Paleontology provides insights into the history of the planet, from the origins of life billions of years ago to the biotic changes of the Recent. The scope of paleontological research is as vast as it is varied, and the field is constantly evolving. In an effort to identify “Big Questions” in paleontology, experts from around the world came together to build a list of priority questions the field can address in the years ahead. The 89 questions presented herein (grouped within 11 themes) represent contributions from nearly 200 international scientists. These questions touch on common themes including biodiversity drivers and patterns, integrating data types across spatiotemporal scales, applying paleontological data to contemporary biodiversity and climate issues, and effectively utilizing innovative methods and technology for new paleontological insights. In addition to these theoretical questions, discussions touch upon structural concerns within the field, advocating for an increased valuation of specimen-based research, protection of natural heritage sites, and the importance of collections infrastructure, along with a stronger emphasis on human diversity, equity, and inclusion. These questions offer a starting point—an initial nucleus of consensus that paleontologists can expand on—for engaging in discussions, securing funding, advocating for museums, and fostering continued growth in shared research directions.

Metabolic imprinting refers to lasting metabolic changes from early-life environmental exposures, especially nutritional, that impact adult health and chronic disease risk. We investigated whether metabolic imprinting by small litter size (SL) activates interscapular brown adipose tissue (iBAT) and affects glucose and lipid metabolism, oxidative damage, and insulin resistance (IR) in young rats exposed to a high-sucrose diet (HSD) over eight weeks. Male Wistar rats (n = 48) were assigned to control (eight pups/ dam; CL) and small litter (four pups/ dam; SL) groups. Post-weaning (21 days), they were divided into four dietary groups: (i) standard diet (STD, chow diet) from CL, or (ii) SL; (iii) HSD (30% sucrose) from CL, or (iv) SL, for eight weeks. Afterward, animals were euthanized for analysis of iBAT and serum samples. HSD caused hypertrophy, IR, and oxidative damage in iBAT. However, the SL model attenuated HSD-induced IR by up-regulating p-AKT (Ser 473) and activating iBAT thermogenesis, resulting in decreased PGC1-α expression and up-regulating UCP1 expression, which contributed to iBAT hyperplasia. Additionally, SL reduced PKA activation and free fatty acid (FFA) release, decreasing the lipid oxidative damage observed in HSD-fed iBAT. These findings suggest that SL-induced metabolic imprinting enhances iBAT thermogenesis through p-AKT (Ser 473) and PGC1-α signaling, increases UCP1 expression, and reduces PKA substrates phosphorylation, decreasing FFA levels and oxidative damage following HSD exposure. While our results challenge the existing literature, we propose that the metabolic plasticity from the SL model allows rats to adapt to dietary variations and may protect against HSD-induced IR in adulthood.

Methods comprise a significant part of the knowledge engineers are taught and that they use in professional practice. However, methods have been largely neglected in discussions of the nature of engineering knowledge. In particular, methods prove to be hard to track down in the best-known and most influential typology of engineering knowledge, put forward by Walter G. Vincenti in his book What Engineers Know and How They Know It. This article discusses contemporary views of what engineering methods are and what they contain, how methods (fail to) fit into Vincenti’s analysis, and some characteristics of method knowledge. It argues that methods should be seen as a distinct type of engineering knowledge. While characterizing the knowledge that methods include can be done in different ways for different purposes, the core of method knowledge that does not fit into other categories is explicit ‘how-to’ knowledge of procedures, that draw on other types of knowledge.

In an experimental evolutionary game framework we investigate whether subjects end up in a socially efficient state. We examine two games, a game where the socially efficient state is also an equilibrium and a game which has no equilibrium in pure strategies at all. Furthermore, we distinguish between a situation in which the subjects are completely informed about the payoff function and a situation in which they are incompletely informed. We observe that subjects spend the greater part of the time at or near the efficient state. If the efficient state is an equilibrium, they spend more time there than otherwise. Furthermore, incomplete information increases the time spent at the efficient state.

Objectives: The primary aim of this study is to assess the relationship between different aspects of physical activity (PA) and dementia occurrence in older adults from Brazil.

