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1.
Nature ; 625(7993): 134-147, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38093007

RESUMO

Scientific evidence regularly guides policy decisions1, with behavioural science increasingly part of this process2. In April 2020, an influential paper3 proposed 19 policy recommendations ('claims') detailing how evidence from behavioural science could contribute to efforts to reduce impacts and end the COVID-19 pandemic. Here we assess 747 pandemic-related research articles that empirically investigated those claims. We report the scale of evidence and whether evidence supports them to indicate applicability for policymaking. Two independent teams, involving 72 reviewers, found evidence for 18 of 19 claims, with both teams finding evidence supporting 16 (89%) of those 18 claims. The strongest evidence supported claims that anticipated culture, polarization and misinformation would be associated with policy effectiveness. Claims suggesting trusted leaders and positive social norms increased adherence to behavioural interventions also had strong empirical support, as did appealing to social consensus or bipartisan agreement. Targeted language in messaging yielded mixed effects and there were no effects for highlighting individual benefits or protecting others. No available evidence existed to assess any distinct differences in effects between using the terms 'physical distancing' and 'social distancing'. Analysis of 463 papers containing data showed generally large samples; 418 involved human participants with a mean of 16,848 (median of 1,699). That statistical power underscored improved suitability of behavioural science research for informing policy decisions. Furthermore, by implementing a standardized approach to evidence selection and synthesis, we amplify broader implications for advancing scientific evidence in policy formulation and prioritization.


Assuntos
Ciências do Comportamento , COVID-19 , Prática Clínica Baseada em Evidências , Política de Saúde , Pandemias , Formulação de Políticas , Humanos , Ciências do Comportamento/métodos , Ciências do Comportamento/tendências , Comunicação , COVID-19/epidemiologia , COVID-19/etnologia , COVID-19/prevenção & controle , Cultura , Prática Clínica Baseada em Evidências/métodos , Liderança , Pandemias/prevenção & controle , Saúde Pública/métodos , Saúde Pública/tendências , Normas Sociais
2.
Nature ; 592(7855): 590-595, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33731933

RESUMO

In recent years, there has been a great deal of concern about the proliferation of false and misleading news on social media1-4. Academics and practitioners alike have asked why people share such misinformation, and sought solutions to reduce the sharing of misinformation5-7. Here, we attempt to address both of these questions. First, we find that the veracity of headlines has little effect on sharing intentions, despite having a large effect on judgments of accuracy. This dissociation suggests that sharing does not necessarily indicate belief. Nonetheless, most participants say it is important to share only accurate news. To shed light on this apparent contradiction, we carried out four survey experiments and a field experiment on Twitter; the results show that subtly shifting attention to accuracy increases the quality of news that people subsequently share. Together with additional computational analyses, these findings indicate that people often share misinformation because their attention is focused on factors other than accuracy-and therefore they fail to implement a strongly held preference for accurate sharing. Our results challenge the popular claim that people value partisanship over accuracy8,9, and provide evidence for scalable attention-based interventions that social media platforms could easily implement to counter misinformation online.


Assuntos
Atenção , Desinformação , Disseminação de Informação , Internet/normas , Julgamento , Humanos , Disseminação de Informação/ética , Política , Mídias Sociais/normas , Inquéritos e Questionários , Confiança
3.
Proc Natl Acad Sci U S A ; 121(10): e2315195121, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38412133

RESUMO

A great deal of empirical research has examined who falls for misinformation and why. Here, we introduce a formal game-theoretic model of engagement with news stories that captures the strategic interplay between (mis)information consumers and producers. A key insight from the model is that observed patterns of engagement do not necessarily reflect the preferences of consumers. This is because producers seeking to promote misinformation can use strategies that lead moderately inattentive readers to engage more with false stories than true ones-even when readers prefer more accurate over less accurate information. We then empirically test people's preferences for accuracy in the news. In three studies, we find that people strongly prefer to click and share news they perceive as more accurate-both in a general population sample, and in a sample of users recruited through Twitter who had actually shared links to misinformation sites online. Despite this preference for accurate news-and consistent with the predictions of our model-we find markedly different engagement patterns for articles from misinformation versus mainstream news sites. Using 1,000 headlines from 20 misinformation and 20 mainstream news sites, we compare Facebook engagement data with 20,000 accuracy ratings collected in a survey experiment. Engagement with a headline is negatively correlated with perceived accuracy for misinformation sites, but positively correlated with perceived accuracy for mainstream sites. Taken together, these theoretical and empirical results suggest that consumer preferences cannot be straightforwardly inferred from empirical patterns of engagement.


