Proteomic and biochemical analyses reveal the activation of unfolded protein response, ERK-1/2 and ribosomal protein S6 signaling in experimental autoimmune myocarditis rat model

<p>Abstract</p> <p>Background</p> <p>To investigate the molecular and cellular pathogenesis underlying myocarditis, we used an experimental autoimmune myocarditis (EAM)-induced heart failure rat model that represents T cell mediated postinflammatory heart disorders.</p> <p>Results</p> <p>By performing unbiased 2-dimensional electrophoresis of protein extracts from control rat heart tissues and EAM rat heart tissues, followed by nano-HPLC-ESI-QIT-MS, 67 proteins were identified from 71 spots that exhibited significantly altered expression levels. The majority of up-regulated proteins were confidently associated with unfolded protein responses (UPR), while the majority of down-regulated proteins were involved with the generation of precursor metabolites and energy metabolism in mitochondria. Although there was no difference in AKT signaling between EAM rat heart tissues and control rat heart tissues, the amounts and activities of extracellular signal-regulated kinase (ERK)-1/2 and ribosomal protein S6 (rpS6) were significantly increased. By comparing our data with the previously reported myocardial proteome of the Coxsackie viruses of group B (CVB)-mediated myocarditis model, we found that UPR-related proteins were commonly up-regulated in two murine myocarditis models. Even though only two out of 29 down-regulated proteins in EAM rat heart tissues were also dysregulated in CVB-infected rat heart tissues, other proteins known to be involved with the generation of precursor metabolites and energy metabolism in mitochondria were also dysregulated in CVB-mediated myocarditis rat heart tissues, suggesting that impairment of mitochondrial functions may be a common underlying mechanism of the two murine myocarditis models.</p> <p>Conclusions</p> <p>UPR, ERK-1/2 and S6RP signaling were activated in both EAM- and CVB-induced myocarditis murine models. Thus, the conserved components of signaling pathways in two murine models of acute myocarditis could be targets for developing new therapeutic drugs or methods aimed at treating enigmatic myocarditis.</p

Inhibition of ATR Increases the Sensitivity to WEE1 Inhibitor in Biliary Tract Cancer

Purpose Currently, the DNA damage response (DDR) pathway represents a key target for new cancer drug development. Advanced biliary tract cancer (BTC) has a poor prognosis because of the lack of efficacious treatment options. Although DNA repair pathway alterations have been reported in many patients with BTC, little is known regarding the effects of DDR-targeted agents against BTC. Materials and Methods In this study, nine BTC cell lines were exposed to the WEE1 inhibitor (AZD1775). In vitro, MTT assay, colony-forming assay, cell cycle analysis, phospho-histone H3 staining assay, Transwell migration assay, and western blot were performed. Then, to enhance the antitumor effect of AZD1775, the combination treatment of WEE1 inhibitor and ataxia telangiectasia mutated and Rad3 related (ATR) inhibitor (AZD6738) was conducted using MTT assay and comet assay. Finally, HuCCT-1 and SNU2670 xenograft models were established to confirm the anti-tumor effect of AZD1775 alone. Furthermore, the combination treatment was also evaluated in SNU2670 xenograft models. Results AZD1775 blocked the phosphorylation of CDC2 and CDC25C in all cell lines, but significantly increased apoptosis and S phase arrest in sensitive cells. However, increased p-ATR and phosphorylated ataxia telangiectasia mutated levels were observed in less sensitive cells. In addition, in vitro and in vivo data illustrated that AZD1775 combined with AZD6738 exerted more potent anti-tumor effects than either drug alone. Although WEE1 inhibition has promising anti-tumor effects in some BTC cells, the addition of ATR inhibitors could enhance its efficacy. Conclusion Taken together, this study supports further clinical development of DDR-targeted strategies as monotherapy or combination regimens for BTC.

Breakdown of the interlayer coherence in twisted bilayer graphene

Coherent motion of the electrons in the Bloch states is one of the fundamental concepts of the charge conduction in solid state physics. In layered materials, however, such a condition often breaks down for the interlayer conduction, when the interlayer coupling is significantly reduced by e.g. large interlayer separation. We report that complete suppression of coherent conduction is realized even in an atomic length scale of layer separation in twisted bilayer graphene. The interlayer resistivity of twisted bilayer graphene is much higher than the c-axis resistivity of Bernal-stacked graphite, and exhibits strong dependence on temperature as well as on external electric fields. These results suggest that the graphene layers are significantly decoupled by rotation and incoherent conduction is a main transport channel between the layers of twisted bilayer graphene.Comment: 5 pages, 3 figure

Tiul1 and TGIF are Involved in Downregulation of TGFβ1-induced IgA Isotype Expression

