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PubMed1993

Antigenic signature analysis reflects differences among plant virus isolates.

Antigenic differences among cowpea severe mosaic virus (CPSMV) isolates were clearly reflected in signature analysis employing a panel of seven well-characterized, monoclonal antibodies. Separate binding curves were generated by reacting serial dilutions of extracts from infected plant tissue containing each antigen simultaneously with each antibody in the panel. An iterative procedure was used to align unknown CPSMV antigen concentrations from different antigen preparations to allow comparison of binding profiles from different assays. Signature analysis was shown to be highly useful for the elucidation of subtle antigenic differences among viral agents because it requires neither purified virus nor knowledge of virus concentration in sap from infected plants.

Antibodies, Monoclonal↗

PubMed1985

Brainwave signatures--an index reflective of the brain's functional neuroanatomy: further findings on the effect of EEG sensorimotor rhythm biofeedback training on the neurologic precursors of learning disabilities.

Eight boys, ages 7 years 11 months to 15 years 3 months, were provided with long-term--symptom duration--sensorimotor rhythm biofeedback training for the remediation of their learning disabilities. Concurrently, the simultaneous recording of five frequency bands of brainwave activity (5 Hz, 7 Hz, 10 Hz, 12 Hz and 14 Hz), from one active electrode equidistant from reference and ground, was intended to provide a glimpse of the 'brainwave signature' reflective of the dynamic and synergistic processes involved in such cerebro-neural activation and the brain's global response to such an alteration in the sensorimotor subnetwork. Overall, the main effect of this procedure, for the biofeedback and subsequent conditioning of increased 14 Hz neural discharge patterns over the central Rolandic cortex in a clinical office setting, seems to be to increase bilateral sensorimotor transactions resulting in substantive remediation of the learning disabilities of the recipients of such training--by way of internally exercising of, and/or recruitment of additional neural activation within, the sensorimotor subnetwork/matrix. Observation of the changing brainwave signatures showed a tendency for decreased slow wave activity concomitant with increases in fast wave activity, for cases with a Full Scale I.Q. within the range of 76 and 85; with those cases with a Full Scale I.Q. within the range of 102 and 116 exhibiting increased amplitudes over most of the monitored bands, but with the increases being much less at the slower frequencies. It is noteworthy that those four subjects with either a significant Verbal greater than Performance, or Performance greater than Verbal, I.Q. Score discrepancy exhibited no less than a 40% greater increase in the lower of the two I.Q. scores; indicating that this SMR training procedure also resulted in an increased symmetry in the interhemispheric interactions reflective of the higher cortical functions for these no longer learning disabled boys.

Adolescent↗

PubMed2006

A thermodynamic signature for drug-DNA binding mode.

A number of small molecules bind directly and selectively to DNA, acting as chemotherapeutic agents by inhibiting replication, transcription or topoisomerase activity. Two common binding modes for these small molecules are intercalation or groove-binding. Intercalation results from insertion of a planar aromatic substituent between DNA base pairs, with concomitant unwinding and lengthening of the DNA helix. Groove binding, in contrast, does not perturb the duplex structure to any great extent. Groove-binders are typically crescent-shaped, and fit snugly into the minor groove with little distortion of the DNA structure. Recent calorimetric studies have determined the enthalpic and entropic contributions to the DNA binding of representative DNA binding compounds. Analysis of such thermodynamic data culled from the literature reveals distinctive thermodynamic signatures for groove-binding and intercalating compounds. Plots of the binding enthalpy (DeltaH) against binding entropy (-TDeltaS) for 26 drug-DNA interactions reveal that groove-binding interactions are clustered in a region of the graph with favorable entropy contributions to the free energy, while intercalators are clustered in a region with unfavorable entropy but favorable enthalpy contributions. Groove-binding is predominantly entropically driven, while intercalation in enthalpically driven. The molecular basis of the contrasting thermodynamic signatures for the two binding modes is by no means clear, but the pattern should be of use in categorizing new DNA binding agents.

Antineoplastic Agents↗

PubMed2004

The cystic fibrosis mutation G1349D within the signature motif LSHGH of NBD2 abolishes the activation of CFTR chloride channels by genistein.

