Plant Cell. 2024 Dec 23;37(1):koaf004. doi: 10.1093/plcell/koaf004.

NO ABSTRACT

PMID:39847516 | DOI:10.1093/plcell/koaf004

Cell Rep. 2025 Jan 21;44(2):115224. doi: 10.1016/j.celrep.2024.115224. Online ahead of print.

ABSTRACT

The redox state of proteins is essential for their function and guarantees cell fitness. Peroxiredoxins protect cells against oxidative stress, maintain redox homeostasis, act as chaperones, and transmit hydrogen peroxide signals to redox regulators. Despite the profound structural and functional knowledge of peroxiredoxins action, information on how the different functions are concerted is still scarce. Using global proteomic analyses, we show here that the yeast peroxiredoxin Tsa1 interacts with many proteins of essential biological processes, including protein turnover and carbohydrate metabolism. Several of these interactions are of a covalent nature, and we show that failure of peroxiredoxinylation of Gnd1 affects its phosphogluconate dehydrogenase activity and impairs recovery upon stress. Thioredoxins directly remove TSA1-formed mixed disulfide intermediates, thus expanding the role of the thioredoxin-peroxiredoxin redox cycle pair to buffer the redox state of proteins.

PMID:39847483 | DOI:10.1016/j.celrep.2024.115224

ACS Nano. 2025 Jan 23. doi: 10.1021/acsnano.4c18056. Online ahead of print.

ABSTRACT

As natural agonists of the stimulator of interferon genes (STING) protein, cyclic dinucleotides (CDNs) can activate the STING pathway, leading to the expression of type I interferons and various cytokines. Efficient activation of the STING pathway in antigen-presenting cells (APCs) and tumor cells is crucial for antitumor immune response. Tumor-derived exosomes can be effectively internalized by APCs and tumor cells and have excellent potential to deliver CDNs to the cytoplasm of APCs and tumor cells. Here, we leverage tumor exosomes as a delivery platform, designing an EXOTLR1/2-STING loaded with CDNs. To achieve efficient loading of CDNs onto exosomes, we chemically conjugated CDNs with Pam3CSK4, a compound featuring multiple fatty acid chains, resulting in Pam3CSK4-CDGSF. Utilizing the high lipophilicity of Pam3CSK4, Pam3CSK4-CDGSF could be efficiently loaded onto the exosomes through simple incubation. Moreover, as an agonist for Toll-like receptor 1/2, Pam3CSK4 also exhibits robust immunological synergistic effects in conjunction with CDNs. EXOTLR1/2-STING effectively induced the activation of APCs and triggered tumor cell death, producing a favorable antitumor therapeutic effect. It also demonstrated significant synergistic effects with immune checkpoint therapies.

PMID:39846950 | DOI:10.1021/acsnano.4c18056

J Bacteriol. 2025 Jan 23:e0042824. doi: 10.1128/jb.00428-24. Online ahead of print.

ABSTRACT

The mammalian gut microbiome is a dense and diverse community of microorganisms that reside in the distal gastrointestinal tract. In recent decades, the bacterial members of the gut microbiome have been the subject of intense research. Less well studied is the large community of bacteriophages that reside in the gut, which number in the billions of viral particles per gram of feces, and consist of considerable unknown viral "dark matter." This community of gut-residing bacteriophages, called the gut "phageome," plays a central role in the gut microbiome through predation and transformation of native gut bacteria, and through interactions with their mammalian hosts. In this review, we will summarize what is known about the composition and origins of the gut phageome, as well as its role in microbiome homeostasis and host health. Furthermore, we will outline the interactions of gut phages with their bacterial and mammalian hosts, and plot a course for the mechanistic study of these systems.

PMID:39846747 | DOI:10.1128/jb.00428-24

Biotechnol Prog. 2025 Jan 23:e3520. doi: 10.1002/btpr.3520. Online ahead of print.

