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Rearrangement of the bacterial chromosome: forbidden inversions.

The order of genes in the chromosome of enteric bacteria has been evolutionarily conserved despite the existence of mechanisms for rearrangement. Homologous chromosomal sequences in the same orientation recombine to form deletions or duplications. When homologous sequences in inverse orientation recombine, one expects to form an inversion of the intervening chromosomal segment. This expectation was tested by placing pairs of homologous sequences in inverse order at various points in the chromosome. Sequences at many pairs of sites (permissive) do recombine to generate the expected inversion, while the same sequences placed at other pairs of sites (nonpermissive) do not form an inversion. For the one nonpermissive interval tested, the missing inversion type can be constructed by an alternative transductional method; strains with this inversion are viable. Thus mechanistic limitations must prevent sequences at particular sites from undergoing the recombination event required to form an inversion.

Chromosome Inversion↗

Genetic differentiation and inversion clines in Indian natural populations of Drosophila melanogaster.

To study the genetic differentiation and inversion clines in Indian natural populations of Drosophila melanogaster, 14 natural populations (6 from the north and 8 from the south) were screened for chromosome inversions. The chromosomal analysis revealed the presence of 23 paracentric inversions, which include 4 common cosmopolitan, 4 rare cosmopolitan, 2 recurrent endemic, and 13 unique endemic (new inversions detected for the first time) inversions. The difference in karyotype frequencies between populations from the north and south were highly significant and the level of inversion heterozygosity was higher in populations from the south. Statistically significant negative correlations were found between each of the four common cosmopolitan inversions and latitude. These findings are in accord with results from other worldwide geographic regions and show that Indian populations of D. melanogaster have undergone considerable genetic differentiation at the level of inversion polymorphism.

Animals↗

Uterine inversion: a life-threatening obstetric emergency.

BACKGROUND: Acute puerperal uterine inversion is a rare but potentially life-threatening complication in which the uterine fundus collapses within the endometrial cavity. Although the cause of uterine inversion is unclear, several predisposing factors have been described. Maternal mortality is extremely high unless the condition is recognized and corrected. METHODS: MEDLINE was searched from 1966 to the present using the key phrase "uterine inversion." Nonpuerperal uterine inversion case reports were excluded from review except when providing information on classification and diagnostic techniques. A summarized case involving uterine inversion and a review of the classification, etiology, diagnosis, and management are reported. RESULTS AND CONCLUSIONS: Although uncommon, if left unrecognized, uterine inversion will result in severe hemorrhage and shock, leading to maternal death. Manual manipulation should be attempted immediately to reverse the inversion. Tocolytics, such as magnesium sulfate and terbutaline, or halogenated anesthetics may be administered to relax the uterus to aid in reversal. Intravenous nitroglycerin provides an alternative to the tocolytics and offers several pharmacodynamic advantages. Treatment with hydrostatic pressure may be attempted while waiting for medications to be administered or for general anesthesia to be induced. In the most resistant of inversions, surgical correction might be required.

Adult↗

[The role of inversions in adaptation and speciation].

Studies concerning the effect of population-specific inversions on mating behavior of Drosophila lummei Hackman showed that competitiveness of males carrying the inversion for mating with females without the inversion significantly decreases, independently from the location of inversions in chromosomes and the origin of studied strains. Crossing of the competing males with the female carrying the population-specific inversion showed that the competitiveness of males with the inversion in their genome increases in a series of crosses but, nevertheless, remains lower than that of males without the inversion. Hence, it can be suggested that population-specific inversions can be involved in prezygotic isolation of specific forms during the species divergence.

Adaptation, Physiological↗

Studies on the in vitro inversion of flurbiprofen.

