Exciton delocalization in the antenna of purple bacteria: Exciton spectrum calculations using X-ray data and experimental site inhomogeneity

AbstractElectron absorption and circular dichroism spectra of the peripheral light-harvesting complex (LH2) of photosynthetic purple bacteria were calculated taking into account the real-life spatial arrangement and experimental inhomogeneous broadening of bacteriochlorophyll molecules. It was shown that strong excitonic interactions between 18 bacteriochlorophyll molecules (BChl850) within the circular aggregate of the LH2 complex result in an exciton delocalization over all these pigment molecules. The site inhomogeneity (spectral disorder) practically has no influence on exciton delocalization. The splitting between two lowest exciton levels corresponds to experimentally revealed splitting by hole-burning studies of the LH2 complex

Gene Expression Signature of Cigarette Smoking and Its Role in Lung Adenocarcinoma Development and Survival

Tobacco smoking is responsible for over 90% of lung cancer cases, and yet the precise molecular alterations induced by smoking in lung that develop into cancer and impact survival have remained obscure.We performed gene expression analysis using HG-U133A Affymetrix chips on 135 fresh frozen tissue samples of adenocarcinoma and paired noninvolved lung tissue from current, former and never smokers, with biochemically validated smoking information. ANOVA analysis adjusted for potential confounders, multiple testing procedure, Gene Set Enrichment Analysis, and GO-functional classification were conducted for gene selection. Results were confirmed in independent adenocarcinoma and non-tumor tissues from two studies. We identified a gene expression signature characteristic of smoking that includes cell cycle genes, particularly those involved in the mitotic spindle formation (e.g., NEK2, TTK, PRC1). Expression of these genes strongly differentiated both smokers from non-smokers in lung tumors and early stage tumor tissue from non-tumor tissue (p<0.001 and fold-change >1.5, for each comparison), consistent with an important role for this pathway in lung carcinogenesis induced by smoking. These changes persisted many years after smoking cessation. NEK2 (p<0.001) and TTK (p = 0.002) expression in the noninvolved lung tissue was also associated with a 3-fold increased risk of mortality from lung adenocarcinoma in smokers.Our work provides insight into the smoking-related mechanisms of lung neoplasia, and shows that the very mitotic genes known to be involved in cancer development are induced by smoking and affect survival. These genes are candidate targets for chemoprevention and treatment of lung cancer in smokers

A Statistical Analysis of Radiolabeled Gene Expression Data

This paper considers statistical issues in the analysis of a designed experiment to investigate differential gene expression in colon cancer and normal colon tissue. In this experiment gene expression is measured using radiolabeling--based array filters. Specific statistical issues arise in connection with radiolabeling technology, because of the absence of direct control, which are replaced by empty spots on the filter, and with designed experiments, because of the opportunity to systematically quantify important sources of random variation. Here we consider three aspects in detail: normalization of expression intensities; shrinkage estimates of intensity ratios between cancer and normal tissue; and ranking of genes by the strength of the evidence that they are differentially expressed. We propose a robust and simple--to--implement procedures for normalization and shrinkage, that addresses in a technology--specific way the problem of estimating ratios in presence of small and noisy denominators. We also discuss a graphical display to rank genes using a metric based on quantiles of a null distribution obtained by replicating the array experiment in normal tissue.