Cystic fibrosis (CF) is a common lethal genetic disease caused by autosomal recessive mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel that belongs to the ATP-Binding Cassette (ABC) family of transporters. The class III CF mutations G551D and G1349D are located within the "signature" sequence LSGGQ and LSHGH of NBD1 and NBD2, respectively. We have constructed by site-directed mutagenesis vectors encoding green fluorescent protein (GFP)-tagged wild-type (wt) CFTR or CFTR containing delF508, G551D, G1349D and G551D/G1349D to study their pharmacology after transient expression in COS-7 cells. We show that IBMX and the benzo[c]quinolizinium derivative MPB-91 stimulates the activity of G1349D-, G551D- and G551D/G1349D-CFTR only in the presence of cAMP-promoting agents like forskolin or cpt-cAMP. Similar half-maximal effective concentrations (EC(50)) of MPB-91 (22-36microM) have been determined for wt-, G551D-, G1349D- and G551D/G1349D-CFTR. The isoflavone genistein stimulates wild-type (wt)- and delF508-CFTR channel activity in a non-Michaelis-Menten manner. By contrast, the response of G1349D- and G551D-CFTR to genistein is dramatically altered. First, genistein is not able to stimulate G1349D- and G551D/G1349D-CFTR. Second, genistein stimulates G551D-CFTR without any inhibition at high concentration. We conclude from these results that whereas G551 in NBD1 is an important molecular site for inhibition of CFTR by genistein, the symmetrical G1349 in NBD2 is also one major site but for the activation of CFTR by genistein. Because both mutations alter specifically the mechanism of CFTR channel activation by genistein, we believe that the signature sequences of CFTR act as molecular switches that upon interaction with genistein turn on and off the channel.

Amino Acid Motifs↗

PubMed2004

A gene expression signature for oxidant stress/reactive metabolites in rat liver.

Formation of free radicals and other reactive molecules is responsible for the adverse effects produced by a number of hepatotoxic compounds. cDNA microarray technology was used to compare transcriptional profiles elicited by training and testing sets of 15 oxidant stressors/reactive metabolite treatments to those produced by approximately 85 other paradigm compounds (mostly hepatotoxicants) to determine a shared signature profile for oxidant stress-associated hepatotoxicity. Initially, 100 genes were chosen that responded significantly different to oxidant stressors/reactive metabolites (OS/RM) compared to other samples in the database, then a 25-gene subset was selected by multivariate analysis. Many of the selected genes (e.g., aflatoxin aldehyde reductase, diaphorase, epoxide hydrolase, heme oxgenase and several glutathione transferases) are well-characterized oxidant stress/Nrf-2-responsive genes. Less than 10 other compounds co-cluster with our training and testing set compounds and these are known to generate OS/RMs as part of their mechanisms of toxicity. Using OS/RM signature gene sets, compounds previously associated with macrophage activation formed a distinct cluster separate from OS/RM and other compounds. A 69-gene set was chosen to maximally separate compounds in control, macrophage activator, peroxisome proliferator and OS/RM classes. The ease with which these 'oxidative stressor' classes can be separated indicates a role for microarray technology in early prediction and classification of hepatotoxicants. The ability to rapidly screen the oxidant stress potential of compounds may aid in avoidance of some idiosyncratic drug reactions as well as overtly toxic compounds.

Animals↗

PubMed2006

Multiple detection of food-borne pathogenic bacteria using a novel 16S rDNA-based oligonucleotide signature chip.

There have been many attempts to develop sensitive and accurate techniques for the detection and diagnosis of pathogenic bacteria using nucleic acid-based technology. To achieve efficient multiple detection of seven selected food-borne pathogens, we assessed the respective 16S rDNA pathogen specific sequences using an oligonucleotide-based signature array. Strategic optimal design of specific capture probes was achieved by using the characteristic first variable region. To assess the specificity of this pathogen detection system, we employed a two-step experimental strategy. Under conditions established through experiments with chemically synthesized model targets comprising both conserved and variable regions of 16S rDNA, we confirmed the validity of this system using real 16S rDNA targets. Detection with real targets was successfully performed using our system, and better specificity was obtained compared to experiments with model targets. Moreover, the subtypes of Vibrio pathogens were successfully classified. We developed a two-dimensional visualization plot tool for positive control and specific spots, which allowed facile and minute differentiation between spot intensities. Repeated array formats were employed to ensure experimental uniformity, and included the statistical p-value criterion for pathogen discrimination. The present results thus indicate that our novel oligonucleotide-based signature chip detection system can be employed for the effective detection of multiple pathogens.

