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For 7 consecutive days slugs (Limax maximus) were exposed to escapable, inescapable, or no light-heat stress in an escape task. On Days 8 and 9 they were tested in a different escape task. The slugs in the inescapable light-heat group had reliably longer escape latencies and more failures to escape than the slugs in the escapable light-heat group or the no light-heat control group.
Immune-mediated control of tumors may occur, in part, through lysis of malignant cells by CD8(+) T cells that recognize specific Ag-HLA class I complexes. However, tumor cell populations may escape T cell responses by immune editing, by preventing formation of those Ag-HLA complexes. It remains unclear whether the human immune system can respond to immune editing and recognize newly arising escape variants. We report an example of shifting immune responses to escape variants in a patient with sequential metastases of melanoma and long-term survival after surgery alone. Tumor cells in the first metastasis escaped immune recognition via selective loss of an HLA haplotype (HLA-A11, -B44, and -Cw17), but maintained expression of HLA-A2. In the second metastasis, immune escape from an immunodominant MART-1-specific T cell response was mediated by HLA class I down-regulation, resulting in a failure to present this epitope, but persistent presentation of a tyrosinase-derived epitope. Consequent to this modification in tumor Ag presentation, the dominant CTL response shifted principally toward a tyrosinase-targeted response, even though tyrosinase-specific CTL had been undetectable during the initial metastatic event. Thus, in response to immune editing of tumor cells, a patient's spontaneous T cell response adapted, gaining the ability to recognize and to lyse "edited" tumor targets. The observation of both immune editing and immune adaptation in a patient with long-term survival after surgery alone demonstrates an example of immune system reactivity to counteract the escape mechanism(s) developed by tumor cells, which may contribute to the clinical outcome of malignant disease.
The behavior of 25 rats trained in a homogeneous shuttle box to escape unsignalled grid-shock was analyzed. Three categories of escape were distinguished: (1) species-specific fly away from the charged grid, (2) long-latency crossing preceded and accompanied by other behaviors that compete with the escape response, and (3) short-latency escape which followed an anticipatory postural pose. The animals displayed species-specific fly away only during the initial trials of a session. Subsequently long-latency crossings develops, reflecting a resistance to enter the opposite compartment. A measure based on a comparison of escape latency distributions in the two halves of the 1st session discriminates between good and poor learners. Subgroups of good and poor learners differed in performance efficiency in all five training sessions. Good learners were able to overcome the resistance to enter the opposite compartment and recall the learned short-latency escape.
Transformation of inborn reaction of leg flexion into conditioned escape response of leg extension was studied. The model of the so called precise reflex was used. A dog could avoid or escape the shock applied to the paw by placing this paw in a narrow ,,safety zone located at a definite height above the floor. When the shock is applied to the paw located below this zone, the escape response is flexion, i.e., it coincides with the inborn reaction. When the paw is lifted above this zone, the escape response is extension, i.e., it is opposite to the inborn response. Success of such extension response acquisition depended on the sequence of training conditions. The dogs of Group I at the beginning were accustomed to escape from shock by lifting the paw into the ,,safety zone, i.e., inborn reaction was instrumentalized. A subsequent formation of conditioned extension was extremely difficult and it did not became strong in spite of a very long training. Lowering the paw into the ,,safety zone was usually slow. The dogs of group II were trained from the very beginning to escape from shock by leg extension. Contrary to the results obtained on group I this conditioned response was perfectly established. It was formed rapidly, only when active extension was paired regularly with termination (during extension) of the shock. It is suggested that conditioned connection from one functional center to another is formed and becomes stronger if evoked activity of the first center decreases during (or immediately after) the excitation of the second center.
