAS software package, jointly developed by the ASDC (Italy) and Caltech (USA). This research has also made use of data obtained with XMM-Newton, an ESA science mission with instruments and contributions directly funded by ESA Member States, and with Suzaku, a collaborative mission between the space agencies of Japan (JAXA) and the USA (NASA)

Graphene Photonics and Optoelectronics

The richness of optical and electronic properties of graphene attracts enormous interest. Graphene has high mobility and optical transparency, in addition to flexibility, robustness and environmental stability. So far, the main focus has been on fundamental physics and electronic devices. However, we believe its true potential to be in photonics and optoelectronics, where the combination of its unique optical and electronic properties can be fully exploited, even in the absence of a bandgap, and the linear dispersion of the Dirac electrons enables ultra-wide-band tunability. The rise of graphene in photonics and optoelectronics is shown by several recent results, ranging from solar cells and light emitting devices, to touch screens, photodetectors and ultrafast lasers. Here we review the state of the art in this emerging field.Comment: Review Nature Photonics, in pres

Impact of the roll out of comprehensive emergency obstetric care on institutional birth rate in rural Nepal

© 2017 The Author(s). Background: Increasing institutional births rates and improving access to comprehensive emergency obstetric care are central strategies for reducing maternal and neonatal deaths globally. While some studies show women consider service availability when determining where to deliver, the dynamics of how and why institutional birth rates change as comprehensive emergency obstetric care availability increases are unclear. Methods: In this pre-post intervention study, we surveyed two exhaustive samples of postpartum women before and after comprehensive emergency obstetric care implementation at a hospital in rural Nepal. We developed a logistic regression model of institutional birth factors through manual backward selection of all significant covariates within and across periods. Qualitatively, we analyzed birth stories through immersion crystallization. Results: Institutional birth rates increased after comprehensive emergency obstetric care implementation (from 30 to 77%, OR 7.7) at both hospital (OR 2.5) and low-level facilities (OR 4.6, p < 0.01 for all). The logistic regression indicated that comprehensive emergency obstetric care availability (OR 5.6), belief that the hospital is the safest birth location (OR 44.8), safety prioritization in decision-making (OR 7.7), and higher income (OR 1.1) predict institutional birth (p ≤ 0.01 for all). Qualitative analysis revealed comprehensive emergency obstetric care awareness, increased social expectation for institutional birth, and birth planning as important factors. Conclusion: Comprehensive emergency obstetric care expansion appears to have generated significant demand for institutional births through increased safety perceptions and birth planning. Increasing comprehensive emergency obstetric care availability increases birth safety, but it may also be a mechanism for increasing the institutional birth rate in areas of under-utilization

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Changes observed in radionuclide bone scans during and after teriparatide treatment for osteoporosis

# The Author(s) 2011. This article is published with open access at Springerlink.com Purpose Visual changes on radionuclide bone scans have been reported with teriparatide treatment. To assess this, serial studies were evaluated and quantified in ten postmenopausal women with osteoporosis treated with teriparatide (20 μg/day subcutaneous) who had 99m Tc-methylene diphosphonate (MDP) bone scans (baseline, 3 and 18 months, then after 6 months off therapy). Methods Women were injected with 600 MBq 99m Tc-MDP, and diagnostic bone scan images were assessed at 3.5 h. Additional whole-body scans (10 min, 1, 2, 3 and 4 h) were analysed for 99m Tc-MDP skeletal plasma clearance (Kbone). Regional Kbone differences were obtained for the whole skeleton and six regions (calvarium, mandible, spine, pelvis, upper and lower extremities). Bone turnover markers (BTM) were also measured. Results Most subjects showed visual changes on 3- and 18month bone scan images that disappeared after 6 months off therapy. Enhanced uptake was seen predominantly in the calvarium and lower extremities. Whole skeleton Kbone displayed a median increase of 22 % (3 months, p=0.004) and 34 % (18 months, p=0.002) decreasing to 0.7% (6 months off therapy). Calvarium Kbone changes were three times larger than other sites. After 6 months off therapy, all Kbone and BTM values returned towards baseline