Prostaglandins A1 and E1 influence gene expression in an established insect cell line (BCIRL-HzAM1 cells)

Prostaglandins (PGs) and other eicosanoids exert important physiological actions in insects and other invertebrates, including influencing ion transport and mediating cellular immune defense functions. Although these actions are very well documented, we have no information on the mechanisms of PGs actions in insect cells. Here we report on the outcomes of experiments designed to test our hypothesis that PGs modulate gene expression in an insect cell line established from pupal ovarian tissue of the moth Helicoverpa zea (BCIRL-HzAM1 cells). We treated cells with either PGA1 or PGE1 for 12 or 24 h then analyzed cell lysates by 2-D electrophoresis. Analysis of the gels by densitometry revealed substantial changes in protein expression in some of the protein spots we analyzed. These spots were processed for mass spectrometric analysis by MALDI TOF/TOF, which yielded in silico protein identities for all 34 spots. The apparent changes in three of the proteins were confirmed by semi-quantative PCR, showing that the changes in mRNA expression were reflected in changes in protein expression. The 34 proteins were sorted into six categories, protein actions, lipid metabolism, signal transduction, protection, cell functions and metabolism. The findings support the hypothesis that one mechanism of PG action in insect cells is the modulation of gene expression

Proteins associated with pancreatic cancer survival in patients with resectable pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with a dismal prognosis. However, while most patients die within the first year of diagnosis, very rarely, a few patients can survive for >10 years. Better understanding the molecular characteristics of the pancreatic adenocarcinomas from these very-long-term survivors (VLTS) may provide clues for personalized medicine and improve current pancreatic cancer treatment. To extend our previous investigation, we examined the proteomes of individual pancreas tumor tissues from a group of VLTS patients (survival ≥10 years) and short-term survival patients (STS, survival <14 months). With a given analytical sensitivity, the protein profile of each pancreatic tumor tissue was compared to reveal the proteome alterations that may be associated with pancreatic cancer survival. Pathway analysis of the differential proteins identified suggested that MYC, IGF1R and p53 were the top three upstream regulators for the STS-associated proteins, and VEGFA, APOE and TGFβ-1 were the top three upstream regulators for the VLTS-associated proteins. Immunohistochemistry analysis using an independent cohort of 145 PDAC confirmed that the higher abundance of ribosomal protein S8 (RPS8) and prolargin (PRELP) were correlated with STS and VLTS, respectively. Multivariate Cox analysis indicated that 'High-RPS8 and Low-PRELP' was significantly associated with shorter survival time (HR=2.69, 95% CI 1.46-4.92, P=0.001). In addition, galectin-1, a previously identified protein with its abundance aversely associated with pancreatic cancer survival, was further evaluated for its significance in cancer-associated fibroblasts. Knockdown of galectin-1 in pancreatic cancer-associated fibroblasts dramatically reduced cell migration and invasion. The results from our study suggested that PRELP, LGALS1 and RPS8 might be significant prognostic factors, and RPS8 and LGALS1 could be potential therapeutic targets to improve pancreatic cancer survival if further validated

Deciphering the Pre–solar-storm Features of the 2017 September Storm From Global and Local Dynamics

We investigate whether global toroid patterns and the local magnetic field topology of solar active region (AR) 12673 together can hindcast the occurrence of the biggest X-flares of solar cycle (SC)-24. Magnetic toroid patterns (narrow latitude belts warped in longitude, in which ARs are tightly bound) derived from the surface distributions of ARs, prior and during AR 12673 emergence, reveal that the portions of the south toroid containing AR 12673 was not tipped away from its north-toroid counterpart at that longitude, unlike the 2003 Halloween storms scenario. During the minimum phase there were too few emergences to determine multimode longitudinal toroid patterns. A new emergence within AR 12673 produced a complex nonpotential structure, which led to the rapid buildup of helicity and winding that triggered the biggest X-flare of SC-24, suggesting that this minimum-phase storm can be anticipated several hours before its occurrence. However, global patterns and local dynamics for a peak-phase storm, such as that from AR 11263, behaved like the 2003 Halloween storms, producing the third biggest X-flare of SC-24. AR 11263 was present at the longitude where the north and south toroids tipped away from each other. While global toroid patterns indicate that prestorm features can be forecast with a lead time of a few months, their application to observational data can be complicated by complex interactions with turbulent flows. Complex nonpotential field structure development hours before the storm are necessary for short-term prediction. We infer that minimum-phase storms cannot be forecast accurately more than a few hours ahead, while flare-prone ARs in the peak phase may be anticipated much earlier, possibly months ahead from global toroid patterns

Age-dependent pleiotropy between general cognitive function and major psychiatric disorders

AbstractBackgroundGeneral cognitive function predicts psychiatric illness across the life course. This study examines the role of pleiotropy in explaining the link between cognitive function and psychiatric disorder.MethodsWe used two large genome-wide association study data sets on cognitive function—one from older age, n = 53,949, and one from childhood, n = 12,441. We also used genome-wide association study data on educational attainment, n = 95,427, to examine the validity of its use as a proxy phenotype for cognitive function. Using a new method, linkage disequilibrium regression, we derived genetic correlations, free from the confounding of clinical state between psychiatric illness and cognitive function.ResultsWe found a genetic correlation of .711 (p = 2.26e-12) across the life course for general cognitive function. We also showed a positive genetic correlation between autism spectrum disorder and cognitive function in childhood (rg = .360, p = .0009) and for educational attainment (rg = .322, p = 1.37e-5) but not in older age. In schizophrenia, we found a negative genetic correlation between older age cognitive function (rg = −.231, p = 3.81e-12) but not in childhood or for educational attainment. For Alzheimer’s disease, we found negative genetic correlations with childhood cognitive function (rg = −.341, p = .001), educational attainment (rg = −.324, p = 1.15e-5), and with older age cognitive function (rg = −.324, p = 1.78e-5).ConclusionsThe pleiotropy exhibited between cognitive function and psychiatric disorders changed across the life course. These age-dependent associations might explain why negative selection has not removed variants causally associated with autism spectrum disorder or schizophrenia

