Defensive Escape Research Articles

Characterization of novel recombinant mycobacteriophages derived from homologous recombination between two temperate phages.

Comparative analyses of mycobacteriophage genomes reveals extensive genetic diversity in genome organization and gene content, contributing to widespread mosaicism. We previously reported that the prophage of mycobacteriophage Butters (cluster N) provides defense against infection by Island3 (subcluster I1). To explore the anti-Island3 defense mechanism, we attempted to isolate Island3 defense escape mutants on a Butters lysogen, but only uncovered phages with recombinant genomes comprised of regions of Butters and Island3 arranged from left arm to right arm as Butters-Island3-Butters (BIBs). Recombination occurs within two distinct homologous regions that encompass lysin A, lysin B, and holin genes in one segment, and RecE and RecT genes in the other. Structural genes of mosaic BIB genomes are contributed by Butters while the immunity cassette is derived from Island3. Consequently, BIBs are morphologically identical to Butters (as shown by transmission electron microscopy) but are homoimmune with Island3. Recombinant phages overcome antiphage defense and silencing of the lytic cycle. We leverage this observation to propose a stratagem to generate novel phages for potential therapeutic use.

A Psychoanalytic Lens: Unmasked Layers of the Self among Post-Graduate Psychology Students in Surviving the COVID-19 Lockdown

The World Health Organisation (WHO) classified the Sars-Cov-2, also identified as COVID-19, as a pandemic on the 12th of March 2020 (Qiu et al., 2020), with South Africa recording its first case on the 5th of March 2020. The rapidly spreading virus led the South African government to implement one of the strictest, nationwide lockdowns globally, resulting in the closing down of all institutions of higher learning effective March 18th 2020. Thus, this qualitative study primarily aimed to explore whether post-graduate psychology students were in a state of a depleted or cohesive self, post the psychological isolation of COVID-19 risk-adjusted level 5 lockdown. Semi-structured interviews from a qualitative interpretive approach comprising N = 6 psychology post-graduate students, facilitated a rich understanding of their intra-psychic experiences of the self. Thematic analysis of data gathered from the interviews illuminated how students were forced into the self by the emotional isolation of hard lockdown, with the emergence of core psychic conflict often defended against, through external self-object experiences. The findings also suggest that lockdown stripped off this sample of psychology post-graduate students’ defensive escape from the inner self through external self-object distractions. The external self was stripped to the core of the internal self by the isolation of hard lockdown, thereby uncovering the psychic function of roles and defenses amalgamated throughout modern cultural consciousness that dictate self-functioning. The study suggests modelling reflexivity skills in the integration of internal and external self-experience dynamics as part of a training model for continued personal and professional development for psychology students.

Cerebellar contribution to threat probability in a SCA6 mouse model.

Fear and anxiety have proven to be essential during the evolutionary process. However, the mechanisms involved in recognizing and categorizing threat probability (i.e. low to high) to elicit the appropriate defensive behavior are yet to be determined. In this study, we investigated the cerebellar contribution in evoking appropriate defensive escape behavior using a purely cerebellar, neurodegenerative mouse model for spinocerebellar ataxia type 6 which is caused by an expanded CAG repeat in exon 47 of the P/Q type calcium channel α1A subunit. These mice overexpress the carboxy terminus (CT) of the P/Q type calcium channel containing an expanded 27 CAG repeat specifically in cerebellar Purkinje cells (CT-longQ27PC). We found that our CT-longQ27PC mice exhibit anxiolytic behavior in the open field, elevated plus maze and light/dark place preference tests, which could be recovered with more threatening conditions such as brighter lighting, meowing sounds and an ultrasound repellent. Their innate fear to find safety in the Barnes maze and visual cliff tests was also diminished with subsequent trials, which could be partially recovered with an ultrasound repellent in the Barnes maze. However, under higher threat conditions such as in the light/dark place preference with ultrasound repellent and in the looming tests, CT-longQ27PC mice responded with higher defensive escape behaviors as controls. Moreover, CT-longQ27PC mice displayed increased levels of CT-labeled aggregates compared with controls. Together these data suggest that cerebellar degeneration by overexpression of CT-longQ27PC is sufficient to impair defensive escape responses in those mice.

