Distinct pathways drive anterior hypoblast specification in the implanting human embryo.

Development requires coordinated interactions between the epiblast, which generates the embryo proper; the trophectoderm, which generates the placenta; and the hypoblast, which forms both the anterior signalling centre and the yolk sac. These interactions remain poorly understood in human embryogenesis because mechanistic studies have only recently become possible. Here we examine signalling interactions post-implantation using human embryos and stem cell models of the epiblast and hypoblast. We find anterior hypoblast specification is NODAL dependent, as in the mouse. However, while BMP inhibits anterior signalling centre specification in the mouse, it is essential for its maintenance in human. We also find contrasting requirements for BMP in the naive pre-implantation epiblast of mouse and human embryos. Finally, we show that NOTCH signalling is important for human epiblast survival. Our findings of conserved and species-specific factors that drive these early stages of embryonic development highlight the strengths of comparative species studies.

Comparative analysis of Australian climate change and COVID-19 vaccine audience segments shows climate skeptics can be vaccine enthusiasts.

Denialism and the spreading of misinformation have occurred regarding both climate change and COVID-19, delaying uptake of urgent actions. Audience segmentation analysis identifies audience subgroups likely to have similar responses to messaging, and is a valuable tool for effective campaigns encouraging critical behaviors in both contexts. This study compared audience segmentations based on a representative sample of 1054 Australians. One segmentation was based on the 'Global Warming's Six Americas' online SASSY tool. The second segmentation applied the Theory of Planned Behavior and found five distinct COVID-19 vaccine segments. Both studies showed those most concerned and those most skeptical in the climate change segmentation tended to be in more enthusiastic COVID-19 vaccine segments, while those in the center on climate change were more skeptical on COVID-19 vaccines. Differences identified relating to age, gender, and political views may be explained by a combination of the specific nature and histories of these issues. These findings have implications for effective communication on science and health issues across diverse disciplines.

Audience segmentation analysis of public intentions to get a COVID-19 vaccine in Australia.

While previous studies provide broad categories of the public who intend to get a COVID-19 vaccine, few systematically segment and help understand and engage with distinct publics to improve COVID-19 vaccine uptake. Using data from a national sample of the Australian public (N = 1054) and using measures primarily based on the Theory of Planned Behaviour, a latent class analysis of 16 items was undertaken to identify COVID-19 audience segments for potential future message targeting. We found five different segments of COVID-19 vaccine intentions: vaccine enthusiasts (28%), supporters (26%), socials (20%), hesitant (15%) and sceptics (10%). These five audience segments also differ on demographic variables and their level of trust in mainstream media, scientists and health experts, social media and family and friends. Understanding the COVID-19 vaccine attitudinal and information-seeking characteristics of these sub-publics will help inform appropriate messaging campaigns.

A single cell characterisation of human embryogenesis identifies pluripotency transitions and putative anterior hypoblast centre.

Following implantation, the human embryo undergoes major morphogenetic transformations that establish the future body plan. While the molecular events underpinning this process are established in mice, they remain unknown in humans. Here we characterise key events of human embryo morphogenesis, in the period between implantation and gastrulation, using single-cell analyses and functional studies. First, the embryonic epiblast cells transition through different pluripotent states and act as a source of FGF signals that ensure proliferation of both embryonic and extra-embryonic tissues. In a subset of embryos, we identify a group of asymmetrically positioned extra-embryonic hypoblast cells expressing inhibitors of BMP, NODAL and WNT signalling pathways. We suggest that this group of cells can act as the anterior singalling centre to pattern the epiblast. These results provide insights into pluripotency state transitions, the role of FGF signalling and the specification of anterior-posterior axis during human embryo development.

Association of Environment With the Risk of Developing Psychotic Disorders in Rural Populations: Findings from the Social Epidemiology of Psychoses in East Anglia Study.

