Cortisol coregulation in fish

Cortisol coregulation, which is the up- or down-regulation of partners’ physiological stress responses, has been described for individuals with strong attachment bonds, e.g. parents and their children, and romantic relationship partners. Research into moderating effects on cortisol coregulation suggests stronger covariation among distressed partners. Whether cortisol coregulation is unique to humans or can also be found in other species that share universal features of the vertebrate stress response remains unexplored. Using a repeated measures approach and non-invasive waterborne hormone analysis, we test the hypothesis that dyads of three-spined stickleback fish (Gasterosteus aculeatus) coregulate their cortisol levels in shared environments. Dyadic cortisol levels were unrelated when cohabiting (home tank), but significantly covaried when sharing a more stressful (as indicated by higher cortisol levels) environment (open field). Time-lag analysis further revealed that open field cortisol levels were predicted by partner’s cortisol levels prior to the shared experience. To our knowledge, this study provides the first evidence for coregulatory processes on cortisol responses in a non-human animal that lacks strong bonds and social attachment relationships, suggesting a shared evolutionary origin of cortisol coregulation in vertebrates. From an adaptive perspective, cortisol coregulation may serve to reduce risk in challenging, potentially threatening situations

Computerized acoustic assessment of treatment efficacy of nebulized epinephrine and albuterol in RSV bronchiolitis

<p>Abstract</p> <p>Aim</p> <p>We evaluated the use of computerized quantification of wheezing and crackles compared to a clinical score in assessing the effect of inhaled albuterol or inhaled epinephrine in infants with RSV bronchiolitis.</p> <p>Methods</p> <p>Computerized lung sounds analysis with quantification of wheezing and crackles and a clinical score were used during a double blind, randomized, controlled nebulized treatment pilot study. Infants were randomized to receive a single dose of 1 mgr nebulized l-epinephrine or 2.5 mgr nebulized albuterol. Computerized quantification of wheezing and crackles (PulmoTrack^®) and a clinical score were performed prior to, 10 minutes post and 30 minutes post treatment. Results were analyzed with Student's t-test for independent samples, Mann-Whitney U test and Wilcoxon test.</p> <p>Results</p> <p>15 children received albuterol, 12 received epinephrine. The groups were identical at baseline. Satisfactory lung sounds recording and analysis was achieved in all subjects. There was no significant change in objective quantification of wheezes and crackles or in the total clinical scores either within the groups or between the groups. There was also no difference in oxygen saturation and respiratory distress.</p> <p>Conclusion</p> <p>Computerized lung sound analysis is feasible in young infants with RSV bronchiolitis and provides a non-invasive, quantitative measure of wheezing and crackles in these infants. </p> <p><b>Trial registration number</b>: ClinicalTrials.gov NCT00361452</p

A Trouble Shared Is a Trouble Halved: Social Context and Status Affect Pain in Mouse Dyads

In mice behavioral response to pain is modulated by social status. Recently, social context also has been shown to affect pain sensitivity. In our study, we aimed to investigate the effects of interaction between status and social context in dyads of outbred CD-1 male mice in which the dominance/submission relationship was stable. Mice were assessed for pain response in a formalin (1% concentration) test either alone (individually tested-IT), or in pairs of dominant and subordinate mice. In the latter condition, they could be either both injected (BI) or only one injected (OI) with formalin. We observed a remarkable influence of social context on behavioral response to painful stimuli regardless of the social status of the mice. In the absence of differences between OI and IT conditions, BI mice exhibited half as much Paw-licking behavior than OI group. As expected, subordinates were hypoalgesic in response to the early phase of the formalin effects compared to dominants. Clear cut-differences in coping strategies of dominants and subordinates appeared. The former were more active, whereas the latter were more passive. Finally, analysis of behavior of the non-injected subjects (the observers) in the OI dyads revealed that dominant observers were more often involved in Self-grooming behavior upon observation of their subordinate partner in pain. This was not the case for subordinate mice observing the pain response of their dominant partner. In contrast, subordinate observers Stared at the dominant significantly more frequently compared to observer dominants in other dyads. The observation of a cagemate in pain significantly affected the observer's behavior. Additionally, the quality of observer's response was also modulated by the dominance/submission relationship

Expression of a protein involved in bone resorption, Dkk1, is activated by HTLV-1 bZIP factor through its activation domain

<p>Abstract</p> <p>Background</p> <p>Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia, a malignancy characterized by uncontrolled proliferation of virally-infected CD4+ T-cells. Hypercalcemia and bone lesions due to osteoclast-mediated bone resorption are frequently associated with more aggressive forms of the disease. The HTLV-1 provirus contains a unique antisense gene that expresses HTLV-1 basic leucine zipper (bZIP) factor (HBZ). HBZ is localized to the nucleus where it regulates levels of transcription by binding to certain cellular transcriptional regulators. Among its protein targets, HBZ forms a stable complex with the homologous cellular coactivators, p300 and CBP, which is modulated through two N-terminal LXXLL motifs in the viral protein and the conserved KIX domain in the coactivators.</p> <p>Results</p> <p>To determine the effects of these interactions on transcription, we performed a preliminary microarray analysis, comparing levels of gene expression in cells with wild-type HBZ versus cells with HBZ mutated in its LXXLL motifs. <it>DKK1</it>, which encodes the secreted Wnt signaling inhibitor, Dickkopf-1 (Dkk1), was confirmed to be transcriptionally activated by HBZ, but not its mutant. Dkk1 plays a major role in the development of bone lesions caused by multiple myeloma. In parallel with the initial findings, activation of Dkk1 expression by HBZ was abrogated by siRNA-mediated knockdown of p300/CBP or by a truncated form of p300 containing the KIX domain. Among HTLV-1-infected T-cell lines tested, the detection of Dkk1 mRNA partially correlated with a threshold level of HBZ mRNA. In addition, an uninfected and an HTLV-1-infected T-cell line transfected with an HBZ expression vector exhibited <it>de novo </it>and increased DKK1 transcription, respectively. In contrast to HBZ, The HTLV-1 Tax protein repressed Dkk1 expression.</p> <p>Conclusions</p> <p>These data indicate that HBZ activates Dkk1 expression through its interaction with p300/CBP. However, this effect is limited in HTLV-1-infected T-cell lines, which in part, may be due to suppression of Dkk1 expression by Tax. Consequently, the ability of HBZ to regulate expression of Dkk1 and possibly other cellular genes may only be significant during late stages of ATL, when Tax expression is repressed.</p

