A research synthesis of humans, animals, and environmental compartments exposed to PFAS: A systematic evidence map and bibliometric analysis of secondary literature.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are a class of widely used anthropogenic chemicals. Concerns regarding their persistence and potential adverse effects have led to multiple secondary research publications. Here, we aim to assess the resulting evidence base in the systematic secondary literature by examining research gaps, evaluating the quality of reviews, and exploring interdisciplinary connections. METHODS: This study employed a systematic evidence-mapping approach to assess the secondary literature on the biological, environmental, and medical aspects of exposure to 35 fluorinated compounds. The inclusion criteria encompassed systematic reviews published in peer-reviewed journals, pre-prints, and theses. Comprehensive searches across electronic databases and grey literature identified relevant reviews. Data extraction and synthesis involved mapping literature content and narrative descriptions. We employed a modified version of the AMSTAR2 checklist to evaluate the methodological rigour of the reviews. A bibliometric data analysis uncovered patterns and trends in the academic literature. A research protocol for this study was previously pre-registered (osf.io/2tpn8) and published (Vendl et al., Environment International 158 (2022) 106973). The database is freely accessible through the interactive and user-friendly web application of this systematic evidence map at https://hi-this-is-lorenzo.shinyapps.io/PFAS_SEM_Shiny_App/. RESULTS: Our map includes a total of 175 systematic reviews. Over the years, there has been a steady increase in the annual number of publications, with a notable surge in 2021. Most reviews focused on human exposure, whereas environmental and animal-related reviews were fewer and often lacked a rigorous systematic approach to literature search and screening. Review outcomes were predominantly associated with human health, particularly with reproductive and children's developmental health. Animal reviews primarily focused on studies conducted in controlled laboratory settings, and wildlife reviews were characterised by an over-representation of birds and fish species. Recent reviews increasingly incorporated quantitative synthesis methodologies. The methodological strengths of the reviews included detailed descriptions of study selection processes and disclosure of potential conflicts of interest. However, weaknesses were observed in the critical lack of detail in reporting methods. A bibliometric analysis revealed that the most productive authors collaborate within their own country, leading to limited and clustered international collaborations. CONCLUSIONS: In this overview of the available systematic secondary literature, we map literature content, assess reviews' methodological quality, highlight data gaps, and draw research network clusters. We aim to facilitate literature reviews, guide future research initiatives, and enhance opportunities for cross-country collaboration. Furthermore, we discuss how this systematic evidence map and its publicly available database benefit scientists, regulatory agencies, and other stakeholders by providing access to current systematic secondary literature on PFAS exposure.

Synthesis of sexual selection: a systematic map of meta-analyses with bibliometric analysis.

Sexual selection has been a popular subject within evolutionary biology because of its central role in explaining odd and counterintuitive traits observed in nature. Consequently, the literature associated with this field of study became vast. Meta-analytical studies attempting to draw inferences from this literature have now accumulated, varying in scope and quality, thus calling for a synthesis of these syntheses. We conducted a systematic literature search to create a systematic map with a report appraisal of meta-analyses on topics associated with sexual selection, aiming to identify the conceptual and methodological gaps in this secondary literature. We also conducted bibliometric analyses to explore whether these gaps are associated with the gender and origin of the authors of these meta-analyses. We included 152 meta-analytical studies in our systematic map. We found that most meta-analyses focused on males and on certain animal groups (e.g. birds), indicating severe sex and taxonomic biases. The topics in these studies varied greatly, from proximate (e.g. relationship of ornaments with other traits) to ultimate questions (e.g. formal estimates of sexual selection strength), although the former were more common. We also observed several common methodological issues in these studies, such as lack of detailed information regarding searches, screening, and analyses, which ultimately impairs the reliability of many of these meta-analyses. In addition, most of the meta-analyses' authors were men affiliated to institutions from developed countries, pointing to both gender and geographical authorship biases. Most importantly, we found that certain authorship aspects were associated with conceptual and methodological issues in meta-analytical studies. Many of our findings might simply reflect patterns in the current state of the primary literature and academia, suggesting that our study can serve as an indicator of issues within the field of sexual selection at large. Based on our findings, we provide both conceptual and analytical recommendations to improve future studies in the field of sexual selection.

Air pollution disproportionately impairs beneficial invertebrates: a meta-analysis.

