Widespread convergence towards functional optimization in the lower jaws of crocodile-line archosaurs.

Extant crocodilian jaws are subject to functional demands induced by feeding and hydrodynamics. However, the morphological and ecological diversity of extinct crocodile-line archosaurs is far greater than that of living crocodilians, featuring repeated convergence towards disparate ecologies including armoured herbivores, terrestrial macropredators and fully marine forms. Crocodile-line archosaurs, therefore, present a fascinating case study for morphological and functional divergence and convergence within a clade across a wide range of ecological scenarios. Here, we build performance landscapes of two-dimensional theoretical jaw shapes to investigate the influence of strength, speed and hydrodynamics in the morphological evolution of crocodile-line archosaur jaws, and test whether ecologically convergent lineages evolved similarly optimal jaw function. Most of the 243 sampled jaw morphologies occupy optimized regions of theoretical morphospace for either rotational efficiency, resistance to Von Mises stress, hydrodynamic efficiency or a trade-off between multiple functions, though some seemingly viable shapes remain unrealized. Jaw speed is optimized only in a narrow region of morphospace whereas many shapes possess optimal jaw strength, which may act as a minimum boundary rather than a strong driver for most taxa. This study highlights the usefulness of theoretical morphology in assessing functional optimality, and for investigating form-function relationships in diverse clades.

Social protection and the International Monetary Fund: promise versus performance.

BACKGROUND: Countries in the Global South are currently facing momentous economic and social challenges, including major debt service problems. As in previous periods of global financial instability, a growing number of countries have turned to the International Monetary Fund (IMF) for financial assistance. The organization has a long track-record of advocating for extensive fiscal consolidation-commonly known as 'austerity'-for its borrowers. However, in recent years, the IMF has announced major initiatives for ensuring that its loans support social spending, thus aiding countries in meeting their development targets and the Sustainable Development Goals. To assess this track record, we collected spending data on 21 loans signed in the 2020-2022 period, including from all their periodic reviews up to August 2023. RESULTS: We find that austerity measures remain a core part of the organization's mandated policies for its borrowers: 15 of the 21 countries studied here experience a decrease in fiscal space over the course of their IMF programs. Against this fiscal backdrop, social spending floors have failed to live up to their promise. There is no streamlined definition of these floors, thus rendering their application haphazard and inconsistent. But even on their own terms, these floors lack ambition: they often do not foresee trajectories of meaningful social spending increases over time, and, when they do, many of these gains are eaten up by soaring inflation. In addition, a third of social spending floors are not implemented-a much lower implementation rate from that for austerity conditions, which the IMF prioritizes. In several instances, where floors are implemented, they are not meaningfully exceeded, thus-in practice-acting as social spending ceilings. CONCLUSIONS: The IMF's lending programs are still heavily focused on austerity, and its strategy on social spending has not represented the sea-change that the organization advertised. At best, social spending floors act as damage control for the painful budget cuts: they are instruments of social amelioration, underpinned by principles of targeted assistance for highly disadvantaged groups. Alternative approaches rooted in principles of universalism can be employed to build up durable and resilient social protection systems.

Uncovering the advertising and promotional strategies of tobacco companies in Cambodia: recall of below-the-line marketing among young male smokers.

INTRODUCTION: Tobacco companies have used below-the-line marketing in novel ways to promote their brands to youth in low/middle-income countries in Southeast Asia. This study explores how young male smokers in Cambodia experience below-the-line marketing strategies. METHODS: Convenience sampling was used to recruit 147 young male smokers (18-24 years) in Cambodia in early 2020. Local research assistants conducted mixed-methods interviews with participants in Khmer or English. Participants recalled exposure to below-the-line marketing strategies and provided in-depth descriptions about their experiences with individual sales promotions. Quantitative data were analysed using descriptive statistics and qualitative data were analysed using thematic analysis. RESULTS: 54% of participants recalled exposure to at least one below-the-line marketing strategy, including point-of-sale promotions (32.7%), individual sales promotions (27.9%) and online advertising (14.3%). Participants described individual sales promotions in public settings, and recalled that promoters were mostly female, attractive and targeted young males. Tactics used to encourage young people to accept promotional offers included free cigarettes and sample packets, swapping current cigarettes for new brands and collecting consumer details after interviewing. The brands and product features of cigarettes being promoted were readily described by participants. CONCLUSION: This study provides evidence that illegal below-the-line marketing is still occurring in Cambodia, and increased monitoring and enforcement of advertising restrictions is needed.

