'Like we definitely have to go greener, but ': Analysing affective-discursive practices in populist environmental discourse.

Previous studies on environmental issues in right-wing populism have mostly focused on political actors and their argumentation. In contrast, this study examines environmental populist discourse from the perspective of laypeople in Finland. We used interviews (n = 25) to analyse affective-discursive practices in environmental talk, identifying four partly interrelated practices: belittling the 'annoying liberals', constructing the ordinary rural people as victims, externalizing blame to the 'real' polluters, and glorifying Finnish nature. These practices shed light on subject positions, affect, and functions in environmental discourse. Our contributions to the field of social psychology are threefold. First, we apply an affective-discursive approach in a novel context, deepening our understanding of affect in environmental populism. Second, we explore the nuanced features of populist reasoning and argumentation, shedding light on the functions and social implications of populist environmental discourse. Third, our analysis of identities and the discourse of laypeople provides insights into the dynamics that contribute to the polarization around environmental issues in society. We argue that the sceptical environmental discourse associated with right-wing populism may persist precisely due to the affective and polarized nature of environmental issues.

'You truly are the worst kind of racist!': Argumentation and polarization in online discussions around gender and radical-right populism.

The role of women in populist and radical right-wing parties is a topic that has gained increased scholarly attention. The aim of this article is to add to this literature by analysing how a female right-wing populist leader becomes positioned in online interactions in the hybrid media system. In doing so, the study seeks to make a twofold contribution to research on populist and radical right discourse online: to explore the ways in which notions related to gender and radical-right populism are constructed in such discourse and to shed light on their argumentative character. The study applies a critical discursive psychological approach to study these discursive patterns in two interrelated social media datasets, comprising discussion threads from Facebook and Twitter. The study shows how, through argumentation and dialogue, the commenters' position both each other and the female populist leader as fit or unfit, racist or non-racist, patriotic or non-patriotic and as a victim or culprit of hate-speech and misogyny. The implications of these findings for social psychological research on radical-right populism, political polarization and online hate-speech are discussed.

Red-pilled mama bears and enlightened power goddesses: Discursive constructions of feminine identities in a conspiracy theory space.

Previous research into the gendered social identity work involved in conspiracy theories (CTs) has largely focused on expressions of masculinity. The present study investigates the employment and mobilization of feminine identities in online Covid-19 conspiracy theory seminars through a critical discursive psychological perspective. The analysis finds three interpretative repertoires for representing the pandemic: the totalitarianism repertoire, the corrupt medical profession repertoire and the awakening repertoire. The most prominent feminine subject position constructed in relation to these repertoires is a maternal identity that functions as a category entitlement: mothers are represented as having a unique viewpoint on the purported pandemic conspiracy by virtue of their supposed inherent morality and concern for the welfare of children. Mothers are depicted as the cultural reproducers of the group, tasked with keeping the(ir) children safe from the influence of the conspiracy. Moreover, women are persuaded to take part in anti-conspiracy action by drawing on notions of empowerment, self-actualization, and sisterhood. These findings suggest that feminine identities, and maternal identities in particular, play a key role in the mobilizing power of CTs.

The transcription factor aryl hydrocarbon receptor nuclear translocator functions as an estrogen receptor beta-selective coactivator, and its recruitment to alternative pathways mediates antiestrogenic effects of dioxin.