Bacteria↗

PubMed2006

Orbital based electronic structural signatures of the guanine keto G-7H/G-9H tautomer pair as studied using dual space analysis.

Electronic structural signatures of the guanine-7H and guanine-9H tautomers have been investigated on an orbital by orbital basis using dual space analysis. A combination of density functional theory (B3LYP/TZVP), the statistical average of model orbital potentials (SAOP/TZ2P) method and outer valence Green's function theory (OVGF/TZVP) has been used to generate optimal tautomer geometries and accurate ionization energy spectra for the guanine tautomer pair. The present work found that the non-planar form for both of the guanine keto pair possesses lower energies than their corresponding planar counterparts, and that the canonical form of the guanine-7H tautomer has slightly lower total energy than guanine-9H. This latter result is in agreement with previous experimental and theoretical findings. In the planar guanine pair the geometric parameters and anisotropic molecular properties are compared, focusing on changes caused by the mobile proton transfer. It is demonstrated that the mobile proton only causes limited disturbance to isotropic properties, such as geometry and the energetics, of the guanine keto tautomer pair. The exception to this general statement is for related local changes such as the N((7))-C((8)) and C((8))-N((9)) bond length resonance between the single and double bonds, reflecting the nitrogen atom being bonded with the mobile proton in the tautomers. The mobile proton distorts the electron distribution of the tautomers, which leads to significant changes in the molecular anisotropic properties. The dipole moment of guanine-7H is altered by about a factor of three, from 2.23 to 7.05 D (guanine-9H), and the molecular electrostatic potentials also reflect significant electron charge distortion. The outer valence orbital momentum distributions, which were obtained using the plane wave impulse approximation (PWIA), have demonstrated quantitatively that the outer valence orbitals of the tautomer pair can be divided into three groups. That is orbitals 1a''-7a'' and 18a', which do not have visible alternations in the tautomeric process (which consist of either pi orbitals or are close to the inner valence shell); a second group comprising orbitals 19a'-22a', 25a', 26a', 28a', 29a' and 31a', which show small perturbations as a result of the mobile hydrogen locations; and group three, orbitals 23a', 24a', 27a', 30a' and 32a', which demonstrate significant changes due to the mobile proton transfer and are therefore considered as signature orbitals of the G-7H/G-9H keto tautomeric process.

Guanine↗

PubMed2004

PCBs and HCHs in a salt-marsh sediment record from South-Central Chile: use of tsunami signatures and 137Cs fallout as temporal markers.

This paper documents the occurrence of polychlorinated biphenyl (PCB) and hexachlorocyclohexane (HCH) deposition inferred from a sedimentary record exposed in a salt-marsh trench in South-Central Chile. Sediments were carefully collected every 1 cm from the trench wall. The samples were analyzed for PCBs, HCHs, 137Cs, organic carbon and grain size. The 137Cs fallout and the sedimentary signature left by the 1960 Chilean tsunami were used as temporal markers to estimate the stratigraphic chronology and the sedimentation rates. PCBs were quantified by gas chromatography with electron capture detection (GC-ECD), and positive samples were confirmed by gas chromatography and mass spectrometry detection (GC-MS). Based on these results, PCBs and HCHs deposition over the last 40 years was estimated. No PCBs were detected below the tsunami signature. Total concentrations ranged from undetectable (ND) to 32 ng/g d.w. for PCBs and from undetectable (ND) to 1.29 ng/g d.w. for HCHs. The highest PCB concentrations were found in the upper 7 cm of the core. Even though PCBs were banned in 1982 as electrical fluids in Chile, total estimated PCB fluxes have increased approximately 20 times during the last 40 years: from undetectable values to 102.6 ng/cm2/year, reflecting that PCBs are still in use and being released into the environment.

