Ca(2+)-mediated activation of ERK in hepatocytes by norepinephrine and prostaglandin F(2α): role of calmodulin and src kinases

BACKGROUND: Previous studies have shown that several agents that stimulate heptahelical G-protein coupled receptors activate the extracellular signal regulated kinases ERK1 (p44(mapk)) and ERK2 (p42(mapk)) in hepatocytes. The molecular pathways that convey their signals to ERK1/2 are only partially clarified. In the present study we have explored the role of Ca(2+) and Ca(2+)-dependent steps leading to ERK1/2 activation induced by norepinephrine and prostaglandin (PG)F(2α). RESULTS: Pretreatment of the cells with the Ca(2+) chelators BAPTA-AM or EGTA, as well as the Ca(2+) influx inhibitor gadolinium, resulted in a partial decrease of the ERK response. Furthermore, the calmodulin antagonists W-7, trifluoperazine, and J-8 markedly decreased ERK activation. Pretreatment with KN-93, an inhibitor of the multifunctional Ca(2+)/calmodulin-dependent protein kinase, had no effect on ERK activation. The Src kinase inhibitors PP1 and PP2 partially diminished the ERK responses elicited by both norepinephrine and PGF(2α). CONCLUSION: The present data indicate that Ca(2+) is involved in ERK activation induced by hormones acting on G protein-coupled receptors in hepatocytes, and suggest that calmodulin and Src kinases might play a role in these signaling pathways

Formation of Very Large Conductance Channels by Bacillus cereus Nhe in Vero and GH4 Cells Identifies NheA + B as the Inherent Pore-Forming Structure

The nonhemolytic enterotoxin (Nhe) produced by Bacillus cereus is a pore-forming toxin consisting of three components, NheA, -B and -C. We have studied effects of Nhe on primate epithelial cells (Vero) and rodent pituitary cells (GH4) by measuring release of lactate dehydrogenase (LDH), K+ efflux and the cytosolic Ca2+ concentration ([Ca2+]i). Plasma membrane channel events were monitored by patch-clamp recordings. Using strains of B. cereus lacking either NheA or -C, we examined the functional role of the various components. In both cell types, NheA + B + C induced release of LDH and K+ as well as Ca2+ influx. A specific monoclonal antibody against NheB abolished LDH release and elevation of [Ca2+]i. Exposure to NheA + B caused a similar K+ efflux and elevation of [Ca2+]i as NheA + B + C in GH4 cells, whereas in Vero cells the rate of K+ efflux was reduced by 50% and [Ca2+]i was unaffected. NheB + C had no effect on either cell type. Exposure to NheA + B + C induced large-conductance steps in both cell types, and similar channel insertions were observed in GH4 cells exposed to NheA + B. In Vero cells, NheA + B induced channels of much smaller conductance. NheB + C failed to insert membrane channels. The conductance of the large channels in GH4 cells was about 10 nS. This is the largest channel conductance reported in cell membranes under quasi-physiological conditions. In conclusion, NheA and NheB are necessary and sufficient for formation of large-conductance channels in GH4 cells, whereas in Vero cells such large-conductance channels are in addition dependent on NheC

Quantitative EEG findings in patients with acute, brief depression combined with other fluctuating psychiatric symptoms: a controlled study from an acute psychiatric department

<p>Abstract</p> <p>Background</p> <p>Patients with brief depressive episodes and concurrent rapidly fluctuating psychiatric symptoms do not fit current diagnostic criteria and they can be difficult to diagnose and treat in an acute psychiatric setting. We wanted to study whether these patients had signs of more epileptic or organic brain dysfunction than patients with depression without additional symptomatology.</p> <p>Methods</p> <p>Sixteen acutely admitted patients diagnosed with a brief depressive episode as well as another concurrent psychiatric diagnosis were included. Sixteen patients with major depression served as controls. Three electroencephalographic studies (EEG) were visually interpreted and the background activity was also analysed with quantitative electroencephalography (QEEG).</p> <p>Results</p> <p>The group with brief depression and concurrent symptoms had multiple abnormal features in their standard EEG compared to patients with major depression, but they did not show significantly more epileptiform activity. They also had significantly higher temporal QEEG delta amplitude and interhemispheric temporal delta asymmetry.</p> <p>Conclusion</p> <p>Organic brain dysfunction may be involved in the pathogenesis of patients with brief depressive episodes mixed with rapidly fluctuating psychiatric symptoms. This subgroup of depressed patients should be investigated further in order to clarify the pathophysiology and to establish the optimal evaluation scheme and treatment in an acute psychiatric setting.</p

The Crowdsourced Replication Initiative: Investigating Immigration and Social Policy Preferences. Executive Report.

