Speciation and historical invasions of the Asian black-spined toad (Duttaphrynus melanostictus).

Animal translocations provide striking examples of the human footprint on biodiversity. Combining continental-wide genomic and DNA-barcoding analyses, we reconstructed the historical biogeography of the Asian black-spined toad (Duttaphrynus melanostictus), a toxic commensal amphibian that currently threatens two biodiversity hotspots through biological invasions (Wallacea and Madagascar). The results emphasize a complex diversification shaped by speciation and mitochondrial introgression that comprises two distinct species.

Design and application of synthetic 17B-HSD13 substrates reveals preserved catalytic activity of protective human variants.

Several hydroxysteroid dehydrogenase 17-beta 13 variants have previously been identified as protective against metabolic dysfunction-associated steatohepatitis (MASH) fibrosis, ballooning and inflammation, and as such this target holds significant therapeutic potential. However, over 5 years later, the function of 17B-HSD13 remains unknown. Structure-aided design enables the development of potent and selective sulfonamide-based 17B-HSD13 inhibitors.

The human social cognitive network contains multiple regions within the amygdala.

Reasoning about someone's thoughts and intentions-i.e., forming a "theory of mind"-is a core aspect of social cognition and relies on association areas of the brain that have expanded disproportionately in the human lineage.

Captive Breeding Reveals Insights Into the Ecology and Reproductive Biology of 11 Little-Known Malagasy Frog Species.

Amphibians are facing an extinction crisis, with ex situ programs increasingly being used as a tool for their conservation. However, conservation efforts are often limited because we do not understand the ecological, behavioral, and life history traits of many amphibian species. Here, we report on the seasonal breeding patterns, egg-laying behavior, clutch size, and development of 11 frog species maintained at a conservation breeding facility in Andasibe, Madagascar.

Small population size and possible extirpation of the threatened Malagasy poison frog .

Amphibians are experiencing severe population declines, requiring targeted conservation action for the most threatened species and habitats. Unfortunately, we do not know the basic demographic traits of most species, which hinders population recovery efforts. We studied one of Madagascar's most threatened frog species, the harlequin mantella (), to confirm it is still present at historic localities and estimate annual survival and population sizes.

Rules of river avulsion change downstream.

Avulsing rivers create new pathways on the floodplain and the associated flooding can profoundly affect society. River avulsions are thought to occur when the water column becomes perched above the floodplain or when the slope down the flanks of the channel provides a steeper descent than the existing river channel. We test these classical ideas by quantifying the topography around avulsing rivers and show that these mechanisms, historically invoked separately, work together.

Distributed midbrain responses signal the content of positive identity prediction errors.

Recent work across species has shown that midbrain dopamine neurons signal not only errors in the prediction of reward value but also in the prediction of value-neutral sensory features. To support learning of associative structures in downstream areas, identity prediction errors (iPEs) should signal specific information about the mis-predicted outcome. Here, we used pattern-based analysis of functional magnetic resonance imaging (fMRI) data acquired during reversal learning to characterize the information content of iPE responses in the human midbrain.

"I'm not an anxious person": end-of-life care workers constructing positive psychological states.

Background: Mental health is an issue of social and economic importance. Sociocultural and scholarly attention has largely focused on the negative aspects of mental health. That is, on mental disorders and illness and how they adversely impact our lives.

"They are not taking it seriously": Constructing family dynamics in end-of-life care interactions in Hong Kong.

In Chinese culture, the family is central to the decision-making around care provided to terminally-ill patients. Previous research examined the preferences that patients and relatives have in regard to the family's role in end-of-life care. Our article takes a discourse analytic perspective and focuses on how familial dynamics are interactionally constructed by patients in audio-recorded end-of-life care consultations in Hong Kong hospitals.

A scoping review to map the research on the mental health of students and graduates during their university-to-work transitions.

Objectives: This scoping review maps the extant literature on students' and graduates' mental health experiences throughout their university-to-work transitions. The current review investigates the methodological features of the studies, the main findings, and the theories that the studies draw on to conceptualise mental health and transitions.

Design: This project used a scoping review methodology created and developed by Peters and colleagues and the Joanna Briggs Institute.

Social cognitive regions of human association cortex are selectively connected to the amygdala.

Reasoning about someone's thoughts and intentions - i.e., forming a theory of mind - is an important aspect of social cognition that relies on association areas of the brain that have expanded disproportionately in the human lineage.

Spatial Ecology of an Arboreal Iguana () in a Treeless Landscape.

Understanding the spatial ecology of species has important implications for conservation, as it helps identify suitable habitats and minimum requirements for biodiversity monitoring and management. The spiny-tailed lizard is a widespread endemic iguanid occurring in dry areas of southern and western Madagascar. While the species is known to be mostly arboreal, populations of the Isalo sandstone massif suggest local adaptation to a less forested savannah and a more exposed habitat.

