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Biology subjects

Lim, S. C.

Publications and source records attributed to Lim, S. C..

6 recordsLinked to original sources

From Parametric Guessing to Graph-Grounded Answers: Building Reliable ChatGPT-like tools for Plant Science

Large language models (LLMs) are increasingly used by plant biologists to summarize literature, generate hypotheses, and interpret experimental results. However, LLMs are unreliable sources of exhaustive, source-attributed facts, a critical limitation for the list-style queries that pervade plant biology (e.g., "list all transcription factors regulating secondary cell wall (SCW) biosynthesis in Arabidopsis"). Here, we query ChatGPT, Claude, and Gemini with such queries and demonstrate that none return complete gene lists with reliable citations. We trace these failures to how LLMs store knowledge: as statistical patterns distributed across billions of internal parameters, with no mechanism to guarantee completeness, provenance, or reproducibility. We also review fine-tuning mitigation strategies, including multi-task instruction tuning, parameter-efficient methods, and context engineering, that alleviate but do not resolve these limitations. We then discuss retrieval-augmented generation (RAG), which feeds relevant documents to the LLM at query time, and argue that while it improves source attribution, it remains impractical when answers require synthesizing information scattered across hundreds of papers. As an alternative, we advocate graph retrieval-augmented generation (GraphRAG), in which the LLM serves as a reasoning and language interface over a structured, provenance-linked knowledge graph (KG) that returns complete result sets reproducibly. We outline a practical GraphRAG architecture and survey existing plant KG resources. Finally, we discuss open challenges, including entity disambiguation, relation normalization and evidence grading, and propose a roadmap for building open, continuously updated plant KGs that can turn "read 1,000 papers" into a single reproducible query.

bioinformatics↗

(R,S)-ketamine's rapid-acting antidepressant effects are modulated by NR2B- containing NMDA receptors on adult-born hippocampal neurons

Standard antidepressant treatments often take weeks to reach efficacy and are ineffective for many patients. (R,S)-ketamine, an N-methyl-D-aspartate (NMDA) antagonist, has been shown to be a rapid-acting antidepressant and to decrease depressive symptoms within hours of administration. While previous studies have shown the importance of the NR2B subunit of the NMDA receptor (NMDAR) on interneurons in the medial prefrontal cortex (mPFC), no study has investigated the influence of NR2B-expressing adult-born granule cells (abGCs). In this study, we examined whether (R,S)-ketamines efficacy depends upon these adult-born hippocampal neurons using a genetic strategy to selectively ablate the NR2B subunit of the NMDAR from Nestin+ cells. To validate our findings, we also used several other transgenic lines including one in which NR2B was deleted from an interneuron (Parvalbumin (PV)+) population. We report that in male mice, NR2B expression on 6-week-old adult-born neurons is necessary for (R,S)-ketamines effects on behavioral despair in the forced swim test (FST) and on hyponeophagia in the novelty suppressed feeding (NSF) paradigm, as well on fear behavior following contextual fear conditioning (CFC). In female mice, NR2B expression is necessary for effects on hyponeophagia in the NSF. We also find that ablating neurogenesis increases fear expression in CFC, which is buffered by (R,S)-ketamine administration. In line with previous studies, these results suggest that 6-week-old adult-born hippocampal neurons expressing NR2B partially modulate (R,S)-ketamines rapid-acting effects. Future work targeting these 6-week-old adult-born neurons may prove beneficial for increasing the efficacy of (R,S)-ketamines antidepressant actions.

neuroscience↗

Persistence of spore-forming Clostridium (Clostridioides) difficile through wastewater treatment plants in Western Australia

There is growing evidence that shows Clostridium (Clostridioides) difficile is a pathogen of One Health importance with a complex dissemination pathway involving animals, humans and the environment. Thus, environmental discharge and agricultural recycling of human and animal waste have been suspected as factors behind the dissemination of C. difficile in the community. Here, the presence of C. difficile in 12 wastewater treatment plants (WWTPs) in Western Australia was investigated. Overall, C. difficile was found in 90.5% (114/126) of raw sewage influent, 48.1% (50/104) of treated effluent, 40% (2/5) of reclaimed irrigation water, 100% (38/38) of untreated biosolids, 95.2% (20/21) of anaerobically digested biosolids and 72.7% (8/11) of lime-amended biosolids. Over half the isolates (55.3%, 157/284) were toxigenic and 97 C. difficile ribotypes (RTs) were identified with RT014/020 the most common (14.8%, 42/284). Thirteen C. difficile isolates with the toxin profile A+B+CDT+ were found, including the hypervirulent RT078 strain. Resistance to the antimicrobials fidaxomicin, vancomycin, metronidazole, rifaximin, amoxicillin/clavulanate, meropenem and moxifloxacin was uncommon, however, resistance to clindamycin, erythromycin and tetracycline was relatively frequent at 56.7% (161/284), 14.4% (41/284) and 13.7% (39/284), respectively. This study revealed that toxigenic C. difficile was commonly encountered in WWTPs and being released into the environment. This raises concern about the possible spill-over of C. difficile into animal and/or human populations via land receiving the treated waste. In Western Australia, stringent measures are in place to mitigate the health and environmental risk of recycling human waste, however, further studies are needed to elucidate the public health significance of C. difficile surviving the treatment processes at WWTPs. IMPORTANCEClostridium difficile infection (CDI) is a leading cause of antimicrobial-associated diarrhoea in healthcare facilities. Extended hospital stays and recurrences increase the cost of treatment, and morbidity and mortality. Community-associated CDI (CA-CDI) cases, with no history of antimicrobial use or exposure to healthcare settings, are increasing. The isolation of clinically important C. difficile strains from animals, rivers, soil, meat, vegetables, compost, treated wastewater and biosolids has been reported. The objective of this study was to characterise C. difficile in wastewater treatment plants (WWTPs) in Australia. We found that C. difficile can persist through the treatment processes of WWTPs and toxigenic C. difficile was being released into the environment becoming a potential source/reservoir for CA-CDI.

