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At least 307 records · Page 17Linked to original sources
PubMed1987

Human atrial natriuretic polypeptide during escape from mineralocorticoid excess in man.

1. Plasma concentrations of human alpha-atrial natriuretic polypeptide (h-alpha ANP) during escape from the effects of mineralocorticoid excess were determined in six healthy volunteers. 2. Escape, as indicated by an abrupt increase in sodium excretion on the third to sixth day of 9 alpha-fludrocortisone acetate administration (0.6 mg/day), was observed in all subjects. 3. The mean plasma h-alpha ANP level was 30.9 +/- SEM 8.8 pmol/l on the control day; it increased exponentially in response to 9 alpha-fludrocortisone acetate administration, reached a significant level (114.0 +/- 22.4 pmol/l, P less than 0.05) on the day before escape and remained elevated during escape. 4. The 24 h creatinine clearance and blood pressure did not change significantly before the escape. Plasma h-alpha ANP increased markedly when the cumulative sodium balance exceeded 220 mmol. 5. These results suggest that h-alpha ANP may play a contributory role in natriuresis and diuresis after mineralocorticoid excess.

Adult↗
PubMed1997

Escape of HIV-1 is associated with lack of V3 domain-specific antibodies in vivo.

This study was performed to analyse correlates of viral escape in AIDS patients. Peripheral blood mononuclear cells (PBMC) from HIV- donors were inoculated with AIDS patients' serum to detect neutralization-resistant cell-free virus. Infectious virus was detected by polymerase chain reaction (PCR) and analysed by sequencing the V3 region. The escaped virus species was compared with all V3 virus variants found in the patients' PBMC and plasma. In one patient escaped virus was also compared with variants found in CD4+ T cells isolated by FACS from blood, spleen and lymph node. The frequency of the virus variants was determined by cloning and sequence analysis of 20 V3 clones for each PCR amplification. To monitor anti-V3 antibodies by ELISA, each V3 sequence was expressed as fusion with glutathione S-transferase (GST-V3). In our AIDS patients, a V3-directed antibody response against the infectious virus V3 loop was not detectable. In contrast, virus variants unable to infect the donor PBMC in vitro were well recognized by homologous V3-directed antibody. After an interval of 1 year the frequency of these variants clearly decreased, while at the same time the escaped variants grew out and finally represented the predominant viral species both in plasma and PBMC. The infectious variants lacking V3 antibody response were also predominant in CD4+ T cells in spleen and lymph node. Our data indicate that the escape of virus variants is closely related to the lack of V3-directed antibody.

Amino Acid Sequence↗
PubMed1998

Viral escape from antisense RNA.

RNA coliphage SP was propagated for several generations on a host expressing an inhibitory antisense RNA complementary to bases 31-270 of the positive-stranded genome. Phages evolved that escaped inhibition. Typically, these escape mutants contained 3-4 base substitutions, but different sequences were observed among different isolates. The mutations were located within three different types of structural features within the predicted secondary structure of SP genomic RNA: (i) hairpin loops; (ii) hairpin stems; and (iii) the 5' region of the phage genome complementary to the antisense molecule. Computer modelling of the mutant genomic RNAs showed that all of the substitutions within hairpin stems improved the Watson-Crick pairing of the stem. No major structural rearrangements were predicted for any of the mutant genomes, and most substitutions in coding regions did not alter the amino acid sequence. Although the evolved phage populations were polymorphic for substitutions, many substitutions appeared independently in two selected lines. The creation of a new, perfect, antisense RNA against an escape mutant resulted in the inhibition of that mutant but not of other escape mutants nor of the ancestral, unevolved phage. Thus, at least in this system, a population of viruses that evolved to escape from a single antisense RNA would require a cocktail of several antisense RNAs for inhibition.

Antiviral Agents↗
PubMed2003

Listeria species escape from the phagosomes of interleukin-4-deactivated human macrophages independent of listeriolysin.