Design of Next-Generation DGAT2 Inhibitor PF-07202954 with Longer Predicted Half-Life.

Diacylglycerol O-acyltransferase 2 (DGAT2) inhibitors have been shown to lower liver triglyceride content and are being explored clinically as a treatment for non-alcoholic steatohepatitis (NASH). This work details efforts to find an extended-half-life DGAT2 inhibitor. A basic moiety was added to a known inhibitor template, and the basicity and lipophilicity were fine-tuned by the addition of electrophilic fluorines.

Structural basis of lipid-droplet localization of 17-beta-hydroxysteroid dehydrogenase 13.

Hydroxysteroid 17-beta-dehydrogenase 13 (HSD17B13) is a hepatic lipid droplet-associated enzyme that is upregulated in patients with non-alcoholic fatty liver disease. Recently, there have been several reports that predicted loss of function variants in HSD17B13 protect against the progression of steatosis to non-alcoholic steatohepatitis with fibrosis and hepatocellular carcinoma. Here we report crystal structures of full length HSD17B13 in complex with its NAD cofactor, and with lipid/detergent molecules and small molecule inhibitors from two distinct series in the ligand binding pocket.

6-Azaspiro[2.5]octanes as small molecule agonists of the human glucagon-like peptide-1 receptor.

Activation of the glucagon-like peptide-1 (GLP-1) receptor stimulates insulin release, lowers plasma glucose levels, delays gastric emptying, increases satiety, suppresses food intake, and affords weight loss in humans. These beneficial attributes have made peptide-based agonists valuable tools for the treatment of type 2 diabetes mellitus and obesity. However, efficient, and consistent delivery of peptide agents generally requires subcutaneous injection, which can reduce patient utilization.

Mental Health, Discourse and Stigma.

In this editorial to the special collection "Mental Health, Discourse and Stigma" we outline the concepts of mental, health, discourse and stigma as they are examined through sociolinguistic lenses. We examine the sociolinguistic approach to mental health and stigma and discuss the different theoretical frameworks and methodological approaches that have been applied in such contexts. Sociolinguistics views mental health and stigma as discursively constructed and constituted, i.

Mental health of new and recent graduates during the university-to-work transition: a scoping review protocol.

Introduction: University students face challenges when starting their careers and entering the workforce after tertiary education is associated with negative psychological outcomes. The planned scoping review will synthesise the literature on the impact of university-to-work transitions on the mental health of new and recent graduates. We will describe the characteristics and main findings of the studies, and will examine the variables associated with, and the theories used to explain, the relationship between transitions to work and graduates' mental health.

Hillslope roughness reveals forest sensitivity to extreme winds.

Windthrow, or the uprooting of trees by extreme wind gusts, is a natural forest disturbance that creates microhabitats, turns over soil, alters hydrology, and removes carbon from the above-ground carbon stock. Long recurrence intervals between extreme wind events, however, make direct observations of windthrow rare, challenging our understanding of this important disturbance process. To overcome this difficulty, we present an approach that uses the geomorphic record of hillslope topographic roughness as a proxy for the occurrence of windthrow.

Masked features of task states found in individual brain networks.

Completing complex tasks requires that we flexibly integrate information across brain areas. While studies have shown how functional networks are altered during different tasks, this work has generally focused on a cross-subject approach, emphasizing features that are common across people. Here we used extended sampling "precision" fMRI data to test the extent to which task states generalize across people or are individually specific.

A Small-Molecule Oral Agonist of the Human Glucagon-like Peptide-1 Receptor.

Peptide agonists of the glucagon-like peptide-1 receptor (GLP-1R) have revolutionized diabetes therapy, but their use has been limited because they require injection. Herein, we describe the discovery of the orally bioavailable, small-molecule, GLP-1R agonist PF-06882961 (danuglipron). A sensitized high-throughput screen was used to identify 5-fluoropyrimidine-based GLP-1R agonists that were optimized to promote endogenous GLP-1R signaling with nanomolar potency.

Where rivers jump course.

Rivers can abruptly shift pathways in rare events called avulsions, which cause devastating floods. The controls on avulsion locations are poorly understood as a result of sparse data on such features. We analyzed nearly 50 years of satellite imagery and documented 113 avulsions across the globe that indicate three distinct controls on avulsion location.

Landscape evolution under the southern Laurentide Ice Sheet.

Subglacial landscapes, revealed in regions of recent ice-sheet retreat, provide a window into ice-sheet dynamics and interactions with evolving subglacial topography. Here, we document landscape evolution beneath the southern Laurentide Ice Sheet of North America since the end of the Pliocene, 2.6 million years (Ma) ago, by reconstructing the isostatically adjusted preglacial surface and modern bedrock topography at 250 m horizontal resolution.