The role of TAS2R38 genotype in surgical outcomes and culturable bacteria in chronic rhinosinusitis with or without nasal polyps.

BACKGROUND: Recent studies reported the relationship between genetic variations and TAS2R38, which is a bitter taste receptor expressed in the cilia of human sinonasal epithelial cells, among the predisposing factors playing role in immune response to upper respiratory tract bacterial infection. The present study aims to examine the relationship of TAS2R38 genotype with the active microorganism and the effect of genotype on the surgical outcomes among chronic rhinosinusitis patients. METHODOLOGY: 34 patients undergoing endoscopic sinus surgery (ESS) for chronic rhinosinusitis with or without polyps (23 CRSwNP, 11 CRSsNP) and 30 patients undergoing septoplasty surgery for isolated nasal septum deviation were included. All the patients were genotyped for TAS2R38. Scoring was made using endoscopic Modified Lund-Kennedy and radiological Lund-Mackay systems preoperatively. Sino-Nasal Outcome Test with 22 items (SNOT-22) was implemented preoperatively and postoperatively. Nasal swab culture samples were taken intraoperatively from CRS patients and the active microorganism were isolated. RESULTS: In the TAS2R38 genotyping of the study group, PAV/PAV was found in 32.4% of patients, PAV/AVI in 47.1%, and AVI/AVI in 20.6%. In the control group, PAV/PAV was found in 26.7%, PAV/AVI in 36.7%, and AVI/AVI in 36.7%. In the study group, there was no statistically significant difference between the CRS and CRS subgroups in terms of TAS2R38 genotype distributions. The changes in patients' preoperative and postoperative SNOT-22 scores were similar between the genotypes. Proliferation was detected in culture in the whole AVI-AVI group, 81.8% of PAV-PAV group, and 56.3% of PAV-AVI group but the difference was not found to be statistically significant. The proliferation level of Staphylococcus epidermidis by TAS2R38 genotype was found to be statistically significantly higher among patients, who had AVI-AVI genotype, in CRSwNP. CONCLUSIONS: We did not find a statistically significant relationship between the TAS2R38 genotype and CRS subtype, sinonasal bacterial infection risk increase and surgical success rate in CRS patients. Long-term and large-scale studies are needed, which are to be carried out by individual genotyping and sequencing to provide more information on the effects of these genetic variants.

Mutation detection in the promoter region of survivin gene on N-methyl-N-nitrosourea induced colon tumor model in experiment.

Survivin (also known as BIRC5) is one of the first reported inhibitors of apoptosis proteins (IAPs), which is an important family of proteins that regulate apoptosis. It is developmentally regulated and expressed during cell differentiation in humans, mice and rat. Survivin is expressed in a series of human cancers and it has been widely accepted that survivin is strongly related to the onset and development of cancer. In the present study, we tried to determine differences in the promoter region of survivin gene in colon tissue samples from N-methyl-N-nitrosourea (MNU) induced rat colon tumor model and control group. Polymerase chain reaction (PCR) - single strand conformation polymorphism (SSCP) analysis was used for this aim. No significant differences were found in the promoter region of survivin gene between the normal and tumor tissues (Tab. 2, Fig. 1, Ref. 16).

Imaging, quantification and visualization of spatio-temporal patterning in mESC colonies under different culture conditions.

MOTIVATION: Mouse embryonic stem cells (mESCs) have developed into a prime system to study the regulation of pluripotency in stable cell lines. It is well recognized that different, established protocols for the maintenance of mESC pluripotency support morphologically and functionally different cell cultures. However, it is unclear how characteristic properties of cell colonies develop over time and how they are re-established after cell passage depending on the culture conditions. Furthermore, it appears that cell colonies have an internal structure with respect to cell size, marker expression or biomechanical properties, which is not sufficiently understood. The analysis of these phenotypic properties is essential for a comprehensive understanding of mESC development and ultimately requires a bioinformatics approach to guarantee reproducibility and high-throughput data analysis. RESULTS: We developed an automated image analysis and colony tracking framework to obtain an objective and reproducible quantification of structural properties of cell colonies as they evolve in space and time. In particular, we established a method that quantifies changes in colony shape and (internal) motion using fluid image registration and image segmentation. The methodology also allows to robustly track motion, splitting and merging of colonies over a sequence of images. Our results provide a first quantitative assessment of temporal mESC colony formation and estimates of structural differences between colony growth under different culture conditions. Furthermore, we provide a stream-based visualization of structural features of individual colonies over time for the whole experiment, facilitating visual comprehension of differences between experimental conditions. Thus, the presented method establishes the basis for the model-based analysis of mESC colony development. It can be easily extended to integrate further functional information using fluorescence signals and differentiation markers. AVAILABILITY: The analysis tool is implemented C++ and Mathematica 8.0 (Wolfram Research Inc., Champaign, IL, USA). The tool is freely available from the authors. We will also provide the source code upon request. CONTACT: nico.scherf@tu-dresden.de.

Self-organizing circuitry and emergent computation in mouse embryonic stem cells.

Pluripotency is a cellular state of multiple options. Here, we highlight the potential for self-organization to contribute to stem cell fate computation. A new way of considering regulatory circuitry is presented that describes the expression of each transcription factor (TF) as a branching process that propagates through time, interacting and competing with others. In a single cell, the interactions between multiple branching processes generate a collective process called 'critical-like self-organization'. We explain how this phenomenon provides a valid description of whole genome regulatory circuit dynamics. The hypothesis of exploratory stem cell decision-making proposes that critical-like self-organization (also called rapid self-organized criticality) provides the backbone for cell fate computation in regulative embryos and pluripotent stem cells. Unspecific amplification of TF expression is predicted to initiate this self-organizing circuitry, where cascades of gene expression propagate and may interact either synergistically or antagonistically. The emergent and highly dynamic circuitry is affected by various sources of selection pressure, such as the expression of TFs with disproportionate influence over other genes, and extrinsic biological and physical stimuli that differentially modulate particular gene expression cascades. Extrinsic conditions continuously trigger waves of transcription that ripple throughout regulatory networks on multiple spatiotemporal scales, providing the context within which circuitry self-organizes. In this framework, a distinction between instructive and selective mechanisms of fate determination is misleading because it is the 'interference pattern', rather than any single instructing or selecting factor, that is ultimately responsible for computing and directing cell fate. Using this framework, we consider whether the idea of a naïve ground state of pluripotency and that of a fluctuating transcriptome are compatible, and whether a ground state like that captured in vitro could exist in vivo.