Increased body sway in phobic patients exposed to images of spiders.

Objective:The aim of the present study was to analyze the body sway response in specific phobia (SP) patients and healthy controls while viewing neutral, phobic, and disgusting images.Methods:The participants’ heart rate (HR) and skin conductance were also recorded during the procedure. Nineteen patients with arachnophobia and 19 healthy volunteers matched by age, gender, and years of education underwent a postural control test on a stabilometric platform.Results:The platform recorded increased body sway in the SP group when exposed to spider images (SPI). The SP group presented increases in most parameters (SD, velocity, frequency, area, p ≤ 0.05) when viewing pictures of the SPI category. Psychometric measures of subjective anxiety (State-Trait Anxiety Inventory, STAI) and physiological states (HR; skin conductance responses; spontaneous fluctuations in skin conductance) showed increased anxiety (p ≤ 0.05) in the SP group compared to healthy volunteers. High anxiety levels were observed throughout the assessment, including the task of exposure to SPI (p ≤ 0.05). No significant effect or correlation was found between skin conductance and body sway measures (p > 0.05).Conclusions:The results of the postural control test suggest the occurrence of a defensive escape response in SP, in agreement with previous evidence.

Involvement of Mechanosensory Complex Structures of the Cricket Gryllus bimaculatus Larvae (Orthoptera, Gryllidae) in Triggering of Motor Responses to Sound

Using an ethological approach, we studied the possibility of sound perception as well as probable contribution of diverse mechanosensory systems composing the mechanosensory complex to triggering of motor responses to sound stimulation in the cricket Gryllus bimaculatus larvae. It was shown that larvae can perceive sounds and respond to them by a locomotor reaction in a relatively broad frequency range, which becomes narrower as sound intensity decreases [0.1–6.6 kHz (111 ± 3 dB SPL), 0.1–1.4 kHz (101 ± 3 dB SPL), 0.1–0.8 kHz (91 ± 3 dB SPL]. Sound perception and triggering of motor responses appear to involve the cercal organs (CO), subgenual organs (SO) and, probably, other distant mechanosensory organs (DMO). Normal functioning of CO is essential for triggering locomotor responses to sound within the ranges of 1–1.4 kHz (101 ± 3 dB SPL) and 0.1–0.8 kHz (91 ± 3 dB SPL). CO are not necessary for triggering of motor responses to cues with an intensity of 111 ± 3 dB. SO and, probably, other DMO provide locomotor responses to sound within the ranges of 0.1–6.6 kHz (111 ± 3 dB SPL), 0.1–0.9 kHz (101 ± 3 dB SPL), and 0.1–0.3 kHz (91 ± 3 dB SPL). Thus, last instar larvae of G. bimaculatus lacking the tympanal organs can perceive sounds using CO, SO and, probably, other DMO, which (as in cricket imagoes) are likely to compose an integrated mechanosensory complex providing adequate acoustic behavior of this cricket species. Performance efficiency and sensitivity of the mechanosensory complex (specifically, CO) rely on the thoroughness of grooming. After self-cleaning of CO, the level of larval motor activity in response to cue presentation returned to the baseline and sometimes even increased. We assume that under normal conditions the mechanosensory complex, which triggers motor responses to a sound, is involved in the defensive escape response aimed at rescuing from predators.

Involvement of the mechanosensory complex structures of the cricket Phaeophilacris bredoides in triggering of motor responses to sound

