J Invertebr Pathol. 2025 Mar 17:108313. doi: 10.1016/j.jip.2025.108313. Online ahead of print.

ABSTRACT

Entomopathogenic nematodes (EPNs) are soil-dwelling organisms essential for controlling pest populations across diverse crops and regions worldwide. Over the past century, significant advancements have been made in isolating, identifying, and quantifying EPNs, enhancing our understanding of their natural distribution and influencing factors. This review outlines major milestones in EPN population dynamics research and highlights emerging molecular and biophysical tools that offer new research directions. Here, we examine the factors shaping EPN occurrence in agroecosystems, including interactions between hosts, EPNs, and their resource competitors (viewing EPNs as scavengers) and the biotic and abiotic drivers affecting their spatial and temporal patterns. Additionally, the review explores EPN interactions with plant rhizospheres and the impact of agricultural practices on their efficacy as biological control agents. Understanding EPN population dynamics is crucial for optimizing their use as sustainable pest management tools. By combining traditional insights with innovative methods, we can expand EPN applications in agroecosystems, fostering more resilient and eco-friendly agricultural practices.

PMID:40107567 | DOI:10.1016/j.jip.2025.108313

Curr Biol. 2025 Mar 13:S0960-9822(25)00198-8. doi: 10.1016/j.cub.2025.02.034. Online ahead of print.

ABSTRACT

Discrimination between different signals is crucial for animals' survival. Inhibition that suppresses weak neural activity is crucial for pattern decorrelation. Our understanding of alternative mechanics that allow efficient signal classification remains incomplete. We show that Drosophila olfactory receptor neurons (ORNs) have numerous intraglomerular axo-axonal connections mediated by the G protein-coupled receptor (GPCR), muscarinic type B receptor (mAChR-B). Contrary to its usual inhibitory role, mAChR-B participates in ORN excitation. The excitatory effect of mAChR-B only occurs at high ORN firing rates. A computational model demonstrates that nonlinear intraglomerular or global excitation decorrelates the activity patterns of ORNs of different types and improves odor classification and discrimination, while acting in concert with the previously known inhibition. Indeed, knocking down mAChR-B led to increased correlation in odor-induced ORN activity, which was associated with impaired odor discrimination, as shown in behavioral experiments. Furthermore, knockdown (KD) of mAChR-B and the GABAergic GPCR, GABAB-R, has an additive behavioral effect, causing reduced odor discrimination relative to single-KD flies. Together, this study unravels a novel mechanism for neuronal pattern decorrelation, which is based on nonlinear intraglomerular excitation.

PMID:40107267 | DOI:10.1016/j.cub.2025.02.034

J Pharm Biomed Anal. 2025 Mar 12;260:116806. doi: 10.1016/j.jpba.2025.116806. Online ahead of print.

ABSTRACT

The leaves of Annona muricata Linn. have long been utilized in traditional medicine for diabetes treatment, and there is no study that has employed a metabolomics approach to investigate the plant's effects in managing the disease. We aimed to explore the antidiabetic effects of the standardised A. muricata leaf extract on diabetes-induced rats by alloxan monohydrate (Ax) and nicotinamide (NA) using a proton nuclear magnetic resonance (¹H-NMR)-based metabolomics approach. Absolute quantification was performed on the leaf extract using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Two different doses of the extract were administered orally for four weeks to diabetic rats induced with Ax + NA, and physical evaluations, biochemical analyses, and ¹H-NMR metabolomics of urine and serum were assessed. The results showed that quercetin 3-rutinoside was the most abundant compound in the 80 % ethanolic extract of A. muricata leaf. The induction of type 2 diabetes mellitus (T2DM) in the rat model was confirmed by the clear metabolic distinction between normal rats, diabetic rats, and metformin-treated diabetic rats. The low-dose of A. muricata leaf extract (200 mg/kg) was found to exhibit better results, significantly reducing serum urea levels in diabetic rats, with effects comparable to those of metformin. Additionally, metabolite analysis from ¹H-NMR metabolomics of serum and urine showed a slight shift toward normal metabolic profiles in the treated diabetic rats. Pathway analysis revealed alterations in the tricarboxylic acid cycle (TCA), pyruvate metabolism, and glycolysis/gluconeogenesis pathways in the diabetic rat model, which were improved following treatment with the A. muricata leaf extract. Overall, this study provides scientific support for its traditional use in diabetes management and offers new insights into the underlying molecular mechanisms.

