Adaptive Escape Research Articles

Mouse Escape Behaviors and mPFC-BLA Activity Dataset: Understanding Flexible Defensive Strategies Under Threat

Responding to threats in the real world demands a sophisticated orchestration of freeze and flight behaviors dynamically modulated by the neural activity. While the medial prefrontal cortex-basolateral amygdala (mPFC-BLA) network is known to play a pivotal role in coordinating these responses, the mechanisms underlying its population dynamics remain vague. As traditional Pavlovian fear conditioning models fall short in encapsulating the breadth of natural escape behaviors, we introduce a novel dataset to bridge this gap, capturing the defensive strategies of mice against a spider robot in a natural-like environment. The adaptive escape behaviors and concurrent mPFC-BLA activity in eight mice were monitored using wireless local field potential (LFP) and video recordings, both individually and in groups. Our data offers a unique avenue to explore the neural dynamics that govern fear- and vigilance-induced threat responses in isolated and social contexts. Supplemented by detailed methodologies and validation, the dataset allows for the analysis of the transient neural oscillatory dynamics, with prospective implications for the fields of neuroscience, robotics, and artificial intelligence.

Adaptive Escape of Pseudomonas aeruginosa by Application of Low-Amplitude Electric Pulses.

Marine antibiofouling using low-amplitude electric pulses (EP) is an energy-efficient and eco-friendly approach, but potential mechanisms for preventing biofouling remain unclear. In the present study, the 3D adhesion dynamics of a model microorganism─Pseudomonas aeruginosa (PAO1)─under low-amplitude cathodic EP were examined as a function of applying voltage and its duration (td). The results demonstrated that adhered bacteria escaped from the electrode surface even when EP was removed. The escaped bacteria ratio, induction period of escape, and duration of the detachment were influenced profoundly by EP amplitude but slightly by td when td ≥ 5 min. The acceleration of escaped PAO1 from the surface indicated that their flagellar motor was powered by EP. Particularly, EP enabled swimming bacteria to have adaptive motions that were sustainable and regulated by the gene rsmA. As a result, they had less accumulation near the surface. The propulsion of adhered bacteria and adaptive escape of swimming bacteria were enhanced in response to low-amplitude EP. Hence, low-amplitude and short-duration EP is promising for sustainable antibiofouling applications.

Action selection based on multiple-stimulus aspects in wind-elicited escape behavior of crickets

Escape behavior is essential for animals to avoid attacks by predators. In some species, multiple escape responses could be employed. However, it remains unknown what aspects of threat stimuli affect the choice of an escape response. We focused on two distinct escape responses (running and jumping) to short airflow in crickets and examined the effects of multiple stimulus aspects including the angle, velocity, and duration on the choice between these responses. The faster and longer the airflow, the more frequently the crickets jumped. This meant that the choice of an escape response depends on both the velocity and duration of the stimulus and suggests that the neural basis for choosing an escape response includes the integration process of multiple stimulus parameters. In addition, the moving speed and distance changed depending on the stimulus velocity and duration for running but not for jumping. Running away would be more adaptive escape behavior.

Why Do Birds False Alarm Flight?

False alarm flighting in avian flocks is common, and has been explained as a maladaptive information cascade. If false alarm flighting is maladaptive per se, then its frequency can only be explained by it being net adaptive in relation to some other benefit or equilibrium. However, I argue that natural selection cannot distinguish between false and true alarm flights that have similar energetic costs, opportunity costs, and outcomes. False alarm flighting cannot be maladaptive if natural selection cannot perceive the difference between true and false alarm flighting. Rather, the question to answer is what false and true alarm flighting both have in common that is adaptive per se. The fire drill hypothesis of alarm flighting posits that false alarm flights are an adaptive investment in practicing escape. The fire drill hypothesis predicts that all individuals can benefit from practicing escape, particularly juveniles. Flighting practice could improve recognition of and response time to alarm flighting signals, could compensate for inter-individual and within-day weight differences, and could aid the development of adaptive escape tactics. Mixed-age flocks with many juveniles are expected to false alarm flight more than adult flocks. Flocks that inhabit complex terrain should gain less from escape practice and should false alarm flight less. Behavioural ecology framings can be fruitfully complemented by other research traditions of learning and behaviour that are more focused on maturation and motor learning processes.

