FEBS Letters

Climate-smart agriculture (CSA) dominates African agricultural policy discourse, yet fifteen years post-conceptualization, its transformative potential remains unrealized. Bibliometric analysis of 161 Scopus-indexed publications (2014-2025) reveals exponential field growth (31.3% annually) coupled with on technical dimensions and systemic neglect of financial mechanisms. Network analysis (VOSviewer), semantic mapping and citation bibliometrics expose cognitive oligopolisation--wherein 1.8% of authors generate 45% of output--geographical fragmentation into weakly connected regional clusters, and critical underrepresentation of the vulnerable Sahel. Despite 46.6% of publications addressing economic themes, merely 5.6% rigorously integrate financial analysis with adoption variables; terms including investment, cost-benefit and climate finance remain absent from major semantic clusters. The concept of structural financial ambiguity is introduced to characterize the maintenance of CSA in operational indeterminacy through academic discourse that substitutes description for actionable financial theorization. Paradigmatic transformation conditions are identified through emerging scholarship employing discrete choice experiments and cost-benefit evaluations to construct requisite knowledge foundations. Findings indicate that without comprehensive theorization of microfinance, digital finance, index-based insurance and payments for environmental services, international climate commitments risk implementation failure due to absence of scientifically validated financial instruments rather than technical solutions.

Research using model organisms to tackle questions in life sciences and biomedical sciences has been in the spotlight of scientific literature for the better part of the twentieth century. This attention has perceptibly faded over the last twenty years, at least. We set to document this process by examining the publication trends of 48 journals encompassing a broad range of topics and impact factors for eight classic model organisms. We found that the representation of model-organism research has been in continuous decline in the last three decades, with a significant acceleration since 2010. We investigated the origin of the change, from the size of research communities to the shifts in topics and in use of model organisms. While model organism communities appear stable, model organism papers are outpaced by the rest of scientific literature. Also, among papers using model organisms, we note a progressive shift toward applied research, with differences between different model organism species. The mouse, in particular, logically remains the preferred system to study diseases, while non-mouse model organisms continue to be used predominantly to dissect mechanisms of life. We reflect on the consequences of the fading representation that we measured for the future of life sciences. Fundamentally, model organisms afford a direct access to causality in life sciences and their fading from the picture may impact life sciences as a whole. More pragmatically, it will also affect funding, and thereby jeopardizes the maintenance of model organism resources such as repositories built over decades.

Deoxyribonucleic acid (DNA) stands as one of the most foundational concepts in life sciences, essential for students to master. However, when surveyed about the forces that stabilize the double-stranded DNA structure, many students exhibited a conceptual bias-- favoring base pairing as the primary stabilizing force, while overlooking the equally critical role of base stacking interactions. To investigate the origins of this misconception, students conducted a comprehensive analysis of 35 widely used textbooks. Their findings revealed that one-third of these texts explicitly emphasized base pairing as the sole stabilizing force in their written content. Furthermore, two-thirds of the textbook contained illustrations that reinforced this bias, visually highlighting base pairing while neglecting base stacking. Recognizing this bias, students embarked on a literature review to gain a more accurate and nuanced understanding of DNA stabilization. Through this research, we identified three concept areas--DNA structure and function, environmental effects on DNA, and DNA-protein interactions--to illustrate how base pairing and base stacking work in concert to stabilize the antiparallel double helical structure of DNA. This interplay between base pairing and base stacking is crucial not only for the structural integrity of DNA, but also for its biological functionality. By addressing this conceptual bias, we aim to promote a more balanced and scientifically accurate representation of DNA stabilization in educational materials.

The Acute Respiratory Distress Syndrome (ARDS) is a life-threatening cause of respiratory failure, and patients who develop ARDS frequently require mechanical ventilation, which puts them at risk of developing ventilator induced lung injury (VILI). Both VILI and ARDS can induce pulmonary surfactant dysfunction, but the mechanisms are not known. Here we report a novel role for a phospholipid binding protein, Annexin A2 (AnxA2), in the regulation of surfactant composition and function following injurious ventilation. Wild type and AnxA2-/-mice were subjected to injurious ventilation and we found that AnxA2-/- mice developed stiffer lungs following VILI that was not due to differences in barrier permeability or inflammation. Furthermore, we found that pulmonary surfactant from AnxA2-/- mice had reduced surface tension lowering properties and that this was due to a reduction in 1-palmitoyl-2-oleoylphosphatidylglycerol, or POPG. Quantitative analysis of surface tension-surface area hysteresis loops obtained from surfactant isolated from AnxA2-/- mice showed a defect in phase transitions during compression. In summary, Annexin A2 regulates surfactant function during injurious ventilation and may serve as a novel therapeutic target to prevent surfactant dysfunction in patients with ARDS who require mechanical ventilation.