Importance: Social determinants are important risk factors for the development of first-episode psychosis (FEP); their effects in rural areas are largely unknown. Objective: To investigate neighborhood-level factors associated with FEP in a large, predominantly rural population-based cohort. Design, Setting, and Participants: This study extracted data on referrals for treatment of potential FEP at 6 Early-Intervention Psychosis services from the Social Epidemiology of Psychoses in East Anglia naturalistic cohort study data set, which covered a population of more than 2 million people in a rural area in the East of England for a period of 3.5 years. All individuals aged 16 to 35 years who presented to Early-Intervention Psychosis services and met diagnostic criteria for first episodes of nonaffective psychoses and affective psychoses (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnostic codes F20-33) were included (n = 631). Persons whose disorders had an organic basis (diagnostic codes F06.X) and those meeting the criteria for substance-induced psychosis (diagnostic codes F1X.5) were excluded. We derived 4 neighborhood-level exposures from a routine population data set using exploratory factor analysis (racial/ethnic diversity, deprivation, urbanicity, and social isolation) and investigated intragroup racial/ethnic density and fragmentation. Main Outcomes and Measures: Multilevel Poisson regression was performed to determine associations between incidence rates and neighborhood-level factors, after adjustment for individual factors. Results were reported as incidence rate ratios (IRRs). Results: The study included 631 participants who met criteria for FEP and whose median age at first contact was 23.8 years (interquartile range, 19.6-27.6 years); 416 of 631 (65.9%) were male. Crude incidence of FEP was calculated as 31.2 per 100 000 person-years (95% CI, 28.9-33.7). Incidence varied significantly between neighborhoods after adjustment for age, sex, race/ethnicity, and socioeconomic status. For nonaffective psychoses, incidence was higher in neighborhoods that were more economically deprived (IRR, 1.13; 95% CI, 1.06-1.20) and socially isolated (IRR, 1.11; 95% CI, 1.04-1.19). It was lower in more racially/ethnically diverse neighborhoods (IRR, 0.94; 95% CI, 0.87-1.00). Higher intragroup racial/ethnic density (IRR, 0.97; 95% CI, 0.94-1.00) and lower intragroup racial/ethnic fragmentation (IRR, 0.98; 95% CI, 0.96-1.00) were associated with a reduced risk of affective psychosis. Conclusions and Relevance: Spatial variation in the incidence of nonaffective and affective psychotic disorders exists in rural areas. This suggests that the social environment contributes to psychosis risk across the rural-urban gradient.

Stem cells in veterinary medicine--attempts at regenerating equine tendon after injury.

Stem cells have evoked considerable excitement in the animal-owning public because of the promise that stem cell technology could deliver tissue regeneration for injuries for which natural repair mechanisms do not deliver functional recovery and for which current therapeutic strategies have minimal effectiveness. This review focuses on the current use of stem cells within veterinary medicine, whose practitioners have used mesenchymal stem cells (MSCs), recovered from either bone marrow or adipose tissue, in clinical cases primarily to treat strain-induced tendon injury in the horse. The background on why this treatment has been advocated, the data supporting its use and the current encouraging outcome from clinical use in horses treated with bone-marrow-derived cells are presented together with the future challenges of stem-cell therapy for the veterinary community.

The anterior visceral endoderm of the mouse embryo is established from both preimplantation precursor cells and by de novo gene expression after implantation.

Initiation of the development of the anterior-posterior axis in the mouse embryo has been thought to take place only when the anterior visceral endoderm (AVE) emerges and starts its asymmetric migration. However, expression of Lefty1, a marker of the AVE, was recently found to initiate before embryo implantation. This finding has raised two important questions: are the cells that show such early, preimplantation expression of this AVE marker the real precursors of the AVE and, if so, how does this contribute to the establishment of the AVE? Here, we address both of these questions. First, we show that the expression of another AVE marker, Cer1, also commences before implantation and its expression becomes consolidated in the subset of ICM cells that comprise the primitive endoderm. Second, to determine whether the cells showing this early Cer1 expression are true precursors of the AVE, we set up conditions to trace these cells in time-lapse studies from early periimplantation stages until the AVE emerges and becomes asymmetrically displaced. We found that Cer1-expressing cells are asymmetrically located after implantation and, as the embryo grows, they become dispersed into two or three clusters. The expression of Cer1 in the proximal domain is progressively diminished, whilst it is reinforced in the distal-lateral domain. Our time-lapse studies demonstrate that this distal-lateral domain is incorporated into the AVE together with cells in which Cer1 expression begins only after implantation. Thus, the AVE is formed from both part of an ancestral population of Cerl-expressing cells and cells that acquire Cer1 expression later. Finally, we demonstrate that when the AVE shifts asymmetrically to establish the anterior pole, this occurs towards the region where the earlier postimplantation expression of Cer1 was strongest. Together, these results suggest that the orientation of the anterior-posterior axis is already anticipated before AVE migration.

