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Vrana, Scott R., Ellen L. Spence, and Peter J. Lang. "The startle probe response: A new measure of emotion?" Journal of Abnormal Psychology 97, no. 4 (1988): 487–91. http://dx.doi.org/10.1037/0021-843x.97.4.487.
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Drummond, Neil M., Erin K. Cressman, and Anthony N. Carlsen. "Startle reveals decreased response preparatory activation during a stop-signal task." Journal of Neurophysiology 116, no. 3 (September 1, 2016): 986–94. http://dx.doi.org/10.1152/jn.00216.2016.
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In a stop-signal task participants are instructed to initiate a movement in response to a go signal, but to inhibit this movement if an infrequent stop signal is presented after the go. Reaction time (RT) in a stop-signal task is typically longer compared with that in a simple RT task, which may be attributed to a reduced readiness to initiate the response caused by the possibility of having to inhibit the response. The purpose of this experiment was to probe the preparatory activation level of the motor response during a stop-signal task using a startling acoustic stimulus (SAS), which has been shown to involuntarily trigger sufficiently prepared responses at a short latency. Participants completed two separate tasks: a simple RT task, followed by a stop-signal RT task. During both tasks, an SAS (120 dB) was pseudorandomly presented concurrently with the go signal. As expected, RT during the simple RT task was significantly shorter than during the stop-signal task. A significant reduction in RT was noted when an SAS was presented during the simple RT task; however, during the stop-signal task, an SAS resulted in either a significant speeding or a moderate delay in RT. Additionally, the subset of SAS trial responses with the shortest RT latencies produced during the stop-signal task were also delayed compared with the short-latency SAS trial responses observed during the simple RT task. Despite evidence that a response was prepared in advance of the go signal during a stop-signal task, it appears that the amount of preparatory activation was reduced compared with that achieved during a simple RT task.
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de Jong, Peter J., Arnoud Arntz, and Harald Merckelbach. "The startle probe response as an instrument for evaluating exposure effects in spider phobia." Advances in Behaviour Research and Therapy 15, no. 4 (January 1993): 301–16. http://dx.doi.org/10.1016/0146-6402(93)90015-t.
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Kavussanu, Maria, Adrian Willoughby, and Christopher Ring. "Moral Identity and Emotion in Athletes." Journal of Sport and Exercise Psychology 34, no. 6 (December 2012): 695–714. http://dx.doi.org/10.1123/jsep.34.6.695.
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The purpose of this study was to investigate the effects of moral identity on physiological responses to affective pictures, namely, the startle blink reflex and pain-related evoked potential. Male (n = 48) and female (n = 46) athletes participating in contact team sports were randomly assigned to either a moral identity group or a non-moral identity group and viewed a series of unpleasant, neutral, and pleasant sport-specific pictures. During picture viewing, a noxious electrocutaneous stimulus was delivered as the startle probe and the startle blink and pain-related evoked potential were measured. Upon completion of physiological measures, participants reviewed the pictures and rated them for valence and arousal. ANOVAs revealed that participants in the moral identity group displayed larger startle blinks and smaller pain-related potentials than did those in the non-moral identity group across all picture valence categories. However, the difference in the magnitude of startle blinks between the moral and non-moral identity groups was larger in response to unpleasant than pleasant and neutral pictures. Our findings suggest that moral identity affects physiological responses to sport-specific affective pictures, thereby providing objective evidence for the link between moral identity and emotion in athletes.
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Weike, Almut I., Alfons O. Hamm, and Dieter Vaitl. "Sensorimotor Gating and Attitudes Related to Schizotypal Proneness." Psychological Reports 88, no. 3_suppl (June 2001): 1035–45. http://dx.doi.org/10.2466/pr0.2001.88.3c.1035.
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The magnitude of the startle eyeblink response is diminished when the startle-eliciting probe is shortly preceded by another stimulus. This so called prepulse inhibition is interpreted as an automatic sensorimotor gating mechanism. There is substantial support for prepulse inhibition deficits in subjects suffering from schizophrenia spectrum disorders and in psychosis-prone normals as well. Thus, prepulse inhibition deficits may reflect vulnerability on the hypothesized psychopathological continuum from “normal” to “schizophrenia.” The present experiment investigated the amount of prepulse inhibition in a sample selected for “belief in extraordinary phenomena,” an attitude related to measures of psychosis-proneness. Believers and skeptics were tested in an acoustic prepulse-inhibition paradigm. As expected, presentation of prepulses clearly diminished magnitude of startle response, with greatest inhibition effects gained by lead intervals of 60 and 120 msec. Patterns of response were identical for believers and skeptics, i.e., attitude towards extraordinary phenomena did not seem to be related to functional information-processing deficits as has been observed in psychosis-prone normals.
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Carleton, R. Nicholas, Sophie Duranceau, Katherine A. McMillan, and Gordon J. G. Asmundson. "Trauma, Pain, and Psychological Distress." Journal of Psychophysiology 32, no. 2 (April 1, 2018): 75–84. http://dx.doi.org/10.1027/0269-8803/a000184.
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Abstract. Posttraumatic stress disorder (PTSD) and chronic musculoskeletal pain (CMP) are highly prevalent ( Breslau, 2002 ) and comorbid disorders ( Otis, Keane, & Kerns, 2003 ). The shared vulnerability model explains this overlap in part through a common attentional bias toward threat ( Asmundson, Coons, Taylor, & Katz, 2002 ). The current study made use of the acoustic startle to assess cognitive bias to threat in participants (n = 106; 64% women) who reported experiencing a motor vehicle accident (MVA). Participants were divided into five groups based on their diagnoses: PTSD, CMP, both PTSD and CMP, any general (i.e., non-PTSD) anxiety disorder with no CMP, and a no-disorder Control group. Self-report measures were used to assess psychological symptoms, trauma response, and pain-related factors. Word stimuli (i.e., trauma, sensory pain, health, pleasant, neutral) were presented visually prior to onset of the acoustic startle probe to assess for diagnosis-congruent attentional biases (e.g., persons with PTSD respond differently to trauma words). Relative to the general anxiety and control group, persons with PTSD or chronic pain demonstrated delayed startle peak and greater startle intensity across all word stimuli types; the results suggest there may be psychophysiologically measurable differences associated with PTSD and pain. The startle probe paradigm remains relatively nascent for such research, but has potential utility for assessment and treatment monitoring. Comprehensive results, discussion, and implications are analyzed.
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Drummond, Neil M., Erin K. Cressman, and Anthony N. Carlsen. "Go-activation endures following the presentation of a stop-signal: evidence from startle." Journal of Neurophysiology 117, no. 1 (January 1, 2017): 403–11. http://dx.doi.org/10.1152/jn.00567.2016.
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It has been proposed that, in a stop-signal task (SST), independent go- and stop-processes “race” to control behavior. If the go-process wins, an overt response is produced, whereas, if the stop-process wins, the response is withheld. One prediction that follows from this proposal is that, if the activation associated with one process is enhanced, it is more likely to win the race. We looked to determine whether these initiation and inhibition processes (and thus response outcomes) could be manipulated by using a startling acoustic stimulus (SAS), which has been shown to provide additional response activation. In the present study, participants were to respond to a visual go-stimulus; however, if a subsequent stop-signal appeared, they were to inhibit the response. The stop-signal was presented at a delay corresponding to a probability of responding of 0.4 (determined from a baseline block of trials). On stop-trials, a SAS was presented either simultaneously with the go-signal or stop-signal or 100, 150, or 200 ms following the stop-signal. Results showed that presenting a SAS during stop-trials led to an increase in probability of responding when presented with or following the stop-signal. The latency of SAS responses at the stop-signal + 150 ms and stop-signal + 200 ms probe times suggests that they would have been voluntarily inhibited but instead were involuntarily initiated by the SAS. Thus results demonstrate that go-activation endures even 200 ms following a stop-signal and remains accessible well after the response has been inhibited, providing evidence against a winner-take-all race between independent go- and stop-processes. NEW & NOTEWORTHY In this study, a startling acoustic stimulus (SAS) was used to determine whether response outcome could be manipulated in a stop-signal task. Results revealed that presenting a SAS during stop-signal trials led to an increase in probability of responding even when presented 200 ms following the stop-signal. The latency of SAS responses indicates that go-activation remains accessible and modifiable well after the response is voluntarily inhibited, providing evidence against an irrevocable commitment to inhibition.
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Carlsen, Anthony N., Michael A. Hunt, J. Timothy Inglis, David J. Sanderson, and Romeo Chua. "Altered Triggering of a Prepared Movement by a Startling Stimulus." Journal of Neurophysiology 89, no. 4 (April 1, 2003): 1857–63. http://dx.doi.org/10.1152/jn.00852.2002.
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An experiment is reported that investigated the effects of an auditory startling stimulus on a compound movement task. Previous findings have shown that, in a targeting task, a secondary movement can be initiated based on the proprioceptive information provided by a primary movement. Studies involving the presentation of a startling stimulus have shown that in reaction time (RT) tasks, prepared ballistic movements could be released early when participants are startled. In the present study we sought to determine whether the secondary component in an ongoing movement task, once prepared, could also be triggered by a startling stimulus. Participants performed a slow active elbow extension (22°/s), opening their hand when the arm passed 55° of extension from the starting point. An unexpected 124 dB startle stimulus was presented 5, 25, or 45° into the movement. Findings showed that, when participants were startled, the secondary component was triggered despite incongruent kinesthetic information. However, this only occurred when the startle was presented late in the primary movement. This suggests that the secondary movement was not prepared prior to task initiation, but was “loaded” into lower brain structures at some point during the movement in preparation to be triggered by the CNS. This occurred late in the movement sequence, but ≥400 ms prior to reaching the target. These findings indicate that, in addition to ballistic RT tasks, a startle can be used to probe response preparation in ongoing compound movement tasks.
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Hillman, Charles H., Bruce N. Cuthbert, Margaret M. Bradley, and Peter J. Lang. "Motivated Engagement to Appetitive and Aversive Fanship Cues: Psychophysiological Responses of Rival Sport Fans." Journal of Sport and Exercise Psychology 26, no. 2 (June 2004): 338–51. http://dx.doi.org/10.1123/jsep.26.2.338.
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Psychophysiological responses of two rival sport fan groups were assessed within the context of Lang’s biphasic theory of emotion. Twenty-four participants, placed in two groups based on their identification with local sport teams, viewed 6 pictures from 6 categories: team-relevant pleasant sport, team-irrelevant sport, team-relevant unpleasant sport, erotica, household objects, and mutilation. Fans rated appetitive sport pictures higher in pleasure and arousal compared to aversive sport pictures. Physiological measures (startle probe-P3, the startle eye-blink reflex, slow cortical potentials to picture onset, and skin conductance) differentiated both appetitive and aversive team-relevant categories from team-irrelevant pictures, and increased orbicularis oculi EMG was found only for team-relevant appetitive pictures. These results suggest there are differences between rival sport fans in response to the same pictorial stimuli, and further suggest that fans provide an ideal population in which to measure motivation toward appetitive stimuli.
