Efficient Conditional Proxy Re-encryption with Chosen-Ciphertext Security

Recently, a variant of proxy re-encryption, named conditional proxy re-encryption (C-PRE), has been introduced. Compared with traditional proxy re-encryption, C-PRE enables the delegator to implement fine-grained delegation of decryption rights, and thus is more useful in many applications. In this paper, based on a careful observation on the existing definitions and security notions for C-PRE, we reformalize more rigorous definition and security notions for C-PRE. We further propose a more efficient C-PRE scheme, and prove its chosenciphertext security under the decisional bilinear Diffie-Hellman (DBDH) assumption in the random oracle model. In addition, we point out that a recent C-PRE scheme fails to achieve the chosen-ciphertext security

Somatic mutation and gain of copy number of PIK3CA in human breast cancer

INTRODUCTION: Phosphatidylinositol 3-kinases (PI3Ks) are a group of lipid kinases that regulate signaling pathways involved in cell proliferation, adhesion, survival, and motility. Even though PIK3CA amplification and somatic mutation have been reported previously in various kinds of human cancers, the genetic change in PIK3CA in human breast cancer has not been clearly identified. METHODS: Fifteen breast cancer cell lines and 92 primary breast tumors (33 with matched normal tissue) were used to check somatic mutation and gene copy number of PIK3CA. For the somatic mutation study, we specifically checked exons 1, 9, and 20, which have been reported to be hot spots in colon cancer. For the analysis of the gene copy number, we used quantitative real-time PCR and fluorescence in situ hybridization. We also treated several breast cancer cells with the PIK3CA inhibitor LY294002 and compared the apoptosis status in cells with and without PIK3CA mutation. RESULTS: We identified a 20.6% (19 of 92) and 33.3% (5 of 15) PIK3CA somatic mutation frequency in primary breast tumors and cell lines, respectively. We also found that 8.7% (8 of 92) of the tumors harbored a gain of PIK3CA gene copy number. Only four cases in this study contained both an increase in the gene copy number and a somatic mutation. In addition, mutation of PIK3CA correlated with the status of Akt phosphorylation in some breast cancer cells and inhibition of PIK3CA-induced increased apoptosis in breast cancer cells with PIK3CA mutation. CONCLUSION: Somatic mutation rather than a gain of gene copy number of PIK3CA is the frequent genetic alteration that contributes to human breast cancer progression. The frequent and clustered mutations within PIK3CA make it an attractive molecular marker for early detection and a promising therapeutic target in breast cancer

Mitochondrial DNA Copy Number Is Associated with Breast Cancer Risk

Mitochondrial DNA (mtDNA) copy number in peripheral blood is associated with increased risk of several cancers. However, data from prospective studies on mtDNA copy number and breast cancer risk are lacking. We evaluated the association between mtDNA copy number in peripheral blood and breast cancer risk in a nested case-control study of 183 breast cancer cases with pre-diagnostic blood samples and 529 individually matched controls among participants of the Singapore Chinese Health Study. The mtDNA copy number was measured using real time PCR. Conditional logistic regression analyses showed that there was an overall positive association between mtDNA copy number and breast cancer risk (Ptrend = 0.01). The elevated risk for higher mtDNA copy numbers was primarily seen for women with <3 years between blood draw and cancer diagnosis; ORs (95% CIs) for 2nd, 3rd, 4th, and 5th quintile of mtDNA copy number were 1.52 (0.61, 3.82), 2.52 (1.03, 6.12), 3.12 (1.31, 7.43), and 3.06 (1.25, 7.47), respectively, compared with the 1st quintile (Ptrend = 0.004). There was no association between mtDNA copy number and breast cancer risk among women who donated a blood sample ≥3 years before breast cancer diagnosis (Ptrend = 0.41). This study supports a prospective association between increased mtDNA copy number and breast cancer risk that is dependent on the time interval between blood collection and breast cancer diagnosis. Future studies are warranted to confirm these findings and to elucidate the biological role of mtDNA copy number in breast cancer risk. © 2013 Thyagarajan et al

