Proteomic characterization of the cytotoxic mechanism of gold (III) porphyrin 1a, a potential anticancer drug

There has been increasing interest in the potential applications of gold (III) complexes as anticancer drugs with higher cytotoxicity and fewer side effects than existing metal anticancer drugs. Our previous findings demonstrated that gold (III) porphyrin la preferentially induced apoptosis in a cancer cell line (SUNE1). In this study, we identified differentially expressed proteins related to the drug's cytotoxic action by comparing the protein alterations induced by gold (III) porphyrin la and cisplatin treatments. Several clusters of altered proteins were identified, including cellular structure and stress-related chaperone proteins, proteins involved in reactive oxygen species and enzyme proteins, translation factors, proteins that mediate cell proliferation or differentiation, and proteins participating in the internal degradation systems. Our results indicated that multiple factors leading to apoptosis were involved in drug cytotoxicity in SUNE1 cells. The balance between pro-apoptotic and anti-apoptotic signals determined the final fate of cancer cells. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.postprin

Decreasing time consumption of microscopy image segmentation through parallel processing on the GPU

The computational performance of graphical processing units (GPUs) has improved significantly. Achieving speedup factors of more than 50x compared to single-threaded CPU execution are not uncommon due to parallel processing. This makes their use for high throughput microscopy image analysis very appealing. Unfortunately, GPU programming is not straightforward and requires a lot of programming skills and effort. Additionally, the attainable speedup factor is hard to predict, since it depends on the type of algorithm, input data and the way in which the algorithm is implemented. In this paper, we identify the characteristic algorithm and data-dependent properties that significantly relate to the achievable GPU speedup. We find that the overall GPU speedup depends on three major factors: (1) the coarse-grained parallelism of the algorithm, (2) the size of the data and (3) the computation/memory transfer ratio. This is illustrated on two types of well-known segmentation methods that are extensively used in microscopy image analysis: SLIC superpixels and high-level geometric active contours. In particular, we find that our used geometric active contour segmentation algorithm is very suitable for parallel processing, resulting in acceleration factors of 50x for 0.1 megapixel images and 100x for 10 megapixel images

Small extracellular vesicles secreted from human amniotic fluid mesenchymal stromal cells possess cardioprotective and promigratory potential

Mesenchymal stromal cells (MSCs) exhibit antiapoptotic and proangiogenic functions in models of myocardial infarction which may be mediated by secreted small extracellular vesicles (sEVs). However, MSCs have frequently been harvested from aged or diseased patients, while the isolated sEVs often contain high levels of impurities. Here, we studied the cardioprotective and proangiogenic activities of size-exclusion chromatography-purified sEVs secreted from human foetal amniotic fluid stem cells (SS-hAFSCs), possessing superior functional potential to that of adult MSCs. We demonstrated for the first time that highly pure (up to 1.7 × 1010 particles/µg protein) and thoroughly characterised SS-hAFSC sEVs protect rat hearts from ischaemia–reperfusion injury in vivo when administered intravenously prior to reperfusion (38 ± 9% infarct size reduction, p < 0.05). SS-hAFSC sEVs did not protect isolated primary cardiomyocytes in models of simulated ischaemia–reperfusion injury in vitro, indicative of indirect cardioprotective effects. SS-hAFSC sEVs were not proangiogenic in vitro, although they markedly stimulated endothelial cell migration. Additionally, sEVs were entirely responsible for the promigratory effects of the medium conditioned by SS-hAFSC. Mechanistically, sEV-induced chemotaxis involved phosphatidylinositol 3-kinase (PI3K) signalling, as its pharmacological inhibition in treated endothelial cells reduced migration by 54 ± 7% (p < 0.001). Together, these data indicate that SS-hAFSC sEVs have multifactorial beneficial effects in a myocardial infarction setting