Air pollution has the potential to disrupt ecologically- and economically-beneficial services provided by invertebrates, including pollination and natural pest regulation. To effectively predict and mitigate this disruption requires an understanding of how the impacts of air pollution vary between invertebrate groups. Here we conduct a global meta-analysis of 120 publications comparing the performance of different invertebrate functional groups in unpolluted and polluted atmospheres. We focus on the pollutants ozone, nitrogen oxides, sulfur dioxide and particulate matter. We show that beneficial invertebrate performance is reduced by air pollution, whereas the performance of plant pest invertebrates is not significantly affected. Ozone pollution has the most detrimental impacts, and these occur at concentrations below national and international air quality standards. Changes in invertebrate performance are not dependent on air pollutant concentrations, indicating that even low levels of pollution are damaging. Predicted increases in tropospheric ozone could result in unintended consequences to global invertebrate populations and their valuable ecological services.

Supporting study registration to reduce research waste.

An estimated 82-89% of ecological research and 85% of medical research has limited or no value to the end user because of various inefficiencies. We argue that registration and registered reports can enhance the quality and impact of ecological research. Drawing on evidence from other fields, chiefly medicine, we support our claim that registration can reduce research waste. However, increasing registration rates, quality and impact will be very slow without coordinated effort of funders, publishers and research institutions. We therefore call on them to facilitate the adoption of registration by providing adequate support. We outline several aspects to be considered when designing a registration system that would best serve the field of ecology. To further inform the development of such a system, we call for more research to identify the causes of low registration rates in ecology. We suggest short- and long-term actions to bolster registration and reduce research waste.

A systematic review and meta-analysis of unimodal and multimodal predation risk assessment in birds.

Despite a wealth of studies documenting prey responses to perceived predation risk, researchers have only recently begun to consider how prey integrate information from multiple cues in their assessment of risk. We conduct a systematic review and meta-analysis of studies that experimentally manipulated perceived predation risk in birds and evaluate support for three alternative models of cue integration: redundancy/equivalence, enhancement, and antagonism. One key insight from our analysis is that the current theory, generally applied to study cue integration in animals, is incomplete. These theories specify the effects of increasing information level on mean, but not variance, in responses. In contrast, we show that providing multiple complementary cues of predation risk simultaneously does not affect mean response. Instead, as information richness increases, populations appear to assess risk more accurately, resulting in lower among-population variance in response to manipulations of perceived predation risk. We show that this may arise via a statistical process called maximum-likelihood estimation (MLE) integration. Our meta-analysis illustrates how explicit consideration of variance in responses can yield important biological insights.

Leveraging AI to improve evidence synthesis in conservation.

Systematic evidence syntheses (systematic reviews and maps) summarize knowledge and are used to support decisions and policies in a variety of applied fields, from medicine and public health to biodiversity conservation. However, conducting these exercises in conservation is often expensive and slow, which can impede their use and hamper progress in addressing the current biodiversity crisis. With the explosive growth of large language models (LLMs) and other forms of artificial intelligence (AI), we discuss here the promise and perils associated with their use. We conclude that, when judiciously used, AI has the potential to speed up and hopefully improve the process of evidence synthesis, which can be particularly useful for underfunded applied fields, such as conservation science.

Maternal transfer of per- and polyfluoroalkyl substances (PFAS) in wild birds: A systematic review and meta-analysis.

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals widely used in consumer products. PFAS can accumulate in animal tissues, resulting in biomagnification and adverse effects on wildlife, such as reproductive impairment. In bird species, PFAS are transferred from mothers to eggs along with essential nutrients and may affect embryo development. However, the extent of maternal PFAS transfer across different species and compounds remains poorly understood. Here, we conducted a systematic review and meta-analysis to quantify maternal PFAS transfer in wild birds and investigate potential sources of variation. We tested the moderating effects of compounds' physicochemical properties and biological traits of studied birds. The dataset included 505 measurements of PFAS concentration and 371 effect sizes derived from 13 studies on 16 bird species and 25 compounds. Overall, across all studies and species, we found a 41% higher concentration of PFAS in offspring than in mothers. Specifically, contaminants were concentrated in the yolk, longer and heavier compounds showed preferential transfer, larger clutch size was associated with decreased PFAS transfer and a higher transfer rate was shown in species with piscivorous and opportunistic/diverse diets. A validation assessment showed good robustness of the overall meta-analytic result. Given the crucial role of birds in maintaining ecological balance, this research article has relevant implications for modelling the impacts of PFAS on wildlife, ecosystems, and human health.