Neural regeneration in the escape circuit of the first-instar cockroach is described using behavioral analysis, electrophysiology, intracellular staining, and electron microscopy. Each of the two filiform hairs on each of the animal's cerci is innervated by a single sensory neuron, which specifically synapses with a set of giant interneurons (GIs) in the terminal ganglion. These trigger a directed escape run. Severing the sensory axons causes them to degenerate and perturbs escape behavior, which is restored to near normal after 4-6 days. Within this time, afferents regenerate and reestablish arborizations in the terminal ganglion. In most cases, regenerating afferents enter the cercal glomerulus and re-form most of the specific monosynaptic connections they acquired during embryogenesis, although their morphology deviates markedly from normal; these animals reestablish near normal escape behavior. In a few cases, regenerating afferents remain within the cercus or bypass the cercal glomerulus, and thereby fail to re-form synapses with GIs; these animals continue to exhibit perturbed escape behavior. We conclude that in most cases, specific synapses are reestablished and appropriate escape behavior is restored. This regeneration system therefore provides a tractable model for the establishment of synaptic specificity in a simple neuronal circuit.
The shock-escape behavior of preweanling rats in a multidirectional escape situation was examined in 3 experiments. In Experiment I, 5-, 7-, 9-, and 11-day-old rats were given shock-escape training on each of 3 days. Rats younger than 7 days of age did not improve escape responding within or over sessions. Animals 7 days of age and older, however, showed both an intrasession improvement and an intersession improvement that could not be attributed solely to maturation. In Experiment II, the escape behavior of 3-, 5-, and 7-day-old was examined in an apparatus modified to take into account the poor locomotor abilities of these animals. They were given escape training on 3 successive days. Again; no within-session improvement was found in rats under 7 days of age. However, an intersession improvement was found in rats whose training began at 5 days of age. This improvement was due to maturation and did not reflect a cumulative effect of training. Experiment III, like Experiment I, demonstrated that the intersession improvement in the older rats was not simply a maturation effect. It also demonstrated that the improvement could not be attributed to the stress of prior handling, shock, or body temperature loss, but was, rather, a retention effect. These results support the contention that the emergence of memory is task specific.
Two dengue 2-specific IgM monoclonal antibodies (MAb) recognised spatially unrelated epitopes on the envelope (E) protein of dengue 2 virus, which were also recognised by serum from 20 and 50%, respectively, of patients with a primary dengue 2 infection. Dengue 2 virus populations escaping neutralisation by MAb 6B2 (representing the majority population of dengue 2-specific IgM MAbs ) had a deduced amino acid change (G-S) in the pre-Membrane (prM) protein at position 15 and a second in the E protein at E311 (E-G). The change in the E protein was adjacent to the only other epitopes on dengue 2 virus (E307, E383-385) involved in neutralisation that have been identified but that were recognised by IgG antibodies. Dengue 2 virus escaping neutralisation by IgM MAb 10F2, representing the minority population of dengue 2-specific IgM MAbs, had the same deduced amino acid change (G-S) at prM15 as the 6B2 neutralisation escape mutant dengue 2 virus population and four deduced amino acid changes in the E protein (E69, T-I, in the glycosylation motif; E71, E-D; E112, S-G; E124, I-N), which may be close enough to each other to form a single epitope and a fifth at E402 (F-L) in a region of the E protein of TBE virus essential for the low pH-induced E protein dimer-trimer transition. The 10F2 neutralisation escape mutant, but not the 6B2 one, had lost its ability to cause fusion from within Aedes albopictus mosquito cells and was inactivated more rapidly than the 6B2 neutralisation escape mutant and wild type viruses at 42 degrees C. Dengue 2 viruses passaged in BHK cells in the absence of a selecting antibody, shared a common amino acid (S) at E53, which differed from both wild type and neutralisation escape mutant virus populations at this position (P) and may have been responsible for a significant reduction in the ability of these "passage control" virus populations to be neutralised by both 6B2 and 10F2 antibodies.
In nature, animals are classified into two large groups. Those that form the prey and that form the predator. A prey animal runs for its life when chased by a predatory animal. When prey animals escape from the chasing enemy, they generally use two types of evasive motion. Those are a straight-line escape motion and a zigzag-line escape motion. A fleeing prey switches between two types of evasive behavior in a manner depending on the predator's performance.I propose a mathematical model that expresses behaviors between a prey and a predator. This model brings that a straight-line escape motion is a better solution for an escape from a slow and far predator. On the other hand, an evasive motion for a near or fast enemy is a zigzag-line escape motion. This model suggests that animals have the best evasive strategy.
