The COOH-terminus of TM4SF5 in hepatoma cell lines regulates c-Src to form invasive protrusions via EGFR Tyr845 phosphorylation

AbstractTransmembrane 4 L six family member 5 (TM4SF5) enhances cell migration and invasion, although how TM4SF5 mechanistically mediates these effects remains unknown. In the study, during efforts to understand TM4SF5-mediated signal transduction, TM4SF5 was shown to bind c-Src and thus hepatoma cell lines expressing TM4SF5 were analyzed for the significance of the interaction in cell invasion. The C-terminus of TM4SF5 bound both inactive c-Src that might be sequestered to certain cellular areas and active c-Src that might form invasive protrusions. Wildtype (WT) TM4SF5 expression enhanced migration and invasive protrusion formation in a c-Src-dependent manner, compared with TM4SF5-null control hepatoma cell lines. However, tailless TM4SF5ΔC cells were more efficient than WT TM4SF5 cells, suggesting a negative regulatory role by the C-terminus. TM4SF5 WT- or TM4SF5ΔC-mediated formation of invasive protrusions was dependent or independent on serum or epidermal growth factor treatment, respectively, although they both were dependent on c-Src. The c-Src activity of TM4SF5 WT- or TM4SF5ΔC-expressing cells correlated with enhanced Tyr845 phosphorylation of epidermal growth factor receptor. Y845F EGFR mutation abolished the TM4SF5-mediated invasive protrusions, but not c-Src phosphorylation. Our findings demonstrate that TM4SF5 modulates c-Src activity during TM4SF5-mediated invasion through a TM4SF5/c-Src/EGFR signaling pathway, differentially along the leading protrusive edges of an invasive cancer cell

Genomic characterization of Nocardia seriolae strains isolated from diseased fish

Members of the genus Nocardia are widespread in diverse environments; a wide range of Nocardia species are known to cause nocardiosis in several animals, including cat, dog, fish, and humans. Of the pathogenic Nocardia species, N. seriolae is known to cause disease in cultured fish, resulting in major economic loss. We isolated two N. seriolae strains, CK‐14008 and EM15050, from diseased fish and sequenced their genomes using the PacBio sequencing platform. To identify their genomic features, we compared their genomes with those of other Nocardia species. Phylogenetic analysis showed that N. seriolae shares a common ancestor with a putative human pathogenic Nocardia species. Moreover, N. seriolae strains were phylogenetically divided into four clusters according to host fish families. Through genome comparison, we observed that the putative pathogenic Nocardia strains had additional genes for iron acquisition. Dozens of antibiotic resistance genes were detected in the genomes of N. seriolae strains; most of the antibiotics were involved in the inhibition of the biosynthesis of proteins or cell walls. Our results demonstrated the virulence features and antibiotic resistance of fish pathogenic N. seriolae strains at the genomic level. These results may be useful to develop strategies for the prevention of fish nocardiosis.

O-GlcNAc modulation at Akt1 Ser473 correlates with apoptosis of murine pancreatic β cells

O-GlcNAc transferase (OGT)-mediated modification of protein Ser/Thr residues withO-GlcNAc influences protein activity, similar to the effects of phosphorylation. The anti-apoptotic Akt1 is both activated by phosphorylation and modified with O-GlcNAc. However, the nature and significance of the Akt1 O-GlcNAc modification is unknown. The relationship of O-GlcNAc modification and phosphorylation at Akt1 Ser473 was examined with respect to apoptosis of murine β-pancreatic cells. Glucosamine treatment induced apoptosis, which correlated with enhanced O-GlcNAc modification of Akt1 and concomitant reduction in Ser473 phosphorylation. Pharmacological inhibition of OGT or O-GlcNAcase revealed an inverse correlation between O-GlcNAcmodification and Ser473 phosphorylation of Akt1. MALDI-TOF/TOFmass spectrometry analysis of Akt1 immunoprecipitates fromglucosamine-treated cells, but not untreated controls, showed a peptide containing S473/T479 that was presumably modified withO-GlcNAc. Furthermore, in vitroO-GlcNAc-modification analysis of wildtype and mutant Akt1 revealed that S473 was targeted by recombinant OGT. A S473A Akt1 mutant demonstrated reduced basal and glucosamine-induced Akt1 O-GlcNAc modification compared with wildtype Akt1. Furthermore, wildtype Akt1, but not the S473A mutant, appeared to be associated with OGT following glucosamine treatment. Together, these observations suggest that Akt1 Ser473 may undergo both phosphorylation and O-GlcNAc modification, and the balance between these may regulatemurine β-pancreatic cell fate