Listeria monocytogenes is the causative agent of infections like sepsis and meningitis, especially in immunocompromised hosts. Human macrophages are able to phagocytose and digest L. monocytogenes but IL-4 prevents human macrophages from killing the bacteria, the mechanisms of which are unknown. In the present study, we examined various listeria species and strains including wild-type and deletion mutants in human macrophages pretreated with IL-4. To analyse the IL-4-mediated deactivation process, we combined quantitative infection assays with various morphologic methods. IL-4 facilitates survival and escape of the pathogenic L. monocytogenes wild-type strain 10403S from the macrophage phagosomes. In untreated macrophages, the isogenic listeriolysin deletion mutant strain DP-L2161 was killed and did not escape from the phagolysosomes. However, after macrophage deactivation with IL-4 DP-L2161 survived and escaped from the phagosomes. This was also the case, but to a lesser extent, even for the naturally avirulent L. innocua. As detected by confocal laser-scanning fluorescence microscopy and electron microscopy, IL-4 permitted the escape of all listeria species tested, including DP-L2161 and L. innocua from the phagosomal compartment of the macrophages. We conclude that escape from the phagosome and survival of the listeria species tested in IL-4-deactivated human macrophages is independent of the virulence factor listeriolysin.

Anti-Bacterial Agents↗
PubMed2001

Effects of systemic morphine on escape latency and a hindlimb reflex response in the rat.

The present study uses focal electrical stimulation of myelinated nociceptors to simultaneously assess behavioral responses that are organized at spinal and supraspinal sites in the rat. Hindlimb reflex amplitude and the latency to operant escape responses by a forelimb were recorded for each stimulus presentation to a hindlimb across a wide range of intensities. This paradigm provided a tool whereby effects of morphine on conscious escape responses could be delineated from effects on a segmental flexion reflex over a range of doses. Administration of morphine (3 mg/kg and 10 mg/kg, subcutaneously) increased the latency of escape responses and decreased the amplitude of reflex responses in a dose-dependent manner. However, morphine produced a greater suppression of reflex responses compared with the increase in effects on escape latencies. The effects of morphine on escape latency were not expressed at the highest stimulus intensities (0.6 to 0.8 mA), whereas reflex responses were attenuated at all suprathreshold stimulus intensities. Thus, electrically evoked, spinal-mediated responses of rats are not affected by morphine in the same manner as electrically evoked supraspinal-mediated nociceptive behaviors. However, both measures confirm evidence that responses elicited by activation of myelinated afferents are less powerfully affected by morphine than responses to input from unmyelinated nociceptors.

Journal Article↗
PubMed2003

Geometry and topology of escape. I. Epistrophes.

We consider a dynamical system given by an area-preserving map on a two-dimensional phase plane and consider a one-dimensional line of initial conditions within this plane. We record the number of iterates it takes a trajectory to escape from a bounded region of the plane as a function along the line of initial conditions, forming an "escape-time plot." For a chaotic system, this plot is in general not a smooth function, but rather has many singularities at which the escape time is infinite; these singularities form a complicated fractal set. In this article we prove the existence of regular repeated sequences, called "epistrophes," which occur at all levels of resolution within the escape-time plot. (The word "epistrophe" comes from rhetoric and means "a repeated ending following a variable beginning.") The epistrophes give the escape-time plot a certain self-similarity, called "epistrophic" self-similarity, which need not imply either strict or asymptotic self-similarity.

Fractals↗
PubMed1999

Diffusion and scaling in escapes from two-degrees-of-freedom Hamiltonian systems.

