Contrasting local and long-range-transported warm ice-nucleating particles during an atmospheric river in coastal California, USA

Ice-nucleating particles (INPs) have been found to influence the amount, phase and efficiency of precipitation from winter storms, including atmospheric rivers.Warm INPs, those that initiate freezing at temperatures warmer than -10°C, are thought to be particularly impactful because they can create primary ice in mixed-phase clouds, enhancing precipitation efficiency. The dominant sources of warm INPs during atmospheric rivers, the role of meteorology in modulating transport and injection of warm INPs into atmospheric river clouds, and the impact of warm INPs on mixed-phase cloud properties are not well-understood. In this case study, time-resolved precipitation samples were collected during an atmospheric river in northern California, USA, during winter 2016. Precipitation samples were collected at two sites, one coastal and one inland, which are separated by about 35 km. The sites are sufficiently close that air mass sources during this storm were almost identical, but the inland site was exposed to terrestrial sources of warm INPs while the coastal site was not. Warm INPs were more numerous in precipitation at the inland site by an order of magnitude. Using FLEXPART (FLEXible PARTicle dispersion model) dispersion modeling and radar-derived cloud vertical structure, we detected influence from terrestrial INP sources at the inland site but did not find clear evidence of marine warm INPs at either site.We episodically detected warm INPs from long-range-transported sources at both sites. By extending the FLEXPART modeling using a meteorological reanalysis, we demonstrate that long-range-transported warm INPs were observed only when the upper tropospheric jet provided transport to cloud tops. Using radar-derived hydrometeor classifications, we demonstrate that hydrometeors over the terrestrially influenced inland site were more likely to be in the ice phase for cloud temperatures between 0 and -10°C. We thus conclude that terrestrial and long-rangetransported aerosol were important sources of warm INPs during this atmospheric river. Meteorological details such as transport mechanism and cloud structure were important in determining (i) warm INP source and injection temperature and (ii) ultimately the impact of warm INPs on mixed-phase cloud properties

track2KBA: An R package for identifying important sites for biodiversity from tracking data

Identifying important sites for biodiversity is vital for conservation and management. However, there is a lack of accessible, easily applied tools that enable practitioners to delineate important sites for highly mobile species using established criteria. We introduce the R package ‘track2KBA’, a tool to identify important sites at the population level using tracking data from individual animals based on three key steps: (a) identifying individual core areas, (b) assessing population-level representativeness of the sample and (c) quantifying spatial overlap among individuals and scaling up to the population. We describe package functionality and exemplify its application using tracking data from three taxa in contrasting environments: a seal, a marine turtle and a migratory land bird. This tool facilitates the delineation of sites of ecological relevance for diverse taxa and provides output useful for assessing their importance to a population or species, as in the Key Biodiversity Area (KBA) Standard. As such, ‘track2KBA’ can contribute directly to conservation planning at global and regional levels

Cognitive Processing Biases Associated With Fear of Childbirth

Fear of childbirth (FOC) is a phobic-like response concerning the prospect of giving birth. FOC can have negative implications for women during pregnancy and can impact their birthing experience. Cognitive processing biases (e.g., difficulty disengaging from threatening information, interpreting ambiguous information as threatening, and preferentially recalling threatening content) have previously been found to maintain general anxiety and low mood. To date, there has been no research assessing these attention, interpretation, and memory biases and their relationship with FOC in pregnant women. Accordingly, in this cross-sectional study, participants who were at least 12 weeks pregnant (n = 116), recruited through a local hospital trust, completed tasks assessing attention (emotional Stroop task), interpretation (scrambled sentences test), and explicit memory (recognition task) biases with materials including FOC-related content. They also completed three separate measures of FOC and measures of low mood, general anxiety, worry, and rumination. We found that a negative interpretation bias (but not attention or explicit memory biases) was associated with higher levels of FOC. These findings indicate that women presenting with higher FOC are more likely to demonstrate negative interpretation biases for ambiguous information relating to childbirth, which may inform research developing interventions to support women presenting with FOC

Neuroprotective effects of the triterpenoid, CDDO methyl amide, a potent inducer of Nrf2-mediated transcription.

The NF-E2-related factor-2 (Nrf2)/antioxidant response element (ARE) signaling pathway regulates phase 2 detoxification genes, including a variety of antioxidative enzymes. We tested neuroprotective effects of the synthetic triterpenoid CDDO-MA, a potent activator of the Nrf2/ARE signaling. CDDO-MA treatment of neuroblastoma SH-SY5Y cells resulted in Nrf2 upregulation and translocation from cytosol to nucleus and subsequent activation of ARE pathway genes. CDDO-MA blocked t-butylhydroperoxide-induced production of reactive oxygen species (ROS) by activation of ARE genes only in wild type, but not Nrf2 knockout mouse embryonic fibroblasts. Oral administration of CDDO-MA resulted in significant protection against MPTP-induced nigrostriatal dopaminergic neurodegeneration, pathological alpha-synuclein accumulation and oxidative damage in mice. Additionally, CDDO-MA treatment in rats produced significant rescue against striatal lesions caused by the neurotoxin 3-NP, and associated increases in the oxidative damage markers malondialdehyde, F(2)-Isoprostanes, 8-hydroxy-2-deoxyguanosine, 3-nitrotyrosine, and impaired glutathione homeostasis. Our results indicate that the CDDO-MA renders its neuroprotective effects through its potent activation of the Nrf2/ARE pathway, and suggest that triterpenoids may be beneficial for the treatment of neurodegenerative diseases like Parkinson's disease and Huntington's disease

