The description and delineation of trematode species is a major ongoing task. Across the field there has been, and currently still is, great variation in the standard of this work and in the sophistication of the proposal of taxonomic hypotheses. Although most species are relatively unambiguously distinct from their congeners, many are either morphologically very similar, including the major and rapidly growing component of cryptic species, or are highly variable morphologically despite little to no molecular variation for standard DNA markers. Here we review challenges in species delineation in the context provided to us by the historical literature, and the use of morphological, geographical, host, and molecular data. We observe that there are potential challenges associated with all these information sources. As a result, we encourage careful proposal of taxonomic hypotheses with consideration for underlying species concepts and frank acknowledgement of weaknesses or conflict in the data. It seems clear that there is no single source of data that provides a wholly reliable answer to our taxonomic challenges but that nuanced consideration of information from multiple sources (the ‘integrated approach’) provides the best possibility of developing hypotheses that will stand the test of time.

The global population and status of Snowy Owls Bubo scandiacus are particularly challenging to assess because individuals are irruptive and nomadic, and the breeding range is restricted to the remote circumpolar Arctic tundra. The International Union for Conservation of Nature (IUCN) uplisted the Snowy Owl to “Vulnerable” in 2017 because the suggested population estimates appeared considerably lower than historical estimates, and it recommended actions to clarify the population size, structure, and trends. Here we present a broad review and status assessment, an effort led by the International Snowy Owl Working Group (ISOWG) and researchers from around the world, to estimate population trends and the current global status of the Snowy Owl. We use long-term breeding data, genetic studies, satellite-GPS tracking, and survival estimates to assess current population trends at several monitoring sites in the Arctic and we review the ecology and threats throughout the Snowy Owl range. An assessment of the available data suggests that current estimates of a worldwide population of 14,000–28,000 breeding adults are plausible. Our assessment of population trends at five long-term monitoring sites suggests that breeding populations of Snowy Owls in the Arctic have decreased by more than 30% over the past three generations and the species should continue to be categorised as Vulnerable under the IUCN Red List Criterion A2. We offer research recommendations to improve our understanding of Snowy Owl biology and future population assessments in a changing world.

Early adversity increases risk for child mental health difficulties. Stressors in the home environment (e.g., parental mental illness, household socioeconomic challenges) may be particularly impactful. Attending out-of-home childcare may buffer or magnify negative effects of such exposures. Using a longitudinal observational design, we leveraged data from the NIH Environmental influences on Child Health Outcomes Program to test whether number of hours in childcare, defined as 1) any type of nonparental care and 2) center-based care specifically, was associated with child mental health, including via buffering or magnifying associations between early exposure to psychosocial and socioeconomic risks (age 0–3 years) and later internalizing and externalizing symptoms (age 3–5.5 years), in a diverse sample of N = 2,024 parent–child dyads. In linear regression models, childcare participation was not associated with mental health outcomes, nor did we observe an impact of childcare attendance on associations between risk exposures and symptoms. Psychosocial and socioeconomic risks had interactive effects on internalizing and externalizing symptoms. Overall, the findings did not indicate that childcare attendance positively or negatively influenced child mental health and suggested that psychosocial and socioeconomic adversity may need to be considered as separate exposures to understand child mental health risk in early life.

As many American states have considered policies consistent with democratic backsliding in recent years, political elites and scholars have speculated on the consequences of these policies for political behavior. We examine the effect of backsliding policies on Americans’ preferences over leisure travel destinations; because vacationing is transitory, this focus allows us to isolate the role of individuals’ democratic predispositions and values in preference formation from the implications of these policies on their self-interest that they would experience from living under those policies themselves. Through pre-registered conjoint and vignette survey experiments, we find that Americans, and especially Democrats, express less interest in vacationing in states that recently adopted backsliding policies. Our results spotlight an accountability mechanism by which Americans may sanction backsliding states, though the modest magnitude of these sanctions – less than 1% of backsliding states’ gross domestic products – may not deter backsliding behavior on their own.

