Effects of exposure to gadolinium on the development of geographically and phylogenetically distant sea urchins species

Gadolinium (Gd), a metal of the lanthanide series used as contrast agent for magnetic resonance imaging, is released into the aquatic environment. We investigated the effects of Gd on the development of four sea urchin species: two from Europe, Paracentrotus lividus and Arbacia lixula, and two from Australia, Heliocidaris tuberculata and Centrostephanus rodgersii. Exposure to Gd from fertilization resulted in inhibition or alteration of skeleton growth in the plutei. The similar morphological response to Gd in the four species indicates a similar mechanism underlying abnormal skeletogenesis. Sensitivity to Gd greatly varied, with the EC50 ranging from 56 nM to 132 μM across the four species. These different sensitivities highlight the importance of testing toxicity in several species for risk assessment. The strong negative effects of Gd on calcification in plutei, together with the plethora of marine species that have calcifying larvae, indicates that Gd pollution is urgent issue that needs to be addressed

Crater population and resurfacing of the Martian north polar layered deposits

Present-day accumulation in the north polar layered deposits (NPLD) is thought to occur via deposition on the north polar residual cap. Understanding current mass balance in relation to current climate would provide insight into the climatic record of the NPLD. To constrain processes and rates of NPLD resurfacing, a search for craters was conducted using images from the Mars Reconnaissance Orbiter Context Camera. One hundred thirty craters have been identified on the NPLD, 95 of which are located within a region defined to represent recent accumulation. High Resolution Imaging Science Experiment images of craters in this region reveal a morphological sequence of crater degradation that provides a qualitative understanding of processes involved in crater removal. A classification system for these craters was developed based on the amount of apparent degradation and infilling and where possible depth/diameter ratios were determined. The temporal and spatial distribution of crater degradation is interpreted to be close to uniform. Through comparison of the size-frequency distribution of these craters with the expected production function, the craters are interpreted to be an equilibrium population with a crater of diameter D meters having a lifetime of ~30.75D^(1.14) years. Accumulation rates within these craters are estimated at 7.2D^(−0.14) mm/yr, which corresponds to values of ~3–4 mm/yr and are much higher than rates thought to apply to the surrounding flat terrain. The current crater population is estimated to have accumulated in the last ~20 kyr or less

Complement activation contributes to subretinal fibrosis through the induction of epithelial-to-mesenchymal transition (EMT) in retinal pigment epithelial cells

Inflammation; Macular fibrosis; Subretinal fibrosisInflamación; Fibrosis macular; Fibrosis subretinianaInflamació; Fibrosi macular; Fibrosi subretinalBackground We previously reported higher plasma levels of complement fragments C3a and C5a in neovascular Age-related Macular Degeneration (nAMD) patients with macular fibrosis. This study aimed to understand whether complement activation contributes to the development of macular fibrosis and the underlying mechanisms involved. Methods Complement activation was blocked using a C5 neutralizing antibody (BB5.1) in C57BL/6J mice after induction of subretinal fibrosis using the two-stage laser protocol. Fibrotic lesions were examined 10 days after the 2nd laser through fundus examination and immunohistochemistry. The expression of C5aR in fibrotic lesions and retinal pigment epithelial (RPE) cultures were examined by confocal microscopy. Primary murine RPE cells were treated with C3a or C5a (10–100 ng/mL) or TGF-β2 (10 ng/mL). Epithelial-to-mesenchymal transition (EMT) was assessed through various readouts. The expression of E-cadherin, vimentin, fibronectin, α-SMA, Slug, ERK/AKT and pSMAD2/3 were determined by Western blot and immunocytochemistry. Collagen contraction and wound-healing assays were used as functional readouts of EMT. The production of IL-6, TGF-β1, TGF-β2 and VEGF by RPE cells were determined by ELISA. PMX53 was used to block C5aR in RPE cultures and in vivo in mice with subretinal fibrosis. Results Extensive C5b-9 deposition was detected at the site of subretinal fibrosis. BB5.1 treatment completely abrogated complement activation and significantly reduced subretinal fibrosis. C5aR was detected in RPE and infiltrating MHC-II+ cells in subretinal fibrosis. In vitro, RPE cells constitutively express C5/C5a and C5aR, and their expression was increased by TGF-β2 treatment. C5a but not C3a increased fibronectin, α-SMA, vimentin and Slug expression, and decreased E-cadherin expression in RPE cells. C5a treatment also increased the contractility and migration of RPE cells and enhanced the production of VEGF and TGF-β1/2. C5a treatment induced pSmad2/3 and pERK1/2 expression in RPE cells and this was blocked by PMX53. PMX53 treatment significantly reduced sodium fluorescein leakage in the subretinal fibrosis model, while collagen-I+ lesions only mildly reduced. Conclusions Complement activation is critically involved in the development of subretinal fibrosis, partially through C5a–C5aR-mediated EMT in RPE cells. Targeting complement activation rather than C5a may be a novel approach for the management of macular fibrosis.This study was supported by a grant from Fight for Sight (5057/5058; 5105/5106)

