Systems Biology

Leaf venation network evolution across clades and scales

Fri, 2025-06-06 06:00

Nat Plants. 2025 Jun 6. doi: 10.1038/s41477-025-02011-y. Online ahead of print.

ABSTRACT

Leaf venation architecture varies greatly among living and fossil plants. However, we still have a limited understanding of when, why and in which clades new architectures arose and how they impacted leaf functioning. Using data from 1,000 extant and extinct (fossil) plants, we reconstructed approximately 400 million years of venation evolution across clades and vein sizes. Overall, venation networks evolved from having fewer veins and less smooth loops to having more veins and smoother loops, but these changes only occurred in small and medium vein sizes. The diversity of architectural designs increased biphasically, first peaking in the Paleozoic, then decreasing during the Cretaceous, then increasing again in the Cenozoic, when recent angiosperm lineages initiated a second and ongoing phase of diversification. Vein evolution was not associated with temperature and CO2 fluctuations but was associated with insect diversification. Our results highlight the complexity of the evolutionary trajectory and potential drivers of venation network architecture.

PMID:40481299 | DOI:10.1038/s41477-025-02011-y

Categories: Literature Watch

Rewired m6A of promoter antisense RNAs in Alzheimer's disease regulates neuronal genes in 3D nucleome

Fri, 2025-06-06 06:00

Nat Commun. 2025 Jun 6;16(1):5251. doi: 10.1038/s41467-025-60378-0.

ABSTRACT

N6-methyladenosine (m6A) is an abundant internal RNA modification that can impact gene expression at both post-transcriptional and transcriptional levels. However, the landscapes and functions of m6A in human brains and neurodegenerative diseases, including Alzheimer's disease (AD), are under-explored. Here, we examined RNA m6A methylome using total RNA-seq and meRIP-seq in middle frontal cortex of post-mortem brains from individuals with or without AD, which revealed m6A alteration on both mRNAs and various noncoding RNAs. Notably, many promoter-antisense RNAs (paRNAs) displayed cell-type-specific expression and changes in AD, including one produced adjacent to MAPT that encodes the Tau protein. MAPT-paRNA is highly expressed in neurons, and m6A positively controls its expression. In iPSC-derived human excitatory neurons, MAPT-paRNA does not impact the nearby MAPT mRNA, but instead promotes expression of hundreds of neuronal and synaptic genes, and is protective against excitotoxicity. Analysis of single nuclei RNA-DNA interactome in human brains supports that brain paRNAs interact with both cis- and trans-chromosomal target genes to impact their transcription. These data reveal landscapes and functions of noncoding RNAs and m6A in brain gene regulation and AD pathogenesis.

PMID:40480976 | DOI:10.1038/s41467-025-60378-0

Categories: Literature Watch

Multi-species analysis of inflammatory response elements reveals ancient and lineage-specific contributions of transposable elements to NF-kB binding

Fri, 2025-06-06 06:00

Genome Res. 2025 Jun 6. doi: 10.1101/gr.280357.124. Online ahead of print.

ABSTRACT

Transposable elements (TEs) provide a source of transcription factor (TF) binding sites that can rewire gene regulatory networks. NF-kB is an evolutionarily conserved TF complex primarily involved in innate immunity and inflammation. The extent to which TEs have contributed to NF-kB responses during mammalian evolution is not well established. Here, we performed a multi-species analysis of TEs bound by the NF-kB subunit RELA in response to the proinflammatory cytokine TNF. By comparing RELA ChIP-seq data from TNF-stimulated primary aortic endothelial cells isolated from human, mouse, and cow, we find that 55 TE subfamilies are associated with RELA-bound regions, many of which reside near TNF-responsive genes. A prominent example of lineage-specific contribution of transposons comes from the bovine SINE subfamilies Bov-tA1/2/3 which collectively contributed over 14,000 RELA-bound regions in cow. By comparing RELA binding data across species, we also find several examples of RELA motif-bearing TEs that colonized the genome prior to the divergence of the three species and contributed to species-specific RELA binding. For example, we find human RELA-bound MER81 instances are enriched for the interferon gamma pathway and demonstrate that one RELA-bound MER81 element can control the TNF-induced expression of interferon gamma receptor 2 (IFNGR2). Using ancestral reconstructions, we find that RELA containing MER81 instances rapidly decayed during early primate evolution (>50 million years ago [MYA]) before stabilizing since the separation of Old World monkeys (<50 MYA). Taken together, our results suggest ancient and lineage-specific transposon subfamilies contributed to mammalian NF-kB regulatory networks.

