Protein Sci. 2025 Mar;34(3):e70061. doi: 10.1002/pro.70061.

ABSTRACT

Condensates formed by liquid-liquid phase separation are promising candidates for the development of synthetic cells and organelles. Here, we show that bacterial microcompartment shell proteins from Haliangium ochraceum (BMC-H) assemble into coatings on the surfaces of protein condensates formed by tandem RGG-RGG domains, an engineered construct derived from the intrinsically disordered region of the RNA helicase LAF-1. WT BMC-H proteins formed higher-order assemblies within RGG-RGG droplets; however, engineered BMC-H variants fused to RGG truncations formed coatings on droplet surfaces. These intrinsically disordered tags controlled the interaction with the condensed phase based on their length and sequence, and one of the designs, BMC-H-T2, assembled preferentially on the surface of the droplet and prevented droplet coalescence. The formation of the coatings is dependent on the pH and protein concentration; once formed, the coatings are stable and do not exchange with the dilute phase. Coated droplets could sequester and concentrate folded proteins, including TEV protease, with selectivity similar to uncoated droplets. Addition of TEV protease to coated droplets resulted in the digestion of RGG-RGG to RGG and a decrease in droplet diameter, but not in the dissolution of the coatings. BMC shell protein-coated protein condensates are entirely encodable and provide a way to control the properties of liquid-liquid phase-separated compartments in the context of synthetic biology.

PMID:39969154 | DOI:10.1002/pro.70061

Elife. 2025 Feb 19;13:RP102788. doi: 10.7554/eLife.102788.

ABSTRACT

Artificial intelligence (AI) models have been used to study the compositional regularities of proteins in nature, enabling it to assist in protein design to improve the efficiency of protein engineering and reduce manufacturing cost. However, in industrial settings, proteins are often required to work in extreme environments where they are relatively scarce or even non-existent in nature. Since such proteins are almost absent in the training datasets, it is uncertain whether AI model possesses the capability of evolving the protein to adapt extreme conditions. Antibodies are crucial components of affinity chromatography, and they are hoped to remain active at the extreme environments where most proteins cannot tolerate. In this study, we applied an advanced large language model (LLM), the Pro-PRIME model, to improve the alkali resistance of a representative antibody, a VHH antibody capable of binding to growth hormone. Through two rounds of design, we ensured that the selected mutant has enhanced functionality, including higher thermal stability, extreme pH resistance, and stronger affinity, thereby validating the generalized capability of the LLM in meeting specific demands. To the best of our knowledge, this is the first LLM-designed protein product, which is successfully applied in mass production.

PMID:39968946 | DOI:10.7554/eLife.102788

Aging Cell. 2025 Feb 19:e70015. doi: 10.1111/acel.70015. Online ahead of print.

ABSTRACT

Senescence is a cell fate associated with age-related pathologies; however, senescence markers are not well-defined. Using single cell multi-isotope imaging mass spectrometry (MIMS), we identified hypercondensed, transcriptionally silent DNA globules in a senescence model induced by dysfunctional telomeres. This architectural phenomenon was associated with geographically clustered transcriptional repression across somatic chromosomes with over-representation of cell cycle genes. Senescence-stimuli was associated with a higher frequency of cells that exhibited geographically concentrated transcriptional repression relative to control cells. This phenomenon was also observed in multiple other senescence models, including replicative senescence and irradiation. We further identified an enrichment of common pathways in all models of senescence, suggesting a common cellular response to this silencing phenomenon. Such large-scale clustered silencing of chromosomal segments rather than individual genes may explain senescence heterogeneity and a putative trajectory toward deep, irreversible senescence.

PMID:39968744 | DOI:10.1111/acel.70015

J Sep Sci. 2025 Feb;48(2):e70099. doi: 10.1002/jssc.70099.

