Sex differences in brain activation patterns during processing of positively and negatively valenced emotional words

BACKGROUND: Previous studies have suggested that men and women process emotional stimuli differently. In this study, we used event-related functional magnetic resonance imaging (fMRI) to investigate gender differences in regional cerebral activity during the perception of positive or negative emotions. METHOD: The experiment comprised two emotional conditions (positively/negatively valenced words) during which fMRI data were acquired. RESULTS: Thirty-eight healthy volunteers (19 males, 19 females) were investigated. A direct comparison of brain activation between men and women revealed differential activation in the right putamen, the right superior temporal gyrus, and the left supramarginal gyrus during processing of positively valenced words versus non-words for women versus men. By contrast, during processing of negatively valenced words versus non-words, relatively greater activation was seen in the left perirhinal cortex and hippocampus for women versus men, and in the right supramarginal gyrus for men versus women. CONCLUSIONS: Our findings suggest gender-related neural responses to emotional stimuli and could contribute to the understanding of mechanisms underlying the gender disparity of neuropsychiatric diseases such as mood disorders.     

Autonomic nervous system functioning in early childhood: Responses to cognitive and negatively valenced emotional challenges

Although autonomic nervous system (ANS) functioning is “context-dependent,” few studies examined children's normative sympathetic and parasympathetic autonomic responses to distinct challenges in early childhood years. Examining children's ANS responsivity to distinct challenges is important for understanding normative autonomic responses toward everyday life stressors and identifying paradigms that effectively elicit a “stress response.” We examined children's (N = 278) sympathetic (preejection period [PEP]) and parasympathetic (respiratory sinus arrhythmia [RSA]) responses to cognitive (i.e., problem-solving and cognitive control) and negatively valenced emotional (i.e., blocked goal and unfairness) challenges in preschool, kindergarten, and grade 1. Children, on average, demonstrated parasympathetic inhibition (RSA withdrawal) in response to all challenges but the magnitude of these responses depended on the task. Children showed sympathetic activation (PEP shortening) toward the problem-solving task at each assessment and there was no sample-level change in the magnitude of this response over time. Children showed greater sympathetic responsivity toward the cognitive control task over time, with evidence for a sympathetic activation response only in grade 1. Children experienced sympathetic inhibition (PEP lengthening) toward the unfairness tasks but did not experience significant sympathetic responsivity toward the blocked goal tasks. Parasympathetic responsivity to most challenges were modestly stable but there was no stability in sympathetic responsivity across time.     

Antibodies against polyalanyl determinants attached to negatively or positively charged carriers

Polyalanyl determinants, when attached to acidic or basic carriers, provoke a specific anti-polyalanyl antibody population, the majority of which possesses an electrical charge which is inversely related to that of the carrier. The alanine chains in the immunogens form complete determinants and the contribution of the carrier to the specificity of the antibodies is minimal. The anti-polyalanyl antibodies, when fractionated into a more acidic and a more basic fraction, possess similar properties of their combining sites, as judged from hapten inhibition and equilibrium dialysis studies. Thus, the specificity of the antibodies and the combining site features are determined by the hapten determinants, whereas the net charge of the antibodies is determined by the net charge of the immunogen. The difference in the net electrical charge of the antibodies may reflect differences in areas of the molecule other than the combining site. A comparison of anti-polyalanyl antibodies obtained with different carriers has shown that the specificity and size of the combining sites are similar regardless of the nature of the carrier molecule, whereas different affinities of the antibodies are obtained with different immunogens.     

Cdc13 both positively and negatively regulates telomere replication

Cdc13 is a single-strand telomeric DNA-binding protein that positively regulates yeast telomere replication by recruiting telomerase to chromosome termini through a site on Cdc13 that is eliminated by the cdc13-2 mutation. Here we show that Cdc13 has a separate role in negative regulation of telomere replication, based on analysis of a new mutation, cdc13-5. Loss of this second regulatory activity results in extensive elongation of the G strand of the telomere by telomerase, accompanied by a reduced ability to coordinate synthesis of the C strand. Both the cdc13-5 mutation and DNA polymerase alpha mutations (which also exhibit elongated telomeres) are suppressed by increased expression of the Cdc13-interacting protein Stn1, indicating that Stn1 coordinates action of the lagging strand replication complex with the regulatory activity of CDC13. However, the association between Cdc13 and Stn1 is abolished by cdc13-2, the same mutation that eliminates the interaction between Cdc13 and telomerase. We propose that Cdc13 participates in two regulatory steps-first positive, then negative-as a result of successive binding of telomerase and the negative regulator Stn1 to overlapping sites on Cdc13. Thus, Cdc13 coordinates synthesis of both strands of the telomere by first recruiting telomerase and subsequently limiting G-strand synthesis by telomerase in response to C-strand replication.     