ABSTRACT

The biopharmaceutical industry is shifting toward employing digital analytical tools for improved understanding of systems biology data and production of quality products. The implementation of these technologies can streamline the manufacturing process by enabling faster responses, reducing manual measurements, and building continuous and automated capabilities. This study discusses the use of soft sensor models for prediction of viability and viable cell density (VCD) in CHO cell culture processes by using in-line optical density and permittivity sensors. A significant innovation of this study is the development of a simplified empirical model and adoption of an integrated systems approach for in-line viability prediction. The initial evaluation of this viability model demonstrated promising accuracy with 96% of the residuals within a ±5% error limit and a Final Day mean absolute percentage error of ≤5% across various scales and process conditions. This model was integrated with a VCD prediction model utilizing Gaussian Process Regressor with Matern Kernel (nu = 0.5), selected from over a hundred advanced machine learning techniques. This VCD prediction model had an R2 of 0.92 with 89% predictions within ±10% error and significantly outperformed the commonly used partial least squares regression models. The results validated the use of these models for real-time in-line prediction of viability and VCD and highlighted the potential to substantially reduce reliance on labor-intensive discrete offline measurements. The integration of these innovative technologies aligns with regulatory guidelines and establishes a foundation for further advancements in the biomanufacturing industry, promising improved process control, efficiency, and compliance with quality standards.

PMID:39846513 | DOI:10.1002/btpr.3520

Circ Genom Precis Med. 2025 Jan 23:e004594. doi: 10.1161/CIRCGEN.124.004594. Online ahead of print.

ABSTRACT

BACKGROUND: Transcriptional dysregulation, possibly affected by genetic variation, contributes to disease development. Due to dissimilarities in development, function, and remodeling during disease progression, transcriptional differences between the left atrial (LA) and right atrial (RA) may provide insight into diseases such as atrial fibrillation.

METHODS: Lateral differences in atrial transcription were evaluated in CATCH ME (Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly) using a 2-stage discovery and replication design. The design took advantage of the availability of 32 paired samples, for which both LA and RA tissue were obtained, as a discovery cohort, and 98 LA and 69 RA unpaired samples utilized as a replication cohort.

RESULTS: A total of 714 transcripts were identified and replicated as differentially expressed (DE) between LA and RA, as well as 98 exons in 55 genes. Approximately 50% of DE transcripts were colocated with another frequently correlated DE transcript (PFDR ≤0.05 for 579 regions). These transcription disequilibrium blocks contained examples including side-specific differential exon usage, such as the PITX2 locus, where ENPEP showed evidence of differential exon usage. Analysis of this region in conjunction with BMP10 identified rs9790621 as associated with ENPEP transcription in LA, while rs7687878 was associated with BMP10 expression in RA. In RA, BMP10 and ENPEP were strongly correlated in noncarriers, which was attenuated in risk-allele carriers, where BMP10 and PITX2 expression were strongly correlated.

CONCLUSIONS: These results significantly expand knowledge of the intricate, tissue-specific transcriptional landscape in human atria, including DE transcripts and side-specific isoform expression. Furthermore, they suggest the existence of blocks of transcription disequilibrium influenced by genetics.

PMID:39846178 | DOI:10.1161/CIRCGEN.124.004594

Front Pharmacol. 2025 Jan 8;15:1462193. doi: 10.3389/fphar.2024.1462193. eCollection 2024.

ABSTRACT

INTRODUCTION: Tuberculosis (TB) poses a significant threat to global health, with millions of new infections and approximately one million deaths annually. Various modeling efforts have emerged, offering tailored data-driven and physiologically-based solutions for novel and historical compounds. However, this diverse modeling panorama may lack consistency, limiting result comparability. Drug-specific models are often tied to commercial software and developed on various platforms and languages, potentially hindering access and complicating the comparison of different compounds.

METHODS: This work introduces stormTB: SimulaTOr of a muRine Minimal-pbpk model for anti-TB drugs. It is a web-based interface for our minimal physiologically based pharmacokinetic (mPBPK) platform, designed to simulate custom treatment scenarios for tuberculosis in murine models. The app facilitates visual comparisons of pharmacokinetic profiles, aiding in assessing drug-dose combinations.

RESULTS: The mPBPK model, supporting 11 anti-TB drugs, offers a unified perspective, overcoming the potential inconsistencies arising from diverse modeling efforts. The app, publicly accessible, provides a user-friendly environment for researchers to conduct what-if analyses and contribute to collective TB eradication efforts. The tool generates comprehensive visualizations of drug concentration profiles and pharmacokinetic/pharmacodynamic indices for TB-relevant tissues, empowering researchers in the quest for more effective TB treatments. stormTB is freely available at the link: https://apps.cosbi.eu/stormTB.