Assuntos
Comportamento do Consumidor , Mídias Sociais , Humanos , Comunicação , Inquéritos e Questionários , Cognição , Pesquisa Empírica
4.
Proc Natl Acad Sci U S A ; 121(3): e2307008121, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38215187

RESUMO

Concern over democratic erosion has led to a proliferation of proposed interventions to strengthen democratic attitudes in the United States. Resource constraints, however, prevent implementing all proposed interventions. One approach to identify promising interventions entails leveraging domain experts, who have knowledge regarding a given field, to forecast the effectiveness of candidate interventions. We recruit experts who develop general knowledge about a social problem (academics), experts who directly intervene on the problem (practitioners), and nonexperts from the public to forecast the effectiveness of interventions to reduce partisan animosity, support for undemocratic practices, and support for partisan violence. Comparing 14,076 forecasts submitted by 1,181 forecasters against the results of a megaexperiment (n = 32,059) that tested 75 hypothesized effects of interventions, we find that both types of experts outperformed members of the public, though experts differed in how they were accurate. While academics' predictions were more specific (i.e., they identified a larger proportion of ineffective interventions and had fewer false-positive forecasts), practitioners' predictions were more sensitive (i.e., they identified a larger proportion of effective interventions and had fewer false-negative forecasts). Consistent with this, practitioners were better at predicting best-performing interventions, while academics were superior in predicting which interventions performed worst. Our paper highlights the importance of differentiating types of experts and types of accuracy. We conclude by discussing factors that affect whether sensitive or specific forecasters are preferable, such as the relative cost of false positives and negatives and the expected rate of intervention success.


Assuntos
Problemas Sociais , Estados Unidos , Previsões
5.
Proc Natl Acad Sci U S A ; 120(32): e2301491120, 2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37523571

RESUMO

The highly influential theory of "Motivated System 2 Reasoning" argues that analytical, deliberative ("System 2") reasoning is hijacked by identity when considering ideologically charged issues-leading people who are more likely to engage in such reasoning to be more polarized, rather than more accurate. Here, we fail to replicate the key empirical support for this theory across five contentious issues, using a large gold-standard nationally representative probability sample of Americans. While participants were more accurate in evaluating a contingency table when the outcome aligned with their politics (even when controlling for prior beliefs), we find that participants with higher numeracy were more accurate in evaluating the contingency table, regardless of whether or not the table's outcome aligned with their politics. These findings call for a reconsideration of the effect of identity on analytical reasoning.


Assuntos
Política , Resolução de Problemas , Humanos , Estados Unidos , Estudos de Amostragem
6.
Proc Natl Acad Sci U S A ; 120(25): e2216261120, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37307486

RESUMO

Much concern has been raised about the power of political microtargeting to sway voters' opinions, influence elections, and undermine democracy. Yet little research has directly estimated the persuasive advantage of microtargeting over alternative campaign strategies. Here, we do so using two studies focused on U.S. policy issue advertising. To implement a microtargeting strategy, we combined machine learning with message pretesting to determine which advertisements to show to which individuals to maximize persuasive impact. Using survey experiments, we then compared the performance of this microtargeting strategy against two other messaging strategies. Overall, we estimate that our microtargeting strategy outperformed these strategies by an average of 70% or more in a context where all of the messages aimed to influence the same policy attitude (Study 1). Notably, however, we found no evidence that targeting messages by more than one covariate yielded additional persuasive gains, and the performance advantage of microtargeting was primarily visible for one of the two policy issues under study. Moreover, when microtargeting was used instead to identify which policy attitudes to target with messaging (Study 2), its advantage was more limited. Taken together, these results suggest that the use of microtargeting-combining message pretesting with machine learning-can potentially increase campaigns' persuasive influence and may not require the collection of vast amounts of personal data to uncover complex interactions between audience characteristics and political messaging. However, the extent to which this approach confers a persuasive advantage over alternative strategies likely depends heavily on context.

