BlyS is up-regulated by hypoxia and promotes migration of human breast cancer cells

<p>Abstract</p> <p>Background</p> <p>The role of B Lymphocyte Stimulator (BLyS) in the survival of malignant B cells and the maintenance of normal B cell development and homeostasis has been intensively studied in the literature. However, the influence of BLyS on breast cancer progression remains unclear. The study aimed to investigate the effect of hypoxia on BLyS regulation, cell migratory response to BLyS and the possible molecular mechanisms.</p> <p>Methods</p> <p>In this study, we examined the role of BLyS in the migration of human breast cancer cells by transwell assay. We also explored whether BLyS and its receptors expressed in human breast cancer cell lines by immunofluorescence and Western Blotting. Then we detected the expression level of BLyS in both normoxic and hypoxic conditions by real time-PCR and Western Blotting. Pathways involved were confirmed by Western Blotting, immunofluorescence, transwell assay and luciferase assay.</p> <p>Results</p> <p>According to our study, the expression level of BlyS was increased in human breast cancer cell lines in hypoxic conditions. Up-regulation of this protein led to activation and nuclear translocation of NF-kappa B p65. We also found that the number of migrated cells was increased in the presence of BLyS and inhibition of phosphorylation of Akt attenuated the enhanced migratory response.</p> <p>Conclusions</p> <p>It suggested that better understanding of BLyS, an immunopotentiator, may offer a potential therapeutic target for the treatment of human breast cancers. In addition, BLyS promoted breast cancer cells migration, underscoring the necessity of appropriate applications of immunopotentiators to cancer treatment.</p

Mechanical, Toughness and Thermal properties of 2D Material- Reinforced Epoxy Composites

Developing epoxy composites with high thermal conductivity and excellent mechanical properties becomes imperative in electronic and aerospace industries. This study investigates and compares the effect of adding boron nitride (BN) sheets and graphene platelets (GnPs) on the mechanical properties and thermal conductivity of epoxy resin. The study shows that incorporation of BN or GnPs into epoxy matrix significantly enhanced both mechanical properties and thermal conductivity of epoxy composites. At fractions ranging 1–4 wt%, GnPs/epoxy composites provide higher Young’s modulus, fracture toughness (K1c) and critical stress energy release rate (G1c) compared to BN/epoxy composites. The thermal conductivity of the epoxy composites is up to the maximum of 0.33 Wm 1 K 1 at 4 wt% of GnP loading, which is much higher than that of the composites filled with the same loading of BN (0.23 Wm 1 K 1 ). The study emphasizes the importance of adding thin nanosheets (thickness 3–5 nm) at low loadings in developing epoxy composites to achieve desired mechanical and thermal properties

Identification and Functional Analysis of a Novel von Willebrand Factor Mutation in a Family with Type 2A von Willebrand Disease

von Willebrand factor (VWF) is essential for normal hemostasis. VWF gene mutations cause the hemorrhagic von Willebrand disease (VWD). In this study, a 9-year-old boy was diagnosed as type 2A VWD, based on a history of abnormal bleeding, low plasma VWF antigen and activity, low plasma factor VIII activity, and lack of plasma high-molecular-weight (HMW) VWF multimers. Sequencing analysis detected a 6-bp deletion in exon 28 of his VWF gene, which created a mutant lacking D1529V1530 residues in VWF A2 domain. This mutation also existed in his family members with abnormal bleedings but not in >60 normal controls. In transfected HEK293 cells, recombinant VWF ΔD1529V1530 protein had markedly reduced levels in the conditioned medium (42±4% of wild-type (WT) VWF, p<0.01). The mutant VWF in the medium had less HMW multimers. In contrast, the intracellular levels of the mutant VWF in the transfected cells were significantly higher than that of WT (174±29%, p<0.05), indicating intracellular retention of the mutant VWF. In co-transfection experiments, the mutant reduced WT VWF secretion from the cells. By immunofluorescence staining, the retention of the mutant VWF was identified within the endoplasmic reticulum (ER). Together, we identified a unique VWF mutation responsible for the bleeding phenotype in a patient family with type 2A VWD. The mutation impaired VWF trafficking through the ER, thereby preventing VWF secretion from the cells. Our results illustrate the diversity of VWF gene mutations, which contributes to the wide spectrum of VWD