On the rising incidence of early breast development: puberty as an adaptive escape from ectopic adiposity in mismatch girls

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Abstract 134: Targeting NLMP prevents drug adaptive prostate cancer evolution

Tumour necrosis factor (TNF) is synthesized initially as a membrane-bound precursor which is then cleaved to yield soluble, mature protein. The 26,000 MW TNF precursor isolated from the lysate of activated RAW 264.7 (mouse macrophage) cells by immunoprecipitation was used to identify pro-TNF cleavage enzyme in the same cells. A significant amount of mature protein was formed in samples containing Nonidet P-40 (NP-40)-lysed cells, whereas sonicated cells showed negligible activity. Most of the cleavage activity in macrophages was localized in the membrane/particulate fraction and remained largely insoluble after sonication or treatment with 2 mM EDTA/1 M NaCl, indicating that the enzyme is associated with the membrane/particulate fraction. The crude cleavage activity in membrane/particulate was partially inhibited by a spectrum of serine, cysteine and aspartate proteinase inhibitors, whereas secretion of TNF from activated macrophages was inhibited exclusively by serine and serine/cysteine proteinase inhibitors. This result suggested that, among heterogenous pro-TNF cleavage activities, the enzyme responsible for the processing of TNF is a serine proteinase. Pro-TNF cleavage activity was present in non-stimulated macrophages and decreased significantly 8 hr after lipopolysaccharide (LPS) stimulation, suggesting that it is negatively regulated after an initial burst of TNF synthesis.

Correcting for Population Stratification Reduces False Positive and False Negative Results in Joint Analyses of Host and Pathogen Genomes.

Studies of host genetic determinants of pathogen sequence variations can identify sites of genomic conflicts, by highlighting variants that are implicated in immune response on the host side and adaptive escape on the pathogen side. However, systematic genetic differences in host and pathogen populations can lead to inflated type I (false positive) and type II (false negative) error rates in genome-wide association analyses. Here, we demonstrate through a simulation that correcting for both host and pathogen stratification reduces spurious signals and increases power to detect real associations in a variety of tested scenarios. We confirm the validity of the simulations by showing comparable results in an analysis of paired human and HIV genomes.

How cognitive and reactive fear circuits optimize escape decisions in humans

Flight initiation distance (FID), the distance at which an organism flees from an approaching threat, is an ecological metric of cost-benefit functions of escape decisions. We adapted the FID paradigm to investigate how fast- or slow-attacking "virtual predators" constrain escape decisions. We show that rapid escape decisions rely on "reactive fear" circuits in the periaqueductal gray and midcingulate cortex (MCC), while protracted escape decisions, defined by larger buffer zones, were associated with "cognitive fear" circuits, which include posterior cingulate cortex, hippocampus, and the ventromedial prefrontal cortex, circuits implicated in more complex information processing, cognitive avoidance strategies, and behavioral flexibility. Using a Bayesian decision-making model, we further show that optimization of escape decisions under rapid flight were localized to the MCC, a region involved in adaptive motor control, while the hippocampus is implicated in optimizing decisions that update and control slower escape initiation. These results demonstrate an unexplored link between defensive survival circuits and their role in adaptive escape decisions.

Parallel In Vivo Assessment of Drug Phenotypes at Various Time Points during Systemic BRAF Inhibition Reveals Tumor Adaptation and Altered Treatment Vulnerabilities.