Electrophysiological indicators of emotion processing biases in depressed undergraduates

It has been proposed that depressed individuals are biased towards and have more difficulty disengaging from negative information once it has been made salient (e.g. Joormann, J., 2004. Attentional bias in dysphoria: the role of inhibitory processes. Cognition & Emotion 18 (1), 125-147). The current study examined whether attention- and inhibition-related brain potentials were sensitive to both of these phenomena in depression using an affective go/no-go paradigm. Eighteen undergraduates who scored high on the Inventory to Diagnose Depression (IDD; Zimmerman, M., Coryell, W., 1987. The inventory to diagnose depression (IDD): a self-report scale to diagnose major depressive disorder. Journal of Consulting and Clinical Psychology 55 (1), 55-59) and 19 who scored low on the IDD completed the experiment. Results indicated that across all trials, subjects high on depressive symptomatology exhibited larger P3s in response to negative compared to positive stimuli. Examination of ERPs on trials uncontaminated by task-switching effects revealed larger N2s on “no-go” than “go” trials, and, specific to the depressive group, larger N2s in response to positive compared to negative stimuli. These data provide electrophysiological evidence that depressive subjects differentially categorize positive and negative emotional pictures. The P3 valence effect may help to explain difficulties inhibiting negative information seen in depression.     

Degradation behavior of dextran hydrogels composed of positively and negatively charged microspheres

This paper reports on the degradation behavior of in situ gelling hydrogel matrices composed of positively and negatively charged dextran microspheres. Rheological analysis showed that, once the individual microspheres started to degrade, the hydrogel changed from a mainly elastic to a viscoelastic network. It was shown with gels composed of equal amounts of cationic and anionic microspheres, that both a higher crosslink density of the particles and a decrease in water content of the hydrogels resulted in a slower degradation, ranging from 65 to 140 days. Dispersions containing cationic, neutral or anionic microspheres completely degraded within 30, 55 or 120 days, respectively. The microspheres were loaded with rhodamine-B-dextran and degradation was studied with confocal microscopy and fluorescence spectroscopy. After a lag time of 3 days rhodamine-B-dextran started to release from the positive microspheres with a 50% release after 16 days. In contrast, release of rhodamine-B-dextran from the negative microspheres started after 10 days with a 50% release after 36 days. The faster degradation of the positively charged microspheres as compared to the negatively charged microspheres is attributed to stabilization of the transition state in the hydrolysis process by the protonated tertiary amine groups present in the cationic microspheres. On the other hand, the presence of negatively charged groups causes repulsion of hydroxyl anions resulting in a slower degradation. Combining the oppositely charged microspheres in different ratios makes it possible to tailor the network properties and the degradation behavior of these hydrogels, making them suitable for various applications in drug delivery and tissue engineering.     

Dynamics of response to perceptual pop-out stimuli in macaque V1

Contextual modulation due to feature contrast between the receptive field and surrounding region has been reported for numerous stimuli in primary visual cortex. One type of this modulation, iso-orientation surround suppression, has been studied extensively. The degree to which surround suppression is related to other forms of contextual modulation remains unknown. We used shape-from-shading stimuli in a field of distractors to test the latency and magnitude of contextual modulation to a stimulus that cannot be distinguished with an orientation-selective mechanism. This stimulus configuration readily elicits perceptual pop-out in human observers and induces a long-latency contextual modulation response in neurons in macaque early visual cortex. We found that animals trained to detect the location of a pop-out stimulus were better at finding a sphere that appeared to be lit from below in the presence of distractors that were lit from above. Furthermore, neuronal responses were stronger and had shorter latency in the condition where behavioral performance was best. This asymmetry is compatible with earlier psychophysical findings in human observers. In the population of V1 neurons, the latency of the contextual modulation response is 145 ms on average (ranging from 70 to 230 ms). This is much longer than the latency for iso-orientation surround suppression, indicating that the underlying circuitry is distinct. Our results support the idea that a feature-specific feedback signal generates the pop-out responses we observe and suggest that V1 neurons actively participate in the computation of perceptual salience.     

