A Novel Cytoplasmic Protein with RNA-binding Motifs Is an Autoantigen in Human Hepatocellular Carcinoma

In hepatocellular carcinoma (HCC), autoantibodies to intracellular antigens are detected in 30–40% of patients. Patients with chronic hepatitis or liver cirrhosis develop HCC, and when this occurs, some patients exhibit autoantibodies of new specificities. It has been suggested that these novel autoantibody responses may be immune system reactions to proteins involved in transformation-associated cellular events. One HCC serum shown to contain antibodies to unidentified cellular antigens was used to immunoscreen a cDNA expression library, and a full length cDNA clone was isolated with an open reading frame encoding 556 amino acids with a predicted molecular mass of 62 kD. The 62-kD protein contained two types of RNA-binding motifs, the consensus sequence RNA–binding domain (CS-RBD) and four hnRNP K homology (KH) domains. This protein, provisionally called p62, has close identity (66–70%) to three other proteins at the amino acid sequence level, and all four proteins may belong to a family having CS-RBD in the NH2-terminal region and four KH domains in the mid-to-COOH– terminal region. The homologous proteins are: KH domain–containing protein overexpressed in cancer (Koc); zipcode binding protein, a protein which binds to a conserved nucleotide element in chicken β-actin mRNA (ZBP1); and a protein which binds to a promoter cis element in Xenopus laevis TFIIIA gene (B3). p62 protein is cytoplasmic in location, and autoantibodies were found in 21% of a cohort of HCC patients. Patients with chronic hepatitis and liver cirrhosis, conditions which are frequent precursors to HCC, were negative for these autoantibodies, suggesting that the immune response might be related to cellular events leading to transformation. However, the possible involvement of p62 autoantigen as a factor in the transformation process remains to be elucidated

Kinase inhibit region of SOCS3 attenuates IL6-induced proliferation and astrocytic differentiation of neural stem cells via cross talk between signaling pathways

Aims: Efficiency of neural stem cells (NSCs) therapy for brain injury is restricted by astrogliosis around the damaged region, in which JAK2/STAT3 signaling plays a key role. The SOCS3 that can directly inhibit JAK/STAT3 pathway. Here, we investigated the effects of a fusion peptide that combined kinase inhibitory region (KIR) of SOCS3 and virus trans-activator of transcription (TAT) on biological behavior of cultured NSCs under inflammatory conditions. Methods: NSCs were isolated from embryonic brain of SD rats, TAT-KIR was synthesized, and penetration rate was evaluated by flow cytometry (FACS). CCK8, immunostaining, and FACS were used to detected of TAT-KIR on the proliferation of NSCs. The expressions of GFAP and β tubulin III positive cells induced by IL6 with/without TAT-KIR were examined by immunostaining and Western blotting to observe the NSCs differentiation, and the effect of TAT-KIR on signaling cross talk was observed by Western blotting. Results: Penetration rate of TAT-KIR into primary cultured NSCs was up to 94%. TAT-KIR did not affect the growth and viability of NSCs. It significantly reduced the NSCs proliferation that enhanced by IL-6 stimulation via blocking the cell cycle progression from the G0/G1 to S phase. In addition, TAT-KIR attenuated astrocytic differentiation and kept high level of neuronal differentiation derived from IL-6-induced NSCs. The fate of NSCs differentiation under inflammatory conditions was affected by TAT-KIR, which was associated with synchronous inhibition of STAT3 and AKT, while promoting JNK expression. Conclusion: TAT-KIR mimetic of SOCS3 could be a promising approach for brain repair via regulating the biological behaviors of exogenous NSCs

Strong magnetic field dependence of critical current densities and vortex activation energies in an anisotropic clean MgB2 thin film

We report the influence of two-band superconductivity on the flux creep and the critical current densities of a MgB2 thin film. The small magnetic penetration depth of lambda=50 +/- 10 nm at T=4 K is related to a clean pi-band. We find a high self-field critical current density J(C), which is strongly reduced with applied magnetic field, and attribute this to suppression of the superconductivity in the pi-band. The temperature dependence of the creep rate S (T) at low magnetic field can be explained by a simple Anderson-Kim mechanism. The system shows high pinning energies at low field that are strongly suppressed by high field. (C) 2014 Elsevier Ltd. All rights reserved.X1112Ysciescopu

Observation of CR Anisotropy with ARGO-YBJ

The measurement of the anisotropies of cosmic ray arrival direction provides important informations on the propagation mechanisms and on the identification of their sources. In this paper we report the observation of anisotropy regions at different angular scales. In particular, the observation of a possible anisotropy on scales between $\sim$ 10 $^{\circ}$ and $\sim$ 30 $^{\circ}$ suggests the presence of unknown features of the magnetic fields the charged cosmic rays propagate through, as well as potential contributions of nearby sources to the total flux of cosmic rays. Evidence of new weaker few-degree excesses throughout the sky region $195^{\circ}\leq$ R.A. $\leq 315^{\circ}$ is reported for the first time.Comment: Talk given at 12th TAUP Conference 2011, 5-9 September 2011, Munich, German