Best practices in heterotrophic high-cell-density microalgal processes: achievements, potential and possible limitations

Microalgae of numerous heterotrophic genera (obligate or facultative) exhibit considerable metabolic versatility and flexibility but are currently underexploited in the biotechnological manufacturing of known plant-derived compounds, novel high-value biomolecules or enriched biomass. Highly efficient production of microalgal biomass without the need for light is now feasible in inexpensive, well-defined mineral medium, typically supplemented with glucose. Cell densities of more than 100 g l−1 cell dry weight have been achieved with Chlorella, Crypthecodinium and Galdieria species while controlling the addition of organic sources of carbon and energy in fedbatch mode. The ability of microalgae to adapt their metabolism to varying culture conditions provides opportunities to modify, control and thereby maximise the formation of targeted compounds with non-recombinant microalgae. This review outlines the critical aspects of cultivation technology and current best practices in the heterotrophic high-cell-density cultivation of microalgae. The primary topics include (1) the characteristics of microalgae that make them suitable for heterotrophic cultivation, (2) the appropriate chemical composition of mineral growth media, (3) the different strategies for fedbatch cultivations and (4) the principles behind the customisation of biomass composition. The review confirms that, although fundamental knowledge is now available, the development of efficient, economically feasible large-scale bioprocesses remains an obstacle to the commercialisation of this promising technology

Genome-Wide Association Study of Lung Adenocarcinoma in East Asia and Comparison With a European Population

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P interaction  = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Numerical Assessment on Continuous Reinforced Normal-Strength Concrete and High-Strength Concrete Beams

High-strength concrete (HSC) has been broadly applied to various civil structures for its advantages including high compressive strength and excellent durability and creep resistance. However, the brittleness of HSC raises concern about its use in practice. So far study on continuous reinforced HSC beams is limited. This work investigates the structural response of reinforced HSC continuous beams, and the results are compared with those of the counterparts made of normal-strength concrete (NSC). By applying a finite element method verified by experimental data, a comprehensive assessment is performed on two-span reinforced NSC and HSC (compressive strengths of 30, 60 and 90 MPa) continuous beams. A wide range of flexural reinforcement ratios are used to cover both under-reinforced and over-reinforced beams. The results show that reinforced HSC beams exhibit better flexural performance in terms of ultimate load, deformation, flexural ductility and moment redistribution, when compared to reinforced NSC beams. Formulae relating flexural ductility and moment redistribution with either neutral axis depth or tensile steel strain are suggested

Flexural Behavior of Two-Span Continuous CFRP RC Beams

This paper investigates the feasibility of replacing steel bars with carbon-fiber-reinforced polymer (CFRP) bars in continuous reinforced concrete (RC) beams. A numerical model is introduced. Model predictions are compared with the experimental results that are available in the literature. A comprehensive numerical investigation is then performed on two-span CFRP/steel RC beams with ρb2 = 0.61–3.03% and ρb1/ρb2 = 1.5, where ρb1 and ρb2 are tensile bar ratios (ratios of tensile bar area to effective cross-sectional area of beams) over positive and negative moment regions, respectively. The study shows that replacing steel bars with CFRP bars greatly improves the crack mode at a low bar ratio. The ultimate load of CFRP RC beams is 89% higher at ρb2 = 0.61% but 7.2% lower at ρb2 = 3.03% than that of steel RC beams. In addition, CFRP RC beams exhibit around 13% greater ultimate deflection compared to steel RC beams. The difference of moment redistribution between CFRP and steel RC beams diminishes as ρb2 increases. ACI 318-19 appears to be conservative, and it leads to more accurate predictions of moment redistribution in CFRP RC beams than that in steel RC beams