Association between manganese superoxide dismutase promoter gene polymorphism and breast cancer survival

BACKGROUND: Manganese superoxide dismutase (MnSOD) plays a critical role in the detoxification of mitochondrial reactive oxygen species, constituting a major cellular defense mechanism against agents that induce oxidative stress. A genetic polymorphism in the mitochondrial targeting sequence of this gene has been associated with increased cancer risk and survival in breast cancer. This base pair transition (-9 T > C) leads to a valine to alanine amino acid change in the mitochondrial targeting sequence. A polymorphism has also been identified in the proximal region of the promoter (-102 C>T) that alters the recognition sequence of the AP-2 transcription factor, leading to a reduction in transcriptional activity. The aim of our study was to investigate possible associations of the -102 C>T polymorphism with overall and relapse-free breast cancer survival in a hospital-based case-only study. MATERIALS AND METHODS: The relationship between the MnSOD -102 C>T polymorphism and survival was examined in a cohort of 291 women who received chemotherapy and/or radiotherapy for incident breast cancer. The MnSOD -102 C>T genotype was determined using a TaqMan allele discrimination assay. Patient survival was evaluated according to the MnSOD genotype using Kaplan–Meier survival functions. Hazard ratios were calculated from adjusted Cox proportional hazards modeling. All statistical tests were two-sided. RESULTS: In an evaluation of all women, there was a borderline significant reduction in recurrence-free survival with either one or both variant alleles (CT + TT) when compared with patients with wild-type alleles (CC) (odds ratio, 0.65; 95% confidence interval, 0.42–1.01). When the analysis was restricted to patients receiving radiation therapy, there was a significant reduction in relapse-free survival in women who were heterozygous for the MnSOD -102 genotype (relative risk, 0.40; 95% confidence interval, 0.18–0.86). Similarly, when the homozygous and heterozygous variant genotypes were combined, there remained a significant reduction in relapse-free survival in this group (hazard ratio, 0.42; 95% confidence interval, 0.20–0.87). CONCLUSION: The MnSOD -102 variant allele appears to be associated with an improved recurrence-free survival in all patients, and more dramatically in subjects who received adjuvant radiation therapy

An adaptive 5G multiservice and multitenant radio access network architecture

This article provides an overview on objectives and first results of the Horizon 2020 project 5G NOvel Radio Multiservice adaptive network Architecture (5GNORMA). With 5G NORMA, leading players in the mobile ecosystem aim to underpin Europe's leadership position in 5G. The key objective of 5G NORMA is to develop a conceptually novel, adaptive and future-proof 5G mobile network architecture. This architecture will allow for adapting the network to a wide range of service specific requirements, resulting in novel service-aware and context-aware end-to-end function chaining. The technical approach is based on an innovative concept of adaptive (de)composition and allocation of mobile network functions based on end-user requirements and infrastructure capabilities. At the same time, cost savings and faster time to market are to be expected by joint deployment of logically separated multiservice and multitenant networks on common hardware and other physical resources making use of traffic multiplexing gains. In this context architectural enablers such as network function virtualization and software-defined mobile networking will play a key role for introducing the needed flexible resource assignment to logical networks and specific virtual network functions.This work has been performed in the framework of the H2020-ICT-2014-2 project 5G NORMA

Method for determination of (-102C>T) single nucleotide polymorphism in the human manganese superoxide dismutase promoter

BACKGROUND: Manganese superoxide dismutase (MnSOD) plays a critical role in the detoxification of mitochondrial reactive oxygen species constituting a major cellular defense mechanism against agents that induce oxidative stress. The MnSOD promoter contains an activator protein-2 (AP-2) binding site that modifies transcription of MnSOD. Mutations have been identified in the proximal region of the promoter in human tumor cell lines. One of these mutations (-102C>T) has been shown to change the binding pattern of AP-2 leading to a reduction in transcriptional activity. The aim of our study was to develop a method to identify and determine the frequency of this (-102C>T) polymorphism in human tissues. RESULTS: A new TaqMan allelic discrimination genotype method was successfully applied to genomic DNA samples derived from blood, buccal swabs, snap frozen tissue and paraffin blocks. The polymorphism was shown to be in Hardy-Weinberg Equilibrium in an evaluation of 130 Caucasians from Warsaw, Poland: 44 (33.8%) were heterozygous and 6 (4.6%) were homozygous for -102T. CONCLUSION: This report represents the first description of the MnSOD -102C>T polymorphism in human subjects by a novel Taqman allelic discrimination assay. This method should enable molecular epidemiological studies to evaluate possible associations of this polymorphism with malignancies and other diseases related to reactive oxygen species

