A New Architecture for DNA-Templated Synthesis in Which Abasic Sites Protect Reactants from Degradation.

The synthesis of artificial sequence-defined polymers that match and extend the functionality of proteins is an important goal in materials science. One way of achieving this is to program a sequence of chemical reactions between precursor building blocks by means of attached oligonucleotide adapters. However, hydrolysis of the reactive building blocks has so far limited the length and yield of product that can be obtained using DNA-templated reactions. Here, we report an architecture for DNA-templated synthesis in which reactants are tethered at internal abasic sites on opposite strands of a DNA duplex. We show that an abasic site within a DNA duplex can protect a nearby thioester from degradation, significantly increasing the yield of a DNA-templated reaction. This protective effect has the potential to overcome the challenges associated with programmable, sequence-controlled synthesis of long non-natural polymers by extending the lifetime of the reactive building blocks.

Data-driven enzyme immobilisation: a case study using DNA to immobilise galactose oxidase.

Biocatalysis has the potential to enable green chemistry. New methods of enzyme immobilisation will be required to improve enzyme stability, product purification, and compatibility of different enzymes in the same reaction conditions. Deoxyribonucleic acid (DNA) stands out among supramolecular scaffolds, as simple Watson-Crick base-pairing rules can be used to rationally design a unique nanoscale environment around each individual enzyme in a cascade. Enhancements of enzyme activity and stability on DNA nanostructures have previously been reported, but never in the context of industrially relevant chemical syntheses or reaction conditions. Here, the authors show DNA can enhance the activity and stability of a galactose oxidase mutant, which could be used in a cascade to produce bioplastics from lignin. The enzyme was enhanced in the cell-free extract, which to their knowledge has not been shown before for any enzymes on DNA. This is significant because crude biocatalytic reactions are vastly more cost-effective. This opens the door to further work on multienzyme cascades by tuning the properties of individual enzymes.

Developing a graduate training program in Synthetic Biology: SynBioCDT.

This article presents the experience of a team of students and academics in developing a post-graduate training program in the new field of Synthetic Biology. Our Centre for Doctoral Training in Synthetic Biology (SynBioCDT) is an initiative funded by the United Kingdom's Research Councils of Engineering and Physical Sciences (EPSRC), and Biotechnology and Biological Sciences (BBSRC). SynBioCDT is a collaboration between the Universities of Oxford, Bristol and Warwick, and has been successfully running since 2014, training 78 students in this field. In this work, we discuss the organization of the taught, research and career development training. We also address the challenges faced when offering an interdisciplinary program. The article concludes with future directions to continue the development of the SynBioCDT.

Neonicotinoid exposure disrupts bumblebee nest behavior, social networks, and thermoregulation.

Neonicotinoid pesticides can negatively affect bee colonies, but the behavioral mechanisms by which these compounds impair colony growth remain unclear. Here, we investigate imidacloprid's effects on bumblebee worker behavior within the nest, using an automated, robotic platform for continuous, multicolony monitoring of uniquely identified workers. We find that exposure to field-realistic levels of imidacloprid impairs nursing and alters social and spatial dynamics within nests, but that these effects vary substantially with time of day. In the field, imidacloprid impairs colony thermoregulation, including the construction of an insulating wax canopy. Our results show that neonicotinoids induce widespread disruption of within-nest worker behavior that may contribute to impaired growth, highlighting the potential of automated techniques for characterizing the multifaceted, dynamic impacts of stressors on behavior in bee colonies.

Author Correction: Spatial fidelity of workers predicts collective response to disturbance in a social insect.

The original version of the Article contained incorrect citation information in reference 67. The reference should read "Russell, A. L., Morrison, S. J., Moschonas, E. H. & Papaj, D. R. Patterns of pollen and nectar foraging specialization by bumblebees over multiple timescales using RFID. Sci. Rep. 7, 1-13 (2017)." This error has now been corrected in the PDF and HTML versions of the Article.

Spatial fidelity of workers predicts collective response to disturbance in a social insect.

Individuals in social insect colonies cooperate to perform collective work. While colonies often respond to changing environmental conditions by flexibly reallocating workers to different tasks, the factors determining which workers switch and why are not well understood. Here, we use an automated tracking system to continuously monitor nest behavior and foraging activity of uniquely identified workers from entire bumble bee (Bombus impatiens) colonies foraging in a natural outdoor environment. We show that most foraging is performed by a small number of workers and that the intensity and distribution of foraging is actively regulated at the colony level in response to forager removal. By analyzing worker nest behavior before and after forager removal, we show that spatial fidelity of workers within the nest generates uneven interaction with relevant localized information sources, and predicts which workers initiate foraging after disturbance. Our results highlight the importance of spatial fidelity for structuring information flow and regulating collective behavior in social insect colonies.

