Enhancement of RAD51 recombinase activity by the tumor suppressor PALB2

Homologous recombination mediated by RAD51 recombinase helps eliminate chromosomal lesions, such as DNA double-strand breaks induced by radiation or arising from injured DNA replication forks. The tumor suppressors BRCA2 and PALB2 act together to deliver RAD51 to chromosomal lesions to initiate repair. Here we document a new function of PALB2: to enhance RAD51's ability to form the D loop. We show that PALB2 binds DNA and physically interacts with RAD51. Notably, although PALB2 alone stimulates D-loop formation, it has a cooperative effect with RAD51AP1, an enhancer of RAD51. This stimulation stems from the ability of PALB2 to function with RAD51 and RAD51AP1 to assemble the synaptic complex. Our results demonstrate the multifaceted role of PALB2 in chromosome damage repair. Because PALB2 mutations can cause cancer or Fanconi anemia, our findings shed light on the mechanism of tumor suppression in humans.

Mechanistic insights into RAD51-associated protein 1 (RAD51AP1) action in homologous DNA repair

Homologous recombination catalyzed by the RAD51 recombinase is essential for maintaining genome integrity upon the induction of DNA double strand breaks and other DNA lesions. By enhancing the recombinase activity of RAD51, RAD51AP1 (RAD51-associated protein 1) serves a key role in homologous recombination-mediated chromosome damage repair. We show here that RAD51AP1 harbors two distinct DNA binding domains that are both needed for maximal protein activity under physiological conditions. We have finely mapped the two DNA binding domains in RAD51AP1 and generated mutant variants that are impaired in either or both of the DNA binding domains. Examination of these mutants reveals that both domains are indispensable for RAD51AP1 function in cells. These and other results illuminate the mechanistic basis of RAD51AP1 action in homologous DNA repair.

Sans Faute

Sans Faute (without fail) considers how technology has influenced Chinese society, culture and practice. The exhibition seeks to reveal a shared language between Western and Chinese contexts that exists through employing technology as a universal creative meeting point. The pervasive impact of the current digital landscape has been widely recognised, embraced and continues to influence many aspects of Chinese lives. The significance of these shifting contexts on contemporary art is explored in Sans Faute. Through the presentation of a range of video installations, the exhibition aims to initiate rigorous and critical engagement with these provocative works that challenge traditional ideologies to discover emergent ideas. Featuring works by eight artists from mainland China, Sans Faute is an exploration of different attitudes collected together to provide a complete picture of how these artists build a new iconic imagery. "The works of these artists present a younger generation's thinking of the reality of contemporary China through their own emotional and individual life experience," says Stephen Danzig, IDAprojects director. "We are currently witnessing an amazing re-identification in so many elements that make up China's social fabric - none more so than what's happening in the arts currently. You only need to see what's happening in Beijing to realise the pace of change." Sans Faute has been supported by QUT Confucius Institute.

A normal-distribution based reputation model

Rating systems are used by many websites, which allow customers to rate available items according to their own experience. Subsequently, reputation models are used to aggregate available ratings in order to generate reputation scores for items. A problem with current reputation models is that they provide solutions to enhance accuracy of sparse datasets not thinking of their models performance over dense datasets. In this paper, we propose a novel reputation model to generate more accurate reputation scores for items using any dataset; whether it is dense or sparse. Our proposed model is described as a weighted average method, where the weights are generated using the normal distribution. Experiments show promising results for the proposed model over state-of-the-art ones on sparse and dense datasets.

Evidence of associations between cytokine gene polymorphisms and quality of life in patients with cancer and their family caregivers

