bluuebunny/crossref_metadata_2025 huggingface dataset:
The uptake of metallic nanoparticles in breast cancer cell lines is modulated by the HA-CD44 axis.
Authors: Hullo Marie , Mathe Cecile , Fonknechten Nuria , Lallemand Celine , Piton Guillaume , Noireaux Johanna , Chevillard Sylvie , Campalans Anna , Bourneuf Emmanuelle
Published: February 2025

Radio-enhancement is a promising anti-cancer approach based on a local radiation dose increase due to the presence of metallic nanoparticles (NPs) within cancer cells. Depending on their composition, size and cellular properties, NPs can follow multiple cellular pathways and entry routes. We observed that gold, platinum and TiO2 NPs are internalized at higher levels in mesenchymal cells compared to epithelial cells in breast cancer models. A global survey of gene expression between epithelial and mesenchymal cells exposed to 4 different NP types revealed an involvement of membrane structure, and further experiments confirmed that the hyaluronic acid (HA) and its receptor CD44 are mediators of metallic NP uptake into cells. We extended our results to a larger panel of breast cancer cell lines and again showed a preferential uptake of all NPs tested in mesenchymal cells and relying on the HA/CD44 axis. These data provide new considerations for the design of NP-based therapies targeting mesenchymal cancer cells, which are often resistant to treatment and correlate with poor prognosis and tumor recurrence.
Herbaria provide a valuable resource for obtaining informative mRNA
Authors: Tyszka Alexa S. , Chia Khong-Sam , Bretz Eric C. , Mansour Linda , Larson Drew A. , Carella Philip , Walker Joseph F.
Published: February 2025

While DNA has built the framework for molecular insights from museum collections, the utility of archival RNA remains largely unexplored. Likely a consequence of the known instability of RNA relative to DNA, this has effectively nullified the use of herbaria for transcriptomics. Here, we challenge the assumption that herbaria cannot be used for transcriptomics by assembling transcriptomes from RNA extracted from herbarium specimens. Through systematic comparison of transcriptomes from fresh-collected, silica-dried, and archival specimens, we demonstrate the suitability of herbarium-derived RNA for transcriptomics. The practical applicability of archival mRNA was further illustrated by the functional validation of a plant immune receptor synthesized from a specimen collected in 1956. These results contradict the community consensus regarding archival RNA and open the door to subsequent transcriptomic explorations in rare and extinct species. Our findings highlight the importance of preserving and utilizing the diversity embedded within herbarium collections.
Lipid packing and local geometry influence septin curvature sensing
Authors: Curtis Brandy N. , Vogt Ellysa J. D. , Edelmaier Christopher , Gladfelter Amy S.
Published: February 2025

Septins assemble into scaffolds that direct cell growth and morphology that are often localized to the plasma membrane. While septins preferentially bind convex membranes via amphipathic helices, their assembly on varied geometries in cells suggests additional localization cues. We tested the hypothesis that lipid composition directs septin assembly through lipid packing properties. Lipid mixtures varying in lipid packing were designed by molecular dynamics simulations and incorporated onto supported lipid bilayers to measure septin adsorption in vitro. Septins strongly favor loosely-packed, disordered lipid bilayers but additional geometry cues act in conjunction with this membrane property. Introducing tighter lipid packing in cells disrupted septin structures in a curvature dependent manner, specifically limiting septin assembly and retention along flat regions of the plasma membrane. This work demonstrates that packing defects and geometry jointly regulate septin localization and highlights how multiple membrane properties are integrated to control organization of the septin cytoskeleton.

Localization of the septin cytoskeleton is controlled by regulatory factors, membrane curvature, and charge. In this study, changes to lipid composition that modulate lipid packing defects are found to impact septin assemblies in vitro and in cells.
Ribo-seq guided design of enhanced protein secretion inKomagataella phaffii
Authors: Tafrishi Aida , Alva Troy , Chartron Justin , Wheeldon Ian
Published: February 2025

The production of recombinant proteins requires the precise coordination of various biological processes, including protein synthesis, folding, trafficking, and secretion. The overproduction of a heterologous protein can impose various bottlenecks on these networks. Identifying and alleviating these bottlenecks can guide strain engineering efforts to enhance protein production. The methylotrophic yeastKomagataella phaffiiis used for its high capacity to produce recombinant proteins. Here, we use ribosome profiling to identify bottlenecks in protein secretion during heterologous expression of human serum albumin (HSA). Validation of this analysis showed that the knockout of non-essential genes whose gene products target the ER, through co- and post-translational mechanisms, and have high ribosome utilization can increase production of a heterologous protein, HSA. A triple knockout in co-translationally translocated carbohydrate and acetate transporter Gal2p, cell wall maintenance protein Ydr134cp, and the post-translationally translocated cell wall proteinAoa65896.1increased HSA production by 35%. This data-driven strain engineering approach uses cell-level information to identify gene targets for phenotype improvement. This specific case identifies hits and creates strains with improved HSA production, with Ribo-seq and bioinformatic analysis to identify non-essential ER targeted proteins that are high ribosome utilizers.
Defined media reveals the essential role of lipid scavenging to support cancer cell proliferation
Authors: Newsom Oliver J. , Sullivan Lucas B.
Published: February 2025

