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Magnetic coupling between water and creatine protons in human brain and skeletal muscle, as measured using inversion transfer (1)H-MRS.

Using the inversion transfer technique, the possible magnetic coupling between water protons and the protons of low-molecular weight metabolites was investigated in human brain and skeletal muscle at 1.5 T. The localized (1)H-MR spectra were recorded at different times after selective inversion of the water resonance. Water inversion led to a significant transient reduction in the signal intensity of the methyl protons of creatine/phosphocreatine, in both tissues. This is indicative of magnetic coupling between the protons of water and those of creatine/phosphocreatine. Neither the choline and N-acetylaspartate protons in brain nor the protons of the trimethylammonium pool in skeletal muscle showed a significant magnetic coupling to mobile water.

Brain Chemistry↗

Down-regulation of p21 (CDKN1A/CIP1) is inversely associated with microsatellite instability and CpG island methylator phenotype (CIMP) in colorectal cancer.

p21 (CDKN1A/CIP1/WAF1), one of the cyclin-dependent kinase inhibitors, plays a key role in regulating the cell cycle and is transcriptionally regulated by p53. Down-regulation of p21 is caused by TP53 mutations in colorectal cancer. CpG island methylator phenotype (CIMP) appears to be a distinct subtype of colorectal cancer with concordant methylation of multiple gene promoters and is associated with a high degree of microsatellite instability (MSI-H) and BRAF mutations. However, no study to date has evaluated the relationship between p21 expression and CIMP in colorectal cancer. The purpose of this study was to examine the inter-relationships between p21, p53, CIMP, MSI and KRAS/BRAF status in colorectal cancer. We utilized 737 relatively unbiased samples of colorectal cancers from two large prospective cohort studies. Using quantitative real-time PCR (MethyLight), we measured DNA methylation in five CIMP-specific gene promoters [CACNA1G, CDKN2A (p16/INK4A), CRABP1, MLH1 and NEUROG1]. CIMP-high (>or=4/5 methylated promoters) was diagnosed in 118 (16%) of the 737 tumours. We also assessed expression of p21 and p53 by immunohistochemistry. Among the 737 tumours, 371 (50%) showed p21 loss. Both p21 loss and p53 positivity were inversely associated with CIMP-high, MSI-H and BRAF mutations. The associations of p21 with these molecular features were still present after tumours were stratified by p53 status. In contrast, the associations of p53 positivity with the molecular features were no longer present after tumours were stratified by p21 status. When CIMP-high and non-CIMP-high tumours were stratified by MSI or KRAS/BRAF status, CIMP-high and MSI-H (but not BRAF mutations) were still inversely associated with p21 loss. In conclusion, down-regulation of p21 is inversely correlated with CIMP-high and MSI-H in colorectal cancer, independent of TP53 and BRAF status.

Colorectal Neoplasms↗

Inverse modelling for estimating sorption and degradation parameters for pesticides.

The leaching model PESTRAS was used to estimate sorption and degradation values for bentazone from three lysimeter datasets using the inverse modelling package PEST. Investigations were undertaken to assess the influence on calibration results of (1) values attributed to uncertain parameters not included in the calibration, and (2) starting values supplied to the inverse modelling package. Automatic calibrations with different realistic values for the Freundlich exponent n(f) yielded different combinations of K(om) and DT50. Similarly, the supply of different starting values for K(om) and DT50 revealed that different combinations of these two parameters equally calibrated PESTRAS for two of the three lysimeters. Examination of the error surface, ie the forward running of the model for different combinations of K(om) and DT50 values, and the calculation of the goodness-of-fit to the experimental data, was found useful for identifying those instances where non-uniqueness in the calibration is likely to occur. Although the derivation of sorption and degradation values through inverse modelling is expected to offer significant benefits over laboratory determinations, care should be exercised when examining values derived through this approach. Research is needed to identify data requirements for robust estimation of sorption and degradation parameters through calibration of pesticide fate models against leaching data.

Adsorption↗

Membrane protein subunit fractionation by means of inverse pore gradient elution polyacrylamide gel electrophoresis.