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Dackis, Melissa N., Fred A. Rogosch, and Dante Cicchetti. "Child maltreatment, callous–unemotional traits, and defensive responding in high-risk children: An investigation of emotion-modulated startle response." Development and Psychopathology 27, no. 4pt2 (November 2015): 1527–45. http://dx.doi.org/10.1017/s0954579415000929.
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AbstractChild maltreatment is associated with disruptions in physiological arousal, emotion regulation, and defensive responses to cues of threat and distress, as well as increased risk for callous unemotional (CU) traits and externalizing behavior. Developmental models of CU traits have focused on biological and genetic risk factors that contribute to hypoarousal and antisocial behavior, but have focused less on environmental influences (Blair, 2004; Daversa, 2010; Hare, Frazell, & Cox, 1978; Krueger, 2000; Shirtcliff et al., 2009; Viding, Fontaine, & McCrory, 2012). The aim of the present investigation was to measure the independent and combined effects of child maltreatment and high CU traits on emotion-modulated startle response in children. Participants consisted of 132 low-income maltreated (n= 60) and nonmaltreated (n= 72) children between 8 and 12 years old who attended a summer camp program. Acoustic startle response (ASR) was elicited in response to a 110-dB 50-ms probe while children viewed a slideshow of pleasant, neutral, and unpleasant IAPS images. Maltreatment status was assessed through examination of Department of Human Services records. CU traits were measured using counselor reports from the Inventory of Callous and Unemotional Traits (Frick, 2004), and conduct problems were measured using counselor and child self-report. We found no significant differences in emotion-modulated startle in the overall sample. However, significant differences in ASR by maltreatment status, maltreatment subtype, and level of CU traits were apparent. Results indicated differential physiological responses for maltreated and nonmaltreated children based on CU traits, including a pathway of hypoarousal for nonmaltreated/high CU children that differed markedly from a more normative physiological trajectory for maltreated/high CU children. Further, we found heightened ASR for emotionally and physically neglected children with high CU and elevated antisocial behavior in these children. Results provide further support for differential trajectories by which experience and biology may influence the development of antisocial behavior in youth and highlight potential avenues for intervention.
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Gorka, S. M., L. Lieberman, H. Klumpp, K. L. Kinney, A. E. Kennedy, O. Ajilore, J. Francis, et al. "Reactivity to unpredictable threat as a treatment target for fear-based anxiety disorders." Psychological Medicine 47, no. 14 (April 24, 2017): 2450–60. http://dx.doi.org/10.1017/s0033291717000964.
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BackgroundHeightened reactivity to unpredictable threat (U-threat) is a core individual difference factor underlying fear-based psychopathology. Little is known, however, about whether reactivity to U-threat is a stable marker of fear-based psychopathology or if it is malleable to treatment. The aim of the current study was to address this question by examining differences in reactivity to U-threat within patients before and after 12-weeks of selective serotonin reuptake inhibitors (SSRIs) or cognitive-behavioral therapy (CBT).MethodsParticipants included patients with principal fear (n = 22) and distress/misery disorders (n = 29), and a group of healthy controls (n = 21) assessed 12-weeks apart. A well-validated threat-of-shock task was used to probe reactivity to predictable (P-) and U-threat and startle eyeblink magnitude was recorded as an index of defensive responding.ResultsAcross both assessments, individuals with fear-based disorders displayed greater startle magnitude to U-threat relative to healthy controls and distress/misery patients (who did not differ). From pre- to post-treatment, startle magnitude during U-threat decreased only within the fear patients who received CBT. Moreover, within fear patients, the magnitude of decline in startle to U-threat correlated with the magnitude of decline in fear symptoms. For the healthy controls, startle to U-threat across the two time points was highly reliable and stable.ConclusionsTogether, these results indicate that startle to U-threat characterizes fear disorder patients and is malleable to treatment with CBT but not SSRIs within fear patients. Startle to U-threat may therefore reflect an objective, psychophysiological indicator of fear disorder status and CBT treatment response.
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Katz, Andrea C., Anna Weinberg, Stephanie M. Gorka, Randy P. Auerbach, and Stewart A. Shankman. "Effect of Comorbid Post-Traumatic Stress Disorder and Panic Disorder on Defensive Responding." Journal of Psychophysiology 32, no. 2 (April 1, 2018): 43–52. http://dx.doi.org/10.1027/0269-8803/a000193.
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Abstract. Although panic disorder (PD) and post-traumatic stress disorder (PTSD) are characterized by heightened sensitivity to threat, no study to date has examined the effect of comorbid PD and PTSD on defensive responding. The present study probed startle eyeblink response to an acoustic probe in three groups of participants recruited from the community: (1) healthy individuals (n = 63), (2) individuals with PD without PTSD (n = 62), and (3) individuals with comorbid PD and PTSD (n = 24). Results indicated that PD individuals without PTSD exhibited greater sensitivity to threat relative to controls, and comorbid individuals displayed attenuated sensitivity to threat relative to PD individuals without PTSD (both ps < .05). The results are discussed in the context of the anxiety disorder spectrum, which postulates that anxiety disorders exist on a continuum spanning from specific/simple fear to broad distress, with defensive responding decreasing as distress increases.
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Maslovat, Dana, Michael J. Carter, and Anthony N. Carlsen. "Response preparation and execution during intentional bimanual pattern switching." Journal of Neurophysiology 118, no. 3 (September 1, 2017): 1720–31. http://dx.doi.org/10.1152/jn.00323.2017.
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During continuous bimanual coordination, in-phase (IP; 0° relative phase) and anti-phase (AP; 180° relative phase) patterns can be stably performed without practice. Paradigms in which participants are required to intentionally switch between these coordination patterns have been used to investigate the interaction between the performer’s intentions and intrinsic dynamics of the body’s preferred patterns. The current study examined the processes associated with switching preparation and execution through the use of a startling acoustic stimulus (SAS) as the switch stimulus. A SAS is known to involuntarily trigger preprogrammed responses at a shortened latency and, thus, can be used to probe advance preparation. Participants performed cyclical IP and AP bimanual elbow extension-flexion movements in which they were required to switch patterns in response to an auditory switch cue, which was either nonstartling (80 dB) or a SAS (120 dB). Results indicated that reaction time to the switch stimulus (i.e., switch onset) was significantly reduced on startle trials, indicative of advance preparation of the switch response. Similarly, switching time was reduced on startle trials, which was attributed to increased neural activation caused by the SAS. Switching time was also shorter for AP to IP trials, but only when the switching stimulus occurred at either the midpoint or reversal locations within the movement cycle, suggesting that the switch location may affect the intrinsic dynamics of the system. NEW & NOTEWORTHY The current study provides novel information regarding preparation and execution of intentional switching between in-phase and anti-phase bimanual coordination patterns. Using a startling acoustic stimulus, we provide strong evidence that the switching response is prepared before the switch stimulus, and switch execution is accelerated by the startling stimulus. In addition, the time required to switch between patterns and relative limb contribution is dependent upon where in the movement cycle the switch stimulus occurred.
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Knuepfer, Mark M., Robert M. Purcell, Qi Gan, and Khoi M. Le. "Hemodynamic response patterns to acute behavioral stressors resemble those to cocaine." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 281, no. 6 (December 1, 2001): R1778—R1786. http://dx.doi.org/10.1152/ajpregu.2001.281.6.r1778.
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Hemodynamic responses to cocaine vary greatly between animals, and the variability is related to the incidence of cocaine-induced cardiomyopathies and hypertension. The variability in cardiac output and systemic vascular resistance responses to cocaine in individuals is correlated with the responses to acute startle (air jet). This experiment was designed to determine whether responses to cocaine and to air jet are related to those evoked by a conditioned stimulus (tone preceding foot shock) and to an unconditioned stimulus (cold water). We verified the relationship in hemodynamic response patterns between cocaine and cold stress using selective receptor antagonists. Rats were instrumented with a pulsed Doppler flow probe on the ascending aorta for determination of cardiac output and with an arterial cannula for recording arterial pressure and heart rate. After recovery, some rats were tested multiple times with four different stimuli: air jet (6 trials), 15-s tone preceding 1-s foot shock (12 trials), cold water exposure (1 cm deep for 1 min, 4–12 trials), and cocaine (5 mg/kg iv, 4–6 trials) while hemodynamic parameters were recorded. Each stimulus was capable of eliciting a pressor response that was associated with variable changes in cardiac output. The cardiac output response to cocaine was correlated with the initial responses to each stressor in individual rats. Responses evoked by cold stress were most similar to those elicited by cocaine. Furthermore, nicardipine (25 μg/kg iv) or atropine methylbromide (0.5 mg/kg iv) pretreatment prevented the cardiac output differences to acute cold stress, as noted after cocaine administration. On the other hand, propranolol (1 mg/kg iv) exacerbated both the decrease in cardiac output and the stress-induced increase in systemic vascular resistance as previously reported with cocaine. Therefore, the initial response to cold water exposure is a reliable method of evoking characteristic hemodynamic response patterns that, as seen with cocaine, may provide a suitable model for identifying the causes for predilection to stress-induced cardiovascular disease.
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Fani, N., E. B. Tone, J. Phifer, S. D. Norrholm, B. Bradley, K. J. Ressler, A. Kamkwalala, and T. Jovanovic. "Attention bias toward threat is associated with exaggerated fear expression and impaired extinction in PTSD." Psychological Medicine 42, no. 3 (August 22, 2011): 533–43. http://dx.doi.org/10.1017/s0033291711001565.
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BackgroundPost-traumatic stress disorder (PTSD) develops in a minority of traumatized individuals. Attention biases to threat and abnormalities in fear learning and extinction are processes likely to play a critical role in the creation and/or maintenance of PTSD symptomatology. However, the relationship between these processes has not been established, particularly in highly traumatized populations; understanding their interaction can help inform neural network models and treatments for PTSD.MethodAttention biases were measured using a dot probe task modified for use with our population; task stimuli included photographs of angry facial expressions, which are emotionally salient threat signals. A fear-potentiated startle paradigm was employed to measure atypical physiological response during acquisition and extinction phases of fear learning. These measures were administered to a sample of 64 minority (largely African American), highly traumatized individuals with and without PTSD.ResultsParticipants with PTSD demonstrated attention biases toward threat; this attentional style was associated with exaggerated startle response during fear learning and early and middle phases of extinction, even after accounting for the effects of trauma exposure.ConclusionsOur findings indicate that an attentional bias toward threat is associated with abnormalities in ‘fear load’ in PTSD, providing seminal evidence for an interaction between these two processes. Future research combining these behavioral and psychophysiological techniques with neuroimaging will be useful toward addressing how one process may modulate the other and understanding whether these phenomena are manifestations of dysfunction within a shared neural network. Ultimately, this may serve to inform PTSD treatments specifically designed to correct these atypical processes.
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Briffa, Mark, and Rebecca Williams. "Use of chemical cues during shell fights in the hermit crab Pagurus bernhardus." Behaviour 143, no. 10 (2006): 1281–90. http://dx.doi.org/10.1163/156853906778691577.