The potential contribution of dorsal bundle norepinephrine (NE) in the induction of escape disturbances engendered by inescapable shock was evaluated following administration of the NE neurotoxin, DSP4. Treatment with DSP4 produced marked NE reductions in the hippocampus and cortex, a moderate reduction of NE in the locus coeruleus, but only small effects on hypothalamic NE. In contrast to the effect of inescapable shock, DSP4 was found not to influence escape behavior among naive mice or mice that had received inescapable shock. Moreover, DSP4 was without effect on escape performance irrespective of whether animals were individually or group housed, a treatment that has been shown to be sensitive to manipulations that influence escape performance. Treatment with DSP4 was found not to influence the escape interference ordinarily provoked by either haloperidol or alpha-MpT. Interestingly, the escape interference ordinarily engendered by the dopamine-beta-hydroxylase inhibitor, FLA-63, was eliminated among mice that had been pretreated with DSP4. The interference effect induced by inescapable shock is probably not attributable to NE alterations in the hippocampus and locus coeruleus. Serial or parallel effects of shock on more than a single transmitter system are likely to be responsible for the behavioral interference.
The transfer of organelle nucleic acid to the nucleus has been observed in both plants and animals. Using a unique assay to monitor mitochondrial DNA escape to the nucleus in the yeast Saccharomyces cerevisiae, we previously showed that mutations in several nuclear genes, collectively called yme mutants, cause a high rate of mitochondrial DNA escape to the nucleus. Here we demonstrate that mtDNA escape occurs via an intracellular mechanism that is dependent on the composition of the growth medium and the genetic state of the mitochondrial genome, and is independent of an RNA intermediate. Isolation of several unique second-site suppressors of the high rate of mitochondrial DNA-escape phenotype of yme mutants suggests that there are multiple independent pathways by which this nucleic acid transfer occurs. We also demonstrate that the presence of centromeric plasmids in the nucleus can reduce the perceived rate of DNA escape from the mitochondria. We propose that mitochondrial DNA-escape events are manifested as unstable nuclear plasmids that can interact with centromeric plasmids resulting in a decrease in the number of observed events.
In females, most genes on the inactive X Chromosome (Chr) are transcriptionally silenced. However, several dozen genes have been identified in human that escape inactivation and are expressed from both the active and inactive X Chrs. Many of the genes that escape inactivation in human are subject to inactivation in mouse, raising questions concerning the mechanisms that govern expression from the inactive X Chr in the two species. In human, the existence of a cluster of genes in Xp11.21-p11.22 that escape inactivation suggests that control of X inactivation occurs at the level of chromosomal domains. In this study, we have isolated, physically mapped, and determined the X inactivation status of a number of the orthologous mouse genes that correspond to this human "escape domain". In contrast to human, only the mouse Smcx gene has been found to escape inactivation in this region thus far, despite a highly conserved physical map between the two species. Sequence analysis and functional characterization of the mouse Smcx promoter did not reveal any obvious unique features that would explain the difference in the behavior of this gene on the inactive X compared with other nearby genes. Possible mechanisms responsible for the differing inactivation status between genes in the escape domain in human Xp11. 21-p11.22 and the corresponding mouse region are discussed.
Mass fractionation by hydrodynamic hydrogen escape is a promising mechanism for explaining the observed elemental and isotopic abundance patterns in terrestrial planet atmospheres. Previous work has considered only pure hydrogen winds. Here, the theory of mass fractionation by hydrogen escape is extended to atmospheres in which hydrogen is not the only major constituent. Analytical solutions are derived for cases in which all relevant atmospheric constituents escape; both analytical and numerical solutions are obtained for cases in which important heavy constituents are retained. In either case the fractionation patterns that result can differ significantly from those produced by pure hydrogen winds. Three applications of the theory are discussed: (1) The observed fractionation of terrestrial atmospheric neon with respect to mantle neon can be explained as a by-product of diffusion-limited hydrogen escape from a steam atmosphere toward the end of accretion. (2) The anomalously high Martian (SNC) 38Ar/36Ar ratio is attributed to hydrodynamic fractionation by a vigorously escaping, nearly pure hydrogen wind. (3) It is possible that the present high Martian D/H ratio was established during the same hydrodynamic escape phase that fractionated argon, but the predicted degree of D/H enrichment is sensitive to other, less well constrained parameters.
