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At least 1,351 records · Page 75Linked to original sources
PubMed2026

Cerium dioxide nanoparticle exposure attenuates mobility-linked antibiotic resistome signatures across the soil-lettuce continuum.

Antibiotic resistance genes (ARGs) are contaminants of emerging concern in agricultural microbiomes. Their association with mobile genetic elements (MGEs) can enhance dissemination across soil-plant interfaces, creating potential environmental and food-chain exposure risks. However, how engineered nanoparticles modulate relative ARG abundance and mobility-linked resistome features in plant-associated microbiomes remains poorly understood. Here, we examined the effects of graded, experimentally elevated cerium dioxide nanoparticle (CeO2 NP) loadings in a soil-lettuce system by integrating compartment-resolved metagenomics, ARG-MGE co-occurrence analysis, putative host-reservoir profiling, transcriptomics, and functional assays. Metagenomic profiling identified 16 ARG types and 125 subtypes and revealed niche-dependent microbiome restructuring under CeO2 NP exposure. Rhizosphere relative ARG abundance showed a negative dose-associated trend, although overall inter-group differences were not significant, whereas leaf endophytes showed a weaker response. Relative MGE abundance decreased significantly in both compartments, and lower assembly-level ARG-MGE co-occurrence reflected fewer ARGs detected in MGE-associated genomic contexts, whereas fewer multi-ARG contigs suggested reduced ARG clustering and potential co-selection. Putative host-reservoir analysis associated key efflux determinants with bacterial families whose relative representation declined following CeO2 NP exposure. Transcriptomic profiling of representative putative ARG hosts revealed host-specific responses, including downregulation of genes involved in central metabolism and Sec-dependent trafficking. Complementary host assays showed reduced apparent envelope permeability and lower recovery of tetracycline-resistant recipient-identity colonies in the plasmid-associated host system. Together, under the tested elevated-loading conditions, CeO2 NP exposure was associated with lower relative ARG signals and weaker mobility-linked resistome features across the soil-lettuce continuum, providing mechanistic insight into nanoparticle-resistome interactions in soil-plant systems.

ARG dissemination↗
PubMed2005

Hair mercury (signature of fish consumption) and cardiovascular risk in Munduruku and Kayabi Indians of Amazonia.

Fish is an important natural resource in the diet of inhabitants of the Amazon rain forest and a marker of its consumption (hair Hg) was used to compare selected cardiovascular risk parameters between tribes of Eastern Amazonia. Three Munduruku (Terra Preta, Kaburua, Cururu) villages and one Kayabi village at the banks of head rivers (Tapajos, Tropas, Kabitutu, Cururu, Curuzinho, Teles Pires) of the Tapajos Basin were studied in relation to fish Hg concentrations, mercury in hair (fish consumption) and erythrocytes, body mass index (height/weight, kg/cm2), and blood pressure. The mean fish Hg concentrations were higher in predatory (578.6 ng/g) than in nonpredatory species (52.8 ng/g). Overall only 26% of fish Hg concentrations were above 500 ng/g, and only 11% were above 1000 ng/g. There was no systematic trend in fish Hg concentrations from rivers with a history of gold-mining activities. The biomarker of fish consumption (hair Hg) was significantly associated with erythrocyte-Hg (r=0.5181; P=0.0001) and was significantly higher in Kayabi (12.7 microg/g) than in the Munduruku (3.4 microg/g). Biomarker-assessed fish consumption rate was higher in the Kayabi (110 g/day) than in the Munduruku villages (30 g/day). Although no significant differences in body mass index (BMI) were observed between tribes, there was a trend of lower increase in blood pressure with age among the higher fish consumers (Kayabi). Summary clinical evaluation did not detect neurologic complaints compatible with Hg intoxication (paraparesis, numbness, tremor, balancing failure), but endemic tropical diseases such as clinical history of malaria showed a high prevalence (55.4%). Fish is an abundant natural resource, important in the Indian diet, that has been historically consumed without perceived problems and can easily be traced through hair Hg. The exposure to freshwater fish monomethyl mercury is less of an issue than endemic infectious diseases such as malaria and lack of basic medical services.

Adolescent↗
PubMed2026

Early proteomic and metabolic signatures of liver and eye in OAT-deficient mice.