Passively viewing negatively valenced baby faces attenuates left amygdala activity in healthy females scoring high on ‘Harm Avoidance’

The amygdalae play an important role in the evaluation and processing of emotionally salient visual stimuli. However, individual differences in personality traits, such as Harm Avoidance (HA), have been reported to influence emotional amygdalae responses. To trigger strong approach and withdrawal-related emotions in ‘never depressed’ young female subjects under fMRI, we presented them with blocks of happy ‘healthy’ baby faces and baby faces disfigured by severe dermatological conditions and we integrated the temperament dimension HA into our analysis. No other instructions were given than to watch the images attentively. Only in withdrawal-related emotional experience, we observed a negative correlation between HA and left amygdala activity, suggesting that during passive viewing females scoring higher on HA ‘avoid’ images with highly aversive content. When investigating the amygdala's emotional role in passive viewing paradigms, personality features such as HA should be taken into account.     

Expression of housekeeping and immunoproteasome subunit genes is differentially regulated in positively and negatively selecting thymic stroma subsets

The expression of housekeeping and/or immunoproteasomes in isolated thymic stroma subsets has so far not been analyzed but may have important consequences for self peptide repertoires presented by MHC class I molecules during positive and negative thymic selection. Here we determined the expression of housekeeping and immunoproteasome beta subunits and of PA28 in positively and negatively selecting stroma subsets. Positively selecting cortical thymic epithelial cells (cTEC) expressed only housekeeping but no immunoproteasome beta subunit mRNA and proteins. However, immunoproteasome beta subunits could be induced in cTEC by infection with Listeria monocytogenes or injection of IFN-gamma. In negatively selecting stroma including medullary epithelial cells and dendritic cells, incomplete and low representation of housekeeping beta subunit proteins but high and complete expression of immunoproteasome beta subunit proteins suggests absence of proper housekeeping proteasomes and predominance of immunoproteasomes. Expression of immunoproteasome beta subunits in negatively selecting stroma was independent of IFN-gamma receptor as shown in knockout (KO) mice. Absence of LMP2 altered thymic selection of the MHC class I-restricted transgenic P14 TCR in KO mice. The data suggest that negative selection may primarily involve immunoproteasome peptide repertoires and that peripheral infection may influence peptide repertoires involved in positive selection.     

Emotional content modulates response inhibition and perceptual processing

In this study, event‐related potentials were used to investigate the effect of emotion on response inhibition. Participants performed an emotional go/no‐go task that required responses to human faces associated with a “go” valence (i.e., emotional, neutral) and response inhibition to human faces associated with a “no‐go” valence. Emotional content impaired response inhibition, as evidenced by decreased response accuracy and N2 amplitudes in no‐go trials. More importantly, emotional expressions elicited larger N170 amplitudes than neutral expressions, and this effect was larger in no‐go than in go trials, indicating that the perceptual processing of emotional expression had priority in inhibitory trials. In no‐go trials, correlation analysis showed that increased N170 amplitudes were associated with decreased N2 amplitudes. Taken together, our findings suggest that emotional content impairs response inhibition due to the prioritization of emotional content processing.     

