Conserved biological function between Pax-2 and Pax-5 in midbrain and cerebellum development: Evidence from targeted mutations

The development of two major subdivisions of the vertebrate nervous system, the midbrain and the cerebellum, is controlled by signals emanating from a constriction in the neural primordium called the midbrain/hindbrain organizer (Joyner, A. L. (1996) Trends Genet. 12, 15–201). The closely related transcription factors Pax-2 and Pax-5 exhibit an overlapping expression pattern very early in the developing midbrain/hindbrain junction. Experiments carried out in fish (Krauss, S., Maden, M., Holder, N. & Wilson, S. W. (1992) Nature (London) 360, 87–89) with neutralizing antibodies against Pax-b, the orthologue of Pax-2 in mouse, placed this gene family in an regulatory cascade necessary for the development of the midbrain and the cerebellum. The targeted mutation of Pax-5 has been reported to have only slight effects in the development of structures derived from the isthmic constriction, whereas the Pax-2 null mutant mice show a background-dependent phenotype with varying penetrance. To test a possible redundant function between Pax-2 and Pax-5 we analyzed the brain phenotypes of mice expressing different dosages of both genes. Our results demonstrate a conserved biological function of both proteins in midbrain/hindbrain regionalization. Additionally, we show that one allele of Pax-2, but not Pax-5, is necessary and sufficient for midbrain and cerebellum development in C57BL/6 mice

COVID-19 vaccine skeptics are persuaded by pro-vaccine expert consensus messaging

To further understand how to combat COVID-19 vaccination hesitancy, we examined the effects of pro-vaccine expert consensus messaging on lay attitudes about vaccine safety and intention to get a COVID-19 vaccine. We surveyed 729 unvaccinated individuals from four countries in the early stages of the pandemic and 472 unvaccinated individuals from two countries after 2 years of the pandemic. We found belief of vaccine safety strongly correlated with intention to vaccinate in the first sample and less strongly in the second. We also found that consensus messaging improved attitudes toward vaccination even for participants who did not believe the vaccine is safe nor intended to get it. The persuasiveness of expert consensus was unaffected by exposing participants’ lack of knowledge about vaccines. We conclude that highlighting expert consensus may be a way to increase support toward COVID-19 vaccination in those hesitant or skeptical.info:eu-repo/semantics/acceptedVersio

TEN-YEAR STATUS OF THE EASTERN MIGRATORY WHOOPING CRANE REINTRODUCTION

From 2001 to 2010, 132 costume-reared juvenile whooping cranes (Grus americana) were led by ultralight aircraft from Necedah National Wildlife Refuge (NWR) in central Wisconsin to the Gulf Coast of Florida on their first autumn migration (ultralight-led or UL), and 46 juveniles were released directly on Necedah NWR during autumn of the hatch year (direct autumn release or DAR). Return rate in spring was 90.5% for UL and 69.2% for DAR, the lower value of the latter attributable to 1 cohort with migration problems. Overall population survival 1 year and from 1 to 3 years post-release was 81% and 84%, respectively. Survival 1 year post-release was significantly different between UL (85.1%) and DAR (65.7%) cranes. Since summer 2008, DAR migration and wintering have improved, winter distribution of the population has changed, the migration route of the population has shifted westward, and number of yearlings summering in locations used during spring wandering has increased. Human avoidance problems resulted in 2 birds being removed from the population. As in earlier years, homing to the natal area and prolific pair formation continued (29 of 31 adult pairs have formed in the core reintroduction area), predation continued to be the primary cause of mortality, and parental desertion of nests, especially during the initial (primary) nesting period, continued. During 2005-2010, all 43 of these early nests failed; of 15 late nests or renests, chicks hatched from 8 nests, and 3 chicks fledged. As of 31 March 2011, the population contained a maximum 105 individuals (54 males and 51 females) including 20 adult pairs

NEST DESERTION IN A REINTRODUCED POPULATION OF MIGRATORY WHOOPING CRANES

Reintroduction of an eastern migratory population of whooping cranes (Grus americana) into eastern North America began in 2001. Reproduction first occurred in 2005. Through 2008, eggs were produced in 22 first nests and 2 renests. All first nests failed–50% confirmed due to desertion by the parents and the remaining nest failures also consistent with the pattern of parental desertion. Nest failures were not related to stage of incubation, and they were often synchronous. Temperatures in winter and early spring affected timing of nest failure. An environmental factor such as harassment of incubating cranes by black flies (Simulium spp.) may be responsible for widespread nest desertion

How to Motivate Your Dragon: Teaching Goal-Driven Agents to Speak and Act in Fantasy Worlds.