Methods: It is a secondary analysis of the first wave data derived from the ELSI-Brazil study, a longitudinal study of aging in Brazil with a representative sample of Brazilians aged 50 years and older (n = 9,412). We employed two distinct approaches to assess PA. First, participants’ levels of PA were classified in low, moderate and high based on their reported physical exertion over the preceding seven days at the time of interview. Also, PA was classified as sufficient or not sufficient, according to the World Health Organization (WHO) recommendation. Dementia was defined as those who were 60 years and older, had a cognitive performance ≤1.5 z-score compared to a sub- sample defined as control-group, and also had an impairment in instrumental activity of daily living. Logistic regression was used to estimate the association between physical activity and dementia (crude and adjusted for age, gender, schooling, marital status, smoking and alcoholconsumption).

Results: After excluding those younger than 60 years old and had missing data to any of the variables analyzed, our sample was composed by 4,994 individuals (table 1), with a mean age of 69.7 (SD = 7 .5), 4.7 years of schooling (SD = 4.3) and 214 (4.1%) classified as living with dementia. We also found that higher levels of PA were associated with lower occurrences of dementia (table 2) (moderate OR 0.57 95% CI 0.37 –0 .90, p < 0.05; high OR 0.32 95% CI 0.19 –0.56, p < 0.001). Also, practicing the level of PA recommended by WHO had an inverse association with dementia (table 3) (OR 0.49 95% CI 0.30 – 0.79, p < 0.05).

Conclusions: The main limitation of our study is its cross-sectional nature. Therefore, we cannot determine the direction of relationships between variables. Our findings show a significant inverse association between levels of PA and dementia occurrence. Additionally, adherence to the WHO’s recommendation for PA also showed a significant inverse association with dementia occurrence. These results underscore the importance of promoting regular physical activity as a potential preventive measure against dementia among older Brazilian adults.

Objectives: Despite the increasing number of people with dementia (PWD), detection remains low worldwide. In Brazil, PWD is expected to triple by 2050, and diagnosis can be challenging, contributing to high and growing rates of underdiagnosis. At the moment, there is no national estimate of the under detection or characteristics of its distribution according to gender, age and region. We aimed to estimate the proportion of PWD not diagnosed in relation to the estimated number of PWD.

Methods: The number of diagnosed individuals were estimated based on national records of the prescription of anticholinesterases drugs (AChE) in 2022 for the treatment of mild and moderate stages of Alzheimer’s Disease (AD) held by the Unified Health System (SUS). Data were obtained from ftp://ftp.datasus.gov.br and drugs were dispensed according to the national clinical protocol. Studies from the national literature were consulted to estimate: (i) the number of people currently diagnosed with mild and moderate AD; (ii) the proportion of those who obtain AChE from SUS; (iii) the proportion of those who do not take AChE; and (iv) the proportion of AD related to other dementias. We assumed that the under-detection rate of AD would be similar to other dementias and 70% of the diagnosed AD individuals obtain AChE from SUS.

Results: More than 80% of the PWD 60+ are undetected (88.7%, 95% CI = 88.6–88.7). The poorest regions had higher rates (94.6% 95%, CI = 94.5–94.6) than the richest (84.8%, 95% CI = 84.7–84.8). Men had higher rates (89.8%, 95% CI = 89.7–89.9) than women (87.4%, 95% CI = 87.4–87.5). The youngest age group (60-64) had the highest rate (94.6%, 95% CI = 94.5–94.7) which decreased until 85–89 (84.3%, 95% CI = 84.2–84.4), before increasing again to 91.1% (95% CI = 91.0–91.2) among 90+.

Conclusions: Dementia under detection in Brazil is among the highest in the world. Fast populational aging and the highest rates among the youngest individuals are of concern as it may be related to late diagnosis. Gender and regional disparities also need to be considered when developing health policies.