Unilateral Breast Edema: Spectrum of Etiologies and Imaging Appearances

Breast edema is defined as a mammographic pattern of skin thickening, increased parenchymal density, and interstitial marking. It can be caused by benign or malignant diseases, as a result of a tumor in the dermal lymphatics of the breast, lymphatic congestion caused by breast, lymphatic drainage obstruction, or by congestive heart failure

Innovation Capabilities and the Performance of Start-Ups in Korea: The Role of Government Support Policies

What kind of capacity is needed to improve the performance of start-ups? How effective are government support policies in improving start-up performance? Start-ups are critical firm group for ensuring the prospective and sustainable growth of an economy, and thus many countries’ governments have established support policies and they are likely to engage more widely in forward-looking political support activities to ensure further growth and expansion. In this paper, the effect of innovation capabilities and government support policies on start-up performance is examined. We used an unbalanced panel data analysis with a random effect generalized least squares. We investigated the effect of government support policies on 4368 Korean start-ups. The findings indicated that technology and knowledge capabilities had positive effects on the sales performance of start-ups, and government financial support positively affected the relationship between knowledge capability and firm performance. However, when government financial support increased, marketing capability was negatively associated with firm performance. These results demonstrate the significant role of government financial support, including its crowding in but also its crowding out effect. Practical implications: To be more effective, governments should employ innovation-driven entrepreneurship policy approaches to support start-ups. To improve their performance, start-ups need to increase their technology and knowledge capabilities. This study extends recent efforts to understand more fully the effect of government support policies on start-ups differing in their technology, knowledge, and marketing capabilities

A case of a schwannoma in the nasal columella

Schwannoma is a slow-growing, benign tumor of the nerve sheath. It rarely presents in the nasal cavity or the paranasal sinuses. Although schwannomas in the nasal septum have been reported previously, cases of this tumor in the nasal columella are rare in the literature. Here, we report on a 67-year-old woman with a schwannoma in the nasal columella that was successfully removed using a sublabial approach, along with a review of relevant literature

32 × 32 Pixelated High-Power Flip-Chip Blue Micro-LED-on-HFET Arrays for Submarine Optical Communication

This work proposes the use of integrated high-power InGaN/GaN multiple-quantum-well flip-chip blue micro light-emitting diode (μ-LED) arrays on an AlGaN/GaN-based heterojunction field-effect transistor (HFET), also known as a high electron mobility transistor (HEMT), for various applications: underwater wireless optical communication (UWOC) and smart lighting. Therefore, we demonstrate high-power μ-LED-on-HEMT arrays that consist of 32 × 32 pixelated μ-LED arrays and 32 × 32 pixelated HEMT arrays and that are interconnected by a solder bump bonding technique. Each pixel of the μ-LED arrays emits light in the HEMT on-state. The threshold voltage, the off-state leakage current, and the drain current of the HEMT arrays are −4.6 V, <~1.1 × 10−9 A at gate-to-source voltage (VGS) = −10 V, and 21 mA at VGS = 4 V, respectively. At 12 mA, the forward voltage and the light output power (LOP) of μ-LED arrays are ~4.05 V and ~3.5 mW, respectively. The LOP of the integrated μ-LED-on-HEMT arrays increases from 0 to ~4 mW as the VGS increases from −6 to 4 V at VDD = 10 V. Each pixel of the integrated μ-LEDs exhibits a modulated high LOP at a peak wavelength of ~450 nm, showing their potential as candidates for use in UWOC