7.
Proc Natl Acad Sci U S A ; 120(23): e2301836120, 2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-37252992

RESUMO

There is substantial concern about democratic backsliding in the United States. Evidence includes notably high levels of animosity toward out-partisans and support for undemocratic practices (SUP) among the general public. Much less is known, however, about the views of elected officials-even though they influence democratic outcomes more directly. In a survey experiment conducted with state legislators (N = 534), we show that these officials exhibit less animosity toward the other party, less SUP, and less support for partisan violence (SPV) than the general public. However, legislators vastly overestimate the levels of animosity, SUP, and SPV among voters from the other party (though not among voters from their own party). Further, those legislators randomly assigned to receive accurate information about the views of voters from the other party reported significantly lower SUP and marginally significantly lower partisan animosity toward the other party. This suggests that legislators' democratic attitudes are causally linked to their perceptions of other-party voters' democratic attitudes. Our findings highlight the importance of ensuring that office holders have access to reliable information about voters from both parties.

8.
PLoS Comput Biol ; 20(2): e1011779, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38422117

RESUMO

Recent studies have established that the circadian clock influences onset, progression and therapeutic outcomes in a number of diseases including cancer and heart diseases. Therefore, there is a need for tools to measure the functional state of the molecular circadian clock and its downstream targets in patients. Moreover, the clock is a multi-dimensional stochastic oscillator and there are few tools for analysing it as a noisy multigene dynamical system. In this paper we consider the methodology behind TimeTeller, a machine learning tool that analyses the clock as a noisy multigene dynamical system and aims to estimate circadian clock function from a single transcriptome by modelling the multi-dimensional state of the clock. We demonstrate its potential for clock systems assessment by applying it to mouse, baboon and human microarray and RNA-seq data and show how to visualise and quantify the global structure of the clock, quantitatively stratify individual transcriptomic samples by clock dysfunction and globally compare clocks across individuals, conditions and tissues thus highlighting its potential relevance for advancing circadian medicine.


Assuntos
Relógios Circadianos , Humanos , Camundongos , Animais , Relógios Circadianos/genética , Transcriptoma/genética , Perfilação da Expressão Gênica , Ritmo Circadiano/genética
9.
Nature ; 573(7772): 117-121, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31485058

RESUMO

People must integrate disparate sources of information when making decisions, especially in social contexts. But information does not always flow freely. It can be constrained by social networks1-3 and distorted by zealots and automated bots4. Here we develop a voter game as a model system to study information flow in collective decisions. Players are assigned to competing groups (parties) and placed on an 'influence network' that determines whose voting intentions each player can observe. Players are incentivized to vote according to partisan interest, but also to coordinate their vote with the entire group. Our mathematical analysis uncovers a phenomenon that we call information gerrymandering: the structure of the influence network can sway the vote outcome towards one party, even when both parties have equal sizes and each player has the same influence. A small number of zealots, when strategically placed on the influence network, can also induce information gerrymandering and thereby bias vote outcomes. We confirm the predicted effects of information gerrymandering in social network experiments with n = 2,520 human subjects. Furthermore, we identify extensive information gerrymandering in real-world influence networks, including online political discussions leading up to the US federal elections, and in historical patterns of bill co-sponsorship in the US Congress and European legislatures. Our analysis provides an account of the vulnerabilities of collective decision-making to systematic distortion by restricted information flow. Our analysis also highlights a group-level social dilemma: information gerrymandering can enable one party to sway decisions in its favour, but when multiple parties engage in gerrymandering the group loses its ability to reach consensus and remains trapped in deadlock.


Assuntos
Tomada de Decisões , Teoria dos Jogos , Processos Grupais , Conhecimento , Viés , Democracia , Humanos , Modelos Teóricos , Política , Mídias Sociais , Rede Social , Revelação da Verdade
10.
Proc Natl Acad Sci U S A ; 119(5)2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35082145

RESUMO

As the COVID-19 pandemic comes to an end, governments find themselves facing a new challenge: motivating citizens to resume economic activity. What is an effective way to do so? We investigate this question using a field experiment in the city of Zhengzhou, China, immediately following the end of the city's COVID-19 lockdown. We assessed the effect of a descriptive norms intervention providing information about the proportion of participants' neighbors who have resumed economic activity. We find that informing individuals about their neighbors' plans to visit restaurants increases the fraction of participants visiting restaurants by 12 percentage points (37%), among those participants who underestimated the proportion of neighbors who resumed economic activity. Those who overestimated did not respond by reducing restaurant attendance (the intervention yielded no "boomerang" effect); thus, our descriptive norms intervention yielded a net positive effect. We explore the moderating role of risk preferences and the effect of the intervention on subjects' perceived risk of going to restaurants, as well as the contrast with an intervention for parks, which were already perceived as safe. All of these analyses suggest our intervention worked by reducing the perceived risk of going to restaurants.


