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PubMedDate not supplied

Homeostatic signature of anabolic steroids in cattle using 1H-13C HMBC NMR metabonomics.

We used metabonomics to discriminate the urinary signature of different anabolic steroid treatments in cattle having different physiological backgrounds (age, sex, and race). (1)H-(13)C heteronuclear multiple bonding connectivity NMR spectroscopy and multivariate statistical methods reveal that metabolites such as trimethylamine-N-oxide, dimethylamine, hippurate, creatine, creatinine, and citrate characterize the biological fingerprint of anabolic treatment. These urinary biomarkers suggest an overall homeostatic adaptation in nitrogen and energy metabolism. From results obtained in this study, it is now possible to consider metabonomics as a complementary method usable to improve doping control strategies to detect fraudulent anabolic treatment in cattle since the oriented global metabolic response provides helpful discrimination.

Analysis of Variance↗
PubMed2006

Determination of beta-amyloid peptide signatures in cerebrospinal fluid using immunoprecipitation-mass spectrometry.

Early pathogenic events in Alzheimer's disease (AD) involve increased production and/or reduced clearance of beta-amyloid (Abeta), especially the 42 amino acid fragment Abeta1-42. The Abeta1-42 peptide is generated through cleavage of the amyloid precursor protein by beta- and gamma-secretase and is catabolised by a variety of proteolytic enzymes such as insulin-degrading enzyme and neprilysin. Here, we describe a method that employs immunoprecipitation combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to determine the pattern of C-terminally truncated Abeta peptides in cerebrospinal fluid (CSF). Using antibodies coupled to magnetic beads, we have detected 18 C-terminally and 2 N-terminally truncated Abeta peptides in CSF. By determining the identity and profile of the truncated Abeta peptides, more insight may be gained about differences in the metabolism and structural properties of Abeta in AD. Finally, the Abeta fragment signatures may prove useful as a diagnostic test for AD.

Amino Acid Sequence↗
PubMed2005

Use of isotopic signatures for mass spectral detection of protein adduction by chemically reactive metabolites of bromobenzene: studies with model proteins.

The cytotoxicity of many small organic compounds often apparently derives from their metabolic activation and covalent binding to cellular proteins. It is therefore of considerable interest to be able to determine, for a given protoxin, which metabolites modify which proteins at which sites. Our laboratory has identified more than 45 target proteins for bromobenzene metabolites in liver by peptide mass mapping after two-dimensional electrophoresis. Through all of this work, we have never observed a bromine-containing peptide. We therefore generated model adducted proteins by carbodiimide coupling of Nalpha-acetyl-Ntau-(p-bromophenyl)-L-histidine (1) and Nalpha-acetyl-Nepsilon-(p-bromophenyl)-L-lysine (2) to bovine pancreatic ribonuclease A. For the adducts, RNase-(1)n and RNase-(2)n, mass spectrometry indicated that n = 0-2 and 0-6, respectively. RNase-(2)n was submitted to in-gel and in-solution digestion with trypsin, and the digests were analyzed by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) and liquid chromatgraphy electrospray ionization MS (LC/ESI-MS) and tandem MS (MS/MS). Sequence coverages observed ranged from 67% with only three modified lysines observed using in-gel digestion and MALDI-TOF analysis, to 100% coverage with all 10 lysines observed in both modified and unmodified form using in-solution digestion and LC/ESI-MS. In the mass spectra of all modified peptides up to 2000 Da, the bromine isotope pattern was obvious by visual inspection; for peptides up to 3600 Da, the isotopic signature could be recognized by visual comparison to simulated spectra. The presence of Br-containing adducts was confirmed by MS/MS analysis of selected peptides. The selection of peaks for MS/MS analysis was significantly facilitated by visual recognition of the bromine isotope pattern, even at signal-to-noise ratios of 10 (or lower in favorable cases). These results indicate that stable isotope labeling may have considerable potential for detecting and locating protein adducts of reactive metabolites.

Bromobenzenes↗
PubMed1999

Analysis of hexamer and pentamer motifs within a maize database: the presence of motif 'signatures' in functional gene categories.

