Association between polymorphisms in RMI1, TOP3A, and BLM and risk of cancer, a case-control study

BACKGROUND: Mutations altering BLM function are associated with highly elevated cancer susceptibility (Bloom syndrome). Thus, genetic variants of BLM and proteins that form complexes with BLM, such as TOP3A and RMI1, might affect cancer risk as well. METHODS: In this study we have studied 26 tagged single nucleotide polymorphisms (tagSNPs) in RMI1, TOP3A, and BLM and their associations with cancer risk in acute myeloid leukemia/myelodysplatic syndromes (AML/MDS; N = 152), malignant melanoma (N = 170), and bladder cancer (N = 61). Two population-based control groups were used (N = 119 and N = 156). RESULTS: Based on consistency in effect estimates for the three cancer forms and similar allelic frequencies of the variant alleles in the control groups, two SNPs in TOP3A (rs1563634 and rs12945597) and two SNPs in BLM (rs401549 and rs2532105) were selected for analysis in breast cancer cases (N = 200) and a control group recruited from spouses of cancer patients (N = 131). The rs12945597 in TOP3A and rs2532105 in BLM showed increased risk for breast cancer. We then combined all cases (N = 584) and controls (N = 406) respectively and found significantly increased risk for variant carriers of rs1563634 A/G (AG carriers OR = 1.7 [95%CI 1.1-2.6], AA carriers OR = 1.8 [1.2-2.8]), rs12945597 G/A (GA carriers OR = 1.5 [1.1-1.9], AA carriers OR = 1.6 [1.0-2.5]), and rs2532105 C/T (CT+TT carriers OR = 1.8 [1.4-2.5]). Gene-gene interaction analysis suggested an additive effect of carrying more than one risk allele. For the variants of TOP3A, the risk increment was more pronounced for older carriers. CONCLUSION: These results further support a role of low-penetrance genes involved in BLM-associated homologous recombination for cancer risk

Safety climate and increased risk: The role of deadlines in design work

Although much research indicates positive safety climate is associated with reduced safety risk, we argue this association is not universal and may even be reversed in some contexts. Specifically, we argue that positive safety climate can be associated with increased safety risk when there is pressure to prioritize production over safety and where workers have some detachment from the consequences of their actions, such as found in engineering design work. We used two indicators of safety risk: use of heuristics at the individual level and design complexity at the design team level. Using experience sampling data (N = 165, 42 design teams, k = 5752 observations), we found design engineers’ perceptions of team positive safety climate were associated with less use of heuristics when engineers were not working to deadlines, but more use of heuristics when engineers were working to deadlines. Independent ratings were obtained of 31 teams’ designs of offshore oil and gas platforms (N = 121). For teams that worked infrequently to deadlines, positive team safety climate was associated with less design complexity. For teams that worked frequently to deadlines, positive team safety climate was associated with more design complexity

Fluorescent amino acids as versatile building blocks for chemical biology

Fluorophores have transformed the way we study biological systems, enabling non-invasive studies in cells and intact organisms, which increase our understanding of complex processes at the molecular level. Fluorescent amino acids have become an essential chemical tool because they can be used to construct fluorescent macromolecules, such as peptides and proteins, without disrupting their native biomolecular properties. Fluorescent and fluorogenic amino acids with unique photophysical properties have been designed for tracking protein–protein interactions in situ or imaging nanoscopic events in real time with high spatial resolution. In this Review, we discuss advances in the design and synthesis of fluorescent amino acids and how they have contributed to the field of chemical biology in the past 10 years. Important areas of research that we review include novel methodologies to synthesize building blocks with tunable spectral properties, their integration into peptide and protein scaffolds using site-specific genetic encoding and bioorthogonal approaches, and their application to design novel artificial proteins, as well as to investigate biological processes in cells by means of optical imaging. [Figure not available: see fulltext.]

Functional polymorphisms in the TERT promoter are associated with risk of serous epithelial ovarian and breast cancers

Genetic variation at the TERT-CLPTM1L locus at 5p15.33 is associated with susceptibility to several cancers, including epithelial ovarian cancer (EOC). We have carried out fine-mapping of this region in EOC which implicates an association with a single nucleotide polymorphism (SNP) within the TERT promoter. We demonstrate that the minor alleles at rs2736109, and at an additional TERT promoter SNP, rs2736108, are associated with decreased breast cancer risk, and that the combination of both SNPs substantially reduces TERT promoter activity

Predicting the occurrence of riparian woody species to inform environmental water policies in an Australian tropical river

River flows are commonly altered by water resource development, with changes to the natural flow regime potentially impacting riparian vegetation. Increasingly, water resource managers seek to design policy to maintain healthy riparian ecosystems. Models that make explicit the relationship between hydrological variables and vegetation can be used by managers to assess vegetation response under different water management scenarios. We determined the potential impact of water-takeon the spatial distribution of woody riparian plant species in the lower Fitzroy River, in north-western Australia, an area under pressure to increase water resource development. We undertook a plant survey and developed and applied a joint species distribution model to determine the likelihood of occurrence for 26 woody riparian plant species, mapped species occurrence and assessed the change in species distribution under two water-take scenarios. We found that the duration of inundation from flood flows was a strong predictor of species occurrence in our joint species distribution model. We identified species associated with wetter environments, as indicated by their effect size for the inundation metric. Under the 300-Gl water-take scenario we found little change (<2%) in species occurrence, but under the 600-Gl scenario a decline between 5% and 7.4% was predicted for eight species associated with wetter habitats. This decline was generally confined to a localised area. Our approach highlights the usefulness of predictive modelling to identify species most likely to be impacted by water-take, and the benefit of linking modelling to spatial mapping because it can highlight areas where change is likely to occur. This information can assist management to protect ecologically and culturally important species.No Full Tex

Environmental flows synthesis to support uptake of environmental flows research in northern Australia

River flows support healthy ecosystems that provide a wealth of economic, social and cultural goods and services such as fisheries, recreation and tourism attractions, bush tucker, clean water, fertile floodplains and more. Understanding the links between river flows and healthy ecosystems is therefore critical to determining how much water is needed to maintain these goods and services. In places where these links are unknown, water planners need to infer relationships from similar places until enough local field data is collected and analysed.Full Tex