Stimulus Selection Based on Gender Ratios: Gender Ratios are Indicative of Both Stereotypical and Conceptual Gender.

This paper explores how the use of gender ratios to inform stimulus selection affects the activation of gendered social information. It investigates if stimuli selected this way can activate gender stereotype knowledge and/or conceptual gender knowledge. This was tested through attribute naming (Study 1) and rating (Study 2) tasks, with component and regression analysis allowing for examination of the nature of gender ratios at both attribute and component levels. The results provide rich information about the nature of gender ratio information as a means of stimulus selection, and in doing so support both conceptualisations as long as researchers acknowledge their overlap. The results also indicate that these roles elicited both positive/prescriptive (i.e., the role is appropriate for a given gender) and negative/proscriptive beliefs (i.e., the role is not appropriate for a given gender). These findings hold important implications for future research using gender ratios.

Exploring the comparative adequacy of a unimanual and a bimanual stimulus-response setup for use with three-alternative choice response time tasks.

Research often conceptualises complex social factors as being distinct binary categories (e.g., female vs male, feminine vs masculine). While this can be appropriate, the addition of an 'overlapping' category (e.g., non-binary, gender neutral) can contextualise the 'binary', both for participants (allowing more complex conceptualisations of the categories than the 'either/or' conceptualisation in binary tasks), and for the results (by providing a neutral baseline for comparison). However, it is not clear what the best response setup for such a task would be. In this study, we explore this topic through comparing a unimanual (N = 34) and a bimanual response setup (N = 32) for use with a three-alternative choice response time task. Crucially, one of the stimulus categories ('mixed') was composed of stimulus elements from the other two stimulus categories used in that task (Complex Task). A reference button task was included to isolate the motoric component of response registration (Simple Task). The results of the simple task indicated lower motoric costs for the unimanual compared to the bimanual setup. However, when statistically controlling for these motoric costs in the complex task, the bimanual setup had a lower error rate and faster response times than the unimanual setup. Further, in the complex task error rates and response times were higher for the mixed than the matched stimuli, indicating that responding to mixed stimuli is more challenging for encoding and/or decision making processes. This difference was more pronounced in the unimanual than the bimanual setup. Taken together these results indicate that the unimanual setup is more adequate for the reference button task, whereas the intricacy of overlapping categories in the complex task is better contained in the bimanual setup, i.e. when some response alternatives are allocated to one hand and other alternatives to the other hand.

Testing the effectiveness of the Internet-based instrument PsyToolkit: A comparison between web-based (PsyToolkit) and lab-based (E-Prime 3.0) measurements of response choice and response time in a complex psycholinguistic task.

To test the effectiveness of the Internet-based instrument PsyToolkit for use with complex choice tasks, a replicability study was conducted wherein an existing psycholinguistic paradigm was utilised to compare results obtained through the Internet-based implementation of PsyToolkit with those obtained through the laboratory-based implementation of E-Prime 3.0. The results indicated that PsyToolkit is a viable method for conducting both general and psycholinguistic specific experiments that utilise complex response time tasks, with effects found to replicate for both response choice and response time.

Exploring the Onset of a Male-Biased Interpretation of Masculine Generics Among French Speaking Kindergarten Children.

In French, and other gender marked languages, there are two ways to interpret a grammatical masculine form when used to refer to social roles or occupations [e.g., les magiciens (the magicians masculine )]. It can refer to a group composed of only men (specific use of the masculine form), or one composed of both women and men (generic use). Studies of adults revealed that the rule that masculine forms can be interpreted as inclusive of either gender is not readily applied. To gain a better understanding of the processes shaping this phenomenon, we present a follow-up study (N = 52) to Lévy et al. (2016) to explore how French-speaking kindergarten children (3-5 years of age) resolve the semantic ambiguity of the grammatical masculine form when presented with role or occupation nouns. In a paradigm where participants' gazes were monitored, children were presented with pictures of a pair of two boys and a pair of one girl and one boy and were prompted to Look at the [role nounmasculine plural form]. First, the results suggest a stereotype effect in that children more strongly directed their gaze toward the boy-boy picture for stereotypical male role nouns, but toward the girl-boy picture for stereotypical female role nouns. Second, in the non-stereotypical/neutral condition we did not find an indication of any own-sex preference (as in Lévy et al., 2016), but of an influence of the role nouns' grammatical gender, in that children more strongly directed their gaze toward boy-boy pictures than toward girl-boy pictures. We suggest that a specific interpretation of masculine forms might already start to emerge between 3 and 5 years of age, while gender stereotypes are still activated.