PURPOSE/OBJECTIVES: To identify latent classes of individuals with distinct quality-of-life (QOL) trajectories, to evaluate for differences in demographic characteristics between the latent classes, and to evaluate for variations in pro- and anti-inflammatory cytokine genes between the latent classes. DESIGN: Descriptive, longitudinal study. SETTING: Two radiation therapy departments located in a comprehensive cancer center and a community-based oncology program in northern California. SAMPLE: 168 outpatients with prostate, breast, brain, or lung cancer and 85 of their family caregivers (FCs). METHODS: Growth mixture modeling (GMM) was employed to identify latent classes of individuals based on QOL scores measured prior to, during, and for four months following completion of radiation therapy. Single nucleotide polymorphisms (SNPs) and haplotypes in 16 candidate cytokine genes were tested between the latent classes. Logistic regression was used to evaluate the relationships among genotypic and phenotypic characteristics and QOL GMM group membership. MAIN RESEARCH VARIABLES: QOL latent class membership and variations in cytokine genes. FINDINGS: Two latent QOL classes were found: higher and lower. Patients and FCs who were younger, identified with an ethnic minority group, had poorer functional status, or had children living at home were more likely to belong to the lower QOL class. After controlling for significant covariates, between-group differences were found in SNPs in interleukin 1 receptor 2 (IL1R2) and nuclear factor kappa beta 2 (NFKB2). For IL1R2, carrying one or two doses of the rare C allele was associated with decreased odds of belonging to the lower QOL class. For NFKB2, carriers with two doses of the rare G allele were more likely to belong to the lower QOL class. CONCLUSIONS: Unique genetic markers in cytokine genes may partially explain interindividual variability in QOL. IMPLICATIONS FOR NURSING: Determination of high-risk characteristics and unique genetic markers would allow for earlier identification of patients with cancer and FCs at higher risk for poorer QOL. Knowledge of these risk factors could assist in the development of more targeted clinical or supportive care interventions for those identified.

Cidade é uma palavra plural [City is a manifold word]

This text elaborates on the city as cultural construct and representation and Lisbocópio, the installation by Pancho Guedes and Ricardo Jacinto in the context of the Official Representation of Portugal at the 10. Mostra Internazionale di Architettura-La Biennale di Venezia.

Espera

This text relates to Ar, Terra, Água, Luz, Aço, Tempo, an art work by Fernanda Fragateiro. It speculates on time and the space of Casa da Cerca garden as time-specific installation

Figuras de Espaço na Arquitectura de um Vazio [Figures of space in the architecture of a void]

This text discusses the production of space as performance, space as the architecture of a void in relation to Fernanda Fragateiro's art work 'Caixa para Guardar o Vazio'

Paisagem e Escassez : espaço e experimentação

The text elaborates on the creation of Candlestick Park and Parque de la Pedra Tosca as landscape architectural productions that integrated cultural and ecological processes in its spatialization as a response to scarcity and memory

Um Jardim na Mata dos Medos : ou da análise inventiva do pictoresco

This text discusses the project for a garden by Gonçalo Ribeiro-Telles that argues for a different possibility of creating a garden as landscape continuum and exploring picturesque as an apparatus to expand the experience of the place

Silêncio Parlante [Silence Parlant]

The text elaborates on the idea of the void in cultural and urban context as openness

An interview with Eduardo Souto de Moura [艾德瓦尔多·苏托·德·莫拉访谈]

This text is the outcome of a conversation with Eduardo Souto de Moura and relates to its practice and questions the dimension of Architecture in theoretical and practice terms

Manuel Aires Mateus : an architecture for the art of life [曼努埃尔·艾利斯·马特乌斯：建筑，为了生活的艺术]

This text is the outcome of a conversation with Manuel Aires Mateus (Aires Mateus Arquitectos) and discusses the importance of architecture and memory in contemporary architectural productions

Irregular meal timing is associated with helicobacter pylori infection and gastritis

Background Helicobacter pylori (HP) is associated with chronic gastritis and gastric cancer, and more than half of the world’s population is chronically infected. The aim of this retrospective study was to investigate whether an irregular meal pattern is associated with increased risk of gastritis and HP infection. Methods The study involved 323 subjects, divided into three groups: subjects with HP infection and gastritis, with gastritis, and a control group. Subjects were interviewed on eating habits and meal timing. Multivariate logistic regression was used to compare groups. Adjusted odds ratios (OR) were derived controlling for gender, age, stress and probiotic consumption. Results Subjects who deviated from their regular meals by 2 hours or more had a significantly higher incidence of HP infection with gastritis (adjusted OR= 13.3, 95% CI 5.3–33.3, p<0.001) and gastritis (adjusted OR=6.1, 95% CI 2.5–15.0, p<0.001). Subjects who deviated their meals by 2 hours or more, twice or more per week, had an adjusted OR of 6.3 and 3.5 of acquiring HP infection with gastritis (95% CI 2.6–15.2, p<0.001) and gastritis (95% CI 1.5–8.5, p<0.001) respectively. Conclusion Frequent deviation in meal timing over a prolonged period appears associated with increased risk of developing HP infection and gastritis.