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Identifying high-quality causal explanations is key to scientific understanding. This research (N = 202; 50% girls; M age : 5.82 years; 64% Asian, 33% White, and 3% multiracial; data collected from 2018 to 2024) examined how explanation circularity and informants' social dominance impact children's learning preferences for causal explanations. Raised in a culture valuing circular logic, Chinese children still preferred non-circular explanations and learning from informants providing non-circular explanations (d ≥ 0.50). When informants with non-circular explanations were subordinate to those with circular explanations, Chinese and American children preferred non-circular over circular explanations (d = 1.10), but did not prefer learning new information from either informant. Although children weigh explanation quality over informant dominance when seeking explanations for given questions, they consider both cues when evaluating informants' credibility., (© 2024 The Author(s). Child Development published by Wiley Periodicals LLC on behalf of Society for Research in Child Development.)

Background: Understanding similarities and differences between groups with intersecting social identities provides key information in research and practice to promote well-being. Building on the intersectionality literature indicating significant gender and racial/ethnic differences in depressive symptoms, the present study used quantile regression to systematically present the diversity in the development of depressive symptoms for individuals with intersecting gender, race/ethnicity, and levels of symptoms., Methods: Information from the National Longitudinal Survey of Youth 79: Child and Young Adult study was employed. A detailed picture of depressive symptom trajectories from low to high quantiles was illustrated by depicting 13 quantile-specific trajectories using follow-up data from ages 15 to 40 in six gender-race/ethnicity groups: both genders of Black, Hispanic, and non-Black, non-Hispanic individuals., Results: From low to high quantiles, Black and non-Black, non-Hispanic individuals showed mostly curved, and Hispanic individuals showed mostly flat trajectories. Across the six gender-race/ethnicity groups, the trajectories below 0.50 quantiles were similar in levels and shapes from mid-adolescence to young adulthood. The differences between the six gender-race/ethnicity groups widened, indicated by outspreading trajectories, especially at quantiles above 0.50. Furthermore, non-Black, non-Hispanic males and females showed especially fast-increasing patterns at quantiles above 0.75. Among those without or with only a high school degree, Black females and non-Black, non-Hispanic females tended to report similar levels of depressive symptoms higher than other groups at high quantiles. These unique longitudinal trajectory profiles cannot be captured by the mean trajectories., Conclusions: The intersectionality of gender, race/ethnicity, and quantile of symptoms on the development of depressive symptoms was identified. Further studying the mechanism explaining this diversity can help reduce mental health disparities., (© 2023. W. Montague Cobb-NMA Health Institute.)

The Developing Belief Network is a consortium of researchers studying human development in diverse social-cultural settings, with a focus on the interplay between general cognitive development and culturally specific processes of socialization and cultural transmission in early and middle childhood. The current manuscript describes the study protocol for the network's first wave of data collection, which aims to explore the development and diversity of religious cognition and behavior. This work is guided by three key research questions: (1) How do children represent and reason about religious and supernatural agents? (2) How do children represent and reason about religion as an aspect of social identity? (3) How are religious and supernatural beliefs transmitted within and between generations? The protocol is designed to address these questions via a set of nine tasks for children between the ages of 4 and 10 years, a comprehensive survey completed by their parents/caregivers, and a task designed to elicit conversations between children and caregivers. This study is being conducted in 39 distinct cultural-religious groups (to date), spanning 17 countries and 13 languages. In this manuscript, we provide detailed descriptions of all elements of this study protocol, give a brief overview of the ways in which this protocol has been adapted for use in diverse religious communities, and present the final, English-language study materials for 6 of the 39 cultural-religious groups who are currently being recruited for this study: Protestant Americans, Catholic Americans, American members of the Church of Jesus Christ of Latter-day Saints, Jewish Americans, Muslim Americans, and religiously unaffiliated Americans., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Weisman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: This study investigates the efficacy of using a long-acting insulin analog, along with the infusion of regular insulin, in achieving appropriate glycemic control and correcting lactic acidosis in patients post orthotopic heart transplant who demonstrate severe lactic acidosis and insulin resistance., Methods: This was a retrospective study of two cohorts (IRB FLA 20-003) of patients post orthotopic heart transplant with severe lactic acidosis and insulin resistance who were admitted to a tertiary intensive care unit and treated with (group 1) or without long-acting insulin analog (group 2) within the first 24 h of admission to the intensive care unit. Insulin resistance is defined as the requirement for intravenous regular insulin infusion of more than 20 units/h without the ability to achieve appropriate serum glucose level (120-180 mg /dL). Severe lactic acidosis is defined as arterial lactic acid of more than 10 mmol/L. The following parameters were investigated: time to correct lactic acidosis, duration of postoperative mechanical ventilation, the need for periprocedural mechanical circulatory support, and 28-day mortality., Results: The 28-day mortality was zero in both groups. Two patients required periprocedural mechanical support in group one, and ten patients required mechanical support in group two (RR = 0.224, 95%, confidence interval 0.052-0.95, Z = 2.029, p = 0.042). Three patients required tracheostomy in group one, and four patients required tracheostomy in group two (RR 0.84, 95 confidence interval 0.20-3.48, Z = 0.23, P = 0.81). Wilcoxon rank-sum test was used to compare time to correct lactic acidosis, with lactic acid resolution being faster in group one ([Formula: see text] 1  = 19.7 h, SD ± 12.6 h [Formula: see text] 2  = 29.3 h, SD ± 19.6 h, Z-value - 2.02, p-value 0.043). The duration of mechanical ventilation was less in group one ([Formula: see text] 1  = 29 h, SD ± 12.7 h, [Formula: see text] 2  = 55.1 h, SD ± 44.5 h, Z-value: - 1.92, p-value 0.05)., Conclusion: Administration of low-dose long-acting insulin glargine led to the resolution of the lactic acidosis, insulin resistance, and decreased requirements for pressor and inotropic support, which led to decreased need for mechanical circulatory support., (© 2024. The Author(s).)