Ornithine aminotransferase (OAT) deficiency causes hyperornithinemia and gyrate atrophy (GA) of the choroid and retina, a rare inherited retinal degeneration. To understand the early molecular changes that make the eye susceptible to damage, we performed quantitative proteomic and metabolomic profiling of liver, retina, and retinal pigment epithelium and choroid (RPE/Cho) from OAT-deficient (Oatrhg) mice prior to detectable vision impairment. In addition to reduced OAT expression and elevated ornithine, methylation-related metabolites such as N(6)-methyl-lysine were altered in all examined tissues of Oatrhg mice. In the liver, excess ornithine was directed into urea cycle metabolism, together with altered expression of detoxification enzymes and histone H2B proteins. In contrast, the retina showed minimal proteomic changes but pronounced alterations in amino acid pathways that support glutamate homeostasis. The RPE/Cho demonstrated the most extensive proteomic changes, particularly in mitochondrial metabolism, cytoskeleton, and extracellular matrix, along with changes in metabolites involved in lysine metabolism, energy metabolism, and antioxidant capacity. Incubation with 13C lysine demonstrated that lysine was primarily degraded in RPE/Cho but not the retina, and ornithine enhanced lysine degradation in an OAT-dependent manner. Together, these findings highlight common and tissue-specific impacts of OAT on the liver and ocular tissues and provide insight into early molecular changes that contribute to the selective vulnerability of the eye in GA. Proteomics data are available via ProteomeXchange (PXD063614) and metabolomics data via MassIVE repository (MSV000101103).

Animals↗
PubMed2005

Proteomic signature of myeloproliferation and neutrophilia: analysis of serum and plasma from healthy subjects given granulocyte colony-stimulating factor.

OBJECTIVE: Proteomic analysis could improve our understanding of the mechanisms and consequences of myeloproliferation. Healthy subjects treated with granulocyte colony-stimulating factor (G-CSF) were used as a model of myeloproliferation. METHODS: Levels of 80 soluble factors were measured by enzyme-linked immunosorbent assay before and after 5 days of G-CSF. Both serum and plasma levels were measured to generate a comprehensive profile and determine whether serum or plasma best portrays biological and physiological changes. RESULTS: Comparison of samples collected prior to G-CSF demonstrated that 44 factors differed between serum and plasma. Concentrations of several growth factors and chemokines were greater in serum than in plasma, while the opposite was true for several interleukins. Following G-CSF serum levels of 14 factors and plasma levels of 15 factors changed. Eleven increased in both serum and plasma, including cell adhesion molecules (vascular cell adhesion molecule-1, E-selectin, and L-selectin), matrix metalloproteases (MMP-1, -8, and -13), cytokine receptors (tumor necrosis factor receptor 1 and 2, and interleukin-2 receptor), the acute phase reactant, serum amyloid A, and a growth factor, hepatocyte growth factor. CONCLUSION: Some protein levels differ markedly in serum and plasma. Myeloproliferation is associated with changes in the levels of several proteases, adhesion molecules, and cytokines.

Blood Proteins↗
PubMed2004

Molecular signature associated with plasticity of bone marrow cell under persistent liver damage by self-organizing-map-based gene expression.

The mechanism that regulates the plasticity of bone marrow cells (BMCs) into hepatocytes is poorly understood. We developed a green fluorescent protein/carbon tetrachloride model to find that BMC transplantation recovered liver damage. Serum albumin level and liver fibrosis were recovered by BMC transplantation. To understand the mechanism, we used DNA-chip technology to profile the change of transient gene expression before and after BMC transplantation. On the basis of gene expression with self-organizing map using specific equation, genes were classified into 153 clusters. The information is useful to understand the dramatic gene activation during the process of the plasticity of BMC.

Animals↗
PubMed2005

Self-organizing-map-based molecular signature representing the development of hepatocellular carcinoma.