The biological effects of dioxins are mediated by the aryl hydrocarbon receptor (AhR) and its dimerization partner, the AhR nuclear translocator (ARNT), and include interference with hormonal signaling pathways like the response to estrogens. The effects of estrogens are mediated by two estrogen receptor (ER) isoforms, ERalpha and ERbeta, which belong to the family of nuclear receptors. We have previously shown that ARNT can act as coactivator of the ERs. In this study, we show that recruitment of ARNT to AhR or hypoxia-inducible factor-1alpha signaling pathways as well as small interfering RNA-mediated down-regulation of ARNT levels lead to a reduction in ER transcriptional activity. Using chromatin immunoprecipitation assays, we demonstrate that this decrease coincides with reduced recruitment of ARNT to estradiol-regulated promoters. We show further that coactivation by ARNT as well as inhibition by dioxin acts stronger on ERbeta than on ERalpha activity. Additionally, we demonstrate that the effects of ARNT are dependent on the A/B domain of the ERs with the A/B domain of ERbeta being considerably stronger in mediating the coactivating effects of ARNT. Taken together, our studies show that recruitment of ARNT to the AhR after dioxin treatment can account for the antiestrogenic effect of dioxins. Moreover, we show for the first time that the inhibitory effects of dioxin are more pronounced on ERbeta than on ERalpha.

3-Methylcholanthrene displays dual effects on estrogen receptor (ER) alpha and ER beta signaling in a cell-type specific fashion.

The biological effects of 17beta-estradiol (E(2)) are mediated by the two estrogen receptor (ER) isoforms ERalpha and ERbeta. These receptors are ligand-inducible transcription factors that belong to the nuclear receptor superfamily. These receptors are also targets for a broad range of natural and synthetic compounds that induce ER activity, including dietary compounds, pharmaceuticals, and various types of environmental pollutants such as bisphenols and polychlorinated hydroxy-biphenyls. Here, we study the effect of the combustion byproduct 3-methylcholanthrene (3-MC) on ERalpha and ERbeta. 3-MC is a compound identified previously as an activator of the aryl hydrocarbon receptor (AhR). Activation of AhR is traditionally associated with an inhibition of the E(2) signaling network. In this study, we demonstrate that 3-MC is a cell-specific activator or inhibitor of E(2) signaling pathways. We show that 3-MC acts as a repressor in some cells, presumably via the AhR, whereas it is a potent activator of ER activity in other cells. It is interesting that we demonstrate that the estrogenic effects of 3-MC are dependent on the ability of cells to metabolize parental 3-MC to alternative compounds. In summary, our results suggest that exposure to AhR ligands like 3-MC can lead to either activation or repression of E(2) signaling, depending on the cellular context.

An amphioxus orthologue of the estrogen receptor that does not bind estradiol: insights into estrogen receptor evolution.

BACKGROUND: The origin of nuclear receptors (NRs) and the question whether the ancestral NR was a liganded or an unliganded transcription factor has been recently debated. To obtain insight into the evolution of the ligand binding ability of estrogen receptors (ER), we comparatively characterized the ER from the protochordate amphioxus (Branchiostoma floridae), and the ER from lamprey (Petromyzon marinus), a basal vertebrate. RESULTS: Extensive phylogenetic studies as well as signature analysis allowed us to confirm that the amphioxus ER (amphiER) and the lamprey ER (lampER) belong to the ER group. LampER behaves as a "classical" vertebrate ER, as it binds to specific DNA Estrogen Responsive Elements (EREs), and is activated by estradiol (E2), the classical ER natural ligand. In contrast, we found that although amphiER binds EREs, it is unable to bind E2 and to activate transcription in response to E2. Among the 7 natural and synthetic ER ligands tested as well as a large repertoire of 14 cholesterol derivatives, only Bisphenol A (an endocrine disruptor with estrogenic activity) bound to amphiER, suggesting that a ligand binding pocket exists within the receptor. Parsimony analysis considering all available ER sequences suggest that the ancestral ER was not able to bind E2 and that this ability evolved specifically in the vertebrate lineage. This result does not support a previous analysis based on ancestral sequence reconstruction that proposed the ancestral steroid receptor to bind estradiol. We show that biased taxonomic sampling can alter the calculation of ancestral sequence and that the previous result might stem from a high proportion of vertebrate ERs in the dataset used to compute the ancestral sequence. CONCLUSION: Taken together, our results highlight the importance of comparative experimental approaches vs ancestral reconstructions for the evolutionary study of endocrine systems: comparative analysis of extant ERs suggests that the ancestral ER did not bind estradiol and that it gained the ability to be regulated by estradiol specifically in the vertebrate lineage, before lamprey split.