Treatment of BRAF-mutated melanoma tumors with BRAF inhibitor-based therapy produces high response rates, but of limited duration in the vast majority of patients. Published investigations of resistance mechanisms suggest numerous examples of tumor adaptation and signal transduction bypass mechanisms, but without insight into biomarkers that would predict which mechanism will predominate. Monitoring phenotypic response of multiple adaptive mechanisms simultaneously within the same tumor as it adapts during treatment has been elusive. This study reports on a method to provide a more complete understanding of adaptive tumor responses. We simultaneously measured in vivo antitumor activity of 12 classes of inhibitors, which are suspected of enabling adaptive escape mechanisms, at various time points during systemic BRAF inhibition. We used implantable microdevices to release multiple compounds into distinct regions of a tumor to measure the efficacy of each compound independently and repeated these measurements as tumors progressed on systemic BRAF treatment. We observed varying phenotypic responses to specific inhibitors before, during, and after prolonged systemic treatment with BRAF inhibitors. Our results specifically identify PI3K, PDGFR, EGFR, and HDAC inhibitors as becoming significantly more efficacious during systemic BRAF inhibition. The sensitivity to other targeted inhibitors remained mostly unchanged, whereas local incremental sensitivity to PLX4720 declined sharply. These findings suggest redundancy of several resistance mechanisms and may help identify optimal constituents of more effective combination therapy in BRAF-mutant melanoma. They also represent a new paradigm for dynamic measurement of adaptive signaling mechanisms within the same tumor during therapy. Clin Cancer Res; 22(24); 6031-8. ©2016 AACR.

The Influence of subway climatology on gas dispersion and the effectiveness of guided evacuations in a complex subway station

This paper discusses a strategy that integrates data from tracer gas experiments with results from pedestrian simulation software in the evaluation of different evacuation procedures for subway stations in response to a fire or a terrorist attack with chemical, biological, radiological, nuclear and enhanced conventional weapons (CBRNE). The study demonstrates that by combining the two data sets a greater understanding of the impact of different evacuations routes on an evacuee’s health is gained. It is shown that by controlling the routes pedestrians would use to exit a subway station, the number of fatalities and evacuees with long term health issues can be reduced. It is highlighted that a dynamic evacuation guiding system based on subway climatology would take into account the source of the toxin, the resulting dispersal of gas, smoke, etc. and the subway climatology at the time. In doing so, it would be possible to identify the most endangered areas and guide passengers via an adaptive escape route using audio and visual techniques. Information on the evolution of the emergency situation could also simultaneously be relayed back to the rescue forces to help to plan the rescue and evacuation procedures and optimise the deployment of the search and rescue teams.

Abstract 3718: Adaptive drug escape of EML4-ALK lung cancer against targeted ALK inhibitor involving TGFβ2-mitochondrial priming

Abstract Lung cancer is the second most common malignancy with the highest cancer-mortality rate. EML4-ALK chromosomal translocation is now known to represent a highly actionable unique molecular target in approximately 5% of non-small cell lung cancer (NSCLC) patients. The ALK tyrosine kinase inhibitor (TKI) crizotinib induces remarkably high response rates in molecularly-selected NSCLC patients harboring EML4-ALK driven tumors, and is being used in first-line therapy. Nonetheless, responsive tumors ultimately develop acquired drug resistance. We have recently investigated non-mutational mechanisms of tumor resistant escape emerging under early TKI treatment time-window. Our recent studies in EGFR-mutant NSCLC in early adaptive drug escape against EGFR TKI identified an autocrine upregulation of TGFβ2 within these survivor cells. Here, we found that TGFβ2 was elevated significantly in the EML4-ALK-driven H3122 cells undergoing early adaptive drug escape against ALK TKI (TAE684) at treatment day 14. Interestingly, we found that the augmented TGFβ signaling was specific to TGFβ2, but not TGFβ1 or TGFβ3. We also found correlative enhanced mitochondrial BCL-2/BCL-xL prosurvival signaling in the day 14 TKI surviving H3122 cells. The upregulated TGFβ2-BCL-2/BCL-xL prosurvival mitochondrial priming was further validated in H3122 xenografts by IHC. Exogenous TGFβ2 stimulation in vitro for 7 days induced a dose-dependent upregulated BCL-2 and BCL-xL expression. Inhibiting mitochondrial BCL-2/BCL-xL priming using dual BCL-2/BCL-xL inhibitor ABT-263 as BH3-mimetic led to significant reduction in early adaptive drug escape induced by ALK TKIs. Our study showed that EML4-ALK NSCLC could escape ALK TKI early in treatment through cell plasticity that involved TGFβ2-mitochondrial priming in an upregulated prosurvival state. We also found that the early adaptive drug-escaping cancer cells possessed inherently increased EMT-ness (upregulated vimentin, AXL, GAS6) and cancer stemness (upregulated OCT4, NANOG). These findings provide deeper insights into the process of drug resistance emergence and highlighted potential window-of-opportunities to therapeutically target early adaptive escape to eradicate targeted drug resistance and impact long term survival. Citation Format: Lihong Yin, Wei Zhang, Ivy Shi, Yan Feng, Rakesh Bagai, Daniel Lindner, Patrick C. Ma. Adaptive drug escape of EML4-ALK lung cancer against targeted ALK inhibitor involving TGFβ2-mitochondrial priming. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3718. doi:10.1158/1538-7445.AM2014-3718