Both talent and effort are considered essential sources of achievement, but past research suggests a preference for people who appear to achieve through talent. This research examined the potential naturalness preference in 306 Chinese children (M age : 6.12 years; 164 girls) and 352 adults (M age : 19.87 years; 182 women) in 2019. In Study 1, participants evaluated a natural or striver protagonist of equal achievement. Children attributed greater competence and warmth to naturals than strivers; adults exhibited this preference only when attributing competence. In Study 2, participants indicated their behavioral preferences between the two protagonists. Children, but not adults, interacted more with naturals than strivers. These findings indicate the naturalness preference emerges early (ds ≥ .27) but declines in strength over time., (© 2022 The Authors. Child Development © 2022 Society for Research in Child Development.)

Silibinin, also known as silybin, is isolated from milk thistle ( Silybum marianum ). Silibinin has been demonstrated to be a good lead compound due to its potential to prevent and treat prostate cancer. Its moderate potency and poor pharmacokinetic profile hindered it from moving forward to therapeutic use. Our research group has been working on optimizing silibinin for the potential treatment of castration-resistant prostate cancer. Our previous studies established 5,7,20- O -trimethylsilybins as promising lead compounds as they can selectively suppress androgen receptor (AR)-positive LNCaP cell proliferation. Encouraged by the promising data, the present study aims to investigate the relationships between the core structure of 5,7,20- O -trimethylsilybin and their antiproliferative activities towards AR-positive (LNCaP) and AR-negative prostate cancer cell lines (PC-3 and DU145). The structure-activity relationships among the four different core structures (including flavanonol-type flavonolignan (silibinin), flavone-type flavonolignan (hydnocarpin D), chalcone-type flavonolignan, and taxifolin (a flavonolignan precursor) indicate that 5,7,20- O -trimethylsilybins are the most promising scaffold to selectively suppress AR-positive LNCaP prostate cancer cell proliferation. Further investigation on the antiproliferative potency of their optically enriched versions of the most promising 5,7,20- O -trimethylsilybins led to the conclusion that (10 R ,11 R ) derivatives (silybin A series) are more potent than (10 S ,11 S ) derivatives (silybin B series) in suppressing AR positive LNCaP cell proliferation.