Managing stake and accountability in Prime Ministers' accounts of the "refugee crisis": A longitudinal analysis.

Taking a (critical) discursive psychological approach, the present study explores the identity management of the Finnish and Swedish Prime Ministers (PM) in relation to the "refugee crisis" and their countries' asylum policies. By taking a longitudinal approach and analysing the PMs' accounts of the "refugee crisis" from 1-year period, we focused on the ways rhetorical devices related to ethos, logos, and pathos were used to manage the issues of stake and accountability, as well as on the ways in which categories were worked up to serve particular functions. Our comparative analysis demonstrated significant similarities in the Finnish and Swedish PMs' talk, especially with regard to the transfer from a discourse of pathos and ethos, describing refugees in terms of individualism and humaneness, to a discourse of logos, emphasizing rationality, justifying sharpened immigration policies, and homogenizing refugees. However, the different historical paths of the two countries' immigration policies and the specific political situation had implications for the PMs' discourse. The Swedish PM could feasibly scapegoat the Sweden Democrats and the political right in opposition, whereas the Finnish PM, with the populist radical right as a government partner, engaged more heavily in distinctions between "real, needing" and "false, undeserving" refugees. We argue for the longitudinal approach in the analysis of political discourse, as such an approach allows to identify the changes and continuities in the discourse, as well as to grasp the dialogical interplay between the discourse and its context.

Diet-derived polyphenol metabolite enterolactone is a tissue-specific estrogen receptor activator.

Numerous dietary compounds can modify gene expression by binding to the members of the nuclear receptor superfamily of transcription factors. For example, dietary polyphenols, such as soy isoflavones genistein and daidzein, modulate the activity of the estrogen receptors (ERs)-alpha and ERbeta. An additional class of dietary polyphenols that modulate cellular signaling pathways are lignans, compounds that are common constituents of Western diets. In this study, we show that a metabolite of dietary lignans, enterolactone, at physiological concentrations, activates ER-mediated transcription in vitro with preference for ERalpha. The effects of enterolactone are mediated by the ER ligand binding domain and are susceptible to antiestrogen treatment. Furthermore, the affinity of enterolactone toward ERalpha, measured by a novel ligand binding assay, is augmented in cell culture conditions. Moreover, our results demonstrate for the first time that enterolactone has estrogenic activity in vivo. In transgenic estrogen-sensitive reporter mice, enterolactone induces tissue-specific estrogen-responsive reporter gene expression as well as promotes uterine stromal edema and expression of estrogen-responsive endogenous genes (CyclinD1 and Ki67). Taken together, our data show that enterolactone is a selective ER agonist inducing ER-mediated transcription both in vitro in different cell lines and in vivo in the mouse uterus.

Regulation of postnatal lung development and homeostasis by estrogen receptor beta.

Estrogens have well-documented effects on lung development and physiology. However, the classical estrogen receptor alpha (ERalpha) is undetectable in the lung, and this has left many unanswered questions about the mechanism of estrogen action in this organ. Here we show, both in vivo and in vitro, that ERbeta is abundantly expressed and biologically active in the lung. Comparisons of lungs from wild-type mice and mice with an inactivated ERbeta gene (ERbeta(-/-)) revealed decreased numbers of alveoli in adult female ERbeta(-/-) mice and findings suggesting deficient alveolar formation as well as evidence of surfactant accumulation. Platelet-derived growth factor A (PDGF-A) and granulocyte-macrophage colony-stimulating factor (GM-CSF), key regulators of alveolar formation and surfactant homeostasis, respectively, were decreased in lungs of adult female ERbeta(-/-) mice, and direct transcriptional regulation of these genes by ERbeta was demonstrated. This suggests that estrogens act via ERbeta in the lung to modify PDGF-A and GM-CSF expression. These results provide a potential molecular mechanism for the gender differences in alveolar structure observed in the adult lung and establish ERbeta as a previously unknown regulator of postnatal lung development and homeostasis.

