Expression of the SmB′ splicing protein in rodent cells capable of following an alternative RNA splicing pathway

AbstractThe expression of the SmB and SmB′ spliceosome proteins in a variety of cell types and tissues has been investigated. Although SmB is found in all cells studied, the SmB′ protein is found only in a small number of rodent cell types. The presence of this protein is correlated with the ability to utilize an alternative pathway of RNA splicing which is not available in most cell types. This is the first demonstration of tissue specific expression of a protein component of the spliceosome and suggests a role for SmB′ in the regulation of some cases of alternative RNA splicing

Homologous and heterologous desensitization of guanylyl cyclase-B signaling in GH3 somatolactotropes

The guanylyl cyclases, GC-A and GC-B, are selective receptors for atrial and C-type natriuretic peptides (ANP and CNP, respectively). In the anterior pituitary, CNP and GC-B are major regulators of cGMP production in gonadotropes and yet mouse models of disrupted CNP and GC-B indicate a potential role in growth hormone secretion. In the current study, we investigate the molecular and pharmacological properties of the CNP/GC-B system in somatotrope lineage cells. Primary rat pituitary and GH3 somatolactotropes expressed functional GC-A and GC-B receptors that had similar EC50 properties in terms of cGMP production. Interestingly, GC-B signaling underwent rapid homologous desensitization in a protein phosphatase 2A (PP2A)-dependent manner. Chronic exposure to either CNP or ANP caused a significant down-regulation of both GC-A- and GC-B-dependent cGMP accumulation in a ligand-specific manner. However, this down-regulation was not accompanied by alterations in the sub-cellular localization of these receptors. Heterologous desensitization of GC-B signaling occurred in GH3 cells following exposure to either sphingosine-1-phosphate or thyrotrophin-releasing hormone (TRH). This heterologous desensitization was protein kinase C (PKC)-dependent, as pre-treatment with GF109203X prevented the effect of TRH on CNP/GC-B signaling. Collectively, these data indicate common and distinct properties of particulate guanylyl cyclase receptors in somatotropes and reveal that independent mechanisms of homologous and heterologous desensitization occur involving either PP2A or PKC. Guanylyl cyclase receptors thus represent potential novel therapeutic targets for treating growth-hormone-associated disorders

Inhibition of Neuroblastoma Tumor Growth by Targeted Delivery of MicroRNA-34a Using Anti-Disialoganglioside GD2 Coated Nanoparticles

Neuroblastoma is one of the most challenging malignancies of childhood, being associated with the highest death rate in paediatric oncology, underlining the need for novel therapeutic approaches. Typically, patients with high risk disease undergo an initial remission in response to treatment, followed by disease recurrence that has become refractory to further treatment. Here, we demonstrate the first silica nanoparticle-based targeted delivery of a tumor suppressive, pro-apoptotic microRNA, miR-34a, to neuroblastoma tumors in a murine orthotopic xenograft model. These tumors express high levels of the cell surface antigen disialoganglioside GD2 (GD(2)), providing a target for tumor-specific delivery.Nanoparticles encapsulating miR-34a and conjugated to a GD(2) antibody facilitated tumor-specific delivery following systemic administration into tumor bearing mice, resulted in significantly decreased tumor growth, increased apoptosis and a reduction in vascularisation. We further demonstrate a novel, multi-step molecular mechanism by which miR-34a leads to increased levels of the tissue inhibitor metallopeptidase 2 precursor (TIMP2) protein, accounting for the highly reduced vascularisation noted in miR-34a-treated tumors.These novel findings highlight the potential of anti-GD(2)-nanoparticle-mediated targeted delivery of miR-34a for both the treatment of GD(2)-expressing tumors, and as a basic discovery tool for elucidating biological effects of novel miRNAs on tumor growth

In Situ Formation of Ti-TiAl₃ Metallic-Intermetallic Composite by Electric Current Activated Sintering Method

In this study we have investigated fabrication of in situ metallic- intermetallic Ti-TiAl₃ composites from powder mixture containing 40 wt % Ti-Al, 50 wt % Ti-Al and 60 wt % Ti-Al by electric current activated sintering method. Powder mixtures without additive were compressed uniaxially under 130 MPa of pressure and sintered 2000 A current for 20 minutes in a steel mould. Microstructures of sintered samples were investigated by optic and scanning electron microscopes, phases in samples were analyzed by XRD and their hardness was measured by Vickers hardness tester. Optic and scanning electron microscopes investigations showed that microstructures of samples were consisting of two components: Main component was titanium aluminide and other was metallic titanium. Besides this there was a trace amount of aluminium oxide in the sintered body. XRD analyses also demonstrated that main phase is TiAl₃. It was determined that as weight percentage of titanium in the mixture was decreasing, also the amount of metallic titanium has decreased in the sintered body. Additionally, average hardness values of samples were about 500 H

Influence of Al and Ti elements on the microstructure and properties of crnifecoalxtiy heas fabricated by ECAS