This paper reports in vitro studies on the metabolic inversion of flurbiprofen (FL), an arylpropionic acid antiinflammatory agent (2-APA). The inversion was studied with both rac-FL and R-FL, by incubation with rat hepatic microsomes, in the presence of either CoASH and ATP or NADPH. The two isomers of the drug were separated as their (+)-(R)-1-phenylethylamides by direct phase high-performance liquid chromatography on a silica gel column with an achiral mobile phase. The inversion was more pronounced in the presence of CoASH and ATP for both the racemate and the R-isomer, which supports the key role of CoA thioesters in the metabolic inversion of profens. The inversion observed in the presence of NADPH suggests that, when the incubation is run with hepatic microsomes, a CYP450-mediated pathway is also active. In order to get more insight into the CYP450-mediated inversion pathway, we studied the effect of irradiating microsomes with a low dose of He-Ne laser radiation (0.2 J). Such irradiation caused a significant increase in inversion at all times studied and normalized the anomalous value of inversion observed at 15 min in this pathway.

Animals↗

Preparation of Colloidal Low-Density Polyethylene Latexes by Flow-Induced Phase Inversion Emulsification of Polymer Melt in Water.

The aim of this study is to prepare colloidal polymeric latexes by using the flow-induced phase inversion emulsification method given by G. Akay [Chem. Eng. Sci. 53, 203 (1998)] of polymer melts followed by the solidification of polymer melt droplets. We also investigate the mechanism of emulsification and stabilization in polymeric dispersions which undergo a phase change after emulsification. The history of the emulsification and emulsion structure are monitored by using a process rheometer and off-line scanning electron microscopy with energy-dispersive X-ray analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, and particle size measurements. It is shown that the molecular structure of the surface-active material is the most important parameter in achieving phase inversion emulsificationin polymer melts. Molecular surfactants could not be used to provide surface activity in polymeric melts. Several experimental polymeric surfactants are used and their ability to form a [water-in-polymer melt] emulsion is tested. The successful polymeric surfactants are known as hydrophobically modified water-soluble polymers. It is postulated that the surface-active materials should conform at the water/polymer melt interface and not be removed from the interface by surface deformations. The ability of hydrophobically modified water-soluble polymers to remain at the interface is reduced if the hydrophobic moeties which anchor into the polymer melt have chain length approaching 18 carbons or more. After the first phase inversion and subsequent dilution of the [polymer melt-in-water], if mixing is carried out while cooling, a second phase inversion takes place from [polymer melt-in-water] to [water-in-solid polymer] despite high water content of the polymer/water system. If the water content is high (25-40% investigated) the second phase inversion yields a powdered material with encapsulated water. A third phase inversion occurs if the powdered microcapsules from the second phase inversion is heated while mixing to yield a [(water-in-polymer)-in-water] multiple emulsion which can be inverted back to [polymer melt-in-water] emulsion by increasing the temperature and subjecting the emulsion to high deformation rate flows. However, if this last phase inversion is not allowed to proceed to completion, and the [(water-in-polymer)-in-water] multiple emulsion is cooled, microporous polymeric particles are obtained. Copyright 2001 Academic Press.

Journal Article↗

A local algorithm for DNA sequence alignment with inversions.

A dynamic programming algorithm to find all optimal alignments of DNA subsequences is described. The alignments use not only substitutions, insertions and deletions of nucleotides but also inversions (reversed complements) of substrings of the sequences. The inversion alignments themselves contain substitutions, insertions and deletions of nucleotides. We study the problem of alignment with non-intersecting inversions. To provide a computationally efficient algorithm we restrict candidate inversions to the K highest scoring inversions. An algorithm to find the J best non-intersecting alignments with inversions is also described. The new algorithm is applied to the regions of mitochondrial DNA of Drosophila yakuba and mouse coding for URF6 and cytochrome b and the inversion of the URF6 gene is found. The open problem of intersecting inversions is discussed.

Algorithms↗

An optimized multislice acquisition sequence for the inversion-recovery MR imaging.

An optimized multislice data acquisition scheme for inversion-recovery MR imaging is proposed and experimental results are presented. In this new scheme, instead of forming a set of multislice inversion-recovery sequences in series for a given phase encoding step, 180 degrees inversion pulses corresponding to different slices are interwoven with the spin echo data acquisition sequence in an optimal way depending on the desired inversion-recovery time. For example, between the 180 degrees inversion RF pulse and the spin-echo imaging sequence, a number of imaging and inversion sequences are inserted with different slice combinations, i.e., long inversion-recovery time is effectively utilized for the other slice pre-inversion and data acquisition. With the optimized sequence, imaging time has been reduced by as much as a factor of four compared with the existing methods.