Blocking conduction between the sinus node and the atria (SA block) can be responsible for symptomatic rhythm problems. However, in atrial escape-capture bigeminy with SA block, when atrial escape P waves originate in a site within or close to the sinus node, the diagnosis of SA block is not easy. Electrocardiograms were selected from 7 people with atrial bigeminy because (1) all atrial deflections (P waves) were almost the same in shape and in length of PR intervals, (2) comparatively long PP intervals alternated with comparatively short PP intervals, and (3) occasionally the atrial bigeminy changed to normal regular sinus rhythm in which 2 or more sinus P waves were found in succession. An attempt is made to clarify the mechanism for these cases. When regular sinus rhythm changed to bigeminal rhythm, the long PP interval introduced the bigeminy in 3 cases, indicating the presence of "sinus" escape-capture bigeminy; whereas the short PP interval introduced the bigeminy in the other 4 cases, indicating the presence of "sinus" extrasystolic bigeminy. In cases of sinus escape-capture bigeminy associated with SA block, the cases may occasionally be diagnosed wrongly as ordinary sinus arrhythmia not associated with SA block. Therefore, it seems that sinus escape-capture bigeminy is not so rare as is generally believed. Patients with SA block often require implantation of the artificial pacemaker. Thus, the authors believe that differentiation of sinus escape-capture bigeminy from other forms of "sinus" bigeminy is clinically important.
Cytotoxic T lymphocytes (CTL) play a central role in containment of HIV infection. Evasion of the immune response by CTL escape is associated with progression to disease. It is therefore hypothesised that transmitted viruses encode escape mutations within epitopes that are required for successful control of viraemia. In order to test this hypothesis, escape through the dominant HLA-A2-restricted CTL epitope SLYNTVATL (p17 Gag residues 77-85 SL9) in the setting of mother-to-child-transmission (MTCT) was investigated. Initial data from two families in which the HIV-infected mother expressed HLA-A*0201 and had transmitted the virus to other family members were consistent with this hypothesis. In addition, analysis of the gag sequence phylogeny in one family demonstrated that CTL escape variants can be successfully transmitted both horizontally and vertically. To test the hypothesis further, a larger cohort of transmitting mothers (n=8) and non-transmitters (n=14) were studied. Variation within the SL9 epitope was associated with expression of HLA-A2 (P=0.04) but overall no clear link between variation from the SL9 consensus sequence and MTCT was established. However, the high level of background diversity within p17 Gag served to obscure any possible association between escape and MTCT. In conclusion, these studies highlighted the obstacles to demonstrating CTL escape arising at this particular epitope. Alternative strategies likely to be more definitive are discussed.
BACKGROUND/AIMS: Circulatory abnormalities with activation of vasoconstrictor systems after large-volume paracentesis are generally considered secondary to an increased extravasation of fluid from the intravascular compartment to the extravascular space with subsequent reduction in plasma volume. To test this hypothesis, plasma volume, the transvascular escape rate of albumin, the absolute escape rate of albumin and the activity of vasoconstrictor systems were measured in 25 cirrhotic patients with ascites in baseline conditions and 2 days after total paracentesis with plasma volume expansion. METHODS: Plasma volume and the transvascular escape rate of albumin, the fraction of albumin passing from the intravascular to the extravascular space per unit of time, were assessed through the plasma disappearance curve of radioiodinated human albumin. The absolute escape rate of albumin, the total flux of albumin from intravascular to extravascular space per unit of time, was also calculated. RESULTS: Eight of the 25 patients (32%) developed marked activation of vasoconstrictor systems after paracentesis. In these patients, plasma renin activity and plasma norepinephrine concentration increased from 6.6+/-2 to 23.4+/-11 ng x ml(-1) x h(-1) and 776+/-229 to 989+/-258 pg/ml, respectively (p<0.05). No significant changes in these parameters were found in the remaining 17 patients. The activation of vasoconstrictor systems occurred in the absence of changes in plasma volume (3456+/-276 vs 3476+/-264 ml, NS), transvascular escape rate of albumin (10.4+/-1 vs 10.9+/-2%/h, NS) and absolute escape rate of albumin (9.9+/-1.9 vs 10.5+/-0.7 g/h, NS). CONCLUSIONS: These results do not support a contraction of plasma volume as the mechanism responsible for activation of vasoconstrictor systems after paracentesis. Rather, the activation of vasoconstrictor systems in the absence of changes in plasma volume suggests that paracentesis accentuates the impairment of "effective" blood volume present in cirrhotic patients with ascites.