Forecasts of the trajectory of an infectious agent can help guide public health decision making. A traditional approach to forecasting fits a computational model to structured data and generates a predictive distribution. However, human judgment has access to the same data as computational models plus experience, intuition, and subjective data. We propose a chimeric ensemble-a combination of computational and human judgment forecasts-as a novel approach to predicting the trajectory of an infectious agent. Each month from January, 2021 to June, 2021 we asked two generalist crowds, using the same criteria as the COVID-19 Forecast Hub, to submit a predictive distribution over incident cases and deaths at the US national level either two or three weeks into the future and combined these human judgment forecasts with forecasts from computational models submitted to the COVID-19 Forecasthub into a chimeric ensemble. We find a chimeric ensemble compared to an ensemble including only computational models improves predictions of incident cases and shows similar performance for predictions of incident deaths. A chimeric ensemble is a flexible, supportive public health tool and shows promising results for predictions of the spread of an infectious agent., (© 2022. The Author(s).)

Background: Many countries have enforced strict regulations on travel since the emergence of the SARS-CoV-2 (COVID-19) pandemic in December 2019. However, with the development of several vaccines and tests to help identify it, international travel has mostly resumed in the United States (US). Community pharmacists have long been highly accessible to the public and are capable of providing travel health services and are in an optimal position to provide COVID-19 patient care services to those who are now starting to travel again. Objectives: (1) To discuss how the COVID-19 pandemic has changed the practice of travel health and pharmacist provided travel health services in the US and (2) to discuss the incorporation COVID-19 prevention measures, as well as telehealth and other technologies, into travel health care services. Methods: A literature review was undertaken utilizing the following search engines and internet websites: PubMed, Google Scholar, Centers for Disease Control Prevention (CDC), World Health Organization (WHO), and the United States Department of Health and Human Services to identify published articles on pharmacist and pharmacy-based travel health services and patient care in the US during the COVID-19 pandemic. Results: The COVID-19 pandemic has changed many country's entry requirements which may now include COVID-19 vaccination, testing, and/or masking requirements in country. Telehealth and other technological advancements may further aid the practice of travel health by increasing patient access to care. Conclusions: Community pharmacists should consider incorporating COVID-19 vaccination and testing services in their travel health practices in order to meet country-specific COVID-19 entry requirements. Further, pharmacists should consider utilizing telehealth and other technologies to increase access to care while further limiting the potential spread and impact of COVID-19.

Aggregated human judgment forecasts for coronavirus disease 2019 (COVID-19) targets of public health importance are accurate, often outperforming computational models. Our work shows that aggregated human judgment forecasts for infectious agents are timely, accurate, and adaptable, and can be used as a tool to aid public health decision making during outbreaks., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The impact of social group information on the learning and socializing preferences of Hong Kong Chinese children were examined. Specifically, the degree to which variability in racial out-group exposure affects children's use of race to make decisions about unfamiliar individuals (Chinese, White, Southeast Asian) was investigated. Participants (N = 212; M age  = 60.51 months) chose functions for novel objects after informants demonstrated their use; indicated with which peer group member to socialize; and were measured on racial group recognition, preference, and identification. Overall, children preferred in-group members, though out-group exposure and the relative social status of out-groups mattered as well. At a young age, children's specific experiences with different races influence how they learn and befriend others across racial group lines., (© 2018 Society for Research in Child Development.)

Although children often believe an adult's claims, they may have opportunities to check these claims by gathering relevant empirical evidence themselves. Here, we examine whether children seize such opportunities, especially when the claim is counterintuitive. Chinese preschool and elementary schoolchildren were presented with five different-sized Russian dolls and asked to indicate the heaviest doll. Almost all children selected the biggest doll. Half of the children then heard a false, counterintuitive claim (i.e., smallest = heaviest). The remaining children heard a claim confirming their initial intuition (i.e., biggest = heaviest). Children in both age groups typically endorsed the experimenter's claim even when it was counterintuitive. However, during the experimenter's subsequent absence, elementary schoolchildren explored the dolls more if they had received counterintuitive rather than confirming testimony whereas preschool children rarely explored, no matter what testimony they had received. Thus, with increasing age, children seize opportunities to test counterintuitive claims. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

The decisions voters make-and whether those decisions are rational-have profound implications on the functionality of a democratic society. In this study, we delineated two criteria in evaluating voter rationality and weigh evidence of voter rationality versus irrationality. Furthermore, we compared models in two different elections in Taiwan to explore the reasons behind the irrational choices voters can make. Survey questions and an implicit association test (IAT) were administered prior to both elections among 197 voters in Taipei. These voters then reported their actual votes post-election. Model testing suggests that voters often are rational, but are more likely to make irrational choices in more important elections. Our findings indicate that voters generally aim to be diligent and to optimize their choices, even if they make less rational choices in the end. Further implications regarding elections and human rationality are discussed.