Using an ethological approach, we studied the possibility of sound perception as well as probable contribution of diverse mechanosensory systems composing the mechanosensory complex to triggering of motor responses to sound stimulation in imaginal crickets Phaeophilacris bredoides lacking the tympanal organs (“deaf”). It was shown that Ph. bredoides imagoes are able to perceive sounds and respond to sound cues by a locomotor reaction in a relatively broad frequency range which becomes narrower as sound intensity decreases [0.1–6.0 kHz (111 ± 3 dB SPL), 0.1–1.5 kHz (101 ± 3 dB SPL), 0.1–1.3 kHz (91 ± 3 dB SPL), 0.1–0.6 kHz (81 ± 3 dB SPL), and 0.1 kHz (71 ± 3 dB SPL)]. Sound perception and triggering ofmotor responses appear to involve the cercal organs (CO), subgenual organs (SO) and, probably, other distant mechanosensory organs (DMO). CO are essential for triggering of locomotor responses to sound within the ranges of 1.6–6.0 kHz (111 ± 3 dB SPL), 1–1.5 kHz (101 ± 3 dB SPL), 0.9–1.3 kHz (91 ± 3 dB SPL), and 0.5–0.6 kHz (81 ± 3 dB SPL). SO and, probably, other DMO provide locomotor responses to sound within the ranges of 0.1–6.0 kHz (111 ± 3 dB SPL), 0.1–0.8 kHz (101 ± 3 dB SPL), 0.1–0.4 kHz (91 ± 3 dB SPL), and 0.1–0.4 kHz (81 ± 3 dB SPL). From this, it follows that “deaf” (nonsinging) Ph. bredoides can perceive sounds using CO, SO and, probably, other DMO, which (as in singing crickets) are likely to compose an integrated mechanosensory complex providing adequate acoustic behavior of this cricket species. Performance efficiency and sensitivity of the mechanosensory complex (specifically, of CO) rely on the thoroughness of grooming. Following self-cleaning of CO, the level of cricket motor activity in response to cue presentation returned to the baseline and sometimes even increased. Whether or not crickets of this species communicate acoustically is yet to be found out, however, we suggest that the mechanosensory complex, which triggers motor responses to a sound, is normally involved in the defensive escape response aimed at rescuing from predators.

Independent Regulation of Type VI Secretion in Vibrio cholerae by TfoX and TfoY.

SummaryType VI secretion systems (T6SSs) are nanomachines used for interbacterial killing and intoxication of eukaryotes. Although Vibrio cholerae is a model organism for structural studies on T6SSs, the underlying regulatory network is less understood. A recent study showed that the T6SS is part of the natural competence regulon in V. cholerae and is activated by the regulator TfoX. Here, we identify the TfoX homolog TfoY as a second activator of the T6SS. Importantly, despite inducing the same T6SS core machinery, the overall regulons differ significantly for TfoX and TfoY. We show that TfoY does not contribute to competence induction. Instead, TfoY drives the production of T6SS-dependent and T6SS-independent toxins, together with an increased motility phenotype. Hence, we conclude that V. cholerae uses its sole T6SS in response to diverse cues and for distinctive outcomes: either to kill for the prey’s DNA, leading to horizontal gene transfer, or as part of a defensive escape reaction.

Development of a Side-Impact (Gy) Neck Injury Criterion for Use in Aircraft and Vehicle Safety Evaluation