PMID:40106911 | DOI:10.1016/j.jpba.2025.116806

Sci Transl Med. 2025 Mar 19;17(790):eadp0675. doi: 10.1126/scitranslmed.adp0675. Epub 2025 Mar 19.

ABSTRACT

The diverse T cell receptor (TCR) repertoire confers the ability to recognize an almost unlimited array of antigens. Characterization of antigen specificity of tumor-infiltrating lymphocytes (TILs) is key for understanding antitumor immunity and for guiding the development of effective immunotherapies. Here, we report a large-scale comprehensive examination of the TCR landscape of TILs across the spectrum of pediatric brain tumors, the leading cause of cancer-related mortality in children. We show that a T cell clonality index can inform patient prognosis, where more clonality is associated with more favorable outcomes. Moreover, TCR similarity groups' assessment revealed patient clusters with defined human leukocyte antigen associations. Computational analysis of these clusters identified putative tumor antigens and peptides as targets for antitumor T cell immunity, which were functionally validated by T cell stimulation assays in vitro. Together, this study presents a framework for tumor antigen prediction based on in situ and in silico TIL TCR analyses. We propose that TCR-based investigations should inform tumor classification and precision immunotherapy development.

PMID:40106578 | DOI:10.1126/scitranslmed.adp0675

Sci Adv. 2025 Mar 21;11(12):eadp8100. doi: 10.1126/sciadv.adp8100. Epub 2025 Mar 19.

ABSTRACT

Exposure to airborne particulate matter (PM) has been attributed to millions of deaths annually. However, the PM components responsible for observed health effects remain unclear. Oxidative potential (OP) has gained increasing attention as a key property that may explain PM toxicity. Using online measurement methods that impinge particles for OP quantification within seconds, we reveal that 60 to 99% of reactive oxygen species (ROS) and OP in secondary organic aerosol and combustion-generated PM have a lifetime of minutes to hours and that the ROS activity of ambient PM decays substantially before offline analysis. This implies that current offline measurement methods substantially underestimate the true OP of PM. We demonstrate that short-lived OP components activate different toxicity pathways upon direct deposition onto reconstituted human bronchial epithelia. Therefore, we suggest that future air pollution and health studies should include online OP quantification, allowing more accurate assessments of links between OP and health effects.

PMID:40106561 | DOI:10.1126/sciadv.adp8100

STAR Protoc. 2025 Mar 18;6(2):103681. doi: 10.1016/j.xpro.2025.103681. Online ahead of print.

ABSTRACT

As genes tend to be co-regulated as gene modules, feature selection in machine learning (ML) on gene expression data can be challenged by the complexity of gene regulation. Here, we present a protocol for reconciling differences in classifier features identified using different ML approaches. We describe steps for loading the PathwaySpace R package, preparing input for analysis, and creating density plots of gene sets. We then detail procedures for testing whether apparently distinct feature sets are related in pathway space. For complete details on the use and execution of this protocol, please refer to Ellrott et al.1.

PMID:40106435 | DOI:10.1016/j.xpro.2025.103681

Am J Physiol Renal Physiol. 2025 Mar 19. doi: 10.1152/ajprenal.00285.2024. Online ahead of print.