Fetal bovine serum (FBS) is a nearly ubiquitous, yet undefined additive in mammalian cell culture media whose functional contributions to promoting cell proliferation remain poorly understood. Efforts to replace serum supplementation in culture media have been hindered by an incomplete understanding of the environmental requirements fulfilled by FBS in culture. Here, we use a combination of live-cell imaging and liquid chromatography-mass spectrometry to elucidate the role of serum in supporting proliferation. We show that serum provides consumed factors that enable proliferation and demonstrate that the serum metal and lipid components are crucial to sustaining proliferation in culture. Importantly, despite access to a wide range of lipid classes, albumin-bound lipids are the primary species consumed during cancer cell proliferation. Furthermore, we find that combinations of the additive ITS, containing necessary metals, and albumin-associated lipid classes are sufficient to replace FBS in culture media. We show that serum-free media enables sensitive quantification of lipid consumption dynamics during cell proliferation, which indicate that fatty acids (FA) are consumed through a mass-action mechanism, with minimal competition from other lipid classes. Finally, we find that pharmacologic disruption of FA activation and incorporation into the cellular lipidome reduces uptake from the environment and impairs cell proliferation. This work therefore identifies metabolic contributions of serum in cell culture settings and provides a framework for building cell culture systems that sustain cell proliferation without the variable and undefined contributions of FBS.
Expression of MMP-11, an estrogen-suppressed gene in MCF-7 cells, is elevated upon acquisition of tamoxifen resistance
Authors: Sonia Ningthoujam , Mondal Sreeja , Limaye Anil Mukund
Published: February 2025

Matrix metalloproteinase-11 (MMP-11), also known as stromelysin-3, is a member of a large family of zinc-dependent proteinases. Known to be expressed in breast tumor stroma, the epithelium, and the associated mononuclear inflammatory cells, its expression is associated with invasion, metastasis, and poor clinical outcomes and survival rates. Despite the known effects of estrogen on extracellular matrix remodeling, and breast cancer metastasis, the role of MMP-11 therein is not understood. Here, we show that estrogen suppresses MMP-11 expression in MCF-7 breast cancer cells via a mechanism that involves binding of the estrogen receptor α (ERα) to an estrogen response element located in the intron-1 of MMP-11. ERαknockdown alone upregulates MMP-11 expression, highlighting its crucial role in this regulatory axis. Additionally, the anti-estrogen tamoxifen (4-OHT) blocks estrogen-mediated MMP-11 suppression. However, prolonged 4-OHT exposure or 4-OHT resistance leads to increased MMP-11 expression. This suggests that MMP-11 may play a role in 4-OHT resistance, potentially leading to a more aggressive tumor phenotype. Our study underscores the importance of estrogen-ERαsignaling in breast cancer progression, emphasizing the need for further investigation into MMP-11’s role in 4-OHT resistance and cancer metastasis.
Laboratory yeast strains are highly diverse in lipid metabolism
Authors: Renne Mike F. , Bachmann Richard , Klose Christian , Hentrich Thomas , Schulze-Hentrich Julia M. , Ernst Robert
Published: February 2025

The impact of the genetic background on the lipidome of yeast strains remains underexplored. This study systematically compares the lipidomes of five commonly used laboratory yeast strains: BY4741, W303, D273-10B, RM11-1a, and CEN.PK2-1c. Shotgun lipidomics reveals significant variations in lipid class and acyl chain composition down to the level of molecular species. Notably, the most abundant lipid class differed between the strains: phosphatidylinositol (PI) lipids are predominant in BY4741, while phosphatidylethanolamine (PE) lipids are in D273. Ergosterol esters, which are the storage form of the major yeast sterol ergosterol, are at higher levels in all strains other than BY4741, correlating with a low gene expression of lipid metabolic enzymes Hmg1 and Are2 in BY4741. Despite these lipidomic differences, transcriptomic analysis did not show significant changes in most genes related to lipid metabolism, suggesting post-transcriptional modifications, protein abundance, and metabolic flux as potential regulatory mechanisms. This study underscores the complexity of lipidome regulation and the need for further investigation into the underlying mechanisms.
Predicting hybrid fitness: the effects of ploidy and complex ancestry
Authors: Schneemann Hilde , Welch John J.
Published: February 2025

Hybridization between divergent populations places alleles in novel genomic contexts. This can inject adaptive variation – which is useful for breeders and conservationists – or reduce fitness, leading to reproductive isolation. Most theoretical work on hybrids involves haploid or diploid hybrids between two parental lineages, but real-world hybridization is often more complex. We introduce a simple fitness landscape model to predict hybrid fitness with arbitrary ploidy and an arbitrary number of hybridizing lineages. We test our model on published data from maize (Zea mays) and rye (Secale cereale), including hybrids between multiple inbred lines, both as diploids and synthetic tetraploids. Quantitative predictions for the effects of inbreeding, and the strength of progressive heterosis, are well supported. This suggests that the model captures the important properties of dosage and genetic interactions, and may help to unify theories of heterosis and reproductive isolation.
Effects of using deep learning to predict the geographic origin of barley genebank accessions on genome-environment association studies
Authors: Chang Che-Wei , Schmid Karl J
Published: February 2025