ABSTRACT

Metabolomics, a powerful discipline within systems biology, aims at comprehensive profiling of small molecules in biological samples. The challenges of biological sample complexity are addressed through innovative sample preparation methods, including solid-phase extraction and microextraction techniques, enhancing the detection and quantification of low-abundance metabolites. Advances in chromatographic separation, particularly liquid chromatography (LC) and gas chromatography (GC), coupled with high-resolution (HR) mass spectrometry (MS), have significantly improved the sensitivity, selectivity, and throughput of metabolomic studies. Cutting-edge techniques, such as ion-mobility mass spectrometry (IM-MS) and tandem MS (MS/MS), further expand the capacity for comprehensive metabolite profiling. These advanced analytical platforms each offer unique advantages for metabolomics, with continued technological improvements driving deeper insights into metabolic pathways and biomarker discovery. By providing a detailed overview of current trends and techniques, this review aims to offer valuable insights into the future of metabolomics in human health research and its translational potential in clinical settings. Toward the end, this review also highlights the biomedical applications of metabolomics, emphasizing its role in biomarker discovery, disease diagnostics, personalized medicine, and drug development.

PMID:39968702 | DOI:10.1002/jssc.70099

Proc Biol Sci. 2025 Feb;292(2041):20242805. doi: 10.1098/rspb.2024.2805. Epub 2025 Feb 19.

ABSTRACT

Music and rhythm are typical features of all human cultures, but their biological origins remain unclear. Recent investigations suggest that rhythmic features of human music are shared with animal vocalizations. Moreover, arousal is known to influence the structure of both human speech and animal sounds. We investigated coppery titi monkeys' (Plecturocebus cupreus) duet rhythms to assess adherence to rhythmic patterns previously observed only in Old World primates and to deepen our understanding of the proximate causes of non-human primate song rhythm. Titis' songs were remarkably isochronous, but their tempo depended on the social context: songs sung during territorial confrontations have a slower pace than during early morning singing. Songs had a faster tempo and were less regular when infants were present, suggesting a speed-accuracy trade-off. Finally, we found that pair-mates perform isochronous songs with the same precision, suggesting that isochrony plays a role in boosting pair coordination, as it does in other singing primates. Our investigation sheds light on the ultimate and proximate causes of primates' isochronous rhythm, to our knowledge confirming its presence for the first time in a New World monkey and highlighting the role of social factors in shaping its timing and regularity in the short term.

PMID:39968619 | DOI:10.1098/rspb.2024.2805

Med J Islam Repub Iran. 2024 Nov 6;38:129. doi: 10.47176/mjiri.38.129. eCollection 2024.

ABSTRACT

BACKGROUND: Diffuse large B-cell lymphoma (DLBL) and systemic lupus erythematosus (SLE) are complex autoimmune disorders that present unique clinical challenges. These conditions may share underlying genetic and signaling pathways despite their distinct manifestations. Uncovering these commonalities could offer invaluable insights into disease pathogenesis, paving the way for more targeted and effective therapeutic interventions. This study embarks on a comprehensive investigation of the common genes and signaling pathways between SLE and DLBL.

METHODS: The researchers scoured the Gene Expression Omnibus database, meticulously gathering microarray datasets for SLE (GSE61635) and DLBL (GSE56315). Differential expression analysis was performed, allowing the team to identify the genes that were commonly dysregulated across these 2 autoimmune conditions. To delve deeper into the biological significance of these shared genes, the researchers conducted functional enrichment analysis, network analysis, and core gene identification. Notably, the diagnostic potential of the identified hub genes was assessed using a cutting-edge neural network model.

RESULTS: The data analysis revealed a remarkable 146 genes that were shared between SLE and DLBL, of which 111 were upregulated and 45 downregulated. Functional enrichment analysis unveiled the involvement of these shared genes in vital immune system-related processes-such as defense response to viruses, interferon signaling, and broader immune system pathways. Network analysis pinpointed 5 hub genes (IFIT3, IFIT1, DDX58, CCL2, and OASL) that emerged as central players, exhibiting a high degree of centrality and predicted to hold crucial roles in the underlying molecular mechanisms. Remarkably, the neural network model demonstrated exceptional diagnostic accuracy in distinguishing between the disease states (DLBL and SLE) based solely on the expression patterns of these hub genes.

