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Selection and endpoint distribution of bacterial inversion mutations.

This paper describes the isolation and characterization of spontaneous inversion mutants of Salmonella typhimurium. The mutants are selected by demanding that an unexpressed hisD gene acquire a new promoter. Chromosome rearrangements that juxtapose the hisD gene and a foreign promoter are obtained by this selection. Although a number of inversions are found, the frequency was lower than expected. The breakpoint of these inversions are not distributed randomly either in the his operon or on the chromosome. The his breakpoint lies in the hisG-hisD intercistronic region, a sequence known to occur at several places on the bacterial chromosome. In most of the inversions, the 'non-his' breakpoint lies across the chromosome, so that the inverted region includes the origin or terminus of DNA replication. The significance of these results is discussed.

Chromosome Mapping↗

Contribution of adolescent and early adult personality to the inverse association between education and cardiovascular risk behaviours: prospective population-based cohort study.

BACKGROUND: The role of early personality in socioeconomic inequalities in health is not well understood. We investigated the extent to which type A components in adolescence and early adulthood contributed to the inverse association between education and behavioural cardiovascular disease risk factors in adulthood. METHODS: Prospective cohort study with a population-based random sample of 477 men and 648 women, aged 12-21 years at baseline. Baseline data included information on pathogenic and protective components of type A behaviours (impatience, aggression, hard-driving, and engagement-involvement) and parental education. The 9-year follow-up data included information on the participant's educational level and health behaviours (smoking, alcohol consumption, physical inactivity, butter use). RESULTS: After adjustment for parental education, high levels of impatience and low levels of hard-driving in adolescence and early adulthood predicted low educational level in adulthood (Ps < 0.01 for men, Ps < 0.001 for women). Adulthood education was inversely associated with smoking in women and men (odds ratios [OR] = 8.5 and 7.9, 95% CI: 3.4-18.4 and 3.1-23.9, respectively), and with physical inactivity in women (OR = 5.4, 95% CI: 2.6-11.4). In men, components of type A behaviour explained 28.5% of the inverse association between education and smoking, even after controlling for parental education. In women, the corresponding proportions were 20.5% and 17.7% for smoking and physical inactivity, respectively. CONCLUSIONS: The inverse associations of adulthood education with smoking in men and women and physical inactivity in women may be partly rooted in personality-related factors present earlier in life. Our evidence suggests that personality should be studied as a potential contributor to socioeconomic differences in health behaviours.

Adolescent↗

Parasitism in patchy environments: inverse density dependence can be stabilizing.

There are now many examples in the literature where the spatial distribution of per cent parasitism by insect parasitoids is either directly or inversely dependent on host density per patch. While it is well known that direct density dependent relationships can contribute markedly to the stability of a host-parasitoid interaction, inverse relationships have been more-or-less ignored. Using difference equation models, the dynamics of host-parasitoid interactions are described where parasitism per patch varies across the range from direct to inversely density dependent. These models demonstrate for a variety of host distributions that inverse relationships can also strongly promote stability.

Animals↗

Inverse splicing of a discontinuous pre-mRNA intron generates a circular exon in a HeLa cell nuclear extract.

We have recently reported the first example of inverse splicing of a eukaryotic pre-mRNA intron using a whole cell extract from the yeast Saccharomyces cerevisiae. The concomitant circularization of the exon in the course of this splicing reaction gave rise to the hypothesis that the circular RNA species, which had been recently discovered in vivo in mammalian cells, were generated by inverse splicing. Here we report the formation of a circular exon in HeLa cell nuclear extracts by an inverse splicing reaction of the second intron of the human beta-globin gene from a pre-mRNA transcript in which the two intron halves flanked an artificially fused, single exon. Our data demonstrate that the mammalian pre-mRNA splicing system has indeed an intrinsic capability of aligning splice sites in reverse order and that this alignment can be followed by a complete splicing reaction, whereby the discontinuous intron sequences are removed. Thus we propose that circular exons in vivo arise as a result of an inverse splicing reaction following the pairing of a 5' splice site with an upstream 3' splice site and that the frequency of this event is influenced by the presence and strength of other, competing splice sites.

Cell Extracts↗

Sequence-structure specificity--how does an inverse folding approach work?