Background: Less than half of American children meet national physical activity (PA) recommendations. This study tested the feasibility, acceptability, and preliminary effectiveness of using wearable PA monitors to increase PA in school-age children., Methods: In Phase 1 of this study, conducted in 2014, 32 fifth-grade students enrolled in a low-resource middle school were given a waist-worn Fitbit Zip monitor for 4 weeks to test its feasibility (adherence) and acceptability. Adherence, wear time of ≥8 hours per day, was examined. Feedback was solicited from parents through structured interviews. In Phase 2 , conducted in 2015, 42 sixth-grade students were assigned, by classroom, to one of three conditions (Fitbit + goal and incentive-based intervention, Fitbit only, or control) to test the feasibility of the wrist-worn Fitbit Charge and its preliminary effectiveness in increasing PA over 6 weeks., Results: In Phase 1 , average adherence was 64.1%. In Phase 2 , it was 73.4% and 80.2% for participants in the Fitbit + intervention and Fitbit only groups, respectively ( p = .07). After controlling for baseline values, weight status, and sex, there were no significant group differences in changes in MVPA or steps from baseline to follow-up., Conclusions: While moderately acceptable, wearable PA monitors did not increase PA levels in this sample. They may be more effective within a coordinated school-based physical activity program.

The present study discusses the impact of union and parenthood transitions on individuals' self-esteem and sense of mastery development from midadolescence to young adulthood by using multilevel analyses with longitudinal data of 7,339 individuals between ages 15 and 38. The results show that, first, individuals in marital unions show significantly greater rates of growth in self-esteem and sense of mastery, compared with singles. Therefore, entering into marriage provides greater protections to individuals' self-esteem and sense of mastery. Second, the transition to parenthood brings significant decreases in levels and increases in rates of change in self-esteem and sense of mastery among new parents. The degree of the aforementioned changes differs by new parents' gender, union status, and living arrangement with the child at childbirth. Women are influenced more negatively than men. Living with the child at childbirth reduces the degree of decreases in self-esteem and sense of mastery, especially for mothers. In sum, from midadolescence to young adulthood, the development of individuals' self-esteem and sense of mastery is shaped by their union and parenthood transitions. Moreover, the context where these transitions take place, including the type of union and the living arrangement, moderates the degree of the impact. Our findings have important implications for research and practice in promoting the family transition experience., ((c) 2016 APA, all rights reserved).)

Human rationality--the ability to behave in order to maximize the achievement of their presumed goals (i.e., their optimal choices)--is the foundation for democracy. Research evidence has suggested that voters may not make decisions after exhaustively processing relevant information; instead, our decision-making capacity may be restricted by our own biases and the environment. In this paper, we investigate the extent to which humans in a democratic society can be rational when making decisions in a serious, complex situation-voting in a local political election. We believe examining human rationality in a political election is important, because a well-functioning democracy rests largely upon the rational choices of individual voters. Previous research has shown that explicit political attitudes predict voting intention and choices (i.e., actual votes) in democratic societies, indicating that people are able to reason comprehensively when making voting decisions. Other work, though, has demonstrated that the attitudes of which we may not be aware, such as our implicit (e.g., subconscious) preferences, can predict voting choices, which may question the well-functioning democracy. In this study, we systematically examined predictors on voting intention and choices in the 2014 mayoral election in Taipei, Taiwan. Results indicate that explicit political party preferences had the largest impact on voting intention and choices. Moreover, implicit political party preferences interacted with explicit political party preferences in accounting for voting intention, and in turn predicted voting choices. Ethnic identity and perceived voting intention of significant others were found to predict voting choices, but not voting intention. In sum, to the comfort of democracy, voters appeared to engage mainly explicit, controlled processes in making their decisions; but findings on ethnic identity and perceived voting intention of significant others may suggest otherwise.

Norenzayan et al. argue that prosocial religion develops through cultural evolution. Surprisingly, they give little attention to developmental accounts of prosocial religious beliefs. A consideration of the developmental literature supports some, but not all, of the authors' conclusions.