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AbstractChemical communication is likely to play an important role during agonistic encounters in aquatic crustaceans but the use of chemical signals is difficult to observe. An alternative approach to direct observation is to collect water that has contained fighting animals and then expose a focal animal of the same species to the cue water and monitor its behaviour. Here we investigate the possibility of the use of chemical cues during 'shell fights' in the hermit crab Pagurus bernhardus. Focal crabs exposed to the fighting cue spent more time withdrawn into their gastropod shell, less time on locomotion and less time searching for food than did those exposed to cues from non-fighting hermit crabs or those treated with plain sea water. At the end of the observation period we used a novel stimulus to induce a startle response in order to probe the focal crab's motivational state for this exploratory behaviour. Those exposed to the fighting cue water took longer to recover than crabs in the other groups, indicating that their motivation was lower. These findings provide clear evidence that chemical cues are a feature of these contests.
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Mann, Kara D., Carlton Hoyt, Shaina Feldman, LaChelle Blunt, Aaron Raymond, and Patrick S. Page-McCaw. "Cardiac response to startle stimuli in larval zebrafish: sympathetic and parasympathetic components." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 298, no. 5 (May 2010): R1288—R1297. http://dx.doi.org/10.1152/ajpregu.00302.2009.
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Central regulation of cardiac output via the sympathetic and parasympathetic branches of the autonomic nervous system allows the organism to respond to environmental changes. Sudden onset stimuli, startle stimuli, are useful probes to study central regulatory responses to the environment. In mammals, startle stimuli induce a transient bradycardia that habituates with repeated stimulation. Repeated presentation of the stimulus results in tachycardia. In this study, we investigate the behavioral regulation of heart rate in response to sudden stimuli in the zebrafish. Larval zebrafish show a stereotyped heart rate response to mild electrical shock. Naïve fish show a significant increase in interbeat interval that resolves in the 2 s following stimulation. This transient bradycardia decreases on repeated exposure to the stimulus. Following repeated stimulation, the fish become tachycardic within 1 min of stimulation. Both the transient bradycardia and following tachycardia responses are blocked with administration of the ganglionic blocker hexamethonium, demonstrating that these responses are mediated centrally. The transient bradycardia is blocked by the muscarinic antagonist atropine, suggesting that this response is mediated by the parasympathetic system, while the following tachycardia is specifically blocked by the beta-adrenergic antagonist propranolol, suggesting that this response is mediated by the sympathetic nervous system. Together, these results demonstrate that at the larval stage, zebrafish actively regulate cardiac output to changes in their environment using both the parasympathetic and sympathetic branches of the autonomic nervous system, a behavioral response that is markedly similar to that observed in mammals to similar sudden onset stimuli.
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Balada, Ferran, Angel Blanch, and Anton Aluja. "Arousal and Habituation Effects (Excitability) on Startle Responses to the International Affective Picture Systems (IAPS)." Journal of Psychophysiology 28, no. 4 (January 1, 2014): 233–41. http://dx.doi.org/10.1027/0269-8803/a000115.
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The magnitude and habituation of startle reflex responses have been used to evaluate the excitability of the neural structures involved in this psychophysiological response. We analyzed the magnitude and habituation responses to startle reflex probes in 112 women. Results confirmed the modulation of eyeblink reflex by affective valence for arousing (F = 34.79, p < .001), but not for nonarousing pictures (F = 1.08, ns). Our results indicate that there is a linear adjustment for habituation in all picture groups, except for arousing unpleasant pictures where there is a quadratic adjustment that could be due to initial sensitization followed by the subsequent habituation. Multiple linear regression analysis revealed that the startle magnitude was partially determined by arousal and startle presentation order. In conclusion, our results emphasize the usefulness of arousing pictures to study startle reflex response and show evidence of different response mechanisms for pleasant and unpleasant pictures conditions.
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VRANA, SCOTT R. "Emotional modulation of skin conductance and eyeblink responses to a startle probe." Psychophysiology 32, no. 4 (July 1995): 351–57. http://dx.doi.org/10.1111/j.1469-8986.1995.tb01217.x.
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Krippl, Martin, Stephanie Ast-Scheitenberger, Ina Bovenschen, and Gottfried Spangler. "Maternal Perception of Infants’ Expressions of Emotion." Journal of Psychophysiology 24, no. 3 (January 2010): 173–85. http://dx.doi.org/10.1027/0269-8803/a000008.
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In light of Lang’s differentiation of the aversive and the approach system – and assumptions stemming from attachment theory – this study investigates the role of the approach or caregiving system for processing infant emotional stimuli by comparing IAPS pictures, infant pictures, and videos. IAPS pictures, infant pictures, and infant videos of positive, neutral, or negative content were presented to 69 mothers, accompanied by randomized startle probes. The assessment of emotional responses included subjective ratings of valence and arousal, corrugator activity, the startle amplitude, and electrodermal activity. In line with Lang’s original conception, the typical startle response pattern was found for IAPS pictures, whereas no startle modulation was observed for infant pictures. Moreover, the startle amplitudes during negative video scenes depicting crying infants were reduced. The results are discussed with respect to several theoretical and methodological considerations, including Lang’s theory, emotion regulation, opponent process theory, and the parental caregiving system.
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Taylor-Clift, A., B. H. Morris, J. Rottenberg, and M. Kovacs. "Emotion-modulated startle in anxiety disorders is blunted by co-morbid depressive episodes." Psychological Medicine 41, no. 1 (March 16, 2010): 129–39. http://dx.doi.org/10.1017/s003329171000036x.
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BackgroundWhile anxiety has been associated with exaggerated emotional reactivity, depression has been associated with blunted, or context insensitive, emotional responding. Although anxiety and depressive disorders are frequently co-morbid, surprisingly little is known about emotional reactivity when the two disorders co-occur.MethodWe utilized the emotion-modulated startle (EMS) paradigm to examine the effects of a concurrent depressive episode on emotional reactivity in young adults with anxiety disorders. Using an archival dataset from a multi-disciplinary project on risk factors in childhood-onset depression, we examined eye-blink startle reactions to late-onset auditory startle probes while participants viewed pictures with affectively pleasant, unpleasant and neutral content. EMS response patterns were analyzed in 33 individuals with a current anxiety (but no depressive) disorder, 24 individuals with a current anxiety disorder and co-morbid depressive episode and 96 healthy controls.ResultsControl participants and those with a current anxiety disorder (but no depression) displayed normative linearity in startle responses, including potentiation by unpleasant pictures. By contrast, individuals with concurrent anxiety and depression displayed blunted EMS.ConclusionsAn anxiety disorder concurrent with a depressive episode is associated with reactivity that more closely resembles the pattern of emotional responding that is typical of depression (i.e. context insensitive) rather than the pattern that is typical for anxiety (i.e. exaggerated).
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Lang, Peter J., Margaret M. Bradley, and Bruce N. Cuthbert. "A Motivational Analysis of Emotion: Reflex-Cortex Connections." Psychological Science 3, no. 1 (January 1992): 44–49. http://dx.doi.org/10.1111/j.1467-9280.1992.tb00255.x.
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This analysis postulates a motivational continuity from reflex reactions to complex, cognitively elaborated emotional expressions. Responses are motivated by either the positive-appetitive or the negative-aversive brain systems. Reflexes evoked during emotional processing are augmented if their affective valence (positive or negative) matches that of the active motivational system and inhibited when a mismatch is present. Research testing this biphasic model is described using the defensive startle probe reflex. It is shown that probe responses are reliably potentiated during perception and imagery of unpleasant events and reduced during pleasant events. The neurobehavioral foundations of this conception are presented, and the implications of probe analysis are elucidated for theories of emotion organization, the assessment of mood, and practical applications in psychopathology and neurological disorder.
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Elash, Celeste A., Stephen T. Tiffany, and Scott R. Vrana. "Manipulation of smoking urges and affect through a brief-imagery procedure: Self-report, psychophysiological, and startle probe responses." Experimental and Clinical Psychopharmacology 3, no. 2 (1995): 156–62. http://dx.doi.org/10.1037/1064-1297.3.2.156.
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Lipp, Ottmar V., David L. Neumann, David A. T. Siddle, and Patricia J. Dall. "Assessing the Effects of Attention and Emotion on Startle Eyeblink Modulation." Journal of Psychophysiology 15, no. 3 (July 2001): 173–82. http://dx.doi.org/10.1027//0269-8803.15.3.173.
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Abstract Two experiments were conducted to assess simultaneously the effects of attentional and emotional processes on startle eyeblink modulation. In each experiment, participants were presented with a pleasant and an unpleasant picture. Half the participants were asked to attend to the pleasant picture and to ignore the unpleasant picture, whereas the reverse was the case for the other participants. Startle probes were presented at 3500 and 4500 ms after stimulus onset in Experiment 1 and at 250, 750, and 4450 ms after stimulus onset and 950 ms after stimulus offset in Experiment 2. Attentional processing affected startle eyeblink modulation and electrodermal responses in both experiments. However, effects of picture valence on startle eyeblink modulation were found only in Experiment 2. The results confirm the utility of startle eyeblink modulation as an index of attentional and emotional processing. They also illustrate that procedural characteristics, such as the nature of the lead intervals and how attention and emotion are operationalized, can determine whether emotional or attentional processes will be reflected in startle eyeblink.
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Inoue, Masato, and Akichika Mikami. "Top-Down Signal of Retrieved Information From Prefrontal to Inferior Temporal Cortices." Journal of Neurophysiology 98, no. 4 (October 2007): 1965–74. http://dx.doi.org/10.1152/jn.00911.2006.
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We compared neuronal activities in the ventrolateral prefrontal cortex (VLPFC) and the inferior temporal cortex (IT) during the retrieval of an object from the working memory. About one third of IT neurons showed color- and target-selective (CT) or target-selective (T) response during the color cue period of the serial probe reproduction (SPR) task. These object-selective (CT and T) responses in IT could be correlated with the retrieval process of an object from the memorized multiple objects because no objects were presented during this period. However, proportion of CT and T responses was smaller in IT than in VLPFC, where two thirds of neurons showed object-selective response. In addition, object-selective response started earlier in VLPFC than in IT. These results suggest that VLPFC retrieves particular object information from the working memory and sends the retrieved object information to IT. The fact that the responses in the error trials did not decrease in IT suggests that IT is not a critical area for the retrieval process from the working memory.
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Lyamzaev, Konstantin G., Alisa A. Panteleeva, Anna A. Karpukhina, Ivan I. Galkin, Ekatherina N. Popova, Olga Yu Pletjushkina, Bettina Rieger, Karin B. Busch, Armen Y. Mulkidjanian, and Boris V. Chernyak. "Novel Fluorescent Mitochondria-Targeted Probe MitoCLox Reports Lipid Peroxidation in Response to Oxidative Stress In Vivo." Oxidative Medicine and Cellular Longevity 2020 (February 10, 2020): 1–11. http://dx.doi.org/10.1155/2020/3631272.
