Systems Biology

Pseudomonas aeruginosa maintains an inducible array of novel and diverse prophages over lengthy persistence in cystic fibrosis lungs

Fri, 2025-01-31 06:00

FEMS Microbiol Lett. 2025 Jan 31:fnaf017. doi: 10.1093/femsle/fnaf017. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa has increasing clinical relevance and commonly occupies the cystic fibrosis (CF) airways. Its ability to colonize and persist in diverse niches is attributed to its large accessory genome, where prophages represent a common feature and may contribute to its fitness and persistence. We focused on the CF airways niche and used 197 longitudinal isolates from 12 patients persistently infected by P. aeruginosa. We computationally predicted intact prophages for each longitudinal group and scored their long-term persistence. We then confirmed prophage inducibility and mapped their location in the host chromosome with lysate sequencing. Using comparative genomics, we evaluated prophage genomic diversity, long-term persistence and level of genomic maintenance. Our findings support previous findings that most P. aeruginosa genomes harbour prophages some of which can self-induce, and that a common CF-treating antibiotic, ciprofloxacin, can induce prophages. Induced prophage genomes displayed high diversity and even genomic novelty. Finally, all induced prophages persisted long-term with their genomes avoiding gene loss and degradation over four years of host replication in the stressful CF airways niche. This and our detection of phage genes which contribute to host competitiveness and adaptation, lends support to our hypothesis that the vast majority of prophages detected as intact and inducible in this study facilitated their host fitness and persistence.

PMID:39890605 | DOI:10.1093/femsle/fnaf017

Categories: Literature Watch

Use of termination events and mortality data recorded during the lactation as a proxy to predict the genetics of resilience and health of dairy cattle

Fri, 2025-01-31 06:00

J Dairy Sci. 2025 Jan 29:S0022-0302(25)00046-3. doi: 10.3168/jds.2024-25812. Online ahead of print.

ABSTRACT

Increasing production and environmental challenges in dairy cattle means that selecting for resilience is becoming more important. This study explored whether data on cows that exit before completing their lactation and those that die during lactation can be used to predict resilience. To identify predictors of resilience, exiting the herd by 60, 120, 180, and 240 d were defined as traits. Additional traits were defined, by including all the cows that died during the entire lactation to the cows that exited at different times up to 240 d of lactation. For all traits, cows that exited the herd or died were coded as 1, otherwise as 0 at the end of the lactation. We used performance and exit data of Holstein (H) and Jersey (J) cows that calved between 1998 and 2023. The data were analyzed using a multi-trait sire model to estimate heritability and correlations with milk yield (MY), somatic cell count (SCC), calving interval (CIN), and selected type traits. The results showed that the proportion of cows that exited by 60 d was 2%, increasing by about 2% every 2 mo until exit by 240 d. The trend over the years in the proportion of exits, taking Exit 180d and Exit 180 + death as an example, showed an undesirable increase from 5.6% in 2000 to 9.4% in 2022. Heritability of all exit traits was low, increasing from below 1% for exit by 60 to 2.8% for exit by 240 d + all deaths over the lactation. The genetic correlation of early exit (i.e., 60 or 120 d) with first test-day MY was positive (unfavorable) and higher at the beginning (0.4), decreasing over time to be favorable in J (-0.2) and near zero in H (0.1) by the end of the lactation. On the other hand, the genetic correlation of exit with first test-day SCC became stronger (favorable) at the end of the lactation (0.3 to 0.4). Exit at any time during the lactation had the strongest genetic correlation with CIN (i.e., fertility). The genetic correlation of exit traits with body condition score (BCS) and angularity showed that the likelihood of cow exit, especially up to 180 d, was higher for thin and more angular cows. The genetic correlation estimates imply that cows with high potential for MY, poor fertility, poor BCS, and high scores for angularity are more likely to exit early due to metabolic stress. The change in genetic correlation between exit and MY early from unfavorable to favorable in J is due to more culling for milk and less for fertility and udder health is leading to an undesirable genetic trend for exit by 180 d as well as exit by 180 d + all death. However, the increasing phenotypic trend of exit rates in both breeds suggests a need for close monitoring. The selective use of exit data can help to develop genetic evaluations for resilience and health traits and validate and complement data collected to improve health and welfare during the transition period.

