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Chromosome inversions, local adaptation and speciation.

We study the evolution of inversions that capture locally adapted alleles when two populations are exchanging migrants or hybridizing. By suppressing recombination between the loci, a new inversion can spread. Neither drift nor coadaptation between the alleles (epistasis) is needed, so this local adaptation mechanism may apply to a broader range of genetic and demographic situations than alternative hypotheses that have been widely discussed. The mechanism can explain many features observed in inversion systems. It will drive an inversion to high frequency if there is no countervailing force, which could explain fixed differences observed between populations and species. An inversion can be stabilized at an intermediate frequency if it also happens to capture one or more deleterious recessive mutations, which could explain polymorphisms that are common in some species. This polymorphism can cycle in frequency with the changing selective advantage of the locally favored alleles. The mechanism can establish underdominant inversions that decrease heterokaryotype fitness by several percent if the cause of fitness loss is structural, while if the cause is genic there is no limit to the strength of underdominance that can result. The mechanism is expected to cause loci responsible for adaptive species-specific differences to map to inversions, as seen in recent QTL studies. We discuss data that support the hypothesis, review other mechanisms for inversion evolution, and suggest possible tests.

Adaptation, Physiological↗

Evaluation of the genomic extent of effects of fixed inversion differences on intraspecific variation and interspecific gene flow in Drosophila pseudoobscura and D. persimilis.

There is increasing evidence that chromosomal inversions may facilitate the formation or persistence of new species by allowing genetic factors conferring species-specific adaptations or reproductive isolation to be inherited together and by reducing or eliminating introgression. However, the genomic domain of influence of the inverted regions on introgression has not been carefully studied. Here, we present a detailed study on the consequences that distance from inversion breakpoints has had on the inferred level of gene flow and divergence between Drosophila pseudoobscura and D. persimilis. We identified the locations of the inversion breakpoints distinguishing D. pseudoobscura and D. persimilis in chromosomes 2, XR, and XL. Population genetic data were collected at specific distances from the inversion breakpoints of the second chromosome and at two loci inside the XR and XL inverted regions. For loci outside the inverted regions, we found that distance from the nearest inversion breakpoint had a significant effect on several measures of divergence and gene flow between D. pseudoobscura and D. persimilis. The data fitted a logarithmic relationship, showing that the suppression of crossovers in inversion heterozygotes also extends to loci located outside the inversion but close to it (within 1-2 Mb). Further, we detected a significant reduction in nucleotide variation inside the inverted second chromosome region of D. persimilis and near one breakpoint, consistent with a scenario in which this inversion arose and was fixed in this species by natural selection.

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↗

[Genetic control of chromosome synapsis in mice heterozygous for a paracentric inversion].

Frequencies of formation of inversion loops and their relative sizes were studied in laboratory mice heterozygous at paracentric inversion In1(1)Rk in chromosome 1, depending on the genetic background. Homozygotes In1/In1 were crossed with mice from five inbred strains (A/HeJ, BALB/cJ, C3H/HeJ, C57BL/6J, DBA2/J). The frequency of formation of inversion loops, their relative sizes, and the dependence of these parameters on the stage of pachitene were analyzed on electron-microscopic slides of spread spermatocytes in first-generation hybrids. It was shown that the genetic background and cross direction statistically significantly influenced the duration of individual pachitene stages and the frequency of inversion loops, but not relative loop size. Using a database on SNP distribution in the inbred strains examined, we carried out in silico mapping of genes affecting the genotype-dependent characters. We have found that the efficiency of synapsis in the inversion does not depend on interstrain differences in homology of the chromosome 1 region involved in the inversion. Genes controlling the inversion loop frequency in the inversion heterozygotes were mapped to chromosome 7, and genes controlling the duration of individual pachitene stages, to chromosomes 2 and 5.

Animals↗

[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↗

Catastrophic phase inversion in region II of an ionomeric polymer-water system.

Previous work has identified distinct regions, on a phase inversion map, for dispersions of polyurethane ionomer (PUI) and water. In this study, events that occur, before, during, and after catastrophic phase inversion (provoked by adding water to polyurethane ionomer (PUI) in the RII regions of the phase inversion map) have been studied in order to characterise the inversion mechanism. Before phase inversion, initial water addition leads to the hydration of ionic groups and eventually water drops start to form in the hydrophobic portions of the polymer matrix. At the phase inversion point, the PUI-water interface restructures and the ionomer disintegrates into a dispersion of spherical particles enclosed by a continuous aqueous phase. It is suggested that pseudo-drop structures are formed simultaneously during the production of the small polymer-in-water drops. After phase inversion, water addition dilutes the emulsion and destroys the apparent ionic-centre-rich environment surrounding any isolated ionic groups on a particle surface. The larger water-in-polymer drops are likely to have participated in the phase inversion and the smaller water drops form the primary water drops in the multiple emulsions. The resultant emulsions are stable over a period of a few months but very few multiple drops remain after 1(1/4) years.