Brain↗

Early T wave inversion after thrombolytic therapy predicts better coronary perfusion: clinical and angiographic study.

OBJECTIVES: This study was undertaken to test the hypothesis that early inversion of T waves after thrombolytic therapy for acute myocardial infarction predicts patency of the infarct-related artery with high Thrombolysis in Myocardial Infarction (TIMI) perfusion flow and better in-hospital outcome. BACKGROUND: Although numerous studies have demonstrated a strong association between early resolution of ST segment elevation after acute myocardial infarction and successful thrombolysis, little is known about early changes in T waves after thrombolytic therapy. METHODS: Ninety-four consecutive patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA) were studied with admission and predischarge radionuclide ventriculography and with coronary angiography within 72 h of admission. Patient stratification was based on the presence or absence of early (within 24 h) T wave inversion. RESULTS: Early T wave inversion was associated with a higher patency rate of the infarct-related artery (90% vs. 65%, p < 0.02) and less severe residual stenosis ([mean +/- SD] 73 +/- 27 vs. 83 +/- 22, p = 0.06), and when only TIMI perfusion grade 3 was considered, the difference was even greater (77% vs. 41%, p < 0.001). Patients with early inversion of T waves had a lower peak creatine kinase value ([mean +/- SD] 678 +/- 480 vs. 1,076 +/- 620, p < 0.01), and although a similar percent of patients with and without early T wave inversion had a normal ejection fraction (> or = 55%) on admission, a higher percent of patients with early inversion had a normal ejection fraction at hospital discharge (71% vs. 44%, p < 0.03). Early T wave inversion anticipated a more benign in-hospital clinical course with a lower incidence of adverse cardiac events (10% vs. 33%, p < 0.02). CONCLUSIONS: Early inversion of T waves in patients with acute myocardial infarction treated with thrombolytic therapy suggests patency of the infarct-related artery, better perfusion grade and left ventricular function and a more benign in-hospital course.

Coronary Angiography↗

A feasibility study of automated inverse treatment planning for cancer of the prostate.

PURPOSE: The development of automated "inverse planning," utilizing intensity-modulated radiation therapy (IMRT) raises the question of whether this new technique can provide a practical and efficient means of dose escalation in conformal treatment of cancer of the prostate. The purpose of this feasibility study was to determine a single set of inverse-planning parameters that can be used for a variety of different prostate patient geometries to automatically generate escalated dose (> or = 81 Gy) IMRT plans that satisfy normal tissue constraints for rectal and bladder walls. METHODS: We studied a subset of the 46 patients who were previously treated at Memorial Sloan Kettering Cancer Center (MSKCC) to a total dose of 81 Gy using a 3D conformal approach. Six patients were selected for our study and replanned using an analytical inverse-planning algorithm (referred to as OPT3D) applied to 8 intensity modulated, co-axial radiation beams. A set of more than a dozen inverse planning parameters were adjusted by trial and error until the resulting dose distributions satisfied the critical organ dose-volume constraints imposed by our study rules (D30 < or = 75.6 Gy and D10 < or = 80 Gy for the rectal wall; D15 < or = 80 Gy for the bladder wall) for the sample of patients selected. The OPT3D-generated plans were compared to hand-generated BEV plans using cumulative DVH analysis. RESULTS: A single set of inverse-planning parameters was found that was able to automatically generate IMRT plans meeting all critical organ dose-volume constraints for all but one of the patients in our study. [The exception failed to meet bladder dose constraints for both IMRT and BEV methods, due to extensive overlap between the planning target volume (PTV) and bladder contours]. Based upon analysis of the cumulative dose-volume histogram (DVH) for the prostate PTV, the D95 (DX is defined such that x% of the volume receives a dose > or = DX), averaged over all patients, was approximately 81 Gy. The average D90 and mean dose values were 85 Gy and 93 Gy, respectively. Although a similar D95 was achieved using the BEV-generated plans, the D90 and mean dose values were substantially higher for the inverse planning (OPT3D) method. CONCLUSION: This limited "paper study" shows IMRT with inverse planning to be a promising technique for the treatment of prostate cancer to high doses. We determined a small set of inverse-planning parameter values that was able to automatically design intensity-modulated radiotherapy (IMRT) plans for a subset of 6 patients previously treated at MSKCC to 81 Gy using BEV planning techniques. With one minor exception, the resulting plans succeeded in meeting predetermined dose-volume constraints while at the same time allowing an increase in the mean dose and D90 to the prostate PTV. These 8 field plans also resulted in reduced dosage to the femoral heads. This automated technique is efficient in terms of planning effort and, with proper software for computer-controlled MLC, may be appropriate for clinical use. The clinical feasibility of this approach for a larger group of patients is currently under study.