Gauging the Impact of Gender Grammaticization in Different Languages: Application of a Linguistic-Visual Paradigm.

Employing a linguistic-visual paradigm, we investigated whether the grammaticization of gender information impacts readers' gender representations. French and German were taken as comparative languages, taking into account the male gender bias associated to both languages, as well as the comparative gender biases associated to their plural determiners (French: les [generic] vs. German: die [morphologically feminine]). Bilingual speakers of French and German had to judge whether a pair of facial images representing two men or a man and a woman could represent a gender stereotypical role noun prime (e.g., nurses). The prime was presented in the masculine plural form with or without a plural determiner. Results indicated that the overt grammaticization of the male gender in the masculine form dominated the representation of the role nouns (though interpretable as generic). However, the effect of the determiner was not found, indicating that only gender information associated to a human reference role noun had impacted readers' representations. The results, discussed in the framework of the thinking-for-speaking hypothesis, demonstrated that linguistic-visual paradigms are well-suited to gauge the impact of both stereotype information and grammaticization when processing role nouns.

Stereotype or grammar? The representation of gender when two-year-old and three-year-old French-speaking toddlers listen to role nouns.

Using a preferential looking paradigm, the current study examined the role that grammatical gender plays when preschool French-speaking toddlers process role nouns in the masculine form (e.g., chanteurs masculine 'singers'). While being auditorily prompted with "Look at the 'a role noun'!", two- and three-year-olds were presented with two pictures of two characters ('boy-boy' versus 'girl-boy') with attributes of the given role noun (e.g., singers with microphone and music notes). All role nouns were presented in the masculine plural form, which, despite its use to refer to mixed-gender groups, can be interpreted as referring to men. We expected toddlers to be biased by stereotypes, yet when non-stereotypical role nouns were presented, toddlers were not influenced by grammatical gender, but by their own sex (even more so for three-year-old toddlers). The absence of sensitivity to grammatical cues for either age group is discussed in terms of the developmental awareness of grammatical gender.

Warm-hearted businessmen, competitive housewives? Effects of gender-fair language on adolescents' perceptions of occupations.

Recent studies from countries with grammatical gender languages (e.g., French) found both children and adults to more frequently think of female jobholders and to consider women's success in male dominated occupations more likely when the jobs were described in pair forms (i.e., by explicit reference to male and female jobholders, e.g., inventeuses et inventeurs; French feminine and masculine plural forms for inventors), rather than masculine only forms (e.g., inventors). To gain a better understanding of this phenomenon, we systematically varied the gender connotation of occupations (males overrepresented, females overrepresented, equal share of males and females) and measured additional dependent variables, predicting that gender fair language would reduce the impact of the gender connotation on participants' perceptions. In a sample of 222 adolescents (aged 12-17) from French speaking Switzerland, we found that pair forms attenuated the difference in the ascription of success to male and female jobholders in gendered occupations and attenuated the differential ascription of warmth to prototypical jobholders in male vs. female dominated jobs. However, no effect of language form on the ascription of competence was found. These findings suggest that language policies are an effective tool to impact gendered perceptions, however, they also hint at competence-related gender stereotypes being in decline.

IL1RN and KRT13 Expression in Bladder Cancer: Association with Pathologic Characteristics and Smoking Status.