PMID:40480832 | DOI:10.1101/gr.280357.124

Categories: Literature Watch

Systematic engineering of the sterol synthesis pathway for Saccharomyces cerevisiae promotes the efficient production of β-caryophyllene

Fri, 2025-06-06 06:00

Metab Eng. 2025 Jun 4:S1096-7176(25)00090-4. doi: 10.1016/j.ymben.2025.06.004. Online ahead of print.

ABSTRACT

β-caryophyllene, a plant-derived sesquiterpene, serves as a food flavoring, anti-inflammatory agent, antioxidant, and high-energy fuel source. Extraction of β-caryophyllene from plants is a costly and inefficient process. Therefore, microbial cell factories have been employed for the production of β-caryophyllene. However, the limited yield is insufficient for its industrial application. In this study, we balanced the utilization of cellular resources for growth and production by systematically regulating the sterol synthesis pathway to maximize the synthesis of β-caryophyllene. In the competitive pathways concerning sterol and fatty acid synthesis, genes expression was suppressed by substituting the original promoters with a glucose-sensing promoter PHXT1 and a sterol synthesis promoter PERG7, respectively. This approach effectively increased the production of β-caryophyllene by 6.8 times, reaching 854.7 mg/L. Engineering glucose-sensing pathway altered the strength of PHXT1, resulting in an increase in β-caryophyllene production to 1.25 g/L. The cell growth and β-caryophyllene production were further boosted through diploid fusion, resulting in 21.4 g/L β-caryophyllene in fed-batch fermentation. This represents the highest reported production of β-caryophyllene to date. This study provides a valuable reference for the production of sesquiterpenes in microbial cell factories.

PMID:40480515 | DOI:10.1016/j.ymben.2025.06.004

Categories: Literature Watch

Music-Box: Controlling microfluidic flow with customized melodies for point-of-care testing

Fri, 2025-06-06 06:00

Biosens Bioelectron. 2025 Jun 2;287:117653. doi: 10.1016/j.bios.2025.117653. Online ahead of print.

ABSTRACT

The global prevalence of Human Papillomavirus (HPV) underscores an urgent need for solutions of accessible and rapid diagnostics. Although microfluidic chips have paved a promising pathway for achieving point-of-care-testing (POCT), the reliance on bulky and high-cost pumps has restricted their applicability in decentralized settings. Here, we present "Music-Box", a system leveraging a novel actuation mechanism based on the asymmetric motion of the speaker to achieve precise microfluidic control. By eliminating the need for fixed unidirectional structures, this system enables bidirectional fluid manipulation with high precision. Coupled with a smartphone, Music-Box offers a sample-to-result workflow for HPV nucleic acid detection. Clinical verification using 50 hospital-sourced samples reveals that the device has a 97.3 % sensitivity and 100 % specificity for HPV detection. By integrating portability, affordability, and precision, Music-Box redefines the method of POCT, enabling scalable diagnostics not only under resource-limited settings but also adaptable to scenarios of various infectious diseases.

PMID:40480144 | DOI:10.1016/j.bios.2025.117653

Categories: Literature Watch

From crisis to routine - Standardization of SARS-CoV-2 genome detection by enhanced EQA schemes in a scientific pandemic network

Fri, 2025-06-06 06:00

Int J Med Microbiol. 2025 May 24;319:151656. doi: 10.1016/j.ijmm.2025.151656. Online ahead of print.