Several transposable elements (TEs) have been reported in association with genes in maize and other plants. In this study we found, based on statistical analyses of 951 DNA sequences within a maize computer database, that short hexamer and pentamer DNA motifs from the Activator (Ac) and from the Tourist TEs, respectively, were also associated with maize genes. Moreover, these two short hexamer and pentamer TE motifs were nonrandomly and nearly nonrandomly distributed, respectively, with respect to particular biochemical functions of those maize genes. To determine whether this distribution may be unique to TE motifs, or may be more widespread among hexamers/pentamers in general, we similarly studied six additional hexamer or pentamer sequences not derived from TEs. These also showed nonrandom distribution with respect to functional gene categories in the maize database. However, each of the total of eight short sequence motifs we studied differed in its pattern of association with distinct sets of functional gene categories; that is, there was a unique 'signature' for each of the hexamers and pentameters tested. Potential biological hypotheses to explain these findings are discussed.

DNA Transposable Elements↗
PubMed1999

Evaluation of hemostasis by the Clot Signature Analyzer: a potentially valuable device for the anesthesiologist.

Rapid detection of hemostatic defects presents a challenge for the anesthesiologist who must balance anesthetic and surgical considerations for maintaining adequate platelet and coagulant factors, while keeping allogenic blood exposure to a minimum. The Clot Signature Analyzer, a point-of-care device capable of rapid response and easy interpretation is described here. Its applicability in two obstetrical patients with platelet dysfunction is discussed.

Adult↗
PubMed2004

Changes in chemical signature and host specificity from larval retrieval to full social integration in the myrmecophilous butterfly Maculinea rebeli.

The ant social parasite, Maculinea rebeli shows high levels of host specificity at a regional scale. While 68-88% of caterpillars in the field are adopted by nonhost Myrmica ants, 95-100% of the butterflies emerge from the natural host M. schencki the following year. While retrieval of preadoption caterpillars is specific to the genus Myrmica, it does not explain differential survival with different Myrmica species. We present survival data with host and nonhost Myrmica species suggesting that, with nonhosts (M. sabuleti and M. rubra), survival depends on the physiological state of the colony. We also compared the similarities of the epicuticular surface hydrocarbon signatures of caterpillars that were reared by host and nonhost Myrmica for 3 weeks with those from tending workers. Counterintuitively, the hydrocarbons of postadoption caterpillars were more similar (78%, 73%) to the ant colony profiles of the nonhost species than were caterpillars reared in colonies of M. schencki (42% similarity). However, caterpillars from M. schencki nests that were then isolated for 4 additional days showed unchanged chemical profiles, whereas the similarities of those from nonhost colonies fell to 52 and 56%, respectively. Six compounds, presumably newly synthesized, were detected on the isolated caterpillars that could not have been acquired from M. sabuleti and M. rubra (nor occurred on preadoption caterpillars), five of which were found on the natural host M. schencki. These new compounds may relate to the high rank the caterpillars attain within the hierarchy of M. schencki societies. The same compounds would identify the caterpillars as intruders in non-schencki colonies, where their synthesis appeared to be largely suppressed. The ability to synthesize or suppress additional compounds once adopted explains the pattern of mortalities found among fully integrated caterpillars in Myrmica colonies of different species and physiological states.

Animals↗
PubMed2002

Classification, identification and subtyping of bacteria based on pyrosequencing and signature matching of 16S rDNA fragments.

The rapid identification of the etiological agent of microbial infections can bring about both clinical and financial benefits. Thus, fast and generally applicable classification methods are needed that will enable us to rapidly distinguish pathogenic bacteria from commensals or saprophytic bacteria found in the same habitat. We here show that provisional classification of bacterial isolates can be performed on a large scale based on 16S rRNA sequence comparisons using Pyrosequencing, a recently described real-time DNA sequence analysis technique, and the concept of signature matching. The probes we have developed, together with the new technology, will enable early diagnosis of specific pathogens, which is critical for the rational use of antimicrobial therapy in clinical medicine.

Base Sequence↗
PubMed2006

Visual sharpness contingency in recognition memory for orientation: mnemonic illusion suppressed by sensory signature.

A striking finding about human memory is that people's level of accuracy in remembering the orientation of heads on coins is often not simply at the chance level but significantly below it. However, S. W. Kelly, A. M. Burton, T. Kato, and S. Akamatsu (2001) reported that this is not so when two-alternative forced-choice visual recognition is employed. The Kelly et al. result could not be replicated here with a copy of their stimuli. However, the result was successfully replicated with newly created stimuli. A series of experiments provided converging evidence that the mnemonic illusion is suppressed when recognition alternatives possess sharp visual detail. The role of a sensory signature in suppressing the mnemonic illusion and in modulating visual recognition performance in general is delineated.