ABSTRACT

We have devised a user-friendly downloadable, standalone application that solves a set of ordinary differential equations describing steady-state mass balance for salt (NaCl), urea and water in a single renal tubule with axial flow. The model was programmed in Python using an explicit ordinary differential equation solver. The standalone version allows users to interact with a GUI to insert parameter values and initiate the calculations. It outputs volume flow rate and solute concentrations as a function of position along the tubule. We illustrate the use of the model to address questions about the roles of the mammalian distal convoluted tubule (DCT) in water balance. The simulations suggest an important role for the DCT as a second diluting segment beyond the cortical thick ascending limb (CTAL), consistent with a critical function in excretion of water loads. Simulation of the effect of thiazide diuretics, which inhibit active salt absorption in the DCT, provides an explanation for the observation that these agents can produce hyponatremia when used clinically. The simulations also indicate that the DCT may transport salt in either direction (in accord with micropuncture findings), depending on the salt concentration in the fluid entering from the CTAL. Salt reabsorption by active transport is balanced by passive salt secretion as the luminal salt concentration approaches an asymptotic 'static head' level. The tool will allow users with no mathematical modeling experience to simulate transport in renal tubules, working toward the goal of expanding the use of mathematical modeling in physiology.

PMID:40106383 | DOI:10.1152/ajprenal.00285.2024

Proc Natl Acad Sci U S A. 2025 Mar 25;122(12):e2417588122. doi: 10.1073/pnas.2417588122. Epub 2025 Mar 19.

ABSTRACT

Plants produce diverse specialized metabolites with important ecological functions. It has recently become apparent that the genes for many of these pathways are not dispersed in plant genomes, but rather are arranged like beads on a string in biosynthetic gene clusters (BGCs). Pathways encoded by BGCs are as a rule dedicated linear pathways that do not form parts of wider metabolic networks. In contrast, the genes for the biosynthesis of widely distributed more ancestral metabolites such as carotenoids and anthocyanins are not clustered. Little is known about how these more recently evolved clustered pathways interact with general plant metabolism. We recently characterized a 12-gene BGC for the biosynthesis of the antimicrobial defense compound avenacin A-1, a triterpene glycoside produced by oats. Avenacin A-1 is acylated with the fluorophore N-methyl anthranilate and confers bright blue fluorescence of oat root tips under ultraviolet light. Here, we exploit a suite of >100 avenacin-deficient mutants identified by screening for reduced root fluorescence to identify genes required for the function of this paradigm BGC. Using a combination of mutant chemotyping, biochemical and molecular analysis, and genome resequencing, we identify two nonclustered genes (Sad4 and Pal2) encoding enzymes that synthesize the donors required for avenacin glycosylation and acylation (recruited from the phenylpropanoid and tryptophan pathways). Our finding of these Cluster Auxiliary Enzymes (CAEs) provides insights into the interplay between general plant metabolism and a newly evolved lineage-specific BGC.

PMID:40106352 | DOI:10.1073/pnas.2417588122

Curr Genet. 2025 Mar 19;71(1):7. doi: 10.1007/s00294-025-01311-2.

ABSTRACT

There is great interest in establishing microalgae as new platforms for the sustainable production of high-value products such as recombinant proteins. Many human therapeutic proteins must be glycosylated, which requires their passage through the secretory pathway into the culture medium. While the low complexity of proteins in the culture medium should facilitate affinity purification of secreted recombinant proteins, this has proven challenging for proteins secreted by the unicellular green alga Chlamydomonas reinhardtii. In Leishmania tarentulae, we observed that C-terminally exposed affinity tags are frequently truncated, presumably due to proteolytic activity. We wondered whether this might also occur in Chlamydomonas and contribute to the difficulties in affinity purification of secreted proteins in this alga. Using the methionine-rich 2S albumin from Bertholletia excelsa and the ectodomain of the SARS-CoV-2 spike protein produced and secreted in Chlamydomonas, we demonstrate that they can be efficiently affinity-purified from the culture medium by Ni-NTA chromatography when the 8xHis affinity tag is internalized. This finding represents an important step towards further development of Chlamydomonas as a host for the sustainable production of high-value recombinant proteins.