Genome-environment association (GEA) is an approach for identifying adaptive loci by combining genetic variation with environmental parameters, offering potential for improving crop resilience. However, its application to genebank accessions is limited by missing geographic origin data. To address this limitation, we explored the use of neural networks to predict the geographic origins of barley accessions and integrate imputed environmental data into GEA. Neural networks demonstrated high accuracy in cross-validation but occasionally produced ecologically implausible predictions as models solely considered geographical proximity. For example, some predicted origins were located within non-arable regions, such as the Mediterranean Sea. Using barley flowering time genes as benchmarks, GEA integrating imputed environmental data (N=11,032) displayed partially concordant yet complementary detection of genomic regions near flowering time genes compared to regular GEA (N=1,626), highlighting the potential of GEA with imputed data to complement regular GEA in uncovering novel adaptive loci. Also, contrary to our initial hypothesis anticipating a significant improvement in GEA performance by increasing sample size, our simulations yield unexpected insights. Our study suggests potential limitations in the sensitivity of GEA approaches to the considerable expansion in sample size achieved through predicting missing geographical data. Overall, our study provides insights into leveraging incomplete geographical origin data by integrating deep learning with GEA. Our findings indicate the need for further development of GEA approaches to optimize the use of imputed environmental data, such as incorporating regional GEA patterns instead of solely focusing on global associations between allele frequencies and environmental gradients across large-scale landscapes.
Non-Canonical Role of DNA Mismatch Repair on Sensory Processing in Mice
Authors: Rahman Sadia N. , Neophytou Demetrios , Oviedo-Gray Siboney , Vuong Bao Q. , Oviedo Hysell V.
Published: February 2025

DNA repair mechanisms are essential for cellular development and function. This is particularly true in post-mitotic neurons, where deficiencies in DNA damage response proteins can result in severe neurodegenerative and neurodevelopmental disorders. One highly conserved factor involved in DNA repair is Mut-S Homolog 2 (Msh2), which is responsible for correcting base-base mismatches and insertion/deletion loops during cell proliferation. However, its role in mature neuronal function remains poorly understood. This study investigates the impact ofMsh2loss on sensory processing in a mouse model. Using electrophysiological and molecular assays, we identified significant deficits in cortical and thalamic sound processing inMsh2-/-mice. These deficits were linked to dysfunction of the thalamic reticular nucleus (TRN), a brain region that critically regulates corticothalamic and thalamocortical activity. Our findings revealed increased oxidative damage, aberrant neuronal activity, and elevated parvalbumin (PV) expression in PV+interneurons in the TRN ofMsh2-/-mice. Additionally, we observed the presence of connexin plaques, indicating that disrupted gap junction formation may contribute to impaired TRN function. These results underscore the critical role ofMsh2in supporting the functionality of PV+interneurons in the TRN, thereby profoundly influencing sensory processing pathways. This study provides new insights into the importance of DNA repair mechanisms in neuronal development and function, potentially contributing to our understanding of their role in neurological disorders.
Planetary-scale marine community modeling predicts metabolic synergy and viral impacts
Authors: Régimbeau A. , Tian F. , Smith G. , Riddell J. , Andreani C. , Bordron P. , Budinich M. , Howard-Varona C. , Larhlimi A. , Ser-Giacomi E. , Trottier C. , Guidi L. , Hallam S.J. , Iudicone D. , Karsenti E. , Maass A. , Sullivan M.B. , Eveillard D.
Published: February 2025

The oceans buffer against climate change via biogeochemical cycles underpinned by microbial metabolic networks. While planetary-scale surveys provide baseline microbiome data, inferring metabolic and biogeochemical impacts remains challenging. Here, we constructed a metabolic model for each TARA Ocean metagenome or metatranscriptome, quantified the importance of each metabolic reaction, and used this to assess planetary-scale heterotrophic prokaryotic metabolic phenotypes as a proxy for marine biogeochemistry. This revealed metabolism-inferred ecological zones that matched taxonomy- and function-inferred ones, connections between microbial metabolism and diversity, and predictions about long-sought virus ecological roles, including that virus-encoded metabolic genes target important reactions and identify viral shunt- or shuttle-enriched ocean regions. Together, this framework is agile and resolves planetary-scale community metabolic features to better incorporate microbes and viruses into future predictive ecosystem and climate models.
Identifying a logical specification and a program for an LLM-based generator of lead molecules
Authors: Srinivasan Ashwin , Dash Tirtharaj , Baskar A , Dey Sanjay Kumar , Banerjee Mainak
Published: February 2025

Our interest is in the generation of “lead” molecules in early-stage drug design. Leads are small molecules (ligands) that can bind to a part of pre-specified target and also satisfy multiple physico-chemical constraints. We propose using techniques developed in Inductive Logic Programming (ILP) to identify a logical specification of feasible molecules; and then using this specification to construct a program that uses a large language model (LLM) to generate new molecules. We ensure the program constructed is correct, in the sense that every molecule generated by the program is feasible according the specification. Our focus is on contributing to on-going drug-discovery research on novel inhibitors for Dopamineβ-hydroxylase (DBH), an enzyme that plays a pivotal role in several diseases related to the brain and the heart. We find molecules comparable in affinity to the latest generation drugs currently in clinical trials, and chemical assessment of synthesisablity of the molecules generated. For completeness, we also provide results obtained on the classic benchmark datasets used in recent work reported in [1].
Recombination and retroprocessing in broomrapes reveal a universal roadmap for mitochondrial evolution in heterotrophic plants
Authors: Cai Liming , Havird Justin C , Jansen Robert K
Published: February 2025