Adolescent↗
PubMed1997

A signature motif in transcriptional co-activators mediates binding to nuclear receptors.

The binding of lipophilic hormones, retinoids and vitamins to members of the nuclear-receptor superfamily modifies the DNA-binding and transcriptional properties of these receptors, resulting in the activation or repression of target genes. Ligand binding induces conformational changes in nuclear receptors and promotes their association with a diverse group of nuclear proteins, including SRC-1/p160, TIF-2/GRIP-1 and CBP/p300 which function as co-activators of transcription, and RIP-140, TIF-1 and TRIP-1/SUG-1 whose functions are unclear. Here we report that a short sequence motif LXXLL (where L is leucine and X is any amino acid) present in RIP-140, SRC-1 and CBP is necessary and sufficient to mediate the binding of these proteins to liganded nuclear receptors. We show that the ability of SRC-1 to bind the oestrogen receptor and enhance its transcriptional activity is dependent upon the integrity of the LXXLL motifs and on key hydrophobic residues in a conserved helix (helix 12) of the oestrogen receptor that are required for its ligand-induced activation function. We propose that the LXXLL motif is a signature sequence that facilitates the interaction of different proteins with nuclear receptors, and is thus a defining feature of a new family of nuclear proteins.

Adaptor Proteins, Signal Transducing↗
PubMed1991

The spectral signature method for the analysis of PET brain images.

We introduce the concept of the metabolic centroid spectrum as the feature space to characterize the distribution of metabolic activity in three-dimensional brains. The method computes the metabolic centroid of a brain subvolume for each increment of metabolic activity occurring in the whole brain. The result is the metabolic spectral signature, a continuous three-dimensional curve whose shape reflects the distribution of metabolic rates in the brain. The method's sensitivity to metabolic distribution asymmetries is greatly increased over that of the metabolic centroid method, while retaining its advantages; it is almost invariant to head size, head positioning, photon scatter, and the positron emission tomography (PET) camera's full width at half-maximum. It does not require magnetic resonance, computed tomography, or x-ray images. To test the method we analyzed the metabolic PET images of 40 normal subjects and 20 schizophrenics. The results show a unification of several metabolic characteristics of schizophrenic brains, such as laterality, hypofrontality, cortical/subcortical abnormalities, and overall brain hypometabolism, which were identified by different laboratories in separate studies using differing methodologies. Here they are presented by a single automatic objective method.

Adult↗
PubMed2003

The far-ultraviolet signature of the 'missing' baryons in the Local Group of galaxies.

The number of baryons detected in the low-redshift (z < 1) Universe is far smaller than the number detected in corresponding volumes at higher redshifts. Simulations of the formation of structure in the Universe show that up to two-thirds of the 'missing' baryons may have escaped detection because of their high temperature and low density. One of the few ways to detect this matter directly is to look for its signature in the form of ultraviolet absorption lines in the spectra of background sources such as quasars. Here we show that the amplitude of the average velocity vector of 'high velocity' O vi (O5+) absorption clouds detected in a survey of ultraviolet emission from active galactic nuclei decreases significantly when the vector is transformed to the frames of the Galactic Standard of Rest and the Local Group of galaxies. At least 82 per cent of these absorbers are not associated with any 'high velocity' atomic hydrogen complex in our Galaxy, and are therefore likely to result from a primordial warm-hot intergalactic medium pervading an extended corona around the Milky Way or the Local Group. The total mass of baryons in this medium is estimated to be up to approximately 10(12) solar masses, which is of the order of the mass required to dynamically stabilize the Local Group.

Journal Article↗
PubMed2003

Signature of optimal doping in Hall-effect measurements on a high-temperature superconductor.

High-temperature superconductivity is achieved by doping copper oxide insulators with charge carriers. The density of carriers in conducting materials can be determined from measurements of the Hall voltage--the voltage transverse to the flow of the electrical current that is proportional to an applied magnetic field. In common metals, this proportionality (the Hall coefficient) is robustly temperature independent. This is in marked contrast to the behaviour seen in high-temperature superconductors when in the 'normal' (resistive) state; the departure from expected behaviour is a key signature of the unconventional nature of the normal state, the origin of which remains a central controversy in condensed matter physics. Here we report the evolution of the low-temperature Hall coefficient in the normal state as the carrier density is increased, from the onset of superconductivity and beyond (where superconductivity has been suppressed by a magnetic field). Surprisingly, the Hall coefficient does not vary monotonically with doping but rather exhibits a sharp change at the optimal doping level for superconductivity. This observation supports the idea that two competing ground states underlie the high-temperature superconducting phase.