Assuntos
COVID-19/economia , COVID-19/psicologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , China/epidemiologia , Humanos , Motivação , Parques Recreativos , Percepção , Restaurantes , SARS-CoV-2 , Normas Sociais
11.
Psychol Sci ; 35(4): 435-450, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38506937

RESUMO

The spread of misinformation is a pressing societal challenge. Prior work shows that shifting attention to accuracy increases the quality of people's news-sharing decisions. However, researchers disagree on whether accuracy-prompt interventions work for U.S. Republicans/conservatives and whether partisanship moderates the effect. In this preregistered adversarial collaboration, we tested this question using a multiverse meta-analysis (k = 21; N = 27,828). In all 70 models, accuracy prompts improved sharing discernment among Republicans/conservatives. We observed significant partisan moderation for single-headline "evaluation" treatments (a critical test for one research team) such that the effect was stronger among Democrats than Republicans. However, this moderation was not consistently robust across different operationalizations of ideology/partisanship, exclusion criteria, or treatment type. Overall, we observed significant partisan moderation in 50% of specifications (all of which were considered critical for the other team). We discuss the conditions under which moderation is observed and offer interpretations.


Assuntos
Política , Humanos
12.
Cell ; 139(6): 1170-9, 2009 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-20005809

RESUMO

Photoperiod sensors allow physiological adaptation to the changing seasons. The prevalent hypothesis is that day length perception is mediated through coupling of an endogenous rhythm with an external light signal. Sufficient molecular data are available to test this quantitatively in plants, though not yet in mammals. In Arabidopsis, the clock-regulated genes CONSTANS (CO) and FLAVIN, KELCH, F-BOX (FKF1) and their light-sensitive proteins are thought to form an external coincidence sensor. Here, we model the integration of light and timing information by CO, its target gene FLOWERING LOCUS T (FT), and the circadian clock. Among other predictions, our models show that FKF1 activates FT. We demonstrate experimentally that this effect is independent of the known activation of CO by FKF1, thus we locate a major, novel controller of photoperiodism. External coincidence is part of a complex photoperiod sensor: modeling makes this complexity explicit and may thus contribute to crop improvement.


Assuntos
Arabidopsis/fisiologia , Flores/fisiologia , Regulação da Expressão Gênica de Plantas , Modelos Genéticos , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Relógios Biológicos , Proteínas de Ligação a DNA/genética , Redes Reguladoras de Genes , Fotoperíodo , Fatores de Transcrição/genética
13.
Nature ; 563(7730): 245-248, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30356217

RESUMO

Promoting the adoption of public goods that are not yet widely accepted is particularly challenging. This is because most tools for increasing cooperation-such as reputation concerns1 and information about social norms2-are typically effective only for behaviours that are commonly practiced, or at least generally agreed upon as being desirable. Here we examine how advocates can successfully promote non-normative (that is, rare or unpopular) public goods. We do so by applying the cultural evolutionary theory of credibility-enhancing displays3, which argues that beliefs are spread more effectively by actions than by words alone-because actions provide information about the actor's true beliefs. Based on this logic, people who themselves engage in a given behaviour will be more effective advocates for that behaviour than people who merely extol its virtues-specifically because engaging in a behaviour credibly signals a belief in its value. As predicted, a field study of a programme that promotes residential solar panel installation in 58 towns in the United States-comprising 1.4 million residents in total-found that community organizers who themselves installed through the programme recruited 62.8% more residents to install solar panels than community organizers who did not. This effect was replicated in three pre-registered randomized survey experiments (total n = 1,805). These experiments also support the theoretical prediction that this effect is specifically driven by subjects' beliefs about what the community organizer believes about solar panels (that is, second-order beliefs), and demonstrate generalizability to four other highly non-normative behaviours. Our findings shed light on how to spread non-normative prosocial behaviours, offer an empirical demonstration of credibility-enhancing displays and have substantial implications for practitioners and policy-makers.