This paper summarizes an investigation of the statistical properties of orbits escaping from three different two-degrees-of-freedom Hamiltonian systems which exhibit global stochasticity. Each time-independent H=H(0)+ varepsilon H('), with H(0) an integrable Hamiltonian and varepsilon H(') a nonintegrable correction, not necessarily small. Despite possessing very different symmetries, ensembles of orbits in all three potentials exhibit similar behavior. For varepsilon below a critical varepsilon (0), escapes are impossible energetically. For somewhat higher values, escape is allowed energetically but still many orbits never escape. The escape probability P computed for an arbitrary orbit ensemble decays toward zero exponentially. At or near a critical value varepsilon (1)> varepsilon (0) there is a rather abrupt qualitative change in behavior. Above varepsilon (1), P typically exhibits (1) an initial rapid evolution toward a nonzero P(0)( varepsilon ), the value of which is independent of the detailed choice of initial conditions, followed by (2) a much slower subsequent decay toward zero which, in at least one case, is well fit by a power law P(t) proportional, variant t(-&mgr;), with &mgr; approximately 0.35-0.40. In all three cases, P(0) and the time T required to converge toward P(0) scale as powers of varepsilon - varepsilon (1), i.e., P(0) proportional, variant ( varepsilon - varepsilon (1))(alpha) and T proportional, variant ( varepsilon - varepsilon (1))(beta), and T also scales in the linear size r of the region sampled for initial conditions, i.e., T proportional, variant r(-delta). To within statistical uncertainties, the best fit values of the critical exponents alpha, beta, and delta appear to be the same for all three potentials, namely alpha approximately 0.5, beta approximately 0.4, and delta approximately 0.1, and satisfy alpha-beta-delta approximately 0. The transitional behavior observed near varepsilon (1) is attributed to the breakdown of some especially significant KAM tori or cantori. The power law behavior at late times is interpreted as reflecting intrinsic diffusion of chaotic orbits through cantori surrounding islands of regular orbits. (c) 1999 American Institute of Physics.

Journal Article↗
PubMed2006

Thermally activated escape rate for a Brownian particle in a double-well potential for all values of the dissipation.

The translational Brownian motion in a (2-4) double-well potential is considered. The escape rate, the position correlation function and correlation time, and the generalized susceptibility are evaluated from the solution of the underlying Langevin equation by using the matrix-continued fraction method. The escape rate and the correlation time are compared with the Kramers theory of the escape rate of a Brownian particle from a potential well as extended by Mel'nikov and Meshkov [J. Chem. Phys. 85, 1018 (1986)]. It is shown that in the low-temperature limit, the universal Mel'nikov and Meshkov expression for the escape rate provides a good estimate of both escape rate and inverse position correlation time for all values of the dissipation including the very low damping (VLD), very high damping (VHD), and turnover regimes. Moreover, for low barriers, where the Mel'nikov and Meshkov method is not applicable, analytic equations for the correlation time in the VLD and VHD limits are derived.

Journal Article↗
PubMed2006

Escape from a cavity through a small window: turnover of the rate as a function of friction constant.

To escape from a cavity through a small window the particle has to overcome a high entropy barrier to find the exit. As a consequence, its survival probability in the cavity decays as a single exponential and is characterized by the only parameter, the rate constant. We use simulations to study escape of Langevin particles from a cubic cavity through a small round window in the center of one of the cavity walls with the goal of analyzing the friction dependence of the escape rate. We find that the rate constant shows the turnover behavior as a function of the friction constant, zeta: The rate constant grows at very small zeta, reaches a maximum value which is given by the transition-state theory (TST), and then decreases approaching zero as zeta-->infinity. Based on the results found in simulations and some general arguments we suggest a formula for the rate constant that predicts a turnover of the escape rate for ergodic cavities in which collisions of the particle with the cavity walls are defocusing. At intermediate-to-high friction the formula describes transition between two known results for the rate constant: the TST estimation and the high friction limiting behavior that characterizes escape of diffusing particles. In this range of friction the rate constants predicted by the formula are in good agreement with those found in simulations. At very low friction the rate constants found in simulations are noticeably smaller than those predicted by the formula. This happens because the simulations were run in the cubic cavity which is not ergodic.

Biophysical Phenomena↗
PubMed2002

HIV-1 escape from a small molecule, CCR5-specific entry inhibitor does not involve CXCR4 use.