Over the past two decades, Higher Education Institutions have increasingly prioritised transferrable skills to enhance graduate employability. Graduate Attributes (GAs) now act as key indicators of student competencies for both learners and employers. Final-year research projects, typically high in credit value, represent capstone experiences that promote subject expertise and GA development through research, written work, and oral presentations. This study analyses pre- and post-project survey data from RQF Level 6 biomedical and biomolecular science students at a Russell Group University over four years (2019-2023). Most projects were laboratory-based, though the 2020-2021 cohort completed theirs remotely due to COVID-19. Students reflected on expectations and experiences of GA development, subject knowledge, and employability. Initial responses revealed anxiety and uncertainty, particularly among the 2020-2021 cohort, but most anticipated gains in skills and employability. Post-project feedback confirmed this, identifying critical thinking, confidence, resilience, collaboration, and future focus as key outcomes. Digital capability was notably strengthened, especially during remote delivery. The findings emphasise the importance of a shared understanding of GAs in bioscience education and the value of embedding structured reflection and preparatory support to help students recognise and articulate their evolving skills.

Intrinsically disordered proteins (IDP) or proteins with intrinsically disordered regions (IDR) perform a plethora of functions mostly in a cellular environment. As unfolded proteins, IDPs can adopt molten globule or coil ensembles of conformations. Regarding the latter the question arises whether they are describable as a self-avoiding random coil. Locally, this requires that amino acid residues sample the entire sterically allowed region of the Ramachandran plot with very similar probabilities and independent on the conformational dynamics of their neighbours. However, various lines of experimental and bioinformatic evidence suggest a more restricted, side chain and nearest neighbor dependent conformational space for individual residues. Over the last 25 years short peptides and coil libraries were employed to determine conformational propensities of amino acid residues in unfolded states. The question arises whether conformational ensembles obtained from these two sources are comparable. In this paper, a variety of metrics were used to compare Ramachandran plots of a limited number of GXYG peptides (X,Y: guest residues) with XY dimers in the coil library of Ting et al.(PLOS 6, e1000763, 2010). The results reveal major differences between corresponding plots, which might in part due to the fact that solely the influence of one of the two neighbours of a given residue is probed by the above coil library while averages were taken over the respective opposite neighbours. The presented results suggest that coil libraries alone might not be a sufficient tool for determining the characteristics of statistical coils of IDPS and IDRs alike.

Disparities in formal bioinformatics training exacerbate the global skills gap, impeding the democratized application of advanced genomic technologies. To bridge this divide, we introduce a scalable, hybrid training framework designed to rapidly accelerate regional bioinformatics capacity. We exemplify this approach through the Eastern European Bioinformatics and Genomics (EEBG) workshop series -- a cross-disciplinary initiative that pairs international faculty with local institutions to deliver modular, hands-on curricula. Functioning as a structured knowledge-transfer pipeline, the series has catalyzed a sustainable educational ecosystem, evidenced by the establishment of multiple independent summer schools across the region. The assessment of the 2025 EEBG workshop in Krakow, Poland, validates the models viability; participant metrics confirm high efficacy in skill acquisition (mean satisfaction: 4.4/5.0) and community building. Crucially, the hybrid delivery mode dismantled geographic barriers, serving as a vital mechanism for maintaining scientific continuity for researchers facing displacement and crisis. Synthesizing these outcomes, we define the core features of a replicable blueprint for scientific readiness in resource-constrained environments. We conclude by presenting a strategic roadmap -- organized around infrastructure standardization, governance sustainability, and geographical expansion -- for adapting this regional proof-of-concept into a global export-ready model, offering a critical path toward ensuring universal access to genomic innovation.