Using high-density oligonucleotide array, we comprehensively analyzed expression levels of 12600 genes in 50 hepatocellular carcinoma (HCC) samples with positive hepatitis C virus (HCV) serology (well (G1), moderately (G2), and poorly (G3) differentiated tumors) and 11 non-tumorous livers (L1 and L0) with and without HCV infection. We searched for discriminatory genes of transition (L0 vs. L1, L1 vs. G1, G1 vs. G2, G2 vs. G3) with a supervised learning method, and then arranged the samples by self-organizing map (SOM) with the discriminatory gene sets. The SOM arranged the five clusters on a unique sigmoidal curve in the order L0, L1, G1, G2, and G3. The sample arrangement reproduced development-related features of HCC such as p53 abnormality. Strikingly, G2 tumors without venous invasion were located closer to the G1 cluster, and most G2 tumors with venous invasion were located closer to the G3 cluster (P=0.001 by Fisher's exact test). Our present profiling data will serve as a framework to understand the relation between the development and dedifferentiation of HCC.

Aged↗
PubMed2005

Purkinje-cell degeneration in prion protein-deficient mice is associated with a cerebellum-specific Doppel protein species signature.

PrP(c) (cellular prion protein) and Doppel are antagonizing proteins, respectively neuroprotective and neurotoxic. Evidence for Doppel neurotoxicity came from PrP(c)-deficient (Prnp(0/0)) mouse lines developing late onset Purkinje-cell degeneration caused by Doppel overexpression in brain. To address the molecular underpinnings of this cell-type specificity, we generated Doppel N-terminal-specific antibodies and started to examine the spatio-temporal expression of Doppel protein species in Ngsk Prnp(0/0) brain. Although Doppel overexpression is ubiquitous, Western analyses of normal and deglycosylated protein extracts revealed cerebellar patterns distinct from the rest of the brain, supporting the idea that neurotoxicity might be linked to a particular Doppel species pattern. Furthermore, our newly raised antibodies allowed the first Doppel immunohistochemical analyses in brain, showing a distribution in Prnp(0/0) cerebellum similar to PrP(c) in wild type.

Animals↗
PubMed2026

LC-IMS-MS profiling of avocado acetogenins reveals tissue-dependent distribution and cultivar-specific metabolic signatures.

This study presents a comprehensive characterisation of acetogenin-related metabolites in avocado using an LC-IMS-MS workflow. A total of 26 metabolites were semi-quantified across peel, pulp and seed tissues from three cultivars (Hass, Bacon and Fuerte). The integration of ion mobility spectrometry enabled the generation of the first experimental database of collision cross section (CCS) values for avocado acetogenins, improving confidence in metabolite annotation. Results revealed a pronounced tissue-dependent distribution, with seeds and pulp as the primary reservoir of several acetogenins, whereas the peel consistently exhibited lower concentrations. In contrast, acetogenin levels remained largely stable throughout ripening. Clear cultivar-dependent differences were observed, with Hass displaying a distinct metabolic profile compared to Bacon and Fuerte. Multivariate analysis confirmed these findings, showing tissue-dependent cultivar differentiation. This study provides new insights into avocado chemical diversity and highlights the potential of avocado by-products as consistent and promising sources of bioactive acetogenins.

Persea↗
PubMed2026

Proteomic signatures for sudden cardiac death and related intermediate phenotypes.

BACKGROUND: Novel markers for sudden cardiac death (SCD) are needed. OBJECTIVE: This study aimed to explore whether a protein risk score derived from a large-scale proteomics dataset improves risk prediction of SCD in the general population. METHODS: A total of 52,705 individuals with 1459 unique plasma protein measurements were included from the UK Biobank Pharma Proteomics Project. A protein risk score was developed using lasso-penalized Cox regression on 40,722 participants enrolled at the English centers and validated on 11,983 participants enrolled at the remaining centers. RESULTS: The protein risk score formula developed from the derivation set comprised 64 unique plasma proteins including latent-transforming growth factor beta-binding protein 2, protein tyrosine phosphatase receptor sigma, and spondin-1. In the test set, a per standard deviation increase in protein risk score was associated with a hazard ratio of 2.60 (95% confidence interval [CI] 2.12-3.18) for SCD. Adding a protein risk score to SCD clinical risk factors resulted in a concordance index increase of 0.063 (95% CI 0.037-0.105) for SCD. For ventricular arrhythmia-mediated SCDs, an increase in concordance index when a protein risk score was added to SCD clinical risk factors was 0.070 (95% CI 0.010-0.188). A protein risk score added to SCD clinical risk factors resulted in a risk reclassification of 16.9% (95% CI 9.0-24.7) at a 10-year risk threshold of 5%. A protein risk score was significantly associated with intermediate phenotypes of SCD including corrected QT prolongation, an increase in left ventricular mean myocardial thickness, and a decrease in left ventricular global longitudinal strain. CONCLUSION: A protein risk score derived from a single plasma sample significantly improved risk prediction of SCD and related intermediate phenotypes.