OCCUPATIONAL APPLICATIONSIn this study, a lateral impact (Gy accelerative input), upper-neck, multi-axial, neck injury criterion is developed. This criterion could be used to evaluate the safety of U.S. Air Force ejection systems incorporating helmet-mounted displays or other applications where neck injury risk from side impact occurs (e.g., automotive and civilian fixed-wing or rotary-wing aircraft). Development of the criterion was motivated by military aviation, which increasingly incorporates head-supported mass and an expanded pilot population, including smaller pilots (to 47 kg), raising concerns for pilot safety during ejection. Neck injury criteria based on risk functions constructed with human subject and postmortem human subject data allow system designers to quantify the injury risk and design acceptably safe systems. A maximum allowable value for the criterion applicable to U.S. Air Force ejection aircraft is proposed to limit neck injury risk to a 5% probability of moderate injury. However, the underlying risk function allows practitioners to customize the criterion for their desired level of injury risk and injury classification.TECHNICAL ABSTRACT Background: Neck injury remains a concern in ejection seat–equipped military aircraft with the growing use of helmet-mounted displays (HMDs) worn for entire mission durations, as well as in the automotive and civilian aircraft domains. Existing U.S. Department of Defense criteria are overly complex and not clearly tied to injury risk and thus require improvement. Purpose: This study developed a lateral (Gy) impact, upper neck injury criterion for use in the design and test of U.S. Department of Defense escape systems and HMDs. Methods: A multi-axial lateral impact risk function, referred to as MANIC(Gy), was constructed using the survival analysis of a data set that combined human subject (N = 56) and postmortem human (N = 9) data. The human subject data were analyzed to assess criterion sensitivity to anthropometric factors. Additionally, a risk function was applied to quantify the risk associated with changes in HMD mass and acceleration input. Results: A lateral impact (Gy), upper neck injury criterion is proposed, which yields a 5% risk of Abbreviated Injury Scale (AIS) 2 or greater injury at a criterion value of 0.48 (95% confidence intervals of 0.28 and 0.67, respectively). At an injury level of AIS 3 or greater, a risk function was generated that yields a 5% risk at a criterion value of 0.53 (95% confidence intervals of 0.24 and 0.82, respectively). Conclusions: This initial multi-axial risk function could be applied to quantify the risk of neck injury posed by lateral acceleration. Criterion values were correlated with body mass and related anthropometric factors, indicating that the critical values incorporated in this study may require improvement. This same criterion may be useful for analyzing side impact safety in other vehicle systems (e.g., automotive and civilian fixed wing or rotary wing aircraft).

HDAC2 deregulation in tumorigenesis is causally connected to repression of immune modulation and defense escape.

Histone deacetylase 2 (HDAC2) is overexpressed or mutated in several disorders such as hematological cancers, and plays a critical role in transcriptional regulation, cell cycle progression and developmental processes. Here, we performed comparative transcriptome analyses in acute myeloid leukemia to investigate the biological implications of HDAC2 silencing versus its enzymatic inhibition using epigenetic-based drug(s). By gene expression analysis of HDAC2-silenced vs wild-type cells, we found that HDAC2 has a specific role in leukemogenesis. Gene expression profiling of U937 cell line with or without treatment of the well-known HDAC inhibitor vorinostat (SAHA) identifies and characterizes several gene clusters where inhibition of HDAC2 'mimics' its silencing, as well as those where HDAC2 is selectively and exclusively regulated by HDAC2 protein expression levels. These findings may represent an important tool for better understanding the mechanisms underpinning immune regulation, particularly in the study of major histocompatibility complex class II genes.

Examining face and construct validity of a noninvasive model of panic disorder in Lister-hooded rats

Increasing evidence suggests that defensive escape behavior in Lister-hooded (LH) rats induced by ultrasound application may be an animal model of panic disorder. The objectives of this study were to further explore the face and construct validity of ultrasound-induced escape behavior by characterizing the autonomic and neuroendocrine response to ultrasound, and to examine the underlying neuronal structures by comparing the effects of the anxiolytic with panicolytic properties, diazepam, with a preclinical anxiolytic without panicolytic-like activity, the NOP agonist Ro 64-6198. LH rats were implanted with telemetry transmitters to monitor heart rate and core body temperature before, during, and after ultrasound application. Blood samples were taken after ultrasound application for corticosterone analysis. Ultrasound-induced c-Fos expression was measured in different periaqueductal gray (PAG) and amygdala subregions after treatment with diazepam or Ro 64-6198. Ultrasound application increased heart rate and body temperature, but did not alter plasma corticosterone levels. Ultrasound application increased c-Fos expression in the dorsal and dorsolateral PAG (dPAG, dlPAG) and amygdaloid subregions. Diazepam, but not Ro 64-6198, reduced c-Fos expression in the dPAG/dlPAG, while Ro 64-6198, but not diazepam, reduced c-Fos expression in the central amygdala. Similar to human panic attacks, ultrasound application to LH rats activated the autonomic, but not the neuroendocrine, stress system. Also, like in humans, the current data confirm and extend that the dPAG/dlPAG plays a key role in ultrasound-induced escape behavior. These observations suggest that ultrasound-induced escape behaviors in LH rats have face and construct validity for panic disorders.

