The Ca and Mg isotope record of the Cryogenian Trezona carbon isotope excursion

This work was supported by a grant from the Simons Foundation (SCOL 611878, ASCA) and the Carlsberg Foundation to ASCA. ASCA and CJB also acknowledge support from the Danish National Research Foundation (Grant No. DNRF53). ACM and CVR acknowledge support from NSF (EAR-0842946) for funding fieldwork on the Trezona Formation in South Australia. JAH acknowledges support from NSF (IES-1410317) and from NSF OCE CAREER Grant (1654571).The Trezona carbon isotope excursion is recorded on five different continents in platform carbonates deposited prior to the end-Cryogenian Marinoan glaciation (>635 Ma) and represents a change in carbon isotope values of 16–18‰. Based on the spatial and temporal reproducibility, the excursion previously has been interpreted as tracking the carbon isotopic composition of dissolved inorganic carbon in the global ocean before the descent into a snowball Earth. However, in modern restricted shallow marine and freshwater settings, carbon isotope values have a similarly large range, which is mostly independent from open ocean chemistry and instead reflects local processes. In this study, we combine calcium, magnesium, and strontium isotope geochemistry with a numerical model of carbonate diagenesis to disentangle the degree to which the Trezona excursion reflects changes in global seawater chemistry versus local shallow-water platform environments. Our analysis demonstrates that the most extreme carbon isotope values (∼-10‰ versus +10‰) are preserved in former platform aragonite that was neomorphosed to calcite during sediment-buffered conditions and record the primary carbon isotope composition of platform-top surface waters. In contrast, the downturn and recovery of the Trezona excursion are recorded in carbonates that were altered during early fluid-buffered diagenesis and commonly are dolomitized. We also find that the nadir of the Trezona excursion is associated with a fractional increase in siliciclastic sediments, whereas the recovery from the excursion correlates with a relative increase in carbonate. This relationship suggests that the extreme negative isotopic shift in platform aragonite occurred in concert with periods of increased input of siliciclastic sediments, changes in water depth, and possibly nutrients to platform environments. Although the process for generating extremely negative carbon isotope values in Neoproterozoic platform carbonates remains enigmatic, we speculate that these excursions reflect kinetic isotope effects associated with CO2 invasion in platform waters during periods of intense primary productivity.Publisher PDFPeer reviewe

miR-17 overexpression in cystic fibrosis airway epithelial cells decreases interleukin-8 production.

Interleukin (IL)-8 levels are higher than normal in cystic fibrosis (CF) airways, causing neutrophil infiltration and non-resolving inflammation. Overexpression of microRNAs that target IL-8 expression in airway epithelial cells may represent a therapeutic strategy for cystic fibrosis. IL-8 protein and mRNA were measured in cystic fibrosis and non-cystic fibrosis bronchoalveolar lavage fluid and bronchial brushings (n=20 per group). miRNAs decreased in the cystic fibrosis lung and predicted to target IL-8 mRNA were quantified in βENaC-transgenic, cystic fibrosis transmembrane conductance regulator (Cftr)-/- and wild-type mice, primary cystic fibrosis and non-cystic fibrosis bronchial epithelial cells and a range of cystic fibrosis versus non-cystic fibrosis airway epithelial cell lines or cells stimulated with lipopolysaccharide, Pseudomonas-conditioned medium or cystic fibrosis bronchoalveolar lavage fluid. The effect of miRNA overexpression on IL-8 protein production was measured. miR-17 regulates IL-8 and its expression was decreased in adult cystic fibrosis bronchial brushings, βENaC-transgenic mice and bronchial epithelial cells chronically stimulated with Pseudomonas-conditioned medium. Overexpression of miR-17 inhibited basal and agonist-induced IL-8 protein production in F508del-CFTR homozygous CFTE29o(-) tracheal, CFBE41o(-) and/or IB3 bronchial epithelial cells. These results implicate defective CFTR, inflammation, neutrophilia and mucus overproduction in regulation of miR-17. Modulating miR-17 expression in cystic fibrosis bronchial epithelial cells may be a novel anti-inflammatory strategy for cystic fibrosis and other chronic inflammatory airway diseases

The Curriculum of the University Elementary School

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"They think we're OK and we know we're not". A qualitative study of asylum seekers' access, knowledge and views to health care in the UK

<i>Background</i>: The provision of healthcare for asylum seekers is a global issue. Providing appropriate and culturally sensitive services requires us to understand the barriers facing asylum seekers and the facilitators that help them access health care. Here, we report on two linked studies exploring these issues, along with the health care needs and beliefs of asylum seekers living in the UK. <i>Methods</i>: Two qualitative methods were employed: focus groups facilitated by members of the asylum seeking community and interviews, either one-to-one or in a group, conducted through an interpreter. Analysis was facilitated using the Framework method. <i>Results</i>: Most asylum seekers were registered with a GP, facilitated for some by an Asylum Support nurse. Many experienced difficulty getting timely appointments with their doctor, especially for self-limiting symptoms that they felt could become more serious, especially in children. Most were positive about the health care they received, although some commented on the lack of continuity. However, there was surprise and disappointment at the length of waiting times both for hospital appointments and when attending accident and emergency departments. Most had attended a dentist, but usually only when there was a clinical need. The provision of interpreters in primary care was generally good, although there was a tension between interpreters translating verbatim and acting as patient advocates. Access to interpreters in other settings, e.g. in-patient hospital stays, was problematic. Barriers included the cost of over-the-counter medication, e.g. children's paracetamol; knowledge of out-of-hours medical care; and access to specialists in secondary care. Most respondents came from countries with no system of primary medical care, which impacted on their expectations of the UK system. <i>Conclusion</i>: Most asylum seekers were positive about their experiences of health care. However, we have identified issues regarding their understanding of how the UK system works, in particular the role of general practitioners and referral to hospital specialists. The provision of an Asylum Support nurse was clearly a facilitator to accessing primary medical care. Initiatives to increase their awareness and understanding of the UK system would be beneficial. Interpreting services also need to be developed, in particular their role in secondary care and the development of the role of interpreter as patient advocate