PMID:39890077 | DOI:10.3168/jds.2024-25812

Categories: Literature Watch

CAR T cells, CAR NK cells, and CAR macrophages exhibit distinct traits in glioma models but are similarly enhanced when combined with cytokines

Fri, 2025-01-31 06:00

Cell Rep Med. 2025 Jan 28:101931. doi: 10.1016/j.xcrm.2025.101931. Online ahead of print.

ABSTRACT

Chimeric antigen receptor (CAR) T cell therapy is a promising immunotherapy against cancer. Although there is a growing interest in other cell types, a comparison of CAR immune effector cells in challenging solid tumor contexts is lacking. Here, we compare mouse and human NKG2D-CAR-expressing T cells, natural killer (NK) cells, and macrophages against glioblastoma, the most aggressive primary brain tumor. Invitro we show that T cell cancer killing is CAR dependent, whereas intrinsic cytotoxicity overrules CAR dependence for NK cells, and CAR macrophages reduce glioma cells in co-culture assays. In orthotopic immunocompetent glioma mouse models, systemically administered CAR T cells demonstrate superior accumulation in the tumor, and each immune cell type induces distinct changes in the tumor microenvironment. An otherwise low therapeutic efficacy is significantly enhanced by co-expression of pro-inflammatory cytokines in all CAR immune effector cells, underscoring the necessity for multifaceted cell engineering strategies to overcome the immunosuppressive solid tumor microenvironment.

PMID:39889712 | DOI:10.1016/j.xcrm.2025.101931

Categories: Literature Watch

Integrative proteo-transcriptomic characterization of advanced fibrosis in chronic liver disease across etiologies

Fri, 2025-01-31 06:00

Cell Rep Med. 2025 Jan 27:101935. doi: 10.1016/j.xcrm.2025.101935. Online ahead of print.

ABSTRACT

Chronic hepatic injury and inflammation from various causes can lead to fibrosis and cirrhosis, potentially predisposing to hepatocellular carcinoma. The molecular mechanisms underlying fibrosis and its progression remain incompletely understood. Using a proteo-transcriptomics approach, we analyze liver and plasma samples from 330 individuals, including 40 healthy individuals and 290 patients with histologically characterized fibrosis due to chronic viral infection, alcohol consumption, or metabolic dysfunction-associated steatotic liver disease. Our findings reveal dysregulated pathways related to extracellular matrix, immune response, inflammation, and metabolism in advanced fibrosis. We also identify 132 circulating proteins associated with advanced fibrosis, with neurofascin and growth differentiation factor 15 demonstrating superior predictive performance for advanced fibrosis(area under the receiver operating characteristic curve [AUROC] 0.89 [95% confidence interval (CI) 0.81-0.97]) compared to the fibrosis-4 model (AUROC 0.85 [95% CI 0.78-0.93]). These findings provide insights into fibrosis pathogenesis and highlight the potential for more accurate non-invasive diagnosis.

PMID:39889710 | DOI:10.1016/j.xcrm.2025.101935

Categories: Literature Watch

Decoding the blueprints of embryo development with single-cell and spatial omics

Fri, 2025-01-31 06:00

Semin Cell Dev Biol. 2025 Jan 30;167:22-39. doi: 10.1016/j.semcdb.2025.01.002. Online ahead of print.

