The Interaction of Phospholipase C-{beta}3 with Shank2 Regulates mGluR-mediated Calcium Signal

Phospholipase C-{beta} isozymes that are activated by G protein-coupled receptors (GPCR) and heterotrimeric G proteins carry a PSD-95/Dlg/ZO-1 (PDZ) domain binding motif at their C terminus. Through interactions with PDZ domains, this motif may endow the PLC-{beta} isozyme with specific roles in GPCR signaling events that occur in compartmentalized regions of the plasma membrane. In this study, we identified the interaction of PLC-{beta}3 with Shank2, a PDZ domain-containing multimodular scaffold in the postsynaptic density (PSD). The C terminus of PLC-{beta}3, but not other PLC-{beta} isotypes, specifically interacts with the PDZ domain of Shank2. Homer 1b, a Shank-interacting protein that is linked to group I metabotropic glutamate receptors and IP3 receptors, forms a multiple complex with Shank2 and PLC-{beta}3. Importantly, microinjection of a synthetic peptide specifically mimicking the C terminus of PLC-{beta}3 markedly reduces the mGluR-mediated intracellular calcium response. These results demonstrate that Shank2 brings PLC-{beta}3 closer to Homer 1b and constitutes an efficient mGluR-coupled signaling pathway in the PSD region of neuronal synapses

Delayed massive hemothorax requiring surgery after blunt thoracic trauma over a 5-year period: complicating rib fracture with sharp edge associated with diaphragm injury

Delayed massive hemothorax requiring surgery is relatively uncommon and can potentially be life-threatening. Here, we aimed to describe the nature and cause of delayed massive hemothorax requiring immediate surgery. Over 5 years, 1,278 consecutive patients were admitted after blunt trauma. Delayed hemothorax is defined as presenting with a follow-up chest radiograph and computed tomography showing blunting or effusion. A massive hemothorax is defined as blood drainage >1,500 mL after closed thoracostomy and continuous bleeding at 200 mL/hr for at least four hours. Five patients were identified all requiring emergency surgery. Delayed massive hemothorax presented 63.6±21.3 hours after blunt chest trauma. All patients had superficial diaphragmatic lacerations caused by the sharp edge of a broken rib. The mean preoperative chest tube drainage was 3,126±463 mL. We emphasize the high-risk of massive hemothorax in patients who have a broken rib with sharp edges

Abalone visceral extract inhibit tumor growth and metastasis by modulating Cox-2 levels and CD8+ T cell activity

<p>Abstract</p> <p>Background</p> <p>Abalone has long been used as a valuable food source in East Asian countries. Although the nutritional importance of abalone has been reported through <it>in vitro </it>and <it>in vivo </it>studies, there is little evidence about the potential anti-tumor effects of abalone visceral extract. The aim of the present study is to examine anti-tumor efficacy of abalone visceral extract and to elucidate its working mechanism.</p> <p>Methods</p> <p>In the present study, we used breast cancer model using BALB/c mouse-derived 4T1 mammary carcinoma and investigated the effect of abalone visceral extract on tumor development. Inhibitory effect against tumor metastasis was assessed by histopathology of lungs. Cox-2 productions by primary and secondary tumor were measured by real-time RT-PCR and immunoblotting (IB). Proliferation assay based on [³H]-thymidine incorporation and measurement of cytokines and effector molecules by RT-PCR were used to confirm tumor suppression efficacy of abalone visceral extract by modulating cytolytic CD8+ T cells. The cytotoxicity of CD8⁺T cell was compared by JAM test.</p> <p>Results</p> <p>Oral administration of abalone visceral extract reduced tumor growth (tumor volume and weight) and showed reduced metastasis as confirmed by decreased level of splenomegaly (spleen size and weight) and histological analysis of the lung metastasis (gross analysis and histological staining). Reduced expression of Cox-2 (mRNA and protein) from primary tumor and metastasized lung was also detected. In addition, treatment of abalone visceral extract increased anti-tumor activities of CD8⁺T cells by increasing the proliferation capacity and their cytolytic activity.</p> <p>Conclusions</p> <p>Our results suggest that abalone visceral extract has anti-tumor effects by suppressing tumor growth and lung metastasis through decreasing Cox-2 expression level as well as promoting proliferation and cytolytic function of CD8⁺T cells.</p