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A new mitochondria-targeted probe MitoCLox was designed as a starting compound for a series of probes sensitive to cardiolipin (CL) peroxidation. Fluorescence microscopy reported selective accumulation of MitoCLox in mitochondria of diverse living cell cultures and its oxidation under stress conditions, particularly those known to cause a selective cardiolipin oxidation. Ratiometric fluorescence measurements using flow cytometry showed a remarkable dependence of the MitoCLox dynamic range on the oxidation of the sample. Specifically, MitoCLox oxidation was induced by low doses of hydrogen peroxide or organic hydroperoxide. The mitochondria-targeted antioxidant 10-(6′-plastoquinonyl)decyltriphenyl-phosphonium (SkQ1), which was shown earlier to selectively protect cardiolipin from oxidation, prevented hydrogen peroxide-induced MitoCLox oxidation in the cells. Concurrent tracing of MitoCLox oxidation and membrane potential changes in response to hydrogen peroxide addition showed that the oxidation of MitoCLox started without a delay and was complete during the first hour, whereas the membrane potential started to decay after 40 minutes of incubation. Hence, MitoCLox could be used for splitting the cell response to oxidative stress into separate steps. Application of MitoCLox revealed heterogeneity of the mitochondrial population; in living endothelial cells, a fraction of small, rounded mitochondria with an increased level of lipid peroxidation were detected near the nucleus. In addition, the MitoCLox staining revealed a specific fraction of cells with an increased level of oxidized lipids also in the culture of human myoblasts. The fraction of such cells increased in high-density cultures. These specific conditions correspond to the initiation of spontaneous myogenesis in vitro, which indicates that oxidation may precede the onset of myogenic differentiation. These data point to a possible participation of oxidized CL in cell signalling and differentiation.
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Riesel, Anja, Anna Weinberg, Tim Moran, and Greg Hajcak. "Time Course of Error-Potentiated Startle and its Relationship to Error-Related Brain Activity." Journal of Psychophysiology 27, no. 2 (January 2013): 51–59. http://dx.doi.org/10.1027/0269-8803/a000093.
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Errors are aversive, motivationally-salient events which prime defensive action. This is reflected in a potentiated startle reflex after the commission of an error. The current study replicates and extends previous work examining the time course of error-potentiated startle as a function of startle lag (i.e., 300 ms or 800 ms following correct and error responses). In addition, the relationship between error-potentiated startle and error-related brain activity in both the temporal (error-related negativity, ERN/Ne) and spectral (error-related theta and delta power) domains was investigated. Event-related potentials (ERPs) were recorded from 32 healthy undergraduates while they performed an arrowhead version of a flanker task. Complex Morlet wavelets were applied to compute oscillatory power in the delta- and theta-band range. Consistent with our previous report, startle was larger following errors. Furthermore, this effect was evident at both early and late startle probe times. Increased delta and theta power after an error was associated with larger error-potentiated startle. An association between ERN amplitude and error-potentiated startle was only observed in a subgroup of individuals with relatively large ERN/Ne amplitude. Among these individuals, ERN/Ne magnitude was also related to multiple indices of task performance. This study further supports the notion that errors are aversive events that prime defensive motivation, and that error-potentiated startle is evident beyond the immediate commission of an error and can be predicted from error-related brain activity.
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Pasparakis, E., E. Koiliari, C. Zouraraki, E. M. Tsapakis, P. Roussos, S. G. Giakoumaki, and P. Bitsios. "The effects of the CACNA1C rs1006737 A/G on affective startle modulation in healthy males." European Psychiatry 30, no. 4 (June 2015): 492–98. http://dx.doi.org/10.1016/j.eurpsy.2015.03.004.
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AbstractBackground:The CACNA1C rs1006737 risk A allele has been associated with affective psychoses and functional studies indicate that it is associated with increased hippocampal/amygdala activity during emotional face-processing. Here we studied the impact of the risk A allele on affective startle modulation.Methods:Hundred and ninety-four healthy males stratified for their CACNA1C rs1006737 genotype (GG:111, GA:67, AA:16) were presented with 18 pleasant, 18 unpleasant and 18 neutral pictures with acoustic probes (104 dB) occurring during 12 pictures in each affective category. Baseline startle was assessed during blank screens. State mood was self-rated on arrival, pre- and post-test and the emotional valence and arousal of affective pictures at post-test.Results:Relative to the other genotypes, risk A allele homozygotes presented with higher anxiety/negative affect at pre-test, reduced and exaggerated physiological responses to the pleasant and negative pictures respectively, negative affect with reduced arousal at post-test and rated the affective pictures as less arousing and inconsistently to their physiological responses (all P < 0.05). Sustained contextual negative mood predicted reduced baseline and affective startle reactivity in the AA group.Conclusions:Healthy homozygous males for the risk A allele appear to have marked contextual sensitivity, affective reactivity akin to anxiety and depression and inefficient emotional appraisal. Our findings provide phenotypic detail of the CACNA1C AA genotype in non-symptomatic individuals, which suggest primary effects in emotional circuitry, consistent with previously documented alterations in hippocampal/amygdala processing.
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Tan, Joy Lynn, Thushara Perera, Jennifer L. McGinley, Shivanthan Arthur Curtis Yohanandan, Peter Brown, and Wesley Thevathasan. "Neurophysiological analysis of the clinical pull test." Journal of Neurophysiology 120, no. 5 (November 1, 2018): 2325–33. http://dx.doi.org/10.1152/jn.00789.2017.
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Postural reflexes are impaired in conditions such as Parkinson’s disease, leading to difficulty walking and falls. In clinical practice, postural responses are assessed using the “pull test,” where an examiner tugs the prewarned standing patient backward at the shoulders and grades the response. However, validity of the pull test is debated, with issues including scaling and variability in administration and interpretation. It is unclear whether to assess the first trial or only subsequent repeated trials. The ecological relevance of a forewarned backward challenge is also debated. We therefore developed an instrumented version of the pull test to characterize responses and clarify how the test should be performed and interpreted. In 33 healthy participants, “pulls” were manually administered and pull force measured. Trunk and step responses were assessed with motion tracking. We probed for the StartReact phenomenon (where preprepared responses are released early by a startling stimulus) by delivering concurrent normal or “startling” auditory stimuli. We found that the first pull triggers a different response, including a larger step size suggesting more destabilization. This is consistent with “first trial effects,” reported by platform translation studies, where movement execution appears confounded by startle reflex-like activity. Thus, first pull test trials have clinical relevance and should not be discarded as practice. Supportive of ecological relevance, responses to repeated pulls exhibited StartReact, as previously reported with a variety of other postural challenges, including those delivered with unexpected timing and direction. Examiner pull force significantly affected the postural response, particularly the size of stepping. NEW & NOTEWORTHY We characterized postural responses elicited by the clinical “pull test” using instrumentation. The first pull triggers a different response, including a larger step size suggesting more destabilization. Thus, first trials likely have important clinical and ecological relevance and should not be discarded as practice. Responses to repeated pulls can be accelerated with a startling stimulus, as reported with a variety of other challenges. Examiner pull force was a significant factor influencing the postural response.
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Gyurak, Anett, and Özlem Ayduk. "Defensive Physiological Reactions to Rejection." Psychological Science 18, no. 10 (October 2007): 886–92. http://dx.doi.org/10.1111/j.1467-9280.2007.01996.x.
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We examined the hypothesis that rejection automatically elicits defensive physiological reactions in people with low self-esteem (SE) but that attentional control moderates this effect. Undergraduates ( N = 67) completed questionnaire measures of SE and attentional control. Their eye-blink responses to startle probes were measured while they viewed paintings related to rejection and acceptance themes. The stimuli also included positive-, negative-, and neutral-valence control paintings unrelated to rejection. As predicted, compared with people high in SE, those low in SE showed stronger startle eye-blink responses to paintings related to rejection, but not to negative paintings. Paintings related to acceptance did not attenuate their physiological reactivity. Furthermore, attentional control moderated their sensitivity to rejection, such that low SE was related to greater eye-blink responses to rejection only among individuals who were low in attentional control. Implications of the role of attentional control as a top-down process regulating emotional reactivity in people with low SE are discussed.
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Quevedo, Karina M., Stephen D. Benning, Megan R. Gunnar, and Ronald E. Dahl. "The onset of puberty: Effects on the psychophysiology of defensive and appetitive motivation." Development and Psychopathology 21, no. 1 (January 2009): 27–45. http://dx.doi.org/10.1017/s0954579409000030.
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AbstractWe examined puberty-specific effects on affect-related behavior and on the psychophysiology of defensive and appetitive motivation while controlling for age. Adolescents (N = 94, ages = 12 and 13 years) viewed 75 pictures (International Affective Picture System: pleasant, neutral, and aversive) while listening to auditory probes. Startle response and postauricular (PA) reflex were collected as measures of defensive and appetitive motivation, respectively. Pubertal status and measures of anxiety/stress reaction and sensation/thrill seeking were obtained. Mid-/late pubertal adolescents showed enhanced startle amplitude across all picture valences. A Puberty × Valence interaction revealed that mid-/late pubertal adolescents showed appetitive potentiation of the PA, whereas pre-/early pubertal adolescents showed no modulation of the PA reflex. Mid-/late pubertal adolescents also scored significantly higher on measures of sensation/thrill seeking than did their pre-/early pubertal peers and puberty moderated the association between psychophysiology and behavioral measures, suggesting that it plays a role in reorganizing defensive and appetitive motivational systems.
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Ahkong, Q. F., J. P. Desmazes, D. Georgescauld, and J. A. Lucy. "Movements of fluorescent probes in the mechanism of cell fusion induced by poly(ethylene glycol)." Journal of Cell Science 88, no. 3 (October 1, 1987): 389–98. http://dx.doi.org/10.1242/jcs.88.3.389.
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It has been claimed that purified poly(ethylene glycol) (PEG) is able only to aggregate cells and not to fuse them. In our hands, purified PEG 6000 (recrystallized/dialysed) induces both aggregation and fusion of human erythrocytes, and the mechanism of fusion by the purified polymer has been investigated with fluorescent probes. No movement of a carbocyanine probe or of octadecyl rhodamine B chloride from labelled to unlabelled cells occurred in the absence of PEG or with cells treated with concanavalin A, protamine or spermine. With 40% PEG, however, both probes immediately started to diffuse into the membranes of unlabelled cells. This indicates that continuity between the phospholipid bilayer membranes of adjacent erythrocytes (i.e. membrane fusion) is established within seconds in concentrated solutions of the polymer, and precedes the cell fusion event that is induced by purified PEG. These observations are consistent with the idea that micro-regions of shared phospholipid bilayer may be formed in the membranes of cells when they are forced together as a consequence of the dehydrating action of PEG. Intact erythrocytes were cytoplasmically labelled with 6-carboxyfluorescein to avoid the possibility that loading the cells with a cytoplasmic marker by hypotonic haemolysis might modify their response to PEG. Unlike the lipid probes, carboxyfluorescein did not diffuse from labelled to unlabelled cells in the presence of 40% PEG, and there was little diffusion on subsequent dilution of the polymer solution to 13%. However, after the PEG solution had been replaced by an isotonic buffer, a rapid transfer of the cytoplasmic fluorophore to unlabelled cells often occurred. This is considered to be more consistent with the osmotic rupture of a membranous barrier, such as a shared bilayer, between the labelled and unlabelled cells than with the return of cytoplasmic viscosity to normal when the PEG is removed. Possible reasons are discussed for the reported inability of purified PEG to fuse fibroblasts with hypotonically loaded human erythrocytes.
