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.

Modons, or dipolar vortices, are common and long-lived features of the upper ocean, consisting of a pair of counter-rotating monopolar vortices moving through self-advection. Such structures remain stable over long times and may be important for fluid transport over large distances. Here, we present a semi-analytical method for finding fully nonlinear modon solutions in a multi-layer quasi-geostrophic model with arbitrarily many layers. Our approach is to reduce the problem to a multi-parameter linear eigenvalue problem which can be solved using numerical techniques from linear algebra. The method is shown to replicate previous results for one- and two-layer models and is applied to a three-layer model to find a solution describing a mid-depth propagating, topographic vortex.

Neorickettsia (formerly Ehrlichia) risticii, the agent of Potomac horse fever (PHF), has been recently detected in trematode stages found in the secretions of freshwater snails and in aquatic insects. Insectivores, such as bats and birds, may serve as the definitive host of the trematode vector. To determine the definitive helminth vector, five bats (Myotis yumanensis) and three swallows (Hirundo rustica, Tachycineta bicolor) were collected from a PHF endemic location in northern California. Bats and swallows were dissected and their major organs examined for trematodes and for N. risticii DNA using a nested polymerase chain reaction (PCR) assay. Adult digenetic trematodes, Acanthatrium sp. and/or Lecithodendrium sp., were recovered from the gastrointestinal tract of all bats and from one swallow. The intestine of three bats, the spleen of two bats and one swallow as well as the liver of one swallow tested PCR positive for N. risticii. From a total of seven pools of identical digenetic trematodes collected from single hosts, two pools of Acanthatrium sp. and one pool of Lecithodendrium sp. tested PCR positive. The results of this investigation provide preliminary evidence that at least two trematodes in the family Lecithodendriidae are vectors of N. risticii. The data also suggest that bats and swallows not only act as a host for trematodes but also as a possible natural reservoir for N. risticii.

This work discusses modons, or dipolar vortices, propagating along sloping topography. Two different regimes exist, which are studied separately using the surface quasi-geostrophic equations. First, when the modon propagates in the direction opposite to topographic Rossby waves, steady solutions exist and a semi-analytical method is presented for calculating these solutions. Second, when the modon propagates in the same direction as the Rossby waves, a wave wake is generated. This wake removes energy from the modon, causing it to decay slowly. Asymptotic predictions are presented for this decay and found to agree closely with numerical simulations. Over long times, decaying vortices are found to break down due to an asymmetry resulting from the generation of waves inside the vortex. A monopolar vortex moving along a wall is shown to behave in a similar way to a dipole, though the presence of the wall is found to stabilise the vortex and prevent the long-time breakdown. The problem is equivalent mathematically to a dipolar vortex moving along a density front, hence our results apply directly to this case.

Background: To clarify the landscape of molecular diagnoses (MDs) in early-onset epilepsy individuals, we determined the prevalent MDs stratified by age at seizure onset (SO) and the time to MD in children with SO <36 months of life. Methods: A panel of up to 302 genes associated with epilepsy was utilized and ordering physicians provided the age of SO. Diagnostic yield analyses were performed for SO ages including <1 mo, 1-2 mo, 3-5 mo, 6-11 mo, 12-23 mo, and 24-35 mo. The time to MD (MD age - SO age) was determined for the top 10 genes in each SO category. Results: 15,074 individuals with SO <36 months of life were tested. Predominant MD findings are as follows: KCNQ2 in neonates with SO at <1mo, KCNQ2 and CDKL5 for SO between 1-2 mo, PRRT2 and SCN1A for SO between 3-11 mo, and SCN1A for SO between 12-36 months. The median time to MD varied by gene. For example, there was no delay in the median time to MD for the GLDC, KCNQ2, and SCN2A genes while the median delay for MECP2, SLC2A1, and other genes was ≥ 12 months. Conclusions: These data highlight the importance of comprehensive early testing in children with early-onset epilepsy.

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.