Carbon↗

PubMed2004

New insights in protein phosphorylation: a signature for protein phosphatase 1 interacting proteins.

Protein phosphatase 1 is regulated by the interaction between a catalytic subunit (PP1c) and multiple interacting proteins that allow the specific dephosphorylation of diverse cellular targets. This communication proposes to use the simultaneous presence of distinct consensus PP1c docking motifs R/K-x(0,1)-V-x-F and F-x-x-R/K-x-R/K as a signature to identify proteins putatively interacting with the PP1c. To develop this concept, we propose a new website, http://pp1 signature.pasteur.fr, which allows the identification of putative PP1-interacting proteins containing the two distinct PP1c docking consensus motifs represented in the Swissprot library. To validate the new concept of signature, we were able to characterise, by co-immunoprecipitation, four new PP1c interacting proteins randomly selected from the database in our website.

Amino Acid Motifs↗

PubMed2026

Association of immune and proliferation gene signatures and stromal tumor-infiltrating lymphocytes with clinical outcomes in patients with stage I triple-negative breast cancer.

BACKGROUND: One-third of patients with triple-negative breast cancer (TNBC) are diagnosed with stage I tumors. Biomarkers to stratify prognosis in this setting remain a major unmet need. METHODS: Tissue samples and clinicopathologic data were retrieved from consecutive patients with stage I TNBC (defined as ER <10% and HER2-negative) who underwent upfront breast surgery and received standard of care adjuvant systemic therapy at Dana-Farber/Brigham Cancer Center between 2016 and 2021. The TNBC-DX assay (Core Immune Gene [CIG] signature, proliferation signature) was applied to tumor tissue, and stromal tumor-infiltrating lymphocytes (sTILs) were centrally reviewed. Both biomarkers were tested for association with clinical outcomes using the Kaplan-Meier method. RESULTS: A total of 253 patients with stage I TNBC were included. Most tumors were ductal (88.9%) and high-grade (73.1%); 65.2% of patients received adjuvant chemotherapy. With 18 recurrence events observed, the 3-year recurrence-free survival (RFS) in the overall cohort was 95.0% (95% confidence interval [CI]: 92.1% - 98.1%) and the 3-year overall survival was 97.9% (95% CI: 95.9% - 100.0%). No significant differences in RFS were observed by TNBC-DX (n = 117 patients) or sTILs (n = 123 patients) category. However, a 3-year RFS of 100% (95% CI: 100% - 100%) was observed among the 29 patients with the highest CIG score quartile. A favorable prognosis was also observed in patients with high sTILs (>20%), who experienced a 3-year RFS of 97.0% (95% CI: 90% - 100%). Conversely, a high TNBC-DX proliferation score was numerically associated with poor outcomes, with a 3-year RFS of 83% (95% CI: 68% - 100%). CONCLUSIONS: In this retrospective study, immune and proliferative features showed opposing prognostic trends in stage I TNBC. Their integration may improve risk stratification and warrants further investigation.

Stromal tumor infiltrating lymphocytes (sTILs)↗

PubMed2006

Molecular pathology of breast apocrine carcinomas: a protein expression signature specific for benign apocrine metaplasia.