The essential role of architectural noncoding RNA Neat1 in cold-induced beige adipocyte differentiation in mice.

Neat1 is an architectural RNA that provides the structural basis for nuclear bodies known as paraspeckles. Although the assembly processes by which Neat1 organizes paraspeckle components are well-documented, the physiological functions of Neat1 are not yet fully understood. This is partly because Neat1 knockout (KO) mice, lacking paraspeckles, do not exhibit overt phenotypes under normal laboratory conditions. During our search for conditions that elicit clear phenotypes in Neat1 KO mice, we discovered that the differentiation of beige adipocytes-inducible thermogenic cells that emerge upon cold exposure-is severely impaired in these mutant mice. Neat1_2, the architectural isoform of Neat1, is transiently upregulated during the early stages of beige adipocyte differentiation, coinciding with increased paraspeckle formation. Genes with altered expression during beige adipocyte differentiation typically cluster at specific chromosomal locations, some of which move closer to paraspeckles upon cold exposure. These observations suggest that paraspeckles might coordinate the regulation of these gene clusters by controlling the activity of certain transcriptional condensates that coregulate multiple genes. We propose that our findings highlight a potential role for Neat1 and paraspeckles in modulating chromosomal organization and gene expression, potentially crucial processes for the differentiation of beige adipocytes.

Realism and robustness require increased sample size when studying both sexes.

A recent article claimed that researchers need not increase the overall sample size for a study that includes both sexes. This Formal Comment points out that that study assumed two sexes to have the same variance, and explains why this is a unrealistic assumption.

Influence of habitat features on the colonisation of native and non-indigenous species.

Marine artificial structures provide substrates on which organisms can settle and grow. These structures facilitate establishment and spread of non-indigenous species, in part due to their distinct physical features (substrate material, movement, orientation) compared to natural habitat analogues such as rocky shores, and because following construction, they have abundant resources (space) for species to colonise. Despite the perceived importance of these habitat features, few studies have directly compared distributions of native and non-indigenous species or considered how functional identity and associated environmental preferences drive associations. We undertook a meta-analysis to investigate whether colonisation of native and non-indigenous species varies between artificial structures with features most closely resembling natural habitats (natural substrates, fixed structures, surfaces oriented upwards) and those least resembling natural habitats (artificial materials, floating structures, downfacing or vertical surfaces), or whether functional identity is the primary driver of differences. Analyses were done at global and more local (SE Australia) scales to investigate if patterns held regardless of scale. Our results suggest that functional group (i.e., algae, ascidians. barnacles, bryozoans, polychaetes) rather than species classification (i.e., native or non-indigenous) are the main drivers of differences in communities between different types of artificial structures. Specifically, there were differences in the abundance of ascidians, barnacles, and polychaetes between (1) upfacing and downfacing/vertical surfaces, and (2) floating and fixed substrates. When differences were detected, taxa were most abundant on features least resembling natural habitats. Results varied between global and SE Australian analyses, potentially due to reduced variability across studies in the SE Australian dataset. Thus, the functional group and associated preferences of the highest threat NIS in the area should be considered in design strategies (e.g., ecological engineering) to limit their establishment on newly built infrastructure.

Long noncoding RNA Malat1 protects against osteoporosis and bone metastasis.

MALAT1, one of the few highly conserved nuclear long noncoding RNAs (lncRNAs), is abundantly expressed in normal tissues. Previously, targeted inactivation and genetic rescue experiments identified MALAT1 as a suppressor of breast cancer lung metastasis. On the other hand, Malat1-knockout mice are viable and develop normally. On a quest to discover the fundamental roles of MALAT1 in physiological and pathological processes, we find that this lncRNA is downregulated during osteoclastogenesis in humans and mice. Remarkably, Malat1 deficiency in mice promotes osteoporosis and bone metastasis of melanoma and mammary tumor cells, which can be rescued by genetic add-back of Malat1. Mechanistically, Malat1 binds to Tead3 protein, a macrophage-osteoclast-specific Tead family member, blocking Tead3 from binding and activating Nfatc1, a master regulator of osteoclastogenesis, which results in the inhibition of Nfatc1-mediated gene transcription and osteoclast differentiation. Notably, single-cell transcriptome analysis of clinical bone samples reveals that reduced MALAT1 expression in pre-osteoclasts and osteoclasts is associated with osteoporosis and metastatic bone lesions. Altogether, these findings identify Malat1 as a lncRNA that protects against osteoporosis and bone metastasis.