Feasibility Studies↗

Gated planar technetium 99m-labeled sestamibi myocardial perfusion image inversion for quantitative scintigraphic assessment of left ventricular function.

BACKGROUND: Quantitative assessment of left ventricular systolic performance in conjunction with myocardial perfusion scintigraphy would significantly expand the clinical information obtained from these studies. METHODS AND RESULTS: Left ventricular function was evaluated in 264 patients in whom planar 99mTc-labeled sestamibi myocardial perfusion images were obtained in the best septal left anterior oblique projection. Digital inversion of these perfusion images allows semiautomated evaluation of the left ventricular cavity, with the commonly available edge-detection software designed for equilibrium blood pool imaging. In this study, ejection fractions derived from this technique were compared with those obtained from a myocardial perfusion phantom, first-pass radionuclide angiography, and contrast ventriculography. In vitro validation demonstrated that the myocardial perfusion image inversion ejection fractions correlated linearly with those obtained from a double-chamber phantom (r = 0.999). In vivo, there was good linear correlation between image inversion and first-pass (r = 0.88; image inversion = 0.98 first-pass +0.11), with 95% agreement on the presence or absence of significant left ventricular systolic dysfunction. There was also very good correlation between image inversion and contrast ventriculographic ejection fractions (n = 35; r = 0.85; image inversion = 0.8 contrast +0.05). Intraobserver and interobserver variability of the image inversion ejection fractions was very small (mean difference of 0.4 +/- 0.8 and 2.8 +/- 4.7 units, respectively). CONCLUSION: Gated 99mTc-labeled sestamibi myocardial perfusion image inversion allows evaluation of the dynamics of the left ventricular chamber changes during the cardiac cycle, providing a method for evaluation of systolic function during myocardial perfusion imaging, with highly reproducible results that correlate well with established techniques.

Adult↗

Continuity and development in the acquisition of inversion in yes/no questions: dissociating movement and inflection.

This paper examines two- to five-year-old children's knowledge of inversion in English yes/no questions through a new experimental study. It challenges the view that the syntax for inversion develops slowly in child English and tests the hypothesis that grammatical competence for inversion is present from the earliest testable ages of the child's sentence production. The experimental design is based on the premise that a valid test of this hypothesis must dissociate from inversion various language-specific aspects of English grammar, including its inflectional system. An elicited imitation method was used to test parallel, lexically-matched declarative and question structures across several different verb types in a design which dissociated subject-auxiliary inversion from the English-specific realization of the inflectional/auxiliary system. Using this design, the results showed no significant difference in amount or type of children's errors between declarative (non-inverted) and question (inverted) sentences with modals or auxiliary be, but a significant difference for sentences with main verbs (requiring reconstruction of inflection through do-support) and copula be. The results from sentences with auxiliary be and those with modals indicate that knowledge of inversion is present throughout our very young sample and does not develop during this time. We argue that these results indicate that the grammar of inversion is present from the youngest ages tested. Our results also provide evidence of development relevant to the English-specific inflectional system. We conclude with a new developmental hypothesis: development in question formation occurs in integrating language-specific knowledge related to inflection with the principles of Universal Grammar which allow grammatical inversion.

Child Language↗

Kinetic studies of temperature-induced helix hand inversion in Bacillus subtilis macrofibers.