TGF-β1 is well known to induce Ig germ-line α (GLα) transcription and subsequent IgA isotype class switching recombination (CSR). Homeodomain protein TG-interacting factor (TGIF) and E3-ubiquitin ligases TGIF interacting ubiquitin ligase 1 (Tiul1) are implicated in the negative regulation of TGF-β signaling. In the present study, we investigated the roles of Tiul1 and TGIF in TGFβ1-induced IgA CSR. We found that over-expression of Tiul1 decreased TGFβ1-induced GLα promoter activity and strengthened the inhibitory effect of Smad7 on the promoter activity. Likewise, overexpression of TGIF also diminished GLα promoter activity and further strengthened the inhibitory effect of Tiul1, suggesting that Tiul1 and TGIF can down-regulate TGFβ1-induced GLα expression. In parallel, overexpression of Tiul1 decreased the expression of endogenous IgA CSR-predicitive transcripts (GLTα, PSTα, and CTα) and TGFβ1-induced IgA secretion, but not GLTγ3 and IgG3 secretion. Here, over-expressed TGIF further strengthened the inhibitory effect of Tiul1. These results suggest that Tiul1 and TGIF act as negatively regulators in TGFβ1-induced IgA isotype expression

Production of Hydrogen and Carbon Black by Methane Decomposition Using DC-RF Hybrid Thermal Plasmas

A continuous production of carbon black and hydrogen has been investigated by thermal decomposition of methane using a prototype processing system of DC-RF hybrid thermal plasma, which has great advantage over other thermal sources like combustion or DC plasma torches in synthesizing new nanostructured materials by providing high-temperature environment and longer residence time for reactant gases due to its larger hot core region and lower flow velocity. Appropriate operation conditions and reactor geometries for the effective synthesis process are predicted first from the relevant theoretical bases, such as thermodynamic equilibrium calculations, two-dimensional thermal flow analysis, and chemical kinetic simulation. Based on these derived operation and design parameters, a reaction chamber and a DC-RF hybrid torch are fabricated for the processing system, which is followed by methane decomposition experiments with it. The methane injected into the processing system is converted mostly into hydrogen with a small volume fraction of acetylene, and fine carbon particles of 20-50 nm are identified from their TEM images. Material analyses of BET, DBP and XRD indicate that the synthesized carbon black has excellent properties such as large surface area, high electrical conductivity, and highly graphitized structures with good crystallization

Comparative proteomic analysis of early salt stress-responsive proteins in roots of SnRK2 transgenic rice

<p>Abstract</p> <p>Background</p> <p>The rice roots are highly salt-sensitive organ and primary root growth is rapidly suppressed by salt stress. Sucrose nonfermenting 1-related protein kinase2 (SnRK2) family is one of the key regulator of hyper-osmotic stress signalling in various plant cells. To understand early salt response of rice roots and identify SnRK2 signaling components, proteome changes of transgenic rice roots over-expressing OSRK1, a rice SnRK2 kinase were investigated.</p> <p>Results</p> <p>Proteomes were analyzed by two-dimensional electrophoresis and protein spots were identified by LC-MS/MS from wild type and OSRK1 transgenic rice roots exposed to 150 mM NaCl for either 3 h or 7 h. Fifty two early salt -responsive protein spots were identified from wild type rice roots. The major up-regulated proteins were enzymes related to energy regulation, amino acid metabolism, methylglyoxal detoxification, redox regulation and protein turnover. It is noted that enzymes known to be involved in GA-induced root growth such as fructose bisphosphate aldolase and methylmalonate semialdehyde dehydrogenase were clearly down-regulated. In contrast to wild type rice roots, only a few proteins were changed by salt stress in OSRK1 transgenic rice roots. A comparative quantitative analysis of the proteome level indicated that forty three early salt-responsive proteins were magnified in transgenic rice roots at unstressed condition. These proteins contain single or multiple potential SnRK2 recognition motives. In vitro kinase assay revealed that one of the identified proteome, calreticulin is a good substrate of OSRK1.</p> <p>Conclusions</p> <p>Our present data implicate that rice roots rapidly changed broad spectrum of energy metabolism upon challenging salt stress, and suppression of GA signaling by salt stress may be responsible for the rapid arrest of root growth and development. The broad spectrum of functional categories of proteins affected by over-expression of OSRK1 indicates that OSRK1 is an upstream regulator of stress signaling in rice roots. Enzymes involved in glycolysis, branched amino acid catabolism, dnaK-type molecular chaperone, calcium binding protein, Sal T and glyoxalase are potential targets of OSRK1 in rice roots under salt stress that need to be further investigated.</p

Continuous process of carbon nanotubes synthesis by decomposition of methane using an arc-jet plasma