The developmental origins of health and disease hypothesis have highlighted the link between early life environment and long-term health outcomes in offspring. For example, maternal protein restriction during pregnancy and lactation can result in adverse metabolic and cognitive outcomes in offspring postnatal. Hence, in the present study, we assess whether an isocaloric low-protein diet (ILPD) affects the fatty acid profile in breast milk, the hippocampal synaptophysin (Syn) ratio, and the oxidative stress markers in the neonatal stage of male and female offspring. The aim of this work was to assess the effect of an ILPD on the fatty acid profile in breast milk, quantified the hippocampal synaptophysin (Syn) ratio and oxidative stress markers in neonatal stage of male and female offspring. Female Wistar rats were fed with either a control diet or an ILPD during gestation to day 10 of lactation. Oxidative stress markers were assessed in serum and liver. All quantifications were done at postnatal day 10. The results showed: ILPD led to decreases of 38.5% and 17.4% in breast milk volume and polyunsaturated fatty acids content. Significant decreases of hippocampal Syn ratio in male offspring (decreases of 98% in hippocampal CA1 pyramidal and CA1 oriens, 83%, stratum pyramidal in CA3, 80%, stratum lucidum in CA3, and 81% stratum oriens in CA3). Male offspring showed an increase in pro-oxidant status in serum and liver. Thus, the data suggest that male offspring are more vulnerable than females to an ILPD during gestation and lactation.

The recent reinforcement of CoV surveillance in animals fuelled by the COVID-19 pandemic provided increasing evidence that mammals other than bats might hide further diversity and play critical roles in human infectious diseases. This work describes the results of a two-year survey carried out in Italy with the double objective of uncovering CoV diversity associated with wildlife and of excluding the establishment of a reservoir for SARS-CoV-2 in particularly susceptible or exposed species. The survey targeted hosts from five different orders and was harmonised across the country in terms of sample size, target tissues, and molecular test. Results showed the circulation of 8 CoV species in 13 hosts out of the 42 screened. Coronaviruses were either typical of the host species/genus or normally associated with their domestic counterpart. Two novel viruses likely belonging to a novel CoV genus were found in mustelids. All samples were negative for SARS-CoV-2, with minimum detectable prevalence ranging between 0.49% and 4.78% in the 13 species reaching our threshold sample size of 59 individuals. Considering that within-species transmission in white-tailed deer resulted in raising the prevalence from 5% to 81% within a few months, this result would exclude a sustained cycle after spillback in the tested species.

The mitotic-inhibiting herbicide pronamide controls susceptible annual bluegrass (Poa annua L.) pre- and postemergence, but in some resistant populations, postemergence activity is compromised, hypothetically due to a target-site mutation, lack of root uptake, or an unknown resistance mechanism. Three suspected pronamide-resistant (LH-R, SC-R, and SL-R) and two pronamide-susceptible (BS-S and HH-S) populations were collected from Mississippi golf courses. Dose–response experiments were conducted to confirm and quantify pronamide resistance, as well as resistance to flazasulfuron and simazine. Target sites known to confer resistance to mitotic-inhibiting herbicides were sequenced, as were target sites for herbicides inhibiting acetolactate synthase (ALS) and photosystem II (PSII). Pronamide absorption and translocation were investigated following foliar and soil applications. Dose–response experiments confirmed pronamide resistance of LH-R, SC-R, and SL-R populations, as well as instances of multiple resistance to ALS- and PSII-inhibiting herbicides. Sequencing of the α-tubulin gene confirmed the presence of a mutation that substituted isoleucine for threonine at position 239 (Thr-239-Ile) in LH-R, SC-R, SL-R, and BS-S populations. Foliar application experiments failed to identify differences in pronamide absorption and translocation between the five populations, regardless of harvest time. All populations had limited basipetal translocation—only 3% to 13% of the absorbed pronamide—across harvest times. Soil application experiments revealed that pronamide translocation was similar between SC-R, SL-R, and both susceptible populations across harvest times. The LH-R population translocated less soil-applied pronamide than susceptible populations at 24, 72, and 168 h after treatment, suggesting that reduced acropetal translocation may contribute to pronamide resistance. This study reports three new pronamide-resistant populations, two of which are resistant to two modes of action (MOAs), and one of which is resistant to three MOAs. Results suggest that both target site– and translocation-based mechanisms may be associated with pronamide resistance. Further research is needed to confirm the link between pronamide resistance and the Thr-239-Ile mutation of the α-tubulin gene.