PMID:40105958 | DOI:10.1007/s00294-025-01311-2

Dis Model Mech. 2025 Mar 1;18(3):dmm052113. doi: 10.1242/dmm.052113. Epub 2025 Mar 19.

ABSTRACT

Cancer screening relies upon a linear model of neoplastic growth and progression. Yet, historical observations suggest that malignant progression is uncoupled from growth, which may explain the paradoxical increase in early-stage breast cancer detection without a dramatic reduction in metastasis. Here, we lineage trace millions of transformed cells and thousands of tumors using a cancer rainbow mouse model of HER2 (also known as ERBB2)-positive breast cancer. Transition rates from field cell to screen-detectable tumor to symptomatic tumor were estimated from a dynamical model of tumor development. Field cells were orders of magnitude less likely to transition to a screen-detectable tumor than the subsequent transition from screen-detectable tumor to symptomatic tumor. Our model supports a critical 'occult' transition in tumor development during which a transformed cell becomes a bona fide neoplasm. Lineage tracing and test by transplantation revealed that nonlinear progression during the occult transition gives rise to nascent lethal cancers at screen detection. Simulations illustrated how occult transition rates are a critical determinant of tumor growth and malignancy. Our data provide direct experimental evidence that cancers can deviate from the predictable linear progression model that is foundational to current screening paradigms.

PMID:40105775 | DOI:10.1242/dmm.052113

J Mol Cell Cardiol Plus. 2025 Feb 19;11:100289. doi: 10.1016/j.jmccpl.2025.100289. eCollection 2025 Mar.

ABSTRACT

The regulatory mechanisms underlying the response to pro-inflammatory cytokines in cardiac diseases are poorly understood. Here, we use iPSC-derived cardiovascular progenitor cells (CVPCs) to model the response to interferon gamma (IFNγ) in human cardiac tissue. We generate RNA-seq and ATAC-seq for four CVPCs that were treated with IFNγ and compare them with paired untreated controls. Transcriptional differences after treatment show that IFNγ initiates an innate immune cell-like response, shifts the CVPC transcriptome toward coronary artery and aorta profiles, and stimulates expression of endothelial cell-specific genes. Analysis of the accessible chromatin shows that IFNγ is a potent chromatin remodeler and establishes an IRF-STAT immune-cell like regulatory network. Finally, we show that 11 GWAS risk variants for 8 common cardiac diseases overlap IFNγ-upregulated ATAC-seq peaks. Our findings reveal insights into IFNγ-induced activation of an immune-like regulatory network in human cardiac tissue and the potential role that regulatory elements in this pathway play in common cardiac diseases.

PMID:40104808 | PMC:PMC11919396 | DOI:10.1016/j.jmccpl.2025.100289

World J Transplant. 2025 Mar 18;15(1):96025. doi: 10.5500/wjt.v15.i1.96025.

ABSTRACT

BACKGROUND: Despite the developments in the field of kidney transplantation, the already existing diagnostic techniques for patient monitoring are considered insufficient. Protein biomarkers that can be derived from modern approaches of proteomic analysis of liquid biopsies (serum, urine) represent a promising innovation in the monitoring of kidney transplant recipients.

AIM: To investigate the diagnostic utility of protein biomarkers derived from proteomics approaches in renal allograft assessment.

METHODS: A systematic review was conducted in accordance with PRISMA guidelines, based on research results from the PubMed and Scopus databases. The primary focus was on evaluating the role of biomarkers in the non-invasive diagnosis of transplant-related complications. Eligibility criteria included protein biomarkers and urine and blood samples, while exclusion criteria were language other than English and the use of low resolution and sensitivity methods. The selected research articles, were categorized based on the biological sample, condition and methodology and the significantly and reproducibly differentiated proteins were manually selected and extracted. Functional and network analysis of the selected proteins was performed.

