Protein Phosphatase-1α Interacts with and Dephosphorylates Polycystin-1

Polycystin signaling is likely to be regulated by phosphorylation. While a number of potential protein kinases and their target phosphorylation sites on polycystin-1 have been identified, the corresponding phosphatases have not been extensively studied. We have now determined that polycystin-1 is a regulatory subunit for protein phosphatase-1α (PP1α). Sequence analysis has revealed the presence of a highly conserved PP1-interaction motif in the cytosolic, C-terminal tail of polycystin-1; and we have shown that transfected PP1α specifically co-immunoprecipitates with a polycystin-1 C-tail construct. To determine whether PP1α dephosphorylates polycystin-1, a PKA-phosphorylated GST-polycystin-1 fusion protein was shown to be dephosphorylated by PP1α but not by PP2B (calcineurin). Mutations within the PP1-binding motif of polycystin-1, including an autosomal dominant polycystic kidney disease (ADPKD)-associated mutation, significantly reduced PP1α-mediated dephosphorylation of polycystin-1. The results suggest that polycystin-1 forms a holoenzyme complex with PP1α via a conserved PP1-binding motif within the polycystin-1 C-tail, and that PKA-phosphorylated polycystin-1 serves as a substrate for the holoenzyme

Venous gas embolism as a predictive tool for improving CNS decompression safety

A key process in the pathophysiological steps leading to decompression sickness (DCS) is the formation of inert gas bubbles. The adverse effects of decompression are still not fully understood, but it seems reasonable to suggest that the formation of venous gas emboli (VGE) and their effects on the endothelium may be the central mechanism leading to central nervous system (CNS) damage. Hence, VGE might also have impact on the long-term health effects of diving. In the present review, we highlight the findings from our laboratory related to the hypothesis that VGE formation is the main mechanism behind serious decompression injuries. In recent studies, we have determined the impact of VGE on endothelial function in both laboratory animals and in humans. We observed that the damage to the endothelium due to VGE was dose dependent, and that the amount of VGE can be affected both by aerobic exercise and exogenous nitric oxide (NO) intervention prior to a dive. We observed that NO reduced VGE during decompression, and pharmacological blocking of NO production increased VGE formation following a dive. The importance of micro-nuclei for the formation of VGE and how it can be possible to manipulate the formation of VGE are discussed together with the effects of VGE on the organism. In the last part of the review we introduce our thoughts for the future, and how the enigma of DCS should be approached

Moving to capture children’s attention: developing a methodology for measuring visuomotor attention

Attention underpins many activities integral to a child’s development. However, methodological limitations currently make large-scale assessment of children’s attentional skill impractical, costly and lacking in ecological validity. Consequently we developed a measure of ‘Visual Motor Attention’ (VMA) - a construct defined as the ability to sustain and adapt visuomotor behaviour in response to task-relevant visual information. In a series of experiments, we evaluated the capability of our method to measure attentional processes and their contributions in guiding visuomotor behaviour. Experiment 1 established the method’s core features (ability to track stimuli moving on a tablet-computer screen with a hand-held stylus) and demonstrated its sensitivity to principled manipulations in adults’ attentional load. Experiment 2 standardised a format suitable for use with children and showed construct validity by capturing developmental changes in executive attention processes. Experiment 3 tested the hypothesis that children with and without coordination difficulties would show qualitatively different response patterns, finding an interaction between the cognitive and motor factors underpinning responses. Experiment 4 identified associations between VMA performance and existing standardised attention assessments and thereby confirmed convergent validity. These results establish a novel approach to measuring childhood attention that can produce meaningful functional assessments that capture how attention operates in an ecologically valid context (i.e. attention's specific contribution to visuomanual action)

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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Triumph displays inform eavesdropping little blue penguins of new dominance asymmetries

Agonistic signals used during contests over important resources have been extensively studied; post-conflict signals have received comparatively little attention. While ‘triumph displays’, performed by winners following fights, have been described for many species, no experiment has yet assessed one of the main hypotheses explaining their existence: advertising victory to social eavesdroppers. Our experiments evaluated the impact of triumph calls on the behaviour and stress responses of surrounding penguins. We found that territorial male little blue penguins, Eudyptula minor, having previously been exposed to playback of a vocal exchange between conspecifics followed by the sounds of a fight, had higher heart rates in response to the winner’s call than that of the loser; females had high rates in response to both winners and losers. Males were also less likely to threaten winners than losers vocally during a simulated approach of their burrow, while females remained silent in both contexts. Our findings support the hypothesis that triumph calls facilitate an association of winners’ distinctive vocalizations with stress generated by nearby overt aggression. By advertising their victories, males may establish a ‘reputation’ for winning fights within the social group, potentially reducing the likelihood of being challenged by eavesdroppers in future contests

Does the intensity of the inflammatory reaction in a bruise depend on its proximity to the site of trauma?

Whole blood was withdrawn by tail vessel puncture from anesthetized adult male Sprague-Dawley rats and 0.1 ml was re-injected subcutaneously at each of two sites on their abdominal wall. In addition, two adjacent sites were injected with 0.1 ml of sterile saline, and two more sites were only punctured using an injecting needle. In the second part of the study anesthetized adult male Sprague-Dawley rats had two sites on the abdominal wall pinched using a small pair of forceps, two adjacent sites received an injection of 0.1 ml of whole blood obtained by tail vessel puncture, and two more sites were both pinched and injected with 0.1 ml of whole blood. At intervals of 3, 6, 12 h, 1, 2, 3, 5, and 7 days the animals were euthanized and the skin of the abdomen was processed for histological assessment. Hemosiderin staining in tissues from the first part of the study was assessed qualitatively by scoring sections as 0, 1, 2, or 3 (representing no staining, mild staining, moderate staining, and intense staining) and semi quantitatively using a Nanozoomer Digital Pathology Scanner (NDP Scan U10074-01, Hamamatsu Photonics K.K., Japan). No inflammatory reaction was observed at the sites subjected to needle puncture only. At the sites of saline injection a mild reaction occurred. At the sites where the blood had been injected an intense inflammatory cell response occurred centrally, but not toward the periphery where blood had tracked. In the second experiment the most intense inflammation was also observed in the sites where there had been a pinch and injection of blood. Again, this was maximal centrally with reduced inflammation peripherally. Perls' staining of hemosiderin was comparable in both models, with iron first observed at day 1 at the region of the injection site. At the sites of injection only, and the sites of injection plus pinch, blood had spread laterally. Hemosiderin staining appeared first and more intensely at the site of injection/trauma. The intensity of the inflammatory response in this animal model of bruising was, therefore, directly related to the proximity to the site of trauma; the appearance and intensity of hemosiderin staining was also influenced by the location within the bruises. This study has shown that histological changes that may be utilized to date bruises may be significantly influenced by the site of the biopsy.Claire Ross, Roger W. Byard, Neil E. I. Langloi