If youve ever complained about a species name thats a mouthful--say, the soldier fly Parastratiosphecomyia stratiosphecomyioides or the myxobacterium Myxococcus llanfairpwllgwyngyllgogerychwyrndrobwllllantysiliogogogochensis--youre in very good company. But could the readability of binomial scientific names cause more than complaints? Could it influence how much species are studied and talked about? We examined a random sample of 3,019 species names spanning 29 phyla/divisions. We tested whether name length and reading difficulty are associated with species representation in the scientific literature (measured via literature mentions) and their visibility to the public (measured via Wikipedia pageviews). Both species name traits showed significant negative relationships with literature mentions and Wikipedia reads. Increasing name length from 10 to 30 characters is associated with a 66% decrease in expected mentions and a 65% decrease in Wikipedia reads, while shifting from the most to the least readable name in the dataset corresponds to 53% and 76% decreases. These patterns are consistent with something familiar: the fickleness of human attention, responding to features of the world that are far from rational. While creativity in naming is a cherished part of taxonomy, a touch of orthographic restraint may ultimately benefit both science and the species themselves--especially among understudied uncharismatic taxa.

It is well established that Staphylococcus aureus can incorporate straight-chain unsaturated fatty acids (SCUFAs) into its lipids in addition to the normally biosynthesized branched-chain and straight-chain saturated fatty acids. Incorporation of oleic acid into S. aureus lipids has recently been shown to significantly enhance S. aureus growth at low temperatures due to the greater fluidity imparted to the membrane. Here, we show that low-temperature growth of S. aureus is not limited to oleic acid but enhanced also by various antimicrobial SCUFAs when present at low concentrations. A fakA-deficient strain did not show SCUFA-induced growth stimulation, which indicates that the fatty acid kinase is necessary for SCUFA incorporation into membrane lipids to promote low-temperature growth. Determination of total lipid fatty acid composition showed that incorporated SCUFAs make up [~]12% or less of the total fatty acids. Lipidomic investigations revealed elevated synthesis of diglucosyldiglyceride in the absence or presence of SCUFAs. SCUFAs were incorporated into diglucosyldiglyceride to a greater extent than phosphatidyglycerol at both 12 {degrees}C and 37 {degrees}C. The presence of SCUFAs at low temperatures also enhanced production of the carotenoid staphyloxanthin. The results suggest that multiple strategies are at play in the membrane adaptation of S. aureus to low temperatures. Inclusion of oleic acid in media decreased the minimum growth temperature of S. aureus, suggesting that the presence of SCUFAs in food may facilitate the growth of S. aureus at low temperature. Also, incorporation of SCUFAs into lipids may promote the disruption of the membrane by SCUFAs.

MmpL proteins play an important role in the various mechanisms associated with mycobacterial virulence. Identification of interacting protein partners required for a detailed understanding of their role remains hampered because of their large size (> 100 kDa) and the presence of twelve transmembrane domains by classical methods. In this study, we used two independent biotin proximity labelling assays (APEX2 and BioID) to define the proxisome of MmpL11 in M. smegmatis. Indeed, these techniques are performed directly in the organism of interest, allowing the detection of potentially transient or weak interactions in multiprotein complexes and preserving the subcellular structures and the presence of cofactors or post-translational modifications that can also impact protein-protein interactions. BioID leads to the biotinylation of lysine residues, whereas APEX2 leads to the biotinylation of mainly tyrosine residues; they have also been shown to have different effective labelling radii. On one hand, an interaction was detected between the cytoplasmic C-terminal domain of MmpL11 and MSMEG_0240, a protein of unknown function, using BioID. This interaction was confirmed using both MmpL11 and MSMEG_0240 as fusions with BirA and was corroborated by AlphaFold3 prediction. On the other hand, APEX2 failed to detect an interaction between MmpL11 and MSMEG_0240, probably due to the absence of accessible tyrosines. However, both approaches identified MSMEG_0940 as an additional interactant with MmpL11 that also depends on the C-terminal domain. Overall, this study demonstrates that APEX2 and BioID as complementary tools for defining the proxisome of mycobacterial proteins.

