Stage-Specific Regulation of Reprogramming to Induced Pluripotent Stem Cells by Wnt Signaling and T Cell Factor Proteins

1. Download : Download full-size image

     

18F-FDG PET/CT in lymphomas: assessment difficulties due to illness characteristics, and comparison with literature data

Fluor-18-deoxy-glucose (18F-FDG or FDG) positron emission tomography - computer tomography (PET/CT) has recently become integrated into the clinical routine of patients with lymphoma in Hungary. The basic condition of risk-adapted treatment of these patients is the exact staging and early objective evaluation of the effectiveness of therapy. Between 1 May 2007 and 31 October 2010, 1862 18F-FDG PET/CT examinations were conducted for lymphoma patients at the PET/CT Center in Debrecen. This is more than 15% of the total examined patient population, and this rate shows a slight increase with each year. Based on the experience obtained from lymphoma patients by routine metabolic PET/CT scans we analyzed the difficulties of the evaluation in different time frames of patients' management. It is well known that FDG uptake of lymphomas depends on multiple factors. Although most histological subtypes are associated with uptake of FDG, the intensity of the tracer uptake is different. Different intensity of FDG uptake of the same type of lymphoma following therapeutic procedures might cause difficulties in the evaluation of the scans ensuring that primary staging by PET/CT is highly required for precise measurement and reliable comparison of data. Extranodal involvement was detected in ~40% of the patients with variable rate of prevalence. Extranodal involvement is associated with great diversity and in most cases it is not characteristic of the illness and might appear in different forms and in any organs. Additionally, because accompanying disease may produce false positive results, detailed clinical data and precise case history is highly required.     

Oxygen transfer characteristics of miniaturized bioreactor systems

Since their introduction in 2001 miniaturized bioreactor systems have made great advances in function and performance. In this article the dissolved oxygen (DO) transfer performance of submilliliter microbioreactors, and 1–10 mL minibioreactors was examined. Microbioreactors have reached k_La values of 460 h^?1, and are offering instrumentation and some functionality comparable to production systems, but at high throughput screening volumes. Minibioreactors, aside from one 1,440 h^?1 k_La system, have not offered as high rates of DO transfer, but have demonstrated superior integration with automated fluid handling systems. Microbioreactors have been typically limited to studies with E. coli, while minibioreactors have offered greater versatility in this regard. Further, mathematical relationships confirming the applicability of k_La measurements across all scales have been derived, and alternatives to fluorescence lifetime DO sensors have been evaluated. Finally, the influence on reactor performance of oxygen uptake rate (OUR), and the possibility of its real‐time measurement have been explored. Biotechnol. Bioeng. 2013; 110: 1005–1019. © 2012 Wiley Periodicals, Inc.     

Central Nervous System Functions of PAK Protein Family: From Spine Morphogenesis to Mental Retardation.

Several of the genes currently known to be associated, when mutated, with mental retardation, code for molecules directly involved in Rho guanosine triphosphatase (GTPase) signaling. These include PAK3, a member of the PAK protein kinase family, which are important effectors of small GTPases. In many systems, PAK kinases play crucial roles regulating complex mechanisms such as cell migration, differentiation, or survival. Their precise functions in the central nervous system remain, however, unclear. Although their activity does not seem to be required for normal brain development, several recent studies point to a possible involvement in more subtle mechanisms such as neurite outgrowth, spine morphogenesis or synapse formation, and plasticity. This article reviews this information in the light of the current knowledge available on the molecular characteristics of the different members of this family and discuss the mechanisms through which they might contribute to cognitive functions.     

Ligation of retinoic acid receptor alpha regulates negative selection of thymocytes by inhibiting both DNA binding of nur77 and synthesis of bim

Negative selection refers to the selective deletion of autoreactive thymocytes. Its molecular mechanisms have not been well defined. Previous studies in our laboratory have demonstrated that retinoic acids, physiological ligands for the nuclear retinoid receptors, selectively inhibit TCR-mediated death under in vitro conditions, and the inhibition is mediated via the retinoic acid receptor (RAR) alpha. The present studies were undertaken to investigate whether ligation of RARalpha leads to inhibition of TCR-mediated death in vivo and to identify the molecular mechanisms involved. Three models of TCR-mediated death were studied: anti-CD3-mediated death of thymocytes in wild-type mice, and Ag- and bacterial superantigen-driven thymocyte death in TCR-transgenic mice expressing a receptor specific for a fragment of pigeon cytochrome c in the context of the E(k) (class II MHC) molecule. Our data demonstrate that the molecular program of both anti-CD3- and Ag-driven, but not that of superantigen-mediated apoptosis involves up-regulation of nur77, an orphan nuclear receptor, and bim, a BH3-only member of the proapoptotic bcl-2 protein family, proteins previously implicated to participate in the negative selection. Ligation of RARalpha by the synthetic agonist CD336 inhibited apoptosis, DNA binding of nur77, and synthesis of bim induced by anti-CD3 or the specific Ag, but had no effect on the superantigen-driven cell death. Our data imply that retinoids are able to inhibit negative selection in vivo as well, and they interfere with multiple steps of the T cell selection signal pathway.