Microscopy, Electron, Scanning↗

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↗

Inverse power potentials: virial coefficients and a general equation of state.

Virial coefficients up to the seventh are calculated for pair potentials depending on inverse powers of separation, for inverse powers from 5 to 80. Unlike the limiting (infinite inverse power) hard-sphere potential, some virial coefficients for finite inverse power potentials are found to be negative. This makes resummation of the virial series for general inverse power potentials more difficult than that for hard spheres, and some alternative resummation methods are presented and compared. A general equation of state is proposed for fluids of particles interacting through inverse power pair potentials, for inverse powers greater than about 10. This includes the "molecular" inverse power of 12, for which the current results support and extend the results of previous studies.

Journal Article↗

Mechanisms of inverse agonist action at D2 dopamine receptors.

Mechanisms of inverse agonist action at the D2(short) dopamine receptor have been examined. Discrimination of G-protein-coupled and -uncoupled forms of the receptor by inverse agonists was examined in competition ligand-binding studies versus the agonist [3H]NPA at a concentration labelling both G-protein-coupled and -uncoupled receptors. Competition of inverse agonists versus [3H]NPA gave data that were fitted best by a two-binding site model in the absence of GTP but by a one-binding site model in the presence of GTP. K(i) values were derived from the competition data for binding of the inverse agonists to G-protein-uncoupled and -coupled receptors. K(coupled) and K(uncoupled) were statistically different for the set of compounds tested (ANOVA) but the individual values were different in a post hoc test only for (+)-butaclamol. These observations were supported by simulations of these competition experiments according to the extended ternary complex model. Inverse agonist efficacy of the ligands was assessed from their ability to reduce agonist-independent [35S]GTP gamma S binding to varying degrees in concentration-response curves. Inverse agonism by (+)-butaclamol and spiperone occurred at higher potency when GDP was added to assays, whereas the potency of (-)-sulpiride was unaffected. These data show that some inverse agonists ((+)-butaclamol, spiperone) achieve inverse agonism by stabilising the uncoupled form of the receptor at the expense of the coupled form. For other compounds tested, we were unable to define the mechanism.

Animals↗

A general framework for nonlinear multigrid inversion.

A variety of new imaging modalities, such as optical diffusion tomography, require the inversion of a forward problem that is modeled by the solution to a three-dimensional partial differential equation. For these applications, image reconstruction is particularly difficult because the forward problem is both nonlinear and computationally expensive to evaluate. In this paper, we propose a general framework for nonlinear multigrid inversion that is applicable to a wide variety of inverse problems. The multigrid inversion algorithm results from the application of recursive multigrid techniques to the solution of optimization problems arising from inverse problems. The method works by dynamically adjusting the cost functionals at different scales so that they are consistent with, and ultimately reduce, the finest scale cost functional. In this way, the multigrid inversion algorithm efficiently computes the solution to the desired fine-scale inversion problem. Importantly, the new algorithm can greatly reduce computation because both the forward and inverse problems are more coarsely discretized at lower resolutions. An application of our method to Bayesian optical diffusion tomography with a generalized Gaussian Markov random-field image prior model shows the potential for very large computational savings. Numerical data also indicates robust convergence with a range of initialization conditions for this nonconvex optimization problem.

Algorithms↗

Real time inverse filter focusing through iterative time reversal.

In order to achieve an optimal focusing through heterogeneous media we need to build the inverse filter of the propagation operator. Time reversal is an easy and robust way to achieve such an inverse filter in nondissipative media. However, as soon as losses appear in the medium, time reversal is not equivalent to the inverse filter anymore. Consequently, it does not produce the optimal focusing and beam degradations may appear. In such cases, we showed in previous works that the optimal focusing can be recovered by using the so-called spatiotemporal inverse filter technique. This process requires the presence of a complete set of receivers inside the medium. It allows one to reach the optimal focusing even in extreme situations such as ultrasonic focusing through human skull or audible sound focusing in strongly reverberant rooms. But, this technique is time consuming and implied fastidious numerical calculations. In this paper we propose a new way to process this inverse filter focusing technique in real time and without any calculation. The new process is based on iterative time reversal process. Contrary to the classical inverse filter technique, this iteration does not require any computation and achieves the inverse filter in an experimental way using wave propagation instead of computational power. The convergence from time reversal to inverse filter during the iterative process is theoretically explained. Finally, the feasibility of this iterative technique is experimentally demonstrated for ultrasound applications.

Journal Article↗