Transcriptome and epigenome diversity and plasticity of muscle stem cells following transplantation.

Adult skeletal muscles are maintained during homeostasis and regenerated upon injury by muscle stem cells (MuSCs). A heterogeneity in self-renewal, differentiation and regeneration properties has been reported for MuSCs based on their anatomical location. Although MuSCs derived from extraocular muscles (EOM) have a higher regenerative capacity than those derived from limb muscles, the molecular determinants that govern these differences remain undefined. Here we show that EOM and limb MuSCs have distinct DNA methylation signatures associated with enhancers of location-specific genes, and that the EOM transcriptome is reprogrammed following transplantation into a limb muscle environment. Notably, EOM MuSCs expressed host-site specific positional Hox codes after engraftment and self-renewal within the host muscle. However, about 10% of EOM-specific genes showed engraftment-resistant expression, pointing to cell-intrinsic molecular determinants of the higher engraftment potential of EOM MuSCs. Our results underscore the molecular diversity of distinct MuSC populations and molecularly define their plasticity in response to microenvironmental cues. These findings provide insights into strategies designed to improve the functional capacity of MuSCs in the context of regenerative medicine.

Structural adjustment, alienation, and mass protest.

The International Monetary Fund (IMF) is (in)famous for its structural adjustment programs, which provide fresh credit for borrowing governments in exchange for market-liberalizing policy reforms. While studies have documented a causal relationship between structural adjustment and political instability, scholarly understanding of the mechanisms underlying this relationship remain perfunctory. The received wisdom is that IMF policy conditions generate material hardship which then drives political instability. We advance an additional pathway-that instability is also prompted by alienation effects related to the foreign imposition of policies. Drawing on a sample of up to 168 countries between 1980 and 2014, we test for the presence of both mechanisms. Our results suggest that there are alienation effects, indicated by a persistent protest-inducing impact of IMF program participation when controlling for market-liberalizing conditions, and especially when programs are concluded by left-wing governments and non-repeat borrowers. We also find evidence of hardship effects, indicated by a positive relationship between the intensity of fiscal austerity required and the number of protests. Our findings have important implications for the relationship between structural adjustment, contentious politics, and the role of international organizations in domestic policy reform.

Do health halos and conspicuous consumption influence the appeal and risk perceptions of e-cigarettes among young Cambodian men?

INTRODUCTION: Reduced risk perceptions influence young people's consumption behaviours of e-cigarettes, suggesting that a health halo effect may be associated with these devices. Product, performative, and social factors contribute to the appeal of e-cigarettes, with young people using e-cigarettes with friends as part of social interactions. This study explored the factors that influence the appeal and risk perceptions associated with e-cigarettes among young Cambodian men. METHODS: A mixed-method, interviewer-administered survey with 147 young men in Cambodia, who were aged between 18 and 24 years and identified as cigarette smokers. Participants described their attitudes and consumption behaviours surrounding e-cigarettes, recalled e-cigarette promotions, and described their risk perceptions towards e-cigarettes. Descriptive statistics were calculated for quantitative data, and thematic analysis was conducted for qualitative data. RESULTS: Some participants associated e-cigarettes with affluence and exclusivity, describing these devices as products that rich and/or younger people use. Participants also described product attributes that were appealing about e-cigarettes, such as variety of flavours, vapour, and performing smoke 'styles' with friends, which differentiated the product from combustible cigarettes. Participants also had reduced risk perceptions towards e-cigarettes, with some commenting that e-cigarettes were not harmful or might be health-enhancing. CONCLUSION: Some young people may perceive e-cigarettes as a form of conspicuous consumption, which they associated with social status and identity. A health halo effect appears to be associated with e-cigarettes among some young people. This may influence young people to underestimate the potential health risks associated with these devices.

Exploring the design and introduction of the Ophelia (Optimising Health Literacy and Access) process in the Philippines: A qualitative case study.