The inversion of Bacillus subtilis macrofibers from right to left handedness induced by a temperature upshift was compared with inversion from left to right handedness induced by a temperature downshift. Following an upshift the new steady-state growth rate was achieved prior to inversion of helix orientation. There was no discernible perturbation of growth rate at the time of inversion. The time required after a temperature shift up or down for fiber rotation in the original sense to cease was dependent on the temperature to which the fibers were transferred and was always shortest when this temperature was highest. The results suggest a basic asymmetry in the two inversion processes. Cessation of rotation in the right-to-left inversion appeared to reflect contributions of the old and new wall materials that depended on their twist values, whereas the left-to-right inversion appeared to require that a specific amount of newly made wall material be inserted into the cell surface. The degree of twist of the newly inserted right-handed material appeared not to influence the timing of inversion.

Bacillus subtilis↗

Analysis of DNA inversions in the shufflon of plasmid R64.

The shufflon, a multiple DNA inversion system in the plasmid R64, consists of four DNA segments flanked and separated by seven 19-bp repeat sequences. Site-specific recombinations mediated by the rci product occur between each inverted repeat sequence, resulting in inversions of the four segments independently or in groups. The seven 19-bp repeat sequences are classified into four types (repeat-a, -b, -c, and -d), according to their 3-bp variable sequences. We individually cloned A, B, and C segments of the R64 shufflon and determined the in vivo inversion frequency of each segment. The inversion frequencies of three segments differed greatly. The inversion frequency declined in the following order: segments A, B, and C. Synthetic 19-mer oligonucleotides corresponding to both strands of repeat-a, -b, -c, and -d sequences were inserted into appropriate sites of pBR322. The rci-mediated DNA inversion occurred between two synthetic inverted repeats, indicating that the 19-bp inverted repeat sequences are the sole elements required in cis for the shufflon system. The inversion frequencies of DNA segments flanked by various sequences indicate that the four types of repeat sequences determine the inversion frequency of the four DNA segments of the R64 shufflon. Deletion of a DNA segment flanked by direct repeat sequences could not be detected.

DNA Nucleotidyltransferases↗

Ankle inversion injuries. The role of the dynamic defense mechanism.

We investigated the role of a muscular defense in the stabilization and protection of the ankle joint against sudden forced inversion. Ten volunteers with mechanically stable ankles were tested in different standing and walking situations using a trap door model and lower extremity electromyography and electrogoniometers. Peroneal electromyographic activity was observed 54 msec after the detection of ankle inversion. This latency was shorter when the ankle was already in inversion and longer with the ankle in eversion. Quadriceps and hamstring muscle electromyographic activity occurred 68 msec after the ankle inversion stimulus. Evidence of active eversion was seen 176 msec after sudden inversion. Active changes in knee and hip joint angles occurred even later. In contrast, the trap door rotated 30 degrees in approximately 80 msec. We conclude that the reflex reaction to sudden inversion is initiated at a peripheral level by the inversion motion followed by a reaction pattern mediated by spinal or cortical motor centers. Both peripheral and central reactions, however, seem too slow to protect the ankle in case of sudden inversion occurring at the time of heel contact.

Adult↗

Inversion in Volvox tertius: the effects of con A.

During the development of Volvox tertius spheroids, a single-celled gonidium enlarges and undergoes multiple incomplete cleavages to give an embryo which is 'inside-out' with respect to the adult organism. A morphogenetic movement, termed 'inversion', turns this hollow ball of cells 'inside-out' through a hole, the phialopore. In V. tertius this phialopore possesses 4 inwardly directed lips. Normal inversion was studied in vitro in slide chambers and involved cell-shape changes accompanied by the production of pseudopodia and the bending backwards of the phialopore lips. 100 micrograms/ml Con A specifically and reversibly blocked inversion. Despite the inhibitory effect on cell division, the blocking of inversion was not due to the blocking of the last cell division some 50-100 min prior to inversion. Neither did the first cell-shape change from pear- to spindle-shape appear blocked. A feature of inhibition by Con A was the enhanced production of pseudopodia by embryos blocked at inversion, and the abnormal production of pseudopodia by embryos blocked at earlier stages. Non-inverting embryos showed internal flagella. We suggest that the Con A block to inversion, which may be reversed by alpha-methyl mannoside, arises from the prevention of backwards-bending of the phialopore lips. Fluorescein-isothiocyanate-Con A bound to embryo and cell coat, ane more strongly to the embryo at pre-inversion. SDS-polyacrylamide gel analysis of proteins isolated from embryos showed 4 glycoprotein bands, but Con A binding to these bands could not be demonstrated.

