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PubMed2006

Changes in stable isotopic signatures of soil nitrogen and carbon during 40 years of forest development.

Understanding what governs patterns of soil delta15N and delta13C is limited by the absence of these data assembled throughout the development of individual ecosystems. These patterns are important because stable isotopes of soil organic N and C are integrative indicators of biogeochemical processing of soil organic matter. We examined delta15N of soil organic matter (delta15NSOM) and delta13CSOM of archived soil samples across four decades from four depths of an aggrading forest in southeastern USA. The site supports an old-field pine forest in which the N cycle is affected by former agricultural fertilization, massive accumulation of soil N by aggrading trees over four decades, and small to insignificant fluxes of N via NH3 volatilization, nitrification, and denitrification. We examine isotopic data and the N and C dynamics of this ecosystem to evaluate mechanisms driving isotopic shifts over time. With forest development, delta13CSOM became depth-dependent. This trend resulted from a decline of approximately 2 per thousand in the surficial 15 cm of mineral soil to -26.0 per thousand, due to organic matter inputs from forest vegetation. Deeper layers exhibited relatively little trend in delta13CSOM with time. In contrast, delta15NSOM was most dynamic in deeper layers. During the four decades of forest development, the deepest layer (35-60 cm) reached a maximum delta15N value of 9.1 per thousand, increasing by 7.6 per thousand. The transfer of > 800 kg ha(-1) of soil organic N into aggrading vegetation and the forest floor and the apparent large proportion of ectomycorrhizal (ECM) fungi in these soils suggest that fractionation via microbial transformations must be the major process changing delta15N in these soils. Accretion of isotopically enriched compounds derived from microbial cells (i.e., ECM fungi) likely promote isotopic enrichment of soils over time. The work indicates the rapid rate at which ecosystem development can impart delta15NSOM and delta13CSOM signatures associated with undisturbed soil profiles.

Carbon Isotopes↗

PubMed2000

Skills evaluation in minimally invasive surgery using force/torque signatures.

BACKGROUND: One of the more difficult tasks in surgical education is to teach the optimal application of instrument forces and torques necessary to facilitate the conduct of an operation. For laparoscopic surgery, this type of training has traditionally taken place in the operating room, reducing operating room efficiency and potentially affecting the safe conduct of the operation. The objective of the current study was to measure and compare forces and torques (F/T) applied at the tool/hand interface generated during laparoscopic surgery by novice (NS) and experienced (ES) surgeons using an instrumented laparoscopic grasper and to use this data for evaluating the skill level. METHODS: Ten surgeons (five-NS, five-ES) performed a cholecystectomy and Nissen fundoplication in a porcine model. An instrumented laparoscopic grasper with interchangeable standard surgical tips equipped with a three-axis F/T sensor located at the proximal end of the grasper tube was used to measure the F/T at the hand/tool interface. In addition, one axis force sensor located at the grasper's handle was used to measure the grasping force. F/T data synchronized with visual view of the tool operative maneuvers were collected simultaneously via a novel graphic user interface incorporated picture-in-picture video technology. Subsequent frame-by-frame video analysis of the operation allowed a definition of states associated with different tool/tissue interactions within each step of the operation. F/T measured within each state were further analyzed using vector quantization (VQ). The VQ analysis defines characteristic sets of F/T in the database that were defined as F/T signature. RESULTS: The magnitude of F/T applied by NS and ES were significantly different (p < 0.05) and varied based on the task being performed. Higher F/T magnitudes were applied by NS than by ES when performing tissue manipulation, whereas lower F/T magnitudes were applied by NS than by ES during tissue dissection. Furthermore, the time to complete the surgical procedure was longer for NS by a factor of 1.5-4.8 when compared to the time for ES. State analysis suggests that most of this time is consumed in an [idle] state, in which movements of the surgeon make no tissue contact. CONCLUSIONS: Preliminary data suggest that F/T magnitudes associated with the tool/tissue interactions provide an objective means of distinguishing novices from skilled surgeons. Clinical F/T analysis using the proposed technology and methodology may be helpful in training, developing surgical simulators, and measuring technical proficiency during laparoscopic surgery.

Cholecystectomy, Laparoscopic↗

PubMed2002

Signatures of large-scale and local climates on the demography of white-tailed ptarmigan in Rocky Mountain National Park, Colorado, USA.