Uterine rupture and perinatal outcome.

BACKGROUND: In view of the increasing number of caesarean sections (CS), we wanted to investigate the clinical aspects of uterine rupture including perinatal outcome. METHODS: A retrospective investigation of 24,181 deliveries at Stockholm South General Hospital between 1999 and 2004. Patient notes from cases with ICD-codes 0710 and 0711 were studied together with charts from previous deliveries and neonatal data from the Paediatric Department. RESULTS: Some 22 cases of uterine rupture were found, giving an incidence of 0.9 per 1,000 deliveries. In all cases, the diagnosis was confirmed at laparotomy. In 19/22 cases, the rupture occurred in patients with a previous uterine scar, 18 of whom were delivered at term and one at 16 gestational weeks. One case of intrauterine fetal death was noted. Of the remaining 20 newborns, 9 had a 5-min Apgar

Thyroid hormone-mediated negative transcriptional regulation of Necdin expression.

Unliganded thyroid hormone receptors (apoTRs) repress transcription of hormone-activated genes by recruiting corepressors to the promoters. In contrast, on promoters containing so-called negative thyroid hormone response elements (nTREs), apoTRs activate transcription. A number of different molecular mechanisms have been described as to how apoTRs activate transcription varying with the target gene of the study. Here we demonstrate that thyroid hormone regulates the transcription of the Necdin gene, a developmentally regulated candidate gene for the genomic imprinting-associated neurobehavioural disorder, Prader-Willi syndrome. ApoTRs activate Necdin expression through an nTRE in its promoter, downstream of the transcription start site. The nTRE of the Necdin gene resembles the nTREs of the TSHbeta genes of the hypothalamus-pituitary-thyroid axis in the sequence, position in the promoter, and mode of activation. We show that this group of nTRE-driven genes shares the requirements for binding of the retinoic X receptor and nuclear receptor corepressor/silencing mediator of retinoid and thyroid hormone receptors (NCoR/SMRT) for full ligand-independent activation, whereas there is no need for association of the p160 family of coactivators. In accordance with the requirement for corepressors, Necdin expression is influenced by deacetylase activity, suggesting that histone deacetylases and corepressors as well could function as activators of transcription, depending on the promoter context.

The endogenous retinoid metabolite S-4-oxo-9-cis-13,14-dihydro-retinoic acid activates retinoic acid receptor signalling both in vitro and in vivo.

Retinoic acid receptor (RAR) and retinoid X receptor are ligand-induced transcription factors that belong to the nuclear receptor family. The receptors are activated by small hydrophobic compounds, such as all-trans-retinoic acid and 9-cis-retinoic acid, respectively. Interestingly, these receptors are also targets for a number of exogenous compounds. In this study, we characterized the biological activity of the 9-cis-substituted retinoic acid metabolite, S-4-oxo-9-cis-13,14-dihydro-retinoic acid (S-4o9cDH-RA). The endogenous levels of this metabolite in wild-type mice and rats were found to be higher than those of all-trans-retinoic acid, especially in the liver. Using cell-based luciferase reporter systems, we showed that S-4o9cDH-RA activates the transcription of retinoic acid response element-containing genes in several cell types, both from a simple 2xDR5 element and from the promoter of the natural retinoid target gene RARbeta2. In addition, quantitative RT-PCR analysis demonstrated that S-4o9cDH-RA treatment significantly increases the endogenous mRNA levels of the RAR target gene RARbeta2. Utilizing a limited proteolytic digestion assay, we showed that S-4o9cDH-RA induces conformational changes to both RARalpha and RARbeta in the same manner as does all-trans-retinoic acid, suggesting that S-4o9cDH-RA is indeed an endogenous ligand for these receptors. These in vitro results were corroborated in an in vivo system, where S-4o9cDH-RA induced morphological changes similar to those of all-trans-retinoic acid in the developing chicken wing bud. When locally applied to the wing bud, S-4o9cDH-RA induced digit pattern duplications in a dose-dependent fashion. The results illustrate that S-4o9cDH-RA closely mimics all-trans-retinoic acid with regard to pattern respecification. Finally, using quantitative RT-PCR analysis, we showed that S-4o9cDH-RA induces the transcription of several retinoic acid-regulated genes in chick wing buds, including Hoxb8, RARbeta2, shh, Cyp26 and bmp2. Although S-4o9cDH-RA was less potent when compared with all-trans-retinoic acid, the findings clearly demonstrate that S-4o9cDH-RA has the capacity to bind and activate nuclear retinoid receptors and regulate gene transcription both in vitro and in vivo.