ABSTRACT

In the beginning of 2020, the outbreak of the COVID-19 pandemic led to a crisis in which diagnostic methods for the genome detection of SARS-CoV-2 were urgently needed. Based on the very early publication of the basic principles for a diagnostic test for the genome detection of SARS-CoV-2, the first noncommercial laboratory-developed tests (LDTs) and commercial tests were introduced. As there was considerable uncertainty about the reliability and performance of different tests and different laboratories, INSTAND established external quality assessment (EQA) schemes for the detection of SARS-CoV-2 starting in April 2020. In close partnership in a scientific network, the EQA schemes were enhanced, especially the April, June and November 2020 terms. The enhancement included: (i) immediate provision of suitable virus including variants of concern at the beginning of the pandemic outbreak, (ii) short frequency of EQA schemes, (iii) concentration dependency of the testing and sensitivity check, achieved by using SARS-CoV-2-positive samples from a 10-fold dilution series of the same starting material, (iv) specificity check of the testing, achieved by using SARS-CoV-2-negative samples containing human coronaviruses or MERS CoV, (v) revealed samples for orientation on test performance during an ongoing or at the start of an EQA scheme using a pre-quantified SARS-CoV-2-positive EQA sample with a low viral RNA load of only 1 570 copies/mL assigned by digital PCR (dPCR) in June 2020 and (vi) quantified reference materials based on the experiences of the first two EQA schemes with dPCR-assigned values in copies/mL beginning in November 2020 for self-evaluation of the applied test system. This manuscript summarizes the results of a total of 13 EQA schemes for the detection of SARS-CoV-2 between April 2020 and June 2023 in which a total of 1 413 laboratories from 49 countries participated. The qualitative results for the detection of SARS-CoV-2-positive samples were between 95.8 % and 99.7 % correct positive, excluding extremely low concentration samples. For all SARS-CoV-2-negative EQA samples, the qualitative success rates ranged from 95.1 % to 99.4 % correct negative results. The widely varying values for the cycle threshold (Ct)/crossing point (Cq) reported for the different target genes and test systems were striking. A few laboratories reported quantitative results in copies/mL for several VOCs with an acceptable rate of over 93 % correct positive results in the majority of cases. The description of the enhanced EQA schemes for SARS-CoV-2 detection in terms of timing and scope can serve as a blueprint for the rapid development of a quality assessment of diagnostics for an emerging pathogen.

PMID:40479806 | DOI:10.1016/j.ijmm.2025.151656

Categories: Literature Watch

A Trade-off between Force and Flow May Lead to Reduced Entropy Production Rate during Faster Microbial Growth

Fri, 2025-06-06 06:00

J Phys Chem B. 2025 Jun 6. doi: 10.1021/acs.jpcb.4c08559. Online ahead of print.

ABSTRACT

Thermodynamics dictates that the entropy production rate (EPR) of a steady-state isothermal chemical reaction network rises with reaction rates. Living cells can, in addition, alter reaction rates by changing enzyme concentrations, giving them control over metabolic activities. Here, we ask whether microbial cells can break this relation between EPR and reaction rates by shifting to a metabolism with lower thermodynamic driving force (per unit of biomass) at faster growth. First, we study an example metabolic network to illustrate that maximization of metabolic flux by optimal allocation of resources can indeed lead to selection of a pathway with a lower driving force. This pathway then compensates for the reduction in driving force by relying on fewer enzymes with sufficiently increased concentrations, resulting in a higher flux. Next, we investigate the EPR per unit biomass of microbes that change their catabolic network as a function of their growth rate, using three models for chemostat cultivation of the yeast Saccharomyces cerevisiae that are calibrated with experimental data. Although current experimental evidence proved insufficient to give conclusive results, we derive a general criterion to predict when the specific EPR drops after a metabolic switch. We describe the experiments that are required to show that the specific EPR of a microbe can decrease with its growth rate.

PMID:40479734 | DOI:10.1021/acs.jpcb.4c08559

Categories: Literature Watch

The linker protein ApcI regulates light harvesting under red light in Synechocystis sp. PCC 6803

Fri, 2025-06-06 06:00

Plant Cell. 2025 Jun 6:koaf144. doi: 10.1093/plcell/koaf144. Online ahead of print.