The isotope values of fossil snail shells can be important archives of climate. Here, we present the first carbon (δ13C) and oxygen (δ18O) isotope values of snail shells in interior Alaska to explore changes in vegetation and humidity through the late-glacial period. Snail shell δ13C values were relatively consistent through the late glacial. However, late-glacial shell δ13C values are 2.8‰ higher than those of modern shells. This offset is best explained by the Suess effect and changes in the δ13C values of snail diet. Snail shell δ18O values varied through the late glacial, which can be partially explained by changes in relative humidity (RH). RH during the snail growing period was modeled based on a published flux balance model. Results suggest a dry period toward the beginning of the Bølling–Allerød (~14 ka) followed by two distinct stages of the Younger Dryas, a wetter stage in the early Younger Dryas from 12.9 to 12.3 ka, and subsequent drier stage in the late Younger Dryas between 12.3 and 11.7 ka. The results show that land snail isotopes in high-latitude regions may be used as a supplementary paleoclimate proxy to help clarify complex climate histories, such as those of interior Alaska during the Younger Dryas.

OBJECTIVES/GOALS: Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors that are driven by populations of cancer stem cells (CSCs). In this study, we perform an epigenetic-focused functional genomics screen in GBM organoids and identify WDR5 as an essential epigenetic regulator in the SOX2-enriched, therapy resistant cancer stem cell niche. METHODS/STUDY POPULATION: Despite their importance for tumor growth, few molecular mechanisms critical for CSC population maintenance have been exploited for therapeutic development. We developed a spatially resolved loss-of-function screen in GBM patient-derived organoids to identify essential epigenetic regulators in the SOX2-enriched, therapy resistant niche. Our niche-specific screens identified WDR5, an H3K4 histone methyltransferase responsible for activating specific gene expression, as indispensable for GBM CSC growth and survival. RESULTS/ANTICIPATED RESULTS: In GBM CSC models, WDR5 inhibitors blocked WRAD complex assembly and reduced H3K4 trimethylation and expression of genes involved in CSC-relevant oncogenic pathways. H3K4me3 peaks lost with WDR5 inhibitor treatment occurred disproportionally on POU transcription factor motifs, required for stem cell maintenance and including the POU5F1(OCT4)::SOX2 motif. We incorporated a SOX2/OCT4 motif driven GFP reporter system into our CSC cell models and found that WDR5 inhibitor treatment resulted in dose-dependent silencing of stem cell reporter activity. Further, WDR5 inhibitor treatment altered the stem cell state, disrupting CSC in vitro growth and self-renewal as well as in vivo tumor growth. DISCUSSION/SIGNIFICANCE: Our results unveiled the role of WDR5 in maintaining the CSC state in GBM and provide a rationale for therapeutic development of WDR5 inhibitors for GBM and other advanced cancers. This conceptual and experimental framework can be applied to many cancers, and can unmask unique microenvironmental biology and rationally designed combination therapies.

Recent research has shown that risk and reward are positively correlated in many environments, and that people have internalized this association as a “risk-reward heuristic”: when making choices based on incomplete information, people infer probabilities from payoffs and vice-versa, and these inferences shape their decisions. We extend this work by examining people’s expectations about another fundamental trade-off — that between monetary reward and delay. In 2 experiments (total N = 670), we adapted a paradigm previously used to demonstrate the risk-reward heuristic. We presented participants with intertemporal choice tasks in which either the delayed reward or the length of the delay was obscured. Participants inferred larger rewards for longer stated delays, and longer delays for larger stated rewards; these inferences also predicted people’s willingness to take the delayed option. In exploratory analyses, we found that older participants inferred longer delays and smaller rewards than did younger ones. All of these results replicated in 2 large-scale pre-registered studies with participants from a different population (total N = 2138). Our results suggest that people expect intertemporal choice tasks to offer a trade-off between delay and reward, and differ in their expectations about this trade-off. This “delay-reward heuristic” offers a new perspective on existing models of intertemporal choice and provides new insights into unexplained and systematic individual differences in the willingness to delay gratification.