Humans↗
PubMed2025

Development and validation of a machine learning prognostic model based on an epigenomic signature in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: In Pancreatic Ductal Adenocarcinoma (PDAC), current prognostic scores are unable to fully capture the biological heterogeneity of the disease. While some approaches investigating the role of multi-omics in PDAC are emerging, the analysis of methylation data is under exploited. MATERIALS AND METHODS: We analyzed CpG sites from two publicly available datasets, the TCGA-PAAD used as discovery set and the CPTAC-PDA as external test set. Single mutations and co-mutation of KRAS and TP53 genes were identified as targets, and differentially methylated CpG sites (DMC) were detected accordingly. We trained and validated Random Forest (RF) models to predict each target. Area Under the Receiver Operating Characteristic curve (AUROC) and Area Under the Precision-Recall curve (AUPRC) were used as performance metrics. Then, we performed consensus clustering from the DMCs to identify novel patients' profiles. Finally, we trained and validated a combination of eXtreme Gradient Boosting (XGB) and tree models to select an epigenomic prognostic determinant. RESULTS: From 598 DMCs extracted, an RF model predicted KRAS and TP53 co-mutation on the external test set with AUROC of 0.77 and AUPRC of 0.87. The consensus clustering allowed us to identify 4 clusters (C1, C2, C3, and C4) of patients. The C4 cluster captured a subgroup of patients with favorable Overall Survival (OS) with respect to others. The XGB model perfectly predicted C4 vs other clusters on the discovery set. In both cohorts, patients were stratified into two risk groups according to methylation levels of cg16854533, individuated as the most important CpG site. CONCLUSION: We analyzed methylation data to develop a classifier for the TP53 and KRAS mutational status. Four prognostic clusters were pointed out and a prognostic model using a CpG site was validated in an independent cohort. Our results evidence that the proposed use of methylation data facilitates risk stratification for PDAC.

Humans↗
PubMed2004

Radiation response: an additional unique signature of myxoid liposarcoma.

PURPOSE: Historically, myxoid liposarcoma (MLS) has been reported to show a marked clinical response to radiotherapy (RT), but objective data to support that contention have been lacking. We performed a retrospective analysis of the response of a group of MLS tumors to preoperative RT using tumor dimensions calculated from pretreatment imaging and the subsequent surgical specimen obtained approximately 1 month after RT. METHODS AND MATERIALS: Data were abstracted from the Princess Margaret Hospital prospective database on a series of patients with MLS who had undergone preoperative RT between 1991 and 1999. A group of malignant fibrous histiocytoma (MFH) patients treated on the same protocol served as controls. Pretreatment and posttreatment three-dimensional measurements were obtained; comparison tumor volume measurements were estimated using the ellipsoid formula, and the analysis was also repeated using the maximal tumor dimension. Identical measurement procedures were used for the MLS (experimental) and MFH (control) cases. RESULTS: A total of 16 MLS tumor specimens were available for analysis, and 16 MFH cases were randomly chosen for comparison. The mean pretreatment and posttreatment volume of the MLS tumors was 415 and 199 cm(3), respectively (P = <0.0001). The mean pretreatment and posttreatment volume of the MFH tumors was 264 and 273 cm(3), respectively (p = 0.804). The proportional reduction in the median tumor volume was 59% and -7% for MLS and MFH tumors, respectively. Both the absolute and the proportional reduction in volume for MLS tumors vs. MFH tumors was statistically significant (p = 0.006 and p = 0.002, respectively). CONCLUSION: These results provide the first objective data to support the idea that MLS tumors show a statistically significant reduction in size when treated with RT and that this response is greater than that of MFH tumors given the same RT. These results may be relevant to the management of MLS with combined RT and surgery in difficult anatomic situations in which adequate surgical excision is not feasible. They also confirm another unique characteristic of this unusual subtype of soft tissue sarcoma.