Chemosensory Cues to Conspecific Emotional Stress Activate Amygdala in Humans

Alarm substances are airborne chemical signals, released by an individual into the environment, which communicate emotional stress between conspecifics. Here we tested whether humans, like other mammals, are able to detect emotional stress in others by chemosensory cues. Sweat samples collected from individuals undergoing an acute emotional stressor, with exercise as a control, were pooled and presented to a separate group of participants (blind to condition) during four experiments. In an fMRI experiment and its replication, we showed that scanned participants showed amygdala activation in response to samples obtained from donors undergoing an emotional, but not physical, stressor. An odor-discrimination experiment suggested the effect was primarily due to emotional, and not odor, differences between the two stimuli. A fourth experiment investigated behavioral effects, demonstrating that stress samples sharpened emotion-perception of ambiguous facial stimuli. Together, our findings suggest human chemosensory signaling of emotional stress, with neurobiological and behavioral effects

Sphingomyelin Functions as a Novel Receptor for Helicobacter pylori VacA

The vacuolating cytotoxin (VacA) of the gastric pathogen Helicobacter pylori binds and enters epithelial cells, ultimately resulting in cellular vacuolation. Several host factors have been reported to be important for VacA function, but none of these have been demonstrated to be essential for toxin binding to the plasma membrane. Thus, the identity of cell surface receptors critical for both toxin binding and function has remained elusive. Here, we identify VacA as the first bacterial virulence factor that exploits the important plasma membrane sphingolipid, sphingomyelin (SM), as a cellular receptor. Depletion of plasma membrane SM with sphingomyelinase inhibited VacA-mediated vacuolation and significantly reduced the sensitivity of HeLa cells, as well as several other cell lines, to VacA. Further analysis revealed that SM is critical for VacA interactions with the plasma membrane. Restoring plasma membrane SM in cells previously depleted of SM was sufficient to rescue both toxin vacuolation activity and plasma membrane binding. VacA association with detergent-resistant membranes was inhibited in cells pretreated with SMase C, indicating the importance of SM for VacA association with lipid raft microdomains. Finally, VacA bound to SM in an in vitro ELISA assay in a manner competitively inhibited by lysenin, a known SM-binding protein. Our results suggest a model where VacA may exploit the capacity of SM to preferentially partition into lipid rafts in order to access the raft-associated cellular machinery previously shown to be required for toxin entry into host cells

p27 Deficiency Cooperates with Bcl-2 but Not Bax to Promote T-Cell Lymphoma

The effect of Bcl-2 on oncogenesis is complex and expression may either delay or accelerate oncogenesis. The pro-oncogenic activity is attributed to its well characterized anti-apoptotic function while the anti-oncogenic function has been attributed to its inhibition of cellular proliferation. Recent studies demonstrate that p27 may mediate the effects of Bcl-2 on cellular proliferation. We hypothesized that p27 may suppress tumor formation by Bcl-2 family members. To test this hypothesis, cell cycle inhibition and lymphoma development were examined in Lck-Bcl-2 and Lck-Bax38/1 transgenic mice deficient in p27. Strikingly, p27 deficiency synergistically cooperates with Bcl-2 to increase T cell hyperplasia and development of spontaneous T cell lymphomas. Within 1 year, >90% of these mice had developed thymic T cell lymphomas. This high penetrance contrasts with a one year incidence of <5% of thymic lymphoma in Lck-Bcl-2 or p27 −/− mice alone. In contrast, p27 deficiency had no effect on tumor formation in Lck-Bax38/1 transgenic mice, another model of T cell lymphoma. Histologically the lymphomas in p27 −/− Lck-Bcl-2 mice are lymphoblastic and frequently involve multiple organs suggesting an aggressive phenotype. Interestingly, in mature splenic T cells, Bcl-2 largely retains its anti-proliferative function even in the absence of p27. T cells from p27 −/− Lck-Bcl-2 mice show delayed kinetics of CDK2 Thr-160 phosphorylation. This delay is associated with a delay in the up regulation of both Cyclin D2 and D3. These data demonstrate a complex relationship between the Bcl-2 family, cellular proliferation, and oncogenesis and demonstrate that p27 up-regulation is not singularly important in the proliferative delay observed in T cells expressing Bcl-2 family members. Nonetheless, the results indicate that p27 is a critical tumor suppressor in the context of Bcl-2 expression

Myosin IIA/IIB restrict adhesive and protrusive signaling to generate front–back polarity in migrating cells

Myosin IIA and IIB synergistically generate front–back polarity through their effects on actomyosin bundling formation and stability, and adhesion maturation, which are mediated by localized Rac GEF depletion