Adaptive cell plasticity in autocrine TGFβ2 coordinated transcriptome-metabolome reprogramming of EGFR-mutant lung cancer in precision therapy escape.

e19043 Background: Precision therapy for advanced NSCLC with EGFR mutations is the current standard-of-care. Emergence of acquired resistance to therapy invariably occurs despite effective initial response. Classical rebiopsy studies of EGFR-mutant pts at progression have identified diverse resistance mechanisms involving T790M-EGFR, METactivation and AXL upregulation. Our studies focus on tumor cells adaptation early during therapy to map the initial course of therapeutic resistance evolution. Methods: Drug-sensitive model studies were performed usingHCC827 and PC-9 NSCLC cells under erlotinib, and H1975 cells under CL-387,785 inhibition. Affymetrix microarray profiling was performed at 0h, 8h, 9d and 9d TKI followed by 7d drug-washout. Both in vitro and in vivo xenograft analyses were conducted. Mass-spectrometry based metabolomics profiling was also conducted. Results: We identified an early adaptive drug escape in EGFR-mutant cells that emerged as early as 9 days on therapy. The prosurvival cell state...

Particle swarm optimization algorithm with fast convergence and adaptive escape

In order to overcome the drawbacks of Particle Swarm Optimization(PSO) that converges slowly at the last stage and easily falls into local minima,this paper proposed a new PSO algorithm with convergence acceleration and adaptive escape(FAPSO) inspired by the Artificial Bee Colony(ABC) algorithm.For each particle,FAPSO conducted two search operations.One was global search and the other was local search.When a particle got stuck,the adaptive escape operator was used to search the particle again.Experiments were conducted on eight classical benchmark functions.The simulation results demonstrate that the proposed approach improves the convergence rate and solution accuracy,when compared with some recently proposed PSO versions,such as CLPSO.Besides,the results of t-test show clear superiority.

Targeting the Insulin Growth Factor and the Vascular Endothelial Growth Factor Pathways in Ovarian Cancer

Antiangiogenic therapy is emerging as a highly promising strategy for the treatment of ovarian cancer, but the clinical benefits are usually transitory. The purpose of this study was to identify and target alternative angiogenic pathways that are upregulated in ovarian xenografts during treatment with bevacizumab. For this, angiogenesis-focused gene expression arrays were used to measure gene expression levels in SKOV3 and A2780 serous ovarian xenografts treated with bevacizumab or control. Reverse transcription-PCR was used for results validation. The insulin growth factor 1 (IGF-1) was found upregulated in tumor and stromal cells in the two ovarian xenograft models treated with bevacizumab. Cixutumumab was used to block IGF-1 signaling in vivo. Dual anti-VEGF and IGF blockade with bevacizumab and cixutumumab resulted in increased inhibition of tumor growth. Immunohistochemistry measured multivessel density, Akt activation, and cell proliferation, whereas terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay measured apoptosis in ovarian cancer xenografts. Bevacizumab and cixutumumab combination increased tumor cell apoptosis in vivo compared with therapy targeting either individual pathway. The combination blocked angiogenesis and cell proliferation but not more significantly than each antibody alone. In summary, IGF-1 activation represents an important mechanism of adaptive escape during anti-VEGF therapy in ovarian cancer. This study provides the rationale for designing bevacizumab-based combination regimens to enhance antitumor activity.