ABSTRACT

Phycobilisomes are versatile cyanobacterial antenna complexes that harvest light energy to drive photosynthesis. They can adapt to various light conditions; for example, dismantling under high light to prevent photo-oxidation and arranging in rows under low light to increase light harvesting efficiency. Light quality also influences phycobilisome structure and function, as observed under far-red light exposure. Here, we describe a phycobilisome linker protein, ApcI (previously hypothetical protein Sll1911), expressed specifically under red light (620 nm) or upon chemically induced reduction of the plastoquinone pool. We characterized ApcI in Synechocystis sp. PCC 6803 using mutant analyses, phycobilisome binding experiments, and protein interaction studies. Deletion of apcI conferred high light tolerance on Synechocystis sp. PCC 6803 compared to the wild-type strain, leading to reduced energy transfer from phycobilisomes to the photosystems under high light. Binding experiments revealed that ApcI replaces the linker protein ApcG at the membrane-facing side of the phycobilisome core via a paralogous C-terminal motif. Additionally, the N-terminal region of ApcI interacts with photosystem II. Our findings highlight the importance of phycobilisome remodeling for adaptation to different light conditions. The characterization of ApcI provides insight into the mechanisms by which cyanobacteria optimize light harvesting in response to varying light conditions.

PMID:40479507 | DOI:10.1093/plcell/koaf144

Categories: Literature Watch

The SH protein of mumps virus is a druggable pentameric viroporin

Fri, 2025-06-06 06:00

Sci Adv. 2025 Jun 6;11(23):eads3071. doi: 10.1126/sciadv.ads3071. Epub 2025 Jun 6.

ABSTRACT

Viral infections are on the rise and drugs targeting viral proteins are needed. Viroporins constitute a growing group of virus-encoded transmembrane oligomeric proteins that allow passage of small molecules across the membrane. Despite sparsity in viroporin structures, recent work has revealed diversity in both the number of transmembrane helices and oligomeric states. Here, we provide evidence that the small hydrophobic protein (SH) from mumps virus is a pentameric viroporin. From extensive biophysical data, a HADDOCK model of full-length SH shows its intracellular C-terminal region to form an extended structure crucial to stabilization of the pentamer. Heterologous expression of wild-type SH and variants in Xenopus laevis oocytes reveals the viroporin as a chloride channel, with transport facilitated by conserved hydroxyl-carrying residues lining the pore. The channel function of SH is inhibited by the small-molecule BIT225, highlighting the potential for antiviral targeting through SH.

PMID:40479045 | DOI:10.1126/sciadv.ads3071

Categories: Literature Watch

Challenges and opportunities in systems biology education

Fri, 2025-06-06 06:00

Endocr Relat Cancer. 2025 Jun 1:ERC-25-0024. doi: 10.1530/ERC-25-0024. Online ahead of print.

ABSTRACT

Systems biology requires combining deep understanding in biology with technological methods and computational approaches to acquire new insights. Accordingly, students need to gain knowledge in very different disciplines and their integration to succeed in this truly interdisciplinary field. This review summarizes a variety of study lines at the Master's levels and uses student and alumni feedback to highlight the main challenges and useful teaching approaches. Education in systems biology needs to be carefully designed to deliver deep knowledge in core aspects while still giving a broad overview of others. Teachers will need to find a good balance here. Integrated experimental and computational courses, as well as active learning approaches can be key components of successful curricula. Training native systems biologists needs commitment by teachers and institutions and should start as early as possible.

PMID:40478892 | DOI:10.1530/ERC-25-0024

Categories: Literature Watch

RORγt is crucial for gut homeostasis by regulating the expression of HB-EGF rather than IL-22 in activated ILC3s

Fri, 2025-06-06 06:00

Cell Rep. 2025 Jun 5;44(6):115793. doi: 10.1016/j.celrep.2025.115793. Online ahead of print.

ABSTRACT

RORγt inhibition shows potential for treating T helper 17 (Th17) cell-related inflammatory disorders. However, there is a lack of a comprehensive understanding of its influence on the immune system. RORγt also serves as the master regulator of type 3 innate lymphoid cells (ILC3s). Although previous studies indicated that it might not be essential for ILC3 activation, our single-cell RNA sequencing analysis reveals its fundamental participation. By utilizing an Il22Cre/+Rosa26LSL-TdtomatoRorcfl/fl (interleukin [IL]-22-fate mapping [FM]ΔRorc) mouse model, we discovered that genetic deletion of Rorc does not completely eliminate ILC3s. Only the lymphoid tissue inducer (LTi) subset experiences a reduction. Additionally, the "ex-ILC3s" following Rorc deletion still preserve ILC3 characteristics and produce sufficient IL-22 to maintain gut health and prevent pathogen invasion. Nevertheless, RORγt is found to be crucial for heparin-binding epidermal growth factor (HB-EGF) production in activated ILC3s, which is of great significance in alleviating colitis. Thus, our findings clarify the role of RORγt in ILC3s, thereby providing insights for the clinical evaluation of RORγt inhibition.

