Effects of Positive End-expiratory Pressure on Pulmonary Perfusion Distribution and Intrapulmonary Shunt during One-lung Ventilation in Pigs: A Randomized Crossover Study.

BACKGROUND: During one-lung ventilation (OLV), positive end-expiratory pressure (PEEP) can improve lung aeration but might overdistend lung units and increase intrapulmonary shunt. The authors hypothesized that higher PEEP shifts pulmonary perfusion from the ventilated to the nonventilated lung, resulting in a U-shaped relationship with intrapulmonary shunt during OLV. METHODS: In nine anesthetized female pigs, a thoracotomy was performed and intravenous lipopolysaccharide infused to mimic the inflammatory response of thoracic surgery. Animals underwent OLV in supine position with PEEP of 0 cm H2O, 5 cm H2O, titrated to best respiratory system compliance, and 15 cm H2O (PEEP0, PEEP5, PEEPtitr, and PEEP15, respectively, 45 min each, Latin square sequence). Respiratory, hemodynamic, and gas exchange variables were measured. The distributions of perfusion and ventilation were determined by IV fluorescent microspheres and computed tomography, respectively. RESULTS: Compared to two-lung ventilation, the driving pressure increased with OLV, irrespective of the PEEP level. During OLV, cardiac output was lower at PEEP15 (5.5 ± 1.5 l/min) than PEEP0 (7.6 ± 3 l/min) and PEEP5 (7.4 ± 2.9 l/min; P = 0.004), while the intrapulmonary shunt was highest at PEEP0 (PEEP0: 48.1% ± 14.4%; PEEP5: 42.4% ± 14.8%; PEEPtitr: 37.8% ± 11.0%; PEEP15: 39.0% ± 10.7%; P = 0.027). The relative perfusion of the ventilated lung did not differ among PEEP levels (PEEP0: 65.0% ± 10.6%; PEEP5: 68.7% ± 8.7%; PEEPtitr: 68.2% ± 10.5%; PEEP15: 58.4% ± 12.8%; P = 0.096), but the centers of relative perfusion and ventilation in the ventilated lung shifted from ventral to dorsal and from cranial to caudal zones with increasing PEEP. CONCLUSIONS: In this experimental model of thoracic surgery, higher PEEP during OLV did not shift the perfusion from the ventilated to the nonventilated lung, thus not increasing intrapulmonary shunt.

ATP-dependent roX RNA remodeling by the helicase maleless enables specific association of MSL proteins.

Dosage compensation in Drosophila involves a global activation of genes on the male X chromosome. The activating complex (MSL-DCC) consists of male-specific-lethal (MSL) proteins and two long, noncoding roX RNAs. The roX RNAs are essential for X-chromosomal targeting, but their contributions to MSL-DCC structure and function are enigmatic. Conceivably, the RNA helicase MLE, itself an MSL subunit, is actively involved in incorporating roX into functional DCC. We determined the secondary structure of roX2 and mapped specific interaction sites for MLE in vitro. Upon addition of ATP, MLE disrupted a functionally important stem loop in roX2. This RNA remodeling enhanced specific ATP-dependent association of MSL2, the core subunit of the MSL-DCC, providing a link between roX and MSL subunits. Probing the conformation of roX in vivo revealed a remodeled stem loop in chromatin-bound roX2. The active remodeling of a stable secondary structure by MLE may constitute a rate-limiting step for MSL-DCC assembly.

Implicit and explicit memory for affective passages in temporal lobectomy patients.

