Kin-cohort estimates for familial breast cancer risk in relation to variants in DNA base excision repair, BRCA1 interacting and growth factor genes

BACKGROUND: Subtle functional deficiencies in highly conserved DNA repair or growth regulatory processes resulting from polymorphic variation may increase genetic susceptibility to breast cancer. Polymorphisms in DNA repair genes can impact protein function leading to genomic instability facilitated by growth stimulation and increased cancer risk. Thus, 19 single nucleotide polymorphisms (SNPs) in eight genes involved in base excision repair (XRCC1, APEX, POLD1), BRCA1 protein interaction (BRIP1, ZNF350, BRCA2), and growth regulation (TGFß1, IGFBP3) were evaluated. METHODS: Genomic DNA samples were used in Taqman 5'-nuclease assays for most SNPs. Breast cancer risk to ages 50 and 70 were estimated using the kin-cohort method in which genotypes of relatives are inferred based on the known genotype of the index subject and Mendelian inheritance patterns. Family cancer history data was collected from a series of genotyped breast cancer cases (N = 748) identified within a cohort of female US radiologic technologists. Among 2,430 female first-degree relatives of cases, 190 breast cancers were reported. RESULTS: Genotypes associated with increased risk were: XRCC1 R194W (WW and RW vs. RR, cumulative risk up to age 70, risk ratio (RR) = 2.3; 95% CI 1.3–3.8); XRCC1 R399Q (QQ vs. RR, cumulative risk up to age 70, RR = 1.9; 1.1–3.9); and BRIP1 (or BACH1) P919S (SS vs. PP, cumulative risk up to age 50, RR = 6.9; 1.6–29.3). The risk for those heterozygous for BRCA2 N372H and APEX D148E were significantly lower than risks for homozygotes of either allele, and these were the only two results that remained significant after adjusting for multiple comparisons. No associations with breast cancer were observed for: APEX Q51H; XRCC1 R280H; IGFPB3 -202A>C; TGFß1 L10P, P25R, and T263I; BRCA2 N289H and T1915M; BRIP1 -64A>C; and ZNF350 (or ZBRK1) 1845C>T, L66P, R501S, and S472P. CONCLUSION: Some variants in genes within the base-excision repair pathway (XRCC1) and BRCA1 interacting proteins (BRIP1) may play a role as low penetrance breast cancer risk alleles. Previous association studies of breast cancer and BRCA2 N372H and functional observations for APEX D148E ran counter to our findings of decreased risks. Due to the many comparisons, cautious interpretation and replication of these relationships are warranted

Comparative Analysis of Serine/Arginine-Rich Proteins across 27 Eukaryotes: Insights into Sub-Family Classification and Extent of Alternative Splicing

Alternative splicing (AS) of pre-mRNA is a fundamental molecular process that generates diversity in the transcriptome and proteome of eukaryotic organisms. SR proteins, a family of splicing regulators with one or two RNA recognition motifs (RRMs) at the N-terminus and an arg/ser-rich domain at the C-terminus, function in both constitutive and alternative splicing. We identified SR proteins in 27 eukaryotic species, which include plants, animals, fungi and “basal” eukaryotes that lie outside of these lineages. Using RNA recognition motifs (RRMs) as a phylogenetic marker, we classified 272 SR genes into robust sub-families. The SR gene family can be split into five major groupings, which can be further separated into 11 distinct sub-families. Most flowering plants have double or nearly double the number of SR genes found in vertebrates. The majority of plant SR genes are under purifying selection. Moreover, in all paralogous SR genes in Arabidopsis, rice, soybean and maize, one of the two paralogs is preferentially expressed throughout plant development. We also assessed the extent of AS in SR genes based on a splice graph approach (http://combi.cs.colostate.edu/as/gmap_SRgenes). AS of SR genes is a widespread phenomenon throughout multiple lineages, with alternative 3′ or 5′ splicing events being the most prominent type of event. However, plant-enriched sub-families have 57%–88% of their SR genes experiencing some type of AS compared to the 40%–54% seen in other sub-families. The SR gene family is pervasive throughout multiple eukaryotic lineages, conserved in sequence and domain organization, but differs in gene number across lineages with an abundance of SR genes in flowering plants. The higher number of alternatively spliced SR genes in plants emphasizes the importance of AS in generating splice variants in these organisms