ISSUE ADDRESSED: The Ophelia (Optimising Health Literacy and Access) process is a systematic approach for improving access to health information and services through health literacy interventions. However, there is limited understanding of how this process can be adapted in low- and- middle-income countries. METHODS: A qualitative case study was used to describe how an Ophelia project was designed and introduced in a community setting in the Philippines and to explore the experiences of stakeholders involved in this process. Two qualitative methods were used: document analysis (n = 12) and semi-structured interviews (n = 12). RESULTS: Data showed that the project stakeholders had embedded the eight Ophelia principles in the design of the project, introduced the Ophelia process in one target community, and conducted a health literacy needs assessment. Project stakeholders faced challenges engaging with local authorities and community members in this location, but overcame these issues through building relationships and understanding their needs. Local authorities and stakeholders provided access to resources and knowledge of this target community. CONCLUSIONS: The Ophelia process can be adapted for a community setting in the Philippines. Understanding local communities is crucial for introducing and engaging participation in this process. SO WHAT?: The Ophelia process may have implications for increasing access to health information and services for vulnerable populations in the Philippines and the Asia Pacific.

Ecological opportunity and the rise and fall of crocodylomorph evolutionary innovation.

Understanding the origin, expansion and loss of biodiversity is fundamental to evolutionary biology. The approximately 26 living species of crocodylomorphs (crocodiles, caimans, alligators and gharials) represent just a snapshot of the group's rich 230-million-year history, whereas the fossil record reveals a hidden past of great diversity and innovation, including ocean and land-dwelling forms, herbivores, omnivores and apex predators. In this macroevolutionary study of skull and jaw shape disparity, we show that crocodylomorph ecomorphological variation peaked in the Cretaceous, before declining in the Cenozoic, and the rise and fall of disparity was associated with great heterogeneity in evolutionary rates. Taxonomically diverse and ecologically divergent Mesozoic crocodylomorphs, like marine thalattosuchians and terrestrial notosuchians, rapidly evolved novel skull and jaw morphologies to fill specialized adaptive zones. Disparity in semi-aquatic predatory crocodylians, the only living crocodylomorph representatives, accumulated steadily, and they evolved more slowly for most of the last 80 million years, but despite their conservatism there is no evidence for long-term evolutionary stagnation. These complex evolutionary dynamics reflect ecological opportunities, that were readily exploited by some Mesozoic crocodylomorphs but more limited in Cenozoic crocodylians.

Hepatic gene body hypermethylation is a shared epigenetic signature of murine longevity.

Dietary, pharmacological and genetic interventions can extend health- and lifespan in diverse mammalian species. DNA methylation has been implicated in mediating the beneficial effects of these interventions; methylation patterns deteriorate during ageing, and this is prevented by lifespan-extending interventions. However, whether these interventions also actively shape the epigenome, and whether such epigenetic reprogramming contributes to improved health at old age, remains underexplored. We analysed published, whole-genome, BS-seq data sets from mouse liver to explore DNA methylation patterns in aged mice in response to three lifespan-extending interventions: dietary restriction (DR), reduced TOR signaling (rapamycin), and reduced growth (Ames dwarf mice). Dwarf mice show enhanced DNA hypermethylation in the body of key genes in lipid biosynthesis, cell proliferation and somatotropic signaling, which strongly correlates with the pattern of transcriptional repression. Remarkably, DR causes a similar hypermethylation in lipid biosynthesis genes, while rapamycin treatment increases methylation signatures in genes coding for growth factor and growth hormone receptors. Shared changes of DNA methylation were restricted to hypermethylated regions, and they were not merely a consequence of slowed ageing, thus suggesting an active mechanism driving their formation. By comparing the overlap in ageing-independent hypermethylated patterns between all three interventions, we identified four regions, which, independent of genetic background or gender, may serve as novel biomarkers for longevity-extending interventions. In summary, we identified gene body hypermethylation as a novel and partly conserved signature of lifespan-extending interventions in mouse, highlighting epigenetic reprogramming as a possible intervention to improve health at old age.

Whatever it takes? The global financial safety net, Covid-19, and developing countries.