Assuntos
Terapia Comportamental , Comunicação , Comportamento do Consumidor/estatística & dados numéricos , Difusão de Inovações , Utilização de Equipamentos e Suprimentos/estatística & dados numéricos , Motivação , Energia Solar/estatística & dados numéricos , Evolução Cultural , Cultura , Humanos , Modelos Psicológicos , Formulação de Políticas , Mudança Social , Estados Unidos
14.
Proc Natl Acad Sci U S A ; 118(7)2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33563758

RESUMO

Americans are much more likely to be socially connected to copartisans, both in daily life and on social media. However, this observation does not necessarily mean that shared partisanship per se drives social tie formation, because partisanship is confounded with many other factors. Here, we test the causal effect of shared partisanship on the formation of social ties in a field experiment on Twitter. We created bot accounts that self-identified as people who favored the Democratic or Republican party and that varied in the strength of that identification. We then randomly assigned 842 Twitter users to be followed by one of our accounts. Users were roughly three times more likely to reciprocally follow-back bots whose partisanship matched their own, and this was true regardless of the bot's strength of identification. Interestingly, there was no partisan asymmetry in this preferential follow-back behavior: Democrats and Republicans alike were much more likely to reciprocate follows from copartisans. These results demonstrate a strong causal effect of shared partisanship on the formation of social ties in an ecologically valid field setting and have important implications for political psychology, social media, and the politically polarized state of the American public.


Assuntos
Comportamento Cooperativo , Política , Identificação Social , Mídias Sociais/estatística & dados numéricos , Adulto , Dissidências e Disputas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos
15.
Proc Natl Acad Sci U S A ; 118(5)2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33495336

RESUMO

Countering misinformation can reduce belief in the moment, but corrective messages quickly fade from memory. We tested whether the longer-term impact of fact-checks depends on when people receive them. In two experiments (total N = 2,683), participants read true and false headlines taken from social media. In the treatment conditions, "true" and "false" tags appeared before, during, or after participants read each headline. Participants in a control condition received no information about veracity. One week later, participants in all conditions rated the same headlines' accuracy. Providing fact-checks after headlines (debunking) improved subsequent truth discernment more than providing the same information during (labeling) or before (prebunking) exposure. This finding informs the cognitive science of belief revision and has practical implications for social media platform designers.


Assuntos
Jornais como Assunto , Humanos , Fatores de Tempo
16.
Proc Natl Acad Sci U S A ; 118(47)2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34782473

RESUMO

Concerns about video-based political persuasion are prevalent in both popular and academic circles, predicated on the assumption that video is more compelling than text. To date, however, this assumption remains largely untested in the political domain. Here, we provide such a test. We begin by drawing a theoretical distinction between two dimensions for which video might be more efficacious than text: 1) one's belief that a depicted event actually occurred and 2) the extent to which one's attitudes and behavior are changed. We test this model across two high-powered survey experiments varying exposure to politically persuasive messaging (total n = 7,609 Americans; 26,584 observations). Respondents were shown a selection of persuasive messages drawn from a diverse sample of 72 clips. For each message, they were randomly assigned to one of three conditions: a short video, a detailed transcript of the video, or a control condition. Overall, we find that individuals are more likely to believe an event occurred when it is presented in video versus textual form, but the impact on attitudes and behavioral intentions is much smaller. Importantly, for both dimensions, these effects are highly stable across messages and respondent subgroups. Moreover, when it comes to attitudes and engagement, the difference between the video and text conditions is comparable to, if not smaller than, the difference between the text and control conditions. Taken together, these results call into question widely held assumptions about the unique persuasive power of political video over text.