CrNiFeCoAlxTiy alloy series which fabricated by ECAS, were investigated in view of microstructure and microhardness properties. The differences were determined by changing Al and Ti ratios. The alterations on microstructure and microhardness values were determined by apply homogenization heat treatment. According to the results sintering process was successfully performed in a short time. Diffusion activities as well as interfusion of powders were observed in the microstructures following the sintering process. The bright phase has high Fe and Cr content, while the gray phase holds high Al, Ni and Ti content. Diffusion processes ended by homogenization and obtained more homogeneous distribution. The high microhardness values which obtained by sintering were raised further. © Avestia Publishing, 2017

In Situ Formation of Ti-TiAl3 Metallic-Intermetallic Composite by Electric Current Activated Sintering Method

In this study We have in fabrication of in situ metallic.intermetallic Ti-TiAl3 composites from powder mixture containing 40 wt % Ti-Al, 50 wt 7 Ti-Al and 60 wt % Ti-Al by electric current activated sintering method. Powder mixtures without additive were compressed uniaxially under 130 IMPa of pressure and sintered 2000 A current for 20 minutes in a steel mould. Microstructures of sintered samples were investigated by optic and scanning electron microscopes, phases in samples were analyzed by XRD and their hardness was measured by Vickers hardness tester. Optic and scanning electron microscopes investigations showed that microstructures of samples were consisting of two components: Main component was titanium aluminide and other was metallic titanium. Besides this there was a trace amount of aluminium oxide in the sintered body. XRD analyses also demonstrated that main phase is TiAl3 It was determined that as weight percentage of titanium in the mixture was decreasing, also the amount of metallic titanium has decreased in the sintered both. Additionally, average hardness values of samples were about 500 HV

Determination of the Young Modulus of Ti-TiAl 3 Metallic Intermetallic Laminate Composites by Nano-Indentation

Nano-indentation is an important technique to determine the Young modulus of multiphase materials where normal tensile tests are not appropriate. In this work, Ti-TiAl3 metallic-intermetallic laminate composites have been fabricated successfully in open atmosphere using commercial purity Al and Ti foils with 250 µm and 500 µm initial thicknesses, respectively. Sintering process was performed at 700 • C under 2 MPa pressure for 7.5 h. Mechanical properties including the Young modulus were determined after manufacturing. The Young moduli of metallic and intermetallic phases were determined as 89 GPa and 140 GPa, respectively. Microstructure analyses showed that aluminum foil was almost consumed by forming a titanium aluminide intermetallic compound. Titanium aluminides grow up through spherical shaped islands and metallic-intermetallic interface is a wavy form in Ti-Al system. Thus, the final microstructure consists of alternating layers of intermetallic compound and unreacted Ti metal. Microstructure and phase characterizations were performed by scanning electron microscopy, energy dispersive spectroscopy, and X-ray diffraction. Hardness of test samples was determined as 600 HV for intermetallic zone and 130 HV for metallic zone by the Vickers indentation method

Effects of SiC Particle Size on Properties of Cu-SiC Metal Matrix Composites

This paper was focused on the effects of particle size and distribution on some properties of the SiC particle reinforced Cu composites. Copper powder produced by cementation method was reinforced with SiC particles having 1 and 30 μm particle size and sintered at 700°C. Scanning electron microscopy studies showed that SiC particles were dispersed in copper matrix homogeneously. The presence of Cu and SiC components in composites were verified by X-ray diffraction analysis technique. The relative densities of Cu-SiC composites determined by Archimedes' principle are ranged from 96.2% to 90.9% for SiC with 1 μm particle size, 97.0% to 95.0% for SiC with 30 μm particle size. Measured hardness of sintered compacts varied from 130 to 155 HVN for SiC having 1 μm particle size, 188 to 229 HVN for SiC having 30 μm particle size. Maximum electrical conductivity of test materials was obtained as 80.0% IACS (international annealed copper standard) for SiC with 1 μm particle size and 83.0% IACS for SiC with 30 μm particle size

Determination of the Young Modulus of Ti-TiAl3 Metallic Intermetallic Laminate Composites by Nano-Indentation

Nano-indentation is an important technique to determine the Young modulus of multiphase materials where normal tensile tests are not appropriate. In this work, Ti-TiAl3 metallic-intermetallic laminate composites have been fabricated successfully in open atmosphere using commercial purity Al and Ti foils with 250 mu m and 500 mu m initial thicknesses, respectively. Sintering process was performed at 700 degrees C under 2 MPa pressure for 7.5 h. Mechanical properties including the Young modulus were determined after manufacturing. The Young moduli of metallic and intermetallic phases were determined as 89 GPa and 140 GPa, respectively. Microstructure analyses showed that aluminum foil was almost consumed by forming a titanium aluminide intermetallic compound. Titanium aluminides grow up through spherical shaped islands and metallic-intermetallic interface is a wavy form in Ti-Al system. Thus, the final microstructure consists of alternating layers of intermetallic compound and unreacted Ti metal. Microstructure and phase characterizations were performed by scanning electron microscopy, energy dispersive spectroscopy, and X-ray diffraction. Hardness of test samples was determined as 600 HV for intermetallic zone and 130 HV for metallic zone by the Vickers indentation method