Global climate change may impact wildlife populations by affecting local weather patterns, which, in turn, can impact a variety of ecological processes. However, it is not clear that local variations in ecological processes can be explained by large-scale patterns of climate. The North Atlantic oscillation (NAO) is a large-scale climate phenomenon that has been shown to influence the population dynamics of some animals. Although effects of the NAO on vertebrate population dynamics have been studied, it remains uncertain whether it broadly predicts the impact of weather on species. We examined the ability of local weather data and the NAO to explain the annual variation in population dynamics of white-tailed ptarmigan ( Lagopus leucurus) in Rocky Mountain National Park, USA. We performed canonical correlation analysis on the demographic subspace of ptarmigan and local-climate subspace defined by the empirical orthogonal function (EOF) using data from 1975 to 1999. We found that two subspaces were significantly correlated on the first canonical variable. The Pearson correlation coefficient of the first EOF values of the demographic and local-climate subspaces was significant. The population density and the first EOF of local-climate subspace influenced the ptarmigan population with 1-year lags in the Gompertz model. However, the NAO index was neither related to the first two EOF of local-climate subspace nor to the first EOF of the demographic subspace of ptarmigan. Moreover, the NAO index was not a significant term in the Gompertz model for the ptarmigan population. Therefore, local climate had stronger signature on the demography of ptarmigan than did a large-scale index, i.e., the NAO index. We conclude that local responses of wildlife populations to changing climate may not be adequately explained by models that project large-scale climatic patterns.

Animals↗

PubMed2004

A type of nucleotide motif that distinguishes tobamovirus species more efficiently than nucleotide signatures.

The complete genomic sequences of forty-eight tobamoviruses were classified and found to form at least twelve species clusters. Individual species were not conveniently defined by 'nucleotide signatures' (i.e. strings of one or more nucleotides unique to a taxon) as these were scattered sparsely throughout the genomes and were mostly single nucleotides. By contrast all the species were concisely and uniquely distinguished by short nucleotide motifs consisting of conserved genus-specific sites intercalated with variable sites that provided species-specific combinations of nucleotides (nucleotide combination motifs; NC-motifs). We describe the procedure for finding NC-motifs in a convenient and phylogenetically conserved region of the tobamovirus RNA polymerase gene, the '4404-50 motif'. NC-motifs have been found in other sets of homologous sequences, and are convenient for use in published taxonomic descriptions.

Conserved Sequence↗

PubMed2006

Fixing the conformations of diamineplatinum(II)-GpG chelates: NMR and CD signatures of individual rotamers.

The bulky, asymmetric analog of the antitumor drug cisplatin, [PtCl(2)(tmen)] (tmen = N,N,N'-trimethylethylenediamine), was used to produce crosslinks with the dinucleotide d(GpG), modeling the most frequent lesions that cisplatin and its analogs cause to DNA. The ligand tmen was chosen because it is expected to constrain the guanine cis to the NMe(2) group in the adduct [Pt(tmen){d(GpG)}](+) to an orientation perpendicular to the coordination plane and to stabilize the other guanine in an oblique orientation, thus maintaining a head-to-head geometry typical of cisplatin-d(GpG) crosslinks within single- and double-stranded DNA. Of the four possible combinations of tmen chirality (R or S symmetry of the coordinated NHMe group) and crosslink direction (5'-G bound cis to the secondary or the tertiary amino group of tmen), two isomers were preponderantly formed, [Pt(R-tmen){d(GpG)}](+) with 5'-G bound cis to NMe(2) and [Pt(S-tmen){d(GpG)}](+) with 5'-G bound cis to NHMe. The former was shown to have a right-handed R2 orientation of guanines similar to that found in duplex DNA, whereas the latter had a left-handed L1 orientation that modeled cisplatin-d(GpG) adducts within single-stranded DNA. The R2 rotamer was found to be in an equilibrium (as observed using EXSY spectroscopy) with a minor fraction (< or =4%) of a Delta-HT rotamer related to R2 by rotation of the 3'-G about the Pt-N7 bond. The major rotamers R2 and L1 were isolated using reverse-phase HPLC, and their NMR and CD signatures were compared to those of the corresponding rotamers of the less hindered adduct [Pt(dmen)(GpG)](+) (dmen = N,N-dimethylethylenediamine). From this and other comparisons with previously reported platinum dinucleotide complexes, and from molecular modeling, it could be concluded that both steric repulsion between guanine and substituents of the cis amino group and N-H...O6 hydrogen bonding are significant effects favoring the oblique orientation of one guanine base typical of the HH rotamers of [Pt(diamine){d(GpG)}](+) and [Pt(diamine)(GpG)](+) complexes.