Cardiovascular diseases are the leading cause of death worldwide, accounting for approximately 30% of total mortality. Changes in post-transcriptional regulation have been correlated with the development of cardiopathies. RNA-binding proteins (RBP) are proteins capable of interacting with mRNAs, regulating their stability, localization, and translation. Here, we described CSDC2 as an RBP expressed at the final stages of cardiac differentiation using hPSCs as a model. We showed that the loss of CSDC2 impairs cardiomyocyte differentiation, while the recovery of its expression rescues the differentiation potential of these cells. We characterized the translatome of CSDC2 knockout cells during cardiac differentiation by polysome profiling. In cardiac mesoderm cells, CSDC2 interacts with ribosomal proteins. Furthermore, CSDC2 appears to be able to associate with mRNAs encoding regulators of cardiac progenitor commitment. Altogether, in this study, we describe a new role of CSDC2 in cardiomyocyte commitment using cardiac differentiation of hiPSCs.

Debates about public trust in science often contrast deficit-based models, which emphasize the role of scientific knowledge, with constructivist perspectives that highlight the coexistence of multiple epistemologies. However, both approaches tend to overlook the mechanisms that link scientific knowledge, alternative epistemic orientations, and mistrust in science. To address this gap, the study applies a multilevel structural equation model within a multidimensional framework to examine conspiratorial reasoning as a key mechanism through which scientific knowledge influences science mistrust. Using cross-national survey data from Europe during the COVID-19 pandemic, the analysis also considers how this pathway is moderated by individual cognitive, motivational, and ideological traits, as well as macro-level political, cultural and economic factors. The findings reveal that conspiratorial reasoning significantly mediates the relationship between scientific knowledge and mistrust at both individual and regional levels. Moreover, the strength of these associations is conditioned by factors like informational engagement, regional value climates, and religiosity. Overall, the results suggest that scientific knowledge serves as a conditional epistemic resource, rather than a consistent buffer against mistrust in science.

Collagen prolyl 4-hydroxylase (C-P4H) is an essential enzyme in collagen synthesis and known to be a potential target for drugs that prevent excess collagen formation. Currently known C-P4H inhibitors target the catalytic site of C-P4H, being analogues of 2-oxoglutarate (2OG). However, in mammalian cells there are many other 2OG-dependent dioxygenases with a highly similar catalytic domain, which limits the selective specificity of drugs targeting C-P4H activity. The peptide-substrate-binding (PSB) domain is unique for the C-P4H family and known to be important for the catalytic efficiency of C-P4H. Therefore, interfering with peptide binding to the PSB domain might allow more specific inhibition of the hydroxylation activity of C-P4Hs. We developed a robust FRET-based high-throughput screening assay (Z > 0.73) based on PSB-peptide interactions. This assay was used to screen a peptidomimetic library of 15614 compounds with the PSB domains of C-P4H isoforms I and II. A hit compound (OUL-PSBi-001) was identified with IC50s of 40 {micro}M and 62 {micro}M for PSB-I and PSB-II, respectively. We also showed that this compound indeed inhibits the catalytic activity of the full-length CP4H-I and -II. This FRET assay provides a new strategy for finding selective inhibitors for the treatment of fibrotic diseases and cancer.

BackgroundThe extracellular matrix (ECM) is a dynamic network that provides structural support and maintains tissue homeostasis. Collagens are the main structural components of the ECM, occupying distinct tissue compartments and serving specialized roles. Dysregulated ECM remodeling involves an imbalance between collagen production and degradation, generating neoepitope-specific fragments that can be released into circulation. Serological measurements of these fragments can be used as biomarkers of disease and have been associated with progression and mortality in different fibrotic diseases, including pulmonary fibrosis (PF). This study aimed to investigate whether these systemic biomarkers originate from human lung tissue in patients with PF and non-fibrotic controls. MethodsLung tissue was collected from patients with PF (n = 21) and non-fibrotic controls (n = 21) and processed in parallel as formalin-fixed paraffin-embedded or snap-frozen samples. Serum samples were collected from patients with PF and healthy controls (n = 21). Neoepitope-specific biomarkers reflecting type III, IV, and VI collagen production (PRO-C3, PRO-C4, and PRO-C6) and degradation (C3M, C4M, C4Ma3, and C6M) were quantified in serum and proteolytically degraded lung tissue, and their spatial distribution was assessed by immunohistochemistry in lung tissue sections. ResultsAll collagen remodeling biomarkers were significantly increased in serum of patients with PF compared with healthy controls (PRO-C3: p = 0.0006, all others: p < 0.0001). Collagen degradation fragments (C3M, C4M, and C6M) could be generated and released from both non-fibrotic and fibrotic human lung tissue following proteolytic cleavage with pepsin, collagenase, and/or MMP-9. All biomarkers were detected in lung tissue by immunohistochemical staining, with widespread distribution of type III and IV collagen fragments, whereas type VI collagen (PRO-C6) production showed a more compartment-specific pattern. ConclusionsThese findings demonstrated that neoepitope-specific collagen remodeling biomarkers, usually detected in circulation, are present and can be released from human lung tissue. Their spatial distribution suggests that ECM remodeling is heterogeneous and differs according to collagen type and distinct tissue compartments. Collectively, our findings support the use of collagen remodeling biomarkers as tools to assess ECM remodeling in pulmonary disease.