Cranberry flavonoids (flavonols and flavan-3-ols), in addition to their antioxidant properties, have been shown to possess potential in vitro activity against several cancers. However, the difficulty of isolating cranberry compounds has largely limited anticancer research to crude fractions without well-defined compound composition. In this study, individual cranberry flavonoids were isolated to the highest purity achieved so far using gravity and high performance column chromatography and LC-MS characterization. MTS assay indicated differential cell viability reduction of SKOV-3 and OVCAR-8 ovarian cancer cells treated with individual cranberry flavonoids. Treatment with quercetin aglycone and PAC DP-9, which exhibited the strongest activity, induced apoptosis, led to caspase-3 activation and PARP deactivation, and increased sensitivity to cisplatin. Furthermore, immunofluorescence microscopy and western blot study revealed reduced expression and activation of epidermal growth factor receptor (EGFR) in PAC DP-9 treated SKOV-3 cells. In addition, quercetin aglycone and PAC DP-9 deactivated MAPK-ERK pathway, induced downregulation of cyclin D1, DNA-PK, phospho-histone H3 and upregulation of p21, and arrested cell cycle progression. Overall, this study demonstrates promising in vitro cytotoxic and anti-proliferative properties of two newly characterized cranberry flavonoids, quercetin aglycone and PAC DP-9, against ovarian cancer cells.

Across a wide range of tasks, research has shown that people make poor probabilistic predictions of future events. Recently, the U.S. Intelligence Community sponsored a series of forecasting tournaments designed to explore the best strategies for generating accurate subjective probability estimates of geopolitical events. In this article, we describe the winning strategy: culling off top performers each year and assigning them into elite teams of superforecasters. Defying expectations of regression toward the mean 2 years in a row, superforecasters maintained high accuracy across hundreds of questions and a wide array of topics. We find support for four mutually reinforcing explanations of superforecaster performance: (a) cognitive abilities and styles, (b) task-specific skills, (c) motivation and commitment, and (d) enriched environments. These findings suggest that superforecasters are partly discovered and partly created-and that the high-performance incentives of tournaments highlight aspects of human judgment that would not come to light in laboratory paradigms focused on typical performance., (© The Author(s) 2015.)

In two studies, 5- and 6-year-old children were questioned about the status of the protagonist embedded in three different types of stories. In realistic stories that only included ordinary events, all children, irrespective of family background and schooling, claimed that the protagonist was a real person. In religious stories that included ordinarily impossible events brought about by divine intervention, claims about the status of the protagonist varied sharply with exposure to religion. Children who went to church or were enrolled in a parochial school, or both, judged the protagonist in religious stories to be a real person, whereas secular children with no such exposure to religion judged the protagonist in religious stories to be fictional. Children's upbringing was also related to their judgment about the protagonist in fantastical stories that included ordinarily impossible events whether brought about by magic (Study 1) or without reference to magic (Study 2). Secular children were more likely than religious children to judge the protagonist in such fantastical stories to be fictional. The results suggest that exposure to religious ideas has a powerful impact on children's differentiation between reality and fiction, not just for religious stories but also for fantastical stories., (Copyright © 2014 Cognitive Science Society, Inc.)

Children prefer learning from, and affiliating with, their racial in-group but those preferences may vary for biracial children. Monoracial (White, Black, Asian) and biracial (Black/White, Asian/White) children (N = 246, 3-8 years) had their racial identity primed. In a learning preferences task, participants determined the function of a novel object after watching adults (White, Black, and Asian) demonstrate its uses. In the social preferences task, participants saw pairs of children (White, Black, and Asian) and chose with whom they most wanted to socially affiliate. Biracial children showed flexibility in racial identification during learning and social tasks. However, minority-primed biracial children were not more likely than monoracial minorities to socially affiliate with primed racial in-group members, indicating their in-group preferences are contextually based., (© 2014 The Authors. Child Development © 2014 Society for Research in Child Development, Inc.)

Although very young children are unable to formulate a personal narrative of the life course, their everyday lives are steeped in narratives. Drawing on ethnographic studies in diverse sociocultural worlds, we argue that the early years of life form a vital preamble to the personal narrative. In this phase of life, the universal predisposition to narrative takes root and burgeons as young children step into whichever narrative practices are at hand, practices that are culturally differentiated from the beginning. As children narrate their experiences, they orient themselves in time and establish the interpretive grounds for intelligibility. This process is highly dynamic. Stories recur, stories are repeated, stories are revamped, and stories disappear. These dynamics constitute, for many children, an intense narrative initiation that defines early childhood as a developmental context. By the end of early childhood, they are well versed in making and remaking narratives and show an incipient ability to open a wider temporal window on their own experience., (© 2014 Wiley Periodicals, Inc.)