We report here the preparative scale isolation of the four subunits of the nicotinic acetylcholine receptor (nAChR) applying short inverse pore gradient SDS gels on an elution-PAGE apparatus. The nAChR subunits are of similar molecular weights (alpha, 50.2 kDa; beta, 53.7 kDa; gamma, 56.3 kDa; delta, 57.6 kDa) and isoelectric point (approx 5.5) and share the typical properties of amphiphatic membrane proteins that are difficult to separate by chromatographic procedures. Preparative PAGE, which has proved to be the method of choice for nAChR-subunit fractionation, however, is time-consuming and achieves only moderate resolutions yielding dilute fractions. We present here the fractionation of a membrane preparation of Torpedo electric organ (2 mg of total protein) on short gels (2 cm) with linear or concave inverse pore gradients. All of the four subunits are isolated in homogeneous fractions of approx 70 micrograms/ml within only 4 h. Compared to the standard method, this means a 50% reduction in separation times with threefold higher concentrated protein fractions. We also give the theoretical explanation and experimental validation of the improved features resulting from short inverse-gradient polyacrylamide gels.

Animals↗

Evaluation of microcapsule permeability via inverse size exclusion chromatography.

Inverse aqueous size exclusion chromatography (SEC) was adopted to measure the permeability of microcapsules (hollow hydrogel spheres with diameter < 1 mm) using dextran molecular weight standards. Alginate/poly(L-lysine)/alginate microcapsules were chosen as a column substrate. Data from column SEC experiments were verified by kinetic studies of solute size exclusion. The permeability of tested microcapsules was modified by the reaction time with 0.05wt.% poly(L-lysine) (PLL). The exclusion limit of the microcapsules prepared at 5-min reaction time was found to be 100,000, while the microcapsules that were allowed to react with PLL for 20 min became less permeable and their exclusion limit was approximately 50,000. Based on relationships between solute size and molecular weight, the exclusion limits determined with dextrans were converted to the size and approximate molecular weight of protein presumably excluded by the capsular membrane at "ideal" conditions. The results from both column SEC and batch experiments suggest that the standard alginate/PLL/alginate capsules are permeable to immunoglobulins of IgG class. Unlike other techniques which utilize only a limited number of solutes, inverse SEC enables one to examine the capsule permeability to a homologous series of molecular weight standards. Inverse SEC also provides an opportunity to evaluate the properties of a large series of capsules directly by comparing their calibration curves. In addition, undesirable enthalpic effects in permeability studies with globular proteins as test solutes can be minimized or eliminated by using the inert molecular weight standards such as polysaccharides.

Alginates↗

Patterning of the embryonic avian midbrain after experimental inversions: a polarizing activity from the isthmus.

Rostrocaudal inversions of the prospective midbrain (accompanied in some cases by other adjacent neuroepithelial zones) were performed in the neural tube of 2-day-old chick embryos in the form of autografts or quail/chick chimeras, involving both alar and basal plates. These experiments aimed to analyze causally the histogenetic rostrocaudal patterning of the midbrain, formed normally by diverse neuronal complexes. The experimental embryos were processed for study of the resulting cytoarchitecture or for study of the Engrailed-2 gene expression pattern. The exclusive inversion of the prospective midbrain produced a normal midbrain. Joint inversion of prospective midbrain plus the prospective isthmocerebellar tissue gave rise to an ectopic isthmocerebellar complex plus a symmetric double-caudal midbrain; additionally, the prospective caudal diencephalon was induced to form a polarized isthmomesencephalic phenotype in substitution of the pretectum. All these regulation processes affected both the alar and basal plates. The changes in cytoarchitectural fate were preceded by correlated changes in the gradiental expression of the gene Engrailed-2. These results suggest that the polarized structural pattern of the midbrain is regulated by graded positional information derived from the caudally adjacent isthmocerebellar domain, which is probably a source of morphogens.

Animals↗

Real-time inverse kinematics techniques for anthropomorphic limbs.

In this paper we develop a set of inverse kinematics algorithms suitable for an anthropomorphic arm or leg. We use a combination of analytical and numerical methods to solve generalized inverse kinematics problems including position, orientation, and aiming constraints. Our combination of analytical and numerical methods results in faster and more reliable algorithms than conventional inverse Jacobian and optimization-based techniques. Additionally, unlike conventional numerical algorithms, our methods allow the user to interactively explore all possible solutions using an intuitive set of parameters that define the redundancy of the system.