The ABC of academic writing: non-native speakers' perspective.

Academic writing is difficult, especially for non-native English speakers. We share a perspective on writing with a set of heuristics called the Writing Alphabet, consisting of Accurate, Brief, Clear, Dynamic, Engaging, Flowing, Goal, Habit, and Investment. These points can help struggling writers identify issues and, importantly, internalise good writing practices.

Systematic approaches to assessing high-temperature limits to fertility in animals.

Critical thermal limits (CTLs) gauge the physiological impact of temperature on survival or critical biological function, aiding predictions of species range shifts and climatic resilience. Two recent Drosophila species studies, using similar approaches to determine temperatures that induce sterility (thermal fertility limits [TFLs]), reveal that TFLs are often lower than CTLs and that TFLs better predict both current species distributions and extinction probability. Moreover, many studies show fertility is more sensitive at less extreme temperatures than survival (thermal sensitivity of fertility [TSF]). These results present a more pessimistic outlook on the consequences of climate change. However, unlike CTLs, TFL data are limited to Drosophila, and variability in TSF methods poses challenges in predicting species responses to increasing temperature. To address these data and methodological gaps, we propose 3 standardized approaches for assessing thermal impacts on fertility. We focus on adult obligate sexual terrestrial invertebrates but also provide modifications for other animal groups and life-history stages. We first outline a "gold-standard" protocol for determining TFLs, focussing on the effects of short-term heat shocks and simulating more frequent extreme heat events predicted by climate models. As this approach may be difficult to apply to some organisms, we then provide a standardized TSF protocol. Finally, we provide a framework to quantify fertility loss in response to extreme heat events in nature, given the limitations in laboratory approaches. Applying these standardized approaches across many taxa, similar to CTLs, will allow robust tests of the impact of fertility loss on species responses to increasing temperatures.

The early macrophage response to pathogens requires dynamic regulation of the nuclear paraspeckle.

To ensure a robust immune response to pathogens without risking immunopathology, the kinetics and amplitude of inflammatory gene expression in macrophages need to be exquisitely well controlled. There is a growing appreciation for stress-responsive membraneless organelles (MLOs) regulating various steps of eukaryotic gene expression in response to extrinsic cues. Here, we implicate the nuclear paraspeckle, a highly ordered biomolecular condensate that nucleates on the Neat1 lncRNA, in tuning innate immune gene expression in murine macrophages. In response to a variety of innate agonists, macrophage paraspeckles rapidly aggregate (0.5 h poststimulation) and disaggregate (2 h poststimulation). Paraspeckle maintenance and aggregation require active transcription and MAPK signaling, whereas paraspeckle disaggregation requires degradation of Neat1 via the nuclear RNA exosome. In response to lipopolysaccharide treatment, Neat1 KO macrophages fail to properly express a large cohort of proinflammatory cytokines, chemokines, and antimicrobial mediators. Consequently, Neat1 KO macrophages cannot control replication of Salmonella enterica serovar Typhimurium or vesicular stomatitis virus. These findings highlight a prominent role for MLOs in orchestrating the macrophage response to pathogens and support a model whereby dynamic assembly and disassembly of paraspeckles reorganizes the nuclear landscape to enable inflammatory gene expression following innate stimuli.

A systematic evidence map and bibliometric analysis of the behavioural impacts of pesticide exposure on zebrafish.

Pesticides are indispensable in agriculture and have become ubiquitous in aquatic environments. Pesticides in natural environments can cause many negative impacts on aquatic species, ranging from mortality to sub-lethal physiological and behavioural changes. The complex sub-lethal impacts of pesticides are routinely tested on model species, with zebrafish (Danio rerio) being regularly used as a behavioural model. Although behavioural ecotoxicology research using zebrafish is increasing rapidly, we lack quantitative evidence to support which pesticides have been tested and how study designs are carried out. This shortcoming not only limits the deliberate planning for future primary studies to fill the knowledge gaps but also hinders evidence synthesis. To provide quantitative evidence of what pesticides are currently studied and what study designs are used, we combined a systematic evidence map approach and bibliometric analysis. This novel method has been coined research weaving and allows us to elicit gaps and clusters in our evidence base, whilst showing connections between authors and institutions. The methodology can be summarised in five primary steps: literature searching, screening, extraction, data analysis and bibliometric analysis. We identified four areas where research on the sub-lethal effects of pesticide exposure on zebrafish is lacking. First, some widely used pesticides, such as neonicotinoids, are understudied. Second, most studies do not report important elements of the study design, namely the sex and the life-stage of the zebrafish. Third, some behaviours, such as impacts of pesticide exposure on zebrafish cognition, are underexplored. And last, we revealed through the bibliometric analysis that most of the research is conducted in developed countries and there is limited cross country co-authorships. Upon identifying these gaps, we offer solutions for each limitation, emphasizing the importance of diverse global research output and cross-country co-authorships. Our systematic evidence map and bibliometric analysis provide valuable insights for helping to guide future research, which can be used to help support evidence-based policy decisions.

