SREBP-2/PNPLA8 axis improves non-alcoholic fatty liver disease through activation of autophagy

Dysregulated autophagy is associated with steatosis and non-alcoholic fatty liver disease (NAFLD), however the mechanisms connecting them remain poorly understand. Here, we show that co-administration of lovastatin and ezetimibe (L/E) significantly reverses hepatic triglyceride accumulation concomitant with an increase in SREBP-2 driven autophagy in mice fed a high-fat diet (HFD). We further show that the statin mediated increase in SREBP-2 directly activates expression of patatin-like phospholipase domain-containing enzyme 8 (PNPLA8) gene, and PNPLA8 associates with autophagosomes and is associated with a decrease in cellular triglyceride. Moreover, we show that over-expression of PNPLA8 dramatically decreases hepatic steatosis through increased autophagy in hepatocytes of HFD-fed mice. Live-cell imaging analyses also reveal that PNPLA8 dynamically interacts with LC3 and we suggest that the SREBP-2/PNPLA8 axis represents a novel regulatory mechanism for lipid homeostasis. These data provide a possible mechanism for the reported beneficial effects of statins for decreasing hepatic triglyceride levels in NAFLD patients.ope

Graded structure in sexual definitions: categorizations of having “had sex” and virginity loss among homosexual and heterosexual men and women

Definitions of sexual behavior display a robust hierarchy of agreement regarding whether or not acts should be classed as, for example, sex or virginity loss. The current research offers a theoretical explanation for this hierarchy, proposing that sexual definitions display graded categorical structure, arising from goodness of membership judgments. Moderation of this graded structure is also predicted, with the focus here on how sexual orientation identity affects sexual definitions. A total of 300 18- to 30-year-old participants completed an online survey, rating 18 behaviors for how far each constitutes having “had sex” and virginity loss. Participants fell into one of four groups: heterosexual male or female, gay male or lesbian. The predicted ratings hierarchy emerged, in which bidirectional genital acts were rated significantly higher than unidirectional or nonpenetrative contact, which was in turn rated significantly higher than acts involving no genital contact. Moderation of graded structure was also in line with predictions. Compared to the other groups, the lesbian group significantly upgraded ratings of genital contact that was either unidirectional or nonpenetrative. There was also evidence of upgrading by the gay male sample of anal intercourse ratings. These effects are theorized to reflect group-level variation in experience, contextual perspective, and identity-management. The implications of the findings in relation to previous research are discussed. It is suggested that a graded structure approach can greatly benefit future research into sexual definitions, by permitting variable definitions to be predicted and explained, rather than merely identified

The UV-SCOPE mission: ultraviolet spectroscopic characterization of planets and their environments

UV-SCOPE is a mission concept to determine the causes of atmospheric mass loss in exoplanets, investigate the mechanisms driving aerosol formation in hot Jupiters, and study the influence of the stellar environment on atmospheric evolution and habitability. As part of these investigations, the mission will generate a broad-purpose legacy database of time-domain ultraviolet (UV) spectra for nearly 200 stars and planets. The observatory consists of a 60 cm, f/10 telescope paired to a long-slit spectrograph, yielding simultaneous, almost continuous coverage between 1203 Å and 4000 Å, with resolutions ranging from 6000 to 240. The efficient instrument provides throughputs < 4% (far-UV; FUV) and < 15% (near-UV; NUV), comparable to HST/COS and much better than HST/STIS, over the same spectral range. A key design feature is the LiF prism, which serves as a dispersive element and provides high throughput even after accounting for radiation degradation. The use of two delta-doped Electron-Multiplying CCD detectors with UV-optimized, single-layer anti-reflection coatings provides high quantum efficiency and low detector noise. From the Earth-Sun second Lagrangian point, UV-SCOPE will continuously observe planetary transits and stellar variability in the full FUV-to-NUV range, with negligible astrophysical background. All these features make UV-SCOPE the ideal instrument to study exoplanetary atmospheres and the impact of host stars on their planets. UV-SCOPE was proposed to NASA as a Medium Explorer (MidEx) mission for the 2021 Announcement of Opportunity. If approved, the observatory will be developed over a 5-year period. Its primary science mission takes 34 months to complete. The spacecraft carries enough fuel for 6 years of operations