Circular Dichroism↗

PubMed2026

Integrative pooled transcriptomic analysis reveals shared and distinct molecular signatures in adult T-cell leukemia/lymphoma and peripheral T-cell lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) and peripheral T-cell lymphomas (PTCLs) are aggressive neoplasms of mature T cells with poor prognosis and limited therapies. ATLL originates from HTLV-1 infection, while PTCL comprises heterogeneous subtypes without a defined etiologic factor. Comparative molecular profiling of these malignancies remains limited. We conducted an integrative pooled transcriptomic analysis of publicly available Gene Expression Omnibus (GEO) microarray datasets to compare ATLL, PTCL, and normal T-cell samples. Differential expression, functional enrichment, and protein-protein interaction (PPI) network analyses were performed using STRING, Cytoscape, and Gephi. Key hub genes and functional modules were further analyzed through KEGG and Enrichr databases. Comparative analyses revealed upregulation of extracellular matrix (ECM) components (COL1A1, COL3A1, FN1, SPARC, THBS1) and immune-regulatory molecules (CD163, CXCL12-CXCR4, complement subunits). Shared pathways included ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling. PTCL showed enrichment in coagulation and angiogenesis, while ATLL displayed distinct enrichment of cytoskeletal, chemokine, immune-regulatory, and signaling-associated pathways. PPI networks identified ECM and chemokine signaling as key hubs, with subtype-specific modules related to immune regulation, proliferation, and metabolism. This integrative approach uncovers common and distinct oncogenic programs in ATLL and PTCL, emphasizing ECM remodeling and immune modulation as shared hallmarks. Hub genes such as COL1A1, FN1, and CXCL12-CXCR4 may represent candidate molecular signatures that warrant validation in independent patient cohorts and functional studies before their clinical utility can be established.

Humans↗

PubMed2005

Distinct molecular signature of inflammatory breast cancer by cDNA microarray analysis.

Inflammatory breast cancer (IBC) is a clinically distinct and aggressive form of locally advanced breast cancer with largely unknown genetic determinants. Overexpression of the RhoC GTPase and of HER2, and decreased ER-expression are involved in IBC. Multimodality treatment has increased survival but prognosis is still poor. Novel molecular targets for improved neoadjuvant treatment are necessary. Using cDNA microarrays, we performed genome-wide expression profiling of pre-treatment tumour samples of 16 patients with IBC and 18 patients with non-stage-matched non-IBC. Rigid clinical diagnostic criteria according to the TNM classification of the American Joint Committee on Cancer were adopted. Unsupervised hierarchical clustering accurately distinguished IBC and non-IBC samples. A set of 50 discriminator genes was identified in a learning group of tumour samples and was successful in diagnosing IBC in a validation group of samples (accuracy of 88%). Exclusion of ER-related or HER2-related genes did not alter this discriminatory accuracy, indicating that the expression of other genes in addition to ER and HER2 characterize the IBC phenotype. The molecular signature of IBC revealed the overexpression of a large number of NF-kappaB target genes, explaining at least part of the aggressive nature of IBC. Successful validation of some of the overexpressed genes by immunohistochemistry or real-time quantitative PCR demonstrated the robustness of the cDNA microarray experiments. The results of our study provide potential targets for the treatment of patients with IBC.