Many methods for reducing implicit prejudice have been identified, but little is known about their relative effectiveness. We held a research contest to experimentally compare interventions for reducing the expression of implicit racial prejudice. Teams submitted 17 interventions that were tested an average of 3.70 times each in 4 studies (total N = 17,021), with rules for revising interventions between studies. Eight of 17 interventions were effective at reducing implicit preferences for Whites compared with Blacks, particularly ones that provided experience with counterstereotypical exemplars, used evaluative conditioning methods, and provided strategies to override biases. The other 9 interventions were ineffective, particularly ones that engaged participants with others' perspectives, asked participants to consider egalitarian values, or induced a positive emotion. The most potent interventions were ones that invoked high self-involvement or linked Black people with positivity and White people with negativity. No intervention consistently reduced explicit racial preferences. Furthermore, intervention effectiveness only weakly extended to implicit preferences for Asians and Hispanics., (PsycINFO Database Record (c) 2014 APA, all rights reserved.)

Long traditions in the social sciences have emphasized the gradual internalization of intergroup attitudes and the putatively more basic tendency to prefer the groups to which one belongs. In four experiments (N = 883) spanning two cultures and two status groups within one of those cultures, we obtained new evidence that implicit intergroup attitudes emerge in young children in a form indistinguishable from adult attitudes. Strikingly, this invariance from childhood to adulthood holds for members of socially dominant majorities, who consistently favor their in-group, as well as for members of a disadvantaged minority, who, from the early moments of race-based categorization, do not show a preference for their in-group. Far from requiring a protracted period of internalization, implicit intergroup attitudes are characterized by early enculturation and developmental invariance.

Children prefer to learn from informants in consensus with one another. However, no research has examined whether this preference exists across cultures, and whether the race of the informants impacts that preference. In 2 studies, one hundred thirty-six 4- to 7-year-old European American and Taiwanese children demonstrated a systematic preference for a consensus. Nevertheless, the initial strength and persistence of that preference depended on the racial composition of the consensus. Children's preference for consensus members belonging to the same race as themselves persisted even when only one consensus member remained to provide information. When the consensus consisted of different-race informants, preference for the consensus was initially apparent but lost when only one member from the consensus remained with the dissenting informant., (© 2012 The Authors. Child Development © 2012 Society for Research in Child Development, Inc.)

In this paper we examine how English and Mandarin speakers think about time, and we test how the patterns of thinking in the two groups relate to patterns in linguistic and cultural experience. In Mandarin, vertical spatial metaphors are used more frequently to talk about time than they are in English; English relies primarily on horizontal terms. We present results from two tasks comparing English and Mandarin speakers' temporal reasoning. The tasks measure how people spatialize time in three-dimensional space, including the sagittal (front/back), transverse (left/right), and vertical (up/down) axes. Results of Experiment 1 show that people automatically create spatial representations in the course of temporal reasoning, and these implicit spatializations differ in accordance with patterns in language, even in a non-linguistic task. Both groups showed evidence of a left-to-right representation of time, in accordance with writing direction, but only Mandarin speakers showed a vertical top-to-bottom pattern for time (congruent with vertical spatiotemporal metaphors in Mandarin). Results of Experiment 2 confirm and extend these findings, showing that bilinguals' representations of time depend on both long-term and proximal aspects of language experience. Participants who were more proficient in Mandarin were more likely to arrange time vertically (an effect of previous language experience). Further, bilinguals were more likely to arrange time vertically when they were tested in Mandarin than when they were tested in English (an effect of immediate linguistic context)., (Copyright © 2011 Cognitive Science Society, Inc.)