Freshwater bivalve shells as hydrologic archives in the Congo Basin

We test the applicability of bivalve shell oxygen isotope composition to reconstruct hydrological dynamics in four riverine sites in the Congo River basin. Twenty-three specimens from the Unionoida order were collected from locations where long-term discharge data are available, and in situ measurements and water samples were collected over several years. Due to the highly variable (species-specific) shell morphology, various sampling techniques were used to analyze the shell sections; however, every specimen recorded the seasonality of the host water oxygen stable isotope composition (δ 18 O w ) in its δ 18 O shell record. Discharge data showed an inverse relationship with δ 18 O w values, which was well described with a logarithmic fit. An exception was the Kasai River, where the δ 18 O w record shows an additional peak occurring during the high discharge period, which renders the discharge-δ 18 O w relationship more complex than in the other systems investigated. Low ratios of maximum to minimum discharge (Q max /Q min ) were found to result in a low δ 18 O w amplitude, which was reflected as low δ 18 O shell variability. The Congo and Kasai rivers had Q max /Q min ratios ~2 to 2.5, while the Oubangui showed a much higher Q max /Q min (~19). Shells correspondingly showed a large δ 18 O shell range (amplitude between 2.4 and 5.0‰) for individual Oubangui shells, and lower amplitude for other sites (1.0 to 2.2‰). Thus, shells have a high resolving power to be used to record hydrological variability, since long-term changes in precipitation pattern, discharge, land-use change, or other hydrological changes have an influence on δ 18 O w values. Shells with wide range of δ 18 O values reflect high seasonal variability in rivers, while shells with lower δ 18O amplitude correspond to sites with more steady river conditions over the year. Our study illustrates that fossil shell δ 18 O values could indicate Q max /Q min values in ancient African river systems.AFRIVA

Targeting of mutant hogg1 in mammalian mitochondria and nucleus: effect on cellular survival upon oxidative stress

BACKGROUND: Oxidative damage to mitochondrial DNA has been implicated as a causative factor in a wide variety of degenerative diseases, aging and cancer. The modified guanine, 7,8-dihydro-8-oxoguanine (also known as 8-hydroxyguanine) is one of the major oxidized bases generated in DNA by reactive oxygen species and has gained most of the attention in recent years as a marker of oxidative DNA injury and its suspected role in the initiation of carcinogenesis. 8-hydroxyguanine is removed by hOgg1, a DNA glycosylase/AP lyase involved in the base excision repair pathway. METHODS: We over-expressed wild type and R229Q mutant hOGG1 in the nucleus and mitochondria of cells lacking mitochondrial hOGG1 expression through an expression vector containing nuclear and mitochondrial targeting sequence respectively. We used quantitative real time PCR to analyze mtDNA integrity after exposure to oxidative damaging agents, in cells transfected with or without mitochondrially-targeted mutant hogg1. RESULT: Over-expression of wild type hOgg1 in both nucleus and mitochondria resulted in increased cellular survival when compared to vector or mutant over-expression of hOGG1. Interestingly, mitochondrially-targeted mutant hogg1 resulted in more cell death than nuclear targeted mutant hogg1 upon exposure of cells to oxidative damage. Additional we examined mitochondrial DNA integrity after oxidative damage exposure using real-time quantitative PCR. The presence of mutant hogg1 in the mitochondria resulted in reduced mitochondrial DNA integrity when compared to the wild type. Our work indicates that the R229Q hOGG1 mutation failed to protect cells from oxidative damage and that such mutations in cancer may be more detrimental to cellular survival when present in the mitochondria than in the nucleus. CONCLUSION: These findings suggest that deficiencies in hOGG1, especially in the mitochondria may lead to reduced mitochondrial DNA integrity, consequently resulting in decreased cell viability

Lack of association between mutations of gene-encoding mitochondrial D310 (displacement loop) mononucleotide repeat and oxidative stress in chronic dialysis patients in Taiwan