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Lass-Hennemann, Johanna, Christian E. Deuter, Linn K. Kuehl, André Schulz, Terry D. Blumenthal, and Hartmut Schachinger. "Effects of stress on human mating preferences: stressed individuals prefer dissimilar mates." Proceedings of the Royal Society B: Biological Sciences 277, no. 1691 (March 10, 2010): 2175–83. http://dx.doi.org/10.1098/rspb.2010.0258.
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Although humans usually prefer mates that resemble themselves, mating preferences can vary with context. Stress has been shown to alter mating preferences in animals, but the effects of stress on human mating preferences are unknown. Here, we investigated whether stress alters men's preference for self-resembling mates. Participants first underwent a cold-pressor test (stress induction) or a control procedure. Then, participants viewed either neutral pictures or pictures of erotic female nudes whose facial characteristics were computer-modified to resemble either the participant or another participant, or were not modified, while startle eyeblink responses were elicited by noise probes. Erotic pictures were rated as being pleasant, and reduced startle magnitude compared with neutral pictures. In the control group, startle magnitude was smaller during foreground presentation of photographs of self-resembling female nudes compared with other-resembling female nudes and non-manipulated female nudes, indicating a higher approach motivation to self-resembling mates. In the stress group, startle magnitude was larger during foreground presentation of self-resembling female nudes compared with other-resembling female nudes and non-manipulated female nudes, indicating a higher approach motivation to dissimilar mates. Our findings show that stress affects human mating preferences: unstressed individuals showed the expected preference for similar mates, but stressed individuals seem to prefer dissimilar mates.
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CARMEL, JASON B., ANTHONY GALANTE, PATRICIA SOTEROPOULOS, PETER TOLIAS, MICHAEL RECCE, WISE YOUNG, and RONALD P. HART. "Gene expression profiling of acute spinal cord injury reveals spreading inflammatory signals and neuron loss." Physiological Genomics 7, no. 2 (December 21, 2001): 201–13. http://dx.doi.org/10.1152/physiolgenomics.00074.2001.
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We have completed the first large-scale gene expression study of acute spinal cord injury (SCI) in rat. Oligonucleotide microarrays containing 1,200 gene-specific probes were used to quantify mRNA levels, relative to uninjured controls, in spinal cords injured using a standard contusion model. Our results revealed a marked loss of neuron-specific mRNAs at the injury site. The surviving cells showed a characteristic inflammatory response that started at the injury site and spread to the distal cord. Changes in several mRNA levels were associated with putative regenerative responses in the spinal cord. Notably, phosphodiesterase 4, nestin, glia-derived neurite promoting factor, and GAP-43 mRNAs increased significantly. Other mRNAs clustered temporally and spatially with these regeneration-associated genes. Thus we have described global patterns of gene expression following acute SCI, and we have identified targets for future study and possible therapeutic intervention.
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Schmutz, Maximilian, Manuela Zucknick, Richard F. Schlenk, Konstanze Döhner, Hartmut Döhner, Christoph Plass, Lars Bullinger, and Rainer Claus. "Differential DNA Methylation Predicts Response To Combined Treatment Regimens With a DNA Methyltransferase Inhibitor In Acute Myeloid Leukemia (AML)." Blood 122, no. 21 (November 15, 2013): 2539. http://dx.doi.org/10.1182/blood.v122.21.2539.2539.
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Abstract Deregulated epigenetic mechanisms have been identified as major components of acute myeloid leukemia (AML) pathogenesis. This improved mechanistic understanding has started to translate into clinics and leads to the development of novel therapeutic options as exemplified by the DNA methyltransferase (DNMT) inhibitors 5-azacytidine (5-azaC) and decitabine (DAC). However, biomarkers for response prediction to epigenetic therapy are urgently needed. Recently, we and others demonstrated that in-depth characterization of leukemia-associated DNA-methylation patterns contributes to refinement of the molecular classification and of prognostication in AML. Thus, disease associated methylation patterns might also harbor predictive relevance for identification of patients who will profit from DNMT inhibitor therapy and for support of therapeutic decision making. In order to identify a DNA methylation based response predictor, we applied a two-step strategy and generated genome-wide profiles underlying response and resistance to a combination chemotherapy applied within the AMLSG 12-09 Study (ClinicalTrials.gov Identifier: NCT01180322) comprising the drugs idarubicin and etoposide plus the demethylating agent 5-azaC as induction therapy. By methylated-CpG immune-precipitation and next generation sequencing (MCIp-seq), we generated DNA methylation profiles of responders (n=12) and non-responders (n=23). A supervised empirical Bayes approach for the analysis of sequencing read count data (“edgeR”) was applied to identify differentially methylated regions (DMRs) associated with 5-azaC response. We identified 550 genomic regions (based on 500 bp binning) that exposed highly significant read count differences indicating differential DNA methylation between both patient groups. The GC content distribution within the identified differentially methylated regions (DMRs) was comparable to the entire genome. 14% of the DMRs were located in gene promoter regions, 60% in intragenic and 26% in intergenic regions. Overall, the detected DMRs were considerably enriched in the vicinity of transcriptional start sites and preferentially targeted genes acting as transcriptional regulators (including transcription factors involved in hematopoiesis). Within the set of 550 DMRs, we selected the 40 most significantly discriminating regions and validated them with quantitative DNA methylation data from the Illumina Infinium® HumanMethylation450 Bead Chip. 25% of the selected DMRs were covered by only one probe whereas the majority was covered by up to six probes totaling in 107 probes (CpGs). We detected a good correlation between MCIp-seq und 450k-derived methylation data for each patient (median Spearman’s rho = 0.69, 95%-CI [0.32, 0.87]) and could validate 90% of DMRs via quantitative 450k array data. Comprising 95 probes, these validated DMRs were used to create a multivariable signature for therapy response prediction. Through a penalized logistic regression model (“elastic-net”-penalty) applied to the 450k M-values in our discovery sample set, we identified a signature containing 17 probes (CpGs) associated with 12 genes which predicted response perfectly. Four of the identified CpGs were located in promoters, 11 in intragenic and two in intergenic regions. Among the genes targeted by differential methylation in our signature, we found WNT10A, a component of the WNT-beta-catenin-TCF signaling pathway, and PKMYT1. The latter one is a membrane-associated serine/threonine protein kinase which is regulated by polo-like kinase 1. Its inhibition has been reported recently to sensitize for cytarabine-mediated toxicity in vitro. Furthermore, two DMRs associated with the promoters of miRNAs (miR-3154, miR-3186) were contained in the signature. In summary, by genome-wide screening approaches, we identified differentially methylated genes and genomic regions that are associated with response to treatment regimens containing the DNMT inhibitor 5-azaC. At the same time, the predictive DMRs also harbor high potential to be functionally linked to molecular mechanisms and pathways involved in therapy response. By variable selection, we created a minimal signature that accurately predicts response in our discovery sample set. Further validation of this response-signature in independent cohorts of AML cases also comprising patients treated with decitabine are underway. Disclosures: Schlenk: Celgene: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Chugai: Research Funding; Amgen: Research Funding; Novartis: Research Funding; Ambit: Honoraria.
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Bedoya, Ana Cristina, Christine Ginalis, Jeenia Zaki, and Yoko Nomura. "A-37 Interactions between in-Utero Stress Exposure, Externalizing Behavior, and Psychophysiology in Young Children." Archives of Clinical Neuropsychology 36, no. 6 (August 30, 2021): 1078. http://dx.doi.org/10.1093/arclin/acab062.55.
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Abstract Objective The current study examines the associations between low resting heart rate (HR), low electrodermal activity (EDA), and externalizing behavior (EB) in children 1–5 years old through the following measures: baseline 1 (B1) HR, startle period HR, and recovery-stage HR HR, EDA amplitude and skin conductance responses (SCR). We also investigate whether in-utero stress (exposure to Hurricane Sandy) moderates these relationships. Method A subsample of 206 children was drawn from a NIMH longitudinal study, the Stress in Pregnancy Study, that follows offspring from in-utero to 6 years of age. HR and EDA data was collected during a startle-probe paradigm. Mean age of the participants was 3.89 years. Approximately 52% were female and 50.5% were Hispanic. Participants’ EB was assessed by the Behavioral Assessment Screening for Children Version-2 parent rating scales. Externalizing symptoms were trichotomized (high, medium, and low). Results One-way ANOVA showed that three EB groups differed in baseline-HR (p = 0.034), startle-HR (p = 0.006), and recovery-stage HR (p = 0.008) in 4-year olds. EDA was not significantly different between EB groups. Furthermore, Hurricane Sandy exposure significantly and marginally significantly moderates the relationship between EB and amplitude (b = 3.0344, p = 0.044) and EB and SCR (b = 1.5629, p = 0.056), respectively. Hurricane Sandy exposure did not moderate the relationship between EB and HR. Conclusion Externalizing problem symptom groups significantly differ in HR, but not EDA. Hurricane Sandy exposure moderates the relationship between EB and EDA, but not EB and HR. Results suggest that HR and EDA are differentially susceptible to environmental influence. Results can guide biologically informed treatments/screeners for EB in children.
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Gari, Manju, Kumari Ranjeeta, Lakhan Majhee, Akhilesh Kumar, and Sumit Kumar Mahato. "A comparative study of antinociceptive effect of paroxetine with pethidine in acute pain in albino rats." International Journal of Basic & Clinical Pharmacology 6, no. 7 (June 23, 2017): 1728. http://dx.doi.org/10.18203/2319-2003.ijbcp20172739.
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Background: Pain is the most common reason patients seek medical care. Increased level of monoamines (serotonin and norepinephrine) in synaptic clefts lead to changes in pain threshold and induce antinociception. The study was carried out to evaluate antinociceptive effect of paroxetine in albino rats and to probe into its possible mechanism of action. The study was carried out to evaluate anti-nociceptive effect of paroxetine in albino rats.Methods: Male Albino rats of average weight 150-240gms were used. The drugs used were paroxetine 5mg/Kg, pethidine 5mg/kg (standard drug). Anti-nociceptive effect tested by using thermal method i.e. Tail flick response and Tail warm water immersion method.Results: In this study, Anti-nociceptive effect of respective drugs were measured by using two methods i.e. tail flick test and tail warm water immersion method at 0 min., 30 min., 60 min. and 90min.after administration of drugs. Reaction time started to increase from baseline at 0 min. and peak effect was seen at 60 min. then it started to decrease at 90 min. in almost all the groups except in control group.Conclusions: Paroxetine have significant analgesic effect in acute pain, which may be mediated via central and peripheral mechanisms. Efficacy of Paroxetine is almost equal to that of standard drug pethidine in acute pain management.