RESULTS: In 17 included studies, 58 proteins were studied, with the cytokine CXCL10 being the most investigated. Biological pathways related to immune response and fibrosis have shown to be enriched. Applications of biomarkers for the assessment of renal damage as well as the prediction of short-term and long-term function of the graft were reported. Overall, all studies have shown satisfactory diagnostic accuracy of proteins alone or in combination with conventional methods, as far as renal graft assessment is concerned.

CONCLUSION: Our review suggests that protein biomarkers, evaluated in specific biological fluids, can make a significant contribution to the timely, valid and non-invasive assessment of kidney graft.

PMID:40104186 | PMC:PMC11612886 | DOI:10.5500/wjt.v15.i1.96025

iScience. 2025 Jan 24;28(3):111883. doi: 10.1016/j.isci.2025.111883. eCollection 2025 Mar 21.

ABSTRACT

Early stages of metastasis depend on the collective behavior of cancer cells and their interaction with the extracellular matrix (ECM). Cancer cell clusters are known to exhibit higher metastatic potential than single cells. To explore clustering dynamics, we developed a calibrated computational model describing how motile cancer cells biochemically and biomechanically interact with the ECM during the initial invasion phase, including ECM degradation and mechanical remodeling. The model reveals that cluster formation time, size, and shape are influenced by ECM degradation rates and cellular compliance to external stresses (durotaxis). The results align with experimental observations, demonstrating distinct cell trajectories and cluster morphologies shaped by biomechanical parameters. The simulations provide valuable insights into cancer invasion dynamics and may suggest potential therapeutic strategies targeting early-stage invasive cells.

PMID:40104056 | PMC:PMC11914804 | DOI:10.1016/j.isci.2025.111883

Prostate. 2025 Mar 18. doi: 10.1002/pros.24880. Online ahead of print.

ABSTRACT

BACKGROUND: 177Lu-vipivotide tetraxetan (177Lu-PSMA-617, LuPSMA) improves overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC) after at least one taxane chemotherapy and androgen receptor pathway inhibitor. There are limited data on the clinical course and outcomes of patients with mCRPC after receipt of LuPSMA.

METHODS: We queried an IRB-approved prospectively maintained registry of all patients with mCRPC who received standard-of-care LuPSMA at our institution between June 2022 and January 2024. Clinical data about LuPSMA and subsequent therapies were extracted from the electronic medical record, including the type and number of subsequent systemic therapies, reason for treatment cessation, hematologic toxicity and supportive treatment, and PSA50 response to subsequent therapy (defined as a ≥ 50% decrease in PSA).

RESULTS: A total of 146 patients were evaluated; mean age 72 (range 52-87), observed median follow-up 5.9 months (range 0.51-18.7). Forty-four received systemic treatment after LuPSMA. The most common subsequent treatment after LuPSMA was chemotherapy (n = 27), primarily cabazitaxel ± carboplatin/cisplatin (n = 23), and the median number of cycles received was 4 (range 1-7). In 35/44 men with available hematologic toxicity data, 13 developed grade ≥ 3 anemia, 7 had ≥ grade 3 thrombocytopenia, and 16 received hematologic support. PSA50 to post-LuPSMA treatment occurred in 10/36 (28%) evaluable patients. Median overall survival from subsequent systemic therapy was 7.6 months (95% CI 5.81-NR).

CONCLUSIONS: 30% of patients receiving standard-of-care LuPSMA received subsequent therapy, mostly cabazitaxel-containing regimens. Post-LuPSMA treatment appeared tolerable and was associated with a PSA50 response rate of 28%. These outcomes may be biased by limited standard-of-care life-prolonging treatment options at the time of LuPSMA FDA approval, but it also highlights the continued need to develop novel therapeutic strategies for mCRPC post-LuPSMA.