The altered life history strategies of heterotrophic organisms often leave a profound genetic footprint on energy metabolism related functions. In parasitic plants, the reliance on host-derived nutrients and loss of photosynthesis in holoparasites have led to highly degraded to absent plastid genomes, but its impact on mitochondrial genome (mitogenome) evolution has remained controversial. By examining mitogenomes from 45 Orobanchaceae species including three independent transitions to holoparasitism and key evolutionary intermediates, we identified measurable and predictable genetic alterations in genomic shuffling, RNA editing, and intracellular (IGT) and horizontal gene transfer (HGT) en route to a nonphotosynthetic lifestyle. In-depth comparative analyses revealed DNA recombination and repair processes, especially RNA-mediated retroprocessing, as significant drivers for genome structure evolution. In particular, we identified a novel RNA-mediated IGT and HGT mechanism, which has not been demonstrated in cross-species and inter-organelle transfers. Based on this, we propose a generalized dosage effect mechanism to explain the biased transferability of plastid DNA to mitochondria across green plants, especially in heterotrophic lineages like parasites and mycoheterotrophs. Evolutionary rates scaled with these genomic changes, but the direction and strength of selection varied substantially among genes and clades, resulting in high contingency in mitochondrial genome evolution. Finally, we describe a universal roadmap for mitochondrial evolution in heterotrophic plants where increased recombination and repair activities, rather than relaxed selection alone, lead to differentiated genome structure compared to free-living species.
A Potent Nonapeptide Inhibitor for the CXCL12/HMGB1 heterocomplex: A Computational and Experimental Approach
Authors: Fassi Enrico Mario Alessandro , Pirani Edisa , Cecchinato Valentina , Cavalli Andrea , Roda Gabriella , Uguccioni Mariagrazia , Sgrignani Jacopo , Grazioso Giovanni
Published: February 2025

Inflammation is a vital defense mechanism activated in response to injury or infection, which induces the release of cytokines and chemokines to promote tissue repair. However, persistent inflammation may result in the development of autoimmune diseases.

During pathological conditions such as rheumatoid arthritis, HMGB1 is kept in its reduced isoform and can complex with CXCL12 enhancing cell migration and exacerbating the immune responses. Small organic compounds selective for HMGB1 have been previously reported to be able to disrupt the CXCL12/HMGB1 heterocomplex, but due to their low affinity, they are unsuitable for further development as novel anti-inflammatory drugs.

We previously reported a peptide (HBP08) that binds to HMGB1 with high affinity (Kd= 0.8 µM), and blocks the activity of the heterocomplex, in line with a wide literature that supports the use of peptides to design protein-protein interaction inhibitors. In the present work, we computationally optimized the HBP08 peptide sequence, finding new analogues endowed with improved affinity for HMGB1. In particular, HBP08-2 inhibited the activity of the CXCL12/HMGB1 heterocomplex with an IC5010-fold lower (3.31 µM) and displayed a Kd28-fold lower (28.1 ± 7.0 nM) than the parent peptide HBP08.
Molecular Mechanisms Limiting the Therapeutic Window of AAV Gene Therapy in Mouse Models of Blue Cone Monochromacy
Authors: Brothers Brooke A. , Sechrest Emily R. , Ma Li , Ashcraft Madyson , Guan Tongju , Barbera Robert J. , Cahill Marion E. , Shaw Lee M. , Chen Becky , Baehr Wolfgang , Hu Gangqing , Stoilov Peter , Deng Wen-Tao
Published: February 2025

Blue cone monochromacy (BCM) is an X-linked retinal disorder caused by mutations in theOPN1LW/OPN1MWgene locus, resulting in impaired cone function and structural degeneration. We conducted a comparative analysis of AAV-mediated gene therapy inOpn1lw/Opn1mwdouble knockout (DKO) andOpn1mwC198R/Opn1sw-/-(C198R) BCM mouse models and evaluated the therapeutic window, efficacy, and longevity. Our results demonstrate that the AAV8-Y733F capsid achieved superior cone rescue compared to AAV5. While both DKO and C198R models showed similar therapeutic windows and rescue longevity, treatment efficacy decreased markedly in older mutant mice. Structural analysis revealed that aged cones in both models displayed degenerative changes, including mislocalized mitochondria and compromised connecting cilia. At the molecular level, we observed reduced AAV-mediated transgene expression in DKO and C198R older cones, which may result from decreased transduction efficiency, decreased circular episome stability, genome-wide transcription/translation downregulation, targeted mRNA/protein degradation, or overall cone degeneration. Notably, the cone-specific promoters forPde6candCngb3maintained robust activity in degenerating cones. These findings suggest that combining an efficient AAV serotype with an optimized cone promoter could be a viable approach to extend the therapeutic window and enhance treatment longevity for BCM patients.
cxcl18b-defined transitional state-specific nitric oxide drives injury-induced Müller glia cell-cycle re-entry in the zebrafish retina
Authors: Ye Aojun , Yu Shuguang , Du Meng , Zhou Dongming , He Jie , Chen Chang
Published: February 2025