RationaleIdiopathic pulmonary fibrosis (IPF) is a progressive, incurable scarring disease of the lung. A common genetic variant near AKAP13, a multifunctional scaffold protein that integrates intracellular signalling through its interactions with RhoA and protein kinase A (PKA), has been associated with IPF susceptibility and elevated AKAP13 mRNA expression in lung tissue from patients. However, its contribution to the pathogenesis of IPF remains unclear. ObjectiveThis study investigates how an AKAP13 variant alters epithelial signalling and evaluates the therapeutic potential of targeting AKAP13. Findingsrs62025270-bearing iHBECs exhibited selective upregulation of AKAP13 isoforms, accompanied by increased cell adhesion and reduced proliferation. Transcriptomic profiling revealed upregulated fibrosis-related genes in rs62025270-bearing iHBECs, including SAA1, FGF2, MMP1, CTSB, COL4A1, and CDKN1A. rs62025270-bearing iHBECs also displayed increased RhoA activation and SMAD2 phosphorylation following LPA stimulation. Furthermore, cells harbouring the AKAP13 variant showed reduced intracellular cAMP levels. Pharmacological inhibition of AKAP13 with A13 reversed the pro-adhesive phenotype and reduced RhoA activation in iHBECs. Moreover, in IPF-derived PCLS, A13 suppressed SERPINE1, CCN2, and MMP7 expression, reduced SMAD2 nuclear translocation, and decreased hydroxyproline levels. ConclusionsPresence of an AKAP13 variant disrupts epithelial homeostasis and promotes pro-fibrotic signalling. Inhibition of AKAP13s RhoGEF domain with A13 restores epithelial function and attenuates fibrotic activation, supporting AKAP13 as a therapeutic target in IPF.

Summary (Abstract)An increasing number of research institutions and funding bodies are making sustainability a focal point in research funding and practice. Across the UK, the rapid rollout of auditing processes, such as the Laboratory Efficiency Assessment Framework (LEAF) and changing institutional policies, are creating pressing, focal demand for sustainability accounting upon UK researchers. Despite the increasing expectations on UK researchers to actively report their sustainability and demonstrate improvement, easy-to-use, and accurate reporting tools for sustainability accounting are not widely available. Here, we created WillCO2st - a free program that enables fast, publication-read sustainability reports. WillCO2st makes use of real-time, region-specific conversion factor data freely available through the Carbon Intensity API - a resource unique to the UK - to create experimental carbon footprinting estimates using metadata of experimental files. Data can be simply click-and-dragged into WillCO2st to create an experimental sustainability audit in minutes. Further, we exemplified the utility of WillCO2sts live-nudging feature by quantifying the retrospective theoretical savings in carbon from shifting experimental timing to times of day with lower carbon intensities. Overall, WillCO2st eases time and resource burden on researchers and serves as a national model within the UK that could be replicated in other countries as relevant data on regional energy use becomes available. HighlightsO_LIWillCO2st is a free software platform that enables fast, publication-ready sustainability reporting for papers, grants, and internal audits. C_LIO_LIWillCO2st leverages the Carbon Intensity API to provide real-time, UK region-specific estimations of carbon intensity and nudges users to switch to lower carbon alternative timing of activities. C_LIO_LIPartial conformity (21%) to switching experimental time would have disproportionately produced a large carbon saving (50%) in our most recent publications experimental carbon footprint. C_LI