ABSTRACT

Embryonic development is a complex and intricately regulated process that encompasses precise control over cell differentiation, morphogenesis, and the underlying gene expression changes. Recent years have witnessed a remarkable acceleration in the development of single-cell and spatial omic technologies, enabling high-throughput profiling of transcriptomic and other multi-omic information at the individual cell level. These innovations offer fresh and multifaceted perspectives for investigating the intricate cellular and molecular mechanisms that govern embryonic development. In this review, we provide an in-depth exploration of the latest technical advancements in single-cell and spatial multi-omic methodologies and compile a systematic catalog of their applications in the field of embryonic development. We deconstruct the research strategies employed by recent studies that leverage single-cell sequencing techniques and underscore the unique advantages of spatial transcriptomics. Furthermore, we delve into both the current applications, data analysis algorithms and the untapped potential of these technologies in advancing our understanding of embryonic development. With the continuous evolution of multi-omic technologies, we anticipate their widespread adoption and profound contributions to unraveling the intricate molecular foundations underpinning embryo development in the foreseeable future.

PMID:39889540 | DOI:10.1016/j.semcdb.2025.01.002

Categories: Literature Watch

Spatial metabolic modulation in vascular dementia by Erigeron breviscapus injection using ambient mass spectrometry imaging

Fri, 2025-01-31 06:00

Phytomedicine. 2025 Jan 20;138:156412. doi: 10.1016/j.phymed.2025.156412. Online ahead of print.

ABSTRACT

BACKGROUND: Vascular dementia (VaD), a significant cognitive disorder, is caused by reduced cerebral blood flow. Unraveling the metabolic heterogeneity and reprogramming in VaD is essential for understanding its molecular pathology and developing targeted therapies. However, the in situ metabolic regulation within the specific brain regions affected by VaD has not been thoroughly investigated, and the therapeutic mechanisms of Erigeron breviscapus injection (EBI), a traditional Chinese medicine, require further elucidation.

PURPOSE: To investigate the region-specific metabolic alterations in a VaD rat model, explore the therapeutic effects of EBI at a microregional level, identify the key metabolic pathways and metabolites involved in VaD, and elucidate how EBI modulates these pathways to exert its therapeutic effects.

METHODS: Air-flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI), a novel technique, was employed to investigate the metabolic changes in the brain microregions. We used a bilateral common carotid artery occlusion model to induce VaD in rats. Network analysis and network pharmacology were used to assess the local metabolic effects of the EBI treatment (3.6 mL/kg/day for 2 weeks).

RESULTS: The EBI treatment significantly ameliorated the neurological deficits in VaD rats. AFADESI-MSI revealed 31 key metabolites with significant alterations in the VaD model, particularly within the pathways related to neurotransmitter metabolism, redox homeostasis, and osmoregulation. The metabolic disturbances were primarily observed in the striatum (ST), pyriform cortex (PCT), hippocampus (HP), and other critical brain regions. The EBI treatment effectively reversed these metabolic imbalances, especially in neurotransmitter metabolism, suggesting its potential in mitigating VaD-related cognitive decline.

CONCLUSION: Our findings not only shed light on the molecular underpinnings of VaD but also highlight the potential of EBI as a therapeutic agent in neurodegenerative disorders. Moreover, this study demonstrates the power of advanced mass spectrometry imaging techniques in phytomedicine, offering new insights into the spatial metabolic changes induced by botanical treatments.

PMID:39889490 | DOI:10.1016/j.phymed.2025.156412

Categories: Literature Watch

Computational Drug Repositioning in Cardiorenal Disease: Opportunities, Challenges, and Approaches

Fri, 2025-01-31 06:00

Proteomics. 2025 Jan 31:e202400109. doi: 10.1002/pmic.202400109. Online ahead of print.

NO ABSTRACT

PMID:39888210 | DOI:10.1002/pmic.202400109

Categories: Literature Watch

HOS15 impacts DIL9 protein stability during drought stress in Arabidopsis

Fri, 2025-01-31 06:00

New Phytol. 2025 Jan 31. doi: 10.1111/nph.20398. Online ahead of print.