In lower vertebrates, retinal Müller glia (MG) exhibit a life-long capacity of cell-cycle re-entry to regenerate neurons following the retinal injury. However, the mechanism driving such injury-induced MG cell-cycle re-entry remains incompletely understood. Combining single-cell transcriptomic analysis andin-vivoclonal analysis, we identified previously undescribedcxcl18b-defined MG transitional states as essential routes towards MG proliferation following green/red cone (G/R cone) ablation. Microglial inflammation was necessary for triggering these transitional states, which expressed the gene modules shared by cells of the ciliary marginal zone (CMZ) where life-long adult neurogenesis takes place. Functional studies of the redox properties of these transitional states further demonstrated the regulatory role of nitric oxide (NO) produced byNos2bin injury-induced MG proliferation. Finally, we developed a viral-based strategy to specifically disruptnos2bincxcl18b-defined MG transitional states and revealed the effect of transitional state-specific NO signaling. Our findings elucidate the redox-related mechanism underlying injury-induced MG cell-cycle re-entry, providing insights into species-specific mechanisms for vertebrate retina regeneration.
Predicting Non-Covalent Interactions Between Antioxidants In Biological Membranes Through Molecular Dynamics
Authors: Martin Marving , Chantemargue Benjamin , Fabre Gabin , Gierschner Johannes , Trouillas Patrick
Published: February 2025

The synergistic association of different polyphenols has gained much interest in the food industry to develop efficient antioxidant cocktails, reducing the concentration of active agents and subsequently potential toxicity. The theoretical description and prediction of such processes is of central interest in this development. This study aims at benchmarking the performance of molecular dynamics (MD) to predict the formation of non-covalent complexes between π-conjugated antioxidants, including two prototypes (quercetin and vitamin E), in a pure 1,2-dipalmitoylphosphatidylcholine (DOPC) lipid bilayer. To reproduce the experimentally observed quenching of vitamin E fluorescence by quercetin, a sphere-of-action quenching model was applied. The predictive capability of MD simulations at capturing this non-covalent association was evaluated with five other π-conjugated potential partners of vitamin E, namely catechin, caffeic acid, myricetin, kaempferol, and galangin. The observed trend agreed with experimental studies, validating again the use of MD simulations as a tool to measure the potential synergism between natural antioxidants.
TIPs-VF: An augmented vector-based representation for variable-length DNA fragments with sequence, length, and positional awareness
Authors: De los Santos Marvin I.
Published: February 2025

The ability to accurately encode and represent genetic sequences in machine learning process is critical for advancements in biotechnology, specifically in genetic engineering and synthetic biology. Traditional sequence encoding method face significant limitations in handling sequence variability, maintaining reading frame integrity, and preserving biologically relevant features. This preliminary study presents TIPs-VF (Translator-Interpreter Pre-seeding for Variable-length Fragments), a simple and efficient encoding framework designed to address some of the key challenges in representing genetic sequences for machine learning. The results showed that TIPs- VF enables a variable-length sequence representation that retains biological context while ensuring the alignment of encodings with codon boundary, making it particularly suited for modular genetic construction. TIPs-VF demonstrated superior performance in truncation and fragmentation analysis, sequence homology detection, domain assessment, and splice junction identification. Unlike conventional methods that require fixed-length inputs, TIPs-VF dynamically adapts to sequence length variations, preserving essential features such as domain similarities and sequence motifs. Additionally, TIPs-VF improves open reading frame recognition and enhances the identification of vector parts and plasmid elements by unifying sequence embeddings with the three possible open reading frame. Overall, TIPs-VF offers a robust, biologically meaningful encoding framework that overcomes the constraints of traditional sequence representations by incorporating sequence, length, and positional awareness. The TIPs-VF encoding infrastructure is available athttps://tips.logiacommunications.com.
Subunit specialisation in AAA+ proteins and substrate unfolding during transcription complex remodelling
Authors: Gao Forson , Ye Fuzhou , Buck Martin , Zhang Xiaodong
Published: February 2025

Bacterial RNA polymerase (RNAP) is a multi-subunit enzyme that copies DNA into RNA in a process known as transcription. Bacteria use σ factors to recruit RNAP to promoter regions of genes that need to be transcribed, with 60% bacteria containing at least one specialized σ factor σ54. σ54recruits RNAP to promoters of genes associated with stress responses and forms a stable closed complex that does not spontaneously isomerize to the open state where promoter DNA is melted out and competent for transcription. The σ54-mediated open complex formation requires specific AAA+ proteins (ATPasesAssociated with diverse cellularActivities) known as bacterial enhancer-binding proteins (bEBPs). We have now obtained structures of new intermediate states of bEBP-bound complexes during transcription initiation, which elucidate the mechanism of DNA melting driven by ATPase activity of bEBPs and suggest a mechanistic model that couples the ATP hydrolysis cycle within the bEBP hexamer with σ54unfolding. Our data reveal that bEBP forms a non-planar hexamer with the hydrolysis-ready subunit located at the furthest/highest point of the spiral hexamer relative to the RNAP. ATP hydrolysis induces conformational changes in bEBP that drives a vectoral transiting of the regulatory N-terminus of σ54into the bEBP hexamer central pore causing the partial unfolding of σ54, while forming specific bEBP contacts with promoter DNA. Furthermore, our data suggest a mechanism of AAA+ protein that is distinct from the hand-over-hand mechanism proposed for many AAA+ proteins, highlighting the versatile mechanisms utilized by the large protein family.
Lamin B1 and LAP2β resist cytoskeletal force to maintain lamin A/C meshwork organization and preserve nuclear integrity
Authors: Alabi Yewande , Aksenova Vasilisa , Arnaoutov Alexei , Marin Harold , Dasso Mary , Buchwalter Abigail
Published: February 2025