Development and validation of limited sampling strategies for prediction of the systemic exposure to the novel anticancer agent E7070 (N-(3-chloro-7-indolyl)-1,4-benzenedisulphonamide)

E7070 is a novel, sulphonamide anticancer agent currently under clinical development for the treatment of solid tumours. The aim of this study was to develop and validate limited sampling strategies for the prediction of E7070 exposure in two different treatment schedules for phase II studies using the Bayesian estimation approach. Data from two phase I dose finding studies were used in which E7070 was administered either as a single 1 h infusion or as a daily 1 h infusion for 5 days. Plasma concentration-time data from 75 patients were randomly divided into an index data set, used for the development of the strategies, and a validation data set. Population pharmacokinetic parameters were derived on the basis of the index data set. The D-optimality algorithm was used for the selection of optimal time points for both treatment schedules. The developed strategies were compared by assessment of their predictive performance of exposure, expressed as AUC (area under the plasma concentration vs time curve), in the validation data set. The developed population pharmacokinetic model comprised three compartments, with saturable distribution to one peripheral compartment and both linear and saturable elimination from the central compartment. For the 1 h infusion, a four sample strategy was selected which resulted in unbiased and accurate predictions of AUC (bias 0.74%, precision 13%). A five sample strategy was generated for the daily times five schedule yielding unbiased (bias 3.2%) and precise (12% precision) predictions of AUC. Optimal sampling strategies were developed and validated for estimation of E7070 exposure in two different treatment schedules. Both schedules enabled accurate and unbiased predictions of AU

Analysing ‘seriousness’ in roller derby: Speaking critically with the Serious Leisure Perspective

Item not available in this repository.This article draws on original ethnographic research in the context of roller derby to argue for a sociological analysis of seriousness. Galvanized by the notable divergence between participants’ practices of ‘seriousness’ and the use of this concept in the Serious Leisure Perspective (SLP), the article develops three constructively critical points. Firstly, contra to assumptions at the core of the SLP, ‘seriousness’ in leisure is differently accessible according to familiar intersectional patterns of inequality. Moreover, roller derby occupies a position of gendered alterity in relation to a broader cultural field of sport; ‘getting taken seriously’ in this context is an issue of gender contestation. Secondly, while the normative assumption that seriousness in leisure is individually and socially ‘good’ pervades the SLP, I argue that seriousness is more accurately understood as a generative ‘mode of ordering’ (Law 1994). I analyse seriousness as one discursive resource drawn upon and enacted in participants’ organizational and representational practice. Thirdly seriousness cannot be defined, as the SLP does, predominantly in terms of commitment; commitment is an interactional achievement. Participants’ enactments of seriousness include tactics of ridicule and satire and do not necessarily cohere. This paper thus responds to the question of what a more sociological approach to seriousness might look like and argues that seriousness-in-practice, in leisure and elsewhere, is generative of multiple and ambivalent effects and is thus amenable to, and requires, sociological analysis.https://doi.org/10.5153/sro.323618pubpub

CDDO-MA attenuates MPTP-induced nigrostriatal dopaminergic neurodegeneration.

<p>Mice were pre-treated with either CDDO-MA or control diet 7 days before acute (MPTP 10 mg/kg, i.p. 3 doses every 2 hours in one day) and chronic (MPTP 40 mg/kg, for 28 day through continuous subcutaneous infusion using mini-osmotic pumps) MPTP treatment. Control animals received identical volumes of PBS. <i>A</i> Photomicrographs of TH-immunostained sections through the SNpc of mice on acute MPTP show a significant reduction in TH-positive neurons of SNpc. CDDO-MA treatment significantly blocked MPTP-induced loss of TH-positive neurons. <i>B.</i> Consistent with TH-immunostaining of SNpc, stereologic cell counts of total (Nissl-positive) and TH-immunopositive neurons of SNpc showed a significant loss following MPTP administration which was significantly attenuated by CDDO-MA treatment. <i>C.</i> Photomicrographs of TH-immunostained sections through the SNpc of mice on chronic MPTP show a significant reduction in TH-positive neurons of SNpc. CDDO-MA treatment significantly blocked MPTP-induced loss of TH-positive neurons. <i>D.</i> Consistent with TH-immunostaining of SNpc, stereologic cell counts of total (Nissl-positive) and TH-immunopositive neurons of SNpc showed a significant loss following MPTP administration which was significantly attenuated by CDDO-MA treatment. n = 10 mice per group. ^#<i>p</i><0.05 compared to control diet alone; *<i>P</i><0.05 when compared with the control diets with MPTP group. <i>E.</i> Photomicrographs of malondialdehyde (MDA)-immunostained sections through the SNpc of mice on chronic MPTP show a significant increase of MDA staining in SNpc of MPTP treated animals. CDDO-MA treatment resulted in a marked reduction of MPTP-induced MDA formation. Representative image from n = 5 mice in each group. <i>F.</i> Photomicrographs of α-synuclein stained sections through the SNpc of mice on chronic MPTP show a significant increase of α-synuclein accumulation in SNpc of MPTP treated animals. CDDO-MA treatment resulted in a significant reduction of MPTP-induced α-synuclein accumulation in SNpc neurons. High magnification inserts show the α-synuclein staining in neurons. Representative image from n = 5 mice in each group.</p