Frequency-dependent selection by tree squirrels: adaptive escape of nondormant white oaks

Frequency-dependent selection is theoretically predicted to have an important impact on predator–prey dynamics, but little is understood about this process in nature. We investigated oak–squirrel interactions to test the hypothesis that tree squirrels predate/disperse white oak acorns based on the frequency of their germination phenotypes (dormancy, i.e., delayed germination vs. nondormancy, i.e., immediately germinating), which in turn influences dispersal and establishment of these oaks. In Central China, we manipulated the relative frequency of dormant and nondormant acorns available to Père David's Rock squirrel (Sciurotamias davidianus) with 2 white oaks (QAA, Quercus aliena var. acutesevata and QSB, Quercus serrata var. breviptiolata) that exhibit considerable variation in acorn germination between and within oak species throughout the fruiting season. We predicted that dispersal success (i.e., the probability of a viable acorn being hoarded) of each germination phenotype would vary with the phenotype frequency and hence show either positive or negative frequency-dependent selection. We found that acorn-embryo removal by squirrels may select for the dormant phenotype but is more likely to occur for early germinating acorns. We also found that both absolute and relative dispersal success of each germination phenotype increased with their frequency in the 2 white oaks, thus demonstrating positive frequency-dependent selection. Our results reveal that the frequency of germination phenotypes can account for as much as 40.5% and 21.4% of the observed dispersal success in QAA and QSB, respectively. We show that behavioral preferences of scatter-hoarding animals could result in frequency-dependent selection in nature, and such selection may help maintain variation in germination phenotypes in prey species.

Fecundity increase supports adaptive radiation hypothesis in spider web evolution

Identifying the mechanisms driving adaptive radiations is key to explaining the diversity of life. The extreme reliance of spiders upon silk for survival provides an exceptional system in which to link patterns of diversification to adaptive changes in silk use. Most of the world’s 41,000 species of spiders belong to two apical lineages of spiders that exhibit quite different silk ecologies, distinct from their ancestors. Orb spiders spin highly stereotyped webs that are suspended in air and utilize a chemical glue to make them adhesive. RTA clade spiders mostly abandoned silk capture webs altogether. We recently proposed that these two clades present very different evolutionary routes of achieving the same key innovation – escape from the constraints imposed by spinning webs that contain a relatively costly type of physically adhesive cribellate silk. Here, we test the prediction that orb and RTA clade spiders are not only more diverse, but also have higher fecundity than other spiders. We show that RTA clade spiders average 23% higher fecundity and orb spiders average 123% higher fecundity than their ancestors. This supports a functional link between the adaptive escape from cribellate silk and increased resource allocation to reproduction in spiders.

Tentacled snakes turn C-starts to their advantage and predict future prey behavior

Fish are elusive prey with a short-latency escape behavior--the C-start--initiated to either the left or right by a "race" between 2 giant Mauthner neurons in the fish brainstem. Water disturbances usually excite the ipsilateral neuron, which massively excites contralateral motor neurons, resulting in a rapid turn away from striking predators. Here, it is reported that tentacled snakes (Erpeton tentaculatus) exploit this normally adaptive circuitry by feinting with their body, triggering the Mauthner cell that is furthest from their head milliseconds before a ballistic strike is initiated. As a result, fish that were oriented parallel to the long axis of the snake's head most often turned toward the approaching jaws, sometimes swimming directly into the snake's mouth. When strikes were instead directed at fish oriented at a right angle to the snake's head, snakes anticipated future fish behavior by striking to where fish would later be if they escaped from the snake's body feint, which fish usually did. The results provide an example of a rare predator taking advantage of a prey's normally adaptive escape circuitry and suggest that the snake's sensory-motor system is adapted to predict future behavior.