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Musicò, Angelo, Roberto Frigerio, Alessandro Mussida, Luisa Barzon, Alessandro Sinigaglia, Silvia Riccetti, Federico Gobbi, et al. "SARS-CoV-2 Epitope Mapping on Microarrays Highlights Strong Immune-Response to N Protein Region." Vaccines 9, no. 1 (January 11, 2021): 35. http://dx.doi.org/10.3390/vaccines9010035.
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A workflow for rapid SARS-CoV-2 epitope discovery on peptide microarrays is herein reported. The process started with a proteome-wide screening of immunoreactivity based on the use of a high-density microarray followed by a refinement and validation phase on a restricted panel of probes using microarrays with tailored peptide immobilization through a click-based strategy. Progressively larger, independent cohorts of Covid-19 positive sera were tested in the refinement processes, leading to the identification of immunodominant regions on SARS-CoV-2 spike (S), nucleocapsid (N) protein and Orf1ab polyprotein. A summary study testing 50 serum samples highlighted an epitope of the N protein (region 155–71) providing good diagnostic performance in discriminating Covid-19 positive vs. healthy individuals. Using this epitope, 92% sensitivity and 100% specificity were reached for IgG detection in Covid-19 samples, and no cross-reactivity with common cold coronaviruses was detected. Likewise, IgM immunoreactivity in samples collected within the first month after symptoms onset showed discrimination ability. Overall, epitope 155–171 from N protein represents a promising candidate for further development and rapid implementation in serological tests.
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Musicò, Angelo, Roberto Frigerio, Alessandro Mussida, Luisa Barzon, Alessandro Sinigaglia, Silvia Riccetti, Federico Gobbi, et al. "SARS-CoV-2 Epitope Mapping on Microarrays Highlights Strong Immune-Response to N Protein Region." Vaccines 9, no. 1 (January 11, 2021): 35. http://dx.doi.org/10.3390/vaccines9010035.
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A workflow for rapid SARS-CoV-2 epitope discovery on peptide microarrays is herein reported. The process started with a proteome-wide screening of immunoreactivity based on the use of a high-density microarray followed by a refinement and validation phase on a restricted panel of probes using microarrays with tailored peptide immobilization through a click-based strategy. Progressively larger, independent cohorts of Covid-19 positive sera were tested in the refinement processes, leading to the identification of immunodominant regions on SARS-CoV-2 spike (S), nucleocapsid (N) protein and Orf1ab polyprotein. A summary study testing 50 serum samples highlighted an epitope of the N protein (region 155–71) providing good diagnostic performance in discriminating Covid-19 positive vs. healthy individuals. Using this epitope, 92% sensitivity and 100% specificity were reached for IgG detection in Covid-19 samples, and no cross-reactivity with common cold coronaviruses was detected. Likewise, IgM immunoreactivity in samples collected within the first month after symptoms onset showed discrimination ability. Overall, epitope 155–171 from N protein represents a promising candidate for further development and rapid implementation in serological tests.
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Matrai, Zoltan, Hajnalka Andrikovics, Judit Csomor, Botond Timár, András Kozma, Attila Tordai, and Tamas Masszi. "Extramedullary Myeloid Sarcoma With Eosinophilia and FIP1L1-Pdgfra Rearrangement: Complete Cytogenetic Response To Imatinib Therapy." Blood 122, no. 21 (November 15, 2013): 5033. http://dx.doi.org/10.1182/blood.v122.21.5033.5033.
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Abstract Background Myeloid sarcomas are rare extramedullary manifestations of acute myeloid leukemia (AML) representing less then 1% of all cases. Since they invariably progress into systemic disease, early AML-like chemotherapy is mandated. Myeloproliferations with eosinophilia and involvement of the PDGFRA, PDGFRB or FGFR1 genes are distinct entities in the 2008 WHO classification with peculiar sensitivity to tyrosine kinase inhibitors. Extramedullary myeloid sarcomas with eosinophilia and FIP1L1-PDGFRA fusion gene expression are extremely rare with only two cases described. Here we report a case of extramedullary leukemia, eosinophilia and FIP1L1-PDGFRA rearrangement responding favourably to imatinib. Case history A 32-year old man presented with a 3-month history of subcutaneous nodules growing gradually in the occipital, chest, abdominal and perianal regions, the largest being 50 x 60 x 18 mm in size and exulcerated. There was no weight loss or fever. Complete blood count showed WBC of 6,8 x 109/L, Hb level of 104 g/dl and platelet count of 377 x 109/L. The differential revealed 42% neutrophils, 25% lymphocytes, 5% monocytes and 28% eosinophils with an absolute eosinophil count of 1,92 x 109/L. Apart from mildly elevated LDH (539 U/L, normal range: 153 - 463 U/L), other laboratory results were unremarkable. CT scan found no lymphadenopathy or hepatosplenomegaly. Histology of the nodules showed infiltration with immature monoblasts, negative for CD34, CD117 and weakly positive for MPO and CD68. Mutations of the FLT3 and nucleophosmin genes were not present and TCR gene rearrangement analysis did not reveal clonality. Bone marrow biopsy showed an increase of eosinophilic precursors without apparent blast excess. FISH analysis of the nodules performed with the LSI FIP1L1/PDGFR alpha probe detected deletion of the CHIC2 gene in most interphase nuclei. Bone marrow karyotype was normal, and FISH probes proved negative for AML/ETO and inv(16). In 15% of interphases, the FIP1L1/PDGFR alpha fusion signal could be detected. RT PCR showed FIP1L1-PDGFR alpha gene fusion in the marrow. A diagnosis of extramedullary myeloid sarcoma with concomittant eosinophilia and FIP1L1/PDGFRA fusion gene expression was established. To our knowledge, this is the third such case reported so far. Induction regimen consisted of 7 days of Ara-C (200 mg/m2) and 3 days of daunorubicin (60 mg/m2). This resulted in regression but not complete disappearance of the subcutaneous nodules. After the therapy-induced aplasia, restitution of platelets preceded neutrophils and mild thrombocytosis developed. The bone marrow showed increased eosinophils without blast excess. FISH analysis detected the presence of the FIP1L1-PDGFRA fusion signal in 11% of nuclei. Imatinib mesylate, 100 mg/day was started. In 14 days, the platelet count returned to normal and the residual nodules disappeared completely. After 5 weeks of imatinib therapy, the patient is doing well without any complaints and the bone marrow shows complete cytogenetic response. Conclusion this case of extramedullary AML, eosinophilia and FIP1L1/PDGFRA rearrangement persisting after intensive chemotherapy but responding well to low-dose imatinib emphasizes the importance to screen for mutations of the PDGFR gene in AML with major eosinophilic component due to the major therapeutic implications. Disclosures: No relevant conflicts of interest to declare.
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Benmarouane, Abdelilah, T. Hansen, Pierre Millet, and Alain Lodini. "Investigation of the Hydroxyapatite Crystallites in Bone at the Interface with Implant by Neutron Diffraction." Materials Science Forum 539-543 (March 2007): 612–16. http://dx.doi.org/10.4028/www.scientific.net/msf.539-543.612.
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The basic principles behind human tissue response to artificial surface implantation may be developed under its biological aspect, it is necessary for a medical use to study the mechanical limits of every biomaterials to predict the tissue and the body's response according to the composition, the structure and the design of a biomedical material. To promote a stable and functional direct connection between bone and implant, titanium implants can be coated with materials based on calcium phosphate ceramics such as hydroxyapatite (HAp)(Ca10(P04)6(OH)2). The preferred orientation of HAp crystallites at the interface bone-implant in sheep tibia bones has been measured with the neutron 2-axis diffractometer D20 at the Institut Max von Laue-Paul Langevin (ILL), extracted 60 days after implantation. The implant has two faces, one coated and one non-coated with plasma-sprayed HAp (80 .m). We probed the samples with a spatial resolution of 0.5 mm started from the interface in order to inspect the reorganisation of the HAp crystallite’s distribution after implantation.
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Pokora, Ilona, and Aleksandra Żebrowska. "Application of A Physiological Strain Index in Evaluating Responses to Exercise Stress – A Comparison Between Endurance and High Intensity Intermittent Trained Athletes." Journal of Human Kinetics 50, no. 1 (April 1, 2016): 103–14. http://dx.doi.org/10.1515/hukin-2015-0142.
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AbstractThe study evaluated differences in response to exercise stress between endurance and high-intensity intermittent trained athletes in a thermoneutral environment using a physiological strain index (PSI). Thirty-two subjects participated in a running exercise under normal (23°C, 50% RH) conditions. The group included nine endurance trained athletes (middle-distance runners - MD), twelve high-intensity intermittent trained athletes (soccer players - HIIT) and eleven students who constituted a control group. The exercise started at a speed of 4 km·h–1 which was increased every 3 min by 2 km·h–1 to volitional exhaustion. The heart rate was recorded with a heart rate monitor and aural canal temperature was measured using an aural canal temperature probe. The physiological strain index (PSI) and the contribution of the circulatory and thermal components to the overall physiological strain were calculated from the heart rate and aural canal temperature. The physiological strain index differed between the study and control participants, but not between the MD and HIIT groups. The physiological strain in response to exercise stress in a thermoneutral environment was mainly determined based on the circulatory strain (MD group - 73%, HIIT group – 70%). The contribution of the circulatory and thermal components to the physiological strain did not differ significantly between the trained groups (MD and HIIT) despite important differences in morphological characteristics and training-induced systemic cardiovascular and thermoregulatory adaptations.
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Bernasconi, Paolo, Irene Dambruoso, Marina Boni, Paola Maria Cavigliano, Ilaria Giardini, Rita Zappatore, Silvia Calatroni, et al. "Fluorescence In Situ Hybridisation (FISH) To Reveal Isochromosome 7q, i(7)(q10), in Hepatosplenic T-Cell Lymphoma (HSTCL)." Blood 108, no. 11 (November 16, 2006): 4606. http://dx.doi.org/10.1182/blood.v108.11.4606.4606.