Effectiveness of Endophytes Bacteria in Enhancing Floating Treatment Wetland to Treat Textile Wastewater

This research investigated the association of consortium endophyte bacteria from different hosts to enhance the performance of Vetiveria zizanioides in treating textile wastewater using Floating Treatment Wetlands (FTWs). The endophyte bacteria were isolated from the roots of three natural plants (Oryza sativa, Colocasia esculenta, and Alternanthera philoxeroides) contaminated by textile wastewater. The selected isolated endophyte bacteria were subjected to the four FTWs reactors containing the Vetiveria sp and ran for 30 days in a semi-batch system to evaluate their performance. FTWs reactors-augmented endophyte bacteria could reduce the COD, color, and heavy metals in textile wastewater. The highest removal efficiencies of COD (74%) and color (F4) were observed in FK2 (vegetated control) and F4 reactor, respectively. The addition of endophyte bacteria increased the heavy reductions of Pb (52%) and Cd (33%) in reactors of F3 and F4, respectively. This study exhibited that the consortium endophyte bacteria isolated from the contaminated plants could improve the FTWs reactor performance. Finally, they reduce the plant stresses in the contaminated wastewater by increasing the plant biomass in roots and shoots. These findings reveal that the consortium of natural endophyte bacteria from different hosts does not inhibit their function and association with the other host plant, but they contribute positive responses to plant growth and pollutant degradation

Unshuffling Permutations

International audienceA permutation is said to be a square if it can be obtained by shuffling two order-isomorphic patterns. The definition is intended to be the natural counterpart to the ordinary shuffle of words and languages. In this paper, we tackle the problem of recognizing square permutations from both the point of view of algebra and algorithms. On the one hand, we present some algebraic and combinatorial properties of the shuffle product of permutations. We follow an unusual line consisting in defining the shuffle of permutations by means of an unshuffling operator, known as a coproduct. This strategy allows to obtain easy proofs for algebraic and combinatorial properties of our shuffle product. We besides exhibit a bijection between square (213, 231)-avoiding permutations and square binary words. On the other hand, by using a pattern avoidance criterion on oriented perfect matchings, we prove that recognizing square permutations is NP-complete

Universal constructions in umbral calculus

Modern umbral calculus is steadily approaching maturity, as applications develop in several areas of mathematics. To maximize this utility it is important to work in the most general (as opposed to the most abstract

Trust in anthropology

The article explores some of the assumptions behind the current valence of the notion of trust and in particular its entanglement in discourses of social robustness, the management and reporting of (corporate) knowledge, and its underlying culture and systems of responsibility. It unfolds by contrasting classic and contemporary anthropological work on cultures of suspicion, culpability and spiritual ambiguity with the new vocabulary of capitalist corporate ethics. Finally, the argument examines the work that relationships do when moving in and out of the occult, and contrasts it with the kind of temporal work that capitalism demands from relationships to remain diaphanous. If public trust functions as the political epistemology of neoliberal society, an anthropological theory of trust ought perhaps to reaffirm instead our trust in anthropological theory and comparison.Peer reviewe

The cd-Index of Zonotopes and Arrangements

We investigate a special class of polytopes, the zonotopes, and show that their flag f-vectors satisfy only the affine relations fulfilled by flag f-vectors of all polytopes. In addition, we determine the lattice spanned by flag f-vectors of zonotopes. By duality, these results apply as well to the flag f-vectors of central arrangements of hyperplanes