Journal Article↗
PubMed2005

Trace element signature of subduction-zone fluids, melts and supercritical liquids at 120-180 km depth.

Fluids and melts liberated from subducting oceanic crust recycle lithophile elements back into the mantle wedge, facilitate melting and ultimately lead to prolific subduction-zone arc volcanism. The nature and composition of the mobile phases generated in the subducting slab at high pressures have, however, remained largely unknown. Here we report direct LA-ICPMS measurements of the composition of fluids and melts equilibrated with a basaltic eclogite at pressures equivalent to depths in the Earth of 120-180 km and temperatures of 700-1,200 degrees C. The resultant liquid/mineral partition coefficients constrain the recycling rates of key elements. The dichotomy of dehydration versus melting at 120 km depth is expressed through contrasting behaviour of many trace elements (U/Th, Sr, Ba, Be and the light rare-earth elements). At pressures equivalent to 180 km depth, however, a supercritical liquid with melt-like solubilities for the investigated trace elements is observed, even at low temperatures. This mobilizes most of the key trace elements (except the heavy rare-earth elements, Y and Sc) and thus limits fluid-phase transfer of geochemical signatures in subduction zones to pressures less than 6 GPa.

Journal Article↗
PubMed2005

Conservation of gene expression signatures between zebrafish and human liver tumors and tumor progression.

The zebrafish (Danio rerio) has been long advocated as a model for cancer research, but little is known about the real molecular similarities between zebrafish and human tumors. Comparative analysis of microarray data from zebrafish liver tumors with those from four human tumor types revealed molecular conservation at various levels between fish and human tumors. This approach provides a useful strategy for identifying an expression signature that is strongly associated with a disease phenotype.

Amino Acid Sequence↗
PubMed2005

From signatures to models: understanding cancer using microarrays.

Genomics has the potential to revolutionize the diagnosis and management of cancer by offering an unprecedented comprehensive view of the molecular underpinnings of pathology. Computational analysis is essential to transform the masses of generated data into a mechanistic understanding of disease. Here we review current research aimed at uncovering the modular organization and function of transcriptional networks and responses in cancer. We first describe how methods that analyze biological processes in terms of higher-level modules can identify robust signatures of disease mechanisms. We then discuss methods that aim to identify the regulatory mechanisms underlying these modules and processes. Finally, we show how comparative analysis, combining human data with model organisms, can lead to more robust findings. We conclude by discussing the challenges of generalizing these methods from cells to tissues and the opportunities they offer to improve cancer diagnosis and management.

Algorithms↗
PubMed2005

Multiplexed absolute quantification in proteomics using artificial QCAT proteins of concatenated signature peptides.

Absolute quantification in proteomics usually involves simultaneous determination of representative proteolytic peptides and stable isotope-labeled analogs. The principal limitation to widespread implementation of this approach is the availability of standard signature peptides in accurately known amounts. We report the successful design and construction of an artificial gene encoding a concatenation of tryptic peptides (QCAT protein) from several chick (Gallus gallus) skeletal muscle proteins and features for quantification and purification.

Animals↗
PubMed2004

A sensory signature that distinguishes true from false memories.

Human behavioral studies show that there is greater sensory/perceptual detail associated with true memories than false memories. We therefore hypothesized that true recognition of abstract shapes would elicit greater visual cortical activation than would false recognition. During functional magnetic resonance imaging (fMRI), participants studied exemplar shapes and later made recognition memory decisions ("old" or "new") concerning studied exemplars (old shapes), nonstudied lures (related shapes) and new shapes. Within visual processing regions, direct contrasts between true recognition ("old" response to an old shape; old-hit) and false recognition ("old" response to a related shape; related-false alarm) revealed preferential true recognition-related activity in early visual processing regions (Brodmann area (BA)17, BA18). By comparison, both true and false recognition were associated with activity in early and late (BA19, BA37) visual processing regions, the late regions potentially supporting "old" responses, independent of accuracy. Further analyses suggested that the differential early visual processing activity reflected repetition priming, a type of implicit memory. Thus, the sensory signature that distinguishes true from false recognition may not be accessible to conscious awareness.

Adult↗