Reliance on God's Help, Depression and Fatigue in Female Cancer Patients

Because an increasing number of studies indicate that a religious attitude is associated with lower depression, we intended to investigate the interrelationship between intrinsic religiosity and depressive behavioral symptoms in cancer patients with long-term courses. In 396 female cancer patients recruited in East-Germany, intrinsic religiosity was measured with the scale Reliance on God's Help (RGH) from the AKU questionnaire; anxiety and depression with the Hospital Anxiety and Depression Scale; fatigue with the cancer fatigue scale (CFS-D); physical and mental health with the SF-12; adaptive coping styles and ESCAPE from illness with the AKU; and life satisfaction with a modification of Huebner's Brief Multidimensional Students' Life Satisfaction Scale. Moderate depression-associated fatigue was prevalent in cancer patients with long term-cancer courses, while depression and anxiety were of minor prevalence. RGH, which was valued by several patients, correlated with Reappraisal: Illness as Chance; with life satisfaction dimensions such as future perspectives, overall life, and financial situation; to a small extend with Escape from Illness; and negatively with mental health. No significant correlations were found with respect to depression, anxiety, or fatigue. In contrast to cancer patients in final stages, cancer patients with long-term courses had just a moderate reliance on external divine powers. The addressed depressive behavioral symptoms were connected with internal adaptive coping styles such as Conscious Living/Positive Attitudes rather than intrinsic religiosity in response to disease.

Jumping behaviour in a Gondwanan relict insect (Hemiptera: Coleorrhyncha:Peloridiidae)

Jumping by a relict insect, Hackeriella veitchi (Hacker 1932), belonging to the ancient Coleorrhynchan line that diverged from other Hemiptera in the late Permian, was analysed from high-speed images captured at rates of 2000 s(-1) and from its anatomy. This 3 mm long, flightless insect weighs up to 1.4 mg and can jump by rapid movements of the hind legs that accelerate the body in 1.5 ms to a take-off velocity of 1.5 m s(-1). This performance requires an energy expenditure of 1.1 microJ and a power output 0.74 mW, and exerts a force of 1.24 mN. It achieves this with a body design that shows few specialisations for jumping compared with those of other groups of Hemipterans such as the froghoppers or leafhoppers. The hind legs are only 10% longer than the front and middle legs by virtue of longer tibiae and tarsi, and are only 65% the length of the body. The main thrust for a jump is provided by the rapid rotation of the fused trochanter and femur about the coxa of a hind leg, in a movement that forces the hind tarsus against the ground and raises the body to take off. In some jumps the two hind legs move together, but in others the movements may not be closely synchronised, thereby imparting a rotation on the body that is maintained once airborne. When the time difference is larger, the rapid movement of just one hind leg results in the insect falling from its perch in an adaptive escape response.

Avoiding predators at night: antipredator strategies in red‐tailed sportive lemurs (Lepilemur ruficaudatus)

Although about one-third of all primate species are nocturnal, their antipredator behavior has rarely been studied directly. Crypsis and a solitary lifestyle have traditionally been considered to be the main adaptive antipredator strategies of nocturnal primates. However, a number of recent studies have revealed that nocturnal primates are not as cryptic and solitary as previously suggested. Thus, the antipredator strategies available for diurnal primates that rely on early detection and warning of approaching predators may also be available to nocturnal species. In order to shed additional light on the antipredator strategies of nocturnal primates, I studied pair-living red-tailed sportive lemurs (Lepilemur ruficaudatus) in Western Madagascar. In an experimental field study I exposed adult sportive lemurs that lived in pairs and had offspring to playbacks of vocalizations of their main aerial and terrestrial predators, as well as to their own mobbing calls (barks) given in response to disturbances at their tree holes. I documented the subjects' immediate behavioral responses, including alarm calls, during the first minute following a playback. The sportive lemurs did not give alarm calls in response to predator call playbacks or to playbacks with barks. Other behavioral responses, such as gaze and escape directions, corresponded to the hunting strategies of the two classes of predators, suggesting that the corresponding vocalizations were correctly categorized. In response to barks, they scanned the ground and fled. Because barks do not indicate any specific threats, they are presumably general alarm calls. Thus, sportive lemurs do not rely on early warning of acoustically simulated predators; rather, they show adaptive escape strategies and use general alarm calls that are primarily directed toward the predator but may also serve to warn kin and pair-partners.