Purpose. To validate microarray data on cytokeratin 13 (KRT13) and interleukin-1 receptor antagonist (IL1RN) expression in urothelial carcinoma of the urinary bladder (UCB) and to correlate our findings with pathologic characteristics and tobacco smoking. Methods. UCB tissue samples (n = 109) and control samples (n = 14) were obtained from transurethral resection and radical cystectomy specimens. Immunohistochemical staining of KRT13 and IL1RN was performed and semiquantitative expression scores were assessed. Smoking status was evaluated using a standardized questionnaire. Expression scores were correlated with pathologic characteristics (tumor stage and grade) and with smoking status. Results. Loss of KRT13 and IL1RN expression was observed in UCB tissue samples when compared to controls (P = 0.007, P = 0.008) in which KRT13 and IL1RN expression were high. IL1RN expression was significantly reduced in muscle-invasive tumors (P = 0.003). In tissue samples of current smokers, a significant downregulation of IL1RN was found when compared to never smokers (P = 0.013). Conclusion. Decreased expressions of KRT13 and IL1RN are common features of UCB and are associated with aggressive disease. Tobacco smoking may enhance the loss of IL1RN, indicating an overweight of proinflammatory mediators involved in UCB progression. Further validation of the influence of smoking on IL1RN expression is warranted.

Norms on the gender perception of role nouns in Czech, English, French, German, Italian, Norwegian, and Slovak.

We collected norms on the gender stereotypicality of an extensive list of role nouns in Czech, English, French, German, Italian, Norwegian, and Slovak, to be used as a basis for the selection of stimulus materials in future studies. We present a Web-based tool (available at https://www.unifr.ch/lcg/ ) that we developed to collect these norms and that we expect to be useful for other researchers, as well. In essence, we provide (a) gender stereotypicality norms across a number of languages and (b) a tool to facilitate cross-language as well as cross-cultural comparisons when researchers are interested in the investigation of the impact of stereotypicality on the processing of role nouns.

Social judgment of aggressive language: effects of target and sender sex on the evaluation of slurs.

We investigated the influence of the sex of the target and the sex of the sender on the judgment of slurs (verbal derogation). From previous research, we selected and clustered slurs into seven categories and respondents rated their degree of perceived insult in two consecutive questionnaire surveys (N = 281 and N = 224, respectively). Results confirm that slurs are generally judged as being more insulting when directed towards females than towards males. In comparison, differences in sex of sender were small. When directed towards females, slurs referring to "being loose" were rated as the most insulting. For both target sexes, remarks referring to homosexuality and physical unattractiveness were among those rated as the most insulting. Least insulting were slurs referring to unethical acts, lack of intelligence and cowardliness. A sex of respondent effect was found, suggesting that women rated slurs generally more insulting than men. The pattern of results showed considerable stability across surveys attesting for the reliability of the method for measuring the social evaluation of slurs.

HERV-E-mediated modulation of PLA2G4A transcription in urothelial carcinoma.

Human endogenous retroviruses (HERV) and related elements account for more than 8% of the human genome and significantly contribute to the human transcriptome by long terminal repeat (LTR) promoter activity. In this context, HERVs are thought to intervene in the expression of adjacent genes by providing regulatory sequences (cis-effect) or via noncoding RNA including natural antisense transcripts. To address the potential impact of HERV activity in urothelial carcinoma, we comparatively analyzed the HERV transcription profiles in paired samples of non-malignant urothelium and urothelial carcinoma derived from 13 patients with bladder cancer by means of a retrovirus-specific microarray (RetroArray). We established a characteristic HERV signature consisting of six ubiquitously active HERV subgroups (E4-1, HERV-Rb, ERV9, HERV-K-T47D, NMWV3, HERV-KC4). The transcription pattern is largely identical in human urothelial carcinoma, non-malignant urothelial tissue, four tumor-derived cell lines and in a non-malignant urothelial cell line (UROtsa). Quantitative reverse transcriptase PCR (qRT-PCR) of HERV-E4-1, HERV-K(HML-6) and HERV-T(S71-TK1) revealed a bias to lower HERV activity in carcinoma samples compared to non-malignant tissue. Determination of active HERV-E4-1 loci by cloning and sequencing revealed six HERV-E4-1 proviral loci that are differentially regulated in urothelial carcinoma cells and normal tissue. Two full-length HERV-E4-1 proviruses, HERV-Ec1 and HERV-Ec6, are located in antisense orientation in introns of the genes PLA2G4A and RNGTT, respectively. PLA2G4A encodes a cytosolic phospholipase A2 (cPLA2) that is dysregulated in many human tumors. PLA2G4A and HERV-Ec1 displayed reciprocal transcript levels in 7 of 11 urothelial carcinoma patients. Moreover, reciprocal shifts were observed after treatment of UROtsa cells with HERV-Ec1 and PLA2G4A-directed siRNAs or 5-aza-2'-deoxycytidine (aza-dC) pointing to an antagonistic regulation of PLA2G4A and HERV-Ec1 transcription in human urothelial cells. We suggest that transcription of HERV-Ec1 contributes to fine tuning of cPLA2 expression, thereby facilitating tumorigenesis.