CDDO-MA treatment to SH-SY5Y cells causes Nrf2 translocation to nucleus and subsequent activation of ARE pathway.

<p><i>A.</i> Chemical structures of oleanolic acid and CDDO-MA. Oleanolic acid is a naturally occurring triterpenoid with structural similarities to CDDO. CDDO that is over 200,000 times more potent than the parent oleanolic acid was chemically modified by addition of a methyl group to obtain increased brain bioavailability. <i>B.</i> SH-SY5Y neuroblastoma cells were treated with CDDO-MA (1 µM) or DMSO as a control. In DMSO controls Nrf2 is localized to cytosol as immunostained by anti-Nrf2 antibody (closed arrow) with DAPI (open arrow) a nuclear stain. After 8 hours of CDDO-MA treatment Nrf2 from cytosol translocates to the nucleus and colocalizes with DAPI (straight arrow), Scale bar 12 µm. <i>C.</i> Nuclear translocation of Nrf2 results in a significant increase in mRNA levels of Nrf2 and other ARE genes such as NQO-1, glutathione reductase (GR) and HO-1 measured by RT-PCR at 8 and 24 hours after drug treatment. Data represented as Mean±SEM showing relative levels of mRNA at various time points compared to DMSO controls, **p<0.05 and ***p<0.001. Students-<i>t</i> test, n = 5 samples for each experimental groups. <i>D and E.</i> Increases in mRNA levels of Nrf2 and ARE genes showed corresponding increases in levels of their respective proteins analyzed by western blotting and densitometry at 8 and 24 hours after CDDO-MA treatment. Data represented as Mean±SEM showing relative percent change in levels of protein normalized to actin at various time points compared to DMSO controls, **p<0.05 and ***p<0.001. Students-<i>t</i> test, n = 6 samples for each experimental groups. <i>F.</i> CDDO-MA treatment resulted in a significant dose-response increase in levels of reduced glutathione (GSH) measured at 24 hours. Data represented as Mean±SEM showing GSH levels at 24 hours compared to DMSO controls, **p<0.05 and ***p<0.001 following Students <i>t</i>-test (n = 6). Values represented as nanomoles/mg protein from total cell lysate.</p

Activation of Nrf2/ARE pathway by CDDO-MA is Nrf2 dependent.

<p><i>A.</i> Wild type (WT) and Nrf2 knockout (KO) mouse embryonic fibroblasts were pretreated with either CDDO-MA (1, 10 and 100 nM) or DMSO (as control) for 18 hours. Analysis of ARE genes showed a statistically significant increase in GSTa3, HO-1 and NQO-1 in wild type fibroblasts compared to DMSO treated controls. Nrf2 knockout fibroblasts failed to induce ARE genes following treatment with CDDO-MA compared to respective DMSO controls, implicating that CDDO-MA requires Nrf2 to activate ARE signaling. Data represent mean±SEM, *<i>P</i><0.001 when compared with the controls, by ANOVA, n = 3 from two separate experiments. <i>B.</i> Wild type and Nrf2 knockout mouse embryonic fibroblasts were pretreated with either CDDO-MA (1, 10 and 100 nM) or DMSO (as control) for 18 hours. The next day, 250 µM tert-butyl hydroperoxide was added to these fibroblasts for 15 minutes, and generation of ROS was measured by flow cytometry. CDDO-MA treatment resulted in a significant dose dependent reduction of tBHP-induced ROS generation in wild type fibroblasts. Nrf2 knockout fibroblasts failed to show reduction in tBHP-induced ROS generation. *p<0.05 compared to knockout fibroblasts; #p<0.05 compared to 1 nM CDDO-MA, by ANOVA, n = 3 from two separate experiments.</p

Neuroprotective effects of CDDO-MA on striatal dopamine and its metabolites in MPTP neurotoxicity.

a<p>Data are expressed as mean±SEM. Values represent as ng per mg protein.</p>b<p>#, p<0.05, ##, p<0.01compared to PBS groups; *, p<0.05, **, p<0.01 compared to control diet +MPTP group, ANOVA, Student-Newman-Keul's post test.</p