GABA A receptor blockade in dorsomedial and ventromedial nuclei of the hypothalamus evokes panic-like elaborated defensive behaviour followed by innate fear-induced antinociception

Dysfunction in the hypothalamic GABAergic system has been implicated in panic syndrome in humans. Furthermore, several studies have implicated the hypothalamus in the elaboration of pain modulation. Panic-prone states are able to be experimentally induced in laboratory animals to study this phenomenon. The aim of the present work was to investigate the involvement of medial hypothalamic nuclei in the organization of panic-like behaviour and the innate fear-induced oscillations of nociceptive thresholds. The blockade of GABA A receptors in the neuronal substrates of the ventromedial or dorsomedial hypothalamus was followed by elaborated defensive panic-like reactions. Moreover, innate fear-induced antinociception was consistently elicited after the escape behaviour. The escape responses organized by the dorsomedial and ventromedial hypothalamic nuclei were characteristically more elaborated, and a remarkable exploratory behaviour was recorded during GABA A receptor blockade in the medial hypothalamus. The motor characteristic of the elaborated defensive escape behaviour and the patterns of defensive alertness and defensive immobility induced by microinjection of the bicuculline either into the dorsomedial or into the ventromedial hypothalamus were very similar. This was followed by the same pattern of innate fear-induced antinociceptive response that lasted approximately 40 min after the elaborated defensive escape reaction in both cases. These findings suggest that dysfunction of the GABA-mediated neuronal system in the medial hypothalamus causes panic-like responses in laboratory animals, and that the elaborated escape behaviour organized in both dorsomedial and ventromedial hypothalamic nuclei are followed by significant innate-fear-induced antinociception. Our findings indicate that the GABA A receptor of dorsomedial and ventromedial hypothalamic nuclei are critically involved in the modulation of panic-like behaviour.

Relationship between the types of behavioral reaction in a conditioned shake-off reflex and neocortical lateralization

The nature of the spike activity and interhemisphere interactions of neurons in the parietal cortex (somatosensory representation of the ear) during the intersignal period before active shake-off and passive (freezing) reactions to stimuli was studied in rabbits after acquisition of a conditioned defensive escape reflex. Before passive reactions, in contrast to the situation before active shake-off, there were increases in right-sided influences on cells in the left hemisphere with delays of up to 100 msec, leading to asymmetry in interhemisphere interactions with right-sided dominance. Passive reactions were preceded by increases in the extent of frequencies in the delta range in the spike activity of individual neurons and in interactions between pairs of cells. These data provide evidence that the existence and nature of interhemisphere asymmetry before stimulation is one of the factors determining the passive or active type of behavioral reaction and reflecting the level of activation of the cortex.

Effect of ethanol on aggression and timidity in mice

The effects of ethanol (0.4, 0.8, 1.6, and 2.4 g/kg p.o.) on behavior of aggressive, timid, and sociable male mice treated with the drug on paired interactions with non-aggressive males given water were investigated. Under control interactions, aggressive mice attacked their partners, timid mice showed defensive-escape activities though their partners were completely non-aggressive, and sociable mice intensively investigated their partners. A low dose of ethanol (0.4 g/kg) increased while higher doses (0.8 to 2.4 g/kg) reduced aggressive activities in aggressive mice. Ethanol (0.8 g/kg) also evoked aggressive behavior in non-aggressive timid mice but no dose of ethanol stimulated aggression in non-aggressive sociable mice. Ethanol altered timid defensive-escape activities only in the highest dose of 2.4 g/kg: this dose increased defences and escapes in aggressive males while it reduced defensive upright postures in timid mice. However, 2.4 g/kg of ethanol reduced also another upright movement (exploratory rearing) in timid mice. Sociable activities were not increased by any dose of ethanol tested. By contrast, 0.4 g/kg of ethanol reduced sniffing and following partners in sociable mice. Thus, ethanol exhibit relatively strong aggression-stimulating effects in aversively disposed subjects while the drug was not able to supress timid defensive escape behavior and to stimulate active non-aggressive contacts between strange male mice.