Extinction in Star-Forming Disk Galaxies from Inclination-Dependent Composite Spectra

Extinction in galaxies affects their observed properties. In scenarios describing the distribution of dust and stars in individual disk galaxies, the amplitude of the extinction can be modulated by the inclination of the galaxies. In this work we investigate the inclination dependency in composite spectra of star-forming disk galaxies from the Sloan Digital Sky Survey Data Release 5. In a volume-limited sample within a redshift range 0.065-0.075 and a r-band Petrosian absolute magnitude range -19.5 to -22 which exhibits a flat distribution of inclination, the inclined relative to face-on extinction in the stellar continuum is found empirically to increase with inclination in the g, r, and i bands. Within the central 0.5 intrinsic half-light radius of the galaxies, the g-band relative extinction in the stellar continuum for the highly-inclined objects (axis ratio b/a = 0.1) is 1.2 mag, agreeing with previous studies. The extinction curve of the disk galaxies is given in the restframe wavelengths 3700-8000 angstrom, identified with major optical emission and absorption lines in diagnostics. The Balmer decrement remains constant with inclination, suggesting a different kind of dust configuration and/or reddening mechanism in the HII region from that in the stellar continuum. One factor is shown to be the presence of spatially non-uniform interstellar extinction, presumably caused by clumped dust in the vicinity of the HII region.Comment: To appear in the Astrophysical Journa

Placental endoplasmic reticulum stress negatively regulates transcription of placental growth factor via ATF4 and ATF6β: implications for the pathophysiology of human pregnancy complications.

Low maternal circulating concentrations of placental growth factor (PlGF) are one of the hallmarks of human pregnancy complications, including fetal growth restriction (FGR) and early-onset pre-eclampsia (PE). Currently, PlGF is used clinically with other biomarkers to screen for high-risk cases, although the mechanisms underlying its regulation are largely unknown. Placental endoplasmic reticulum (ER) stress has recently been found to be elevated in cases of FGR, and to an even greater extent in early-onset PE complicated with FGR. ER stress activates the unfolded protein response (UPR); attenuation of protein translation and a reduction in cell growth and proliferation play crucial roles in the pathophysiology of these complications of pregnancy. In this study, we further identified that ER stress regulates release of PlGF. We first observed that down-regulation of PlGF protein was associated with nuclear localization of ATF4, ATF6α and ATF6β in the syncytiotrophoblast of placentae from PE patients. Transcript analysis showed a decrease of PlGF mRNA, and an increase from genes encoding those UPR transcription factors in placentae from cases of early-onset PE, but not of late-onset (>34 weeks) PE, compared to term controls. Further investigations indicated a strong correlation between ATF4 and PlGF mRNA levels only (r = - 0.73, p < 0.05). These results could be recapitulated in trophoblast-like cells exposed to chemical inducers of ER stress or hypoxia-reoxygenation. The stability of PlGF transcripts was unchanged. The use of small interfering RNA specific for transcription factors in the UPR pathways revealed that ATF4 and ATF6β, but not ATF6α, modulate PlGF transcription. To conclude, ATF4 and ATF6β act synergistically in the negative regulation of PlGF mRNA expression, resulting in reduced PlGF secretion by the trophoblast in response to stress. Therefore, these results further support the targeting of placental ER stress as a potential new therapeutic intervention for these pregnancy complications.This study was supported by a grant from The Wellcome Trust (084804/2/08/Z).This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/path.467

Noncanonical mitochondrial unfolded protein response impairs placental oxidative phosphorylation in early-onset preeclampsia.

Preeclampsia (PE) is a dangerous complication of pregnancy, especially when it presents at <34 wk of gestation (PE < 34 wk). It is a major cause of maternal and fetal morbidity and mortality and also increases the risk of cardiometabolic diseases in later life for both mother and offspring. Placental oxidative stress induced by defective placentation sits at the epicenter of the pathophysiology. The placenta is susceptible to activation of the unfolded protein response (UPR), and we hypothesized this may affect mitochondrial function. We first examined mitochondrial respiration before investigating evidence of mitochondrial UPR (UPRmt) in placentas of PE < 34 wk patients. Reduced placental oxidative phosphorylation (OXPHOS) capacity measured in situ was observed despite no change in protein or mRNA levels of electron transport chain complexes. These results were fully recapitulated by subjecting trophoblast cells to repetitive hypoxia-reoxygenation and were associated with activation of a noncanonical UPRmt pathway; the quality-control protease CLPP, central to UPRmt signal transduction, was reduced, while the cochaperone, TID1, was increased. Transcriptional factor ATF5, which regulates expression of key UPRmt genes including HSP60 and GRP75, showed no nuclear translocation. Induction of the UPRmt with methacycline reduced OXPHOS capacity, while silencing CLPP was sufficient to reduce OXPHOS capacity, membrane potential, and promoted mitochondrial fission. CLPP was negatively regulated by the PERK-eIF2α arm of the endoplasmic reticulum UPR pathway, independent of ATF4. Similar changes in the UPRmt pathway were observed in placentas from PE < 34 wk patients. Our results identify UPRmt as a therapeutic target for restoration of placental function in early-onset preeclampsia