Mobile network architecture evolution toward 5G

As a chain is as strong as its weakest element, so are the efficiency, flexibility, and robustness of a mobile network, which relies on a range of different functional elements and mechanisms. Indeed, the mobile network architecture needs particular attention when discussing the evolution of 3GPP EPS because it is the architecture that integrates the many different future technologies into one mobile network. This article discusses 3GPP EPS mobile network evolution as a whole, analyzing specific architecture properties that are critical in future 3GPP EPS releases. In particular, this article discusses the evolution toward a "network of functions," network slicing, and software-defined mobile network control, management, and orchestration. Furthermore, the roadmap for the future evolution of 3GPP EPS and its technology components is detailed and relevant standards defining organizations are listed.This work has been performed in the framework of the H2020-ICT-2014-2 project 5G NORMA

The Effect of Nicotine on Reproduction and Attachment of Human Gingival Fibroblasts In Vitro

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142127/1/jper0658.pd

Characterization of N-acetyltransferase 1 and 2 polymorphisms and haplotype analysis for inflammatory bowel disease and sporadic colorectal carcinoma

<p>Abstract</p> <p>Background</p> <p>N-acetyltransferase 1 (NAT1) and 2 (NAT2) are polymorphic isoenzymes responsible for the metabolism of numerous drugs and carcinogens. Acetylation catalyzed by NAT1 and NAT2 are important in metabolic activation of arylamines to electrophilic intermediates that initiate carcinogenesis. Inflammatory bowel diseases (IBD) consist of Crohn's disease (CD) and ulcerative colitis (UC), both are associated with increased colorectal cancer (CRC) risk. We hypothesized that <it>NAT1 </it>and/or <it>NAT2 </it>polymorphisms contribute to the increased cancer evident in IBD.</p> <p>Methods</p> <p>A case control study was performed with 729 Caucasian participants, 123 CRC, 201 CD, 167 UC, 15 IBD dysplasia/cancer and 223 controls. <it>NAT1 </it>and <it>NAT2 </it>genotyping were performed using Taqman based techniques. Eight single nucleotide polymorphisms (SNPs) were characterized for <it>NAT1 </it>and 7 SNPs for <it>NAT2</it>. Haplotype frequencies were estimated using an Expectation-Maximization (EM) method. Disease groups were compared to a control group for the frequencies at each individual SNP separately. The same groups were compared for the frequencies of <it>NAT1 </it>and <it>NAT2 </it>haplotypes and deduced NAT2 phenotypes.</p> <p>Results</p> <p>No statistically significant differences were found for any comparison. Strong linkage disequilibrium was present among both the <it>NAT1 </it>SNPs and the <it>NAT2 </it>SNPs.</p> <p>Conclusion</p> <p>This study did not demonstrate an association between <it>NAT1 </it>and <it>NAT2 </it>polymorphisms and IBD or sporadic CRC, although power calculations indicate this study had sufficient sample size to detect differences in frequency as small as 0.05 to 0.15 depending on SNP or haplotype.</p

Rifting under steam – how rift magmatism triggers methane venting from sedimentary basins

During opening of a new ocean magma intrudes into the surrounding sedimentary basins. Heat provided by the intrusions matures the host rock creating metamorphic aureoles potentially releasing large amounts of hydrocarbons. These hydrocarbons may migrate to the seafloor in hydrothermal vent complexes in sufficient volumes to trigger global warming, e.g. during the Paleocene Eocene Thermal Maximum (PETM). Mound structures at the top of buried hydrothermal vent complexes observed in seismic data off Norway were previously interpreted as mud volcanoes and the amount of released hydrocarbon was estimated based on this interpretation. Here, we present new geophysical and geochemical data from the Gulf of California suggesting that such mound structures could in fact be edifices constructed by the growth of black-smoker type chimneys rather than mud volcanoes. We have evidence for two buried and one active hydrothermal vent system outside the rift axis. The vent releases several hundred degrees Celsius hot fluids containing abundant methane, mid-ocean-ridge-basalt (MORB)-type helium, and precipitating solids up to 300 m high into the water column. Our observations challenge the idea that methane is emitted slowly from rift-related vents. The association of large amounts of methane with hydrothermal fluids that enter the water column at high pressure and temperature provides an efficient mechanism to transport hydrocarbons into the water column and atmosphere, lending support to the hypothesis that rapid climate change such as during the PETM can be triggered by magmatic intrusions into organic-rich sedimentary basins

On the formation of hydrothermal vents and cold seeps in the Guaymas Basin, Gulf of California