This study provides the first focused investigation of rudist bivalves from the Upper Cretaceous of the Gulf Coastal Plain (GCP) in the southern US and previously undescribed specimens from the Flor de Alba Limestone Member of the Pozas Formation in Puerto Rico. Identified rudists from the GCP comprise the Monopleuridae, including Gyropleura, as well as Radiolitidae, including Biradiolites cardenasensi, Durania maxima, Guanacastea jamaicensis, Radiolites acutocostata, and Sauvagesia. Integrating rudist occurrences within well-established GCP biostratigraphy allows for extension of upper ranges of D. maxima and R. acutocostata into the late Campanian, and extension of the lower ranges of B. cardenasensis and G. jamaicensis into the early Campanian. Identified rudists from Puerto Rico comprise the Hippuritidae and include Barrettia monilifera, which supports the age of the Flor de Alba Limestone Member of the Pozas Formation as middle Campanian. Combined taxonomic, biostratigraphic, and paleobiogeographic analyses indicate there is no rudist fauna endemic to the GCP, and the region marks the northeastern range of the Caribbean genera Biradiolites, Durania, Guanacastea, Gyropleura, Radiolites, and Sauvagesia during the Campanian and Maastrichtian. The new occurrences help inform future updates of Late Cretaceous sea surface-current reconstructions for the Caribbean and Western Interior Seaway, USA.

The purpose of this experiment was to investigate the welfare of pregnant mares kept in straight stalls and given only limited exercise, conditions that are similar to those encountered in the pregnant mare urine industry. Sixteen pregnant mares (eight in each of two years) were randomly assigned to two groups: Ex (exercised in a paddock for 30 min per day) or NoEx (exercised for one 30 min period every 14 days). The horses were housed in straight (or ‘tie’) stalls for six months and had ad libitum access to grass hay. Each horse's behaviour was recorded on videotape once per week for 24 h. The major behaviours were eating hay, standing, and stand-resting (head down and one hind limb flexed). There was no difference between the behaviours or the number of foot lifts per min of the Ex and NoEx groups in their stalls. Nine of 16 mares were not observed in recumbency throughout the whole of the six-month observation period, suggesting that horses with no previous experience in straight stalls may be reluctant to lie down. Thirteen of 16 mares dropped to their knees at least once, probably when they were REM sleeping while standing. There were no significant differences between the Ex and the NoEx mares in baseline plasma Cortisol levels or in Cortisol response to ACTH. Following 30 min of exercise, NoEx mares showed an increase in Cortisol from 5.0 to 5.4 μg dL−1, whereas Ex mares showed a decrease from 4.6 to 3.6 µg dL−1. The NoEx horses that had been confined for two weeks trotted more (NoEx = 22 [6-38; median and range]% of time; Ex = 2.4 [0-8.7]%) and galloped more (NoEx = 6 [2-8]%; Ex = 0 [0-4]%) than the Ex that were released daily, but walked less (NoEx = 17 [10-26]%; Ex = 35 [20-40]%) and grazed less (NoEx = 0%; Ex = 3 [0-12]%). Confined horses show rebound locomotion — that is, a compensatory increase — when released from confinement, indicating a response to exercise deprivation.

This article presents a theory of reasoning about moral propositions that is based on four fundamental principles. First, no simple criterion picks out propositions about morality from within the larger set of deontic propositions concerning what is permissible and impermissible in social relations, the law, games, and manners. Second, the mechanisms underlying emotions and deontic evaluations are independent and operate in parallel, and so some scenarios elicit emotions prior to moral evaluations, some elicit moral evaluations prior to emotions, and some elicit them at the same time. Third, deontic evaluations depend on inferences, either unconscious intuitions or conscious reasoning. Fourth, human beliefs about what is, and isn’t, moral are neither complete nor consistent. The article marshals the evidence, which includes new studies, corroborating these principles, and discusses the relations between them and other current theories of moral reasoning.

As part of surveillance of snail-borne trematodiasis in Knowsley Safari (KS), Prescot, United Kingdom, a collection was made in July 2021 of various planorbid (n = 173) and lymnaeid (n = 218) snails. These were taken from 15 purposely selected freshwater habitats. In the laboratory emergent trematode cercariae, often from single snails, were identified by morphology with a sub-set, of those most accessible, later characterized by cytochrome oxidase subunit 1 (cox1) DNA barcoding. Two schistosomatid cercariae were of special note in the context of human cercarial dermatitis (HCD), Bilharziella polonica emergent from Planorbarius corneus and Trichobilharzia spp. emergent from Ampullacaena balthica. The former schistosomatid was last reported in the United Kingdom over 50 years ago. From cox1 analyses, the latter likely consisted of two taxa, Trichobilharzia anseri, a first report in the United Kingdom, and a hitherto unnamed genetic lineage having some affiliation with Trichobilharzia longicauda. The chronobiology of emergent cercariae from P. corneus was assessed, with the vertical swimming rate of B. polonica measured. We provide a brief risk appraisal of HCD for public activities typically undertaken within KS educational and recreational programmes.