Multilateral financial institutions have pledged to do whatever it takes to enable emerging market and developing countries to fill a $2.5 trillion financing gap to combat Covid-19 and subsequent economic crises. In this article, we present new datasets to track the extent to which multilateral financial institutions are meeting these goals, and conduct a preliminary assessment of progress to date. We find that the International Monetary Fund and the principal regional financial arrangements have made relatively trivial amounts of new financing available and have been slow to disburse the financing at their disposal. As of July 31, 2020, these institutions had committed $89.56 billion in loans and $550 million in currency swaps, totaling $90.11 billion-just 12.6% of their current capacity. The new datasets allow scholars, policymakers, and civil society to continue to track these trends, and eventually examine the impact of such financing on health and development outcomes.

Morphological convergence obscures functional diversity in sabre-toothed carnivores.

The acquisition of elongated, sabre-like canines in multiple vertebrate clades during the last 265 Myr represents a remarkable example for convergent evolution. Due to striking superficial similarities in the cranial skeleton, the same or similar skull and jaw functions have been inferred for sabre-toothed species and interpreted as an adaptation to subdue large-bodied prey. However, although some sabre-tooth lineages have been classified into different ecomorphs (dirk-tooths and scimitar-tooths) the functional diversity within and between groups and the evolutionary paths leading to these specializations are unknown. Here, we use a suite of biomechanical simulations to analyse key functional parameters (mandibular gape angle, bending strength, bite force) to compare the functional performance of different groups and to quantify evolutionary rates across sabre-tooth vertebrates. Our results demonstrate a remarkably high functional diversity between sabre-tooth lineages and that different cranial function and prey killing strategies evolved within clades. Moreover, different biomechanical adaptations in coexisting sabre-tooth species further suggest that this functional diversity was at least partially driven by niche partitioning.

Impact of International Monetary Fund programs on child health.

Parental education is located at the center of global efforts to improve child health. In a developing-country context, the International Monetary Fund (IMF) plays a crucial role in determining how governments allocate scarce resources to education and public health interventions. Under reforms mandated by IMF structural adjustment programs, it may become harder for parents to reap the benefits of their education due to wage contraction, welfare retrenchment, and generalized social insecurity. This study assesses how the protective effect of education changes under IMF programs, and thus how parents' ability to guard their children's health is affected by structural adjustment. We combine cross-sectional stratified data (countries, 67; children, 1,941,734) from the Demographic and Health Surveys and the Multiple Indicator Cluster Surveys. The sample represents ∼2.8 billion (about 50%) of the world's population in year 2000. Based on multilevel models, our findings reveal that programs reduce the protective effect of parental education on child health, especially in rural areas. For instance, in the absence of IMF programs, living in an household with educated parents reduces the odds of child malnourishment by 38% [odds ratio (OR), 0.62; 95% CI, 0.66-0.58]; in the presence of programs, this drops to 21% (OR, 0.79; 95% CI, 0.86-0.74). In other words, the presence of IMF conditionality decreases the protective effect of parents' education on child malnourishment by no less than 17%. We observe similar adverse effects in sanitation, shelter, and health care access (including immunization), but a beneficial effect in countering water deprivation.

Does exceptional preservation distort our view of disparity in the fossil record?

How much of evolutionary history is lost because of the unevenness of the fossil record? Lagerstätten, sites which have historically yielded exceptionally preserved fossils, provide remarkable, yet distorting insights into past life. When examining macroevolutionary trends in the fossil record, they can generate an uneven sampling signal for taxonomic diversity; by comparison, their effect on morphological variety (disparity) is poorly understood. We show here that lagerstätten impact the disparity of ichthyosaurs, Mesozoic marine reptiles, by preserving higher diversity and more complete specimens. Elsewhere in the fossil record, undersampled diversity and more fragmentary specimens produce spurious results. We identify a novel effect, that a taxon moves towards the centroid of a Generalized Euclidean dataset as its proportion of missing data increases. We term this effect 'centroid slippage', as a disparity-based analogue of phylogenetic stemward slippage. Our results suggest that uneven sampling presents issues for our view of disparity in the fossil record, but that this is also dependent on the methodology used, especially true with widely used Generalized Euclidean distances. Mitigation of missing cladistic data is possible by phylogenetic gap filling, and heterogeneous effects of lagerstätten on disparity may be accounted for by understanding the factors affecting their spatio-temporal distribution.

cuRRBS: simple and robust evaluation of enzyme combinations for reduced representation approaches.