The alternative splicing of mRNA is a critical process in higher eukaryotes that generates substantial proteomic diversity. Many of the proteins that are essential to this process contain arginine/serine-rich (RS) domains. ZRANB2 is a widely-expressed and highly-conserved RS-domain protein that can regulate alternative splicing but lacks canonical RNA-binding domains. Instead, it contains 2 RanBP2-type zinc finger (ZnF) domains. We demonstrate that these ZnFs recognize ssRNA with high affinity and specificity. Each ZnF binds to a single AGGUAA motif and the 2 domains combine to recognize AGGUAA(N(x))AGGUAA double sites, suggesting that ZRANB2 regulates alternative splicing via a direct interaction with pre-mRNA at sites that resemble the consensus 5' splice site. We show using X-ray crystallography that recognition of an AGGUAA motif by a single ZnF is dominated by side-chain hydrogen bonds to the bases and formation of a guanine-tryptophan-guanine "ladder." A number of other human proteins that function in RNA processing also contain RanBP2 ZnFs in which the RNA-binding residues of ZRANB2 are conserved. The ZnFs of ZRANB2 therefore define another class of RNA-binding domain, advancing our understanding of RNA recognition and emphasizing the versatility of ZnF domains in molecular recognition.

Previous findings suggest that cultural factors influence ideal affect (i.e., the affective states that people ideally want to feel). Three studies tested the hypothesis that cultural differences in ideal affect emerge early in life and are acquired through exposure to storybooks. In Study 1, the authors established that consistent with previous findings, European American preschoolers preferred excited (vs. calm) states more (indexed by activity and smile preferences) and perceived excited (vs. calm) states as happier than Taiwanese Chinese preschoolers. In Study 2, it was observed that similar differences were reflected in the pictures (activities, expressions, and smiles) of best-selling storybooks in the United States and Taiwan. Study 3 found that across cultures, exposure to exciting (vs. calm) storybooks altered children's preferences for excited (vs. calm) activities and their perceptions of happiness. These findings suggest that cultural differences in ideal affect may be due partly to differential exposure to calm and exciting storybooks.

The most common mutation in cystic fibrosis (deletion of Phe-508 in the first nucleotide binding domain (DeltaF508)) in the cystic fibrosis transmembrane conductance regulator (CFTR) causes retention of the mutant protein in the endoplasmic reticulum. We previously showed that the DeltaF508 mutation causes the CFTR protein to be retained in the endoplasmic reticulum in an inactive and structurally altered state. Proper packing of the transmembrane (TM) segments is critical for function because the TM segments form the chloride channel. Here we tested whether the DeltaF508 mutation altered packing of the TM segments by disulfide cross-linking analysis between TM6 and TM12 in wild-type and DeltaF508 CFTRs. These TM segments were selected because TM6 appears to line the chloride channel, and cross-linking between these TM segments has been observed in the CFTR sister protein, the multidrug resistance P-glycoprotein. We first mapped potential contact points in wild-type CFTR by cysteine mutagenesis and thiol cross-linking analysis. Disulfide cross-linking was detected in CFTR mutants M348C(TM6)/T1142C(TM12), T351C(TM6)/T1142C(TM12), and W356C(TM6)/W1145C(TM12) in a wild-type background. The disulfide cross-linking occurs intramolecularly and was reducible by dithiothreitol. Introduction of the DeltaF508 mutation into these cysteine mutants, however, abolished cross-linking. The results suggest that the DeltaF508 mutation alters interactions between the TM domains. Therefore, a potential target to correct folding defects in the DeltaF508 mutant of CFTR is to identify compounds that promote correct folding of the TM domains.

Background: Endoplasmic reticulum retention of misfolded cystic fibrosis transmembrane conductance regulator (CFTR) mutants and their rapid degradation is the major cause of cystic fibrosis (CF). An important goal is to understand the mechanism of how the misfolded proteins are recognized, retained, and targeted for degradation., Results: Using a web-based algorithm, PESTFind, we found a PEST sequence in the regulatory (R) domain of CFTR. The PEST sequence is found in many short-lived eukaryotic proteins and plays a role in their degradation. To determine its role in the stability and degradation of misprocessed CFTR, we introduced a number of site-directed mutations into the PEST sequence in the cDNA of DeltaF508 CFTR, the most prevalent misprocessed mutation found in CF patients. Analysis of these mutants showed that the disruption of the PEST sequence plays a minor role in the degradation of the CFTR mutants. Multiple mutations to the PEST sequence within the R domain of CFTR inhibit maturation of CFTR and prevent the formation of a 100 kDa degradation product. The mutations, however, do not improve the stability of the mutant DeltaF508 CFTR., Conclusion: These observations show that disruption of the structure of the R domain of CFTR can inhibit maturation of the protein and that the predicted PEST sequence plays no significant role in the degradation of CFTR.