New insights into the influence of cigarette smoking on urothelial carcinogenesis: smoking-induced gene expression in tumor-free urothelium might discriminate muscle-invasive from nonmuscle-invasive urothelial bladder cancer.

Smoking is the main risk factor for urothelial bladder cancer. In former smokers the risk decreases but does not reach the low level of never smokers. This indicates reversible and permanent smoking-derived genetic alterations. Transcriptional changes may point to mechanisms, how smoking promotes urothelial bladder cancer. To identify smoking-derived transcriptional changes we performed gene expression profiling in current, former, and never smokers, using tumor and tumor-free urothelium from patients with nonmuscle-invasive urothelial bladder cancer (NMIBC) or muscle-invasive urothelial bladder cancer (MIBC). Smoking turned out to influence gene expression much less than tumor stage (NMIBC or MIBC) and tumor transformation (tumor-free or tumor). Smoking seemed to influence gene expression in patients with MIBC more strongly compared to those with NMIBC. The least irreversible changes after smoking cessation were proposed in tumor-free urothelium from patients with NMIBC. Growth factors and oncogenes were up-regulated in tumor-free urothelium from smokers with MIBC but not from smokers with NMIBC. A panel of genes up-regulated in smokers have potential for early detection and distinction of MIBC from NMIBC using tumor-free tissue.

Urine from current smokers induces centrosome aberrations and spindle defects in vitro in nonmalignant human cell lines.

Tobacco smoke containing numerous derived chemical carcinogens is the main risk factor for urothelial carcinoma. These carcinogens can induce DNA damage leading to chromosomal instability, which plays a fundamental role in urothelial carcinogenesis. Possible mechanisms could be centrosomal aberrations, which cause defective spindles and may be responsible for genetic instability. We evaluated the effect of urine from never smokers (NS) and current smokers (CS) in concentrations of 0 to 50% on cell proliferation, chromosomes, centrosomes, and the spindle status of normal human dermal fibroblasts and normal human urothelial cells (UROtsa). After 2 weeks of urine treatment, cell cultures were analyzed by centrosome and spindle immunostaining and conventional cytogenetics. Effects were compared to results of untreated controls. Analysis of normal human dermal fibroblasts and UROtsa cells revealed that urine from CS induced higher values of centrosome aberrations in a dose-dependent and cell line-independent manner when compared to cultures treated with urine from NS and untreated controls. Centrosomal alterations correlated with spindle defects and an increase of sporadic chromosomal aberrations. The observations suggest a causative role of chemical carcinogens in urine from CS in the origin of centrosome and spindle defects in vitro leading to chromosomal instability and may be involved in urothelial carcinogenesis.

Smoking increases transcription of human endogenous retroviruses in a newly established in vitro cell model and in normal urothelium.

Human endogenous retroviruses (HERVs) accounting for 9% of the human genome are considered as surrogate markers for genetic instability and as a driving force of genetic variation. Moreover, they modulate regular gene activities and give rise to expression of disease-associated peptides that may serve as diagnostic markers or even targets for T cell-based immune responses. To date, no data are available on the potential link between urothelial carcinogenesis, HERV activity, and tobacco smoking, the main risk for bladder cancer. Here, we report on potential alterations in HERV transcription induced by smoking in a newly established in vitro model and in human urothelium. Normal human dermal fibroblasts were cultivated with urine from never (n = 6) and current smokers (n = 6) and transcription levels for the HERV subfamilies HERV-E 4-1, HERV-T S71-TK1, and HERV-K HML-6 were measured by quantitative real-time PCR. Tendencies toward increased mean transcript levels were detected for cells treated with urine from current smokers. Equally, activity measured in human urothelium supported an increase of HERV transcription in current smokers (n = 9) compared to never smokers (n = 4).

