Fractal assembly of micrometre-scale DNA origami arrays with arbitrary patterns

Self-assembled DNA nanostructures enable nanometre-precise patterning that can be used to create programmable molecular machines and arrays of functional materials. DNA origami is particularly versatile in this context because each DNA strand in the origami nanostructure occupies a unique position and can serve as a uniquely addressable pixel. However, the scale of such structures has been limited to about 0.05 square micrometres, hindering applications that demand a larger layout and integration with more conventional patterning methods. Hierarchical multistage assembly of simple sets of tiles can in principle overcome this limitation, but so far has not been sufficiently robust to enable successful implementation of larger structures using DNA origami tiles. Here we show that by using simple local assembly rules that are modified and applied recursively throughout a hierarchical, multistage assembly process, a small and constant set of unique DNA strands can be used to create DNA origami arrays of increasing size and with arbitrary patterns. We illustrate this method, which we term ‘fractal assembly’, by producing DNA origami arrays with sizes of up to 0.5 square micrometres and with up to 8,704 pixels, allowing us to render images such as the Mona Lisa and a rooster. We find that self-assembly of the tiles into arrays is unaffected by changes in surface patterns on the tiles, and that the yield of the fractal assembly process corresponds to about 0.95^(m − 1) for arrays containing m tiles. When used in conjunction with a software tool that we developed that converts an arbitrary pattern into DNA sequences and experimental protocols, our assembly method is readily accessible and will facilitate the construction of sophisticated materials and devices with sizes similar to that of a bacterium using DNA nanostructures

MSH6 germline mutations in early-onset colorectal cancer patients without family history of the disease

Germline MLH1 and MSH2 mutations are scarce in young colorectal cancer patients with negative family history of the disease. To evaluate the contribution of germline MSH6 mutations to early-onset colorectal cancer, we have analysed peripheral blood of 38 patients diagnosed with this disease before 45 years of age and who presented no family history of hereditary nonpolyposis colorectal cancer-related cancers. Blood samples from 108 healthy volunteers were analysed for those genetic alterations suspected to affect the function of MSH6. Of the seven (18.4%) MSH6 alterations found, we have identified three novel germline mutations, one 8 bp deletion leading to a truncated protein and two missense mutations resulting in the substitution of amino acids belonging to different polarity groups. High-frequency microsatellite instability was found in the patient with the MSH6 deletion, but not in the other 27 carcinomas analysed. No MLH1 promoter methylation was detected in tumour tissue. Our findings suggest that germline MSH6 mutations contribute to a subset of early-onset colorectal cancer. Further studies are warranted to understand the genetic and environmental factors responsible for the variable penetration of MSH6 germline mutations, as well as to identify other causes of early-onset colorectal cancer

Community-based management induces rapid recovery of a high-value tropical freshwater fishery

Tropical wetlands are highly threatened socio-ecological systems, where local communities rely heavily on aquatic animal protein, such as fish, to meet food security. Here, we quantify how a ‘win-win’ community-based resource management program induced stock recovery of the world’s largest scaled freshwater fish (Arapaima gigas), providing both food and income. We analyzed stock assessment data over eight years and examined the effects of protected areas, community-based management, and landscape and limnological variables across 83 oxbow lakes monitored along a ~500-km section of the Juruá River of Western Brazilian Amazonia. Patterns of community management explained 71.8% of the variation in arapaima population sizes. Annual population counts showed that protected lakes on average contained 304.8 (±332.5) arapaimas, compared to only 9.2 (±9.8) in open-access lakes. Protected lakes have become analogous to a high-interest savings account, ensuring an average annual revenue of US$10,601 per community and US$1046.6 per household, greatly improving socioeconomic welfare. Arapaima management is a superb window of opportunity in harmonizing the co-delivery of sustainable resource management and poverty alleviation. We show that arapaima management deserves greater attention from policy makers across Amazonian countries, and highlight the need to include local stakeholders in conservation planning of Amazonian floodplains

Global quantitative indices reflecting provider process-of-care: data-base derivation

Background: Controversy has attended the relationship between risk-adjusted mortality and process-of-care. There would be advantage in the establishment, at the data-base level, of global quantitative indices subsuming the diversity of process-of-care. Methods: A retrospective, cohort study of patients identified in the Australian and New Zealand Intensive Care Society Adult Patient Database, 1993-2003, at the level of geographic and ICU-level descriptors (n = 35), for both hospital survivors and non-survivors. Process-of-care indices were established by analysis of: (i) the smoothed time-hazard curve of individual patient discharge and determined by pharmaco-kinetic methods as area under the hazard-curve (AUC), reflecting the integrated experience of the discharge process, and time-to-peak-hazard (TMAX, in days), reflecting the time to maximum rate of hospital discharge; and (ii) individual patient ability to optimize output (as length-of-stay) for recorded data-base physiological inputs; estimated as a technical production-efficiency (TE, scaled [0,(maximum)1]), via the econometric technique of stochastic frontier analysis. For each descriptor, multivariate correlation-relationships between indices and summed mortality probability were determined. Results: The data-set consisted of 223129 patients from 99 ICUs with mean (SD) age and APACHE III score of 59.2(18.9) years and 52.7(30.6) respectively; 41.7% were female and 45.7% were mechanically ventilated within the first 24 hours post-admission. For survivors, AUC was maximal in rural and for-profit ICUs, whereas TMAX (≥ 7.8 days) and TE (≥ 0.74) were maximal in tertiary-ICUs. For non-survivors, AUC was maximal in tertiary-ICUs, but TMAX (≥ 4.2 days) and TE (≥ 0.69) were maximal in for-profit ICUs. Across descriptors, significant differences in indices were demonstrated (analysisof- variance, P ≤ 0.0001). Total explained variance, for survivors (0.89) and non-survivors (0.89), was maximized by combinations of indices demonstrating a low correlation with mortality probability. Conclusions: Global indices reflecting process of care may be formally established at the level of national patient databases. These indices appear orthogonal to mortality outcome.John L Moran, Patricia J Solomon and the Adult Database Management Committee (ADMC) of the Australian and New Zealand Intensive Care Society (ANZICS