The inverse folding approach is a powerful tool in protein structure prediction when the native state of a sequence adopts one of the known protein folds. This is because some proteins show strong sequence-structure specificity in inverse folding experiments that allow gaps and insertions in the sequence-structure alignment. In those cases when structures similar to their native folds are included in the structure database, the z-scores (which measure the sequence-structure specificity) of these folds are well separated from those of other alternative structures. In this paper, we seek to understand the origin of this sequence-structure specificity and to identify how the specificity arises on passing from a short peptide chain to the entire protein sequence. To accomplish this objective, a simplified version of inverse folding, gapless inverse folding, is performed using sequence fragments of different sizes from 53 proteins. The results indicate that usually a significant portion of the entire protein sequence is necessary to show sequence-structure specificity, but there are regions in the sequence that begin to show this specificity at relatively short fragment size (15-20 residues). An island picture, in which the regions in the sequence that recognize their own native structure grow from some seed fragments, is observed as the fragment size increases. Usually, more similar structures to the native states are found in the top-scoring structural fragments in these high-specificity regions.

Amino Acid Sequence↗

An inverse method for radiation transport.

Adjoint functions have been used with forward functions to compute gradients in implicit (iterative) solution methods for inverse problems in optical tomography, geoscience, thermal science and other fields, but only once has this approach been used for inverse solutions to the Boltzmann transport equation. In this paper, this approach is used to develop an inverse method that requires only angle-independent flux measurements, rather than angle-dependent measurements as was done previously. The method is applied to a simplified form of the transport equation that does not include scattering. The resulting procedure uses measured values of gamma-ray fluxes of discrete, characteristic energies to determine interface locations in a multilayer shield. The method was implemented with a Newton-Raphson optimisation algorithm and it worked very well in numerical 1-D spherical test cases. A more sophisticated optimisation method would better exploit the potential of the inverse method.

Algorithms↗

Cell migration activated by platelet-derived growth factor receptor is blocked by an inverse agonist of the sphingosine 1-phosphate receptor-1.

We have previously identified a novel complex between the platelet-derived growth factor (PDGF)beta receptor and the sphingosine 1-phosphate receptor-1 (S1P1). The complex permits the utilization of active G-protein subunits (made available by constitutively active S1P1 receptor) by the PDGFbeta receptor kinase to transmit signals to p42/p44 MAPK in response to PDGF. Therefore, an inverse agonist of the S1P1 receptor is predicted to reduce signal transduction from PDGFbeta receptor tyrosine kinase by blocking the constitutive activity of the G-protein coupled receptor. SB649146 is a novel inverse agonist of the S1P1 receptor. First, SB649146 displaced the S1P1 receptor agonist dihydrosphingosine 1-phosphate from membranes expressing the recombinant S1P1 receptor. Second, SB649146 reduced basal recombinant S1P1 receptor-induced GTPgammaS binding and S1P-induced GTPgammaS binding in membranes. Third, SB649146 blocked the S1P-induced activation of p42/p44 MAPK in airway smooth muscle cells, a response that is mediated by the S1P1 receptor. We now report that inverse agonism of the S1P1 receptor with SB649146 reduced the endocytosis of the PDGFbeta receptor-S1P1 receptor complex and the stimulation of p42/p44 MAPK and cell migration in response to PDGF. These findings are the first to report that a GPCR inverse-agonist reduces growth factor-induced receptor tyrosine kinase signaling, fundamentally broadening their mechanism of action. The data obtained with SB649146 also suggest that the constitutively active endogenous S1P1 receptor enhances PDGF-induced cell migration.

Animals↗

Correction of recurrent nipple inversion with cartilage graft.

Of the many techniques advocated to correct nipples, all demonstrate a failure rate with a recurrence of the inversion. We report a technique to correct the recurrent nipple inversion in a simple and permanent fashion. This technique consists of releasing all scar tissue and any lactiferous ducts deep to the nipple and inserting a cartilage graft (rib or auricular) under the nipple. This cartilage graft serves to fill in any soft tissue defect and prevent recurrent contraction and nipple inversion. Although generally used for correction of recurrent nipple inversion, we have also used this technique successfully as an initial modality in patients with inverted nipples. We have found this technique to be simple, nondeforming, cosmetically acceptable, and permanent in the treatment of both inverted and recurrent inverted nipples.