G protein-coupled receptors rely on dynamic conformational changes to coordinate G protein activation and recruitment of regulatory transducers such as G protein-coupled receptor kinases and {beta}-arrestins. The chemotactic receptor GPR183 has been implicated in a context-dependent role in hematological malignancies. Here, we investigated the impact of A338V mutation located within the C-terminal tail of GPR183. This mutation is associated with acute myeloid leukaemia. Using bioluminescence resonance energy transfer-based assays in HEK293A cells, we assessed receptor-proximal signaling events. The A338V variant displayed preserved agonist potency and comparable agonist-induced Gi activation relative to wild type, although constitutive activity towards Gi was modestly reduced. In contrast, recruitment of GRK2 and {beta}-arrestin2 was consistently impaired across multiple assay configurations. These differences were not attributable to altered receptor abundance, as the C-tail untagged mutant exhibited increased plasma membrane expression despite reduced regulatory transducer engagement. While intramolecular conformational biosensor measurements revealed subtle differences in global receptor conformation between WT and A338V, extensive molecular dynamics simulations supported the altered conformational sampling of the C-terminal tail in the A338V variant. Together, these data support a model in which the A338V substitution selectively alters C-terminal structural dynamics, impairing GRK2 and {beta}-arrestin2 recruitment while preserving G protein activation.

Ribosomal proteins, because of their RNA-binding capacity, may engage various cellular RNAs and fulfill nonribosomal roles. Previously, we and others described the intergenic regulation mediated by splicing of RPL22 paralogs in Saccharomyces cerevisiae. Here, we prepared a panel of RPL22A/B intronic mutants with respect to their RNAfold-predicted features and analyzed their properties. We tested the splicing and Rpl22-intron interaction using an intron-containing reporter and a three-hybrid yeast system, respectively. We found that the splicing of RPL22 introns can be inhibited by stabilizing a predicted stem as part of a particular type of conformation (I structure). Stabilizing the formation of an alternate stem (P structure) led to a permissive outcome of splicing. Intriguingly, the regulatory capacity of the main stem loop of the I structure was dependent on the rest of the intronic structure. Rpl22 enhanced splicing inhibition in WT and several of the mutants, which we interpret as stabilization of the I structure by protein binding. Mutagenesis identified both the main and alternative 5ss and additional stem loops as part of the regulatory mechanism. The inhibitory conformation of the intron did not prevent recognition of the 5ss and branch point, but rather stalled splicing at a later stage, before the first catalytic step. We concluded that the structural ensemble of the RPL22 pre-mRNA behaves as an allosteric switch that responds to [Rpl22].

Developing scientific reading skills is critical for undergraduate STEM students due to scientific literatures unique formatting and use of specialized jargon. Generative AI tools such as ChatGPT offer students the ability to ask questions about what they are reading interactively. Previously, we reported the development of a ChatGPT-assisted reading guide that combined structured, active reading strategies with using ChatGPT to clarify unfamiliar words and concepts in real time. In the initial study, undergraduates found the use of the ChatGPT-assisted reading guide helpful in their understanding of an abstract and introduction of a journal article. Here, the ChatGPT-assisted reading guide was used in a journal club assignment for an undergraduate chemistry course. ChatGPT transcripts were analyzed for common types of interactions, and students were surveyed about their experience. Overall, students reported that using the ChatGPT-assisted reading guide was helpful in understanding the article and helped them have more productive class discussions. However, some students also expressed skepticism about using AI tools, citing concerns about accuracy of AI-generated information and the effect of using AI on their own learning.

Hydrophobins are low-molecular-weight biosurfactant proteins that coat the cell surface of filamentous fungi, making it hydrophobic and supporting morphogenesis. On conidia, hydrophobins self-assemble to form rod-shaped multimeric structures known as rodlets. Previously, we reported that hydrophobin RolA from the industrial fungus Aspergillus oryzae first forms an amorphous film at the air-water interface and then undergoes structural rearrangement to form a densely packed rodlet film. This raised the question of whether the amorphous or the rodlet film is more important for the biological functions of RolA. In this study, to compare the properties of amorphous films with those of rodlet films, we used RolA mutants that had lost the ability to form rodlets and therefore remained in the amorphous state. We found that the rodlet film was more rigid than the amorphous film and had stronger surface activity and a greater capacity to change surface wettability. RolA altered the properties of A. oryzae conidia only when it was in the rodlet state. These findings highlight the functional versatility of RolA and show that their dynamic structural transitions directly modulate their function.