Algorithms↗

Protein kinase C alpha expression is inversely related to ER status in endometrial carcinoma: possible role in AP-1-mediated proliferation of ER-negative endometrial cancer.

OBJECTIVE: Tamoxifen is the most widely used antiestrogen to treat all stages of estrogen-receptor (ER)-positive breast cancers. However, tamoxifen acts as a partial estrogen in the uterus and is known to increase the risk of endometrial cancer by two- to threefold. Recent evidence indicates that there is a connection between tamoxifen resistance and activation of the activator protein-1 (AP-1) pathway. We have previously reported a possible role for overexpression of protein kinase C alpha (PKCalpha), an upstream activator of the AP-1 pathway, in hormone-independent breast cancer and antiestrogen-stimulated endometrial tumors. We hypothesize that alterations of the PKC isozyme profile of endometrial carcinomas are similar to that of hormone-independent breast cancer and determine whether specific PKC isozyme alterations correlated with known clinicopathological features of endometrial cancer. METHODS: The PKC isozyme profile of endometrial carcinomas from 42 patients who were not previously exposed to antiestrogens was examined by Western blot. The relationship between PKC isozyme expression and key prognostic factors for endometrial carcinoma including hormone receptor status, tumor grade, stage, size, and depth of myometrial invasion was examined using the Spearman's rho correlation coefficient. RESULTS: As previously found in breast cancers, PKCalpha and estrogen receptor alpha (ERalpha) expression are inversely related (r(s) = -0.35, P = 0.046). We report significant inverse correlations among ER/progesterone receptor (PR) expression and tumor grade (r(s) = -0.49, P = 0.001 and r(s) = -0.44, P = 0.004, respectively), ER, and depth of myometrial invasion (r(s) = -0.40, P = 0.009). There were no other significant correlations between PKC isozyme expression and other key prognostic factors examined. CONCLUSION: This study indicates that, similar to what was previously observed in breast cancer, PKCalpha and ER expression is inversely related in endometrial cancer. PKCalpha expression may be a useful prognostic indicator in endometrial cancers. A model is offered which describes the putative role of PKCalpha overexpression in activation of the AP-1 pathway and increased proliferation of ER negative endometrial cancers.

Cell Division↗

Children's understanding of the relation between addition and subtraction: inversion, identity, and decomposition.

In order to understand addition and subtraction fully, children have to know about the relation between these two operations. We looked at this knowledge in two studies. In one we asked whether 5- and 6-year-old children understand that addition and subtraction cancel each other out and whether this understanding is based on the identity of the addend and subtrahend or on their quantity. We showed that children at this age use the inversion principle even when the addend and subtrahend are the same in quantity but involve different material. In our second study we showed that 6- to 8-year-old children also use the inversion in combination with decomposition to solve a + b - (b + 1) problems. In both studies, factor analyses suggested that the children were using different strategies in the control problems, which require computation, than in the inversion problems, which do not. We conclude that young children understand the relations between addition and subtraction and that this understanding may not be based on their computational skills.

Age Factors↗

Freeze fracture electron microscopy of lyotropic lipid systems: quantitative analysis of the inverse micellar cubic phase of space group Fd3m (Q227).

An inverse micellar cubic phase of cubic aspect 15 formed by dioleoylglycerol/dioleoylphosphatidylcholine mixtures has been studied by freeze fracture electron microscopy. The structure was well preserved after freezing samples which had been hydrated either in pure water or in 30 vol% aqueous glycerol solutions. Electron microscopy images of high quality and resolution have been obtained. Four types of fracture planes, perpendicular to the [111], [110], [311] and [100] crystallographic axes, were identified by optical diffraction of the images from selected areas of the replicas. This is the largest number of different fracture planes yet observed in any lipid mesophase by electron microscopy. These planes are also perpendicular to the directions of the lowest order, and most intense reflections in the X-ray patterns from this cubic phase. The images were filtered using correlation averaging techniques, and they revealed the presence of mirror planes, which establishes that the space group is Fd3m (Q227) rather than Fd3. The interpretation of the images was aided by the novel use of standard deviation (s.d.) information obtained from the averaging procedures. The results are easily interpreted with the structure model deduced from X-ray diffraction and consisting of a complex packing of two different sizes of quasi-spherical inverse micelles located at positions (a) and (d) of the Fd3m unit cell. The results also show clearly that the fracture pathways always coincide with the regions of high CH3 concentration, located between the crystallographic planes containing the larger inverse micelles located at positions (a).