Adult↗

Pulse inversion imaging of liver blood flow: improved method for characterizing focal masses with microbubble contrast.

RATIONALE AND OBJECTIVES: To create a microbubble contrast image of vessels that lie below the resolution of an ultrasound system, a technique is required that detects preferentially the agent echo, rejecting that from tissue. Harmonic imaging exploits the nonlinear behavior of microbubbles but forces a compromise between image sensitivity and axial resolution. The authors describe and evaluate a new method that overcomes this compromise and improves contrast imaging performance: pulse inversion imaging. METHODS: Sequences of pulses of alternate phase are transmitted into tissue and their echoes summed. A prototype scanner equipped with pulse inversion was used to image phantoms and 16 patients with focal liver masses. RESULTS: Pulse inversion images show contrast sensitivity and resolution superior to that of harmonic images. Vessels can be imaged at an incident power sufficiently low to avoid destroying the agent, allowing unique visualization of tumor vasculature. Distinct patterns were seen in hemangiomas, metastases, and hepatocellular carcinomas. CONCLUSIONS: Pulse inversion imaging is an improved bubble-specific imaging method that extends the potential of contrast ultrasonography.

Adult↗

The effect of recurrent ankle inversion sprain and taping on proprioception at the ankle.

PURPOSE: A common explanation for the tendency for ankle inversion sprains to recur is that proprioception is impaired by the initial sprain. It is further hypothesized that the application of tape prevents further sprains by enhancing proprioceptive acuity. The purpose of this study was to determine whether proprioception was impaired in people with recurrent ankle inversion sprain, and whether taping the ankle provided enhanced proprioceptive ability. METHODS: We compared the ability to perceive passive plantarflexion and dorsiflexion movements imposed at the relaxed ankle in 25 subjects with recurrent ankle inversion sprain, with a group of 18 healthy control subjects, matched for age, height, weight, and activity level. Subjects were tested with the ankle both taped and untaped. Detection thresholds were determined at three velocities, 0.1 degrees x s(-1), 0.5 degrees x s(-1), and 2.5 degrees x s(-1). Velocity of the imposed movements and testing of the taped and untaped conditions were randomized. RESULTS: There was no significant difference in the ability to perceive ankle movements between subjects with sprains and healthy controls at any velocity of movement tested. In addition, there was no significant difference in movement perception between the taped and untaped conditions for either subject group at any velocity. CONCLUSION: The ability to detect passive plantarflexion and dorsiflexion movements is not impaired in subjects with recurrent ankle inversion sprain. Furthermore, the protective effect of taping was shown not to arise from enhanced proprioception in the dorsiflexion-plantarflexion plane.

Adolescent↗

Inverse relationship of urinary cyclic GMP to blood pressure reactivity in the CARDIA study: vasodilatory regulation of sympathetic vasoconstriction. Coronary Artery Risk Development in Young Adults.

OBJECTIVE: To determine whether urinary cyclic GMP (cGMP), which mediates the actions of the vasodilators nitric oxide and atrial natriuretic factor, is inversely related to blood pressure (BP) reactivity. In previous work, we found that urinary cGMP was inversely related to diastolic BP, but cGMP levels were higher among individuals presumed to have increased adrenergic activity, increased reactivity, and increased risk of hypertension (blacks, individuals with a family history of hypertension). METHOD: We measured 24-hour urinary cGMP levels in a substudy of 529 individuals in the Coronary Artery Risk Development in Young Adults (CARDIA) study; the sample was 23 to 35 years of age and approximately balanced for race (black/white) and gender. BP reactivity to stressors (video game, star-tracing, cold pressor) was tested 3 years earlier. Baseline BP was included as a covariate in all analyses. RESULTS: Diastolic BP reactivity to cold pressor was inversely related to cGMP excretion (p < .05); the relationship was strongest among black women with a family history of hypertension (partial r = -.33, p < .01). Systolic BP reactivity to star-tracing was also inversely related to cGMP (p < .01); the relationship for both star-tracing and video game stressors was strongest among black men (partial r values = -.25 and -.24, respectively; p values < .01). CONCLUSIONS: The results indicate that vasodilatory activity may impact the BP response to stress through modulation of adrenergic activation, particularly among blacks.