Breast cancer is a heterogeneous disease that encompasses a wide range of histopathological types including: invasive ductal carcinoma, lobular carcinoma, medullary carcinoma, mucinous carcinoma, tubular carcinoma, and apocrine carcinoma among others. Pure apocrine carcinomas represent about 0.5% of all invasive breast cancers according to the Danish Breast Cancer Cooperative Group Registry, and despite the fact that they are morphologically distinct from other breast lesions, there are at present no standard molecular criteria available for their diagnosis. In addition, the relationship between benign apocrine changes and breast carcinoma is unclear and has been a matter of discussion for many years. Recent proteome expression profiling studies of breast apocrine macrocysts, normal breast tissue, and breast tumours have identified specific apocrine biomarkers [15-hydroxyprostaglandin dehydrogenase (15-PGDH) and hydroxymethylglutaryl coenzyme A reductase (HMG-CoA reductase)] present in early and advanced apocrine lesions. These biomarkers in combination with proteins found to be characteristically upregulated in pure apocrine carcinomas (psoriasin, S100A9, and p53) provide a protein expression signature distinctive for benign apocrine metaplasias and apocrine cystic lesions. These studies have also presented compelling evidence for a direct link, through the expression of the prostaglandin degrading enzyme 15-PGDH, between early apocrine lesions and pure apocrine carcinomas. Moreover, specific antibodies against the components of the expression signature have identified precursor lesions in the linear histological progression to apocrine carcinoma. Finally, the identification of proteins that characterize the early stages of mammary apocrine differentiation such as 15-PGDH, HMG-CoA reductase, and cyclooxygenase 2 (COX-2) has opened a window of opportunity for pharmacological intervention, not only in a therapeutic manner but also in a chemopreventive setting. Here we review published and recent results in the context of the current state of research on breast apocrine cancer.

Apocrine Glands↗

PubMed2006

A 'cold synthesis' of heroin and implications in heroin signature analysis utility of trifluoroacetic/acetic anhydride in the acetylation of morphine.

Treatment of morphine, at room temperature, with a mixture of trifluoroacetic anhydride (TFAA) and acetic acid (20-30min) affords good yields of heroin. GC-MS and HPLC examination shows that heroin produced by this route to be extremely clean, but the product contains slightly less heroin than observed via the more traditional acetic anhydride (AA) route (76.1% versus 83.55%); and greater quantities of 3-MAM and 6-MAM (6.9% versus 0.75% and 7.13% versus 0.63%). The concentration ratios of the major alkaloid impurities were found to be both production method (TFAA and AA) as well as morphine extraction methodology dependant. Data contained herein describe the impact of this new production method on current intelligence efforts, largely by-passing existing heroin signature programs and the UNDCP's efforts to restrict access to key synthetic precursors. Given the methodology dependency we find that examination of the major alkaloid ratios is unsuitable for the development of a new heroin signature program. Further examination of the TFAA methodology allowed the identification of TFAA specific marker compounds, namely bis-trifluoroacetylmorphine (30), 3-trifluoroacetyl-6-acetylmorphine (31), 3-acetyl-6-trifluoroacetylmorphine (32) and trifluoroacetylcodeine (33). However, the hydrolytic lability of trifluroacetyl esters requires careful treatment of suspect samples, thus we propose a modification to existing HSP's in instances were the 6-MAM/WM ratio falls within the average minimum and maximum values of 6.17 and 17.32.

Journal Article↗

PubMed2006

Identification of a common gene expression signature in dilated cardiomyopathy across independent microarray studies.

OBJECTIVES: This study was designed to identify a common gene expression signature in dilated cardiomyopathy (DCM) across different microarray studies. BACKGROUND: Dilated cardiomyopathy is a common cause of heart failure in Western countries. Although gene expression arrays have emerged as a powerful tool for delineating complex disease patterns, differences in platform technology, tissue heterogeneity, and small sample sizes obscure the underlying pathophysiologic events and hamper a comprehensive interpretation of different microarray studies in heart failure. METHODS: We accounted for tissue heterogeneity and technical aspects by performing 2 genome-wide expression studies based on cDNA and short-oligonucleotide microarray platforms which comprised independent septal and left ventricular tissue samples from nonfailing (NF) (n = 20) and DCM (n = 20) hearts. RESULTS: Concordant results emerged for major gene ontology classes between cDNA and oligonucleotide microarrays. Notably, immune response processes displayed the most pronounced down-regulation on both microarray types, linking this functional gene class to the pathogenesis of end-stage DCM. Furthermore, a robust set of 27 genes was identified that classified DCM and NF samples with >90% accuracy in a total of 108 myocardial samples from our cDNA and oligonucleotide microarray studies as well as 2 publicly available datasets. CONCLUSIONS: For the first time, independent microarray datasets pointed to significant involvement of immune response processes in end-stage DCM. Moreover, based on 4 independent microarray datasets, we present a robust gene expression signature of DCM, encouraging future prospective studies for the implementation of disease biomarkers in the management of patients with heart failure.