In vivo evaluation of intravesical paclitaxel and combined bcl-xL antisense oligodeoxynucleotide treatment for orthotopic urothelial carcinoma.

PURPOSE: To evaluate intravesical paclitaxel monotherapy and combined treatment with antiapoptotic bcl-xL antisense oligodeoxynucleotides (AS-ODNs) on urothelial carcinoma (UC). METHODS: Forty-eight FoxN(rnu) athymic nude rats with orthotopic human bladder UC were randomized to four treatment groups [1, paclitaxel; 2, paclitaxel/bcl-xL AS-ODNs; 3, bcl-xL AS-ODNs (control); 4, medium (control)]. Three consecutive instillations were applied and weekly endoscopic tumor size measurements were performed. RESULTS: Significant tumor size reduction was achieved in groups 1 and 2 (each P < 0.0001), whereas continuous UC growth was observed in control animals (groups 3 and 4; P < 0.0001 and P < 0.0020). Complete tumor eradication was achieved in four treated animals (groups 1 and 2). No significant difference in chemoresection effects was found between groups 1 and 2 (P = 0.2251). CONCLUSIONS: We present an in vivo evaluation of intravesical treatment with paclitaxel and combined bcl-xL AS-ODNs. Despite efficient tumor size reduction, no gain was observed when adding bcl-xL AS-ODNs in this experimental setting.

Topical chemotherapy in human urothelial carcinoma explants: a novel translational tool for preclinical evaluation of experimental intravesical therapies.

BACKGROUND: Urothelial carcinoma (UC) is associated with a high local recurrence rate despite intravesical therapy. There is a lack of representative preclinical models for standardized testing of novel experimental therapies. OBJECTIVE: To develop an ex vivo model for human UC and to evaluate its ability to generate reproducible and reliable results when testing cytotoxic agents. DESIGN, SETTING, AND PARTICIPANTS: Normal human urothelium (NHU) and bladder UC explants were collected from patients treated at our institution. A total of 195 surgical explants were cultured on a gelatine matrix. Tissue viability was regularly assessed using nicotinamide adenine dinucleotide (NADH) diaphorase enzymehistochemistry. Topical paclitaxel (PTX) or mitomycin C (MMC) chemotherapy was performed in a subset of 45 UC specimens. INTERVENTION: All patients underwent radical cystectomy (RC) or primary transurethral resection (TUR) of a bladder UC. MEASUREMENTS: Triple immunofluorescence (pan-cytokeratin [pan-CK]; 4',6-diamidin-2'-phenylindol-dihydrochloride [DAPI]; terminal deoxynucleotidyl transferase biotin-dUTP nick-end labelling [TUNEL]) and caspase-3 staining of paraffin sections was performed. Proliferation rates were assessed using Ki-67 labelling indices. Apoptosis (percent) was quantified in representative tissue areas to characterize culture stability and to assess antineoplastic effects. RESULTS AND LIMITATIONS: No signs of necrosis and no significant changes in apoptosis were observed during the first 12 d of culture. Of all explants, 88.5% were vital after 20 d. In a highly reproducible fashion, topical chemotherapy resulted in significantly increased apoptosis (37.4% [19.0-75.0%] for PTX and 36.2% [18.8-46.7%] for MMC) compared with controls (7.5% [3.0-26.8%]; p<0.001]). No statistically significant difference was observed regarding the effects of the two chemotherapeutic agents (p=0.119). CONCLUSIONS: The presented human ex vivo model takes UC heterogeneity into account and serves as a valuable translational tool. It offers an attractive alternative to preclinical cell line experiments or animal models and may even be used for prospective toxicity and drug efficacy tests in individual patients.