CONCLUSION: The identified hub genes and their associated pathways hold immense potential as diagnostic biomarkers and may serve as valuable targets for future therapeutic explorations.

PMID:39968469 | PMC:PMC11835410 | DOI:10.47176/mjiri.38.129

Front Cell Dev Biol. 2025 Feb 4;12:1526795. doi: 10.3389/fcell.2024.1526795. eCollection 2024.

ABSTRACT

Glucose metabolism is a key factor characterizing the cellular state during multicellular development. In metazoans, the metabolic state of undifferentiated cells correlates with growth/differentiation transition and cell fate determination. Notably, the cell fate of the Amoebozoa species Dictyostelium discoideum is biased by the presence of glucose and is also correlated with early differences in intracellular ATP. However, the relationship between early cell-cell heterogeneity, cell differentiation, and the metabolic state is unclear. To address the link between glucose metabolism and cell differentiation in D. discoideum, we studied the role of phosphoenolpyruvate carboxylase (PEPC), a key enzyme in the PEP-oxaloacetate-pyruvate node, a core junction that dictates the metabolic flux of glycolysis, the TCA cycle, and gluconeogenesis. We demonstrate that there is cell-cell heterogeneity in PEPC promoter activity in vegetative cells, which depends on nutrient conditions, and that cells with high PEPC promoter activity differentiate into spores. The PEPC null mutant exhibited an aberrantly high prestalk/prespore ratio, and the spore mass of the fruiting body was glassy and consisted of immature spores. Furthermore, the PEPC null mutant had high ATP levels and low mitochondrial membrane potential. Our results suggest the importance of cell-cell heterogeneity in the levels of metabolic enzymes during early cell fate priming.

PMID:39968235 | PMC:PMC11832675 | DOI:10.3389/fcell.2024.1526795

Front Pain Res (Lausanne). 2025 Feb 4;6:1501932. doi: 10.3389/fpain.2025.1501932. eCollection 2025.

ABSTRACT

INTRODUCTION: Degenerative joint disease (DJD) occurs very commonly in cats and can be associated with pain. Almost 70% of cats with DJD-associated pain suffer the co-morbidity of chronic kidney disease (CKD). There are currently very limited treatment or management options. A greater understanding of the systems biology of DJD, DJD-associated pain, and CKD may contribute to identifying disease specific biomarkers and relevant targets for the development of therapeutics for the control of these conditions in cats, and help inform human pain therapeutic development.

METHODS: Using mass spectrometry-based proteomic profiling of the serum of 200 highly phenotyped cats with varying burdens of DJD, pain, and CKD, we identified significant individual proteins and pathways.

RESULTS: Functional pathway analysis, based on differentially abundant proteins across individual disease states (DJD, pain, CKD), identified pathways playing a role in DJD and DJD-associated pain including acute phase response signaling, LXR/RXR and FXR/RXR activation and the complement system. With the added co-morbidity of CKD, similar pathways were identified, with the addition of IL-12 signaling and production in macrophages.

DISCUSSION: We identified differentially abundant proteins associated with DJD, pain and CKD and future work should evaluate these proteins as potential biomarkers of disease (individually or as clusters). Further, these data could be leveraged to identify novel therapeutic targets to address the gap in our ability to manage DJD, pain, and CKD in cats. Given that our work was in cats with naturally occurring DJD, these results may have translational applicability to human health.

PMID:39968160 | PMC:PMC11832531 | DOI:10.3389/fpain.2025.1501932

Ecol Evol. 2025 Feb 17;15(2):e71023. doi: 10.1002/ece3.71023. eCollection 2025 Feb.