Formal Quantum Efficiencies for the Photocatalytic Reduction of CO2 in a Gas Phase Batch Reactor

The photocatalytic reduction of CO2 to fuels, or useful products, is an area of active research. In this work, nanoengineering and surface modification of titania were investigated as approaches for improving the CO2 reduction efficiency in a fixed-bed gas phase batch photoreactor under UV–vis irradiation. Titania nanotubes were prepared by a hydrothermal method, and TiO2 (P25) was surface modified with copper clusters. Unmodified TiO2 (P25) was used as the bench-mark comparison. The titania nanotubes and Cu-TiO2 materials showed higher efficiency for the photocatalytic reduction of CO2 to yield CH4 as compared to P25. Carbon monoxide yields were similar for all photocatalysts tested. The photocatalytic reduction of CO2 was observed on all photocatalyst tested, with the nanotubes proving to be the most efficient for the production of CH4. The product yields per mass of catalyst observed in this work are similar to those reported in the literature (with similar reactor parameters) but the calculated formal quantum efficiencies for CO2 reduction are very low (4.41 × 10−5 to 5.95 × 10-4)

Effects of hepatocyte nuclear factor-1A and -4A on pancreatic stone protein/regenerating protein and C-reactive protein gene expression: implications for maturity-onset diabetes of the young

BACKGROUND: There is a significant clinical overlap between patients with hepatocyte nuclear factor (HNF)-1A and HNF4A maturity-onset diabetes of the young (MODY), two forms of monogenic diabetes. HNF1A and HNF4A are transcription factors that control common and partly overlapping sets of target genes. We have previously shown that elevated serum pancreatic stone protein / regenerating protein A (PSP/reg1A) levels can be detected in subjects with HNF1A-MODY. In this study, we investigated whether PSP/reg is differentially regulated by HNF1A and HNF4A. METHODS: Quantitative real-time PCR (qPCR) and Western blotting were used to validate gene and protein expression in cellular models of HNF1A- and HNF4A-MODY. Serum PSP/reg1A levels and high-sensitivity C-reactive protein (hsCRP) were measured by ELISA in 31 HNF1A- and 9 HNF4A-MODY subjects. The two groups were matched for age, body mass index, diabetes duration, blood pressure, lipid profile and aspirin and statin use. RESULTS: Inducible repression of HNF1A and HNF4A function in INS-1 cells suggested that PSP/reg induction required HNF4A, but not HNF1A. In contrast, crp gene expression was significantly reduced by repression of HNF1A, but not HNF4A function. PSP/reg levels were significantly lower in HNF4A subjects when compared to HNF1A subjects [9.25 (7.85-12.85) ng/ml vs. 12.5 (10.61-17.87) ng/ml, U-test P = 0.025]. hsCRP levels were significantly lower in HNF1A-MODY [0.22 (0.17-0.35) mg/L] compared to HNF4A-MODY group [0.81 (0.38-1.41) mg/L, U-test P = 0.002], Parallel measurements of serum PSP/reg1A and hsCRP levels were able to discriminate HNF1A- and HNF4A-MODY subjects. CONCLUSION: Our study demonstrates that two distinct target genes, PSP/reg and crp, are differentially regulated by HNF1A and HNF4A, and provides clinical proof-of-concept that serum PSP/reg1A and hsCRP levels may distinguish HNF1A-MODY from HNF4A-MODY subjects

Toxicity induced by Gadolinium ions on sea urchin embryos: comparison among phylogenetically distant species and focus on stress response and skeletogenesis.

Pharmaceuticals are a class of emerging environmental contaminants. Gadolinium (Gd) is a lanthanide metal whose chelates are employed as contrast agents for magnetic resonance imaging, and subsequently released into the aquatic environment. We investigated the effects of exposure to sublethal Gd concentrations on the development of four phylogenetically and geographically distant sea urchin species: two Mediterranean, Paracentrotus lividus and Arbacia lixula, and two from Australia, Heliocidaris tuberculata and Centrostephanus rodgersii. Sensitivity to Gd greatly varied, with EC50 ranging from 56 nM to 132 µM across the four species. Measures of the Gd and Ca content inside embryos showed a time- and dose-dependent increase in Gd, in parallel with a reduction in Ca. In all the four species, we observed a general delay of embryo development at 24h post-fertilization, and a strong inhibition of skeleton growth at 48h. Further experiments were carried out on P. lividus embryos: RT-PCR gene expression analysis showed the misregulation of several genes implicated both in the skeletogenic and the left-right axis specification networks. WB analysis showed an increase of the LC3 autophagic marker at 24 and 48h. Confocal microscopy studies confirmed the increased number of autophagosomes and autophagolysosomes and showed no apoptotic induction. The results show the hazard of Gd in the marine environment, indicating that Gd is able to affect three different levels in sea urchin embryos: morphogenesis, stress response such as autophagy, and gene expression. Results highlight that pollution assays based on only one species can be misleading with respect to hazard risk assessment