Prediction of the in situ coronal mass ejection rate for solar cycle 25: Implications for Parker Solar Probe in situ observations

The Parker Solar Probe (PSP) and Solar Orbiter missions are designed to make groundbreaking observations of the Sun and interplanetary space within this decade. We show that a particularly interesting in situ observation of an interplanetary coronal mass ejection (ICME) by PSP may arise during close solar flybys ($< 0.1$~AU). During these times, the same magnetic flux rope inside an ICME could be observed in situ by PSP twice, by impacting its frontal part as well as its leg. Investigating the odds of this situation, we forecast the ICME rate in solar cycle 25 based on 2 models for the sunspot number (SSN): (1) the forecast of an expert panel in 2019 (maximum SSN = 115), and (2) a prediction by McIntosh et al. (2020, maximum SSN = 232). We link the SSN to the observed ICME rates in solar cycles 23 and 24 with the Richardson and Cane list and our own ICME catalog, and calculate that between 1 and 7 ICMEs will be observed by PSP at heliocentric distances $< 0.1$ AU until 2025, including 1$\sigma$ uncertainties. We then model the potential flux rope signatures of such a double-crossing event with the semi-empirical 3DCORE flux rope model, showing a telltale elevation of the radial magnetic field component $B_R$, and a sign reversal in the component $B_N$ normal to the solar equator compared to field rotation in the first encounter. This holds considerable promise to determine the structure of CMEs close to their origin in the solar corona.Comment: 11 pages, 6 figures, accepted for publication in the Astrophysical Journal on 2020 September 1

No More Active Galactic Nuclei in Clumpy Disks Than in Smooth Galaxies at z~2 in CANDELS / 3D-HST

We use CANDELS imaging, 3D-HST spectroscopy, and Chandra X-ray data to investigate if active galactic nuclei (AGNs) are preferentially fueled by violent disk instabilities funneling gas into galaxy centers at 1.3<z<2.4. We select galaxies undergoing gravitational instabilities using the number of clumps and degree of patchiness as proxies. The CANDELS visual classification system is used to identify 44 clumpy disk galaxies, along with mass-matched comparison samples of smooth and intermediate morphology galaxies. We note that, despite being being mass-matched and having similar star formation rates, the smoother galaxies tend to be smaller disks with more prominent bulges compared to the clumpy galaxies. The lack of smooth extended disks is probably a general feature of the z~2 galaxy population, and means we cannot directly compare with the clumpy and smooth extended disks observed at lower redshift. We find that z~2 clumpy galaxies have slightly enhanced AGN fractions selected by integrated line ratios (in the mass-excitation method), but the spatially resolved line ratios indicate this is likely due to extended phenomena rather than nuclear AGNs. Meanwhile the X-ray data show that clumpy, smooth, and intermediate galaxies have nearly indistinguishable AGN fractions derived from both individual detections and stacked non-detections. The data demonstrate that AGN fueling modes at z~1.85 - whether violent disk instabilities or secular processes - are as efficient in smooth galaxies as they are in clumpy galaxies.Comment: ApJ accepted. 17 pages, 17 figure

The Coronae of AR Lac

We observed the coronally active eclipsing binary, AR Lac, with the High Energy Transmission Grating on Chandra for a total of 97 ks, spaced over five orbits, at quadratures and conjunctions. Contemporaneous and simultaneous EUV spectra and photometry were also obtained with the Extreme Ultraviolet Explorer. Significant variability in both X-ray and EUV fluxes were observed, dominated by at least one X-ray flare and one EUV flare. We saw no evidence of primary or secondary eclipses. X-ray flux modulation was largest at high temperature, indicative of flare heating of coronal plasma. Line widths interpreted in terms of Doppler broadening suggest that both binary stellar components are active. From line fluxes obtained from total integrated spectra, we have modeled the emission measure and abundance distributions. A strong maximum was found in the differential emission measure, characterized by peaks at log T = 6.9 and 7.4, together with a weak but significant cooler maximum near log T=6.2, and a moderately strong hot tail from log T= 7.6-8.2. Coronal abundances have a broad distribution and show no simple correlation with first ionization potential. While the resulting model spectrum generally agrees very well with the observed spectrum, there are some significant discrepancies, especially among the many Fe L-lines. Both the emission measure and abundance distributions are qualitatively similar to prior determinations from other X-ray and ultraviolet spectra, indicating some long-term stability in the overall coronal structure.Comment: 31 pages, 8 figures, 3 tables; Accepted for publication in the Astrophysical Journal (tentatively October 1, 2003

Investigating the relationship between DNA methylation age acceleration and risk factors for Alzheimer’s disease

This work was supported by a Alzheimer's Research UK Major Project grant (ARUK-PG2017B-10). Generation Scotland received core funding from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006). We are grateful to all the families who took part, the general practitioners and the Scottish School of Primary Care for their help in recruiting them, and the whole Generation Scotland team that includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, health-care assistants and nurses. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland, and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” [STRADL];104036/Z/14/Z). DNA methylation data collection was funded by the Wellcome Trust Strategic Award (10436/Z/14/Z). The research was conducted in the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), part of the cross-council Lifelong Health and Wellbeing Initiative (MR/K026992/1); funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged. CCACE supports I.J.D. with some additional support from the Dementias Platform UK (MR/L015382/1). A.M.M. and H.C.W. have received support from the Sackler Institute.Peer reviewedPublisher PD