Aggression and stereotyped behaviors are not uncommon among people with intellectual disabilities and they are often treated separately as operant behaviors. In this single case study, it is argued that the function of a young woman's aggressive behavior appeared to be that of avoiding or escaping the termination of a chain of complex stereotyped behavior (or "ritual"). She became aggressive only when this chain of stereotyped behavior was terminated and the aggression appeared to extinguish when it no longer led to escape from the termination of the "ritual". It is suggested that this is an example of a complex interaction between two behaviors and that it illustrates the need for very careful analysis of the functions of challenging behavior. Furthermore, it is proposed that the lengthening list of variables already documented as determinants of challenging behavior (provision of attention (verbal and physical), mechanical restraint, sensory or tangible events, escape from demands or from social attention, denials, escape from intrusive medical procedures, escape from task difficulty) be lengthened to include the possibility of escape from (or avoidance of) the interruption of a chain of complex stereotyped behavior or "ritual".
BACKGROUND: The study tests the hypothesis that ablating all inputs to the atrioventricular (AV) node can result in complete heart block with stable junctional escape rhythm. METHODS AND RESULTS: We attempted atrionodal input ablation in 76 consecutive patients with uncontrolled atrial fibrillation. Fast and slow pathways were first ablated. If there was no AV block, additional energy applications were done between fast and slow pathway locations. The patients were followed for 42 +/- 11 months. Group I (n = 57) comprised patients with complete heart block and junctional escape rhythm (53 +/- 4 beats/min) at the end of the procedure. The escape rhythm remained stable throughout follow-up. Group II (n = 15) were patients who failed the stepwise atrionodal input ablation and required AV junctional ablation guided by His bundle potential to achieve complete heart block. Four patients showed a slow escape rhythm after ablation (33 +/- 4 beats/min). Others had no escape rhythm. All 15 pts remained pacemaker dependent. The total death rate of groups I and II was 18/57 (31.6%) vs 10/15 (66.7%), respectively (p < 0.02). These differences could not be explained by a difference of left ventricular ejection fraction (0.42 +/- 0.07 vs 0.41 +/- 0.04, respectively, p = NS). CONCLUSIONS: (1) In most patients, ablation of both fast and slow pathways did not result in complete heart block, indicating the presence of multiple atrionodal inputs. (2) Ablation of all atrionodal inputs may result in complete heart block with stable junctional escape rhythm. (3) As compared with AV junctional ablation, atrionodal input ablation was associated with a lower mortality rate on long-term follow up.
Cytotoxic T-lymphocyte (CTL) responses peak coincident with the decline in acute HIV viremia. Despite two reports of CTL-resistant HIV variants emerging during acute infection, the contribution of acute CTL escape to HIV pathogenesis remains unclear. Difficulties inherent in studying acute HIV infection can be overcome by modeling virus-host interactions in SIV-infected rhesus macaques. We sequenced 21 complete simian immunodeficiency virus (SIV)mac239 genomes at four weeks post-infection to determine the extent of acute CTL escape. Here we show that viruses from 19 of 21 macaques escaped from CTLs during acute infection and that these escape-selecting CTLs were responsive to lower concentrations of peptide than other SIV-specific CTLs. Interestingly, CTLs that require low peptide concentrations for stimulation (high 'functional avidity') are particularly effective at controlling other viral infections. Our results suggest that acute viral escape from CTLs is a hallmark of SIV infection and that CTLs with high functional avidity can rapidly select for escape variants.