Successful Treatment of Primary Sclerosing Cholangitis with a Steroid and a Probiotic

Primary sclerosing cholangitis (PSC) is a serious disease that not only affects quality of life but can also have a significant effect on patient survival. The treatment for PSC is primarily supportive with the aim of controlling cholestatic symptoms and preventing complications. Ursodeoxycholic acid may induce biochemical improvements in affected patients; however, long-term pediatric studies to determine its possible benefits in young patients are lacking. Thus, the treatment of pediatric PSC remains a significant clinical challenge. We describe a patient with PSC and undetermined colitis who was treated with a combination of a steroid, salazosulfapyridine, and a probiotic. This treatment provided benefits both for PSC and the undetermined colitis. These findings suggest that bacterial flora and gut inflammation are closely associated with the pathogenesis of inflammatory bowel disease-related PSC. Suppression of bowel inflammation and maintenance of bacterial homeostasis may be important for treating PSC

Chiral Polymerization in Open Systems From Chiral-Selective Reaction Rates

We investigate the possibility that prebiotic homochirality can be achieved exclusively through chiral-selective reaction rate parameters without any other explicit mechanism for chiral bias. Specifically, we examine an open network of polymerization reactions, where the reaction rates can have chiral-selective values. The reactions are neither autocatalytic nor do they contain explicit enantiomeric cross-inhibition terms. We are thus investigating how rare a set of chiral-selective reaction rates needs to be in order to generate a reasonable amount of chiral bias. We quantify our results adopting a statistical approach: varying both the mean value and the rms dispersion of the relevant reaction rates, we show that moderate to high levels of chiral excess can be achieved with fairly small chiral bias, below 10%. Considering the various unknowns related to prebiotic chemical networks in early Earth and the dependence of reaction rates to environmental properties such as temperature and pressure variations, we argue that homochirality could have been achieved from moderate amounts of chiral selectivity in the reaction rates.Comment: 15 pages, 6 figures, accepted for publication in Origins of Life and Evolution of Biosphere

#WuhanDiary and #WuhanLockdown: gendered posting patterns and behaviours on Weibo during the COVID-19 pandemic

Social media can be both a source of information and misinformation during health emergencies. During the COVID-19 pandemic, social media became a ubiquitous tool for people to communicate and represents a rich source of data researchers can use to analyse users' experiences, knowledge and sentiments. Research on social media posts during COVID-19 has identified, to date, the perpetuity of traditional gendered norms and experiences. Yet these studies are mostly based on Western social media platforms. Little is known about gendered experiences of lockdown communicated on non-Western social media platforms. Using data from Weibo, China's leading social media platform, we examine gendered user patterns and sentiment during the first wave of the pandemic between 1 January 2020 and 1 July 2020. We find that Weibo posts by self-identified women and men conformed with some gendered norms identified on other social media platforms during the COVID-19 pandemic (posting patterns and keyword usage) but not all (sentiment). This insight may be important for targeted public health messaging on social media during future health emergencies

RNA-Seq reveals changes in human placental metabolism, transport and endocrinology across the first-second trimester transition.

The human placenta is exposed to major environmental changes towards the end of the first trimester associated with full onset of the maternal arterial placental circulation. Changes include a switch from histotrophic to hemotrophic nutrition, and a threefold rise in the intraplacental oxygen concentration. We evaluated their impact on trophoblast development and function using RNA-sequencing (RNA-Seq) and DNA-methylation analyses performed on the same chorionic villous samples at 7-8 (n=8) and 13-14 (n=6) weeks of gestation. Reads were adjusted for fetal sex. Most DEGs were associated with protein processing in the endoplasmic reticulum (ER), hormone secretion, transport, extracellular matrix, vasculogenesis, and reactive oxygen species metabolism. Transcripts higher in the first trimester were associated with synthesis and ER processing of peptide hormones, and glycolytic pathways. Transcripts encoding proteins mediating transport of oxygen, lipids, protein, glucose, and ions were significantly increased in the second trimester. The motifs of CBX3 and BCL6 were significantly overrepresented, indicating the involvement of these transcription factor networks in the regulation of trophoblast migration, proliferation and fusion. These findings are consistent with a high level of cell proliferation and hormone secretion by the early placenta to secure implantation in a physiological low-oxygen environment