PMID:40478733 | DOI:10.1016/j.celrep.2025.115793

Categories: Literature Watch

Standardized Quorum Sensing Tools for Gram-Negative Bacteria

Fri, 2025-06-06 06:00

ACS Synth Biol. 2025 Jun 6. doi: 10.1021/acssynbio.5c00036. Online ahead of print.

ABSTRACT

Engineering synthetic consortia to perform distributed functions requires robust quorum sensing (QS) systems to facilitate communication between cells. However, the current QS toolbox lacks standardized implementations, which are particularly valuable for use in bacteria beyond the model species Escherichia coli. We developed a set of three QS systems encompassing both sender and receiver modules, constructed using backbones from the SEVA (Standard European Vector Architecture) plasmid collection. This increases versatility, allowing plasmid features like the origin of replication or antibiotic marker to be easily swapped. The systems were characterized using the synthetic biology chassis Pseudomonas putida. We first tested individual modules, then combined sender and receiver modules in the same host, and finally assessed the performance across separate cells to evaluate consortia dynamics. Alongside the QS set, we provide mathematical models and rate parameters to support the design efforts. Together, these tools advance the engineering of robust and predictable multicellular functions.

PMID:40476774 | DOI:10.1021/acssynbio.5c00036

Categories: Literature Watch

Connectivity and adaptation patterns of the deep-sea ground-forming sponge Geodia hentscheli across its entire distribution

Fri, 2025-06-06 06:00

Mol Biol Evol. 2025 Jun 6:msaf145. doi: 10.1093/molbev/msaf145. Online ahead of print.

ABSTRACT

Geodia hentscheli, a species forming sponge grounds in the North Atlantic and Arctic Oceans, is a common deep-sea organism, playing a fundamental role forming biogenic habitats. However, there is little information about gene flow and adaptation patterns of this species, which is crucial to develop effective management/conservation plans under current global change scenarios. Here, we generated ddRADseq data from 110 specimens of G. hentscheli, together with microbial profiling, transcriptomics and metatranscriptomics for a selection of specimens to investigate their genetic diversity, molecular connectivity and local adaptations. Sampling covered the species' entire distribution within a wide bathymetric range. We obtained 1,115 neutral SNPs and identified long distance genetic connectivity among regions separated 1,000s of km, but strong genetic structure segregating populations by depth at ca. 1,300 m, in line with our microbial analyses. Coalescent analyses inferred the split of these depth-related genetic entities ∼10 KYA, coincident with the last post-glacial maximum. Analyses of SNPs under selection, combined with transcriptomic and metatranscriptomic data highlight the presence of several sponge genes and microbial metabolic pathways involved in adaptation to depth, including heat shock proteins and fatty acids, amongst others. The physiological plasticity of the sponge and its microbiome as a function of depth suggest the existence of a host-microbiome metabolic compensation for G. hentscheli. This study provides a multiscale paradigmatic example of the Depth Differentiation Hypothesis, a phenomenon mainly caused by changes in environmental conditions at different depths, mainly related to the presence of water masses with different characteristics, that drive local adaptations.

PMID:40476758 | DOI:10.1093/molbev/msaf145

Categories: Literature Watch

stGuide advances label transfer in spatial transcriptomics through attention-based supervised graph representation learning

Fri, 2025-06-06 06:00

Front Genet. 2025 May 22;16:1566675. doi: 10.3389/fgene.2025.1566675. eCollection 2025.