In an era of mass migration, social scientists, populist parties and social movements raise concerns over the future of immigration-destination societies. What impacts does this have on policy and social solidarity? Comparative cross-national research, relying mostly on secondary data, has findings in different directions. There is a threat of selective model reporting and lack of replicability. The heterogeneity of countries obscures attempts to clearly define data-generating models. P-hacking and HARKing lurk among standard research practices in this area.This project employs crowdsourcing to address these issues. It draws on replication, deliberation, meta-analysis and harnessing the power of many minds at once. The Crowdsourced Replication Initiative carries two main goals, (a) to better investigate the linkage between immigration and social policy preferences across countries, and (b) to develop crowdsourcing as a social science method. The Executive Report provides short reviews of the area of social policy preferences and immigration, and the methods and impetus behind crowdsourcing plus a description of the entire project. Three main areas of findings will appear in three papers, that are registered as PAPs or in process

Symptoms of epilepsy and organic brain dysfunctions in patients with acute, brief depression combined with other fluctuating psychiatric symptoms: a controlled study from an acute psychiatric department

Background: In psychiatric acute departments some patients present with brief depressive periods accompanied with fluctuating arrays of other psychiatric symptoms like psychosis, panic or mania. For the purpose of the present study we call this condition Acute Unstable Depressive Syndrome (AUDS). The aims of the present study were to compare clinical signs of organic brain dysfunctions and epilepsy in patients with AUDS and Major Depressive Episode (MDE). Methods: Out of 1038 consecutive patients admitted to a psychiatric acute ward, 16 patients with AUDS and 16 age- and gender-matched MDE patients were included in the study. Using standardized instruments and methods we recorded clinical data, EEG and MRI. Results: A history of epileptic seizures and pathologic EEG activity was more common in the AUDS group than in the MDE group (seizures, n = 6 vs. 0, p = 0.018; pathologic EEG activity, n = 8 vs. 1, p = 0.015). Five patients in the AUDS group were diagnosed as having epilepsy, whereas none of those with MDE had epilepsy (p = 0.043). There were no differences between the groups regarding pathological findings in neurological bedside examination and cerebral MRI investigation. Conclusion: Compared to patients admitted with mood symptoms fulfilling DSM 4 criteria of a major depressive disorder, short-lasting atypical depressive symptoms seem to be associated with a high frequency of epileptic and pathologic EEG activity in patients admitted to psychiatric acute departments

Long-term outcome of primary intraocular lens implantation in bilateral congenital cataract in infants with a median age of 35 days at surgery: A case series

Objective: To evaluate the long-term visual outcome and safety after bilateral cataract surgery with primary intraocular lens (IOL) implantation in infants with visually significant cataract at birth operated before 12 weeks of age. Methods and analysis: Medical records of infants with congenital cataract who had bilateral surgery with primary IOL implantation before 12 weeks of age at Oslo University Hospital between 2007 and 2016 were retrospectively reviewed. Fifteen infants (30 eyes) were enrolled for a prospective study examination in 2017. Corrected distance visual acuity (CDVA) and intraocular pressure (IOP) were assessed. Visual axis opacification (VAO) was defined as opacification on the anterior or posterior surface of the IOL, capsular phimosis or fibrinous membrane. Secondary glaucoma was evaluated according to international guidelines. Results: Median age at the time of primary surgery was 35 days (range, 15 to 70 days). There were no serious intraoperative complications, and all eyes had the IOL implanted in the capsular bag. After a median follow-up of 6.1 years (range, 1.5 to 10.2 years), the CDVA was 0.5 logMAR (range, 1.2 to 0.04). All eyes had surgery for VAO and the median number of surgical procedures was 2.0 (range, 1 to 5). The cumulative incidence of secondary glaucoma was 10% after 5 years of follow-up. Conclusion: Primary IOL implantation before 12 weeks of age gave a satisfactory visual outcome, and the incidence of secondary glaucoma was similar to that reported after primary IOL implantation in older infants. However, the risk of VAO was high