Assuntos
Meios de Comunicação , Comunicação Persuasiva , Envio de Mensagens de Texto , Gravação em Vídeo , Atitude , Feminino , Generalização Psicológica , Humanos , Intenção , Masculino , Pessoa de Meia-Idade , Política , Inquéritos e Questionários
17.
Proc Natl Acad Sci U S A ; 118(32)2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34312254

RESUMO

Overcoming the COVID-19 pandemic requires motivating the vast majority of Americans to get vaccinated. However, vaccination rates have become politically polarized, and a substantial proportion of Republicans have remained vaccine hesitant for months. Here, we explore how endorsements by party elites affect Republicans' COVID-19 vaccination intentions and attitudes. In a preregistered survey experiment (n = 1,480), we varied whether self-identified Republicans saw endorsements of the vaccine from prominent Republicans (including video of a speech by former President Donald Trump), from the Democratic Party (including video of a speech by President Joseph Biden), or a neutral control condition including no endorsements. Unvaccinated Republicans who were exposed to the Republican elite endorsement reported 7.0% higher vaccination intentions than those who viewed the Democratic elite endorsement and 5.7% higher than those in the neutral control condition. These effects were statistically mediated by participants' reports of how much they thought Republican politicians would want them to get vaccinated. We also found evidence of backlash effects against Democratic elites: Republicans who viewed the Democratic elite endorsement reported they would be significantly less likely to encourage others to vaccinate and had more negative attitudes toward the vaccine, compared with those who viewed the Republican elite endorsement or the neutral control. These results demonstrate the relative advantage of cues from Republican elites-and the risks of messaging from Democrats currently in power-for promoting vaccination among the largest vaccine-hesitant subgroup in the United States.


Assuntos
Sinais (Psicologia) , Política , Vacinação/psicologia , Atitude , COVID-19/epidemiologia , COVID-19/prevenção & controle , Humanos , Intenção , SARS-CoV-2 , Inquéritos e Questionários , Estados Unidos
18.
Proc Natl Acad Sci U S A ; 118(38)2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34518231

RESUMO

Embryonic development leads to the reproducible and ordered appearance of complexity from egg to adult. The successive differentiation of different cell types that elaborate this complexity results from the activity of gene networks and was likened by Waddington to a flow through a landscape in which valleys represent alternative fates. Geometric methods allow the formal representation of such landscapes and codify the types of behaviors that result from systems of differential equations. Results from Smale and coworkers imply that systems encompassing gene network models can be represented as potential gradients with a Riemann metric, justifying the Waddington metaphor. Here, we extend this representation to include parameter dependence and enumerate all three-way cellular decisions realizable by tuning at most two parameters, which can be generalized to include spatial coordinates in a tissue. All diagrams of cell states vs. model parameters are thereby enumerated. We unify a number of standard models for spatial pattern formation by expressing them in potential form (i.e., as topographic elevation). Turing systems appear nonpotential, yet in suitable variables the dynamics are low dimensional and potential. A time-independent embedding recovers the original variables. Lateral inhibition is described by a saddle point with many unstable directions. A model for the patterning of the Drosophila eye appears as relaxation in a bistable potential. Geometric reasoning provides intuitive dynamic models for development that are well adapted to fit time-lapse data.


Assuntos
Redes Reguladoras de Genes/genética , Genes Reguladores/genética , Animais , Diferenciação Celular/genética , Drosophila/genética , Modelos Genéticos
19.
PLoS Genet ; 17(3): e1008887, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33735180

RESUMO

The winged insects of the order Diptera are colloquially named for their most recognizable phenotype: flight. These insects rely on flight for a number of important life history traits, such as dispersal, foraging, and courtship. Despite the importance of flight, relatively little is known about the genetic architecture of flight performance. Accordingly, we sought to uncover the genetic modifiers of flight using a measure of flies' reaction and response to an abrupt drop in a vertical flight column. We conducted a genome wide association study (GWAS) using 197 of the Drosophila Genetic Reference Panel (DGRP) lines, and identified a combination of additive and marginal variants, epistatic interactions, whole genes, and enrichment across interaction networks. Egfr, a highly pleiotropic developmental gene, was among the most significant additive variants identified. We functionally validated 13 of the additive candidate genes' (Adgf-A/Adgf-A2/CG32181, bru1, CadN, flapper (CG11073), CG15236, flippy (CG9766), CREG, Dscam4, form3, fry, Lasp/CG9692, Pde6, Snoo), and introduce a novel approach to whole gene significance screens: PEGASUS_flies. Additionally, we identified ppk23, an Acid Sensing Ion Channel (ASIC) homolog, as an important hub for epistatic interactions. We propose a model that suggests genetic modifiers of wing and muscle morphology, nervous system development and function, BMP signaling, sexually dimorphic neural wiring, and gene regulation are all important for the observed differences flight performance in a natural population. Additionally, these results represent a snapshot of the genetic modifiers affecting drop-response flight performance in Drosophila, with implications for other insects.