Retinopathy of prematurity and risk factors: a prospective cohort study

BACKGROUND: Increased survival of extremely low birth infants due to advances in antenatal and neonatal care has resulted in a population of infants at high risk of developing retinopathy of prematurity (ROP). Therapeutic interventions include the use of antenatal and postnatal steroids however, their effects on the severity of ROP is in dispute. In addition, it has not been investigated whether severe ROP is due to therapeutic interventions or due to the severity of illness. The aim of the present study was to assess the association between the incidence of severe retinopathy of prematurity (greater than stage 2 – International classification of ROP) and mechanical ventilation, oxygen therapy, gestational age, antenatal and postnatal steroids in extremely low birth weight infants. METHODS: Neonates admitted to the neonatal intensive care unit in Lansing, Michigan, during 1993–2000 were followed to determine factors influencing the development of severe retinopathy of prematurity. Ophthalmologic examinations were started at 6 weeks and followed until resolution. We used logistic regression to estimate the relative risk (odds ratio) associated with risk factors of ROP. RESULTS: Of the neonates with ≤ 1500 g birth weight, admitted to the neonatal intensive care unit, 85% (616/725) survived. Severe retinopathy of prematurity was detected in 7.8% of 576 neonates who had eye examinations. Neonates of lower gestational age (≤ 25 weeks and 26–28 weeks) had an increased odds ratio of 8.49 and 3.19 for the development of severe retinopathy of prematurity, respectively, compared to those 29 weeks and older. Late postnatal steroid treatment starting after 3 weeks of life showed 2.9-fold increased odds ratio, in particular administration for two weeks and more (OR: 4.09, 95% CI: 1.52–11.03). With increasing antenatal steroids courses the risk of severe retinopathy of prematurity decreased, however, it was not significant. Lower gestational age, dependence on ventilation, and use of postnatal steroids were intertwined. Simultaneous presence of these factors seems to indicate severe disease status. CONCLUSION: Prolonged and late postnatal steroids treatment in very low birth weight infants may pose an increased risk for the development of severe retinopathy of prematurity; however, use of postnatal steroids may also be a marker for severity of illness. Further studies need to focus on biologic markers in the pathogenesis of retinopathy of prematurity and to better understand the influence of therapies

Gay, Mostly Gay, or Bisexual Leaning Gay? An Exploratory Study Distinguishing Gay Sexual Orientations Among Young Men

This exploratory study assessed physiological, behavioral, and self-report measures of sexual and romantic indicators of sexual orientation identities among young men (mean age = 21.9 years) with predominant same-sex sexual and romantic interests: those who described themselves as bisexual leaning gay (n = 11), mostly gay (n = 17), and gay (n = 47). Although they were not significantly distinguishable based on physiological (pupil dilation) responses to nude stimuli, on behavioral and self-report measures a descending linear trend toward the less preferred sex (female) was significant regarding sexual attraction, fantasy, genital contact, infatuation, romantic relationship, sex appeal, and gazing time to the porn stimuli. Results supported a continuum of sexuality with distinct subgroups only for the self-report measure of sexual attraction. The other behavioral and self-report measures followed the same trend but did not significantly differ between the bisexual leaning gay and mostly gay groups, likely the result of small sample size. Results suggest that romantic indicators are as good as sexual measures in assessing sexual orientation and that a succession of logically following groups from bisexual leaning gay, mostly gay, to gay. Whether these three groups are discrete or overlapping needs further research

Rhodolith Beds Are Major CaCO3 Bio-Factories in the Tropical South West Atlantic

Rhodoliths are nodules of non-geniculate coralline algae that occur in shallow waters (<150 m depth) subjected to episodic disturbance. Rhodolith beds stand with kelp beds, seagrass meadows, and coralline algal reefs as one of the world's four largest macrophyte-dominated benthic communities. Geographic distribution of rhodolith beds is discontinuous, with large concentrations off Japan, Australia and the Gulf of California, as well as in the Mediterranean, North Atlantic, eastern Caribbean and Brazil. Although there are major gaps in terms of seabed habitat mapping, the largest rhodolith beds are purported to occur off Brazil, where these communities are recorded across a wide latitudinal range (2°N - 27°S). To quantify their extent, we carried out an inter-reefal seabed habitat survey on the Abrolhos Shelf (16°50′ - 19°45′S) off eastern Brazil, and confirmed the most expansive and contiguous rhodolith bed in the world, covering about 20,900 km2. Distribution, extent, composition and structure of this bed were assessed with side scan sonar, remotely operated vehicles, and SCUBA. The mean rate of CaCO3 production was estimated from in situ growth assays at 1.07 kg m−2 yr−1, with a total production rate of 0.025 Gt yr−1, comparable to those of the world's largest biogenic CaCO3 deposits. These gigantic rhodolith beds, of areal extent equivalent to the Great Barrier Reef, Australia, are a critical, yet poorly understood component of the tropical South Atlantic Ocean. Based on the relatively high vulnerability of coralline algae to ocean acidification, these beds are likely to experience a profound restructuring in the coming decades