ABSTRACT

HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE 15 (HOS15) acts as a substrate receptor of E3 ligase complex, which plays a negative role in drought stress tolerance. However, whether and how HOS15 participates in controlling important transcriptional regulators remains largely unknown. Here, we report that HOS15 physically interacts with and tightly regulates DROUGHT-INDUCED LIKE 19 (DIL9) protein stability. Moreover, application of exogenous abscisic acid (ABA) stabilizes the interaction between DIL9 and HOS15, leading to ABA-induced proteasomal degradation of DIL9 by HOS15. Genetic analysis revealed that DIL9 functions downstream to HOS15 and that the drought tolerance of hos15-2 plants was impaired in dil9/hos15 double mutants. Notably, DIL9 is directly associated with the promoter regions of ABF transcription factors and facilitates their expression, which is pivotal in enhancing ABA-dependent drought tolerance. Collectively, these findings demonstrate that HOS15 consistently degrades DIL9 under normal condition, while stress (drought/ABA) promotes the DIL9 activity for binding to the promoter regions of ABFs and positively regulates their expression in response to dehydration.

PMID:39888052 | DOI:10.1111/nph.20398

Categories: Literature Watch

Truncation-Enhanced Aptamer Binding Affinity and Its Potential as a Sensor for Macrobrachium rosenbergii Nodavirus Detection

Fri, 2025-01-31 06:00

J Fish Dis. 2025 Jan 31:e14093. doi: 10.1111/jfd.14093. Online ahead of print.

ABSTRACT

White tail disease in Macrobrachium rosenbergii is caused by M. rosenbergii nodavirus (MrNV) infection, resulting in up to 100% mortality in larvae and post-larvae stages, severely impacting aquaculture production. Existing genome-based detection methods for MrNV are costly and time-consuming, highlighting the need for rapid and cost-effective diagnostic tests. This study evaluated the effects of truncating selected aptamer on its binding affinity to the MrNV capsid protein. The previously isolated and identified aptamer through magnetic-capture SELEX and Next Generation Sequencing demonstrated high binding affinity to the MrNV capsid protein. Truncation at the primer overhang was found to improve binding affinity, reducing the dissociation constant from 347 nM to 30.1 nM. The calculated limit of detection for the truncated aptamer decreased from 5.64 nM to 1.7 nM, while the limit of quantification decreased from 17.1 nM to 5.16 nM. These reductions indicate that the truncated aptamer has higher sensitivity compared to the full-length aptamer. In tests with MrNV-infected M. rosenbergii samples, both the enzyme-linked aptamer assay and the gold nanoparticle aptasensor assay showed consistent results when 0.5 μg of total protein lysate was used. This indicates that the prawn protein concentration interferes with the detection of the viral protein. These findings suggest the potential application of the truncated aptamer as a sensor in the development of a practical aptamer-based diagnostic kit. For instance, an aptamer-based lateral flow assay test kit could provide a user-friendly, cost-effective solution that eliminates the need for sophisticated instrumentation for diagnosis or data interpretation, making it ideal for detecting MrNV infection in M. rosenbergii aquaculture.

PMID:39887434 | DOI:10.1111/jfd.14093

Categories: Literature Watch

SEC-MX: an approach to systematically study the interplay between protein assembly states and phosphorylation

Thu, 2025-01-30 06:00

Nat Commun. 2025 Jan 30;16(1):1176. doi: 10.1038/s41467-025-56303-0.

ABSTRACT

A protein's molecular interactions and post-translational modifications (PTMs), such as phosphorylation, can be co-dependent and reciprocally co-regulate each other. Although this interplay is central for many biological processes, a systematic method to simultaneously study assembly states and PTMs from the same sample is critically missing. Here, we introduce SEC-MX (Size Exclusion Chromatography fractions MultipleXed), a global quantitative method combining Size Exclusion Chromatography and PTM-enrichment for simultaneous characterization of PTMs and assembly states. SEC-MX enhances throughput, allows phosphopeptide enrichment, and facilitates quantitative differential comparisons between biological conditions. Conducting SEC-MX on HEK293 and HCT116 cells, we generate a proof-of-concept dataset, mapping thousands of phosphopeptides and their assembly states. Our analysis reveals intricate relationships between phosphorylation events and assembly states and generates testable hypotheses for follow-up studies. Overall, we establish SEC-MX as a valuable tool for exploring protein functions and regulation beyond abundance changes.