microbiology↗

Protist.guru: a comparative transcriptomics database for the protist kingdom

SummaryDuring the last few decades, the study of microbial ecology has been enabled by molecular and genomic data. DNA sequencing has revealed the surprising extent of microbial diversity and how microbial processes run global ecosystems. However, significant gaps in our understanding of the microbial world remain, and one example is that microbial eukaryotes, or protists, are still neglected. To address this gap, we used gene expression data from 15 distinct protist species to create protist.guru: an online database equipped with tools for identifying functional co-expression networks, gene families, and enriched gene clusters. Here, we show how our database can be used to reveal genes involved in essential pathways, such as the synthesis of secondary carotenoids in Haematococcus lacustris. We expect protist.guru to serve as a valuable resource for protistologists, as well as a catalyst for discoveries and new insights into the biological processes of microbial eukaryotes. AvailabilityThe database and co-expression networks are freely available from http://protist.guru/. The expression matrices and sample annotations are found in the supplementary data.

evolutionary biology↗

Increased isoDGR motifs in plasma fibronectin are associated with atherosclerosis through facilitation of vascular fibrosis

Abnormal matrix deposition on vessels and recruitment of inflammatory cells into the arterial wall are critical events in atherosclerotic plaque formation. Fibronectin protein is a key matrix component that exhibits high levels of deamidation in atherosclerotic plaques and blood plasma, but it is unclear how this structural change impacts on endothelial function or modifies interactions with recruited leukocytes. This study aimed to determine how deamidation-induced isoDGR motifs in fibronectin influence extracellular matrix accumulation on endothelial cells, and to investigate possible effects on integrin outside-in signalling in matrix-bound monocytes which are key mediators of human atherosclerosis. Blood plasma fibrinogen and fibronectin displayed marked accumulation of isoDGR motifs in ischemic heart disease (IHD) as determined by ELISA analysis of patients undergoing coronary artery bypass grafting compared with age-matched healthy controls. Biochemical and functional assays confirmed that isoDGR-containing fibronectin promoted activation of integrin {beta}1 in monocytes and facilitated protein deposition and fibrillogenesis on endothelial cell layers. In addition, isoDGR interactions with integrins on the monocyte cell surface triggered an ERK:AP-1 signalling cascade that induced potent secretion of chemotactic mediators (including CCL2, CCL4, IL-8, and TNF), that promoted further leukocyte recruitment to the assembling plaque. Fibronectin deamidation forms isoDGR motifs that increase binding to {beta}1 integrins on the surface of endothelial cells and monocytes. Subsequent activation of integrin outside-in signalling pathways elicits a range of potent cytokines and chemokines that drive additional leukocyte recruitment to the developing atherosclerotic matrix and likely constitutes a key early event in progression to IHD.

biochemistry↗

Fungi.guru: comparative genomic and transcriptomic database for the Fungi kingdom

The fungi kingdom is composed of eukaryotic heterotrophs, which are responsible for balancing the ecosystem and play a major role as decomposers. They also produce a vast diversity of secondary metabolites, which have antibiotic or pharmacological properties. However, our lack of knowledge of gene function in fungi precludes us from tailoring them to our needs and tapping into their metabolic diversity. To remedy this, we gathered genomic and gene expression data of 19 most widely-researched fungi to build a database, fungi.guru, which contains tools for cross-species identification of conserved pathways, functional gene modules, and gene families. We exemplify how our database can elucidate the molecular function, biological process and cellular component of genes involved in various biological processes, by identifying a secondary metabolite pathway producing gliotoxin in Aspergillus fumigatus, the catabolic pathway of cellulose in Coprinopsis cinerea and the conserved DNA replication pathway in Fusarium graminearum and Pyricularia oryzae. The database is available at www.fungi.guru.

bioinformatics↗