Belgium↗

PubMed2005

cDNA microarray analysis of isogenic paclitaxel- and doxorubicin-resistant breast tumor cell lines reveals distinct drug-specific genetic signatures of resistance.

cDNA microarray analysis is a highly useful tool for the classification of tumors and for prediction of patient prognosis to specific cancers based on this classification. However, to date, there is little evidence that microarray approaches can be used to reliably predict patient response to specific chemotherapy drugs or regimens. This is likely due to an inability to differentiate between genes affecting patient prognosis and genes that play a role in response to specific drugs. Thus, it would be highly useful to identify genes whose expression correlates with tumor cell sensitivity to specific chemotherapy agents in a drug-specific manner. Using cDNA microarray analysis of wildtype MCF-7 breast tumor cells and isogenic paclitaxel-resistant (MCF-7(TAX)) or doxorubicin-resistant (MCF-7(DOX)) derivative cell lines, we have uncovered drug-specific changes in gene expression that accompany the establishment of paclitaxel or doxorubicin resistance. These changes in gene expression were confirmed by quantitative reverse transcription polymerase chain reaction and immunoblotting experiments, with a confirmation rate of approximately 91-95%. The genes identified may prove highly useful for prediction of response to paclitaxel or doxorubicin in patients with breast cancer. To our knowledge this is the first report of drug-specific genetic signatures of resistance to paclitaxel or doxorubicin, based on a comparison of gene expression between isogenic wildtype and drug-resistant tumor cell lines. Moreover, this study provides significant insight into the wide variety of mechanisms through which resistance to these agents may be acquired in breast cancer.

Antibiotics, Antineoplastic↗

PubMed2006

Gene expression signatures and outcome prediction in mature B-cell malignancies.

Non-Hodgkin's lymphomas comprise a diverse group of diseases that are subclassified by the state of differentiation of the malignant B cells, presence of specific cytogenetic abnormalities, and characteristic morphology. Gene expression profiling has revealed that within each category of non-Hodgkin's lymphoma, there exists a significant molecular heterogeneity that can be reflected in differences in tumor behavior and patient outcome. Appreciation of gene expression signatures that are associated with patient outcome will allow better prognostication of disease course and aid the application of molecularly selective patients to improve patient outcome.

Forecasting↗

PubMed2026

Machine learning-based integration develops a novel lysosome-related prognostic signature associated with prognosis and immune infiltration landscape in acute myeloid leukemia.

BACKGROUND: Lysosomes are essential for intracellular degradation and recycling, and changes in their function significantly contribute to tumor growth. Nonetheless, the exact role of lysosome-related genes (LRGs) in the pathogenesis of acute myeloid leukemia (AML) is still inadequately comprehended. METHODS: Differentially expressed LRGs (DE-LRGs) between AML and control groups were identified using AML-related data extracted from the Gene Expression Omnibus (GEO). The LRGs-related prognostic genes were identified and the risk model was established using univariate COX regression analysis and machine learning algorithms, based on the data obtained from The Cancer Genome Atlas (TCGA). Subsequently, we performed comprehensive analyses regarding clinical features, functional pathways, immune microenvironment, and chemotherapeutic drugs sensitivity between the high- and low-risk groups. Reverse transcription Quantitative polymerase chain reaction (RT-qPCR) and western blot were adopted to validate the expression of prognostic genes in human bone marrow-derived cell line HS-27 A and human AML cell line MOLM-13. RESULTS: Through comprehensive analysis, a risk model was developed utilizing ten LRGs (ATP6V0E2, CALCRL, TMEM165, GZMB, HCK, TCIRG1, CD1D, GPRASP1, ABCA1, and NAGA), and this model was further validated using GEO datasets. Significant differences in clinical characteristics, functional pathways, immune microenvironment characteristics, and chemotherapeutic drug sensitivity were observed between the two risk groups In vitro validation experiment illustrated that the expression trends of ATP6V0E2, TMEM165, and ABCA1 were consistent with our bioinformatics analysis. CONCLUSION: Our study demonstrates that lysosome-associated signature might forecast the prognosis of AML patients and offer guidance for subsequent immunotherapy and chemotherapy strategies.

Acute myeloid leukemia↗

PubMed2026

Genomic diversity, inbreeding, and selection signatures in duroc, landrace, and yorkshire pigs from a long-term closed breeding system.