Antibody Formation↗

PubMed2025

Proteomic signature of dementia risk in type 2 diabetes.

INTRODUCTION: Type 2 diabetes (T2D) significantly increases dementia risk, yet the molecular mechanisms underlying this association remain unclear. OBJECTIVES: This study aimed to identify protein signatures that distinguish dementia risk in T2D patients, develop a proteomic prediction model, and elucidate biological pathways connecting T2D and dementia. METHODS: We analyzed 2,920 plasma proteins from 52,958 participants (including 3,292 with T2D) in the UK Biobank Pharma Proteomics Project with a median follow-up of 14.6 years. Cox regression models with interaction terms identified T2D-specific protein associations with dementia risk. Machine learning models were developed to predict dementia in T2D patients. Pathway analysis and weighted gene co-expression network analysis identified biological mechanisms linking T2D and dementia. RESULTS: We identified 471 proteins with significant interaction effects between T2D and dementia risk. In non-T2D individuals, elevated levels of neuronal pentraxin receptor (NPTXR, HR = 0.74, 95 %CI:0.66-0.83) and carbonic anhydrase 14 (CA14, HR = 0.67, 95 %CI:0.60-0.75) were exclusively associated with decreased dementia risk. Conversely, in T2D patients, elevated rho guanine nucleotide exchange factor 12 (ARHGEF12, HR = 1.45, 95 %CI:1.10-1.91) was specifically associated with increased dementia risk. A 51-protein model accurately predicted 15-year dementia risk in T2D patients (AUC = 0.835, C-index = 0.829), outperforming conventional clinical risk scores and maintaining high accuracy for Alzheimer's disease and vascular dementia. Pathway analysis revealed enrichment of IL6-JAK-STAT3 signaling in T2D-related dementia, while dysregulation of fatty acid metabolism was specific to T2D-associated Alzheimer's disease. CONCLUSIONS: This large-scale proteomic analysis identifies specific molecular signatures that differentiate dementia risk in diabetic and non-diabetic populations, with potential applications for early risk stratification and targeted interventions. The identified pathways provide novel insights into the pathophysiological processes connecting T2D and dementia and suggest potential therapeutic targets.

Humans↗

PubMed2006

Helical flow as fluid dynamic signature for atherogenesis risk in aortocoronary bypass. A numeric study.

The main purpose of the study was to verify if helical flow, widely observed in several vessels, might be a signature of the blood dynamics of vein graft anastomosis. We investigated the existence of a relationship between helical flow structures and vascular wall indexes of atherogenesis in aortocoronary bypass models with different geometric features. In particular, we checked for the existence of a relationship between the degree of helical motion and the magnitude of oscillating shear stress in conventional hand-sewn proximal anastomosis. The study is based on the numerical evaluation of four bypass geometries that are attached to a simplified computer representation of the ascending aorta with different angulations relative to aortic outflow. The finite volume technique was used to simulate realistic graft fluid dynamics, including aortic compliance and proper aortic and graft flow rates. A quantitative method was applied to evaluate the level of helicity in the flow field associated with the four bypass models under investigation. A linear inverse relationship (R = -0.97) was found between the oscillating shear index and the helical flow index for the models under investigation. The results obtained support the hypothesis that an arrangement of the flow field in helical patterns may elicit damping in wall shear stress temporal gradients at the proximal graft. Accordingly, helical flow might play a significant role in preventing plaque deposition or in tuning the mechanotransduction pathways of cells. Therefore, results confirm that helical flow constitutes an important flow signature in vessels, and its strength as a fluid dynamic index (for instance in combination with magnetic resonance imaging flow visualization techniques) for risk stratification, in the activation of both mechanical and biological pathways leading to fibrointimal hyperplasia.

Biomechanical Phenomena↗

PubMed2006

Determination of VOC source signature of vehicle exhaust in a traffic tunnel.