The nuclear lamins are extremely long-lived proteins in most cell types. As a consequence, lamin function cannot be effectively dissected with temporal precision using standard knock-down approaches. Here, we apply the auxin-inducible degron (AID) system to rapidly deplete each lamin isoform within one cell cycle and reveal the immediate impacts of lamin loss on the nucleus. Surprisingly, neither acute lamin A/C (LA/C), lamin B1 (LB1), nor lamin B2 (LB2) depletion altered nuclear shape or induced nuclear blebbing, indicating that acute lamin loss is not sufficient to alter nuclear morphology. LB1 depletion is immediately followed by LA/C meshwork disorganization due to actin cytoskeletal forces on the lamina, yet neither LA/C nor LB1 depletion induced nuclear rupturing. We found that the abundant inner nuclear membrane protein LAP2β protects nuclear integrity in the absence of LB1, as depletion of both LB1 and LAP2β induced severe LA/C disorganization and frequent nuclear rupturing. Depolymerization of the actin cytoskeleton prevents nuclear rupture in LAP2β- and LB1-depleted nuclei. We conclude that both LB1 and LAP2β resist cytoskeletal force to maintain regular lamin A/C meshwork organization and preserve nuclear integrity.
Evaluating the toxicity of methanol, formaldehyde and formate on the growth fitness ofYarrowia lipolytica
Authors: Kuang Wei , Hong Yuxiang , Hu Zimu , Xu Peng
Published: February 2025

Liquid C1 feedstock, including methanol, formaldehyde and formic acid can be easily manufactured from greenhouse gases CO2and CH4.Yarrowia lipolytica, isolated from marine ecosystem, is a non-conventional yeast which is capable of assimilating multiple range of hydrophobic compounds including alcohols, lipids, hydrocarbons, and volatile fatty acidset al. This yeast has been extensively engineered to produce lipids, carotenoids, squalene and other natural products. Herein we tested the growth fitness ofY. lipolyticawhen exposed to various one-carbon (C1) liquid feedstocks (methanol, formaldehyde, and formic acid). We firstly captured the cell growth kinetics with an automatic Cell Growth Analyzer and fitted the data with a Monod-type growth model. We obtained the inhibition constants of the three liquid C1s from the growth fitness dose-response curves. We found that the lagging phase duration is exponentially correlated with the toxicity of the tested C1 solvents. Notably,Y. lipolyticaexhibited tolerance to methanol (IC50871 mM) and formic acid (IC5042.6 mM), but showed sensitivity to formaldehyde (IC503.8 mM). We next chose fromate as the co-substrate to cultivateY. lipolytica, confirmed thatY. lipolyticacan upcycle formic acid to improve lipid yields and biomass in fed-batch culture. This work broadensY. lipolytica’s substrate scope and facilitates sustainable and cost-efficient production of fuels and chemicals.
Human pluripotent stem cell-derived intestinal epithelial cells maintain small intestine-specific functions over time, even with repeated cell division
Authors: Chen Junlong , Kuramochi So , Horiuchi Shinichiro , Kawasaki Tomoyuki , Kakizaki Hiroto , Tabata Lirika , Kimura Tohru , Nakamura Kazuaki , Akutsu Hidenori , Ishida Seiichi , Kikuchi Atsuo , Umezawa Akihiro
Published: February 2025

The human colon cancer-derived cell line Caco-2 is widely used in drug discovery due to its barrier function and transporter activity. However, Caco-2 cells have extremely low drug metabolic capacity, resulting in discrepancies with human physiology. In this study, we conducted experiments on human intestinal epithelial cells generated from pluripotent stem cell-derived organoids. We assessed cell morphology, gene expression, barrier and transporter functions, drug metabolic capacity, and cytotoxicity in relation to cell growth and the effects of cellular aging. The results indicate that organoid-derived intestinal epithelial cells may be helpful as a new model cell for drug discovery. Understanding the advantages of drug metabolic capacity and cytotoxicity among cryopreserved human enterocytes, the human colon cancer-derived cell line Caco-2, and human pluripotent stem cell-derived intestinal epithelial cells within microphysiological systems and organ-on-chip technologies is essential for the development of an appropriate model system for the small intestine.
The Mn-motif protein MAP6d1 assembles ciliary doublet microtubules
Authors: Gopal Dharshini , Wu Juliette , Delaroche Julie , Bosc Christophe , De Andrade Manon , Denarier Eric , Effantin Gregory , Andrieux Annie , Gory-Fauré Sylvie , Serre Laurence , Arnal Isabelle
Published: February 2025