Returning home: heritage work among the Stl'atl'imx of the Lower Lillooet River Valley

This article focusses on heritage practices in the tensioned landscape of the Stl’atl’imx (pronounced Stat-lee-um) people of the Lower Lillooet River Valley, British Columbia, Canada. Displaced from their traditional territories and cultural traditions through the colonial encounter, they are enacting, challenging and remaking their heritage as part of their long term goal to reclaim their land and return ‘home’. I draw on three examples of their heritage work: graveyard cleaning, the shifting ‘official’/‘unofficial’ heritage of a wagon road, and marshalling of the mountain named Nsvq’ts (pronounced In-SHUCK-ch) in order to illustrate how the past is strategically mobilised in order to substantiate positions in the present. While this paper focusses on heritage in an Indigenous and postcolonial context, I contend that the dynamics of heritage practices outlined here are applicable to all heritage practices

Surviving the Anthropocene: the resilience of marine animals to climate change

If marine organisms are to persist through the Anthropocene, they will need to be resilient, but what is resilience, and can resilience of marine organisms build within a single lifetime or over generations? The aim of this review is to evaluate the resilience capacity of marine animals in a time of unprecedented global climate change. Resilience is the capacity of an ecosystem, society, or organism to recover from stress. Marine organisms can build resilience to climate change through phenotypic plasticity or adaptation. Phenotypic plasticity involves phenotypic changes in physiology, morphology, or behaviour which improve the response of an organism in a new environment without altering their genotype. Adaptation is an evolutionary longer process, occurring over many generations and involves the selection of tolerant genotypes which shift the average phenotype within a population towards the fitness peak. Research on resilience of marine organisms has concentrated on responses to specific species and single climate change stressors. It is unknown whether phenotypic plasticity and adaptation of marine organisms including molluscs, echinoderms, polychaetes, crustaceans, corals, and fish will be rapid enough for the pace of climate change

Perspectives of pharmacists on facilitating experiential learning placements for pharmacy students in non-patient facing settings

Full text available via ShareLink until August 07 2020: https://authors.elsevier.com/a/1bFq96gprIBGQ%7EIntroduction: Recently, the model of pharmacy education in Ireland changed to a five-year pharmacy degree, with three distinct blocks of experimental placements dispersed throughout the degree. The United Kingdom is also considering the introduction of a similar five-year pharmacy degree, while the United States is looking to further expand non-clinical experiential learning opportunities. This study was carried out to ascertain the perspectives of pharmacists working in non-patient facing roles on the barriers to and facilitators of placements to aid in identifying placement recruitment strategies for non-patient facing placements. Methods: A questionnaire was distributed to pharmacists employed in non-patient facing settings, including in pharmaceutical industry, education, and regulation. Quantitative responses were analyzed using descriptive statistics, while qualitative questions were analyzed thematically. Results: Regardless of experience in the practice setting or supervision, the majority expressed a preference for offering paid placements of six months' duration. There was divided opinion regarding whether students should be given study leave, whether the student's supervisor should be a pharmacist, and whether students should undertake specialized postgraduate training. The main barriers to placements were time, the placement structure, availability of suitable projects or supervisors, and awareness of placement opportunities. Prior experience in the practice area, developing the talent pipeline, and personal interests were all placement facilitators. Conclusions: Given the increasing roles for pharmacists in non-patient facing practice settings, this study highlights the importance of stakeholder involvement during the implementation of a new model of education to ensure that placements in all settings are feasible

Circulating miR-330-3p in Late Pregnancy is Associated with Pregnancy Outcomes Among Lean Women with GDM

Gestational Diabetes Mellitus (GDM) is characterised by insulin resistance accompanied by reduced beta-cell compensation to increased insulin demand, typically observed in the second and third trimester and associated with adverse pregnancy outcomes. There is a need for a biomarker that can accurately monitor status and predict outcome in GDM, reducing foetal-maternal morbidity and mortality risks. To this end, circulating microRNAs (miRNAs) present themselves as promising candidates, stably expressed in serum and known to play crucial roles in regulation of glucose metabolism. We analysed circulating miRNA profiles in a cohort of GDM patients (n=31) and nondiabetic controls (n=29) during the third trimester for miRNA associated with insulin-secretory defects and glucose homeostasis. We identified miR-330-3p as being significantly upregulated in lean women with GDM compared to nondiabetic controls. Furthermore, increased levels of miR-330-3p were associated with better response to treatment (diet vs. insulin), with lower levels associated with exogenous insulin requirement. We observed miR-330-3p to be significantly related to the percentage of caesarean deliveries, with miR-330-3p expression significantly higher in spontaneously delivered GDM patients. We report this strong novel association of circulating miR-330-3p with risk of primary caesarean delivery as a pregnancy outcome linked with poor maternal glycaemic control, strengthening the growing body of evidence for roles of diabetes-associated miRNAs in glucose homeostasis and adaptation to the complex changes related to pregnancy