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Abstract We report two HSTCL patients who were studied with conventional cytogenetics (CC) and FISH on clinical diagnosis and during the follow-up to better understand the genetic events underlying this type of lymphoma. They were a 21-year old male and a 44-year old woman who came to our clinic for evaluation because of B-symptoms. On physical examination they presented massive splenomegaly and hepatomegaly. A peripheral blood count revealed anemia and thrombocytopenia in one patient and anemia in the other. They both presented high lactic dehydrogenase levels. A bone marrow biopsy demonstrated that a malignant T-cell population constituted 30% of all marrow cells in one patient and entirely substituted normal hemopoiesis in the other. This malignant T-cell population was CD2+,CD3+,CD7+,CD56+,CD4−,CD5−,CD8−. In addition, the T-cell clone, which showed a sinusal localization, was TCRα/β + in one case and TCRγ/δ + in the other. The two patients underwent splenectomy and it was shown that the red pulp had been completely infiltrated by a malignant cell population identical to that present in the marrow of the two patients. Therefore, a diagnosis of α/β + and γ/δ+ HSTCL in stage IVB was made and the patients started treatment. The male succeeded in entering a complete remission (CR) of only three month duration and after a bone marrow relapse was unable to achieve a second CR. The female did not respond to chemotherapy and died of disease related complications. CC and FISH studies were performed on bone marrow cells. CC discovered a normal chromosome pattern in the twenty metaphases obtained from the first patient, and an abnormal pattern in the eighteen mitotic cells obtained from the second whose karyotype was: 46,XX[7]/46,XX,i(7)(q10)[5]/47,XX,i(7)(q10),+i(7)(q10)[6]. FISH on mitotic and interphase cells was performed with the 7q31/CEP11 probe (Vysis) and the Bacterial Artificial Chromosome (BAC) probes RP11-79N1, RP11-299F5, RP11-1132K14, RP11-163M21 (kindly provided by the Wellcome Trust Sanger Institute, Cambridge UK and by the BACPAC Resources Children’s Hospital, Oakland, USA), which were localized on 7p15 and covered the HOXA cluster. The commercial probes were applied according to manufacturer’s guidelines. Hybridization procedures were carried out first with the BAC probes and subsequently with the commercial probes. On clinical diagnosis a significant cell population with the aberrant pattern (1×7p/2×7cen/3×7q) corresponding to i(7)(q10) was discovered in 25% of marrow cells from the first patient and in 90% marrow cells from the second. Interestingly, in the first patient the percentage of cells displaying this pattern equalled the percentage of cells infiltrating the marrow on morphologic examination. However, when this patient relapsed we did not succeed in identifying any cell carrying the 1×7p/2×7cen/3×7q pattern (cut-off fixed at 2%), even if the percentage of malignant T-cells infiltrating the marrow was higher than on diagnosis. In addition, CC revealed an absolutely normal chromosome pattern leading us to hypothesize that a cryptic genetic event might have occurred. In conclusion, our findings further underscore the association between i(7)(q10) and HSTCL, suggest that the number of i(7)(q10) present in the malignant cell might reduce response to treatment, lead us to hypothesize that patients who relapse might develop a second more subtle genetic lesion.
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Luño, E., C. Sanzo, M. González, A. Alonso, F. Jonte, M. Balbin, F. Fresno, and A. Ramírez. "B-Diffuse Large Cell Lymphoma and Nonrandon Karyotipic Abnormalities in Ph Negative Cells of Patients with Ph-Positive Chronic Myeloid Leukemia Imatinib Treated." Blood 110, no. 11 (November 16, 2007): 4579. http://dx.doi.org/10.1182/blood.v110.11.4579.4579.
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Abstract Aim: Investigate other chromosome abnormalities (OCAs) in Ph-cells of CML imatinib treated patients and analyze whether these changes have some implication to establish clonal disorders. 44 patients, 31 males and 13 females. Median age 51 years (R 14–81). Two patients were in accelerated phase (AP) and one in blast crisis (BC) at the beginning of imatinib (IM). Dose: 400 mg daily with subsequent escalations. 25 received IM up-front but 6 had a short outcome and 19 have been treated with prior CML therapy. Only one imatinib up-front failed to reach the hematological response. 89,5% of valuable cases IM up-front reached complete cytogenetic response (CCgR), 82% at 12 months vs 68% CCgR (31% at 12 mo) for patients with prior therapy(p=0,01). FISH was performed using LSI BCR/ABL ES probe. 500 cells were scored. Cases with +8, FISH was performed using simultaneous BCR/ABL and CEP8 probes. FISH was require to confirm CCgR, because conventional cytogenetic (CC) cannot theoretically detect disease <3–5% since usually 20–30 metaphases are evaluated. Two had a variant t(2;9;22) and t(16;22). 5 had additional chromosome abnormalities (ACAs): 2 at diagnosis, 1 in IM resistance and 2 in AP. Unexpectedly, a der del(9q) was detect in 2 patients when IM resistance and only a third at diagnosis. None of 4 mutation cases had ACAs. Three cases, above reported, developed clonal changes in Ph- cells. Case 1: A 72 years man diagnosed in December 2002 with CP-CML. He received IM 600 mg daily and achieved CCgR at 18 mo and molecular complete response (CMolR) at 30 mo. A routine BM at 36 mo, showed a isolated lymphoid proliferation resemble a normal lymph node. CC demonstrated a karyotype with 46,XY,add(14q),−19,+mar [2/29] and a derivative clone near-tetraploid [2/29]. No Ph was found. FISH confirmed BCR/ABL- and 15% hyperploid cells. RQ-PCR showed CMolR. After 30 days, he develops a B-DLCL with generalised lymphadenopathy. Lymphoid cells were CD20+, CD10−, 60% Ki67. CC showed the pseudodiploid Ph- clone before detect in BM but not hyperploidy. FISH confirmed a variant BCL2 rearrangement at 97% and BCR/ABL negativity. PCR demonstrated B clonatity. Retrospective FISH and PCR of previous BM showed 15% t(14;18), hyperploidy and B clonality. The patient died promptly. Necropsy confirmed B-NHL. Case 2: A 47 years woman diagnosed with CML in june 2000 received multiples therapy without CgR. No OCAs are detected at this time. In January 2003 started 400 mg IM daily. CCgR was reached at 12 mo and MMolR at 18 mo. BM at 36 mo didn’t show dysplasia. All 16 metaphases were Ph- and 44% of them had +8. By FISH bcr/abl was negative and 51% cells Ph- showed +8. At 54 mo, she hasn’t cytopenias but a loss of CCgR and MMolR are evident. IM dose was increased. Case 3: A 42 years woman with CML t(2;9;22) diagnosed in June 2006. At 6 months, a BM showed no dysplasia. CC showed t(2;9;22) in 5/20 metaphases and +8 in 3/15 Ph- metaphases. At 12 months, the Ph were present in 2/45 metaphases, 4/43 Ph- cells had +8, 2/43 had +8, −17 and 37/45 were 46,XX. At this time have myeloid dysplasia without cytopenias. Dasatinib treatment was started. Conclusion: Though the cause of this phenomenon remains to determined, our observations in this small series suggest that clonal OCAs are becoming more evident when more patients achieving CCgR with imatinib. This treatment may favour the manifestation of Ph-negative clonal disorders, even a B-NHL not previously reported. In two cases with trisomy 8 the Imatinib response was affected.
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BLOM, ELMA, and JOHANNE PARADIS. "Sources of individual differences in the acquisition of tense inflection by English second language learners with and without specific language impairment." Applied Psycholinguistics 36, no. 4 (January 27, 2014): 953–76. http://dx.doi.org/10.1017/s014271641300057x.
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ABSTRACTThe goal of this study was to investigate whether individual difference factors influence the second language (L2) learning of children with specific language impairment (SLI) and children with typical development (TD) differently. The study focuses on tense inflection development in English L2 children. The roles of age of L2 acquisition, length of L2 exposure, and first language (L1) were examined. Twenty-four pairs of 4- and 5-year-old English L2 children with SLI and English L2 children with TD participated in the study. Children's responses on the third person singular and regular past tense probes of the Test of Early Grammatical Impairment (Rice & Wexler, 2001) were analyzed using logistic mixed regression modeling and classification procedures. For all children, those who started learning English later performed better than children who started learning English earlier, but the advantage of an older age of acquisition was particularly present in the L2 with SLI group. For children in the L2 group with TD, their accuracy with tense inflection clearly increased with longer L2 exposure, but this was not found for the L2 children with SLI. Finally, L2 children with TD were better able to transfer L1 knowledge than L2 children with SLI.
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Vergani, G. B., M. S. D. Lima, K. M. Silva, A. W. U. Monteiro, A. F. Ramos, R. I. T. P. Batista, W. R. R. Vicente, M. E. F. Oliveira, and J. F. Fonseca. "225 Evaluation of superovulatory response in Brazilian native sheep by B-mode ultrasonography." Reproduction, Fertility and Development 32, no. 2 (2020): 240. http://dx.doi.org/10.1071/rdv32n2ab225.
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The objective of this study was to evaluate the correlation between the number of corpora lutea (CL), as determined by B-mode ultrasonography, and the total number of structures recovery by non-surgical embryo recovery (NSER) from superovulated ewes. Somali (n=18), Santa Inês (n=18), and Morada Nova (n=16) ewes received an intravaginal device with progesterone (0.33g, controlled internal drug release device, CIDR, Zoetis), which was maintained for 9 days. The superovulatory protocol started 60h before device removal, with 6 decreasing doses (25, 25, 15, 15, 10, and 10%) of p-FSH (IM 133mg, Folltropin V, Vetoquinol) injected every 12h. D-Cloprostenol (IM 37.5μg, Prolise, Agener Union) was injected 12h before and at the moment of device removal. Ewes in oestrus were mated by fertile male rams three times after the onset of oestrus with a 12-h interval. Flunixin meglumine (24.9 mg; Banamine, MSD Animal Health) was injected IM on Days 12, 13, and 15. One day before NSER, B-mode ultrasound evaluations were performed using portable equipment (Z5 Vet, Mindray) with a stiffened multifrequency linear probe to evaluate the number of structures present in the ovaries. Embryo recovery was performed 7 days after progesterone CIDR removal (Day 16). The number of CL and the number of recovered structures were determined and their association evaluated using the Pearson correlation test (P<0.05). Only 17 Somali, 16 Santa Inês, and 15 Morada Nova ewes were submitted to NSER; the other 4 ewes could not be flushed because of low cervical dilation or cervical puncture. After B-mode ultrasound evaluation, 168, 217, and 131 CL were observed, with an average of 9.9 (range: 1 to 12), 13.5 (range: 2 to 47), and 8.7 (range: 3 to 18) CL per donor for Somali, Santa Inês, and Morada Nova ewes, respectively. The recovery rates (i.e. structures recovered by the number of CL counted) were 60.1% (101/168), 96.3% (209/217), and 103.5% (135/131) for the 3 breeds, respectively. There was a positive correlation (r=0.69; P<0.01) between the number of recovered structures and number of CL. Those findings confirm results from other studies, in which the recovery rate varied from 35 to 91%. In some cases, recovery rate can be overestimated because of the difficulty in quantifying CL. In conclusion, B-mode ultrasonography can be used to estimate superovulatory response in ewes and thus as a criterion to decide whether a donor will undergo embryo flushing. Financial support for this study was provided by Embrapa (02.13.06.026.00.04) and Fapemig (CVZ-PPM 00201-17).
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Schnittger, Susanne, Frank Dicker, Tamara Alpermann, Christiane Eder, Annette Fasan, Simone Weber, Sabine Jeromin, et al. "Characterization and Quantification Of Rare BCR-ABL1 Fusion Transcripts." Blood 122, no. 21 (November 15, 2013): 4013. http://dx.doi.org/10.1182/blood.v122.21.4013.4013.