Multifractality in Human Heartbeat Dynamics

Recent evidence suggests that physiological signals under healthy conditions may have a fractal temporal structure. We investigate the possibility that time series generated by certain physiological control systems may be members of a special class of complex processes, termed multifractal, which require a large number of exponents to characterize their scaling properties. We report on evidence for multifractality in a biological dynamical system --- the healthy human heartbeat. Further, we show that the multifractal character and nonlinear properties of the healthy heart rate are encoded in the Fourier phases. We uncover a loss of multifractality for a life-threatening condition, congestive heart failure.Comment: 19 pages, latex2e using rotate and epsf, with 5 ps figures; to appear in Nature, 3 June, 199

Comparative proteomic analysis of esophageal squamous cell carcinoma

Ranking as the fourth commonest cancer, esophageal squamous cell carcinoma (ESCC) represents one of the leading causes of cancer death in China. One of the main reasons for the low survival rate is that neoplasms in esophagus are not detected until they have invaded into surrounding tissues or spread throughout the body at advanced stages. A better understanding of the malignant mechanism and early diagnosis are important for fighting ESCC. In this study, we used proteomics to analyze ESCC tissues, aiming at defining the proteomic features implicated in the multistage progression of esophageal carcinogenesis. Proteins that exhibited significantly different expressions were identified by peptide mass fingerprinting and validated by Western blotting and reverse transcriptase-polymerase chain reaction. The protein changes were then correlated to the different grades of disease differentiation. Compared to those in adjacent normal epitheliums, the expression of 15 proteins including enolase, elongation factor Tu, isocitrate dehydrogenase, tubulin alpha-1 chain, tubulin beta-5 chain, actin (cytoplasmic 1), glyceraldehyde-3 phosphate dehydrogenase, tropomyosin isoform 4 (TPM4), prohibitin, peroxiredoxin 1 (PRX1), manganese-containing superoxide dismutase (MnSOD), neuronal protein, and transgelin was up-regulated; and the expression of five proteins including TPM1, squamous cell carcinoma antigen 1 (SCCA1), stratifin, peroxiredoxin 2 isoform a, and alpha B crystalline was down-regulated in cancer tissues with a statistical significance (p < 0.05). In addition, the differential expression of SCCA1, PRX1, MnSOD, TPM4, and prohibitin can be observed in precancerous lesions of ESCC. The expression of stratifin, prohibitin, and SCCA1 dropped with increasing dedifferentiation of ESCC. These data may suggest that these proteins contribute to the multistage process of carcinogenesis, tumor progression, and invasiveness of ESCC. © 2005 WILEY-VCH Verlag GmbH & Co. KGaA.postprin

The Core of the Participatory Budgeting Problem

In participatory budgeting, communities collectively decide on the allocation of public tax dollars for local public projects. In this work, we consider the question of fairly aggregating the preferences of community members to determine an allocation of funds to projects. This problem is different from standard fair resource allocation because of public goods: The allocated goods benefit all users simultaneously. Fairness is crucial in participatory decision making, since generating equitable outcomes is an important goal of these processes. We argue that the classic game theoretic notion of core captures fairness in the setting. To compute the core, we first develop a novel characterization of a public goods market equilibrium called the Lindahl equilibrium, which is always a core solution. We then provide the first (to our knowledge) polynomial time algorithm for computing such an equilibrium for a broad set of utility functions; our algorithm also generalizes (in a non-trivial way) the well-known concept of proportional fairness. We use our theoretical insights to perform experiments on real participatory budgeting voting data. We empirically show that the core can be efficiently computed for utility functions that naturally model our practical setting, and examine the relation of the core with the familiar welfare objective. Finally, we address concerns of incentives and mechanism design by developing a randomized approximately dominant-strategy truthful mechanism building on the exponential mechanism from differential privacy