A quantitative study of the equine soft palate using histomorphometry.

Dorsal displacement of the soft palate is a common cause of upper airway obstruction in racehorses and is of unknown aetiology. To determine whether the palate may displace for structural reasons, knowledge of the normal soft palate is required. The present study aimed to describe, qualitatively and quantitatively, the structure of the normal equine soft palate using histomorphometry. In soft palates from 12 Thoroughbreds, glandular tissue predominated (ca. 40% of total area), located mainly in the rostral and ventral regions. Rostrally, muscles attached to a tendinous aponeurosis located dorsal to the glandular tissue. Muscle was most abundant in the dorsal mid region and decreased caudally. The oral mucosa consisted of a non-keratinised stratified squamous epithelium whereas the nasopharyngeal mucosa was pseudostratified, columnar and ciliated. Elastin fibres were observed in the nasopharyngeal submucosa, becoming more prevalent caudally. The palates were bilaterally symmetrical although the proportion of tissue types varied considerably between individuals.

Regionalised signalling within the extraembryonic ectoderm regulates anterior visceral endoderm positioning in the mouse embryo.

The development of the anterior-posterior (AP) axis in the mammalian embryo is controlled by interactions between embryonic and extraembryonic tissues. It is well established that one of these extraembryonic tissues, the anterior visceral endoderm (AVE), can repress posterior cell fate and that signalling from the other, the extraembryonic ectoderm (ExE), is required for posterior patterning. Here, we show that signals from the prospective posterior ExE repress AVE gene expression and affect the distribution of the AVE cells. Surgical ablation of the prospective posterior, but not the anterior, extraembryonic region at 5.5 days of development (E5.5) perturbs the characteristic distal-to-anterior distribution of AVE cells and leads to a dramatic expansion of the AVE domain. Time-lapse imaging studies show that this increase is due to the ectopic expression of an AVE marker, which results in a symmetrical positioning of the AVE. Surgical ablation of this same ExE region after the distal-to-anterior migration has already commenced, at E5.75, does not affect the localisation of the AVE, indicating that this effect takes place within a short time window. Conversely, transplanting the prospective posterior, but not the anterior, extraembryonic region onto isolated E5.5 embryonic explants drastically reduces the AVE domain. Further, transplantation experiments demonstrate that the signalling regulating AVE gene expression originates from the posterior ExE, rather than its surrounding VE. Together, our results show that signals emanating from the future posterior ExE within a temporal window both restrict the AVE domain and promote its specific positioning. This indicates for the first time that the ExE is already regionalised a day before the onset of gastrulation in order to correctly set the orientation of the AP axis of the mouse embryo. We propose a reciprocal function of the posterior ExE and the AVE in establishing a balance between the antagonistic activities of these two tissues, essential for AP patterning.

Similarity as transformation.

We propose that similarity is determined by the transformation distance between representations: entities which are perceived to be similar have representations which are readily transformed into one another, whereas transforming between dissimilar entities requires many transformations. We present three experiments that indicate that similarity is strongly influenced by transformation distance. These data present a challenge for featural or spatial accounts of similarity. Finally, we introduce a family of transformation-based accounts of similarity, called 'Representational Distortion', as a specific example of a transformational approach to similarity.

Effects of aging on absolute identification of duration.

Experiments to examine the effects of aging on the ability to identify temporal durations in an absolute identification task are reported. In Experiment 1, older adults were worse than younger adults in identifying a tone's position within a series of 6 tones of varied durations. In Experiment 2, participants were required to identify a tone's position in 9 tones of varied durations. Older adults' performance was again worse than that of younger adults; moreover, they showed a qualitatively different pattern of errors than younger adults. In Experiment 3, in which the tones varied in pitch, the performance of older adults was worse than that of younger adults, but the error patterns of the 2 groups were similar. The results suggest that older adults have distorted memory representations for durations but not for pitch.