ABSTRACT

The growing availability of spatial transcriptomics data offers key resources for annotating query datasets using reference datasets. However, batch effects, unbalanced reference annotations, and tissue heterogeneity pose significant challenges to alignment analysis. Here, we present stGuide, an attention-based supervised graph learning model designed for cross-slice alignment and efficient label transfer from reference to query datasets. stGuide leverages supervised representations guided by reference annotations to map query slices into a shared embedding space using an attention-based mechanism. It then assigns spot-level labels by incorporating information from the nearest neighbors in the learned representation. Using human dorsolateral prefrontal cortex and breast cancer datasets, stGuide demonstrates its capabilities by (i) producing category-guided, low-dimensional features with well-mixed slices; (ii) transferring labels effectively across heterogeneous tissues; and (iii) uncovering relationships between clusters. Comparisons with state-of-the-art methods demonstrate that stGuide consistently outperforms existing approaches, positioning it as a robust and versatile tool for spatial transcriptomics analysis.

PMID:40476268 | PMC:PMC12137301 | DOI:10.3389/fgene.2025.1566675

Categories: Literature Watch

Real-time inference of the end of an outbreak: Temporally aggregated disease incidence data and under-reporting

Fri, 2025-06-06 06:00

Infect Dis Model. 2025 Apr 1;10(3):935-945. doi: 10.1016/j.idm.2025.03.009. eCollection 2025 Sep.

ABSTRACT

Professor Pierre Magal made important contributions to the field of mathematical biology before his death on February 20, 2024, including research in which epidemiological models were used to study the ends of infectious disease outbreaks. In related work, there has been interest in inferring (in real-time) when outbreaks have ended and control interventions can be relaxed. Here, we analyse data from the 2018 Ebola outbreak in Équateur Province, Democratic Republic of the Congo, during which an Ebola Response Team (ERT) was deployed to implement public health measures. We use a renewal equation transmission model to perform a quasi real-time investigation into when the ERT could be withdrawn safely at the tail end of the outbreak. Specifically, each week following the arrival of the ERT, we calculate the probability of future cases if the ERT is withdrawn. First, we show that similar estimates of the probability of future cases can be obtained from either daily or weekly case reports. This demonstrates that high temporal resolution case reporting may not always be necessary to determine when interventions can be relaxed. Second, we demonstrate how case under-reporting can be accounted for rigorously when estimating the probability of future cases. We find that, the lower the level of case reporting, the longer it is necessary to wait after the apparent final case before interventions can be removed safely (with only a small probability of additional cases). Finally, we show how uncertainty in the extent of case reporting can be included in estimates of the probability of future cases. Our research highlights the importance of accounting for under-reporting in deciding when to remove interventions at the tail ends of infectious disease outbreaks.

PMID:40475698 | PMC:PMC12138552 | DOI:10.1016/j.idm.2025.03.009

Categories: Literature Watch

No Evidence of Anti-Influenza Nucleoprotein Antibodies in Retail Milk from Across Canada (April-July 2024)

Fri, 2025-06-06 06:00

Viral Immunol. 2025 Jun 6. doi: 10.1089/vim.2025.0029. Online ahead of print.

ABSTRACT

Following reports of highly pathogenic avian influenza H5N1 infections of dairy cattle in the United States in March 2024, we established a Pan-Canadian Milk network to monitor retail milk in Canada. Milk samples from across Canada that had previously tested negative for influenza A virus (IAV) RNA were tested for the presence of anti-IAV nucleoprotein (NP) antibodies as an indicator of past infection of dairy cattle. None of the 109 milk samples tested had evidence of anti-IAV NP antibodies. This is consistent with previous findings from our academic group as well as others including federal testing initiatives that have not found any IAV RNA in milk. Although not surprising given that no cases of H5N1 in cattle have been reported in Canada to date, this work further supports that the extensive outbreak in dairy cattle in the United States has not extended northward into Canada, and the integrity of the Canadian milk supply remains intact.

PMID:40474813 | DOI:10.1089/vim.2025.0029

Categories: Literature Watch

Epistasis regulates genetic control of cardiac hypertrophy

Thu, 2025-06-05 06:00

Nat Cardiovasc Res. 2025 Jun 5. doi: 10.1038/s44161-025-00656-8. Online ahead of print.