PMID:39845781 | PMC:PMC11750688 | DOI:10.3389/fphar.2024.1462193

Front Plant Sci. 2025 Jan 8;15:1446383. doi: 10.3389/fpls.2024.1446383. eCollection 2024.

ABSTRACT

INTRODUCTION: Rice samples exposed to the space environment have generated diverse phenotypic variations. Miniature-inverted-repeat transposable elements (MITEs), often found adjacent to genes, play a significant role in regulating the plant genome. Herein, the contribution of MITEs in regulating space-mutagenic phenotypes was explored.

METHODS: The space-mutagenic phenotype changes in the F3 to F5 generations of three space-mutagenic lines from the rice varieties Dongnong423 (DN423) and Dongnong (DN416) were meticulously traced. Rice leaves samples at the heading stage from three space-mutagenic lines were subjected to high coverage whole-genome bisulfite sequencing and whole-genome sequencing. These analyses were conducted to investigate the effects of MITEs related epigenetic and genetic variations on space-mutagenic phenotypes.

RESULTS AND DISCUSSION: Studies have indicated that MITEs within gene regulatory regions might contribute to the formation and differentiation of space-mutagenic phenotypes. The space environment has been shown to induce the transposable elements insertion polymorphisms of MITEs (MITEs-TIPs), with a notable preference for insertion near genes involved in stress response and phenotype regulation. The space-induced MITEs-TIPs contributed to the formation of space-mutagenic phenotype by modulating the expression of gene near the insertion site. This study underscored the pivotal role of MITEs in modulating plant phenotypic variation induced by the space environment, as well as the transgenerational stability of these phenotypic variants.

PMID:39845491 | PMC:PMC11751223 | DOI:10.3389/fpls.2024.1446383

Front Plant Sci. 2025 Jan 8;15:1457713. doi: 10.3389/fpls.2024.1457713. eCollection 2024.

NO ABSTRACT

PMID:39845489 | PMC:PMC11750989 | DOI:10.3389/fpls.2024.1457713

Microb Biotechnol. 2025 Jan;18(1):e70068. doi: 10.1111/1751-7915.70068.

NO ABSTRACT

PMID:39844583 | DOI:10.1111/1751-7915.70068

BMC Bioinformatics. 2025 Jan 22;26(1):26. doi: 10.1186/s12859-024-06026-8.

ABSTRACT

BACKGROUND: Interpretability is a topical question in recommender systems, especially in healthcare applications. An interpretable classifier quantifies the importance of each input feature for the predicted item-user association in a non-ambiguous fashion.

RESULTS: We introduce the novel Joint Embedding Learning-classifier for improved Interpretability (JELI). By combining the training of a structured collaborative-filtering classifier and an embedding learning task, JELI predicts new user-item associations based on jointly learned item and user embeddings while providing feature-wise importance scores. Therefore, JELI flexibly allows the introduction of priors on the connections between users, items, and features. In particular, JELI simultaneously (a) learns feature, item, and user embeddings; (b) predicts new item-user associations; (c) provides importance scores for each feature. Moreover, JELI instantiates a generic approach to training recommender systems by encoding generic graph-regularization constraints.

CONCLUSIONS: First, we show that the joint training approach yields a gain in the predictive power of the downstream classifier. Second, JELI can recover feature-association dependencies. Finally, JELI induces a restriction in the number of parameters compared to baselines in synthetic and drug-repurposing data sets.

PMID:39844056 | DOI:10.1186/s12859-024-06026-8

NPJ Antimicrob Resist. 2024 Oct 3;2(1):29. doi: 10.1038/s44259-024-00047-2.

ABSTRACT

While the rise of antibiotic resistance poses a global health challenge, the development of new antibiotics has slowed down over the past decades. This turned the attention of researchers towards the rational design of drug combination therapies to combat antibiotic resistance. In this review we discuss how drug combinations can exploit the deleterious pleiotropic effects of antibiotic resistance and conclude that each drug interaction has its prospective therapeutic application.

