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Antibody secreting cell (ASC) function and longevity determines the strength and durability of a humoral immune response. Previously, we identified the inactivation of the CREB-regulated transcriptional coactivator-2 (CRTC2) in an in vitro B cell differentiation assay that produced functional ASCs. However, the requirement for CRTC2 inactivation in ASC physiology in vivo remains unknown. Using transgenic (TG) mice that express a constitutively active form of CRTC2 (Crtc2-AA) as an experimental tool, we demonstrate that Crtc2 repression in plasma cells (PCs) is an intrinsic requirement for ASC metabolic fitness. Sustained CRTC2 activity shortens the survival of splenic and bone marrow PCs, resulting in reduced numbers of long-lived PCs and antibody deficits against T cell dependent and independent antigens, and an acute viral infection. TG PCs resemble short-lived PCs with reductions in glycolysis, oxidative metabolism, spare respiratory capacity, and antibody secretion. Mechanistically, Crtc2 repression is necessary for the fidelity of PC gene expression and mRNA alternative-splicing programs. Combined, Crtc2 repression in PCs must occur to support PC metabolism and extend ASC survival during a humoral immune response.

© 2018 Elsevier Ltd A pilot-scale hybrid constructed wetland with vertical flow and horizontal flow in series was constructed and used to investigate organic material and nutrient removal rate constants for wastewater treatment and establish a practical predictive model for use. For this purpose, the performance of multiple parameters was statistically evaluated during the process and predictive models were suggested. The measurement of the kinetic rate constant was based on the use of the first-order derivation and Monod kinetic derivation (Monod) paired with a plug flow reactor (PFR) and a continuously stirred tank reactor (CSTR). Both the Lindeman, Merenda, and Gold (LMG) analysis and Bayesian model averaging (BMA) method were employed for identifying the relative importance of variables and their optimal multiple regression (MR). The results showed that the first-order–PFR (M2) model did not fit the data (P > 0.05, and R2 < 0.5), whereas the first-order–CSTR (M1) model for the chemical oxygen demand (CODCr) and Monod–CSTR (M3) model for the CODCr and ammonium nitrogen (NH4−N) showed a high correlation with the experimental data (R2 > 0.5). The pollutant removal rates in the case of M1 were 0.19 m/d (CODCr) and those for M3 were 25.2 g/m2∙d for CODCr and 2.63 g/m2∙d for NH4-N. By applying a multi-variable linear regression method, the optimal empirical models were established for predicting the final effluent concentration of five days' biochemical oxygen demand (BOD5) and NH4-N. In general, the hydraulic loading rate was considered an important variable having a high value of relative importance, which appeared in all the optimal predictive models.

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim The integration of novel luminescent nanomaterials into glassy matrix can lead to new hybrid materials and photonic devices with promising material performance and device functions. Lanthanide-containing upconversion nanocrystals have become unique candidates for sensing, bioimaging, photon energy management, volumetric displays, and other photonic applications. Here, a versatile direct-doping approach is developed to integrate bright upconversion nanocrystals in tellurite glass with tailored nanoscale properties. Following our two-temperature glass-melting technique, the doping temperature window of 550–625 °C and a 5 min dwell time at 577 °C are determined as the key to success, which balances the survival and dispersion of upconversion nanocrystals in glass. It is identified that the fine spectra of upconversion emissions can be used to diagnose the survival and dissolution fraction of doped nanocrystals in the glass. Moreover, 3D dispersion of nanocrystals in the glass is visualized by upconversion scanning confocal microscopy. It is further demonstrated that a low-loss fiber, drawn from the highly transparent nanocrystals-doped glass retains the distinct optical properties of upconversion nanocrystals. These results suggest a robust strategy for fabrication of high-quality upconversion nanocrystal-doped glasses. The new class of hybrid glasses allows for fiber-based devices to be developed for photonic applications or as a useful tool for tailoring light–nanoparticles interactions study.