ABSTRACT

Although genetic variant effects often interact nonadditively, strategies to uncover epistasis remain in their infancy. Here we develop low-signal signed iterative random forests to elucidate the complex genetic architecture of cardiac hypertrophy, using deep learning-derived left ventricular mass estimates from 29,661 UK Biobank cardiac magnetic resonance images. We report epistatic variants near CCDC141, IGF1R, TTN and TNKS, identifying loci deemed insignificant in genome-wide association studies. Functional genomic and integrative enrichment analyses reveal that genes mapped from these loci share biological process gene ontologies and myogenic regulatory factors. Transcriptomic network analyses using 313 human hearts demonstrate strong co-expression correlations among these genes in healthy hearts, with significantly reduced connectivity in failing hearts. To assess causality, RNA silencing in human induced pluripotent stem cell-derived cardiomyocytes, combined with novel microfluidic single-cell morphology analysis, confirms that cardiomyocyte hypertrophy is nonadditively modifiable by interactions between CCDC141, TTN and IGF1R. Our results expand the scope of cardiac genetic regulation to epistasis.

PMID:40473955 | DOI:10.1038/s44161-025-00656-8

Categories: Literature Watch

Synergy and antagonism in the integration of BCR and CD40 signals that control B-cell population expansion

Thu, 2025-06-05 06:00

Mol Syst Biol. 2025 Jun 5. doi: 10.1038/s44320-025-00124-2. Online ahead of print.

ABSTRACT

In response to infection or vaccination, lymph nodes must select antigen-reactive B-cells while eliminating auto-reactive B-cells. B-cells are instructed via B-cell receptor (BCR), which binds antigen, and CD40 receptor by antigen-recognizing T-cells. How BCR and CD40 signaling are integrated quantitatively to jointly determine B-cell fate decisions remains unclear. Here, we developed a differential-equations-based model of BCR and CD40 signaling networks activating NFκB. The model recapitulates NFκB dynamics upon BCR and CD40 stimulation, and when linked to established cell decision models of cell cycle and survival control, the resulting cell population dynamics. However, upon costimulation, NFκB dynamics were correctly predicted but the predicted potentiated population expansion was not observed experimentally. We found that this discrepancy was due to BCR-induced caspase activity that may trigger apoptosis in founder cells, unless timely NFκB-induced survival gene expression protects them. Iterative model predictions and sequential co-stimulation experiments revealed how complex non-monotonic integration of BCR and CD40 signals controls positive and negative selection of B-cells. Our work suggests a temporal proof-reading mechanism for regulating the stringency of B-cell selection during antibody responses.

PMID:40473841 | DOI:10.1038/s44320-025-00124-2

Categories: Literature Watch

Raman on the palm: handheld Raman spectroscopy for enhanced traceability of palm oil

Thu, 2025-06-05 06:00

NPJ Sci Food. 2025 Jun 5;9(1):95. doi: 10.1038/s41538-025-00462-3.

ABSTRACT

Determining the geographic origin of palm oil in West Africa is vital for economic, environmental, and health reasons. It enhances traceability, protects local farmers, supports conservation by monitoring deforestation, and reduces food fraud, ensuring quality and regulatory compliance. Portable Raman spectroscopy offers a rapid method to identify the origin of palm oils from West Africa. Using principal component analysis (PCA), distinct clusters in scores plots were observed which reflected the geographic origin of the palm oils, with loadings from the first principal component (PC-1) highlighting β-carotene as a major source of variation among the samples. To quantify β-carotene content, a partial least squares regression (PLS-R) model was developed in coconut oil as the base oil as it is known to be β-carotene free. Once calibrated, PLS-R was used to rank the palm oil from West Africa based on their β-carotene levels. The resulting models in coconut oil demonstrated strong linearity and predictive performance, with R² and Q² values of 0.9848 and 0.9552, respectively, alongside low root mean square errors of cross-validation (0.1282 mM) and prediction (0.0747 mM); moreover, this model allows the palm oils to be ranked based on β-carotene content which was entirely reflective of the oils position in PC-1 from PCA. These findings underscore the potential of Raman spectroscopy as an effective tool for authenticating the geographic origin of palm oil from West Africa.

PMID:40473674 | DOI:10.1038/s41538-025-00462-3

Categories: Literature Watch

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