PMID:39885126 | DOI:10.1038/s41467-025-56303-0

Categories: Literature Watch

Metagenomic global survey and in-depth genomic analyses of Ruminococcus gnavus reveal differences across host lifestyle and health status

Thu, 2025-01-30 06:00

Nat Commun. 2025 Jan 30;16(1):1182. doi: 10.1038/s41467-025-56449-x.

ABSTRACT

Ruminococcus gnavus is a gut bacterium found in > 90% of healthy individuals, but its increased abundance is also associated with chronic inflammatory diseases, particularly Crohn's disease. Nevertheless, its global distribution and intraspecies genomic variation remain understudied. By surveying 12,791 gut metagenomes, we recapitulated known associations with metabolic diseases and inflammatory bowel disease. We uncovered a higher prevalence and abundance of R. gnavus in Westernized populations and observed bacterial relative abundances up to 83% in newborns. Next, we built a resource of R. gnavus isolates (N = 45) from healthy individuals and Crohn's disease patients and generated complete R. gnavus genomes using PacBio circular consensus sequencing. Analysis of these genomes and publicly available high-quality draft genomes (N = 333 genomes) revealed multiple clades which separated Crohn's-derived isolates from healthy-derived isolates. Presumed R. gnavus virulence factors could not explain this separation. Bacterial genome-wide association study revealed that Crohn's-derived isolates were enriched in genes related to mobile elements and mucin foraging. Together, we present a large R. gnavus resource that will be available to the scientific community and provide novel biological insights into the global distribution and genomic variation of R. gnavus.

PMID:39885121 | DOI:10.1038/s41467-025-56449-x

Categories: Literature Watch

Identification and characterization of GRAS genes in passion fruit (Passiflora edulis Sims) revealed their roles in development regulation and stress response

Thu, 2025-01-30 06:00

Plant Cell Rep. 2025 Jan 30;44(2):46. doi: 10.1007/s00299-025-03432-x.

ABSTRACT

Twenty-nine GRAS genes were identified in passion fruit, the N-terminal regions and 3D (three-dimensional) structures were closely related with their tissue-specific expression patterns. Candidate PeGRASs for enhancing stress resistance were identified. Passion fruit (Passiflora edulis Sims) is a tropical fruit crop with significant edible and ornamental value, but its growth and development are highly sensitive to environmental conditions. The plant-specific GRAS gene family plays critical roles in regulating growth, development, and stress responses. Here, we performed the first comprehensive analysis of the GRAS gene family in passion fruit. A total of 29 GRAS genes were identified and named PeGRAS1 to PeGRAS29 based on their chromosomal locations. Phylogenetic analysis using GRAS proteins from passion fruit, Arabidopsis, and rice revealed that PeGRAS proteins could be classified into 10 subfamilies. Compared to Arabidopsis, passion fruit lacked members from the LAS subfamily but gained one GRAS member (PeGRAS9) clustered with the rice-specific Os4 subfamily. Structural analysis performed in silico revealed that most PeGRAS members were intron less and exhibited conserved motif patterns near the C-terminus, while the N-terminal regions varied in sequence length and composition. Members within certain subfamilies including DLT, PAT1, and LISCL with similar unstructured N-terminal regions and 3D structures, exhibited similar tissue-specific expression patterns. While PeGRAS members with difference in these structural features, even within the same subfamily (e.g., DELLA), displayed distinct expression patterns. These findings highlighted that the N-terminal regions of GRAS proteins may be critical for their specific functions. Moreover, many PeGRAS members, particularly those from the PAT1 subfamily, were widely involved in stress responses, with PeGRAS19 and PeGRAS26 likely playing roles in cold tolerance, and PeGRAS25 and PeGRAS28 in drought resistance. This study provides a foundation for further functional research on PeGRASs and offers potential candidates for molecular breeding aimed at enhancing stress tolerance in passion fruit.

