0% (i.e. the sequence similarities were less
than 96.0%). DNA-DNA hybridization experiments showed that the levels of DNA-DNA relatedness between strain Gsoil 3046(T) and its phylogenetically closest neighbours were below 25%. The G+C content of the genomic DNA was 66.6 mol%. In addition, the presence of ubiquinone 0-8 as the predominant respiratory quinone, iso-C(17):(1) MK-1775 clinical trial omega 99C, iso-C(16:0), iso-C(15:0) and iso-C(17:0) as the major cellular fatty acids and iso-C(13:0) 3-OH and iso-C(11:0) 3-OH as the major hydroxy fatty acids supported the affiliation of strain Gsoil 3046(T) to the genus Dyella. On the basis of its phenotypic properties and phylogenetic; distinctiveness, strain Gsoil 3046(T) represents a novel species in the genus Dyella, for which the name Dyella ginsengisoli sp. nov. is proposed. The type strain is Gsoil 3046 T (=KCTC 12599(T) =DSM 18387(T)).”
“Background: Altered interoception, i.e., processing of stimuli from inside the body, has been considered an important component of drug-taking
behavior. However, approaches to examine interoceptive sensitivity in humans have been limited. This selleck compound study examined the hypothesis that adolescents with substance use disorder show altered interoceptive processing, measured by stimulating mechano-receptive C-fibers (MR-CF) via soft touch.\n\nMethods: Adolescents with substance use disorders (SUD, n = 15) and comparison youth (CON, n = 17) underwent functional magnetic resonance imaging (fMRI) during anticipation or reception of a positively valenced “Soft Touch” consisting of MR-CF stimulation to the palm or forearm. Visual analog scales (VAS) indexed subjective interoceptive experience (e.g., pleasantness, intensity).\n\nResults: Across all conditions, SUD displayed attenuated left posterior insula activation compared to CON. Greater left anterior insula and right lentiform nucleus activation was evident during the application of soft GSK1120212 solubility dmso touch for SUD but not for CON. Whereas for CON,
greater left anterior insula activation was associated with higher pleasantness ratings, pleasantness was linked to less anterior insula activation in SUD. Finally, within SUD, attenuated posterior insula activation was related to more recent cannabis use.\n\nConclusions: SUD adolescents exhibit blunted somatovisceral processing of pleasant stimulation, heightened sensitivity in regions responsible for processing reward value, and altered relationships between interoceptive processing and subjective experience. (C) 2013 Elsevier Ireland Ltd. All rights reserved.”
“One of the most important diseases of eucalyptus plantations is caused by the rust fungus Puccinia psidii. While the genetic basis of rust resistance has been addressed recently, little is known about the physiological aspects of Eucalyptus-P. psidii interaction. In order to fill this gap, we undertook a study investigating the effects of P. psidii infection on photosynthetic processes of two E.
We analyze two different physical settings, with the thermal
gradient orthogonal or parallel to the gravity field. In both settings, we follow the formation of the convective flows from the initial time, when the perturbation is turned on, to the steady state. In the first setting (orthogonal fields) we investigate several different cases, varying the initial stationary ensemble and the perturbing field. We find that the final steady-state convective cell is independent of the specific sequence of perturbation fields, which only affects the transient behavior. In all cases, we find that the convective roll is formed through a sequence of damped oscillations of the local fields (density, temperature, and velocity), superimposed to an overall this website relaxation toward the local steady-state values. Then, we show how D-NEMD can be applied to the Rayleigh-Beacutenard (RB) setting (parallel fields). In these conditions,
the convective flow only establishes above a threshold, without a preferred verse of rotation. We analyze only the response to the ignition of the gravity field in a stationary system under the action of a vertical thermal gradient. Also in this case we characterize the transient response by following the evolution of the density, temperature, and velocity fields until the steady-state RB convective cell is formed. The observed transients are similar to those observed in the case of orthogonal fields. However, the
final steady states are quite different. Finally, we briefly discuss the conditions selleck kinase inhibitor for the general applicability of the D-NEMD method.”