ABSTRACT

Estimating species extinction risk is crucial to reverse biodiversity loss and to adopt proper conservation measures. Different sources may play a pivotal role in prioritising species conservation. Recently, citizen science demonstrated a substantial role, especially when it comes to butterflies. This study examines species records and richness in Aosta Valley, which represents one of the highest mountain areas in Europe. Through 30,351 data points from 1825 to 2022, the impact and efficiency of three groups of data sources were investigated: literature (i.e., publications and collections), sampling (butterfly experts' recording), and citizen science (open-source databases). The study also aims to assess the extinction potential of the butterflies in relation to functional traits. The results showed that even if there were significant differences in the number of records between the three sources, there were no significant differences for species recorded. Moreover, 2.9% of the butterfly community risks extinction, and it is related to some response traits. Indeed, extinction risks increase when the altitudinal range decreases and for multivoltines. In conclusion, citizen science has a strong impact on the amount of data and could be exploited to fill data gaps at low/medium altitudes. However, professional sampling is needed to focus on species no longer reported, and in particular on species that are difficult to identify, have specific distributions or particular traits (e.g., limited altitudinal range). Using different data sources, extinction risk estimation, and trait analysis, it is possible to prioritise studies on some species using different efforts (sampling and/or citizen sciences).

PMID:39967758 | PMC:PMC11832908 | DOI:10.1002/ece3.71023

Ecol Evol. 2025 Feb 17;15(2):e70984. doi: 10.1002/ece3.70984. eCollection 2025 Feb.

ABSTRACT

In shared environments, where different species interact depending on overlapping resources, complex interspecific interactions emerge, with human activities impacting these dynamics and influencing wildlife abundance and distribution. In the Alps, the presence of multiple species of ungulates, such as roe deer and red deer, and a predator, the wolf, creates a web of spatial and behavioral interactions in an area where farming, hunting and tourism have persisted over time, with tourism recently experiencing a substantial growth. Accounting for these multiple interactions, we modelled the co-occurrence probabilities of roe deer, red deer and wolves in an area of the Maritime Alps using data derived from 60 camera traps. We applied multi-species occupancy models to investigate (i) the role of species co-occurrences in explaining the occupancy of model species across the landscape, (ii) the role of human presence and activities on species occupancy and (iii) the potential effect of the hunting season on the species detection probabilities. Among the identified species, roe deer reported the highest frequency of recorded events and were the most widespread species. We provided important evidence of interspecific dependence, revealing that pairwise interactions among species had a greater impact than only considering individual environmental effects. We documented that the setting of cameras on trails increased the likelihood of detecting wolves but decreased the likelihood of detecting ungulates. Most importantly, the hunting season significantly reduced the likelihood of capturing roe deer, while having no effect on either red deer or wolves. Our results confirmed the relevance of including prey, predators, and human dynamics as a whole. Since the sharing of habitat makes human activities significantly important in defining predator-prey mechanisms, our insights are particularly relevant for defining solutions to optimize human-wildlife coexistence, especially in a highly anthropogenic system such as Europe.

PMID:39967757 | PMC:PMC11832906 | DOI:10.1002/ece3.70984

Brief Bioinform. 2024 Nov 22;26(1):bbaf029. doi: 10.1093/bib/bbaf029.

ABSTRACT

Modelling biological systems depends on the availability of data and components of the system at hand. As our understanding of these systems evolves, the ability to gradually refine models by adding new components of different formalisms covering stochastic, discrete, deterministic, and uncertainty without starting from scratch becomes essential. However, there remains a significant gap in the availability of methodologies and tool support for incrementally modelling and analysing complex biological systems in a flexible and intuitive manner. In this paper, we employ fuzzy hybrid Petri nets as a powerful expressive tool for presenting an incremental modelling and analysis protocol of biological systems. We demonstrate the utility of our protocol through a case study on cholesterol and lipoprotein metabolism and hypercholesterolemia therapy. Our model not only captures the underlying biochemical processes, but also quantitatively analyses how cholesterol levels are regulated, offering insights into potential therapeutic strategies for diseases associated with elevated cholesterol levels. The results confirm the validity and flexibility of our approach in representing complex biological processes and therapeutic interventions.