We seek to create agents that both act and communicate with other agents in pursuit of a goal. Towards this end, we extend LIGHT (Urbanek et al. 2019)—a large-scale crowd-sourced fantasy text-game—with a dataset of quests. These contain natural language motivations paired with in-game goals and human demonstrations; completing a quest might require dialogue or actions (or both). We introduce a reinforcement learning system that (1) incorporates large-scale language modeling-based and commonsense reasoning-based pre-training to imbue the agent with relevant priors; and (2) leverages a factorized action space of action commands and dialogue, balancing between the two. We conduct zero-shot evaluations using held-out human expert demonstrations, showing that our agents are able to act consistently and talk naturally with respect to their motivations

You ≠ Me: Individual differences in the structure of social cognition

This study investigated the structure of social cognition, and how it is influenced by personality; specifically, how various socio-cognitive capabilities, and the pattern of inter-relationships and co-dependencies among them differ between divergent personality styles. To measure social cognition, a large non-clinical sample (n = 290) undertook an extensive battery of self-report and performance-based measures of visual perspective taking, imitative tendencies, affective empathy, interoceptive accuracy, emotion regulation, and state affectivity. These same individuals then completed the Personality Styles and Disorders Inventory. Latent Profile Analysis revealed two dissociable personality profiles that exhibited contrasting cognitive and affective dispositions, and multivariate analyses indicated further that these profiles differed on measures of social cognition; individuals characterised by a flexible and adaptive personality profile expressed higher action orientation (emotion regulation) compared to those showing more inflexible tendencies, along with better visual perspective taking, superior interoceptive accuracy, less imitative tendencies, and lower personal distress and negativity. These characteristics point towards more efficient self-other distinction, and to higher cognitive control more generally. Moreover, low-level cognitive mechanisms served to mediate other higher level socio-emotional capabilities. Together, these findings elucidate the cognitive and affective underpinnings of individual differences in social behaviour, providing a data-driven model that should guide future research in this area

Topical Treatment of Nonhealing Venous Leg Ulcer with Propolis Ointment

An investigation of effectiveness of topical treatment of nonhealing chronic venous leg ulcers with propolis ointment was conducted. 56 patients were included in the study and randomized into two groups. In group 1, there were 28 patients (ulceration area: 6.9–9.78 cm2) treated by means of topical propolis ointment application and short stretch bandage compression. In group 2, there were 29 patients (ulceration area: 7.2–9.4 cm2) treated by means of Unna boot leg compression without topical propolis treatment. In the study, the efficacy of both treatment methods in patients with resistive venous leg ulcers was compared. The ulceration of patients from group 1 healed completely after 6 weeks of therapy in all cases. In all patients from group 2, the process of healing was longer but successfully completed after 16 weeks of the therapy. We found that an adjunctive propolis ointment treatment increases the efficacy of the short stretch bandage compression stocking, and this combined treatment is more effective than Unna’s boot compression alone

Amino acid substitution equivalent to human chorea-acanthocytosis I2771R in yeast Vps13 protein affects its binding to phosphatidylinositol 3-phosphate

The rare human disorder chorea-acanthocytosis (ChAc) is caused by mutations in hVPS13A gene. The hVps13A protein interacts with actin and regulates the level of phosphatidylinositol 4-phosphate (PI4P) in the membranes of neuronal cells. Yeast Vps13 is involved in vacuolar protein transport and, like hVps13A, participates in PI4P metabolism. Vps13 proteins are conserved in eukaryotes, but their molecular function remains unknown. One of the mutations found in ChAc patients causes amino acids substitution I2771R which affects the localization of hVps13A in skeletal muscles. To dissect the mechanism of pathogenesis of I2771R, we created and analyzed a yeast strain carrying the equivalent mutation. Here we show that in yeast, substitution I2749R causes dysfunction of Vps13 protein in endocytosis and vacuolar transport, although the level of the protein is not affected, suggesting loss of function. We also show that Vps13, like hVps13A, influences actin cytoskeleton organization and binds actin in immunoprecipitation experiments. Vps13-I2749R binds actin, but does not function in the actin cytoskeleton organization. Moreover, we show that Vps13 binds phospholipids, especially phosphatidylinositol 3-phosphate (PI3P), via its SHR_BD and APT1 domains. Substitution I2749R attenuates this ability. Finally, the localization of Vps13-GFP is altered when cellular levels of PI3P are decreased indicating its trafficking within the endosomal membrane system. These results suggest that PI3P regulates the functioning of Vps13, both in protein trafficking and actin cytoskeleton organization. Attenuation of PI3P-binding ability in the mutant hVps13A protein may be one of the reasons for its mislocalization and disrupted function in cells of patients suffering from ChAc

Scalar on time-by-distribution regression and its application for modelling associations between daily-living physical activity and cognitive functions in Alzheimer's Disease

Wearable data is a rich source of information that can provide deeper understanding of links between human behaviours and human health. Existing modelling approaches use wearable data summarized at subject level via scalar summaries using regression techniques, temporal (time-of-day) curves using functional data analysis (FDA), and distributions using distributional data analysis (DDA). We propose to capture temporally local distributional information in wearable data using subject-specific time-by-distribution (TD) data objects. Specifically, we propose scalar on time-by-distribution regression (SOTDR) to model associations between scalar response of interest such as health outcomes or disease status and TD predictors. We show that TD data objects can be parsimoniously represented via a collection of time-varying L-moments that capture distributional changes over the time-of-day. The proposed method is applied to the accelerometry study of mild Alzheimer's disease (AD). Mild AD is found to be significantly associated with reduced maximal level of physical activity, particularly during morning hours. It is also demonstrated that TD predictors attain much stronger associations with clinical cognitive scales of attention, verbal memory, and executive function when compared to predictors summarized via scalar total activity counts, temporal functional curves, and quantile functions. Taken together, the present results suggest that the SOTDR analysis provides novel insights into cognitive function and AD