“Objective: In transoral robotic surgery (TORS), if an endoscopic arm equipped with two integrated cameras is placed close to a lesion, a three-dimensionally magnified view of the operative field can be obtained. More important is that the operation can be performed precisely and bimanually using two instrument arms that can move Epigenetics inhibitor freely within a limited working space. We performed TORS to treat several diseases that occur in the parapharyngeal space (PPS) and subsequently analyzed the treatment outcomes to confirm the validity of this procedure.\n\nPatients and Methods: Between February 2009 and February 2012, 11 patients who required surgical treatment for the removal of a parapharyngeal lesion were enrolled in this prospective study. Nine patients received TORS for parapharyngeal tumor resection, and 2 patients with stylohyoid syndrome underwent TORS for resection of an elongated styloid process. The average age of the patients included in this study was 42 years. Five patients were male, and 6 patients were female.\n\nResults: TORS was successfully performed in all 11 patients. The average robotic system docking and operation times were 9.9 minutes (range, 5-24 minutes) and 54.2 minutes (range, 26-150 minutes), respectively. Patients were able to swallow normally the day after the operation.
Sperm transit through the epididymal duct relies on spontaneous phasic
contractions (SC) of the peritubular smooth muscle wall. Isometric tension studies revealed SC-enhancing effects of the erg channel blockers E-4031, dofetilide, cisapride, and haloperidol and SC-suppressing effects of the activator NS-1643. In the corpus epididymidis, EC50 values of 32 nM and 8.3 mu M were determined for E-4031 and NS-1643, respectively. E-4031 was also able to elicit contraction in epithelium-denuded corpus segments, which lacked SC. In the cauda region, E-4031 and NS-1643 exerted effects on agonist-induced contraction similar to those observed in the proximal duct. Experiments with nifedipine and thapsigargin LGX818 suggested that the excitatory effects of E-4031 depended mainly on external calcium influx and not on intracellular calcium release. Western blot and RT-PCR assays revealed the expression of both, erg1a and erg1b, in all duct regions. Because erg1b appears to predominate in the epididymal duct, patch-clamp experiments were performed on heterologously expressed erg1b channels to investigate the sensitivity of this splice variant to NS-1643. In contrast to its effects on erg1a, NS-1643 induced a concentration-dependent current AZD8055 increase mainly due to a marked leftward shift in
erg1b channel activation by similar to 30 mV at 10 mu M, explaining the inhibitory effect of the drug on epididymal SC. In summary, these data provide strong evidence for a physiological role of erg1 channels in regulating epididymal motility patterns.”
“Alpha amylase (E.C. 220.127.116.11) of Bacillus amyloliquefaciens produced by submerged fermentation was purified to near homogeneity by ion exchange chromatography. Through the process 38.6-fold increase in purity with a specific activity of 72 U/mg proteins was obtained. The apparent molecular weight of the purified enzyme was found to be 58 kDa by SDS-PAGE. The enzyme was relatively stable between pH 5.0-8.0 and temperature between 50 and 60 degrees’C. buy Stattic The enzyme did not show any obligate requirement of metal ions but Ca(2+) and Cu(2+) enhanced
the enzyme activity marginally and the thermostability was enhanced in the presence of Ca(2+) ions. The purified enzyme exhibited maximal substrate specificity for amylose and efficiency in digesting various raw starches. The K(m) and V(max) of the enzyme was determined using both amylose and soluble starch as substrate. The analysis of the hydrolyzed products of soluble starch by thin layer chromatography showed the yield of maltosaccharides after 6 h of hydrolysis.”
“BACKGROUND: The value of frozen sections in the intraoperative examination of sentinel nodes (SN) remains controversial. Accurate frozen sections will spare those patients with node metastasis from a second procedure to complete the axillary dissection. We examined our own experience with intraoperative examination of SN.
In this study we report the analysis of ripe papaya transcriptome by using a cross-species (XSpecies) microarray technique based on the phylogenetic proximity between papaya and Arabidopsis thaliana.\n\nResults: Histone Methyltransf inhibitor Papaya transcriptome analyses resulted
in the identification of 414 ripening-related genes with some having their expression validated by qPCR. The transcription profile was compared with that from ripening tomato and grape. There were many similarities between papaya and tomato especially with respect to the expression of genes encoding proteins involved in primary metabolism, regulation of transcription, biotic and abiotic stress and cell wall metabolism. XSpecies microarray data indicated that transcription factors (TFs) of the MADS-box, NAC and AP2/ERF
gene families were involved in the control of papaya ripening and revealed that cell wall-related gene expression in papaya had similarities to the expression profiles seen in Arabidopsis during hypocotyl development.\n\nConclusion: The cross-species array experiment identified a ripening-related set of genes in papaya allowing the comparison of transcription control between papaya and other fruit bearing taxa during the ripening process.”