PMID:39843924 | DOI:10.1038/s44259-024-00047-2

Nature. 2025 Jan 22. doi: 10.1038/s41586-024-08455-0. Online ahead of print.

ABSTRACT

Rubisco is the primary CO2-fixing enzyme of the biosphere1, yet it has slow kinetics2. The roles of evolution and chemical mechanism in constraining its biochemical function remain debated3,4. Engineering efforts aimed at adjusting the biochemical parameters of rubisco have largely failed5, although recent results indicate that the functional potential of rubisco has a wider scope than previously known6. Here we developed a massively parallel assay, using an engineered Escherichia coli7 in which enzyme activity is coupled to growth, to systematically map the sequence-function landscape of rubisco. Composite assay of more than 99% of single-amino acid mutants versus CO2 concentration enabled inference of enzyme velocity and apparent CO2 affinity parameters for thousands of substitutions. This approach identified many highly conserved positions that tolerate mutation and rare mutations that improve CO2 affinity. These data indicate that non-trivial biochemical changes are readily accessible and that the functional distance between rubiscos from diverse organisms can be traversed, laying the groundwork for further enzyme engineering efforts.

PMID:39843747 | DOI:10.1038/s41586-024-08455-0

Nature. 2025 Jan 22. doi: 10.1038/s41586-024-08422-9. Online ahead of print.

ABSTRACT

The assessment of research performance is widely seen as a vital tool in upholding the highest standards of quality, with selection and competition believed to drive progress. Academic institutions need to take critical decisions on hiring and promotion, while facing external pressure by also being subject to research assessment1-4. Here we present an outlook on research assessment for career progression with specific focus on promotion to full professorship, based on 314 policies from 190 academic institutions and 218 policies from 58 government agencies, covering 32 countries in the Global North and 89 countries in the Global South. We investigated how frequently various promotion criteria are mentioned and carried out a statistical analysis to infer commonalities and differences across policies. Although quantitative methods of assessment remain popular, in agreement with what is found in more geographically restricted studies5-9, they are not omnipresent. We find differences between the Global North and the Global South as well as between institutional and national policies, but less so between disciplines. A preference for bibliometric indicators is more marked in upper-middle-income countries. Although we see some variation, many promotion policies are based on the assumption of specific career paths that become normative rather than embracing diversity. In turn, this restricts opportunities for researchers. These results challenge current practice and have strategic implications for researchers, research managers and national governments.

PMID:39843736 | DOI:10.1038/s41586-024-08422-9

World J Microbiol Biotechnol. 2025 Jan 23;41(2):45. doi: 10.1007/s11274-025-04262-5.

ABSTRACT

Vibrio parahaemolyticus poses a notable threat to marine ecosystems and can cause infections and disease outbreaks in seafood species, which can affect humans upon consumption. The global impacts of such infections and outbreaks on human and animal health led to a growing number of studies from various countries discussing the prevention, control, treatment, and overall implications of V. parahaemolyticus. Hence, this study aims to retrieve relevant studies on V. parahaemolyticus using a bibliometric analysis to understand current research status, trends, and hotspots regarding this bacteria. Relevant literature was searched across the Scopus database, and the data were subsequently analyzed using Biblioshiny software. In addition, a manual examination was conducted to identify the hosts of V. parahaemolyticus and diseases caused by the bacteria. Overall, 7,096 records were obtained from Scopus from 1963 to 2023. A bibliometric analysis identified 17,220 authors, with China emerging as the global leader. The analysis also highlighted significant keywords such as "Vibrio parahaemolyticus," "Litopenaeus vannamei," and "innate immunity," suggesting a focus on the impact of V. parahaemolyticus on L. vannamei, specifically emphasizing the shrimp's innate immune responses. Host-disease interaction network also uncovered 53 interactions between hosts and diseases involving L. vannamei or Penaeus vannamei as the primary host, with acute hepatopancreas necrosis disease (AHPND) emerging as the most prevalent among them. This study can enhance our understanding of infections caused by V. parahaemolyticus and contribute to the development of effective strategies for their prevention and management.

PMID:39843643 | DOI:10.1007/s11274-025-04262-5

Nat Biotechnol. 2025 Jan 22. doi: 10.1038/s41587-024-02534-3. Online ahead of print.