Eighteen temporal lobectomy patients (9 left, LTL; 9 right, RTL) were administered four verbal tasks, an Affective Implicit Task, a Neutral Implicit Task, an Affective Explicit Task, and a Neutral Explicit Task. For the Affective and Neutral Implicit Tasks, participants were timed while reading aloud passages with affective or neutral content, respectively, as quickly as possible, but not so quickly that they did not understand. A target verbal passage was repeated three times; this target passage was alternated with other previously unread passages, and all passages had the same number of words. The Explicit Affective and Neutral Tasks were administered at the end of testing, and consisted of multiple choice questions regarding passage content. Verbal priming effects in terms of improved reading speed with repetition for the target but not non-target passages were found for patients with both left and right temporal lobectomies. As in the Burton, Rabin et al. [Burton, L., Rabin, L., Vardy, S.B., Frohlich, J., Wyatt, G., Dimitri, D., Constante, S., Guterman, E. (2004). Gender differences in implicit and explicit memory for affective passages. Brain and Cognition, 54(3), 218-224] normative study, there were no interactions between this priming effect and affective/neutral content. For the explicit tasks, items from the repeated passages were remembered better than the unrepeated passages, and there was a trend for information from the affective passages to be remembered better than the neutral passages, similar to the normative pattern. The RTL group did not show the normative pattern of slower reading speed for affective compared to neutral passages that the LTL group showed. Thus, the present findings support the idea that intact right medial temporal structures are important for affective content to influence some aspects of verbal processing.

Hormonal and genetic influences on arousal--sexual and otherwise.

Genetic influences on lordosis, a mammalian social behavior, are amenable for study because of the relative simplicity of both stimuli and response. The neural circuit for lordosis involves a supraspinal loop, which is controlled by an estrogen- and progesterone-dependent signal from the medial hypothalamus and results in heightened sexual motivation. In turn, this involves elevated states of arousal, defined by increased sensory alertness, motor activity and emotional reactivity. Mice in which the gene encoding the alpha form of the estrogen receptor (ERalpha) has been knocked out show that ERalpha is crucial for lordosis behavior. Comparing ERalpha-, ERbeta- and double knockouts reveals that different patterns of sexual behaviors in mice require different patterns of ER activity. Understanding how hormonal and genetic effects on deep motivational and arousal processes contribute to their effects on specific sexual and aggressive behaviors pose significant challenges for mouse functional genomics.

CENP-C facilitates the recruitment of M18BP1 to centromeric chromatin.

Centromeres are important structural constituents of chromosomes that ensure proper chromosome segregation during mitosis by providing defined sites for kinetochore attachment. In higher eukaryotes, centromeres have no specific DNA sequence and thus, they are rather determined through epigenetic mechanisms. A fundamental process in centromere establishment is the incorporation of the histone variant CENP-A into centromeric chromatin, which provides a binding platform for the other centromeric proteins. The Mis18 complex, and, in particular, its member M18BP1 was shown to be essential for both incorporation and maintenance of CENP-A. Here we show that M18BP1 displays a cell cycle-regulated association with centromeric chromatin in mouse embryonic stem cells. M18BP1 is highly enriched at centromeric regions from late anaphase through to G1 phase. An interaction screen against 16 core centromeric proteins revealed a novel interaction of M18BP1 with CENP-C. We mapped the interaction domain in M18BP1 to a central region containing a conserved SANT domain and in CENP-C to the C-terminus. Knock-down of CENP-C leads to reduced M18BP1 association and lower CENP-A levels at centromeres, suggesting that CENP-C works as an important factor for centromeric M18BP1 recruitment and thus for maintaining centromeric CENP-A.

Priming effects for affective vs. neutral faces.

Affective and Neutral Tasks (faces with negative or neutral content, with different lighting and orientation) requiring reaction time judgments of poser identity were administered to 32 participants. Speed and accuracy were better for the Affective than Neutral Task, consistent with literature suggesting facilitation of performance by affective content. Priming effects were significant for the Affective but not Neutral Task. An Explicit Post-Test indicated no conscious knowledge of the stimulus frequency that was associated with performance facilitation. Faster performance by female vs. male participants, and differential speeds and susceptibility to priming of different emotions were also found. Anger and shock were responded to most rapidly and accurately in several conditions, showed no gender differences, and showed significant priming for both RT and accuracy. Fear and pain were responded to least accurately, were associated with faster female than male reaction time, and the accuracy data showed a kind of reverse priming.

Statistical analysis of hormonal influences on arousal measures in ovariectomized female mice.