“The flexibility of flapping-wing strongly affects the aerodynamic performance of Flapping-wing Micro Air Vehicle (FMAV), and the deformations Entinostat in span-wise and chord-wise directions are coupled together in flight. In this study,
check details the flexible deformation is formulated in span-wise and chord-wise separately in order to analyze its effects on aerodynamic behavior. The preconditioned Navier-Stokes equations based on chimera grid are used in the computational fluid dynamics method to study the aerodynamic effects caused by flexible deformation, and the simulation results are compared with experimental test to illustrate the capability of above method. Based on our results, it is clearly showed that the span-wise flexible deformation should be limited in a small range to achieve higher aerodynamic performance and the chord-wise deformation could enhance the aerodynamic performance. The results also suggest that FMAV designers should design the flapping-wing with high stiffness leading edge to limit the span-wise deformation, and more flexible chord ribs to keep chord-wise deformation in suitable range.”
“Background: We hypothesize that implantation of left ventricular assist device through off-pump technique is feasible and has a comparable result to implantation on cardiopulmonary bypass and could improve one-year survival.\n\nMethods: This retrospective, observational, single-center study was conducted on 29 consecutive patients at our institution who underwent off-pump left ventricular assist device implantation by a single surgeon.\n\nResults: Twenty-seven procedures were performed successfully using the off-pump technique.
(C) 2012 Elsevier www.selleckchem.com/products/tariquidar.html Inc. All rights reserved.”
dropout is a problem of great prevalence and stands as an obstacle to recovery in cocaine-dependent (CD) individuals. Treatment attrition in CD individuals may result from impairments in cognitive control, which can be reliably measured by the Stroop color-word interference task. The present analyses contrasted baseline performance on the color-naming, word-reading, and interference subtests of the Stroop task in CD subjects who completed a cocaine treatment trial (completers: N = 50) and those who dropped out of the trial before completion (non-completers: N = 24). A logistic regression analysis was used to predict trial completion using three models with the following variables: the Stroop task subscale scores (Stroop model); the Hamilton depression rating scale (HDRS) scores (HDRS model); and both the Stroop task subscale scores and HDRS scores (Stroop and HDRS model). Each model was able to significantly predict group membership (completers vs non-completers) better than a model based on a simple constant (HDRS model p = 0.02, Stroop model p = 0.006, and Stroop and HDRS
model p = 0.003). Models using the Stroop preformed better than the HDRS model. These findings suggest that the Stroop task can be used to identify cocaine-dependent subjects at risk for treatment dropout. The Stroop task is a widely available, reliable, and valid instrument that can be easily employed to identify and tailor interventions of at risk individuals in the hope of improving treatment AZD2171 mouse compliance.”
“The abbreviated impactor measurement concept
is a potential improvement to the labor-intensive full-resolution cascade impactor methodology for inhaler aerosol aerodynamic particle size distribution (APSD) measurement by virtue of being simpler and therefore quicker to execute. At the same time, improved measurement precision should be possible by eliminating stages upon which little or no drug mass is collected. Although several designs of abbreviated impactor systems have been developed in recent years, experimental GSK1904529A work is lacking to validate the technique with aerosols produced by currently available inhalers. In part 1 of this two-part article that focuses on aerosols produced by pressurized metered dose inhalers (pMDIs), the evaluation of two abbreviated impactor systems (Copley fast screening Andersen impactor and Trudell fast screening Andersen impactor), based on the full-resolution eight-stage Andersen nonviable cascade impactor (ACI) operating principle, is reported with a formulation producing dry particles. The purpose was to investigate the potential for non-ideal collection behavior associated with particle bounce in relation to internal losses to surfaces from which particles containing active pharmaceutical ingredient are not normally recovered.