Magmatic sill intrusions into organic-rich sediments cause the release of thermogenic CH4 and CO2. Pore fluids from the Guaymas Basin (Gulf of California), a sedimentary basin with recent magmatic activity, were investigated to constrain the link between sill intrusions and fluid seepage as well as the timing of sill-induced hydrothermal activity. Sampling sites were close to a hydrothermal vent field at the northern rift axis and at cold seeps located up to 30km away from the rift. Pore fluids close to the active hydrothermal vent field showed a slight imprint by hydrothermal fluids and indicated a shallow circulation system transporting seawater to the hydrothermal catchment area. Geochemical data of pore fluids at cold seeps showed a mainly ambient diagenetic fluid composition without any imprint related to high temperature processes at greater depth. Seep communities at the seafloor were mainly sustained by microbial methane, which rose along pathways formed earlier by hydrothermal activity, driving the anaerobic oxidation of methane (AOM) and the formation of authigenic carbonates. Overall, our data from the cold seep sites suggest that at present, sill-induced hydrothermalism is not active away from the ridge axis, and the vigorous venting of hydrothermal fluids is restricted to the ridge axis. Using the sediment thickness above extinct conduits and carbonate dating, we calculated that deep fluid and thermogenic gas flow ceased 28 to 7kyr ago. These findings imply a short lifetime of hydrothermal systems, limiting the time of unhindered carbon release as suggested in previous modeling studies. Consequently, activation and deactivation mechanisms of these systems need to be better constrained for the use in climate modeling approaches

Toll-Like Receptor (TLR) and Nucleosome-binding Oligomerization Domain (NOD) gene polymorphisms and endometrial cancer risk

Background: Endometrial cancer is the most common gynaecological malignancy in women of developed countries. Many risk factors implicated in endometrial cancer trigger inflammatory events; therefore, alterations in immune response may predispose an individual to disease. Toll-like receptors (TLRs) and nucleosome-binding oligomerization domain (NOD) genes are integral to the recognition of pathogens and are highly polymorphic. For these reasons, the aim of the study was to assess the frequency of polymorphic variants in TLR and NOD genes in an Australian endometrial cancer population. Methods: Ten polymorphisms were genotyped in 191 endometrial cancer cases and 291 controls using real-time PCR: NOD1 (rs2075822, rs2907749, rs2907748), NOD2 (rs5743260, rs2066844, rs2066845), TLR2 (rs5743708), TLR4 (rs4986790) and TLR9 (rs5743836, rs187084). Results: Haplotype analysis revealed that the combination of the variant alleles of the two TLR9 polymorphisms, rs5743836 and rs187084, were protective for endometrial cancer risk: OR 0.11, 95% CI (0.03-0.44), p = 0.002. This result remained highly significant after adjustment for endometrial cancer risk factors and Bonferroni correction for multiple testing. There were no other associations observed for the other polymorphisms in TLR2, TLR4, NOD1 and NOD2. Conclusions: The variant 'C' allele of rs5743836 causes greater TLR9 transcriptional activity compared to the 'T' allele, therefore, higher TLR9 activity may be related to efficient removal of microbial pathogens within the endometrium. Clearly, the association of these TLR9 polymorphisms and endometrial cancer risk must be further examined in an independent population. The results point toward the importance of examining immune response in endometrial tumourgenesis to understand new pathways that may be implicated in disease

Development of the PREMature Infant Index (PREMII™), a clinician-reported outcome measure assessing functional status of extremely preterm infants

Background: Comprehensive measures to evaluate the effectiveness of medical interventions in extremely preterm infants are lacking. Although length of stay is used as an indicator of overall health among preterm infants in clinical studies, it is confounded by nonmedical factors (e.g. parental readiness and availability of home nursing support). Objectives: To develop the PREMature Infant Index (PREMII™), an electronic content-valid clinician-reported outcome measure for assessing functional status of extremely preterm infants (<28 weeks gestational age) serially over time in the neonatal intensive care unit. We report the development stages of the PREMII, including suggestions for scoring. Methods: We developed the PREMII according to US Food and Drug Administration regulatory standards. Development included five stages: (1) literature review, (2) clinical expert interviews, (3) Delphi panel survey, (4) development of items/levels, and (5) cognitive interviews/usability testing. Scoring approaches were explored via an online clinician survey. Results: Key factors reflective of functional status were identified by physicians and nurses during development of the PREMII, as were levels within each factor to assess functional status. The resulting PREMII evaluates eight infant health factors: respiratory support, oxygen administration, apnea, bradycardia, desaturation, thermoregulation, feeding, and weight gain, each scored with three to six gradations. Factor levels are standardized on a 0–100 scale; resultant scores are 0–100. No usability issues were identified. The online clinician survey identified optimal scoring methods to capture functional status at a given time point. Conclusions: Our findings support the content validity and usability of the PREMII as a multifunction outcome measure to assess functional status over time in extremely preterm infants. Psychometric validation is ongoing