Diglycerides↗

Application of multiple inversion recovery for suppression of macromolecule resonances in short echo time (1)H NMR spectroscopy of human brain.

Macromolecules contribute broad "background" resonances to the (1)H NMR brain spectra at short echo times. The application of long echo times is the most widely used method for removing these resonances. Here, it is demonstrated that these background resonances may be suppressed at short echo times using multiple inversion recovery (MIR). In the technique presented, the MIR sequence consists of four adiabatic inversion pulses, applied preparatory to a 20-ms echo time stimulated echo localization sequence. The inversion times (359, 157, 69, and 20 ms) were selected to preferentially suppress macromolecules with longitudinal relaxation times between 38 and 300 ms. While the resulting spectra have lower overall signal-to-noise, baseline contributions from macromolecules are greatly reduced. Unlike the typical long TE acquisitions, the short TE MIR acquisition preserves the myo-inositol resonance.

Adult↗

Hyperfine Structure of Rotation-Inversion Levels in the Excited nu2 State of Ammonia

Hyperfine structures of the rotation-inversion transitions with J = 3 <-- 2, s <-- a, and K = 0, 1, 2, and with J = 0 <-- 1, a <-- s, and K = 0 in the excited nu2 vibrational state have been resolved and measured by sub-Doppler saturation spectroscopy using the Cologne terahertz spectrometer with an accuracy of about 1 kHz. The line frequencies of the hyperfine structures of the rotation inversion transitions (at 466, 769, 742, and 763 GHz) have been simultaneously analyzed with the previously published J = 2 <-- 1, s <-- a, K = 1, nu2 transition in terms of effective nuclear quadrupole and spin-rotation parameters. The corresponding pure rotation-inversion frequencies, deperturbed from the hyperfine effects, have also been derived. Copyright 1998 Academic Press.

Journal Article↗

High Resolution FTIR Study on NH(2)Cl Molecule: Inversion and Anharmonicity.

The high-resolution FTIR absorption spectra of the NH(2)Cl molecule have been measured in the region 500-3600 cm(-1). The rotational structures of all the fundamental bands and a number of overtone and combination bands have been analyzed. Every rotational line of the observed bands except the NH(2) twisting and stretching fundamental bands splits into two components due to the amino inversion motion. The vibrational anharmonicity and the direction of the transition moments have been studied with the help of B3LYP/6-31++G(**) calculations. The amount of inversion splitting depends on the molecular rotation, and the J,K-dependence of the inversion splitting has been determined. Copyright 2001 Academic Press.

Journal Article↗

Visualization of subthalamic nuclei with cortex attenuated inversion recovery MR imaging.

There is a significant amount of interest in studying the thalamus because of its central location in the brain and its role as a gatekeeper to higher centers of cognition. Imaging and measuring of the individual subnuclei of the thalamus has proven extremely difficult in MR because of the contrast-to-noise (CNR) of the MR sequences used. This report describes a novel MR pulse sequence known as cortex attenuated inversion recovery (CAIR), which increases the CNR in images and allows the individual subnuclei of the thalamus to be visualized by selectively nulling the gray matter in the brain using an inversion recovery sequence with an inversion time of 700 ms at 1.5 T.

Adult↗

Inversion and contrast polarity reversal affect both encoding and recognition processes of unfamiliar faces: a repetition study using ERPs.

