Kalirin12 interacts with dynamin

<p>Abstract</p> <p>Background</p> <p>Guanine nucleotide exchange factors (GEFs) and their target Rho GTPases regulate cytoskeletal changes and membrane trafficking. Dynamin, a large force-generating GTPase, plays an essential role in membrane tubulation and fission in cells. Kalirin12, a neuronal RhoGEF, is found in growth cones early in development and in dendritic spines later in development.</p> <p>Results</p> <p>The IgFn domain of Kalirin12, not present in other Kalirin isoforms, binds dynamin1 and dynamin2. An inactivating mutation in the GTPase domain of dynamin diminishes this interaction and the isolated GTPase domain of dynamin retains the ability to bind Kalirin12. Co-immunoprecipitation demonstrates an interaction of Kalirin12 and dynamin2 in embryonic brain. Purified recombinant Kalirin-IgFn domain inhibits the ability of purified rat brain dynamin to oligomerize in response to the presence of liposomes containing phosphatidylinositol-4,5-bisphosphate. Consistent with this, expression of exogenous Kalirin12 or its IgFn domain in PC12 cells disrupts clathrin-mediated transferrin endocytosis. Similarly, expression of exogenous Kalirin12 disrupts transferrin endocytosis in cortical neurons. Expression of Kalirin7, a shorter isoform which lacks the IgFn domain, was previously shown to inhibit clathrin-mediated endocytosis; the GTPase domain of dynamin does not interact with Kalirin7.</p> <p>Conclusion</p> <p>Kalirin12 may play a role in coordinating Rho GTPase-mediated changes in the actin cytoskeleton with dynamin-mediated changes in membrane trafficking.</p

Cell-type specific gene expression profiles of leukocytes in human peripheral blood

BACKGROUND: Blood is a complex tissue comprising numerous cell types with distinct functions and corresponding gene expression profiles. We attempted to define the cell type specific gene expression patterns for the major constituent cells of blood, including B-cells, CD4+ T-cells, CD8+ T-cells, lymphocytes and granulocytes. We did this by comparing the global gene expression profiles of purified B-cells, CD4+ T-cells, CD8+ T-cells, granulocytes, and lymphocytes using cDNA microarrays. RESULTS: Unsupervised clustering analysis showed that similar cell populations from different donors share common gene expression profiles. Supervised analyses identified gene expression signatures for B-cells (427 genes), T-cells (222 genes), CD8+ T-cells (23 genes), granulocytes (411 genes), and lymphocytes (67 genes). No statistically significant gene expression signature was identified for CD4+ cells. Genes encoding cell surface proteins were disproportionately represented among the genes that distinguished among the lymphocyte subpopulations. Lymphocytes were distinguishable from granulocytes based on their higher levels of expression of genes encoding ribosomal proteins, while granulocytes exhibited characteristic expression of various cell surface and inflammatory proteins. CONCLUSION: The genes comprising the cell-type specific signatures encompassed many of the genes already known to be involved in cell-type specific processes, and provided clues that may prove useful in discovering the functions of many still unannotated genes. The most prominent feature of the cell type signature genes was the enrichment of genes encoding cell surface proteins, perhaps reflecting the importance of specialized systems for sensing the environment to the physiology of resting leukocytes

Medical conditions mimicking the acute surgical abdomen in children

Background: We present our experience with children landing up in our pediatric surgery emergency with potentially confounding medical conditions that evade diagnosis. It is imperative to apply sound clinical judgement in the evaluation of these patients so that an unnecessary laparotomy can be avoided but, at the same time, a lifesaving intervention is not denied.Patients and methods: This is a retrospective descriptive analysis pertaining to all patients who were admitted in our department from 1 January 2014 to 31 July 2017. A total of 27 867 patients presented to our out-patient department of these, 3034 were admitted to our ward. A total of 1531 surgeries were performed, of which 288 were for various abdominal surgical conditions. A total of 16 patients, representing 0.5 % of the admissions, were eventually found to have an acute abdomen secondary to a medical cause.Results: Out of the above 16 patients, 10 had to undergo exploratory laparotomy (62.5%). Eight patients of the 10 operated had a negative laparotomy. Two of the 10 operated were found to have a surgically correctable cause, one with ovarian torsion and one with severe colonic edema secondary to Kawasaki’s disease causing intestinal obstruction.Conclusion: Although eight patients with negative laparotomy result constitute only 0.5% of all the surgeries and 2.7% of all the laparotomies, it still forms the bulk (i.e. 8/16=50%) of the patients with underlying medical cause of the surgical abdomen. There were two deaths, representing a mortality of 12.5% (2/16=12.5%), with one in the operated group and one in the nonoperated group. This is why we want to stress the importance of caution and sound clinical judgement in evaluating this subset of patients.Keywords: acute abdomen, medical conditions mimicking, surgical abdomen in childre