NO ABSTRACT

PMID:39843580 | DOI:10.1038/s41587-024-02534-3

Oncogene. 2025 Jan 22. doi: 10.1038/s41388-024-03262-3. Online ahead of print.

NO ABSTRACT

PMID:39843564 | DOI:10.1038/s41388-024-03262-3

Nat Commun. 2025 Jan 22;16(1):952. doi: 10.1038/s41467-024-55806-6.

ABSTRACT

Colonies of the social bacterium Myxococcus xanthus go through a morphological transition from a thin colony of cells to three-dimensional droplet-like fruiting bodies as a strategy to survive starvation. The biological pathways that control the decision to form a fruiting body have been studied extensively. However, the mechanical events that trigger the creation of multiple cell layers and give rise to droplet formation remain poorly understood. By measuring cell orientation, velocity, polarity, and force with cell-scale resolution, we reveal a stochastic local polar order in addition to the more obvious nematic order. Average cell velocity and active force at topological defects agree with predictions from active nematic theory, but their fluctuations are substantially larger than the mean due to polar active forces generated by the self-propelled rod-shaped cells. We find that M. xanthus cells adjust their reversal frequency to tune the magnitude of this local polar order, which in turn controls the mechanical stresses and triggers layer formation in the colonies.

PMID:39843452 | DOI:10.1038/s41467-024-55806-6

Exp Anim. 2025 Jan 22. doi: 10.1538/expanim.24-0174. Online ahead of print.

ABSTRACT

Rats (Rattus norvegicus) have been widely utilized as model animals due to their physiological characteristics, making them suitable for surgical and long-term studies. They have played a crucial role in biomedical research, complementing studies conducted in mice. The advent of genome editing technologies has facilitated the generation of genetically modified rat strains, advancing studies in experimental animals. Among these innovations, Cre-driver rat models have emerged as powerful tools for spatiotemporal control of gene expression. However, their development and characterization remain less advanced compared to mouse models. In this study, we developed liver-targeting Cre knock-in rats and reporter knock-in rats to evaluate Cre recombinase expression profiles in different genetic contexts. Our results revealed that insertion orientation and promoter origin significantly influence Cre expression patterns. Notably, forward insertion of the Albumin (Alb) promoter-driven Cre sequence at the ROSA26 locus resulted in ubiquitous Cre expression, while reverse insertion confined Cre expression predominantly to the liver. Interestingly, Cre expression under an endogenous Alb promoter unexpectedly induced expression in non-liver tissues, which may suggest a potential link to the in vivo dynamics of albumin. These findings underscore the importance of rigorous characterization in Cre-based transgenic systems. By elucidating the roles of promoter origin, insertion site, and orientation, our study provides valuable insights for optimizing Cre-driver rat models. These findings pave the way for refining genetic strategies to enhance tissue specificity and reliability in functional genomics and disease modeling.

PMID:39842783 | DOI:10.1538/expanim.24-0174

Biochim Biophys Acta Rev Cancer. 2025 Jan 20:189269. doi: 10.1016/j.bbcan.2025.189269. Online ahead of print.

ABSTRACT

Tumor microenvironment (TME) has become a major focus of cancer research as a promising therapeutic target. TME comprises cancer cells surrounded by nonmalignant cells, vessels, lymphoid organs, immune cells, nerves, intercellular components, molecules and metabolites located within or near the tumor lesion. Neuromedin U (NMU), a secretory peptide identified in the TME, has gained much attention as an important player in cancer and nonmalignant cell crosstalk. NMU receptors were detected in cancer cells as well as in nonmalignant TME components, such as immune, stromal and endothelial cells. We propose here to discuss the concept that NMU secreted by cancer cells activates cellular components of TME and thus contributes to the formation of microenvironment that favors tumor growth and cancer progression. We summarized the available data on cancer tissues and cell types that have been identified as a source of NMU and/or receptor-expressing NMU targets. We made a critical selection of NMU-receptor positive cell types that are known components of the TME of most malignant tumors. Finally, we discussed whether NMUs and NMU receptors represent a potential therapeutic target for cancer treatment, and summarized information on the tools available to modulate their activity.

PMID:39842617 | DOI:10.1016/j.bbcan.2025.189269