PMID:39885065 | DOI:10.1007/s00299-025-03432-x

Categories: Literature Watch

Natural Products Analysis Through Time: From Past Achievements to Future Prospects

Thu, 2025-01-30 06:00

Methods Mol Biol. 2025;2895:3-13. doi: 10.1007/978-1-0716-4350-1_1.

ABSTRACT

This introductory chapter traces the evolution of (bio)chemical assays, emphasizing the critical role of robust protocols in ensuring reproducibility-a fundamental aspect of scientific research. With the advent of systems biology, the need for standardized methods has intensified, particularly for integrating vast datasets in open-access formats. The historical progression from basic plant morphology to advanced chromatographic and spectroscopic techniques in phytochemistry highlights the necessity for precise, reproducible protocols.As metabolomics advances, there is a renewed focus on targeted approaches, shifting from broad, untargeted analyses to more specific, hypothesis-driven studies. This chapter also explores the future of analytical techniques, including cellomics and real-time metabolic flux measurements, which offer new insights into dynamic biochemical processes.Ultimately, this introduction underscores the importance of innovation in developing new methods that address current scientific challenges, particularly in pharmacognosy and analytical phytochemistry. The chapter sets the stage for the broader discussion on the necessity of well-designed protocols that facilitate effective data sharing and collaboration across research disciplines.

PMID:39885019 | DOI:10.1007/978-1-0716-4350-1_1

Categories: Literature Watch

Caps-ac4C: an effective computational framework for identifying N4-acetylcytidine sites in human mRNA based on deep learning

Thu, 2025-01-30 06:00

J Mol Biol. 2025 Jan 28:168961. doi: 10.1016/j.jmb.2025.168961. Online ahead of print.

ABSTRACT

N4-acetylcytidine (ac4C) is a crucial post-transcriptional modification in human mRNA, involving the acetylation of the nitrogen atom at the fourth position of cytidine. This modification, catalyzed by N-acetyltransferases such as NAT10, is primarily found in mRNA's coding regions and enhances translation efficiency and mRNA stability. ac4C is closely associated with various diseases, including cancer. Therefore, accurately identifying ac4C in human mRNA is essential for gaining deeper insights into disease pathogenesis and provides potential pathways for the development of novel medical interventions. In silico methods for identifying ac4C are gaining increasing attention due to their cost-effectiveness, requiring minimal human and material resources. In this study, we propose an efficient and accurate computational framework, Caps-ac4C, for the precise detection of ac4C in human mRNA. Caps-ac4C utilizes chaos game representation to encode RNA sequences into "images" and employs capsule networks to learn global and local features from these RNA "images". Experimental results demonstrate that Caps-ac4C achieves state-of-the-art performance, achieving 95.47% accuracy and 0.912 MCC on the test set, surpassing the current best methods by 10.69% accuracy and 0.216 MCC. In summary, Caps-ac4C represents the most accurate tool for predicting ac4C sites in human mRNA, highlighting its significant contribution to RNA modification research. For user convenience, we developed a user-friendly web server, which can be accessed for free at:https://awi.cuhk.edu.cn/Caps-ac4C/index.php.

PMID:39884569 | DOI:10.1016/j.jmb.2025.168961

Categories: Literature Watch

Evaluating the performance of the PREDAC method in flu vaccine recommendations over the past decade (2013-2023)

Thu, 2025-01-30 06:00

Virol Sin. 2025 Jan 28:S1995-820X(25)00004-5. doi: 10.1016/j.virs.2025.01.004. Online ahead of print.

NO ABSTRACT

PMID:39884360 | DOI:10.1016/j.virs.2025.01.004

Categories: Literature Watch

Computational design and improvement of a broad influenza virus HA stem targeting antibody

Thu, 2025-01-30 06:00

Structure. 2025 Jan 21:S0969-2126(25)00002-4. doi: 10.1016/j.str.2025.01.002. Online ahead of print.