This study describes the methodology used to obtain the volatile organic compound (VOC) source signature of vehicle exhaust. To accomplish this, C(2)-C(9) VOCs were measured in a traffic tunnel located in Seoul, South Korea. The effect of VOC concentrations from the outside ambient air was considered in the determination of the source signature. To examine the effects of ambient air on VOC concentrations inside the tunnel, the ratio of propane to the total VOC concentrations was compared between the entrance and middle sites in the tunnel. Propane was used as a standard not only because of its insignificant contribution to vehicle exhaust gas, but also the fact that propane is the most abundant VOC in the atmosphere of Seoul. The ratio of propane to the total VOC concentrations was higher at the entrance site than at the middle location by, on average, 60%. This suggests that ambient air affects the inside tunnel air to a greater extent at the entrance site as compared to the middle site. The contribution of ambient air to the air inside the tunnel at the entrance location varied from 30% to 67%, with an average of 55%. This is 1.5 times higher than the value measured at the middle location, which ranged from 20% to 48%, with an average of 36%. This shows that ambient air substantially affects the inside air of the tunnel. Excluding the effects of ambient air on the air inside the tunnel can provide an improved chemical composition for vehicle exhaust using tunnel measurements. We believe that the concentration difference between the two sites within the tunnel provides a more accurate chemical composition of vehicle exhaust as compared to that obtained from a measurement taken at only one point inside the tunnel.

Environmental Monitoring↗

PubMed2006

Biogeochemical signatures in the lichen Hypogymnia physodes in the mid Urals.

Multi-element content and uranium (U) isotopes were investigated in the lichen Hypogymnia physodes (native and transplants) sampled across a 60-km transect, centred on Karabash smelter town, from Turgoyak Lake (SW) to Kyshtym (NE) to investigate the origin of U. Kyshtym was the site of a major nuclear accident in 1957. (234)U/(238)U activity ratios in native thalli sampled during July 2001 were within the natural isotopic ratio in minerals. Uranium/thorium (U/Th) ratios were higher in native thalli towards the NE (average 0.73) than those in the SW (average 0.57). Element signatures in native thalli and transplants suggest U was derived from fossil fuel combustion from Karabash and sources lying further to the east. Systematic and significant U enrichment indicative of a nuclear fuel cycle source was not detected in any sample. Element signatures in epiphytic lichen transplants and native thalli provide a powerful method to evaluate U deposition.

Cluster Analysis↗

PubMed2024

Integrated Multi-Omics Analyses Reveal Lipid Metabolic Signature in Osteoarthritis.

Osteoarthritis (OA) is the most common degenerative joint disease and the second leading cause of disability worldwide. Single-omics analyses are far from elucidating the complex mechanisms of lipid metabolic dysfunction in OA. This study identified a shared lipid metabolic signature of OA by integrating metabolomics, single-cell and bulk RNA-seq, as well as metagenomics. Compared to the normal counterparts, cartilagesin OA patients exhibited significant depletion of homeostatic chondrocytes (HomCs) (P = 0.03) and showed lipid metabolic disorders in linoleic acid metabolism and glycerophospholipid metabolism which was consistent with our findings obtained from plasma metabolomics. Through high-dimensional weighted gene co-expression network analysis (hdWGCNA), weidentified PLA2G2A as a hub gene associated with lipid metabolic disorders in HomCs. And an OA-associated subtype of HomCs, namely HomC1 (marked by PLA2G2A, MT-CO1, MT-CO2, and MT-CO3) was identified, which also exhibited abnormal activation of lipid metabolic pathways. This suggests the involvement of HomC1 in OA progression through the shared lipid metabolism aberrancies, which were further validated via bulk RNA-Seq analysis. Metagenomic profiling identified specific gut microbial species significantly associated with the key lipid metabolism disorders, including Bacteroides uniformis (P < 0.001, R = -0.52), Klebsiella pneumonia (P = 0.003, R = 0.42), Intestinibacter_bartlettii (P = 0.009, R = 0.38), and Streptococcus anginosus (P = 0.009, R = 0.38). By integrating the multi-omics features, a random forest diagnostic model with outstanding performance was developed (AUC = 0.97). In summary, this study deciphered the crucial role of a integrated lipid metabolic signature in OA pathogenesis, and established a regulatory axis of gut microbiota-metabolites-cell-gene, providing new insights into the gut-joint axis and precision therapy for OA.

Humans↗