MicroRNA-362 negatively and positively regulates SMAD4 expression in TGF-β/SMAD signaling to suppress cell migration and invasion

Cell migration and invasion are modulated by epithelial-to-mesenchymal transition (EMT) and the reverse MET process. Despite the detection of microRNA-362 (miR-362, both the miR-362-5p and -3p species) in cancers, none of the identified miR-362 targets is a mesenchymal or epithelial factor to link miR-362 with EMT/MET and metastasis. Focusing on the TGF-β/SMAD signaling pathway in this work, luciferase assays and western blot data showed that miR-362 targeted and negatively regulated expression of SMAD4 and E-cadherin, but not SNAI1, which is regulated by SMAD4. However, miR-362 knockdown also down-regulated SMAD4 and SNAI1, but up-regulated E-cadherin expression. Wound-healing and transwell assays further showed that miR-362 knockdown suppressed cell migration and invasion, effects which were reversed by over-expressing SMAD4 or SNAI1, or by knocking down E-cadherin in the miR-362 knockdown cells. In orthotopic mice, miR-362 knockdown inhibited metastasis, and displayed the same SMAD4 and E-cadherin expression profiles in the tumors as in the in vitro studies. A scheme is proposed to integrate miR-362 negative regulation via SMAD4, and to explain miR-362 positive regulation of SMAD4 via miR-362 targeting of known SMAD4 suppressors, BRK and DACH1, which would have resulted in SMAD4 depletion and annulment of subsequent involvement in TGF-β signaling actions. Hence, miR-362 both negatively and positively regulates SMAD4 expression in TGF-β/SMAD signaling pathway to suppress cell motility and invasiveness and metastasis, and may explain the reported clinical association of anti-miR-362 with suppressed metastasis in various cancers. MiR-362 knockdown in miR-362-positive cancer cells may be used as a therapeutic strategy to suppress metastasis.     

Heart rate and perceptual response to exercise with different pedalling speed in normal subjects and patients

Summary The perceived exertion rating (RPE) scale of Borg was used to investigate the relationship between perceived exertion and pedalling rate. Normal subjects and patients with chronic obstructive lung disease (Cold) were studied in repeated test series. Work load, applied in a random order, varied from 2.5 to 10 mkp/s (patients) and 5 to 20 mkp/s (normals). Pedalling rate varied from 40 to 60, 80, 100 rpm. At constant work load, RPE decreases during increasing pedalling rate. With respect to validity, RPE, showing a closer relationship to work load than to heart rate, seems to reflect perception of physical stress rather than perception of physiological strain.In addition, the results raise the question of standardization of pedalling rate in bicycle ergometry.Preliminary results have been presented at the XXth World Congress of Sports Medicine, Melbourne, 1974     

Motor activity correlates negatively with free-running period, while positively with serotonin contents in SCN in free-running rats

Free-running period of blinded rats kept in a cage with a running wheel varied markedly, while it varied little in rats kept in a cage without a running wheel. The mean free-running period of the former group is significantly shorter than that of the latter. In the former, the free-running period correlated negatively with motor activity, indicating that activity affects the free-running period. In both groups, essentially similar diurnal patterns of biogenic amines and their metabolites were observed in various discrete areas in the brain examined. However, there was a significant difference between the two groups in several areas. In the SCN, 5-HT content correlated positively with motor activity, consequently correlated negatively to the free-running period at 3 out of 4 sampling times over 24 h but no such correlation was observed in other monoamines and their metabolites examined. These facts suggest that 5-HT may be associated with modification of the free-running period.     

Soluble PD-L1 in blood correlates positively with neutrophil and negatively with lymphocyte mRNA markers and implies adverse sepsis outcome

Immunologic Research - Sepsis causes a myriad of immunological reactions that result in life-threatening alterations in the human body. Immunosuppression in sepsis is partly attributed to the...     

Schizophrenia patients show impaired response switching in saccade tasks

Action control deficits of schizophrenia patients result from frontostriatal brain abnormalities and presumably reflect an impairment of selective cognitive processes. This study aimed at dissociating two different levels of action control in saccades toward and away from visual stimuli (pro- and antisaccades). Results of previous studies suggested that task switch effects (between pro- and antisaccades) reflect the persistence of a task-specific production rule and refer to the level of task selection, whereas response switch effects (between leftward and rightward saccades) point to the persistence of a specific response program, referring to the level of response selection. In the present study, task switching and response switching were investigated in 20 schizophrenia patients and 20 control subjects. Groups did not differ concerning task switch effects. In contrast, response switching entailed a stronger enhancement of error rates in patients, suggesting a specific deficit on the level of response selection in schizophrenia. The deficit was associated with spatial working memory capacities, confirming and specifying existing hypotheses on a relationship between working memory and action control.