In a previous article (J. Frohlich, M. Morgan, S. Ogawa, L. Burton, and D. Pfaff, 2001, Horm. Behav. 39, 39-47) an experiment to explore the structure of behavioral arousal in female mice was described. The present study extends this, to investigate the roles of thyroid hormone and estradiol in altering the statistical structure of arousal measures. Each of four groups of ovariectomized female mice was administered either thyroxine (T4), estradiol benzoate (EB), both (T4 + EB), or neither (control). They were then subjected to the same rigid protocol of tests bearing on arousal concepts used in our previous study. T4-treated mice manifested significantly increased freezing behavior relative to control mice in a fear-conditioning paradigm. When compared with EB mice, T4-treated mice evinced significantly increased acoustic startle and open-field behavior. T4 mice were also significantly more active in the open field than EB + T4-treated mice. Mice administered EB demonstrated significantly decreased acoustic startle and open-field performance than controls. Evidence for increased anxiety in the open-field test was obtained in the EB condition. Factor and cluster analysis indicated the statistical structure of arousal measures to be reasonably robust across hormonal conditions. Hormone effects on arousal components are of interest because of their likely contributions to emotional states and cognitive performance.

Gender differences in implicit and explicit memory for affective passages.

Thirty-two participants were administered 4 verbal tasks, an Implicit Affective Task, an Implicit Neutral Task, an Explicit Affective Task, and an Explicit Neutral Task. For the Implicit Tasks, participants were timed while reading passages aloud as quickly as possible, but not so quickly that they did not understand. A target verbal passage was repeated three times, and alternated with other previously unread passages. The Implicit Affective and Neutral passages had strong affective or neutral content, respectively. The Explicit Tasks were administered at the end of testing, and consisted of multiple choice questions regarding the passages. Priming effects in terms of more rapid reading speed for the target compared to non-target passages were seen for both the Implicit Affective Task and the Implicit Neutral Task. Overall reading speed was faster for the passages with neutral compared to affective content, consistent with studies of the emotional Stroop effect. For the Explicit memory tasks, overall performance was better on the items from the repeated passage, and on the Affective compared to Neutral Task. The male subjects showed greater priming for affective material than female subjects, and a greater gain than female subjects in explicit memory for affective compared to neutral material.

Perception and priming of affective faces in temporal lobectomy patients.

Eighteen patients who had undergone standard anterior temporal lobectomy including removal of the amygdala and hippocampus (9 left, LTL; 9 right, RTL) were administered an Affective Task composed of faces depicting negative emotions, and a Neutral Task consisting of faces with different lighting and orientation conditions. Both tasks required judgment of poser identity and indication of decision by pressing a reaction time button. Subjects were shown a set of photos in an Exposure Phase, followed by a Test Phase in which the photos previously seen (primed) were mixed with new photos (unprimed). The LTL subjects performed better than the RTL subjects for both the RT and accuracy data in both the Neutral and Affective Tasks. The performance of the LTL subjects improved when the task had an affective component (Affective vs. Neutral Task), whereas the RTL subjects did not show this benefit. In terms of specific emotions, for the LTL group, pain was responded to most slowly and shock was the emotion responded to most quickly, and significantly more quickly than in the RTL group. Fear was the emotion responded to most slowly by the RTL group and significantly more slowly when compared to the LTL group. The only priming effect was a reverse priming for pain, such that stimuli seen before were respondedto less accurately than new stimuli; this was not related to lesion side.

Affective tasks elicit material-specific memory effects in temporal lobectomy patients.

Eighteen patients who had undergone a right (9) or left (9) temporal lobectomy (RTL, LTL) including removal of the amygdala and hippocampus were evaluated. Sixteen male and sixteen female undergraduate subjects were evaluated for normative comparison. All subjects were administered Verbal (words) and Visual (faces) paired associates tasks. The present study sought to evaluate material-specific memory after temporal lobectomy, and to compare affective versus neutral memory as well. Thus, there were 4 tasks: Verbal Affective, Verbal Neutral, Visual Affective, and Visual Neutral. The material-specific effects of better Verbal memory performance by the RTL subjects compared to the LTL subjects and better Visual memory performance by the LTL subjects than the RTL subjects were only significant for the Affective tasks, and not the Neutral tasks. Perhaps adding an affective dimension to the material-specific memory tasks engaged the amygdala in addition to the other structures known to be important in memory. A strong interpretaion of the present data is made difficult by task differences and the low average IQ and possible reorganization of function that may have occurred in the patient sample.