The Role of For-Profit Actors in Implementing Targeted Sanctions:The Case of the European Union

The evolution of sanctions from comprehensive to targeted has favored the inclusion of for-profit actors in the policy process. Sanctions are used to deal with security challenges and while the role of for-profit actors in the provision of public goods has been investigated, less has been said about their role in the provision of security. This chapter investigates the role of for-profit actors in the implementation of sanctions. More specifically, this chapter suggests a typology of regulatory environments that facilitates explaining and understanding the behavior of for-profit actors in implementing targeted sanctions. By looking at the quality of instructions provided by state authorities and their capacity to monitor the implementation of such decisions, the chapter argues that overcompliance, uneven and lack of compliance are more likely in certain regulatory environments rather than in others. The theoretical framework is tested on the case study of the restrictive measures of the EU. The data for this research was collected through semi-opened interviews and focus groups held in Brussels from 2013 to 2015

Effect of Operating and Sampling Conditions on the Exhaust Gas Composition of Small-Scale Power Generators

Small stationary diesel engines, like in generator sets, have limited emission control measures and are therefore responsible for 44% of the particulate matter (PM) emissions in the United States. The diesel exhaust composition depends on operating conditions of the combustion engine. Furthermore, the measurements are influenced by the used sampling method. This study examines the effect of engine loading and exhaust gas dilution on the composition of small-scale power generators. These generators are used in different operating conditions than road-transport vehicles, resulting in different emission characteristics. Experimental data were obtained for gaseous volatile organic compounds (VOC) and PM mass concentration, elemental composition and nitrate content. The exhaust composition depends on load condition because of its effect on fuel consumption, engine wear and combustion temperature. Higher load conditions result in lower PM concentration and sharper edged particles with larger aerodynamic diameters. A positive correlation with load condition was found for K, Ca, Sr, Mn, Cu, Zn and Pb adsorbed on PM, elements that originate from lubricating oil or engine corrosion. The nitrate concentration decreases at higher load conditions, due to enhanced nitrate dissociation to gaseous NO at higher engine temperatures. Dilution on the other hand decreases PM and nitrate concentration and increases gaseous VOC and adsorbed metal content. In conclusion, these data show that operating and sampling conditions have a major effect on the exhaust gas composition of small-scale diesel generators. Therefore, care must be taken when designing new experiments or comparing literature results

The Use of Sexually Explicit Internet Material and Its Antecedents: A Longitudinal Comparison of Adolescents and Adults

An implicit assumption in research on adolescents’ use of sexually explicit internet material (SEIM) is that they may feel more attracted to such material than adults, given the “forbidden” character of SEIM for minors. However, systematic comparisons between adolescents’ and adults’ SEIM use and of its antecedents are missing. We conducted a two-wave panel survey among a nationally representative sample of 1,445 Dutch adolescents and a nationally representative sample of 833 Dutch adults. Adolescents’ and adults’ SEIM use was similar. When significant differences in the SEIM use occurred, they indicated that adults used SEIM more often than adolescents. Male adults were the most frequent users of SEIM. No difference in the antecedent structure of SEIM use emerged between adolescents and adults. In both groups, males, sensation seekers, as well as people with a not exclusively heterosexual orientation used SEIM more often. Among adolescents and adults, lower life satisfaction increased SEIM use. Our findings suggest that the frequency of SEIM use and its antecedents are largely the same among adolescents and adults

Pupil Dilation to Explicit and Non-Explicit Sexual Stimuli

Pupil dilation to explicit sexual stimuli (footage of naked and aroused men or women) can elicit sex and sexual orientation differences in sexual response. If similar patterns were replicated with non-explicit sexual stimuli (footage of dressed men and women), then pupil dilation could be indicative of automatic sexual response in fully noninvasive designs. We examined this in 325 men and women with varied sexual orientations to determine whether dilation patterns to non-explicit sexual stimuli resembled those to explicit sexual stimuli depicting the same sex or other sex. Sexual orientation differences in pupil dilation to non-explicit sexual stimuli mirrored those to explicit sexual stimuli. However, the relationship of dilation to non-explicit sexual stimuli with dilation to corresponding explicit sexual stimuli was modest, and effect magnitudes were smaller with non-explicit sexual stimuli than explicit sexual stimuli. The prediction that sexual orientation differences in pupil dilation are larger in men than in women was confirmed with explicit sexual stimuli but not with non-explicit sexual stimuli