People often use tools for tasks, and sometimes there is uncertainty about whether a given task can be completed with a given tool. This project explored whether, when, and how people’s optimism about successfully completing a task with a given tool is affected by the contextual salience of a better or worse tool. In six studies, participants were faced with novel tasks. For each task, they were assigned a tool but also exposed to a comparison tool that was better or worse in utility (or sometimes similar in utility). In some studies, the tool comparisons were essentially social comparisons, because the tool was assigned to another person. In other studies, the tool comparisons were merely counterfactual rather than social. The studies revealed contrast effects on optimism, and the effect worked in both directions. That is, worse comparison tools boosted optimism and better tools depressed optimism. The contrast effects were observed regardless of the general type of comparison (e.g., social, counterfactual). The comparisons also influenced discrete decisions about which task to attempt (for a prize), which is an important finding for ruling out superficial scaling explanations for the contrast effects. It appears that people fail to exclude irrelevant tool-comparison information from consideration when assessing their likelihood of success on a task, resulting in biased optimism and decisions.

Gastropods are an important component of subtidal Antarctic communities including in common association with macroalgae. Nonetheless, limited data exist detailing their abundance and distribution on macroalgal species. This study documents the abundance and species composition of gastropod assemblages on the two largest, blade-forming Antarctic macroalgae, Himantothallus grandifolius and Sarcopeltis antarctica, sampled across two depths (9 and 18 m) at four sites for each species off Anvers Island, Antarctica. Gastropods were also enumerated on Desmarestia anceps, Desmarestia antarctica and Plocamium sp. but were not included in the main analyses because of small sample sizes. There were major differences between the gastropod assemblages on deep vs shallow H. grandifolius and S. antarctica with much higher numbers of individuals and also greater numbers of gastropod species at the greater depth. Differences between the gastropod assemblages on H. grandifolius and S. antarctica across sampling sites were apparent in non-parametric, multivariate analyses, although depth contributed more than site to these differences. Within common sites, assemblages on H. grandifolius were significantly different from those on S. antarctica at 18 m depth but not at 9 m depth, indicating that the host species can be but is not always more important than site in influencing the gastropod assemblages.

Seeman, Morris, and Summers misrepresent or misunderstand the arguments we have made, as well as their own previous work. Here, we correct these inaccuracies. We also reiterate our support for hypothesis-driven and evidence-based research.

We present a broadband radio study of the transient jets ejected from the black hole candidate X-ray binary MAXI J1535–571, which underwent a prolonged outburst beginning on 2017 September 2. We monitored MAXI J1535–571 with the Murchison Widefield Array (MWA) at frequencies from 119 to 186 MHz over six epochs from 2017 September 20 to 2017 October 14. The source was quasi-simultaneously observed over the frequency range 0.84–19 GHz by UTMOST (the Upgraded Molonglo Observatory Synthesis Telescope) the Australian Square Kilometre Array Pathfinder (ASKAP), the Australia Telescope Compact Array (ATCA), and the Australian Long Baseline Array (LBA). Using the LBA observations from 2017 September 23, we measured the source size to be $34\pm1$ mas. During the brightest radio flare on 2017 September 21, the source was detected down to 119 MHz by the MWA, and the radio spectrum indicates a turnover between 250 and 500 MHz, which is most likely due to synchrotron self-absorption (SSA). By fitting the radio spectrum with a SSA model and using the LBA size measurement, we determined various physical parameters of the jet knot (identified in ATCA data), including the jet opening angle ( $\phi_{\rm op} = 4.5\pm1.2^{\circ}$ ) and the magnetic field strength ( $B_{\rm s} = 104^{+80}_{-78}$ mG). Our fitted magnetic field strength agrees reasonably well with that inferred from the standard equipartition approach, suggesting the jet knot to be close to equipartition. Our study highlights the capabilities of the Australian suite of radio telescopes to jointly probe radio jets in black hole X-ray binaries via simultaneous observations over a broad frequency range, and with differing angular resolutions. This suite allows us to determine the physical properties of X-ray binary jets. Finally, our study emphasises the potential contributions that can be made by the low-frequency part of the Square Kilometre Array (SKA-Low) in the study of black hole X-ray binaries.