Species sensitivities to artificial light at night: A phylogenetically controlled multilevel meta-analysis on melatonin suppression.

The rapid urbanization of our world has led to a surge in artificial lighting at night (ALAN), with profound effects on wildlife. Previous research on wildlife's melatonin, a crucial mechanistic indicator and mediator, has yielded inconclusive evidence due to a lack of comparative analysis. We compiled and analysed an evidence base including 127 experiments with 437 observations across 31 wild vertebrates using phylogenetically controlled multilevel meta-analytic models. The evidence comes mainly from the effects of white light on melatonin suppression in birds and mammals. We show a 36% average decrease in melatonin secretion in response to ALAN across a diverse range of species. This effect was observed for central and peripheral melatonin, diurnal and nocturnal species, and captive and free-living populations. We also reveal intensity-, wavelength-, and timing-dependent patterns of ALAN effects. Exposure to ALAN led to a 23% rise in inter-individual variability in melatonin suppression, with important implications for natural selection in wild vertebrates, as some individuals may display higher tolerance to ALAN. The cross-species evidence has strong implications for conservation of wild populations that are subject to natural selection of ALAN. We recommend measures to mitigate harmful impacts of ALAN, such as using 'smart' lighting systems to tune the spectra to less harmful compositions.

Ecological filtering shapes the impacts of agricultural deforestation on biodiversity.

The biodiversity impacts of agricultural deforestation vary widely across regions. Previous efforts to explain this variation have focused exclusively on the landscape features and management regimes of agricultural systems, neglecting the potentially critical role of ecological filtering in shaping deforestation tolerance of extant species assemblages at large geographical scales via selection for functional traits. Here we provide a large-scale test of this role using a global database of species abundance ratios between matched agricultural and native forest sites that comprises 71 avian assemblages reported in 44 primary studies, and a companion database of 10 functional traits for all 2,647 species involved. Using meta-analytic, phylogenetic and multivariate methods, we show that beyond agricultural features, filtering by the extent of natural environmental variability and the severity of historical anthropogenic deforestation shapes the varying deforestation impacts across species assemblages. For assemblages under greater environmental variability-proxied by drier and more seasonal climates under a greater disturbance regime-and longer deforestation histories, filtering has attenuated the negative impacts of current deforestation by selecting for functional traits linked to stronger deforestation tolerance. Our study provides a previously largely missing piece of knowledge in understanding and managing the biodiversity consequences of deforestation by agricultural deforestation.

Malat1 fine-tunes bone homeostasis by orchestrating cellular crosstalk and the ß-catenin-OPG/Jagged1 pathway.

The IncRNA Malat1 was initially believed to be dispensable for physiology due to the lack of observable phenotypes in Malat1 knockout (KO) mice. However, our study challenges this conclusion. We found that both Malat1 KO and conditional KO mice in the osteoblast lineage exhibit significant osteoporosis. Mechanistically, Malat1 acts as an intrinsic regulator in osteoblasts to promote osteogenesis. Interestingly, Malat1 does not directly affect osteoclastogenesis but inhibits osteoclastogenesis in a non-autonomous manner in vivo via integrating crosstalk between multiple cell types, including osteoblasts, osteoclasts and chondrocytes. Our findings substantiate the existence of a novel remodeling network in which Malat1 serves as a central regulator by binding to ß-catenin and functioning through the ß-catenin-OPG/Jagged1 pathway in osteoblasts and chondrocytes. In pathological conditions, Malat1 significantly promotes bone regeneration in fracture healing. Bone homeostasis and regeneration are crucial to well-being. Our discoveries establish a previous unrecognized paradigm model of Malat1 function in the skeletal system, providing novel mechanistic insights into how a lncRNA integrates cellular crosstalk and molecular networks to fine tune tissue homeostasis, remodeling and repair.