PMID:39967018 | DOI:10.1093/bib/bbaf029

BMC Cancer. 2025 Feb 18;25(1):292. doi: 10.1186/s12885-025-13713-z.

NO ABSTRACT

PMID:39966798 | DOI:10.1186/s12885-025-13713-z

BMC Genomics. 2025 Feb 18;26(1):158. doi: 10.1186/s12864-025-11351-0.

ABSTRACT

BACKGROUND: The nematode phylum includes many species key to soil food webs with trophic behaviours extending from feeding on microbes to macrofauna and plant roots. Among these, the plant parasitic cyst nematodes retain their eggs in protective cysts prolonging their survival under harsh conditions. These nematodes, including those from the genus Heterodera, cause significant economic losses in agricultural systems. Understanding of nematode diversity and ecology has expanded through application of genomic research, however, for Heterodera species there are very few available whole genome sequences. Sequencing and assembling Heterodera genomes is challenging due to various technical limitations imposed by the biology of Heterodera. Overcoming these limitations is essential for comprehensive insights into Heterodera parasitic interactions with plants, population studies, and for Australian biosecurity implications.

RESULTS: We hereby present draft genomes of six species of which Heterodera australis, H. humuli, H. mani and H. trifolii are presently recorded in Australia and two species, H. avenae and H. filipjevi, currently absent from Australia. The draft genomes were sequenced from genomic DNA isolated from 50 cysts each using an Illumina NovaSeq short read sequencing platform. The data revealed disparity in sequencing yield between species. What was previously identified as H. avenae in Australia using morphological traits is now confirmed as H. australis and may have consequences for wheat breeding programs in Australia that are breeding for resistance to H. avenae. A multigene phylogeny placed the sequenced species into taxonomic phylogenetic perspective. Genomic comparisons within the Avenae species group revealed orthologous gene clusters within the species, emphasising the shared and unique features of the group. The data also revealed the presence of a Wolbachia species, a putative bacterial endosymbiont from Heterodera humuli short read sequencing data.

CONCLUSION: Genomic research holds immense significance for agriculture, for understanding pest species diversity and the development of effective management strategies. This study provides insight into Heterodera, cyst nematode genomics and the associated symbionts and this work will serve as a baseline for further genomic analyses in this economically important nematode group.

PMID:39966714 | DOI:10.1186/s12864-025-11351-0

Nat Methods. 2025 Feb 18. doi: 10.1038/s41592-025-02594-6. Online ahead of print.

ABSTRACT

An ideal tool for the study of cellular biology would enable the measure of molecular activity nondestructively within living cells. Single-molecule localization microscopy (SMLM) techniques, such as single-molecule tracking (SMT), enable in situ measurements in cells but have historically been limited by a necessary tradeoff between spatiotemporal resolution and throughput. Here we address these limitations using oblique line scan (OLS), a robust single-objective light-sheet-based illumination and detection modality that achieves nanoscale spatial resolution and sub-millisecond temporal resolution across a large field of view. We show that OLS can be used to capture protein motion up to 14 μm2 s-1 in living cells. We further extend the utility of OLS with in-solution SMT for single-molecule measurement of ligand-protein interactions and disruption of protein-protein interactions using purified proteins. We illustrate the versatility of OLS by showcasing two-color SMT, STORM and single-molecule fluorescence recovery after photobleaching. OLS paves the way for robust, high-throughput, single-molecule investigations of protein function required for basic research, drug screening and systems biology studies.

PMID:39966678 | DOI:10.1038/s41592-025-02594-6

Nat Metab. 2025 Feb 18. doi: 10.1038/s42255-025-01220-1. Online ahead of print.