<p>Abstract</p> <p>Background</p> <p>Mitochondria (mt) are highly susceptible to reactive oxygen species (ROS). In this study, we investigated the association between a region within the displacement loop (D-loop) in mtDNA that is highly susceptible to ROS and oxidative stress markers in chronic dialysis patients. We enrolled 184 chronic dialysis patients and 213 age-matched healthy subjects for comparison. Blood levels of oxidative stress markers, such as thiobarbituric acid reactive substances (TBARS) and free thiol, and the mtDNA copy number were determined. A mononucleotide repeat sequence (CCCC...CCCTCCCCCC) between nucleotides 303 and 316-318 (D310) was identified in mtDNA.</p> <p>Results</p> <p>Depending on alterations in the D310 mononucleotide repeat, subjects were categorized into 4 subgroups: 7-C, 8-C, 9 or 10-C, and T-to-C transition. Oxidative stress was higher in chronic dialysis patients, evidenced by higher levels of TBARS and mtDNA copy number, and a lower level of free thiol. The distribution of 7-C, 8-C, and 9-10C in dialysis and control subjects was as follows: 7-C (38% <it>vs. </it>31.5%), 8-C (35.3% <it>vs. </it>43.2%), and 9-10C (24.5% <it>vs. </it>22.1%). Although there were significant differences in levels of TBARS, free thiol, and the mtDNA copy number in the D310 repeat subgroups (except T-to-C transition) between dialysis patients and control subjects, post hoc analyses within the same study cohort revealed no significant differences.</p> <p>Conclusion</p> <p>Although oxidative stress was elevated in chronic dialysis patients and resulted in a compensatory increase in the mtDNA copy number, homopolymeric C repeats in the mtDNA region (D310), susceptible to ROS, were not associated with oxidative stress markers in these patients.</p

Reduced repair of 8-hydroxyguanine in the human breast cancer cell line, HCC1937

BACKGROUND: Breast cancer is the second leading cause of cancer deaths in women in the United States. Although the causes of this disease are incompletely understood, oxidative DNA damage is presumed to play a critical role in breast carcinogenesis. A common oxidatively induced DNA lesion is 8-hydroxyguanine (8-OH-Gua), which has been implicated in carcinogenesis. The aim of this study was to investigate the ability of HCC1937 and MCF-7 breast cancer cell lines to repair 8-OH-Gua relative to a nonmalignant human mammary epithelial cell line, AG11134. METHODS: We used oligonucleotide incision assay to analyze the ability of the two breast cancer cell lines to incise 8-OH-Gua relative to the control cell line. Liquid chromatography/mass spectrometry (LC/MS) was used to measure the levels of 8-OH-Gua as its nucleoside, 8-OH-dG in the cell lines after exposure to H(2)O(2 )followed by 30 min repair period. Protein expression levels were determined by Western blot analysis, while the hOGG1 mRNA levels were analyzed by RT-PCR. Complementation of hOGG1 activity in HCC1937 cells was assessed by addition of the purified protein in the incision assay, and in vivo by transfection of pFlagCMV-4-hOGG1. Clonogenic survival assay was used to determine sensitivity after H(2)O(2)-mediated oxidative stress. RESULTS: We show that the HCC1937 breast cancer cells have diminished ability to incise 8-OH-Gua and they accumulate higher levels of 8-OH-dG in the nuclear genome after H(2)O(2 )treatment despite a 30 min repair period when compared to the nonmalignant mammary cells. The defective incision of 8-OH-Gua was consistent with expression of undetectable amounts of hOGG1 in HCC1937 cells. The reduced incision activity was significantly stimulated by addition of purified hOGG1. Furthermore, transfection of pFlagCMV-4-hOGG1 in HCC1937 cells resulted in enhanced incision of 8-OH-Gua. HCC1937 cells are more sensitive to high levels of H(2)O(2 )and have up-regulated SOD1 and SOD2. CONCLUSION: This study provides evidence for inefficient repair of 8-OH-Gua in HCC1937 breast cancer cell line and directly implicates hOGG1 in this defect