Cellular uptake and ex vivo urothelial penetration by oligodeoxynucleotides for optimizing treatment of transitional cell carcinoma.

OBJECTIVE: To evaluate cellular uptake and urothelial penetration of oligodeoxynucleotides (ODNs) in transitional cell carcinoma (TCC) cell lines and in a porcine ex vivo model, respectively. STUDY DESIGN: A panel of human TCC cell lines (RT 112, HT 1197 and UM-UC3) were exposed tofluorescein-labeled ODNs. Transfection rates were assessed byfluorescence microscopy and fluorescence-activated cell sorting (FACS). Intravesical treatment with ODNs was performed in a porcine ex vivo model. Urothelial penetration was evaluated using fluorescence microscopy of cryosections. RESULTS: Treatment with ODNs provided transfection rates of at least 96.8% of TCC cells, irrespective of use of a transfection agent. Effective urothelial penetration by ODNs was detected when compared with controls (p = 0.0325). The addition of a liposomal transfection agent significantly increased the penetration depth, allowing affection of deep urothelial cell layers (p = 0.0082). CONCLUSION: High transfection rates of ODNs can be achieved in TCC cells. Urothelial penetration of ODNs was observed down to the deepest cell layers when a transfection agent is added, suggesting a high potential for complementing the chemoresection effects on residual tumor areas during intravesical therapy of non-muscle-invasive TCC.

Evaluation of cytotoxic effects induced by bcl-2 and bcl-xL antisense-oligodeoxynucleotides in normal urothelium and transitional cell carcinoma.

We report on cytotoxic effects of bcl-2 and bcl-xL antisense-oligodeoxynucleotides (AS-ODNs) in benign urothelial and transitional cell carcinoma (TCC) cell lines. The benign urothelial cell line (UROtsa) and four TCC cell lines (UM-UC-3, RT 112 , HT 1197 and T 24/83) were incubated with bcl-2 and bcl-xL AS-ODNs and cell mortality rates were assessed. Bcl-2 and bcl-xL AS-ODN treatment resulted in low toxicity in UROtsa cells (6% and 10% cell mortality, respectively). After bcl-2 AS-ODN treatment, cell mortality rates in TCC cell lines were significantly higher than in UROtsa cells (mean values: 33% vs. 6%, respectively). Bcl-2 AS-ODN treatment also caused significantly higher cell death rates in the majority of TCC cell lines when compared to bcl-xL-AS-ODN therapy (mean values: 33% vs. 11%, respectively). In conclusion, bcl-2 AS-ODNs show significantly higher cell mortality in TCC cells, whereas toxic effects on normal urothelium seem to be minor. Our results suggest favourable characteristics for the clinical application of AS-ODN in intravesical chemotherapy of TCC.

Can societal language amendments change gender representation? The case of Norway.

This study investigates the influence of stereotypical information and the grammatical masculine on the representation of gender in Norwegian by applying a sentence evaluation paradigm. In this study participants had to decide whether a second sentence containing explicit information about the gender of one of more of the characters (e.g. . . . one of the women . . . ) was a sensible continuation of a first sentence introducing a role name (e.g. The spies came out . . . ). Participants' representations were biased by the stereotypicality of the role names when reading female (e.g. nurses) and male (e.g. pilots) stereotyped role names (replicating findings from the English sample in a previous publication), but male biased when reading neutral role names (replicating findings from the French and the German samples in a previous publication).

Au pairs are rarely male: norms on the gender perception of role names across English, French, and German.

A list of role names for future use in research on gender stereotyping was created and evaluated. In two studies, 126 role names were rated with reference to their gender stereotypicality by English-, French-, and German-speaking students of universities in Switzerland (French and German) and in the U.K. (English). Role names were either presented in specific feminine and masculine forms (Study 1) or in the masculine form (generic masculine) only (Study 2). The rankings of the stereotypicality ratings were highly reliable across languages and questionnaire versions, but the overall mean of the ratings was less strongly male if participants were also presented with the female versions of the role names and if the latter were presented on the left side of the questionnaires.