Assuntos
Drosophila melanogaster/genética , Drosophila/genética , Regulação da Expressão Gênica no Desenvolvimento , Variação Genética , Neurogênese/genética , Animais , Drosophila/embriologia , Drosophila melanogaster/metabolismo , Epigênese Genética , Feminino , Voo Animal , Estudos de Associação Genética , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único
20.
Physiol Genomics ; 55(6): 259-274, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37184227

RESUMO

Cigarette smoking increases the risk of acute respiratory distress syndrome (ARDS; Calfee CS, Matthay MA, Eisner MD, Benowitz N, Call M, Pittet J-F, Cohen MJ. Am J Respir Crit Care Med 183: 1660-1665, 2011; Calfee CS, Matthay MA, Kangelaris KN, Siew ED, Janz DR, Bernard GR, May AK, Jacob P, Havel C, Benowitz NL, Ware LB. Crit Care Med 43: 1790-1797, 2015; Toy P, Gajic O, Bacchetti P, Looney MR, Gropper MA, Hubmayr R, Lowell CA, Norris PJ, Murphy EL, Weiskopf RB, Wilson G, Koenigsberg M, Lee D, Schuller R, Wu P, Grimes B, Gandhi MJ, Winters JL, Mair D, Hirschler N, Sanchez Rosen R, Matthay MA, TRALI Study Group. Blood 119: 1757-1767, 2012) and causes emphysema. However, it is not known why some individuals develop disease, whereas others do not. We found that smoke-exposed AKR mice were more susceptible to lipopolysaccharides (LPS)-induced acute lung injury (ALI) than C57BL/6 mice (Sakhatskyy P, Wang Z, Borgas D, Lomas-Neira J, Chen Y, Ayala A, Rounds S, Lu Q. Am J Physiol Lung Cell Mol Physiol 312: L56-L67, 2017); thus, we investigated strain-dependent lung transcriptomic responses to cigarette smoke (CS). Eight-week-old male AKR and C57BL/6 mice were exposed to 3 wk of room air (RA) or cigarette smoke (CS) for 6 h/day, 4 days/wk, followed by intratracheal instillation of LPS or normal saline (NS) and microarray analysis of lung homogenate gene expression. Other groups of AKR and C57 mice were exposed to RA or CS for 6 wk, followed by evaluation of static lung compliance and tissue elastance, morphometric evaluation for emphysema, or microarray analysis of lung gene expression. Transcriptomic analyses of lung homogenates show distinct strain-dependent lung transcriptional responses to CS and LPS, with AKR mice having larger numbers of genes affected than similarly treated C57 mice, congruent with strain differences in physiologic and inflammatory parameters previously observed in LPS-induced ALI after CS priming. These results suggest that genetic differences may underlie differing susceptibility of smokers to ARDS and emphysema. Strain-based differences in gene transcription contribute to CS and LPS-induced lung injury. There may be a genetic basis for smoking-related lung injury. Clinicians should consider cigarette smoke exposure as a risk factor for ALI and ARDS.NEW & NOTEWORTHY We demonstrate that transcriptomes expressed in lung homogenates also differ between the mouse strains and after acute (3 wk) exposure of animals to cigarette smoke (CS) and/or to lipopolysaccharide. Mouse strains also differed in physiologic, pathologic, and transcriptomic, responses to more prolonged (6 wk) exposure to CS. These data support a genetic basis for enhanced susceptibility to acute and chronic lung injury among humans who smoke cigarettes.


Assuntos
Lesão Pulmonar Aguda , Fumar Cigarros , Enfisema , Síndrome do Desconforto Respiratório , Humanos , Masculino , Camundongos , Animais , Lipopolissacarídeos/farmacologia , Transcriptoma , Camundongos Endogâmicos AKR , Camundongos Endogâmicos C57BL , Pulmão/patologia , Lesão Pulmonar Aguda/patologia , Síndrome do Desconforto Respiratório/genética , Enfisema/metabolismo , Enfisema/patologia , Modelos Animais de Doenças
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