Method development is at the heart of design research as methods are a formalised way to express knowledge about how aspects of design could or should be done. However, assuring that methods are in fact used in industry has remained a challenge. Industry will only use methods that they can understand and that they feel will give them benefit reliably. To understand the challenges involved in adopting a method, the method needs to be seen in context: it does not exist in isolation but forms a part of an ecosystem of methods for tackling related design problems. A method depends on the knowledge and skills of the practitioners using it: while a description of a method is an artefact that is a formalisation of engineering knowledge, a method in use constitutes a socio-technical system depending on the interaction of human participants with each other as well as with the description of the method, representations of design information and, often, tools for carrying out the method’s tasks. This paper argues that crucial factors in the adoption of methods include how well they are described and how convincingly they are evaluated. The description of a method should cover its core idea, the representations in which design information is described, the procedure to be followed, its intended use, and the tools it uses. The account of a method’s intended use should cover its purpose, the situations or product types within its scope, its coverage of kinds of problems within its scope, its expected benefit and conditions for its use. The different elements need to be evaluated separately as well as the method as an integrated whole. While verification and validation are important for some elements of methods, it is rarely possible to prove the validity of a method. Rather the developers of methods need to gather sufficient evidence that a method will work within a clearly articulated scope. Most design methods do not have binary success criteria, and their usefulness in practice depends as much on simplicity and usability as on the outcomes they produce. Evaluation should focus on how well they work, and how they can be customised and improved.

Nothofagus alessandrii, categorized as Endangered on the IUCN Red List, is an endemic, deciduous tree species of the coastal range of central Chile. We assessed the effects of fire severity, invasion by the exotic fire-prone Pinus radiata, and land-cover composition and configuration of the landscape on the resilience of fragments of N. alessandrii after a mega-fire in 2017. We used remote sensing data to estimate land-use classes and cover, fire severity and invasion cover of P. radiata. We monitored forest composition and structure and post-fire responses of N. alessandrii forests in situ for 2 years after the mega-fire. In the coastal Maule region wildfires have been favoured by intense drought and widespread exotic pine plantations, increasing the ability of fire-adapted invasive species to colonize native forest remnants. Over 85% of N. alessandrii forests were moderately or severely burnt. The propagation and severity of fire was probably amplified by the exotic pines located along the edges of, or inside, the N. alessandrii fragments and the highly flammable pine plantations surrounding these fragments (> 60% of land use is pine plantations). Pinus radiata, a fire-adapted pioneer species, showed strong post-fire recruitment within the N. alessandrii fragments, especially those severely burnt. Positive feedback between climate change (i.e. droughts and heat waves), wildfires and pine invasions is driving N. alessandrii forests into an undesirable and probably irreversible state (i.e. a landscape trap). A large-scale restoration programme to design a diverse and less flammable landscape is needed to avoid the loss of these highly threatened forest ecosystems.

Tree-ring chronologies encode interannual variability in forest growth rates over long time periods from decades to centuries or even millennia. However, each chronology is a highly localized measurement describing conditions at specific sites where wood samples have been collected. The question whether these local growth variabilites are representative for large geographical regions remains an open issue. To overcome the limitations of interpreting a sparse network of sites, we propose an upscaling approach for annual tree-ring indices that approximate forest growth variability and compute gridded data products that generalize the available information for multiple tree genera. Using regression approaches from machine learning, we predict tree-ring indices in space and time based on climate variables, but considering also species range maps as constraints for the upscaling. We compare various prediction strategies in cross-validation experiments to identify the best performing setup. Our estimated maps of tree-ring indices are the first data products that provide a dense view on forest growth variability at the continental level with 0.5° and 0.0083° spatial resolution covering the years 1902–2013. Furthermore, we find that different genera show very variable spatial patterns of anomalies. We have selected Europe as study region and focused on the six most prominent tree genera, but our approach is very generic and can easily be applied elsewhere. Overall, the study shows perspectives but also limitations for reconstructing spatiotemporal dynamics of complex biological processes. The data products are available at https://www.doi.org/10.17871/BACI.248.