Most eukaryotic cells have cilia that serve vital functions in sensing, signaling, motility. The core architecture of cilia is an array of microtubule doublets, which consist of a complete A-tubule and an incomplete B-tubule. The mechanisms governing the assembly of this complex structure remain poorly understood. Here, using total internal reflection fluorescence microscopy and cryo-electron tomography, we investigate the role of MAP6d1, a brain-specific protein containing microtubule lumen-targeting Mn-motifs. We show that MAP6d1 assembles stable microtubule doublets by recruiting tubulin dimers onto the lattice of the A-tubule to initiate the nucleation of the B-tubule. MAP6d1 also promotes the formation of luminal protofilaments in singlet and doublet microtubules, a previously undescribed phenomenon that likely enhances microtubule stability. In neurons, MAP6d1 localises to the proximal part of primary cilia via its Mn-motif, with its loss resulting in shortened cilia, a characteristic of ciliopathies. MAP6d1 is thus the first microtubule-associated protein found to assemble microtubule doublets, uncovering new functions for Mn-motif proteins in neurons.
MRPL47 Deficiency Drives Mitochondrial Dysfunction via ROS/p38-MAPK/CDKN1A Signaling in Non-Small Cell Lung Cancer
Authors: Bhandari Nikita , Acharya Disha , Chatterjee Annesha , Yelshetti Shweta , Bhat Vinita , Chaube Bal Krishna , Shukla Sudhanshu
Published: February 2025

Mitoribosomes play a pivotal role in cellular energy metabolism by synthesizing proteins involved in oxidative phosphorylation (OXPHOS) system. Dysregulation of mitoribosomes has been linked to Cancer, yet there have been no studies demonstrating the genetics and epigenetic landscape of mitoribosomal proteins (MRPs). In this study, we conducted a comprehensive analysis of expression, copy number variations, mutations, data from TCGA NSCLC patients to elucidate the genetic mechanism regulating MRPs in NSCLC. Consequently, we identified MRPL47, a significantly amplified and overexpressed mitoribosomal gene. We also found significant correlation of MRPL47 expression and copy number with patients’ survival. Functionally, we showed that inhibition of MRPL47 was associated with reduced cell proliferation and migration. Furthermore, silencing MRPL47 impaired the enzymatic activity of electron chain complex I & III leading to a defective OXPHOS system and elevated mitochondrial ROS level. Further, we showed ROS-mediated increase in CDKN1A through the p38 MAPK pathway. The increased CDKN1A level induced G1 cell cycle arrest by inhibiting E2F activity. RNA sequencing analysis further confirmed that MRPL47 hinders cell growth by inhibiting E2F pathway. Additionally, we found that MRPL47 selectively regulates mitochondrial translation of specific OXPHOS proteins rather than influencing all mitochondrial proteins. Altogether, these findings suggest that MARPL47, is amplified and overexpressed in NSCLC and plays a critical role in tumor progression by regulating ROS signaling pathways.
Multi-stage deep learning artifact reduction for parallel-beam computed tomography
Authors: Shi Jiayang , Pelt Daniël M. , Batenburg K. Joost
Published: February 2025

Computed tomography (CT) using synchrotron radiation is a powerful technique that, compared with laboratory CT techniques, boosts high spatial and temporal resolution while also providing access to a range of contrast-formation mechanisms. The acquired projection data are typically processed by a computational pipeline composed of multiple stages. Artifacts introduced during data acquisition can propagate through the pipeline and degrade image quality in the reconstructed images. Recently, deep learning has shown significant promise in enhancing image quality for images representing scientific data. This success has driven increasing adoption of deep learning techniques in CT imaging. Various approaches have been proposed to incorporate deep learning into computational pipelines, but each has limitations in addressing artifacts effectively and efficiently in synchrotron CT, either in properly addressing the specific artifacts or in computational efficiency. Recognizing these challenges, we introduce a novel method that incorporates separate deep learning models at each stage of the tomography pipeline — projection, sinogram and reconstruction — to address specific artifacts locally in a data-driven way. Our approach includes bypass connections that feed both the outputs from previous stages and raw data to subsequent stages, minimizing the risk of error propagation. Extensive evaluations on both simulated and real-world datasets illustrate that our approach effectively reduces artifacts and outperforms comparison methods.
Consumers’ acceptance and valuation of healthier rice: implications for promoting healthy diets in the Philippines
Authors: Custodio Marie Claire , Ynion Jhoanne , Demont Matty , De Steur Hans
Published: February 2025

Purpose

This paper aims to analyze and compare consumers’ acceptance and valuation of brown, colored and low glycemic index rice and identify the factors that influence their willingness to pay (WTP).

Design/methodology/approach

A stated-preference survey was conducted among 600 middle-class urban consumers in the Philippines, using a contingent valuation approach with a between-subjects design. The data were analyzed using hierarchical multiple linear regression.

Findings

Consumers accepted healthier rice types, but they discounted them relative to premium white rice, despite receiving product-specific information on health benefits. Consumers’ household income, attitude toward healthy eating and their diet quality had significant effects on WTP. Snack occasions could serve as entry points for healthier rice rather than targeting the substitution of white rice during main eating occasions. Generic information on nutritional benefits of healthier rice products was insufficient to nudge consumers’ intentions toward integrating these products into their diets.

Practical implications

The empirical contribution provides insights for breeding programs on the design of rice target product profiles that incorporate nutritional attributes.