Nanodispersions containing astaxanthin were prepared by an emulsification evaporation processing technique. The influence of the processing conditions, buy DZNeP namely,
the pressure of the high-pressure homogenizer (20-90 MPa), the number of passes through the homogenizer (0-4) and the evaporation temperature (16-66 degrees C) on the physicochemical properties of the prepared astaxanthin nanodispersions were evaluated using a three-factor central composite design. Average particle size, polydispersity index (POI) and astaxanthin loss in the prepared nanodispersions were considered as response variables. The multiple-response optimization predicted that using three passes through the high-pressure homogenizer at 30 MPa for the preparation of the astaxanthin nanoemulsion and then removing the organic phase (solvent) from the system by evaporation at 25 degrees C provided astaxanthin nanodispersions with optimum physicochemical properties. (C) 2011 Elsevier Ltd. All rights reserved.”
“Objective. The goal of this investigation was to assess validity of predictive models of stress relaxation in dental polymers when applied to extended master curves generated from short time experimental data by WLF time temperature superposition method. Methods. The stress relaxation modulus changes with time at three different temperatures near the ambient body temperature were
GSK621 supplier determined for selected mono-methacrylate (PEMA and PMMA) and
dimethacrylate (bis-acryl) dental polymers. WLF time-temperature superposition procedure of logarithmic shift of the data from other temperatures to those at 37 degrees C was used to generate extended master curves of relaxation modulus changes with time. The extended data were analyzed for conformity to three different predictive models of stress relaxation including Maxwell, KWW stretched exponential function and Nutting’s power law equation. Results. Maxwell model was found to be a poor fit for the extended data in all polymers tested, but the data showed a much better fit for KWW (0.870 smaller than R-2 smaller than 0.901) and Nutting’s (0.980 smaller than R-2 smaller than 0.986) models. The non-exponential factor beta in the KWW function and the fractional JPH203 cost power exponent n in Nutting’s equation were both significantly different for PEMA based system when compared to that of PMMA and bis-acryl systems. Significance. The mean values of beta in KWW function and power exponent n in Nutting’s equation for PEMA resin is consistent with significant viscoplastic contribution to its deformation under stress unlike in PMMA and bis-acryl resin systems. This may have significant bearing for PEMA use in medium to longer term stress-bearing applications even as a temporization material. (C) 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.
In addition, we show that CDT-2 physically interacts with SEM-5 (GRB2), a known negative modulator of LET-23
signalling that directly binds LET-23, and provide genetic evidence consistent with CDT-2 functioning at or downstream BYL719 molecular weight of LET-23. Interestingly, both SEM-5 and CDT-2 were identified independently in a screen for genes involved in receptor-mediated endocytosis in oocytes, suggesting that attenuation of LET-23 by CDT-2 might be through regulation of endocytosis.\n\nConclusions: In this study, we have shown that CDT-2 and CUL-4, members of the CUL-4/DDB-1/CDT-2 E3 ubiquitin ligase complex attenuate LET-23 signalling in vulval precursor cells. In future, it will be interesting to investigate the potential link to endocytosis and to determine whether other signalling pathways dependent on endocytosis, e.g. LIN-12 (Notch) could be regulated by this ubiquitin ligase complex. This work has uncovered a novel function for the CUL-4/DDB-1/CDT-2 E3 ligase that may be relevant for its mammalian oncogenic activity.”
“Aims: We evaluated biological activity in leukemia cells lines of R and S enantiomers of tert-butyl 4-[(3-nitrophenoxy)-methyl]-2,2-dimethyloxazolidine-3-carboxylate (BNDC).\n\nMain methods: Cytotoxic activity was assessed by MTT assay. Flow cytometry assays were used to determined DNA fragmentation (Propidium Iodide-PI staining) and phosphatidylserine exposure (Annexin-V
and PI staining). DNA condensation was evaluated by fluorescence microscopy using double-staining in leukemia cells (Hoechst and PI). Caspase activities were measured using Z-VAD-FMK, a non-selective caspase inhibitor, by https://www.selleckchem.com/products/AZD8931.html flow cytometry and Z-DEVD-AMC, a selective caspase-3 substrate, by fluorescence spectrometry.\n\nKey findings: Both enantiomers displayed cytotoxic activity against leukemia cell lines (HL60, HL60.Bcl-2, HL60.Bcl-XL and Jurkat) with low toxicity against human peripheral blood mononuclear cell – PBMC based on IC(50) values. In HL60 cell lines, compounds induce exposure of phosphatidylserine and DNA fragmentation, which could be blocked
by pretreatment of cells with Z-VAD-FMK. Confirming this observation, both enantiomers induced caspase-3 activation. Additional analysis revealed an increased percentage of apoptotic cells (defined as those with fragmented nuclei and condensed chromatin) after BB-94 mouse treatment with compounds.\n\nSignificance: Taken together, the results indicate that BNDC compounds exhibited cytotoxic and pro-apoptotic activities and have a potential for developing a new class of anticancer drugs. (C) 2011 Elsevier Inc. All rights reserved.”