GAIT ASYMMETRY IN CHILDREN WITH DOWN SYNDROME

It has been reported that approximately 80% of children with Down syndrome (OS) exhibit gait problems (Matteo, 2002), characterized by flat-footed contact with no heel-strike, excessive abduction of the leg in the swing phase, and abnormal knee and hip f1exions throughout the gait cycle (Parker et aI., 1986). Due to muscle hypotonia, muscle weakness, !igamentous laXity, and other orthopedic abnormalities, different gait characteristics exist. The purpose of this study was to investigate the gait (walking and running) asymmetry in children with OS

Failure Modes of Silicon Powder Negative Electrode in Lithium Secondary Batteries

Si composite negative electrodes for lithium secondary batteries degrade in the dealloying period with an abrupt increase in internal resistance that is caused by a breakdown of conductive network made between Si and carbon particles. This results from a volume contraction of Si particles after expansion in the previous alloying process. Due to the large internal resistance, the dealloying reaction is not completed while Si remains as a lithiated state. The anodic performance is greatly improved either by applying a pressure on the cells or loading a larger amount of conductive carbon in the composite electrodes.This work was partially supported by KOSEF through Research Center for Energy Conversion and Storage, and by the financial support of Center for Nanostructured Materials Technology under 21st Century Frontier R&D Programs of the Ministry of Science and Technology, Korea. Financial support from LG Chem. Ltd. is also acknowledged

Depression and increased risk of nonalcoholic fatty liver disease in individuals with obesity

Aims: the longitudinal relationship between depression and the risk of nonalcoholic fatty liver disease (NAFLD) is uncertain. We examined: a) the association between depressive symptoms and incident hepatic steatosis (HS), both with and without liver fibrosis; and b) the influence of obesity on this association. Methods: cohort of 142,005 Korean adults with neither HS nor excessive alcohol consumption at baseline were followed for up to 8.9 years. The validated Center for Epidemiologic Studies-Depression score (CES-D) was assessed at baseline, and subjects were categorized as non-depressed (a CES-D &lt;8, reference) or depression (CES-D ≥16). HS was diagnosed by ultrasonography. Liver fibrosis was assessed by the fibrosis-4 index (FIB-4). Parametric proportional hazards models were used to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Results: during a median follow-up of 4.0 years, 27,810 people with incident HS and 134 with incident HS plus high FIB-4 were identified. Compared with the non-depressed category, the aHR (95% CIs) for incident HS was 1.24 (1.15-1.34) for CES-D ≥16 among obese individuals, and 1.00 (0.95-1.05) for CES-D ≥16 among non-obese individuals (P for interaction with obesity &lt;0.001). The aHR (95% CIs) for developing HS plus high FIB-4 was 3.41 (1.33-8.74) for CES-D≥16 among obese individuals, and 1.22 (0.60-2.47) for CES-D≥16 among non-obese individuals (P for interaction =0.201). Conclusions: depression was associated with an increased risk of incident HS and HS plus high probability of advanced fibrosis, especially among obese individuals

Expression and functional role of formyl peptide receptor in human bone marrow-derived mesenchymal stem cells

AbstractWe investigated the expression of formyl peptide receptor (FPR) and its functional role in human bone marrow-derived mesenchymal stem cells (MSCs). We analyzed the expression of FPR by using ligand-binding assay with radio-labeled N-formyl-met-leu-phe (fMLF), and found that MSCs express FPR. FMLF stimulated intracellular calcium increase, mitogen-activated protein kinases activation, and Akt activation, which were mediated by Gi proteins. MSCs were chemotactically migrated to fMLF. FMLF-induced MSC chemotaxis was also completely inhibited by pertussis toxin, LY294002, and PD98059, indicating the role of Gi proteins, phosphoinositide 3-kinase, and extracellular signal regulated protein kinase. N-terminal fragment of annexin-1, Anx-1(2–26), an endogenous agonist for FPR, also induced chemotactic migration of MSCs. Thus MSCs express functional FPR, suggesting a new (patho)physiological role of FPR and its ligands in regulating MSC trafficking during induction of injured tissue repair