Association between Yoga Participation and Arterial Stiffness: A Cross-Sectional Study

Background: Yoga may help adults of all fitness levels increase their physical activity and decrease their cardiovascular disease risk. Aim: To determine if arterial stiffness is lower (beneficial) in yoga versus non-yoga participants. Method: This cross-sectional study included 202 yoga (48.4 + 14.1 years, 81% female) and 181 (42.8 + 14.1 years, 44% female) non-yoga participants. The primary outcome was carotid–femoral pulse wave velocity (cfPWV). The two groups were compared using analysis of covariance with adjustments for demographic (age and sex), hemodynamic (mean arterial pressure and heart rate), lifestyle (physical activity levels, sedentary behaviour, smoking status and perceived stress score) and cardiometabolic (waist-to-hip ratio, total cholesterol and fasting glucose) factors. Results: Following adjustments, cfPWV was significantly lower in yoga compared to non-yoga participants with a mean difference: −0.28 m.s−1, (95% CI = −0.55 to 0.08). Conclusion: At a population level, yoga participation may assist with decreasing the risk of cardiovascular disease in adults

FLIP: A Targetable Mediator of Resistance to Radiation in Non-Small Cell Lung Cancer

Resistance to radiotherapy due to insufficient cancer cell death is a significant cause of treatment failure in non-small cell lung cancer (NSCLC). The endogenous caspase-8 inhibitor, FLIP, is a critical regulator of cell death that is frequently overexpressed in NSCLC and is an established inhibitor of apoptotic cell death induced via the extrinsic death receptor pathway. Apoptosis induced by ionizing radiation (IR) has been considered to be mediated predominantly via the intrinsic apoptotic pathway; however, we found that IR-induced apoptosis was significantly attenuated in NSCLC cells when caspase-8 was depleted using RNA interference (RNAi), suggesting involvement of the extrinsic apoptosis pathway. Moreover, overexpression of wild-type FLIP, but not a mutant form that cannot bind the critical death receptor adaptor protein FADD, also attenuated IR-induced apoptosis, confirming the importance of the extrinsic apoptotic pathway as a determinant of response to IR in NSCLC. Importantly, when FLIP protein levels were down-regulated by RNAi, IRinduced cell death was significantly enhanced. The clinically relevant histone deacetylase (HDAC) inhibitors vorinostat and entinostat were subsequently found to sensitize a subset of NSCLC cell lines to IR in a manner that was dependent on their ability to suppress FLIP expression and promote activation of caspase-8. Entinostat also enhanced the anti-tumor activity of IR in vivo. Therefore, FLIP down-regulation induced by HDAC inhibitors is a potential clinical strategy to radio-sensitize NSCLC and thereby improve response to radiotherapy. Overall, this study provides the first evidence that pharmacological inhibition of FLIP may improve response of NCSLC to IR

Effect of increasing the time between slurry application and first rainfall event on phosphorus concentrations in runoff

Publication history: Accepted - 26 May 2021; Published online - 12 August 2021.Minimizing slurry phosphorus (P) losses in runoff requires careful management in the context of both soil P surpluses and changing patterns in rainfall. Increasing the time interval between slurry application and the first rainstorm event is known to reduce P loss in runoff although the risk period for elevated P concentrations in runoff can extend for weeks. This study investigated the impact of increasing the time interval between slurry application and first rainstorm event on P concentrations in runoff. Simulated rainfall (40 mm h−1) was applied at 2, 4, 10, 18, 30 and 49 days after dairy slurry was surface-applied to a grassland sward in Ireland. Increasing time to runoff resulted in a decrease in dissolved reactive P concentrations from 5.0 to 1.0 mg P L−1 and a P signal in runoff for 18 days. Beyond 18 days, elevated P concentrations were observed in runoff collected from natural rainfall that preceded the day 49 rainstorm event. A published surface phosphorus and runoff model (SurPhos) was used to understand the slurry P dynamics controlling P interactions with runoff. Dissolved reactive P in runoff was predicted with accuracy by SurPhos, R2 = .89. The SurPhos model implied thatslurry P mineralization occurred during the experimental period that resulted in a small spike in P concentrations beyond the defined risk period. This study shows that the experimental data have the potential to be extrapolated to different weather scenarios using SurPhos and could test when and where slurry P could be most safely spread.Open access funding provided by IReL. WOA Institution: University College Dublin Blended DEAL: IReL

Sensitivity of Colorectal Cancer to Arginine Deprivation Therapy is Shaped by Differential Expression of Urea Cycle Enzymes

We thank Polaris Pharmaceuticals and Bio-Cancer Treatment for providing drugs and reagents. This work was supported by the Cancer Prevention Research Trust, with assistance from the Wellcome Trust Institutional Strategic Support Fund [097828/z/11/B], and Cancer Research UK in conjunction with the Department of Health as part of an Experimental Cancer Medicine Centre grant [C325/A15575]. C.A. was funded by a PhD fellowship from the Cancer Prevention Research Trust, S.S.A. was funded by a studentship from the Iraqi Government. We are thankful to John Bomalaski and Sara Galavotti for their critical reading of the manuscript and insightful suggestions. Finally, we are profoundly indebted to Professor Andreas Gescher for his constant support during the execution of this project and the writing of this manuscript.Peer reviewedPublisher PD