PMID:40103237 | DOI:10.1002/pros.24880

Nat Commun. 2025 Mar 18;16(1):2643. doi: 10.1038/s41467-025-57929-w.

NO ABSTRACT

PMID:40102433 | DOI:10.1038/s41467-025-57929-w

Open Biol. 2025 Mar;15(3):240302. doi: 10.1098/rsob.240302. Epub 2025 Mar 19.

ABSTRACT

The molecular clock rests upon the assumption that the observed changes among sequences capture the differentiation of lineages, or kinship, as dissimilarity increases with time. Although it has been questioned over the years, this paradigmatic principle continues to underlie the idea that the polymorphic space of a gene is so vast that it is unattainable in evolutionary time. Thus, the molecular clock has been used to obtain taxonomic annotations, proving to be very effective at delivering testable results. In this article, however, we ask how often this assumption leads to inaccuracies when inferring the lineage of prokaryotic genes. Thus, we open an interesting discussion by simulating, in realistic scenarios, the critical times in which specific 5S rRNA sequences of two distant lineages are exhausting the polymorphic space. We contend that certain genes in one lineage will become increasingly similar to those in another over time, as the space for new variants is finite, mimicking phylogenetic features by convergence or by chance, without implying true kinship.

PMID:40101780 | DOI:10.1098/rsob.240302

Cell Rep Methods. 2025 Mar 13:101005. doi: 10.1016/j.crmeth.2025.101005. Online ahead of print.

ABSTRACT

Generating metagenome-assembled genomes from DNA shotgun sequencing datasets can demand considerable computational resources. Here, we describe a sequential co-assembly method that reduces the assembly of duplicate reads through successive application of single-node computing tools for read assembly and mapping. Using a simulated mouse microbiome DNA shotgun sequencing dataset, we demonstrated that this approach shortens assembly time, uses less memory than traditional co-assembly, and produces significantly fewer assembly errors. Applying sequential co-assembly to shotgun sequencing reads from (1) a longitudinal study of gut microbiomes from undernourished Bangladeshi children and (2) a 2.3-terabyte dataset generated from gnotobiotic mice colonized with pooled microbiomes from these children that was too large to be handled by a traditional co-assembly approach also demonstrated significant reductions in assembly time and memory requirements. These results suggest that this approach should be useful in resource-constrained settings, including in low- and middle-income countries.

PMID:40101714 | DOI:10.1016/j.crmeth.2025.101005

Vaccine. 2025 Mar 17;54:126860. doi: 10.1016/j.vaccine.2025.126860. Online ahead of print.

ABSTRACT

Rift Valley fever (RVF) is a zoonotic viral disease that causes epidemics and epizootics among humans and livestock, resulting in substantial health and socioeconomic consequences. Currently, there are no RVF vaccines licensed for humans, but several candidates show promise in early-stage development. Existing gaps in RVF epidemiological data and challenges associated with predicting RVF outbreak risk complicate the planning of efficacy studies, making the pathway to licensure for promising candidates unclear. In June 2024, the Coalition for Epidemic Preparedness Innovations (CEPI) convened a two-day workshop in Nairobi, Kenya, to discuss RVF epidemiology, modeling priorities, and specific gaps relevant to human RVF vaccine development. The workshop included representatives from multiple RVF-endemic countries, key global collaborators, and international health organizations. Workshop participants identified five key priorities: (1) Looking beyond outbreaks: There is a need to better characterize the complex One Health epidemiology of RVF and understand interepidemic persistence of the virus; (2) Better data for better models: Epidemiological modeling is crucial for research, prediction, and planning, but it requires accurate and representative data; (3) New, improved and accessible diagnostics and serological assays: These are needed to inform epidemiology and case definitions, without which RVF research will continue to suffer due to paucity of data and challenges in determining infection and exposure; (4) Defining use cases, regulatory pathways, and implementation strategies for human vaccines: Clarity on these topics will facilitate licensure and effective use of RVF vaccines; and (5) People-centered approaches: Community engagement and involvement of social and behavioral scientists are key to the success of human vaccine research and development and implementation, particularly as the virus impacts livestock and livelihoods. Workshop participants welcomed a renewed focus for RVF epidemiology and modeling, and expressed enthusiasm for continued multidisciplinary collaborations to support enabling sciences for human RVF vaccine research and development.