Adolescent↗

Increase in spinal canal area after inverse laminoplasty: an anatomical study.

STUDY DESIGN: In vitro measurement of the area of the spinal canal in the rostral and caudal portions of lumbar vertebrae before and after application of a new technique called "inverse laminoplasty." OBJECTIVES: To quantify the normal area of the spinal canal in the rostral and caudal portions of lumbar vertebrae and the amount of enlargement gained after inverse laminoplasty. SUMMARY AND BACKGROUND DATA: Other types of laminoplasty have been proven to increase the area of the spinal canal. Inverse laminoplasty has been performed in 10 patients but has not been evaluated in vitro. METHODS: The transverse and anteroposterior diameter of the spinal canal was measured in 34 vertebrae from seven cadavers using digital calipers. In each vertebra, the laminae and spinous process were removed en bloc using a high-speed drill. The removed piece was inverted and reattached with titanium mini-plates. The area of the spinal canal was again measured and compared with the prelaminoplasty measurements using paired Student's t tests. RESULTS: The anteroposterior diameter and area of the spinal canal were significantly smaller before surgery in the rostral than in the caudal part of the vertebrae (P <10(-3)). The rostral and caudal areas of the spinal canal increased by 61% and 17%, respectively, after the laminae were inverted (P <10(-3)). CONCLUSION: Because inverse laminoplasty is simple and increases the area of the spinal canal, it may prove to be a useful surgical technique for the treatment of lumbar spinal stenosis. Further studies are needed to determine whether the technique is biomechanically sound and whether it helps prevent perineural scarring.

Adult↗

Inverse relationship between density of cutaneous hair and pigmented lesion count in patients with malignant melanoma.

The aim of this study was to investigate whether there is an inverse relationship between the density of cutaneous hair and the number of pigmented lesions in patients with malignant melanoma, and to review the clinical and experimental findings with regard to this relationship. Cutaneous hair density and pigmented lesion counts were determined at nine sites by two physicians using specified criteria in 10 patients with a history of malignant melanoma and 22 control subjects. Study participants were Caucasian males of similar age, height and weight, and had similar occupational, ethnic, socioeconomic and sun exposure backgrounds. Statistical analysis was performed using combined data from all the sites and individual site data to determine whether an inverse relationship between cutaneous hair density and pigmented lesion counts exists. The results demonstrated statistically significant inverse relationships for the chest, upper back, upper arm and forearm in the melanoma patients, but not in the controls. For all the sites combined, both groups demonstrated statistically significant inverse relationships. The study findings are consistent with the hypothesis that some pigmented lesions may arise from the melanocytes of the hair follicle. This hypothesis may lead to new approaches to studying and treating melanoma.

Adult↗

Number and orientation of beams in inversely planned intensity-modulated radiotherapy of the female breast and the parasternal lymph nodes.

Intensity-modulated radiotherapy (IMRT) provides better sparing of normal tissue. We evaluated the optimum beam configuration for IMRT based on inverse treatment planning in adjuvant radiotherapy for breast cancer in a case of left-sided tumor. In addition to radiotherapy planning with the conventional technique of tangential wedged 6-MV photon beams and an oblique 15-MeV electron beam, we performed inversely planned IMRT with the step-and-shoot-technique. Dose calculation was carried out using the treatment planning system Virtuos with the inverse optimization module KonRad adapted to it. IMRT plans were generated for 2 to 16 beams. The results were compared with conventional techniques. For a maximum treatment time of 20 minutes, it is shown that IMRT with 12 modulated photon beams and 7 intensity steps is best suited for treatment in the presented case. Compared with a conventional technique with photons combined with electrons, dose conformality and homogeneity of the planning target volume was increased. The mean heart dose was reduced from 9.1 Gy to 6.1 Gy. The volume of heart irradiated with a dose higher than 30 Gy was reduced from 7.6% to 1.9%, and the volume of the left lung from 13.6% to 11.5% as well. Inverse optimization for IMRT with multiple beams is feasible in the adjuvant treatment of breast cancer. Because of the reduction of the high-dose area of a substantial cardiac volume, it is superior to conventional techniques in cases where the parasternal lymph nodes should be integrated into the target volume. Here, a clinical advantage might be detectable.