Duroc (DD), Landrace (LL), and Yorkshire (YY) are among the most widely used commercial pig breeds, having undergone intense long-term selection within closed breeding systems. This study presents a comprehensive genomic analysis of genetic diversity, inbreeding patterns, and selection signatures in DD, LL, and YY populations that have been subject to close breeding for over 15 years. Genomic and pedigree data were available for 1,088 animals (DD = 348, LL = 276, YY = 464), genotyped using the GenoBaits® Porcine 100 K SNP panel. Principal component analysis and genetic diversity metrics revealed distinct population structures among the three breeds. Pairwise genetic differentiation supported this pattern, with DD showing the greatest divergence from LL (0.34 ± 0.24) and YY (0.33 ± 0.24), while LL and YY were more closely related (FST = 0.22 ± 0.19). Linkage disequilibrium (LD) analysis further confirmed these differences, as DD exhibited the highest average r² (0.34), followed by LL (0.28) and YY (0.25). Within-breed genetic diversity metrics, including observed heterozygosity (HO: 0.37 in DD, 0.39 in LL, 0.38 in YY), expected heterozygosity (HE: 0.36 in DD, 0.37 in LL, 0.38 in YY), and minor allele frequency (MAF: 0.27 in DD, 0.28 in LL, 0.29 in YY), indicated greater genetic variability in LL and YY compared to DD. Runs of homozygosity (ROH) analyses revealed different patterns of autozygosity, with DD exhibiting more long ROH indicative of recent inbreeding, while YY harbored a higher number of short ROH, suggestive of more ancient demographic events. ROH-based inbreeding coefficients (FROH) consistently exceeded pedigree-based estimates (FPED) across all breeds, highlighting the presence of recent or unrecorded inbreeding that pedigree data may not fully capture. According to Generation Proxy Selection Mapping (GPSM), 17, 1, and 12 significant SNPs were detected in DD, LL, and YY, respectively. Functional annotation of ROH islands and GPSM-significant loci revealed both breed-specific and overlapping QTLs related to traits such as growth, reproduction, and carcass. In general, the findings of this study contribute to a deeper understanding of the genomic consequences of long-term closed breeding and provide reference information to support consideration of breeding strategies that balance continued selection for productivity with the maintenance of genetic diversity in modern commercial pig populations.

Animals↗

PubMed1991

Mass spectrometric signature of S-prenylated cysteine peptides.

The fast atom bombardment mass spectra of peptides containing S-prenylated cysteine display signature fragmentations characteristic of this modified amino acid. The fragmentation is independent of the nature of the cysteine carbonyl substituent, easily differentiates prenyl from nonprenyl alkylation, and readily identifies the oligomer count of the prenyl. This screening method, which requires little time, effort, or material (compared with previous analysis methods based on chemical degradation), greatly facilitates the identification of these prenylated proteins.

Amino Acid Sequence↗

PubMed1996

Isolation of an ion channel gene from Arabidopsis thaliana using the H5 signature sequence from voltage-dependent K+ channels.

A degenerate oligonucleotide corresponding to the K+ channel signature sequence (TMTTVGYGD) was used to isolate the genomic and cDNA forms of a new channel gene, AKT3, from Arabidopsis thaliana. The deduced protein sequence has a predicted membrane topography similar to Shaker-like K+ channels. Three distinct modules comprise the carboxyl-terminal half: a nucleotide-binding motif, an ankyrin repeat domain, and a polyglutamate track. Xenopus oocytes injected with cRNA exhibited an inward-rectifying K+ current, demonstrating that the AKT3 polypeptide is a functional transport protein. Two other Arabidopsis K+ transporters (AKT1 and KAT1) share 60% homology with AKT3; together these proteins constitute a family of plant inward-rectifying K+ channels.

Amino Acid Sequence↗

PubMed1980

Protein signatures--a novel way to classify proteins.

A method is developed to classify proteins by establishing their familial identity based on the presence and the absence of characteristic signature dipeptides. It is hoped that this method will lead to the establishment of a theoretical basis for the determination of interrelationships among proteins.

Amino Acid Sequence↗

PubMed1991

Lysine 335, part of the KMSKS signature sequence, plays a crucial role in the amino acid activation catalysed by the methionyl-tRNA synthetase from Escherichia coli.