High-throughput protein production--lessons from scaling up from 10 to 288 recombinant proteins per week.

The demand for high-throughput recombinant protein production has markedly increased with the increased activity in the field of proteomics. Within the Human Protein Atlas project recombinantly produced human protein fragments are used for antibody production. Here we describe how the protein expression and purification protocol has been optimized in the project to allow for handling of nearly 300 different proteins per week. The number of manual handling steps has been significantly reduced (from 18 to 9) and the protein purification has been completely automated.

The basic helix-loop-helix-PAS protein ARNT functions as a potent coactivator of estrogen receptor-dependent transcription.

The biological effects of estrogens are mediated by the estrogen receptors ERalpha and ERbeta. These receptors regulate gene expression through binding to DNA enhancer elements and subsequently recruiting factors such as coactivators that modulate their transcriptional activity. Here we show that ARNT (aryl hydrocarbon receptor nuclear translocator), the obligatory heterodimerization partner for the aryl hydrocarbon receptor and hypoxia inducible factor 1alpha, functions as a potent coactivator of ERalpha- and ERbeta- dependent transcription. The coactivating effect of ARNT depends on physical interaction with the ERs and involves the C-terminal domain of ARNT and not the structurally conserved basic helix-loop-helix and PAS (Per-ARNT-Sim) motifs. Moreover, we show that ARNT/ER interaction requires the E2-activated ligand binding domain of ERalpha or ERbeta. These observations, together with the previous role of ARNT as an obligatory partner protein for conditionally regulated basic helix-loop-helix-PAS proteins like the aryl hydrocarbon receptor or hypoxia inducible factor 1alpha, expand the cellular functions of ARNT to include regulation of ERalpha and ERbeta transcriptional activity. ARNT was furthermore recruited to a natural ER target gene promoter in a estrogen-dependent manner, supporting a physiological role for ARNT as an ER coactivator.

The Ah receptor inhibits estrogen-induced estrogen receptor beta in breast cancer cells.

We have studied the effect of the aryl hydrocarbon receptor ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on estrogen receptor (ER) beta gene expression in the human breast cancer cell line, T47D. TCDD inhibited 17beta-estradiol (E2)-induced up-regulation of both ER beta wild type and ER beta cx mRNA. Cycloheximide pre-treatment had no inhibitory effect, and the estimated half-life of ER beta mRNA of about 33 min was not changed by any hormone administration. Chromatin immunoprecipitation experiments showed recruitment of ER alpha to the ER beta promoter. Gel mobility shift experiments revealed an E2-induced protein binding to a half site estrogen response element in the ER beta promoter, and TCDD reduced that binding. These results show that ER alpha regulates the expression of its own heterodimerization partner, ER beta, in T47D cells. TCDD, an anti-estrogenic compound, inhibits ER alpha-mediated induction of ER beta mRNA. These findings add to our understanding of cross talk between dioxin and estrogen signaling in human cells.