Breast Neoplasms↗

The inversion In(2L)t impacts complex, environmentally sensitive behaviors in Drosophila melanogaster.

Genetic variation in behavioral traits allows organisms to respond and adapt to environmental challenges. Genetic variation in behavior is often affected by many genes and thus has a complex genetic basis. Inversions, the reorientation of genes along the chromosome, tightly link genetic variants together because they suppress recombination. Therefore, inversions are believed to have a major impact on phenotypic variation because they combine the effects of multiple genes, which can pleiotropically alter multiple aspects of behavior. This study investigates how the inversion In(2L)t, found in Drosophila melanogaster populations around the world, impacts different aspects of behavior in an environment-sensitive manner. We test the activity, foraging, and startle-induced behavior of flies with different In(2L)t genotypes across sex and temperatures. We observe that Drosophila homozygous for In(2L)t sleep less frequently, spend more time away from a food source, and have a longer duration of startle response. Additionally, the impacts of In(2L)t on aspects of behavior can be sex-specific and are largely consistent across temperatures. Taken together, our research demonstrates that inversions can regulate aspects of behavior, and suggests hypotheses explaining the distribution of In(2L)t across space and time.

Behavior↗

Adsorption of charged particles on an oppositely charged surface: oscillating inversion of charge.

Adsorption of multivalent counterions on the charged surface of a macroion is known to lead to inversion of the macroion charge due to the strong lateral correlations of counterions. We consider a nontrivial role of the excluded volume of counterions on this effect. It is shown analytically that when the bare charge of the macroion increases, its net charge including the adsorbed counterions oscillates with the number of their layers. Charge inversion vanishes every time the top layer of counterions is completely full and becomes incompressible. These oscillations of charge inversion are confirmed by Monte Carlo simulations. Another version of this phenomenon is studied for a metallic electrode screened by multivalent counterions when the potential of the electrode is controlled instead of its charge. In this case, oscillations of the compressibility and charge inversion lead to oscillations of capacitance of this electrode with the number of adsorbed layers of multivalent counterions.

Journal Article↗

Field theory of the inverse cascade in two-dimensional turbulence.

A two-dimensional fluid, stirred at high wave numbers and damped by both viscosity and linear friction, is modeled by a statistical field theory. The fluid's long-distance behavior is studied using renormalization-group (RG) methods, as begun by Forster, Nelson, and Stephen [Phys. Rev. A 16, 732 (1977)]. With friction, which dissipates energy at low wave numbers, one expects a stationary inverse energy cascade for strong enough stirring. While such developed turbulence is beyond the quantitative reach of perturbation theory, a combination of exact and perturbative results suggests a coherent picture of the inverse cascade. The zero-friction fluctuation-dissipation theorem (FDT) is derived from a generalized time-reversal symmetry and implies zero anomalous dimension for the velocity even when friction is present. Thus the Kolmogorov scaling of the inverse cascade cannot be explained by any RG fixed point. The beta function for the dimensionless coupling ĝ is computed through two loops; the ĝ3 term is positive, as already known, but the ĝ5 term is negative. An ideal cascade requires a linear beta function for large ĝ, consistent with a Padé approximant to the Borel transform. The conjecture that the Kolmogorov spectrum arises from an RG flow through large ĝ is compatible with other results, but the accurate k(-5/3) scaling is not explained and the Kolmogorov constant is not estimated. The lack of scale invariance should produce intermittency in high-order structure functions, as observed in some but not all numerical simulations of the inverse cascade. When analogous RG methods are applied to the one-dimensional Burgers equation using an FDT-preserving dimensional continuation, equipartition is obtained instead of a cascade--in agreement with simulations.

Journal Article↗

Charge inversion by multivalent ions: dependence on dielectric constant and surface-charge density.

Charge inversion occurs when the effective charge of a surface exposed to solution reverses polarity due to an excess of counterions accumulating in the immediate vicinity of the surface. Using atomic force spectroscopy, we have directly measured the effect on charge inversion of changing the dielectric constant of the solvent and the surface-charge density. Both decreasing the dielectric constant and increasing the bare surface-charge density lower the charge-inversion concentration. These observations are consistent with the theoretical proposal that spatial correlations between ions are the dominant driving mechanism for charge inversion.

Journal Article↗