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Abstract Background In chronic myeloid leukemia (CML) treatment with tyrosine kinase inhibitors induces extremely good responses in most of the patients (pts). To control for treatment responses molecular monitoring by quantitative real time PCR has become a standard procedure. Many international efforts have been done to standardize PCR assays, an international conversion factor has been introduced which allows comparison of results between laboratories, and response criteria have been defined based on %BCR-ABL1/ABL1 values. A drawback of the current state is that standardization, so far, addressed only the most common BCR-ABL1 fusion transcripts e13a2 and e14a2. For rare fusion types response criteria have not been applied and biological and prognostic significance are widely unknown. Aim 1) Analyze incidence and associations of rare BCR-ABL1 fusion types with other biological parameters. 2) Develop assays for rare BCR-ABL1 fusions to allow molecular monitoring and analysis of therapy response in CML patients with rare fusion types. Patients and Methods In 5,730 individual CML pts a detailed molecular characterization of the BCR-ABL1 rearrangement was performed between 8/2005 and 6/2013. Rare fusion transcripts were further characterized by Sanger sequencing, and quantification was performed by a LightCycler based real time assay using hybridization probes. Probes and reverse primers delevoped for M-bcr transcripts were used (Emig et al., Leukemia, 1999). Solely the forward primer was modified and adapted to the BCR breakpoint. Assays were optimized to obtain similar efficiencies and sensitivities (1:10,000) compared to the standard p210 assay. Results In the entire cohort of 5,730 CML pts rare fusion types were detected in 112 cases (2.0%). In detail, of the rare types 49/112 (43.8%) had breakpoints in the m-bcr (minor breakpoint cluster region, corresponding to p190): e1a2 (n=46, 41.1%) and e1a3 (n=3, 2.7%). 26 cases (23.2%) had rare M-bcr types (major breakpoint cluster region, corresponding to p210): e13a3 (n=8), e14a3 (n=15), e13e14a3 (n=2) and one case with e14a3 and insertion of 45 nucleotides. 20 pts (17.9%) had a typical µ-bcr breakpoint with e19a2 (corresponding to p230), including one case with an additional alternative splicing event that leads to an e13a2 fusion with 19 bp insertion. Further very rare fusions were: e4a2 (n=2), e6a2 (n=5), e16a2 (n=1), e18a2 (n=2), and e8a2 (n=7) (e8a2 fusions had in frame additions or deletions of 39-70 bp). The male/female ratio in this cohort was 65/47 (1.4), and median age was 66.9 years (y) (range: 20-87y). In 77 of the 112 cases a sample at diagnosis was available. In the remaining 35 pts monitoring started later. Of the 61 cases with available cytogenetics 38 pts had t(9;22) sole and 23 (37.7%) had additional chromosomal aberrations (ACA): -7 (n=2), +8 (n=4), i(17q) (n=1), dup(17)(q23q25) (n=1), -Y (n=7), +der(22)t(9;22) (n=3), rare translocations (n=5). Thus, the frequency of ACA was significantly higher than has been described for CML in general (6.9%, Fabarius et al., Blood, 2011). Of the 112 patients 714 individual samples were quantified (e1a2 and e1a3: n=237, e13a3 and e14a3: n=191, e19a2: n=144, e16a2: n=24, e18a2: n=21, e8a2: n=60, e6a2: n=28 e4a2: n=9). Regular monitoring at every 3 months was available in 76 pts who were treated with firstline imatinib (n=64), followed by second line nilotinib (n=4) or dasatinib (n=3); firstline dasatinib (n=7), followed by nilotinib (n=1), or firstline nilotinib (n=5). Response was evaluated after 1 year and subdivided as follows: 1) CMolR (complete molecular response): undetectable BCR-ABL1, 2) MMolR (major molecular response): ≤0.1% BCR-ABL1/ABL1, 3) no response: no or less that 1 log decrease, 4) suboptimal response: > 0.1% BCR-ABL1/ABL1. In 15 pts (19.7%) a CMolR and in 20 pts (26.3%) a MMolR was reached (in 1 case after switch from imatinib to nilotinib and in 1 from imatinib to dasatinib). However, there was a large number of cases with no response: n=19 (25.0%) or suboptimal response: n=22 (28.9%). In 55 of the 76 continuously monitored pts cytogenetics at time of diagnosis was available. In the poor responders slightly more cases had ACA (12/28; 42.9%) compared to the good responders (7/27; 25.9%) (n.s.). Conclusion Rare BCR-ABL1 fusion types 1) occur in 2% of all CML, 2) are associated with higher number of ACA, 3) have no or suboptimal response to TKI treatment in more than 50% of pts. Disclosures: Schnittger: MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Dicker:MLL Munich Leukemia Laboratory: Employment. Alpermann:MLL Munich Leukemia Laboratory: Employment. Eder:MLL Munich Leukemia Laboratory: Employment. Fasan:MLL Munich Leukemia Laboratory: Employment. Weber:MLL Munich Leukemia Laboratory: Employment. Jeromin:MLL Munich Leukemia Laboratory: Employment. Meggendorfer:MLL Munich Leukemia Laboratory: Employment. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.
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Fan, W., X. Li, W. Wang, J. S. Mo, H. Kaplan, and N. G. F. Cooper. "Early Involvement of Immune/Inflammatory Response Genes in Retinal Degeneration in DBA/2J Mice." Ophthalmology and Eye Diseases 2 (January 2010): 117917211000200. http://dx.doi.org/10.1177/117917211000200005.
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Purpose The DBA/2J (D2) mouse carries mutations in two of its genes, Tyrp1 and Gpnmb. These alterations result in the development of an immune response in the iris, leading to iris atrophy and pigment dispersion. The development of elevated intraocular pressure (IOP) in this model of glaucoma is considered to be a significant factor leading to the death of retinal ganglion cells (RGCs). Changes in gene expression in the retina have already been correlated with the appearance of elevated IOP in the D2 mouse. The purpose of the present study was to determine if any changes in gene expression occur prior to the development of IOP. Methods The IOP was measured monthly using a rebound tonometer in D2 and age-matched C57/BL6 (B6) mice (normal controls). D2 animals with normal IOP at 2 and 4 M were used. In addition, mice at the age of 6–7 M were included to look for any trends in gene expression that might develop during the progression of the disease. Separate RNA samples were prepared from each of three individual retinas for each age, and gene expression profiles were determined with the aid of mouse oligonucleotide arrays (Agilent). A subset of genes was examined with the aid of real-time PCR. Immunocytochemistry was used to visualize changes in the retina for some of the gene-products. Results Four hundred and thirteen oligonucleotide probes were differentially expressed in the retinas of 4 M versus 2 M old D2 mice. The most significantly up-regulated genes (181) were associated with immune responses including interferon signaling, the complement system and the antigen presentation pathway, whereas the down-regulated genes (232) were linked to pathways related to cell death and known neurological diseases/disorders. These particular changes were not revealed in the age-matched B6 mice. By 6 M, when IOP started to increase in many of the D2 mice, more robust changes of these same genes were observed. Changes in the levels of selected genes, representative of different functions/pathways, were validated with RT-PCR, and changes in glial responses were visualized in the retina with immunocytochemistry. Conclusions The results showed that the expression of genes related to the immune response and acute stress were altered independently of the development of elevated IOP, and indicated early involvement of the immune system in the onset of the disease. The later development of elevated IOP, observed in this animal model, was coincident with continued changes in expression of genes observed at earlier time points. Further studies are warranted to identify the roles of specific genes identified here with respect to the death of the RGCs.
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Matsumura, M., J. Kojima, T. W. Gardiner, and O. Hikosaka. "Visual and oculomotor functions of monkey subthalamic nucleus." Journal of Neurophysiology 67, no. 6 (June 1, 1992): 1615–32. http://dx.doi.org/10.1152/jn.1992.67.6.1615.
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1. Single-unit recordings were obtained from the subthalamic nuclei of three monkeys trained to perform a series of visuooculomotor tasks. The monkeys were trained to fixate on a spot of light on the screen (fixation task). When the spot was turned off and a target spot came on, they were required to fixate on the target quickly by making a saccade. Visually guided saccades were elicited when the target came on without a time gap (saccade task). Memory-guided saccades were elicited by delivering a brief cue stimulus while the monkey was fixating; after a delay, the fixation spot was turned off and the monkey made a saccade to the remembered target (delayed saccade task). 2. Of 265 neurons tested, 95 showed spike activity that was related to some aspects of the visuooculomotor tasks, whereas 66 neurons responded to active or passive limb or body movements. The task-related activities were classified into the following categories: eye fixation-related, saccade-related, visual stimulus-related, target- and reward-related, and lever release-related. 3. Activity related to eye fixation (n = 22) consisted of a sustained spike discharge that occurred while the animal was fixating on a target light during the tasks. The activity increased after the animal started fixating on the target and abruptly ceased when the target went off. The activity was unrelated to eye position. It was not elicited during eye fixation outside the tasks. The activity decreased when the target spot was removed. 4. Activity related to saccades (n = 22) consisted of a phasic increase in spike frequency that was time locked with a saccade made during the tasks. The greatest increases occurred predominantly after saccade onset. This activity usually was unrelated to spontaneous saccades made outside the task. The changes in activity typically were optimal in one direction, generally toward the contralateral side. 5. Visual responses (n = 14) consisted of a phasic excitation in response to a visual probe stimulus or target. Response latencies usually were 70-120 ms. The receptive fields generally were centered in the contralateral hemifield, sometimes extending into the ipsilateral field. The receptive fields included the foveal region in seven neurons; most of these neurons responded best to parafoveal stimulation. Peripheral stimuli sometimes suppressed the activity of visually responsive neurons. 6. Activity related to target and reward (n = 29) consisted of sustained spike discharge that occurred only when the monkey could expect a reward by detecting the dimming of the light spot that he was fixating.(ABSTRACT TRUNCATED AT 400 WORDS)
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Liu, Gang, Arnaud Friggeri, Yanping Yang, Jadranka Milosevic, Qiang Ding, Victor J. Thannickal, Naftali Kaminski, and Edward Abraham. "miR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis." Journal of Experimental Medicine 207, no. 8 (July 19, 2010): 1589–97. http://dx.doi.org/10.1084/jem.20100035.
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Uncontrolled extracellular matrix production by fibroblasts in response to tissue injury contributes to fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF), a progressive and ultimately fatal process that currently has no cure. Although dysregulation of miRNAs is known to be involved in a variety of pathophysiologic processes, the role of miRNAs in fibrotic lung diseases is unclear. In this study, we found up-regulation of miR-21 in the lungs of mice with bleomycin-induced fibrosis and also in the lungs of patients with IPF. Increased miR-21 expression was primarily localized to myofibroblasts. Administration of miR-21 antisense probes diminished the severity of experimental lung fibrosis in mice, even when treatment was started 5–7 d after initiation of pulmonary injury. TGF-β1, a central pathological mediator of fibrotic diseases, enhanced miR-21 expression in primary pulmonary fibroblasts. Increasing miR-21 levels promoted, whereas knocking down miR-21 attenuated, the pro-fibrogenic activity of TGF-β1 in fibroblasts. A potential mechanism for the role of miR-21 in fibrosis is through regulating the expression of an inhibitory Smad, Smad7. These experiments demonstrate an important role for miR-21 in fibrotic lung diseases and also suggest a novel approach using miRNA therapeutics in treating clinically refractory fibrotic diseases, such as IPF.