Originality/value

The current study addresses the gap in consumer preference studies by evaluating nutrition-related attributes of rice. Measures of attitude toward food-based dietary guidelines and indicators of diet quality were included in the set of predictors that may influence WTP. The results provide insights for designing nutrition education programs to promote healthier rice in the context of healthy eating habits and to enhance the health benefits of consumers’ current diets. Future studies should further explore different types of nutrition nudges that encourage consumers to eat healthier rice-based dishes and test nutrition communication strategies that move from a narrow product focus to a broader emphasis on dietary diversity by promoting healthier dishes based on healthier rice products.
Low income among Canadian seniors: interactions between immigration status, racial identity and gender
Authors: Sogaolu Moyosore , Sweetman Arthur
Published: February 2025

Purpose

Population aging is prompting concern over the viability of public pension systems in many Organisation for Economic Co-operation and Development (OECD) nations. In Canada, over the past 2 decades, one response has been to significantly increase immigration, increasing the immigrant share of the population. However, policy and academic analyses have largely overlooked the aging of the immigrant population. This study aims to document disparities in low-income rates and labour market outcomes between immigrants and non-immigrants at older ages, focusing on the intersectionality of immigration status, racial identity and gender.

Design/methodology/approach

We employ the 2021 Canadian Census to undertake a descriptive analysis of low-income patterns and the underlying income sources.

Findings

Compared to non-racialized non-immigrant men, seniors’ low-income rates increase with each of immigrant, racialized and female status – and the effects are cumulative. Low-income differences are linked to variations in prime-age employment and earnings, and access to pension benefits for immigrants. To a large extent, the gaps are driven by variations in Canada Pension Plan (CPP) benefits, mostly due to limited years of Canadian residency.

Originality/value

We characterize differences in low income across eight population subgroups and examine the complete set of tax-relevant income sources to understand how each underlying income stream is associated with the observed differences in low income. We emphasize the intersectionality between immigration status and racial identity, and how both vary by gender.
The effect of firm’s knowledge coherence on partners’ technological distance: from the perspective of supply chain network
Authors: Li Xiaodong , Ma Zheng , Dong Feng , Su Mengyan
Published: February 2025

Purpose

According to the resource dependence theory and peer effect theory, this paper explores the mechanism of the focal firm’s knowledge coherence on technological distance among its supply chain partners.

Design/methodology/approach

Based on patent data of 301 Information Technology and Communication Services firms over 18 years from 1998 to 2015, this paper conducts panel regression analysis.

Findings

Empirical results find the positive relationship between the focal firm’s knowledge coherence and technological distance among its supply chain partners. Furthermore, conclusions indicate that the focal firm’s degree centrality and ego network density negatively and positively moderate this relationship respectively.

Originality/value

The findings of this paper contribute to the existing research in supply chain network innovation and offers guidelines to choose partners with varying technological compositions according to their knowledge bases and network structure characteristics.
Marketing modern femininity: Shiseidō’s approach to selling beauty in interwar Japan
Authors: Tso Erica
Published: February 2025

Purpose

This study aims to examine the evolution of cosmetic advertising in Japan during the 1920s and 1930s, a time characterised by notable cultural upheaval and Western influences. Focussing on Shiseidō as a case study, it explores the interplay between traditional and Western beauty standards, highlighting how this leading cosmetic brand shaped perceptions of femininity and cultural aesthetics.

Design/methodology/approach

This research analyses Shiseidō’s brand magazines, packaging and store designs from the interwar period. Primary sources, including Shiseidō Geppo, Shiseidō Gurafu and Hanatsubaki, offer insights into cosmetics marketing and its cultural impact.

Findings

The findings reveal that Japanese cosmetic advertising during this era adopted both traditional and Western beauty ideals. Shiseidō and other brands skilfully integrated these diverse influences to create a unique aesthetic that appealed to modern Japanese women. This approach not only promoted beauty products but also reflected and reinforced the evolving notions of a new modern femininity.

Originality/value

While numerous cosmetic companies thrived in interwar Japan, this study focuses on Shiseidō for its luxury positioning and broad cultural impact. This research addresses gaps in current scholarship which has mainly focused on Western cosmetic practices. Additionally, the study offers a nuanced perspective on moga (Japanese modern women), presenting them as a hybrid of Western and traditional styles and highlighting the complex, non-linear nature of their transformation.
Virtual reality (VR) meets religiosity: introducing the Q-R CAT model to predict visit intention to religious destinations
Authors: Rafdinal Wahyu , Wibisono Nono , Setiawati Lina , Juniarti Cahaya
Published: February 2025

Purpose

Virtual reality (VR) technology has emerged as a crucial solution in the tourism industry, allowing tourists to explore destinations virtually. However, there are still limited studies examining the role of this technology in the context of religious tourism destinations. Thus, this study investigates factors influencing the intention to visit religious tourism destinations by integrating VR applications’ quality, religiosity and the cognitive appraisal theory (CAT) model.

Design/methodology/approach

Data were collected from 638 VR application users and analysed using partial least squares-structural equation modelling (PLS-SEM) and importance performance map analysis (IPMA).

Findings

Based on the results from PLS-SEM and IPMA, the findings revealed that VR quality, religiosity and constructs in the CAT model are essential to visiting religious tourism destinations.

Practical implications

This study highlights the necessity for the religious tourism industry to advance VR application technology, aiming to enrich visitor experiences. The study provides a framework for marketing managers, government agencies and other relevant stakeholders to develop strategic initiatives to elevate visitor numbers at religious tourism sites.

Originality/value

This study offers a new perspective on the theory and application of VR quality, religiosity and CAT in the religious tourism industry.