Patient perceptions of breast biopsy procedures for screen-detected lesions.

OBJECTIVE: This study was undertaken to compare patient perceptions of 2 common image-guided breast biopsy procedures on 3 main outcomes: decision making about which procedure to undergo, its convenience, and its side effects. METHODS: Women who had either an excisional or ultrasound-guided core needle breast biopsy in 1997 for a screen-detected lesion had telephone interviews 1 to 3 months after the biopsy. Bivariate associations were tested by using chi(2) and t test statistics. Mulitvariate analyses were used to control for effects of demographic characteristics. RESULTS: Most women (66%) could not remember being offered a choice of procedures, and of those who did have a choice, a higher proportion had an excisional biopsy. Only 2% reported being told the cost of the biopsy procedure. Women who had an excisional biopsy compared with those who had undergone a core needle biopsy reported statistically more hours and days off from work and reported more side effects 1 to 3 days after the biopsy (P<.05). Associations between side effects and type of biopsy procedure were unchanged when adjustment was made for demographic characteristics. CONCLUSION: Women who had the ultrasound-guided needle biopsy reported significantly fewer side effects and needed less time off from work. When a suspicious lesion is noticed on a screening mammogram, it is important that women and their physicians discuss the benefits and risks of the various biopsy procedures before deciding how to proceed, allowing for informed choice.

Influence of breast cancer histology on the relationship between ultrasound and pathology tumor size measurements.

Establishing an accurate primary invasive breast cancer size is crucial for patient management. Although ultrasonographic measurement is reported to correlate reliably with the gold standard pathology measurement, few authors have examined the influence of histologic subtype on ultrasound measurement. The common subtypes of invasive breast carcinoma, ductal and lobular, have different growth patterns, which may influence the ability of ultrasound to predict pathologic size. For this analysis, ultrasound and pathology reports were retrospectively reviewed for 204 women with 210 invasive breast cancers, including 129 ductal, 41 lobular, and 40 mixed pattern ductal and lobular carcinomas. For each tumor, the largest pathology and ultrasound dimensions were compared using Pearson's correlations, linear regression, paired t-tests and Wilcoxon signed ranks tests, stratified by histologic subtype. The Hodges-Lehmann approach was used to obtain 95% confidence intervals (CI) for median difference of the sizes. Ultrasonography consistently underestimated pathologic tumor size; the overall median difference was 3.5 mm (CI: 2.5-4.0 mm) and for subtypes: 2.5 mm (CI: 1.5-3.5 mm) for ductal pattern; 3.0 mm (CI: 1.5-4.5 mm) for mixed pattern; and in contrast, 7.5 mm (CI: 5.0-13.5 mm) for lobular pattern tumors. Significant correlations of similar magnitude, were observed between size measurements for ductal, lobular, and mixed subtypes (r=0.816, 0.811 and 0.672, respectively; all P<0.001); however, linear regression models differed between subtypes. Although practical and widely available, ultrasonography tends to underestimate pathologic tumor size. The size difference may be large for lobular carcinomas, potentially influencing stage; differences are less pronounced for ductal and mixed subtypes. Pathologic tumor size can be estimated from the ultrasonographic measurement, particularly if the histologic tumor subtype is known. The results of this study underscore the continued benefit of pretreatment tumor histology.

Increase in cancer detection and recall rates with independent double interpretation of screening mammography.

OBJECTIVE: This study reports the increase in cancer detection that resulted from independent double interpretation of screening mammography. Although screening mammography is used to detect occult breast cancer, its sensitivity and specificity are limited. Double interpretation of screening mammograms is one proven method used to improve detection, with studies reporting a 5-15% increase in cancer detection. MATERIALS AND METHODS: Two radiologists independently double-interpreted 25,369 screening mammograms performed from November 1998 to April 2000. The second reviewer could add but could not delete recalls. The subsequent additional diagnostic imaging was performed in the same way whether generated from the first or the second reviewer. The outcome of each case was determined. The cancer detection rate and sensitivity are reported. RESULTS: Double interpretation of screening mammograms detected 143 breast malignancies. The second reviewer found nine (6.3%) of 143 cancers and all except one were stage 0 or I. The sensitivity increased from 74.4% to 79.4% with double interpretation. The second reviewer contributed 371 of the 3591 total recalls, increasing the absolute rate of recalls by 1.5% (371/25,369) and the relative rate by 11.5% (371/3220). Six hundred seventy-two total biopsies were performed; 38 were generated by the second interpretation. CONCLUSION: The relative increase in cancer detection as a result of the second reviewer is 6.3%, similar to the 5-15% reported in the literature. All but one of the nine additional cancers detected were in the early stages.