Conceptual design of a cellular filter to remove trace viral contaminants in blood.

Various process alternatives and designs of using a filter containing cellular adsorbents to remove trace viral contaminants from blood and other protein solutions have been studied. Sterilization charts have been developed that can be used to estimate the filter size required to achieve a desired sterilization criterion. A parametric study was carried out to identify various process parameters that may affect this physical trace removal process. It has been demonstrated that the adsorption rate constant is a critical parameter in the design of an efficient cellular filter for viral contaminant removal. This constant is characteristic of the virus-cell system under consideration and is shown to be particularly sensitive to the cell surface receptor density, adsorbent diameter, and fluid flow rate. Higher log titer reduction in virus concentrations can be achieved with low flow rates and no recycle. Preliminary analyses indicate the feasibility of using a magnetically stabilized fluidized filter (MSFF) reactor design for effective virus removal from these complex solutions.     

Hydroxysafflor yellow A (HYSA) inhibited the proliferation and differentiation of 3T3-L1 preadipocytes

Hydroxysafflor yellow A (HSYA), a main component of safflor yellow, has been demonstrated to prevent steroid-induced avascular necrosis of femoral head by inhibiting primary bone marrow-derived mesenchymal stromal cells adipogenic differentiation induced by steroid. In this study, we investigate the effect of HSYA on the proliferation and adipogenesis of mouse 3T3-L1 preadipocytes. The effects of HSYA on proliferation and differentiation of 3T3-L1 cells and its possible mechanism were studied by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide spectrophotometry, Oil Red O staining, intracellular triglyceride assays, real-time quantitative RT-PCR, transient transfection and dual luciferase reporter gene methods. HSYA inhibited the proliferation of 3T3-L1 preadipocytes and cell viability greatly decreased in a dose and time dependent manner. HSYA (1 mg/l) notably reduced the amount of intracellular lipid and triglyceride content in adipocytes by 21.3 % (2.13 ± 0.36 vs 2.71 ± 0.40, P < 0.01) and 22.6 % (1.33 ± 0.07 vs 1.72 ± 0.07, P < 0.01) on days 8 following the differentiation, respectively. HSYA (1 mg/l) significantly increased hormone-sensitive lipase (HSL) mRNA expression and promoter activities by 2.4- and 1.55-fold, respectively (P < 0.01), in differentiated 3T3-L1 adipocytes. HSYA inhibits the proliferation and adipogenesis of 3T3-L1 preadipocytes. The inhibitory action of HYSA on adipogenesis may be due to the promotion of lipolytic-specific enzyme HSL expression by increasing HSL promoter activity.     

Accelerating Neuroimage Registration through Parallel Computation of Similarity Metric

Neuroimage registration is crucial for brain morphometric analysis and treatment efficacy evaluation. However, existing advanced registration algorithms such as FLIRT and ANTs are not efficient enough for clinical use. In this paper, a GPU implementation of FLIRT with the correlation ratio (CR) as the similarity metric and a GPU accelerated correlation coefficient (CC) calculation for the symmetric diffeomorphic registration of ANTs have been developed. The comparison with their corresponding original tools shows that our accelerated algorithms can greatly outperform the original algorithm in terms of computational efficiency. This paper demonstrates the great potential of applying these registration tools in clinical applications.     

Impaired secretion and fluid-phase endocytosis in the End4 mutant of Chinese hamster ovary cells

Mutant V.24.1 defines the End4 complementation group of temperature-sensitive Chinese hamster ovary cell mutants selected for resistance to protein toxins. We investigated the secretory pathway in the mutant cells and found: 1) The hemagglutinin of influenza virus failed to reach the plasma membrane and was retained in a form sensitive to endoglycosidase H at the restrictive temperature. 2) Transferrin receptors synthesized at the restrictive temperature remained sensitive to endoglycosidase H. 3) Secretion of total soluble protein into the medium was strongly reduced at high temperature. These data indicate that V.24.1 cells are defective in secretion at the restrictive temperature. To see what effect the lesion had on the endocytic pathway, we measured the accumulation and recycling of the fluid-phase marker horseradish peroxidase. Accumulation was inhibited by 50% while recycling was barely affected, suggesting that the rate of fluid-phase endocytosis was reduced. We previously showed that the clathrin-coated pit pathway of endocytosis was not affected in the mutant, indicated by a normal transferrin cycle (Colbaugh, P. A., Stookey, M., and Draper, R. K. (1989) J. Cell Biol. 108, 2211-2219). Thus, the secretory lesion correlates with reduced fluid-phase endocytosis without impairing the clathrin-dependent pathway of receptor-mediated endocytosis. We also investigated the delivery of endocytosed material to lysosomes and found that delivery was partially, but not completely, impaired in the mutant. This suggests that endocytosed material can enter lysosomes, although slowly, in the absence of a functional secretory pathway.     

Fungi short-chain carboxylate transporter: shift from microbe hereditary functional component to metabolic engineering target

Applied Microbiology and Biotechnology - Short-chain carboxylic acids and their derivatives are widely utilized in all aspects of our daily life. Given their specific functional groups, these...     

Screening of significant biomarkers related with prognosis of liver cancer by lncRNA-associated ceRNAs analysis

This study aimed to identify significant biomarkers related to the prognosis of liver cancer using long noncoding RNA (lncRNA)-associated competing endogenous RNAs (ceRNAs) analysis. Differentially expressed mRNA and lncRNAs between liver cancer and paracancerous tissues were screened, and the functions of these mRNAs were predicted by gene ontology and pathway enrichment analyses. A ceRNA network consisting of differentially expressed mRNAs and lncRNAs was constructed. LncRNA FENDRR and lncRNA HAND2-AS1 were hub nodes in the ceRNA network. A risk score assessment model consisting of eight genes (PDE2A, ESR1, FBLN5, ALDH8A1, AKR1D1, EHHADH, ADRA1A, and GNE) associated with prognosis were developed. Multivariate Cox regression suggested that both pathologic_T and risk group could be regarded as independent prognostic factors. Furthermore, a nomogram model consisting of pathologic_T and risk group showed a good prediction ability for predicting the survival rate of liver cancer patients. The nomogram model consisting of pathologic_T and a risk score assessment model could be regarded as an independent factor for predicting prognosis of liver cancer.