To study HIV-1 escape from a coreceptor antagonist, the R5 primary isolate CC1/85 was passaged in peripheral blood mononuclear cells with increasing concentrations of the CCR5-specific small molecule inhibitor, AD101. By 19 passages, an escape mutant emerged with a >20,000-fold resistance to AD101. This virus was cross-resistant to a related inhibitor, SCH-C, and partially resistant to RANTES but still sensitive to CCR5-specific mAbs. The resistant phenotype was stable; the mutant virus retained AD101 resistance during nine additional passages of culture in the absence of inhibitor. Replication of the escape mutant in peripheral blood mononuclear cells completely depended on CCR5 expression and did not occur in cells from CCR5-Delta32 homozygous individuals. The escape mutant was unable to use CXCR4 or any other tested coreceptor to enter transfected cells. Acquisition of CXCR4 use is not the dominant in vitro escape pathway for a small molecule CCR5 entry inhibitor. Instead, HIV-1 acquires the ability to use CCR5 despite the inhibitor, first by requiring lower levels of CCR5 for entry and then probably by using the drug-bound form of the receptor.

Amino Acid Sequence↗
PubMed1999

Dual roles for transcription factor IIF in promoter escape by RNA polymerase II.

Transcription factor (TF) IIF is a multifunctional RNA polymerase II transcription factor that has well established roles in both transcription initiation, where it functions as a component of the preinitiation complex and is required for formation of the open complex and synthesis of the first phosphodiester bond of nascent transcripts, and in transcription elongation, where it is capable of interacting directly with the ternary elongation complex and stimulating the rate of transcription. In this report, we present evidence that TFIIF is also required for efficient promoter escape by RNA polymerase II. Our findings argue that TFIIF performs dual roles in this process. We observe (i) that TFIIF suppresses the frequency of abortive transcription by very early RNA polymerase II elongation intermediates by increasing their processivity and (ii) that TFIIF cooperates with TFIIH to prevent premature arrest of early elongation intermediates. In addition, our findings argue that two TFIIF functional domains mediate TFIIF action in promoter escape. First, we observe that a TFIIF mutant selectively lacking elongation activity supports TFIIH action in promoter escape, but is defective in suppressing the frequency of abortive transcription by very early RNA polymerase II elongation intermediates. Second, a TFIIF mutant selectively lacking initiation activity is more active than wild type TFIIF in increasing the processivity of very early elongation intermediates, but is defective in supporting TFIIH action in promoter escape. Taken together, our findings bring to light a function for TFIIF in promoter escape and support a role for TFIIF elongation activity in this process.

Base Sequence↗
PubMed1997

Oxygen consumption and ventilation during simulated escape from an offshore oil platform.

Twenty-six male workers from the North Sea offshore oil industry took part in a simulated escape exercise at the Offshore Fire Training Centre. The course was 370 m long and had 19.4 m of vertical ascent and descent using the stairs on simulated offshore structures. Inspired ventilation and oxygen consumption were measured using the P. K. Morgan "Oxylog' and subjects breathed through the apparatus by mouthpiece and one-way valve assembly while wearing a nose clip. On comparison with anthropometric data from larger studies, this sample of the offshore work-force was thought to be representative. The mean duration of the exercise period was 371 s (SD = 24 s, range = 325-424 s). Mean oxygen consumption standing still at the start of the trial was 0.421 min-1 (SD = 0.101 min-1, max. = 0.611 min-1) and mean ventilation 12.351 min-1 (SD = 4.251 min-1, max. = 22.271 min-1). During exercise, the mean oxygen consumption rose to 2.711 min-1 (SD = 0.641 min-1, max = 4.051 min-1) and mean ventilation reached 46.341 min-1 (SD = 15.831 min-1, max = 87.361 min-1) during the fifth minute of exercise. At the end of the exercise period, oxygen consumption returned to resting values after 2 min and ventilation after 3 min. There was no indication of an oxygen debt. Oxygen consumption and ventilation were related to body weight and the maximum figures for ventilation and oxygen consumption were seen in individuals of over the 95th centile for weight who completed the exercise more quickly than other subjects. Draft standards for respiratory protective equipment for use during escape from fire do not specify the breathing volumes identified in this study, and which are considerably higher than those being currently considered. Additionally, the atmospheric conditions near a fire are likely to stimulate ventilation to considerably higher levels than those identified here. Accordingly, such equipment is likely to limit physical performance if a similar intensity of exercise is necessary during an escape. The architecture of offshore installations and protocols for escape from them should be structured to minimize exercise, and stair climbing should be avoided if emergency respirators are to be used. Workers should be trained in the use of escape breathing equipment and instruction should include information regarding its limitations and the need to limit exercise to an appropriate level.