DNA methylation is an important epigenetic modification in many species that is critical for development, and implicated in ageing and many complex diseases, such as cancer. Many cost-effective genome-wide analyses of DNA modifications rely on restriction enzymes capable of digesting genomic DNA at defined sequence motifs. There are hundreds of restriction enzyme families but few are used to date, because no tool is available for the systematic evaluation of restriction enzyme combinations that can enrich for certain sites of interest in a genome. Herein, we present customised Reduced Representation Bisulfite Sequencing (cuRRBS), a novel and easy-to-use computational method that solves this problem. By computing the optimal enzymatic digestions and size selection steps required, cuRRBS generalises the traditional MspI-based Reduced Representation Bisulfite Sequencing (RRBS) protocol to all restriction enzyme combinations. In addition, cuRRBS estimates the fold-reduction in sequencing costs and provides a robustness value for the personalised RRBS protocol, allowing users to tailor the protocol to their experimental needs. Moreover, we show in silico that cuRRBS-defined restriction enzymes consistently out-perform MspI digestion in many biological systems, considering both CpG and CHG contexts. Finally, we have validated the accuracy of cuRRBS predictions for single and double enzyme digestions using two independent experimental datasets.

How structural adjustment programs affect inequality: A disaggregated analysis of IMF conditionality, 1980-2014.

This article highlights an important yet insufficiently understood international-level determinant of inequality in the developing world: structural adjustment programs by the International Monetary Fund (IMF). Studying a panel of 135 countries for the period 1980 to 2014, we examine income inequality using multivariate regression analysis corrected for non-random selection into both IMF programs and associated policy reforms (known as 'conditionality'). We find that, overall, policy reforms mandated by the IMF increase income inequality in borrowing countries. We also test specific pathways linking IMF programs to inequality by disaggregating conditionality by issue area. Our analyses indicate adverse distributional consequences for four policy areas: fiscal policy reforms that restrain government expenditure, external sector reforms stipulating trade and capital account liberalization, financial sector reforms entailing inflation-control measures, and reforms that restrict external debt. These effects occur one year after the incidence of an IMF program, and persist in the medium term. Taken together, our findings suggest that the IMF's recent attention to inequality neglects the multiple ways through which the organization's own policy advice has contributed to inequality in the developing world.

Morphological innovation did not drive diversification in Mesozoic-Cenozoic brachiopods.

Over long spans of geological time, various groups of organisms may wax and wane, experiencing times of apparent success and contraction. These rises and falls are often said to reflect either opportunities created by climate change or the relative success of innovative characteristics. Phylum Brachiopoda was one of the most successful marine clades before the Permian/Triassic mass extinction (PTME), but after this event, they became marginal components of marine communities through to the present day. How brachiopod morphological innovations reacted to swiftly declining diversity has long remained poorly understood. Here we analyse morphological evolution over the 300 Myr (Permian-Quaternary) history of the four major Mesozoic-Cenozoic brachiopod orders (Terebratulida, Rhynchonellida, Spiriferinida, Athyridida). Unexpectedly, their disparities reached or exceeded pre-PTME levels, but were decoupled from generic richness, which was generally low. Distribution of taxa in morphospace and shifts in centroid indicate that all four orders exploited new morphospaces when adapting to post-Permian environments. A comparison of morphospace occupation and diversity evolution suggests that the high extinction rate of brachiopods and the limited diversification of new forms may have accounted for the depauperate nature of modern-day brachiopods.

Predatory synapsid ecomorphology signals growing dynamism of late Palaeozoic terrestrial ecosystems.