ABSTRACT

Broadly neutralizing antibodies (nAbs) are vital therapeutic tools to counteract both pandemic and seasonal influenza threats. Traditional strategies for optimizing nAbs generally rely on labor-intensive, high-throughput mutagenesis screens. Here, we present an innovative structure-based design framework for the optimization of nAbs, which integrates epitope-paratope analysis, computational modeling, and rational design approaches, complemented by comprehensive experimental assessment. This approach was applied to optimize MEDI8852, a nAb targeting the stalk region of influenza A virus hemagglutinin (HA). The resulting variant, M18.1.2.2, shows a marked enhancement in both affinity and neutralizing efficacy, as demonstrated both in vitro and in vivo. Computational modeling reveals that this improvement can be attributed to the fine-tuning of interactions between the antibody's side-chains and the epitope residues that are highly conserved across the influenza A virus HA stalk. Our dry-wet iterative protocol for nAb optimization presented here yielded a promising candidate for influenza intervention.

PMID:39884272 | DOI:10.1016/j.str.2025.01.002

Categories: Literature Watch

Artificial intelligence enhanced microfluidic system for multiplexed point-of-care-testing of biological thiols

Thu, 2025-01-30 06:00

Talanta. 2025 Jan 23;287:127619. doi: 10.1016/j.talanta.2025.127619. Online ahead of print.

ABSTRACT

Cysteamine (CA) serves as a cystine-depleting agent employed in the management of cystinosis and a range of other medical conditions. Monitoring blood CA levels at the point of care is imperative due to the risk of toxicity associated with elevated CA dosages. An additional significant challenge is presented by the intricate composition of human plasma and the presence of various interfering biological thiols, which possess similar structures or properties. Here, this work proposes an AI-enhanced Lab-on-a-disc system, also termed AI-LOAD, for multiplexed point-of-care testing of cysteamine. The AI-LOAD system incorporates an online whole blood separation mechanism alongside a naked-eye colorimetric detection module, facilitating the rapid and precise visual identification of cysteamine. Remarkably, the system necessitates only 40 μL of whole blood to analyze eight samples within 3-min, achieving a limit of detection as low as 10 μM, which is lower than the physiological toxic concentration of 0.1 mM. By leveraging diverse colorimetric responses generated through interactions between gold nanoparticles of varying sizes and different biological thiols, combined with artificial intelligence methodologies, the system successfully accomplished specific recognition of various biological thiols with 100 % accuracy. The proposed AI-LOAD will drive advancements in centrifugal microfluidics for point-of-care testing, thereby holding potential for broader applications in future biomedical research and in vitro diagnosis.

PMID:39884122 | DOI:10.1016/j.talanta.2025.127619

Categories: Literature Watch

Considerations for Domestication of Novel Strains of Filamentous Fungi

Thu, 2025-01-30 06:00

ACS Synth Biol. 2025 Jan 30. doi: 10.1021/acssynbio.4c00672. Online ahead of print.

ABSTRACT

Fungi, especially filamentous fungi, are a relatively understudied, biotechnologically useful resource with incredible potential for commercial applications. These multicellular eukaryotic organisms have long been exploited for their natural production of useful commodity chemicals and proteins such as enzymes used in starch processing, detergents, food and feed production, pulping and paper making and biofuels production. The ability of filamentous fungi to use a wide range of feedstocks is another key advantage. As chassis organisms, filamentous fungi can express cellular machinery, and metabolic and signal transduction pathways from both prokaryotic and eukaryotic origins. Their genomes abound with novel genetic elements and metabolic processes that can be harnessed for biotechnology applications. Synthetic biology tools are becoming inexpensive, modular, and expansive while systems biology is beginning to provide the level of understanding required to design increasingly complex synthetic systems. This review covers the challenges of working in filamentous fungi and offers a perspective on the approaches needed to exploit fungi as microbial cell factories.