“The asymmetric unit of the title compound, C(21)H(25)ClN(2)O, contains four crystallographically independent molecules, which differ mainly in the orientation of the isobutyl groups. The benzene rings are almost orthogonal to each other, forming dihedral angles of 87.40 (6), 88.69 (6), 84.88 (6) and 85.
These compounds show selectivity against hCA XII over hCA I, II and IX. In this study, molecular modeling and docking studies were applied to understand this preference of the compounds for hCA XII. Most likely, the compounds can displace the zinc-bound water molecule of hCA
XII to form a direct interaction with the Zn2+ ion. In the other isozymes, the compounds might not be able to displace the water molecule nor are they expected to interact with the Zn2+ ion.”
“The early onsets of breast cancer metastasis involve cell retention, survival, and resistant to apoptosis and subsequent growth at target vascular beds and tissues in distant organs. We previously reported that angiopoietin-2 (Ang2), an angiogenic regulator stimulates MCF-7 breast tumor metastasis from their orthotopic sites to distant organs through the alpha(5)beta(1) this website integrin/integrin-linked kinase (ILK)/Akt pathway. Here, by using an experimental tumor metastasis model and in vitro studies, we further dissect the underlying mechanism by which Ang2 promotes the initial growth and survival of MCF-7 breast cancer metastasis in the lung of animals. We show that Ang2 increases cell survival and suppresses cell apoptosis through ILK-induced phosphorylation of Akt1, Akt2,
and up-regulation of Bcl-2 in breast cancer cells. Inhibition of ILK, Akt1, and Akt2, and their effector Bcl-2 diminishes Ang2-stimulated breast cancer cell survival and Ang2-attenuated apoptosis in vitro, and initial survival and growth of breast cancer metastasis in the lung of animals. Additionally, siRNA knockdown of endogenous Ang2 MLN4924 purchase in three human metastatic breast
cancer cell lines also inhibits phosphorylation of Akt, expression of Bcl-2, and tumor cell survival, migration, STI571 and increases cell apoptosis. Since increased expression of Ang2 correlates with elevated potential of human breast cancer metastasis in clinic, our data underscore the importance that up-regulated Ang2 not only stimulates breast cancer growth and metastasis at late stages of the process, but is also critical at the initiating stages of metastases onset, thereby suggesting Ang2 as a promising therapeutic target for treating patients with metastatic breast cancer.”
“Fatty acids have gained therapeutic attention because of their nutritional and health implications. The potentialities of different fatty acids as PLA(2) binders have been analysed using molecular docking studies. Among the 46 fatty acids selected for docking studies, erucic acid and linoleic acid gave the highest glide scores. The earlier reported palmitic acid gave only a lower value, being the third in the order of high glide scores. The isothermal titration calorimetric analysis of these fatty acids was also done. The conclusions and inferences from the present study indirectly validate the rigorous use of medicated oils rich in erucic, linoleic and palmitic acids for the treatment of rheumatic symptoms in the traditional medical system of India, Ayurveda.
A synergistic interaction was observed between GTPP constituents, with unfractionated GTPP more potently preconditioning cells than EGCG. GTPP-induced preconditioning required the 67-kDa laminin receptor (67LR), to which EGCG binds with high affinity. 67LR also mediated the generation of reactive oxygen species (ROS) via activation
of NADPH oxidase. An exogenous ROS-generating system bypassed 67LR to induce preconditioning, suggesting that sublethal levels of ROS are indeed an important mediator in GTPP-induced preconditioning. This role for ROS was further supported by the fact that antioxidants blocked GTPP-induced preconditioning. Additionally, ROS induced an activation and translocation of protein kinase C (PKC), particularly selleck screening library PKC epsilon from the cytosol to the membrane/mitochondria, which was also blocked by antioxidants. The crucial role of PKC in GTPP-induced preconditioning was supported by use of its specific inhibitors. Preconditioning was increased by conditional overexpression of PKC epsilon and decreased by its knock-out with siRNA. Collectively, these results suggest that GTPP stimulates 67LR and thereby induces NADPH oxidase-dependent generation
of ROS, which in turn induces activation of PKC, particularly prosurvival isoenzyme PKC epsilon, resulting in preconditioning against cell death induced by OGD/R.”