Cell Division↗

Very slow chiral inversion of clopidogrel in rats: a pharmacokinetic and mechanistic investigation.

Clopidogrel hydrogen sulfate, a thienopyridine derivative, is an ADP receptor antagonist that inhibits platelet aggregation. Clopidogrel is an enantiopure carboxylic ester of S-configuration. The R-enantiomer is devoid of antithrombotic activity and can provoke convulsions at high doses in animals. During preclinical safety evaluation, the possible chiral inversion of clopidogrel has, therefore, been investigated in vivo after repeated oral administration of different dose levels of clopidogrel to male and female rats. Due to rapid metabolism in the liver and low plasma levels of unchanged drug, possible chiral inversion was assessed by monitoring the plasma concentrations of the carboxylic acid metabolites, i.e., the (S)- and (R)-acid, by means of a stereoselective assay. The production of 4 to 8% of (R)-acid was observed. This could be the result of chiral inversion of either clopidogrel or its main metabolite, the (S)-acid. Thus, the possibility of nonenzymatic and enzymatic inversion of clopidogrel and its carboxylic acid metabolite was studied in vitro by chiral HPLC and (1)H NMR. Nonenzymatic chiral inversion of clopidogrel at 37 degrees C in 0.1 M phosphate buffers could be observed but was found to be slow, with estimated half-lives of 7 to 12 days, depending on the pH. The (S)-acid was configurationally fully stable up to 45 days in phosphate buffers. Neither clopidogrel nor its carboxylic acid metabolites were subject to enzymatic chiral inversion in isolated rat hepatocyte suspensions. We conclude that the nonenzymatic inversion of clopidogrel accounts for the 4 to 8% of chiral inversion seen in vivo in the rat.

Algorithms↗

Presystemic and systemic chiral inversion of R-(-)-fenoprofen in the rat.

Fenoprofen (FN), a member of the 2-arylpropionic acid (2-APA) class of nonsteroidal anti-inflammatory drugs is administered clinically as a racemate. In humans, FN has been shown to rapidly undergo substantial in vivo unidirectional chiral inversion with the inactive R-isomer converted to its active antipode. As with any p.o. administered drug, before reaching the systemic circulation. FN may undergo first-pass metabolism, the major organs involved being the gastrointestinal tract and/or the liver. The site(s) of inversion for the 2-APAs have been a subject of debate, with presystemic intestinal metabolism in humans and hepatic systemic metabolism in rats receiving the most attention. The inversion of R-FN was studied in the male Sprague-Dawley rat 1) in vivo after p.o. and i.v. administration of racemic-FN and R-FN, 2) after perfusion of R-FN into isolated liver (single-pass and recirculation) and 3) after a 2-hr incubation with everted intestinal tissue (duodenum, jejunum, ileum and colon) and noneverted stomach pouch. The enantiomers and their acyl-glucuronides were quantitated using a previously developed stereospecific assay. With the isolated liver, R-FN was shown to invert in both the single-pass and recirculation systems, with a first-pass extraction ratio of 0.3. A significant but variable inversion in all intestinal segments was observed. Substantial inversion by the duodenum was observed (serosal S:R ratio, 1.2) with maximal inversion by the jejunum (serosal S:R ratio, 2.2), whereas inversion of R-FN was absent in the stomach. Considerable glucuronidation was observed in all tissues studied including first-pass glucuronidation of both enantiomers after single-pass perfusion through the isolated liver and stereoselective glucuronidation in intestinal tissue segments. The results indicate that, in the male Sprague-Dawley rat, R-FN undergoes presystemic inversion by both the gastrointestinal tract and liver. These results, however, must be viewed with caution as they may not necessarily be extrapolated to other 2-APAs or species.

Animals↗