Adult↗
PubMed2005

Molecular signatures associated with clinical outcome in patients with high-risk head-and-neck squamous cell carcinoma treated by surgery and radiation.

PURPOSE: The local-regional control rate for advanced head-and-neck squamous cell carcinoma (HNSCC) remains poor and is unpredictable for a given individual. This study examined whether gene expression patterns developed from tumors from surgicopathologic, criteria-defined, high-risk HNSCC patients could be correlated with clinical outcomes, namely, metastasis or nonrecurrent disease. METHODS AND MATERIALS: Fifteen primary tumors from patients treated with a consistent protocol of surgery followed by radiotherapy were examined. Seven of these tumors were from high-risk patients who developed distant metastasis (DM), and eight tumors were from patients with no recurrence (NR) (median follow-up, 59 months). RESULTS: Unsupervised clustering of gene expression did not separate the two groups from one another, but when supervised methodologies were applied, 205 genes discriminated the two groups. Within the DM group, genes associated with cell growth and proliferation; DNA replication, recombination, and repair; antiapoptotic pathways; cell adhesion; and angiogenesis were identified. For NR samples, discriminatory genes were associated with the onset of apoptosis. CONCLUSIONS: Our data suggest that gene expression analysis of surgically excised HNSCC tumors from patients considered at high risk for recurrence has the potential to identify individuals susceptible to metastasis on the basis of distinct gene-expression patterns. These patients would be ideal candidates for testing systemic therapy.

Carcinoma, Squamous Cell↗
PubMed2004

A gene-expression signature can quantify the degree of hepatic fibrosis in the rat.

BACKGROUNDS/AIMS: A more accurate and objective quantification of hepatic fibrosis would provide clinically useful information for the monitoring of chronic liver disease progression and therapy recommendation. METHODS: Using a cDNA microarray of 14,814 clones, we analyzed the gene-expression profiles of fibrotic livers in a rat model. RESULTS: We identified 750 up- and 345 down-regulated genes by combining a signal-to-noise score and a random permutation test (P<0.01). The functions of these genes provided insight into the underlying molecular mechanisms of both structural remodeling and functional deficits in cirrhosis. To quantify the extent of liver fibrosis, we have generated for the first time a 'genetic fibrosis index' based on gene-expression profiling of 95 genes by combining a Pearson correlation coefficient and a 'leave-one-out' cross-validation procedure. This technique based on a supervised learning analysis correctly quantified the various degrees of fibrosis in both 20 training samples (R(2)=0.829, P<0.001) and 6 test samples (R(2)=0.822, P<0.05). CONCLUSIONS: Our method will assist researchers in identifying rational targets for intervention and might help clinicians to objectively monitor the severity of liver fibrosis.

Animals↗
PubMed2006

Identifying the morphological signatures of hybridization in primate and human evolution.

Recent studies point to contact and possible admixture among contemporaneous hominin species during the Plio-Pleistocene. However, detection of hybridization in fossils-and especially fossil hominins-is contentious, and it is hindered in large part by our lack of understanding about how morphological hybridity is manifested in the primate skeleton. Here, we report on a study of known-pedigree, purebred yellow and olive baboons (n = 112) and their hybrids (n = 57), derived from the baboon colony of the Southwest Foundation for Biomedical Research. The hybrids were analyzed in two different groups: (1) F1 = olive x yellow first-generation hybrids; (2) B1 = olive x F1 backcross hybrids. Thirty-nine metric variables were tested for heterosis and dysgenesis. Nonmetric data were also collected from the crania. Results show that these primate hybrids are somewhat heterotic relative to their parental populations, are highly variable, and display novel phenotypes. These effects are most evident in the dentition and probably indicate the mixing of two separately coadapted genomes and the breakdown in the coordination of early development, despite the fact that these populations diverged fairly recently. Similar variation is also observed in museum samples drawn from natural hybrid zones. The results offer a strategy for detecting hybrid zones in the fossil record; implications for interpreting the hominin fossil record are discussed.

Analysis of Variance↗