“The essential process of dosage compensation equalizes X-chromosome gene expression between Caenorhabditis elegans XO males Selleck LY2090314 and XX hermaphrodites through a dosage compensation complex (DCC) that is homologous to condensin. The DCC
binds to both X chromosomes of hermaphrodites to repress transcription by half. Here, we show that posttranslational modification by the SUMO (small ubiquitin-like modifier) conjugation pathway is essential for sex-specific assembly and function of MK-2206 cell line the DCC on X. Depletion of SUMO in vivo severely disrupts binding of particular DCC subunits and causes changes in X-linked gene expression similar to those caused by deleting genes encoding DCC subunits. Three DCC subunits are SUMOylated, and SUMO depletion preferentially reduces their binding to X, suggesting that SUMOylation of DCC subunits is essential for robust association with X. DCC SUMOylation is triggered by the signal that initiates DCC assembly onto X. The initial step of assembly-binding of X-targeting factors to recruitment sites on X-is independent of SUMOylation, but robust binding of the complete complex requires SUMOylation. SUMOylated DCC subunits are enriched at recruitment sites, and SUMOylation likely enhances interactions between X-targeting factors and condensin subunits that facilitate DCC binding beyond the low level achieved without SUMOylation.
(C) 2013 AIP Publishing LLC.”
“C4b-binding protein (C4BP) is known as one of the circulating complement regulators that prevents excessive activation of the host-defense complement system. We have reported previously S63845 molecular weight that C4BP is expressed abundantly in the rodent epididymis, one
of the male reproductive organs connecting the testis and vas deferens, where immature spermatozoa acquire their motility and fertilizing ability during their transit through the duct. Epididymal C4BP (EpC4BP) is synthesized androgen-dependently by the epithelial cells, secreted into the lumen, and bound to the outer membrane of the passing spermatozoa. In this study, we found that EpC4BP is secreted as a large oligomer, similar to the serum C4BP, but is digested during the epididymal transit and is almost lost from both the luminal fluid and the sperm surface in the vas deferens. Selleckchem ATM/ATR inhibitor Such a processing pattern
is not known in serum C4BP, suggesting that EpC4BP and serum C4BP might have different functional mechanisms, and that there is a novel function of EpC4BP in reproduction. In addition, the disappearance of EpC4BP from the sperm surface prior to ejaculation suggests that EpC4BP works only in the epididymis and would not work in the female reproductive tract to protect spermatozoa from complement attack. Next, we generated C4BP-deficient (C4BP-/-) mice to examine the possible role of EpC4BP in reproduction. However, the C4BP-/- mice were fertile and no significant differences were observed between the C4BP-/- and wild-type mouse spermatozoa in terms SRT2104 of morphology, motility, and rate of the spontaneous acrosome reaction. These results suggest that EpC4BP is involved in male reproduction, but not essential for sperm maturation. (C) 2014 Elsevier GmbH.
All rights reserved.”
“The inv(16)(p13q22)/t(16;16)(p13;q22) in acute myeloid leukemia results in multiple CBFB-MYH11 fusion transcripts, with type A being most frequent. The biologic and prognostic implications of different fusions are unclear. We analyzed CBFB-MYH11 fusion types in 208 inv(16)/t(16; 16) patients with de novo disease, and compared clinical and cytogenetic features and the KIT mutation status between type A (n = 182; 87%) and non-type A (n = 26; 13%) patients. At diagnosis, non-type A patients had lower white blood counts (P = .007), and more often trisomies of chromosomes 8 (P = .01) and 21 (P < .001) and less often trisomy 22 (P = .02). No patient with non-type A fusion carried a KIT mutation, whereas 27% of type A patients did (P = .002). Among the latter, KIT mutations conferred adverse prognosis; clinical outcomes of non-type A and type A patients with wild-type KIT were similar. We also derived a fusion-type-associated global gene-expression profile.