Biophysical and electrochemical studies of protein-nucleic acid interactions

This review is devoted to biophysical and electrochemical methods used for studying protein-nucleic acid (NA) interactions. The importance of NA structure and protein-NA recognition for essential cellular processes, such as replication or transcription, is discussed to provide background for description of a range of biophysical chemistry methods that are applied to study a wide scope of protein-DNA and protein-RNA complexes. These techniques employ different detection principles with specific advantages and limitations and are often combined as mutually complementary approaches to provide a complete description of the interactions. Electrochemical methods have proven to be of great utility in such studies because they provide sensitive measurements and can be combined with other approaches that facilitate the protein-NA interactions. Recent applications of electrochemical methods in studies of protein-NA interactions are discussed in detail

Stable Field Emitters for a Miniature X-ray Tube Using Carbon Nanotube Drop Drying on a Flat Metal Tip

Stable carbon nanotube (CNT) field emitters for a vacuum-sealed miniature X-ray tube have been fabricated. The field emitters with a uniform CNT coating are prepared by a simple drop drying of a CNT mixture solution that is composed of chemically modified multi-walled CNTs, silver nanoparticles, and isopropyl alcohol on flat tungsten tips. A highly thermal- and electrical-conductive silver layer strongly attaches CNTs to the tungsten tips. Consequently, the field emitters exhibit good electron emission stability: continuous electron emission of around 100 μA at 2.3 V/μm has stably lasted over 40 h even at non-high vacuum ambient (~10−3 Pa)

Foxa1 Reduces Lipid Accumulation in Human Hepatocytes and Is Down-Regulated in Nonalcoholic Fatty Liver

Triglyceride accumulation in nonalcoholic fatty liver (NAFL) results from unbalanced lipid metabolism which, in the liver, is controlled by several transcription factors. The Foxa subfamily of winged helix/forkhead box (Fox) transcription factors comprises three members which play important roles in controlling both metabolism and homeostasis through the regulation of multiple target genes in the liver, pancreas and adipose tissue. In the mouse liver, Foxa2 is repressed by insulin and mediates fasting responses. Unlike Foxa2 however, the role of Foxa1 in the liver has not yet been investigated in detail. In this study, we evaluate the role of Foxa1 in two human liver cell models, primary cultured hepatocytes and HepG2 cells, by adenoviral infection. Moreover, human and rat livers were analyzed to determine Foxa1 regulation in NAFL. Results demonstrate that Foxa1 is a potent inhibitor of hepatic triglyceride synthesis, accumulation and secretion by repressing the expression of multiple target genes of these pathways (e.g., GPAM, DGAT2, MTP, APOB). Moreover, Foxa1 represses the fatty acid transporter protein FATP2 and lowers fatty acid uptake. Foxa1 also increases the breakdown of fatty acids by inducing peroxisomal fatty acid β-oxidation and ketone body synthesis. Finally, Foxa1 is able to largely up-regulate UCP1, thereby dissipating energy and consistently decreasing the mitochondria membrane potential. We also report that human and rat NAFL have a reduced Foxa1 expression, possibly through a protein kinase C-dependent pathway. We conclude that Foxa1 is an antisteatotic factor that coordinately tunes several lipid metabolic pathways to block triglyceride accumulation in hepatocytes. However, Foxa1 is down-regulated in human and rat NAFL and, therefore, increasing Foxa1 levels could protect from steatosis. Altogether, we suggest that Foxa1 could be a novel therapeutic target for NAFL disease and insulin resistance

Observation of the cosmic ray moon shadowing effect with the ARGO-YBJ experiment

Cosmic rays are hampered by the Moon and a deficit in its direction is expected (the so-called Moon shadow). The Moon shadow is an important tool to determine the performance of an air shower array. Indeed, the westward displacement of the shadow center, due to the bending effect of the geomagnetic field on the propagation of cosmic rays, allows the setting of the absolute rigidity scale of the primary particles inducing the showers recorded by the detector. In addition, the shape of the shadow permits to determine the detector point spread function, while the position of the deficit at high energies allows the evaluation of its absolute pointing accuracy. In this paper we present the observation of the cosmic ray Moon shadowing effect carried out by the ARGO-YBJ experiment in the multi-TeV energy region with high statistical significance (55 standard deviations). By means of an accurate Monte Carlo simulation of the cosmic rays propagation in the Earth-Moon system, we have studied separately the effect of the geomagnetic field and of the detector point spread function on the observed shadow. The angular resolution as a function of the particle multiplicity and the pointing accuracy have been obtained. The primary energy of detected showers has been estimated by measuring the westward displacement as a function of the particle multiplicity, thus calibrating the relation between shower size and cosmic ray energy. The stability of the detector on a monthly basis has been checked by monitoring the position and the deficit of the Moon shadow. Finally, we have studied with high statistical accuracy the shadowing effect in the ''day/night’’ time looking for possible effect induced by the solar wind

Highlights from the ARGO-YBJ experiment

The ARGO-YBJ experiment at YangBaJing in Tibet (4300 m a.s.l.) has been taking data with its full layout since October 2007. Here we present a few significant results obtained in gamma-ray astronomy and cosmic-ray physics. Emphasis is placed on the analysis of gamma-ray emission from point-like sources (Crab Nebula, MRK 421), on the preliminary limit on the antiproton/proton flux ratio, on the large-scale cosmic-ray anisotropy and on the proton–air cross-section. The performance of the detector is also discussed, and the perspectives of the experiment are outlined