© 2015 Published by Elsevier Masson SAS. Traditional chemotherapeutic drugs remain the major treatment for advanced colorectal cancer. However, due to the lack of tumor specificity these drug also destroy healthy tissue and organs, which has been the main reason for treatment failure and mortality. Folate-based drug delivery systems for improving nanoparticle endocytosis have been used to address these problems. Here, folic acid (FA) conjugated mPEG-b-P(CABCL-co-ACL) diblock copolymers were synthesized and characterized by TEM and NMR. Drug loaded nanoparticles were prepared using dialysis method and was obtained with a mean diameter of 45.2 nm with sustained in vitro release profile. In vitro cytotoxicity assay indicated that the cytotoxicity of folate modified nanoparticles were significantly increased compared to free drug and non-folate nanoparticles. In addition, results of hemolytic and histopathologic study suggested that the non-loaded nanoparticle (NL/NP) was non-toxic and biocompatible at the testing concentration. Moreover, in vivo results showed that FA/5-FU/NP effectively inhibited growth of HCT-8 cell-based xenograft tumors in BALB/c mice and revealed stronger antitumor efficacy than other treated groups. Thus, both in vitro and in vivo results exhibited that the folate conjugated mPEG-b-P(CABCL-co-ACL) copolymers have great potential to be used as sustainable and specific colon cancer targeting delivery system for anticancer agents.

Streptococcus parauberis is an increasing threat to aquaculture of olive flounder, Paralichthys olivaceus Temminck & Schlegel, in South Korea. We developed a real-time polymerase chain reaction (PCR) method using the TaqMan probe assay to detect and quantify S. parauberis by targeting the gyrB gene sequences, which are effective for molecular analysis of the genus Streptococcus. Our real-time PCR assay is capable of detecting 10 fg of genomic DNA per reaction. The intra- and interassay coefficient of variation (CV) values ranged from 0.42-1.95%, demonstrating that the assay has good reproducibility. There was not any cross-reactivity to Streptococcus iniae or to other streptococcal/lactococcal fish pathogens, such as S. agalactiae and Lactococcus garvieae, indicating that the assay is highly specific to S. parauberis. The results of the real-time PCR assay corresponded well to those of conventional culture assays for S. parauberis from inoculated tissue homogenates (r = 0.957; P < 0.05). Hence, this sensitive and specific real-time PCR is a valuable tool for diagnostic quantitation of S. parauberis in clinical samples.

The paper deals with methodology to monitor and design bituminous mixes for orthotropic steel decks. This methodology is based on two experimental tests : complex modulus test on cylindrical specimen and the five-point bending test (Arnaud and Houel 2007). In this paper,three different bituminous concrete mixes are tested and compared to an ultra high performance concrete (UHPC) pavement. Non-destructive tests based on ultrasonic waves propagation ensure the continuous evaluation of damage of the wearing courses. It is shown that this methodology enables to characterize and follow up continuously the mechanical evolution of the material throughout fatigue solicitations. Clear differences are observed between the different bituminous mixes. Finally, the UHPC contribute mechanically to reduce the stress level in steel decks whereas it is not the case for the bituminous mixes.

The liver is one of the organs in which hypoxia helps to regulate gene expression under normal physiological conditions and in diseases such as cirrhosis and cancer. We postulated that the expression/activity of some of the ‘liver-enriched’ transcription factors, which control liver-specific genes, was sensitive to hypoxia. We tested hepatocyte nuclear factor-1 (HNF-1), HNF-3 and HNF-4, which play key roles in differentiation, development and hepatic gene expression, using HepG2 human hepatoma cells cultured under hypoxic conditions. Severe hypoxia/anoxia downregulated HNF-4 DNA-binding activity while DNA-binding activity of HNF-1 and HNF-3 remained unaffected. These hypoxic conditions also strongly and specifically decreased cell contents of HNF-4 protein, indicating that the decrease in HNF-4 DNA-binding activity was due to the lower amount of protein and not to decreased DNA-binding affinity. Northern analysis indicated that the expression of the hnf-4 gene was also downregulated in HepG2 cells cultured under hypoxic conditions. These results provide evidence that hypoxic stress triggers a cascade of events that inhibits the transactivation potential of HNF-4 in HepG2 cells. This step may be crucial in modulating the expression of a subset of liver genes that are targets for this nuclear receptor. This relationship provides a new route for the investigation of the effects of hypoxia on the liver cell.