Deep inferior epigastric perforator (DIEP) flap: Impact of drain free donor abdominal site on long term patient outcomes and duration of inpatient stay

Background: The deep inferior epigastric perforator (DIEP) flap is widely regarded as the Gold Standard in autologous breast reconstruction. Although drain-free abdominoplasty is performed in many centres, there is a paucity of evidence comparing outcomes when applied to DIEP breast reconstruction. Method: A retrospective review of patients who underwent DIEP breast reconstruction without abdominal drain insertion at Royal Free Hospital between Jan 2012-Nov 2016 was undertaken. Results were compared to previously published data from our centre on patients undergoing DIEP breast reconstruction with abdominal drains between Jan 2011-Jul 2012. Results: Thirty-five patients underwent abdominal drain-free reconstruction (GroupA). Of 74 patients who previously underwent reconstruction with abdominal drains, 33 patients underwent drain removal by postoperative day (POD)3 regardless of output (GroupB) and 41 underwent drain removal after POD3 following instructions on drainage volume/24 h (GroupC). There was no significant difference in the length of stay between patients in Group A and B (3.6 vs. 3.9 days; p = 0.204). Length of stay in Group C was significantly higher than Group A and B (p = 0.001, p = 0.001). There were no statistically significant differences in total (11.43% vs. 12.12% vs 17.07%, p = 0.780) or specific complications: Seroma: 2.86% vs. 0% vs. 4.88% (p = 0.774); Wound dehiscence: 8.57% vs. 9.09% vs. 4.88% (p = 0.728); Haematoma: 0% vs. 3.00% vs. 7.32% (p = 0.316) between Groups A, B and C, respectively. Conclusion: Our data suggests that drain-free abdominal closure in DIEP reconstruction can be safely achieved without increased postoperative complications. These conclusions support existing evidence on the use of a drain-free approach in cosmetic abdominoplasty

Decoupling of a Current-Biased Intrinsic Josephson Junction from its Environment

We have observed a dissipative phase diffusion branch in arrays of hysteretic high-Tc intrinsic Josephson junctions. By comparing the data with a thermal activation model we extract the impedance seen by the junction in which phase diffusion is occurring. At the plasma frequency this junction is isolated from its environment and it sees its own large (~ kilo Ohm) impedance. Our results suggest that stacks of Josephson junctions may be used for isolation purposes in the development of a solid state quantum computer

Expression of the Rap1 Guanine Nucleotide Exchange Factor, MR-GEF, Is Altered in Individuals with Bipolar Disorder

In the rodent forebrain GABAergic neurons are generated from progenitor cells that express the transcription factors Dlx1 and Dlx2. The Rap-1 guanine nucleotide exchange factor, MR-GEF, is turned on by many of these developing GABAergic neurons. Expression of both Dlx1/2 and MR-GEF is retained in both adult mouse and human forebrain where, in human, decreased Dlx1 expression has been associated with psychosis. Using in situ hybridization studies we show that MR-GEF expression is significantly down-regulated in the forebrain of Dlx1/2 double mutant mice suggesting that MR-GEF and Dlx1/2 form part of a common signalling pathway during GABAergic neuronal development. We therefore compared MR-GEF expression by in situ hybridization in individuals with major psychiatric disorders (schizophrenia, bipolar disorder, major depression) and control individuals. We observed a significant positive correlation between layers II and IV of the dorso-lateral prefrontal cortex (DLPFC) in the percentage of MR-GEF expressing neurons in individuals with bipolar disorder, but not in individuals with schizophrenia, major depressive disorder or in controls. Since MR-GEF encodes a Rap1 GEF able to activate G-protein signalling, we suggest that changes in MR-GEF expression could potentially influence neurotransmission

Simulating eddy current sensor outputs for blade tip timing

Blade tip timing is a contactless method used to monitor the vibration of blades in rotating machinery. Blade vibration and clearance are important diagnostic features for condition monitoring, including the detection of blade cracks. Eddy current sensors are a practical choice for blade tip timing and have been used extensively. As the data requirements from the timing measurement become more stringent and the systems become more complicated, including the use of multiple sensors, the ability to fully understand and optimize the measurement system becomes more important. This requires detailed modeling of eddy current sensors in the blade tip timing application; the current approaches often rely on experimental trials. Existing simulations for eddy current sensors have not considered the particular case of a blade rotating past the sensor. Hence, the novel aspect of this article is the development of a detailed quasi-static finite element model of the electro-magnetic field to simulate the integrated measured output of the sensor. This model is demonstrated by simulating the effect of tip clearance, blade geometry, and blade velocity on the output of the eddy current sensor. This allows an understanding of the sources of error in the blade time of arrival estimate and hence insight into the accuracy of the blade vibration measurement