ABSTRACT

Dietary intake is tightly coupled to gut microbiota composition, human metabolism and the incidence of virtually all major chronic diseases. Dietary and nutrient intake are usually assessed using self-reporting methods, including dietary questionnaires and food records, which suffer from reporting biases and require strong compliance from study participants. Here, we present Metagenomic Estimation of Dietary Intake (MEDI): a method for quantifying food-derived DNA in human faecal metagenomes. We show that DNA-containing food components can be reliably detected in stool-derived metagenomic data, even when present at low abundances (more than ten reads). We show how MEDI dietary intake profiles can be converted into detailed metabolic representations of nutrient intake. MEDI identifies the onset of solid food consumption in infants, shows significant agreement with food frequency questionnaire responses in an adult population and shows agreement with food and nutrient intake in two controlled-feeding studies. Finally, we identify specific dietary features associated with metabolic syndrome in a large clinical cohort without dietary records, providing a proof-of-concept for detailed tracking of individual-specific, health-relevant dietary patterns without the need for questionnaires.

PMID:39966520 | DOI:10.1038/s42255-025-01220-1

Commun Biol. 2025 Feb 18;8(1):256. doi: 10.1038/s42003-025-07685-w.

ABSTRACT

The multi-petal "Hutou" jasmine (Jasminum sambac var. Trifoliatum) is highly valued for bonsai cultivation and landscape design, however, the aroma profile and mechanisms underlying floral scent formation remain elusive. In this study, we generate a nearly complete telomere-to-telomere (T2T) genome assembly of "Hutou" jasmine (487.45 Mb with contig N50 of 38.93 Mb). Metabolomic profiling unveils that 16 significantly differential volatiles (SDVs) may play a crucial role in the formation of flower aroma. Among them, five scented SDVs, particularly α-farnesene and pentanoic acid 1-ethenyl-1,5-dimethyl-4-hexenyl ester, contribute to the characteristic aroma profile of "Hutou" jasmine flowers. Weighted gene co-expression network analysis (WGCNA) identifies HTWRKY41, HTWRKY53, and HTHSP90 as the hub genes potentially regulating the production of these 16 metabolites. The expression of selected genes and duplication events drive the increased relative content of major sesquiterpenoids in terpenoid biosynthetic pathway. Four structural genes (BEAT3, BSMT1, BPBT2, and BPBT3) are potentially implicated in the emission of downstream key volatile esters (benzyl acetate, methyl benzoate, and benzyl benzoate) in the phenylpropanoids synthesis. Our integrated dataset of genomics, transcriptomics, and metabolomics present here provides a theoretical basis for the practical utilization of fragrance and genetic improvement in horticultural applications of "Hutou" jasmine.

PMID:39966493 | DOI:10.1038/s42003-025-07685-w

Nat Commun. 2025 Feb 18;16(1):1735. doi: 10.1038/s41467-025-56890-y.

ABSTRACT

The carbohydrates that fuel gut colonization by S. Typhimurium are not fully known. To investigate this, we designed a quality-controlled mutant pool to probe the metabolic capabilities of this enteric pathogen. Using neutral genetic barcodes, we tested 35 metabolic mutants across five different mouse models with varying microbiome complexities, allowing us to differentiate between context-dependent and context-independent nutrient sources. Results showed that S. Typhimurium uses D-mannose, D-fructose and likely D-glucose as context-independent carbohydrates across all five mouse models. The utilization of D-galactose, N-acetylglucosamine and hexuronates, on the other hand, was context-dependent. Furthermore, we showed that D-fructose is important in strain-to-strain competition between Salmonella serovars. Complementary experiments confirmed that D-glucose, D-fructose, and D-galactose are excellent niches for S. Typhimurium to exploit during colonization. Quantitative measurements revealed sufficient amounts of carbohydrates, such as D-glucose or D-galactose, in the murine cecum to drive S. Typhimurium colonization. Understanding these key substrates and their context-dependent or -independent use by enteric pathogens will inform the future design of probiotics and therapeutics to prevent diarrheal infections such as non-typhoidal salmonellosis.

PMID:39966379 | DOI:10.1038/s41467-025-56890-y

Nat Commun. 2025 Feb 18;16(1):1750. doi: 10.1038/s41467-025-56569-4.