Body Weight↗
PubMed1990

Mathematical investigations of the escape from the Malthusian trap.

"We present a simulation model that synthesizes Malthusian and Boserupian notions of the way population growth and economic development were intertwined. The non-linear stochastic model consists of a system of equations whose dynamics culminate in an industrial revolution after hundreds of iterations. The Industrial Revolution [in Europe] can thus be conceptualized as a permanent 'escape' from the Malthusian trap that occurs once the economy is capable of permanently sustaining an ever growing population. We investigate the conditions for such an escape and their sensitivity to the parameters of the model.... Our results show that the likelihood of an escape is sensitive to the savings rate and to the output elasticities of the two sectors of the economy. When not in a subsistence crisis, the chances that an escape will occur increase for larger values of the ratio of the savings rate to the growth rate of the population. The chances of an escape also increase substantially for larger values of the output elasticities of labor." (SUMMARY IN FRE)

Demography↗
PubMed1983

Escape of mouse mastocytoma P815 after nearly complete rejection is due to antigen-loss variants rather than immunosuppression.

Even though mastocytoma P815 often undergoes a nearly complete rejection in syngeneic mice, the tumor cells almost always escape to form progressive tumors. We found that this was not due to the establishment of an immunosuppressed state because genetically marked P815 cells, that were injected in mice where tumor escape was occurring, were readily rejected. An analysis of escaping tumor cell populations with anti-P815 cytolytic T lymphocyte (CTL) clones showed the presence of stable resistant variants. Using antigen-loss variants found in escaping populations or selected in vitro with CTL clones, we were able to define four different tumor-associated antigenic specificities, each recognized by a specific CTL clone. One of these specificities was absent from all escaping tumor cells and another had been lost by some of them.

Animals↗
PubMed2026

EscaPRRS-ORF5: a structure-aware evolutionary framework for prioritizing immune escape-prone variants in porcine reproductive and respiratory syndrome virus.

MOTIVATION: Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is a rapidly evolving RNA virus causing significant economic losses, posing a formidable challenge to vaccine efficacy due to its high mutational variability and immune escape. As the viral mutants evolve, their ability to sustain in population is driven by a range of host biology factors such as receptor binding, fusion, and uncoating. Existing tools that predict viral fitness and escape propensities rely heavily on extensive, up-to-date sequence data and lack integration of biochemical host interactions, limiting mechanistic understanding of the mutational landscape. We introduce Esca, a sequence-only toolchain framework that identifies immune escape-prone residues by exhaustively scanning each residue position for all amino acid substitutions using a Bayesian Variational Autoencoder (VAE) trained on protein language model embeddings. We demonstrate Esca on the GP5(ORF5) glycoprotein of PRRSV (EscaPRRS-ORF5) by training on ESM-2 embeddings of 32 146 GP5 sequences (2015-2022) spanning 140 sub-lineages. RESULTS: Despite being trained only on GP5 sequence data, EscaPRRS-ORF5 recovered 85.7% of the surface-exposed receptor binding interfaces as escape-prone regions. We use a mutation-sensitive fitness scoring scheme that goes beyond Hamming distances, to predict antibody escape tendencies, supporting surveillance of (re) emerging PRRSV variants. We do not claim that ORF5 alone captures PRRSV evolution or serves as a surveillance endpoint; rather, Esca offers a scalable path toward whole-genome, structure-aware surveillance. AVAILABILITY AND IMPLEMENTATION: EscaPRRS-ORF5 is freely available at https://doi.org/10.6084/m9.figshare.32661033 with an interactive Colab notebook at https://colab.research.google.com/drive/1TEgzAhPwvNAZ01VXeJbIFibfri2jnDA5? usp=sharing.

Porcine respiratory and reproductive syndrome viru↗
PubMed1987

Sequence-dependent gene conversion: can duplicated genes diverge fast enough to escape conversion?