Diverse proteomic alterations in gastric adenocarcinoma

Gastric adenocarcinoma is one of the most common cancers in Asian countries including China. Although its incidence rates in the West are lower than that in Asia, gastric cancer is still a major health problem worldwide, being second only to lung cancers in the number of deaths it causes. Helicobacter pylori infection has been identified as the major pathogen, but the detailed pathogenesis of gastric carcinoma remains elusive. Due to the lack of suitable and specific biomarkers for early detection, most cases of the disease are diagnosed at late stages and the survival rate is low. In this study, we used a proteomic approach to globally analyze the protein profiles of paired surgical specimens of primary gastric adenocarcinoma and nontumor mucosa aiming at identifying specific disease-associated proteins as potential clinical biomarkers and for carcinogenetic study. Compared to nontumor tissues, multiple protein alterations were found in tumor tissues. Some of these alterations involve variations in the expression of cytoskeleton proteins, including an increase in cytokeratin 8 and tropomyosin isoform and a decrease in cytokeratin 20. Co-up-regulations of heat-shock proteins and glycolytic enzymes were observed in tumor tissues, indicating self-protective efforts of cells and the growing energy requirement during malignant transformation. Diverse regulations also occurred with proteins involved in cell proliferation and differentiation, such as GMP reductase 2 and creatine kinase B, and proteins bearing potential tumor suppressor activities, including prohibitin and selenium binding protein 1. More interestingly, a human stomach-specific protein, 18 kDa antrum mucosa protein, was found to be dramatically under-expressed in cancer tissues, implicating a possible special pathological role for this protein in gastric carcinogenesis. Further comprehensive evaluation by globally considering the altered factors may result in the discovery of a biomarker index for effective assessment of the disease and may provide in-depth information for better understanding the pathogenesis of gastric cancer.postprin

Proteomic approach to study the cytotoxicity of dioscin (saponin)

Dioscin, extracted from the root of Polygonatum zanlanscianense pamp, exhibits cytotoxicity towards human myeloblast leukemia HL-60 cells. Proteomic analysis revealed that the expression of mitochondrial associated proteins was substantially altered in HL-60 cells corresponding to the dioscin treatment, suggesting that mitochondria are the major cellular target of dioscin. Mitochondrial functional studies validated that mitochondrial apoptotic pathway was initiated by dioscin treatment. Changes in proteome other than mitochondrial related proteins implicate that other mechanisms were also involved in dioscin-induced apoptosis in HL-60 cells, including the activity impairment in protein synthesis, alterations of phosphatases in cell signaling, and deregulation of oxidative stress and cell proliferation. Current study of protein alterations in dioscin-treated HL-60 cells suggested that dioscin exerts cytotoxicity through multiple apoptosis-inducing pathways. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.postprin

Bound exciton and free exciton states in GaSe thin slab

The photoluminescence (PL) and absorption experiments have been performed in GaSe slab with incident light polarized perpendicular to c-axis of sample at 10K. An obvious energy difference of about 34meV between exciton absorption peak and PL peak (the highest energy peak) is observed. By studying the temperature dependence of PL spectra, we attribute it to energy difference between free exciton and bound exciton states, where main exciton absorption peak comes from free exciton absorption, and PL peak are attributed to recombination of bound exciton at 10K. This strong bound exciton effect is stable up to 50K. Moreover, the temperature dependence of integrated PL intensity and PL lifetime reveals that a non-radiative process, with active energy extracted as 0.5meV, dominates PL emission.Comment: 10 pages, 4 figure

Environmental factors and mortality risks associated influenza

BACKGROUND AND AIMS: The subtropical and tropical regions exhibit a distinct seasonality of influenza incidence from the temperate regions, and the mechanism behind it remains unclear. Environmental factors have been related to the transmission and survival of influenza viruses but no studies have ever explored the role of environmental factors on regulating severity of influenza infection. METHODS: We applied a Poisson regression model to the mortality data of two Asian metropolitan cities located at the subtropical zone, Guangzhou and Hong Kong. Interaction between …postprin