Using ERPs in a face recognition task, we investigated whether inversion and contrast reversal, which seem to disrupt different aspects of face configuration, differentially affected encoding and memory for faces. Upright, inverted, and negative (contrast-reversed) unknown faces were either immediately repeated (0-lag) or repeated after 1 intervening face (1-lag). The encoding condition (new) consisted of the first presentation of items correctly recognized in the two repeated conditions. 0-lag faces were recognized better and faster than 1-lag faces. Inverted and negative pictures elicited longer reaction times, lower hit rates, and higher false alarm rates than upright faces. ERP analyses revealed that negative and inverted faces affected both early (encoding) and late (recognition) stages of face processing. Early components (N170, VPP) were delayed and enhanced by both inversion and contrast reversal which also affected P1 and P2 components. Amplitudes were higher for inverted faces at frontal and parietal sites from 350 to 600 ms. Priming effects were seen at encoding stages, revealed by shorter latencies and smaller amplitudes of N170 for repeated stimuli, which did not differ depending on face type. Repeated faces yielded more positive amplitudes than new faces from 250 to 450 ms frontally and from 400 to 600 ms parietally. However, ERP differences revealed that the magnitude of this repetition effect was smaller for negative and inverted than upright faces at 0-lag but not at 1-lag condition. Thus, face encoding and recognition processes were affected by inversion and contrast-reversal differently.

Brain↗

Attenuation of scopolamine-induced impairment of spontaneous alteration behaviour by antagonist but not inverse agonist and agonist beta-carbolines.

Mice were tested in a simple automated Y-maze. Total number of arm entries and alternation behaviour were measured. The latter is thought to reflect working memory capacity at a rudimentary level. During an 8 min session, vehicle-treated mice performed 32.4 +/- 7.4 arm entries, 51.0 +/- 12.4% of which were organized in alternations (triplets). The two variables showed a negative correlation. Scopolamine (1.0 mg/kg) significantly enhanced activity, reduced alternation behaviour and diminished the correlation between the two variables. The effects of benzodiazepine receptor inverse agonist, antagonist and agonist beta-carbolines on this spontaneous behaviour and on the effects of scopolamine were examined. The effects of inverse agonists and agonists on locomotor activity were complex in interaction with both vehicle and scopolamine. The scopolamine-induced reduction of alternation behaviour was significantly reversed by the antagonist ZK 93426 but not by inverse agonists; furthermore, partial agonists and agonists showed no effects. It is hypothesized that the interaction of antagonist beta-carbolines with scopolamine is based on a direct GABA-ergic control of cholinergic neurotransmission, and suggests an ability of antagonist beta-carbolines to antagonize amnestic properties of scopolamine.

Animals↗

Characterization of a large inversion in the spinach chloroplast genome relative to Marchantia: a possible transposon-mediated origin.

A 7,022 bp BamHI-EcoRI fragment, located in the inverted repeat of spinach chloroplast, has been sequenced. It contains a 2131 codon open reading frame (ORF) homologous to both tobacco ORFs 581 and 1708, and to Marchantia ORF 2136. Relative to the Marchantia chloroplast genome, spinach ORF 2131 is located at the end of a large inversion; the other end point is close to trnL, the position of which is the same in Marchantia, tobacco and spinach. In Marchantia, two 8 bp direct repeats flanking two 10 bp indirect repeats are present near the end points of the inversion. These repeats may result from a transposon-mediated insertion which would have facilitated the subsequent inversion. From a comparison of the gene organization of the spinach, tobacco, and Marchantia genomes in this region, we propose a step-wise process to explain the expansion of the inverted repeat from a Marchantia-like genome to the spinach/tobacco genome.

Base Sequence↗

Ultrastructural studies in epidermolysis bullosa hereditaria. III. Recessive dystrophic types with dermolytic blistering (Hallopeau-Siemens types and inverse type).

Ultrastructural examination was performed in 42 biopsy specimens from 22 patients with the Hallopeau-Siemens types or with the inverse type of epidermolysis bullosa dystrophica recessiva. The patient group consists of 8 cases of the localized Hallopeua-Siemens type, 9 of the generalized Hallopeau-Siemens type and 5 of the inverse type. The origins of the biopsy specimens are involved, intact and experimentally frictioned skin from blister-predilected sites, as well as clinically normal skin from nonpredilection sites. It is confirmed that all the blisters initiate below the basal lamina. Anchoring fibrils are moderately to markedly decreased in most cases, while they are normal in 3 other cases. It is thought that secondary degradation of anchoring fibrils and/or collagen fibrils plays an important role in blistering mechanism in the Hallopeau-Siemens and inverse types of recessive dystrophic epidermolysis bullosa, whereas a primary aplasia of anchoring fibrils as causative defect has been out ruled.

Collagen↗