Terrestrial ecosystems evolved substantially through the Palaeozoic, especially the Permian, gaining much new complexity, especially among predators. Key among these predators were non-mammalian synapsids. Predator ecomorphology reflect interactions with prey and competitors, which are key controls on carnivore diversity and ecology. Therefore, carnivorous synapsids may offer insight on wider ecological evolution as the first complex, tetrapod-dominated, terrestrial ecosystems formed through the late Palaeozoic. Using morphometric and phylogenetic comparative methods, we chart carnivorous synapsid trophic morphology from the latest Carboniferous to the earliest Triassic (307-251.2 Ma). We find a major morphofunctional shift in synapsid carnivory between the early and middle Permian, via the addition of new feeding modes increasingly specialised for greater biting power or speed that captures the growing antagonism and dynamism of terrestrial tetrapod predator-prey interactions. The further evolution of new hypo- and hypercarnivorous synapsids highlight the nascent intrinsic pressures and complexification of terrestrial ecosystems across the mid-late Permian.

Locomotion and the early Mesozoic success of Archosauromorpha.

The Triassic was a time of ecological upheaval as life recovered from the Permian-Triassic mass extinction. Archosauromorphs were a key component of the recovery, diversifying substantially during the Triassic and encompassing the origins of dinosaurs, pterosaurs and crocodylomorphs. Here, we explore the evolution of locomotion in Archosauromorpha to test whether dinosaurs show any distinctive locomotory features that might explain their success. We implement geometric morphometrics on limb bone shapes and use limb ratios to calculate bipedality and cursoriality metrics. We find that the Avemetatarsalia (dinosaurs, pterosaurs and relatives) exhibit more variable limb form and limb ratios than any other group, indicating a wider range of locomotory modes. The earliest avemetatarsalians were bipedal and cursorial, and their range of form increased through the Triassic with notable diversification shifts following extinction events. This is especially true of dinosaurs, even though these changes cannot be discriminated from a stochastic process. By contrast, the Pseudosuchia (crocodilians and relatives) were more restricted in limb form and locomotor mode with disparity decreasing through time, suggesting more limited locomotor adaptation and vulnerability to extinction. Perhaps the greater locomotor plasticity of dinosaurs gave them a competitive advantage in the changing climates of the Late Triassic.

Contrasting macroevolutionary patterns in pelagic tetrapods across the Triassic-Jurassic transition.

The iconic marine raptorial predators Ichthyosauria and Eosauropterygia co-existed in the same ecosystems throughout most of the Mesozoic Era, facing similar evolutionary pressures and environmental perturbations. Both groups seemingly went through a massive macroevolutionary bottleneck across the Triassic-Jurassic (T/J) transition that greatly reduced their morphological diversity, leaving pelagic lineages as the only survivors. However, analyses of marine reptile disparity across the T/J transition have usually employed coarse morphological and temporal data. We comprehensively compare the evolution of ichthyosaurian and eosauropterygian morphology and body size across the Middle Triassic to Early Jurassic interval and find contrasting macroevolutionary patterns. The ecomorphospace of eosauropterygians predominantly reflects a strong phylogenetic signal, resulting in the clustering of three clades with clearly distinct craniodental phenotypes, suggesting 'leaps' towards novel feeding ecologies. Ichthyosaurian diversification lacks a discernible evolutionary trend, as we find evidence for a wide overlap of craniodental morphologies between Triassic and Early Jurassic forms. The temporal evolution of ecomorphological disparity, fin shape and body size of eosauropterygians and ichthyosaurians during the Late Triassic does not support the hypothesis of an abrupt macroevolutionary bottleneck near the T/J transition. Rather, an important turnover event should be sought earlier, during times of rapid sea level falls.

scEpiAge: an age predictor highlighting single-cell ageing heterogeneity in mouse blood.

Ageing is the accumulation of changes and decline of function of organisms over time. The concept and biomarkers of biological age have been established, notably DNA methylation-based clocks. The emergence of single-cell DNA methylation profiling methods opens the possibility of studying the biological age of individual cells. Here, we generate a large single-cell DNA methylation and transcriptome dataset from mouse peripheral blood samples, spanning a broad range of ages. The number of genes expressed increases with age, but gene-specific changes are small. We next develop scEpiAge, a single-cell DNA methylation age predictor, which can accurately predict age in (very sparse) publicly available datasets, and also in single cells. DNA methylation age distribution is wider than technically expected, indicating epigenetic age heterogeneity and functional differences. Our work provides a foundation for single-cell and sparse data epigenetic age predictors, validates their functionality and highlights epigenetic heterogeneity during ageing.