The KMSKS pattern, conserved among several aminoacyl-tRNA synthetase sequences, was first recognized in the Escherichia coli methionyl-tRNA synthetase through affinity labelling with an oxidized reactive derivative of tRNA(Met)f. Upon complex formation, two lysine residues of the methionyl-tRNA synthetase (Lys61 and 335, the latter being part of the KMSKS sequence) could be crosslinked by the 3'-acceptor end of the oxidized tRNA. Identification of an equivalent reactive lysine residue at the active centre of tyrosyl-tRNA synthetase designated the KMSKS sequence as a putative component of the active site of methionyl-tRNA synthetase. To probe the functional role of the labelled lysine residue within the KMSKS pattern, two variants of methionyl-tRNA synthetase containing a glutamine residue at either position 61 or 335 were constructed by using site-directed mutagenesis. Substitution of Lys61 slightly affected the enzyme activity. In contrast, the enzyme activities were very sensitive to the substitution of Lys335 by Gln. Pre-steady-state analysis of methionyladenylate synthesis demonstrated that this substitution rendered the enzyme unable to stabilize the transition state complex in the methionine activation reaction. A similar effect was obtained upon substituting Lys335 by an alanine instead of a glutamine residue, thereby excluding an effect specific for the glutamine side-chain. Furthermore, the importance of the basic character of Lys335 was investigated by studying mutants with a glutamate or an arginine residue at this position. It is concluded that the N-6-amino group of Lys335 plays a crucial role in the activation of methionine, mainly by stabilizing the transient complex on the way to methionyladenylate, through interaction with the pyrophosphate moiety of bound ATP-Mg2+. We propose, therefore, that the KMSKS pattern in the structure of an aminoacyl-tRNA synthetase sequence represents a signature sequence characteristic of both the pyrophosphate subsite and the catalytic centre.

Adenosine Triphosphate↗

PubMed1985

Odor signatures and kin recognition.

The basis of olfactory signatures mediating human kin recognition was investigated in two experiments. The odors of mothers and offspring were correctly matched (by subjects unfamiliar with the stimulus individuals) at a greater than chance frequency. In contrast, subjects were not able reliably to match the odors of husbands and wives. These data support the hypotheses that characteristic individuals odors are genetically mediated and that kin recognition should be facilitated by the similarity of such familiar odors among close relatives.

Adolescent↗

PubMed1992

Intracellular calcium 'signatures' evoked by different agonists in isolated bovine aortic endothelial cells.

Agonist induced increases in intracellular free calcium, [Ca2+]i, were measured in single Fura-2 loaded bovine aortic endothelial (BAE) cells by dual wavelength microspectrofluorimetry. Low doses of ATP (less than 10 microM) induced complex changes in [Ca2+]i. These changes usually consisted of a large initial transient peak with subsequent fluctuations superimposed upon a maintained rise in [Ca2+]i. Higher doses of ATP (greater than 50 microM) produced much simpler biphasic increases in [Ca2+]i in individual cells. Acetylcholine and bradykinin also elicited increases in [Ca2+]i in single cells in confluent monolayers of endothelial cells. However, only acetylcholine produced complex fluctuations. High doses of acetylcholine evoked simple rises in [Ca2+]i similar to those seen with high doses of ATP. In contrast, bradykinin evoked relatively simple rises in [Ca2+]i at all doses used. These results indicate that the mechanisms responsible for generating agonist induced increases in [Ca2+]i in BAE cells are not homogeneous. ATP and acetylcholine produced more complex Ca2+ changes or 'signatures' in single confluent bovine aortic endothelial cells than bradykinin. All three agonists appeared to release Ca2+ from intracellular stores as well as stimulating Ca2+ influx. The possible mechanisms underlying these phenomena are discussed.

Acetylcholine↗

PubMed1992

Elemental source signatures of aerosols from the Canadian high Arctic.

The seasonal fluctuations of antimony, arsenic, indium, manganese and vanadium have been measured in airborne particulate matter from 1982-1987 at Alert in the Canadian high Arctic. Calculations of enrichment factors have shown that arsenic and antimony are very enriched in the wintertime aerosol. While wintertime ratios of non-crustal manganese/non-crustal vanadium were in agreement with previously published work, summertime ratios often resulted in negative values. A re-evaluation of the crustal Mn/V ratio was undertaken by looking at this ratio during the summertime and assuming that nearly all the airborne particulate matter was derived from crustal matter. Principal Source Contribution Function Analyses were performed for arsenic, indium and manganese. The results suggested that these important regional signatures can now be characterized as coming from distinct European and Asian areas. This improvement in area resolution is much more satisfactory than citing the usual attribution of an overall Eurasian source.

Journal Article↗