Programmable disorder in random DNA tilings

Scaling up the complexity and diversity of synthetic molecular structures will require strategies that exploit the inherent stochasticity of molecular systems in a controlled fashion. Here we demonstrate a framework for programming random DNA tilings and show how to control the properties of global patterns through simple, local rules. We constructed three general forms of planar network—random loops, mazes and trees—on the surface of self-assembled DNA origami arrays on the micrometre scale with nanometre resolution. Using simple molecular building blocks and robust experimental conditions, we demonstrate control of a wide range of properties of the random networks, including the branching rules, the growth directions, the proximity between adjacent networks and the size distribution. Much as combinatorial approaches for generating random one-dimensional chains of polymers have been used to revolutionize chemical synthesis and the selection of functional nucleic acids, our strategy extends these principles to random two-dimensional networks of molecules and creates new opportunities for fabricating more complex molecular devices that are organized by DNA nanostructures

The adaptation of the Affective Norms for English Words (ANEW) for European Portuguese

This study presents the adaptation of the Affective Norms for English Words (ANEW; Bradley & Lang, 1999a) for European Portuguese (EP). The EP adaptation of the ANEW was based on the affective ratings made by 958 college students who were EP native speakers. Participants assessed about 60 words by considering the affective dimensions of valence, arousal, and dominance, using the Self-Assessment Manikin (SAM) in either a paper-and-pencil and a web survey procedures. Results of the adaptation of the ANEW for EP are presented. Furthermore, the differences between EP, American (Bradley & Lang, 1999a), and Spanish (Redondo, Fraga, Padrón, & Comesaña, 2007) standardizations were explored. Results showed that the ANEW words were understood in a similar way by EP, American, and Spanish subjects, although some sex and cross-cultural differences were observed. The EP adaptation of the ANEW is shown to be a valid and useful tool that will allow researchers to control and/or manipulate the affective properties of stimuli as well as to develop cross-linguistic studies. The normative values of EP adaptation of the ANEW can be downloaded at http://brm.psychonomic-journals.org/content/supplemental.COMPETE - Programa Operacional Factores de CompetitividadeFundo Europeu de Desenvolvimento Regional - FEDERQuadro de Referência Estratégico Nacional - QRENFundação para a Ciência e a Tecnologia (FCT) - research project “Procura Palavras (P-Pal ): A software program for deriving objective and subjective psycholinguistic indices for European Portuguese words

Contrasting predictors of poor antiretroviral therapy outcomes in two South African HIV programmes: a cohort study

BACKGROUND: Many national antiretroviral therapy (ART) programmes encourage providers to identify and address baseline factors associated with poor treatment outcomes, including modifiable adherence-related behaviours, before initiating ART. However, evidence on such predictors is scarce, and providers judgement may often be inaccurate. To help address this evidence gap, this observational cohort study examined baseline factors potentially predictive of poor treatment outcomes in two ART programmes in South Africa, with a particular focus on determinants of adherence. METHODS: Treatment-naïve patients starting ART were enrolled from a community and a workplace ART programme. Potential baseline predictors associated with poor treatment outcomes (defined as viral load > 400 copies/ml or having discontinued treatment by six months) were assessed using logistic regression. Exposure variables were organised for regression analysis using a hierarchical framework. RESULTS: 38/227 (17%) of participants in the community had poor treatment outcomes compared to 47/117 (40%) in the workplace. In the community, predictors of worse outcomes included: drinking more than 20 units of alcohol per week, having no prior experience of chronic medications, and consulting a traditional healer in the past year (adjusted odds ratio [aOR] 15.36, 95% CI 3.22-73.27; aOR 2.30, 95%CI 1.00-5.30; aOR 2.27, 95% CI 1.00-5.19 respectively). Being male and knowing someone on ART were associated with better outcomes (aOR 0.25, 95%CI 0.09-0.74; aOR 0.44, 95%CI 0.19-1.01 respectively). In the workplace, predictors of poor treatment outcomes included being uncertain about the health effects of ART and a traditional healer's ability to treat HIV (aOR 7.53, 95%CI 2.02-27.98; aOR 4.40, 95%CI 1.41-13.75 respectively). Longer pre-ART waiting time (2-12 weeks compared to <2 weeks) predicted better treatment outcomes (aOR 0.13, 95% CI 0.03-0.56). CONCLUSION: Baseline predictors of poor treatment outcomes were largely unique to each programme, likely reflecting different populations and pathways to HIV care. In the workplace, active promotion of HIV testing may have extended ART to individuals who, without provider initiation, would not have spontaneously sought care. As provider-initiated testing makes ART available to individuals less motivated to seek care, patients may need additional adherence support, especially addressing uncertainty about the health benefits of ART