Conversion between duplicated genes limits their independent evolution. Models in which conversion frequencies decrease as genes diverge are examined to determine conditions under which genes can "escape" further conversion and hence escape from a gene family. A review of results from various recombination systems suggests two classes of sequence-dependence models: (1) the "k-hit" model in which conversion is completely inactivated by a few (k) mutational events, such as the insertion of a mobile element, and (2) more general models where conversion frequency gradually declines as genes diverge through the accumulation of point mutants. Exact analysis of the k-hit model is given and an approximate analysis of a more general sequence-dependent model is developed and verified by computer simulation. If mu is the per nucleotide mutation rate, then neutral duplicated genes diverging through point mutants are likely to escape conversion provided 2 mu/lambda much greater than 0.1, where lambda is the conversion rate between identical genes. If 2 mu/lambda much less than 0.1, the expected number of conversions before escape increases exponentially so that, for biological purposes, the genes never escape conversion. For single mutational events sufficient to block further conversions, occurring at rate nu per copy per generation, many conversions are expected if 2 nu/lambda much less than 1, while the genes essentially evolve independently if 2 nu/lambda much greater than 1. Implications of these results for both models of concerted evolution and the evolution of new gene functions via gene duplication are discussed.

Base Sequence↗
PubMed1996

Escape from het-6 incompatibility in Neurospora crassa partial diploids involves preferential deletion within the ectopic segment.

Self-incompatible het-6OR/het-6PA partial diploids of Neurospora crassa were selected from a cross involving the translocation strain, T(IIL-->IIIR)AR18, and a normal sequence strain. About 25% of the partial diploids exhibited a marked increase in growth rate after 2 weeks, indicating that "escape" from het-6 incompatibility had occurred. Near isogenic tester strains with different alleles (het-6OR and het-6PA) were constructed and used to determine that 80 of 96 escape strains tested were het-6PA, retaining the het-6 allele found in the normal-sequence LGII position; 16 were het-6OR, retaining the allele in the translocated position. Restriction fragment length polymorphisms in 45 escape strains were examined with probes made from cosmids that spanned the translocated region. Along with electrophoretic analysis of chromosomes from three escape strains, RFLPs showed that escape is associated with deletion of part of one or the other of the duplicated DNA segments. Deletions ranged in size from approximately 70 kbp up to putatively the entire 270-kbp translocated region but always included a 35-kbp region wherein we hypothesize het-6 is located. The deletion spectrum at het-6 thus resembles other cases where mitotic deletions occur such as of tumor suppressor genes and of the hprt gene (coding for hypoxanthine-guanine phosphoribosyl-transferase) in humans.

Chromosome Walking↗
PubMed2002

Rapid endo-lysosomal escape of poly(DL-lactide-co-glycolide) nanoparticles: implications for drug and gene delivery.

The endo-lysosomal escape of drug carriers is crucial to enhancing the efficacy of their macromolecular payload, especially the payloads that are susceptible to lysosomal degradation. Current vectors that enable the endo-lysosomal escape of macromolecules such as DNA are limited by their toxicity and by their ability to carry only limited classes of therapeutic agents. In this paper, we report the rapid (<10 min) endo-lysosomal escape of biodegradable nanoparticles (NPs) formulated from the copolymers of poly(DL-lactide-co-glycolide) (PLGA). The mechanism of rapid escape is by selective reversal of the surface charge of NPs (from anionic to cationic) in the acidic endo-lysosomal compartment, which causes the NPs to interact with the endo-lysosomal membrane and escape into the cytosol. PLGA NPs are able to deliver a variety of therapeutic agents, including macromolecules such as DNA and low molecular weight drugs such as dexamethasone, intracellularly at a slow rate, which results in a sustained therapeutic effect. PLGA has a number of advantages over other polymers used in drug and gene delivery including biodegradability, biocompatibility, and approval for human use granted by the U.S. Food and Drug Administration. Hence PLGA is well suited for sustained intracellular delivery of macromolecules.

Biological Transport↗