Author's version; The Joint Meeting of 7th APCPST (Asia Pacific Conference on Plasma Science and Technology) and 17th SPSM (Symposium on Plasma Science for Materials) - 7th APCPST/17th SPSMWe present a method of producing carbon nanotubes by means of the thermal plasma decomposition of methane in an arc-jet plasma of high temperature (5000–20,000 K). Carbon nanotubes are produced under a floating condition by introducing methane and a mixture of Ni–Y powders into the arc-jet plasma flame generated by a non-transferred plasma torch. Material evaluations of the synthesized product by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) reveal that the growth rate of carbon nanotubes is very high, and that the multi-walled carbon nanotubes of high purity are mainly produced. Since this process is continuously operable and easily scalable, it is expected to be a promising technique for large-scale commercial production of carbon nanotubes.Korea Institute of Science and Technology Evaluation and Planning (KISTEP

Bioresorbable silicon electronics for transient spatiotemporal mapping of electrical activity from the cerebral cortex.

Bioresorbable silicon electronics technology offers unprecedented opportunities to deploy advanced implantable monitoring systems that eliminate risks, cost and discomfort associated with surgical extraction. Applications include postoperative monitoring and transient physiologic recording after percutaneous or minimally invasive placement of vascular, cardiac, orthopaedic, neural or other devices. We present an embodiment of these materials in both passive and actively addressed arrays of bioresorbable silicon electrodes with multiplexing capabilities, which record in vivo electrophysiological signals from the cortical surface and the subgaleal space. The devices detect normal physiologic and epileptiform activity, both in acute and chronic recordings. Comparative studies show sensor performance comparable to standard clinical systems and reduced tissue reactivity relative to conventional clinical electrocorticography (ECoG) electrodes. This technology offers general applicability in neural interfaces, with additional potential utility in treatment of disorders where transient monitoring and modulation of physiologic function, implant integrity and tissue recovery or regeneration are required

Efficient Photoelectrochemical Water Oxidation by Metal-Doped Bismuth Vanadate Photoanode with Iron Oxyhydroxide Electrocatalyst

Intensive attention has been currently focused on the discovery of semiconductor and proficient cocatalysts for eventual applications to the photoelectrochemical water splitting system. A W-Mo-doped BiVO4 semiconductor was prepared by the surfactant-assisted thermal decomposition method on a fluorine-doped tin oxide conductive film. The W-Mo-doped BiVO4 films showed a porous morphology with the grain sizes of about 270 nm. Because the hole diffusion length of BiVO4 is about 100 nm, the W-Mo-doped BiVO4 film in this study is an ideal candidate for the photoelectrochemical water oxidation. Iron oxyhydroxide (FeOOH) electrocatalyst was chemically deposited on the W-Mo-doped BiVO4 to investigate the effect of the electrocatalyst on the semiconductor. The W-Mo-doped BiVO4/FeOOH composite electrode showed enhanced activity compared to the pristine W-Mo-doped BiVO4 electrode for water oxidation reaction. The chemical deposition is a promising method for the deposition of FeOOH on semiconductor

Clinical features of infantile hepatic hemangioendothelioma

PurposeInfantile hepatic hemangioendothelioma (IHHE) is the most common type of hepatic vascular tumor in infancy. We conducted this study to review our clinical experience of patients with IHHE and to suggest management strategies.MethodsWe retrospectively analyzed the medical records of 23 IHHE patients (10 males, 13 females) treated at the Asan Medical Center between 1996 and 2009.ResultsMedian age at diagnosis was 38 days (range, 1 to 381 days). Seven patients (30%) were diagnosed with IHHE based on sonographically detected fetal liver masses, 5 (22%) were diagnosed incidentally in the absence of symptoms, 5 (22%) had congestive heart failure, 3 (13%) had skin hemangiomas, 2 (9%) had abnormal liver function tests, and 1 (4%) had hepatomegaly. All diagnoses were based on imaging results, and were confirmed in three patients by histopathology analysis. Six patients were observed without receiving any treatment, whereas 12 received corticosteroids and/or interferon-alpha. One patient with congestive heart failure and a resectable unilobar tumor underwent surgical resection. Three patients with congestive heart failure and unresectable tumors were managed by hepatic artery embolization with/without medical treatment. At a median follow-up of 29 months (range, 1 to 156 months), 21 (91%) patients showed complete tumor disappearance or >50% decrease in tumor size. One patient died due to tumor-related causes.ConclusionIHHE generally has a benign clinical course with low morbidity and mortality rates. Clinical course and treatment outcome did not differ significantly between medically treated and non-treated groups. Surgically unresectable patients with significant symptoms may be treated medically or with hepatic artery embolization