PMID:39883596 | DOI:10.1021/acssynbio.4c00672

Categories: Literature Watch

Food hardness preference reveals multisensory contributions of fly larval gustatory organs in behaviour and physiology

Thu, 2025-01-30 06:00

PLoS Biol. 2025 Jan 30;23(1):e3002730. doi: 10.1371/journal.pbio.3002730. eCollection 2025 Jan.

ABSTRACT

Food presents a multisensory experience, with visual, taste, and olfactory cues being important in allowing an animal to determine the safety and nutritional value of a given substance. Texture, however, remains a surprisingly unexplored aspect, despite providing key information about the state of the food through properties such as hardness, liquidity, and granularity. Food perception is achieved by specialised sensory neurons, which themselves are defined by the receptor genes they express. While it was assumed that sensory neurons respond to one or few closely related stimuli, more recent findings challenge this notion and support evidence that certain sensory neurons are more broadly tuned. In the Drosophila taste system, gustatory neurons respond to cues of opposing hedonic valence or to olfactory cues. Here, we identified that larvae ingest and navigate towards specific food substrate hardnesses and probed the role of gustatory organs in this behaviour. By developing a genetic tool targeting specifically gustatory organs, we show that these organs are major contributors for evaluation of food hardness and ingestion decision-making. We find that ablation of gustatory organs not only results in loss of chemosensation, but also navigation and ingestion preference to varied substrate hardnesses. Furthermore, we show that certain neurons in the primary taste organ exhibit varied and concurrent physiological responses to mechanical and multimodal stimulation. We show that individual neurons house independent mechanisms for multiple sensory modalities, challenging assumptions about capabilities of sensory neurons. We propose that further investigations, across the animal kingdom, may reveal higher sensory complexity than currently anticipated.

PMID:39883595 | DOI:10.1371/journal.pbio.3002730

Categories: Literature Watch

Choosing the right signaling pathway: hormone responses to Phytophthora cinnamomi during compatible and incompatible interactions with chestnut (Castanea spp.)

Thu, 2025-01-30 06:00

Tree Physiol. 2025 Jan 30:tpaf016. doi: 10.1093/treephys/tpaf016. Online ahead of print.

ABSTRACT

Ink disease caused by the hemibiotrophic root pathogen Phytophthora cinnamomi (Pc) is devastating for the European chestnut (Castanea sativa), unlike Asian chestnuts and interspecific hybrids which are resistant to Pc. The role that hormone responses play for Pc resistance remains little understood, especially regarding the temporal regulation of hormone responses. We explored the relationship between changes in tree health and physiology and alterations in leaf and root phytohormones and primary and secondary metabolites during compatible and incompatible Castanea spp.-Pc interactions. Susceptible (S) C. sativa and resistant (R) C. sativa x C. crenata ramets were inoculated with Pc in roots and assessed for disease progression, leaf physiology and biochemistry at 1, 3, 5 and 8 days after inoculation (dai). In S chestnuts, Pc increasingly deteriorated the leaf physiological functioning by decreasing leaf CO2 assimilation, stomatal conductance, transpiration rate, chlorophylls content and the maximum quantum yield of the photosystem II over time, triggering aerial symptoms (leaf wilting and chlorosis) 8 dai. Pc had little impact on the leaf physiological functioning of R chestnuts which remained asymptomatic. In roots of S chestnuts, Pc transiently induced jasmonates signaling (5 dai) while impairing root carbohydrates metabolism over time. In leaves, a transient antioxidant burst (5 dai) followed by abscisic acid (ABA) accumulation (8 dai) was observed. R chestnuts responded to Pc by up-regulating root salicylic acid (SA) at early (1 dai) and late (8 dai) infection stages, in an antagonistic crosstalk with root ABA. Overall, the results pinpoint an important role of SA in mediating the resistant response of chestnuts to Pc, but also show that the specific hormone pathways induced by Pc are genotype dependent. The study also highlights that the dynamic nature of hormone responses over time must be considered when elucidating hormone-regulated responses to Pc.

PMID:39883087 | DOI:10.1093/treephys/tpaf016

Categories: Literature Watch

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