ABSTRACT

Understanding the interaction between genetic and epigenetic variation remains a challenge due to confounding environmental factors. We propose that human induced Pluripotent Stem Cells (iPSCs) are an excellent model to study the relationship between genetic and epigenetic variation while controlling for environmental factors. In this study, we have created a comprehensive resource of high-quality genomic, epigenomic, and transcriptomic data from iPSC lines and three iPSC-derived cell types (neural stem cell (NSC), motor neuron, monocyte) from three healthy donors. We find that epigenetic variation is most strongly associated with genetic variation at the iPSC stage, and that relationship weakens as epigenetic variation increases in differentiated cells. Additionally, cell type is a stronger source of epigenetic variation than genetic variation. Further, we elucidate a utility of studying epigenetic variation in iPSCs and their derivatives for identifying important loci for GWAS studies and the cell types in which they may be acting.

PMID:39966349 | DOI:10.1038/s41467-025-56569-4

Biochem Biophys Res Commun. 2025 Feb 11;753:151479. doi: 10.1016/j.bbrc.2025.151479. Online ahead of print.

ABSTRACT

Neurodevelopmental disorders (NDDs) are characterized by diverse genetic underpinnings and abnormalities in the structure and function of the central nervous system. While the lung-specific SFTPC gene is critical for pulmonary development and homeostasis, its potential involvement in NDDs has not been previously explored. In this study, we identified compound heterozygous variants of SFTPC in two children diagnosed with NDDs, inherited from carrier parents. Bioinformatic analyses predicted these variants to be deleterious, and patient blood samples confirmed reduced SFTPC protein levels. To investigate the functional impact of these mutations, we generated a Sftpc-knock-in (Sftpc-KI) mouse model carrying the defective alleles. The Sftpc-KI mice exhibited significantly reduced Sftpc expression in both lung and blood samples. Remarkably, despite its lung-specific expression, Sftpc-KI mice displayed pronounced impairments in neurobehavioral performance. Proteomic analyses of the Sftpc-KI mouse brain revealed dysregulated proteins associated with neuroinflammation. Furthermore, primary microglial cells isolated from these mice exhibited heightened expression of M1 activation markers, indicating aberrant microglial activation. Our findings uncover a previously unrecognized connection between lung-specific SFTPC dysfunction and neurodevelopmental disorders, suggesting the existence of a novel brain-lung axis and opening new avenues for research into the molecular mechanisms underlying NDDs.

PMID:39965266 | DOI:10.1016/j.bbrc.2025.151479

Adv Sci (Weinh). 2025 Feb 18:e2412256. doi: 10.1002/advs.202412256. Online ahead of print.

ABSTRACT

Most bacterial cells are 1-2 microns in size, limiting intracellular products like polyhydroxyalkanoates (PHA) accumulation. Cell size is regulated by key genes such as mreB and minCD, which encode cellular skeleton protein and control cell fission ring location, respectively. Their expression changes significantly affect microbial growth. This study successfully redesigns the ClpXP protein degradation system by deleting the sspB gene and using mutated SsrA tags with different degradation rates to control MreB degradation. Dynamic degradation of MreB allows non-model bacterium Halomonas bluephagenesis to grow normally and increase cell size simultaneously. Combined with overexpression of minCD, H. bluephagenesis with progressive MreB degradation increases the cell size further, albeit with a reduced growth rate. H. bluephagenesis CYL0307, with the PHB granule-associated protein PhaP1 deleted and phaABRe overexpressed in the MreB-degraded strain, increases cell volume more than nine times compared to the original strain. CYL0307 produces 149 g L-1 cell dry weight containing 82% PHB after 44 h in a 5000 L bioreactor, with cells containing single large PHB granules, simplifying recovery and purification. These results provide a post-translational gene regulation method in H. bluephagenesis and a strategy for enhancing PHB production via morphological engineering.

PMID:39965051 | DOI:10.1002/advs.202412256