PMID:40101455 | DOI:10.1016/j.vaccine.2025.126860

PLoS Negl Trop Dis. 2025 Mar 18;19(3):e0012909. doi: 10.1371/journal.pntd.0012909. eCollection 2025 Mar.

ABSTRACT

BACKGROUND: Scrub typhus, traditionally caused by Orientia tsutsugamushi, is a re-emerging public health concern within the Tsutsugamushi Triangle. Despite growing awareness, prevention strategies remain inadequate on Hainan Island, China, where scrub typhus poses a significant threat, especially in field-related environments.

METHODOLOGY/PRINCIPAL FINDINGS: Gene flow analysis of the tsa56 gene and multilocus sequence typing (MLST) were conducted on 156 previously confirmed scrub typhus cases from 2018 to 2021 across Hainan Island. By integrating published datasets, we identified 12 major sub-genotypes and traced their origins, revealing that these sub-genotypes share origins with isolates from Southeast Asia and coastal provinces and island of China, but also demonstrate unique local adaptations across all isolates. Alpha diversity index analysis was applied across administrative regions to identify hotspot regions. This analysis showed that nine out of the detected fourteen administrative regions, particularly along the northern and western coastlines and inland areas, exhibited relatively high genetic diversity, with the highest incidence observed in Qiongzhong, a centrally located city. Related major sequence types were mapped, and distances between locations were estimated, showing that identical MLST sequence types were observed to transfer across distances of 23 to 125 km between different sites on the island. Pathogen density was analyzed using quantitative real-time PCR targeting the tsa56 gene. Without accounting for potential confounding factors or dataset limitations, the Karp_B_2 sub-genotype showed a significant increasing trend in pathogen density with prolonged fever duration, while Gilliam sub-genotypes exhibited a slower or even declining trend.

CONCLUSIONS/SIGNIFICANCE: These findings emphasize the urgent need for targeted public health interventions, particularly focusing on vulnerable populations in rural and agricultural areas of nine key administrative regions where high genetic diversity and pathogen spread were observed. Additionally, this study provides valuable insights into the transmission dynamics and infection progression of scrub typhus, using gene flow analysis and multilocus sequence typing to identify major sub-genotypes.

PMID:40100922 | DOI:10.1371/journal.pntd.0012909

PLoS Biol. 2025 Mar 18;23(3):e3003052. doi: 10.1371/journal.pbio.3003052. eCollection 2025 Mar.

ABSTRACT

Genome sequencing of cancer and normal tissues, alongside single-cell transcriptomics, continues to produce findings that challenge the idea that cancer is a 'genetic disease', as posited by the somatic mutation theory (SMT). In this prevailing paradigm, tumorigenesis is caused by cancer-driving somatic mutations and clonal expansion. However, results from tumor sequencing, motivated by the genetic paradigm itself, create apparent 'paradoxes' that are not conducive to a pure SMT. But beyond genetic causation, the new results lend credence to old ideas from organismal biology. To resolve inconsistencies between the genetic paradigm of cancer and biological reality, we must complement deep sequencing with deep thinking: embrace formal theory and historicity of biological entities, and (re)consider non-genetic plasticity of cells and tissues. In this Essay, we discuss the concepts of cell state dynamics and tissue fields that emerge from the collective action of genes and of cells in their morphogenetic context, respectively, and how they help explain inconsistencies in the data in the context of SMT.

PMID:40100793 | DOI:10.1371/journal.pbio.3003052