334 research outputs found
Assessing the cost-effectiveness of DNA origami nanostructures for targeted delivery of anti-cancer drugs to tumours
Incompatibility of DFHBI based fluorescent RNA aptamers with particular commercial cell-free expression systems
Modelling DNA Origami Self-Assembly at the Domain Level
We present a modelling framework, and basic model parameterization, for the
study of DNA origami folding at the level of DNA domains. Our approach is
explicitly kinetic and does not assume a specific folding pathway. The binding
of each staple is associated with a free-energy change that depends on staple
sequence, the possibility of coaxial stacking with neighbouring domains, and
the entropic cost of constraining the scaffold by inserting staple crossovers.
A rigorous thermodynamic model is difficult to implement as a result of the
complex, multiply connected geometry of the scaffold: we present a solution to
this problem for planar origami. Coaxial stacking and entropic terms,
particularly when loop closure exponents are taken to be larger than those for
ideal chains, introduce interactions between staples. These cooperative
interactions lead to the prediction of sharp assembly transitions with notable
hysteresis that are consistent with experimental observations. We show that the
model reproduces the experimentally observed consequences of reducing staple
concentration, accelerated cooling and absent staples. We also present a
simpler methodology that gives consistent results and can be used to study a
wider range of systems including non-planar origami
Using ultraviolet absorption spectroscopy to study nanoswitches based on non-canonical DNA structures
Non-canonical forms of DNA are attracting increasing interest for applications in nanotechnology. It is frequently convenient to characterize DNA molecules using a label-free approach such as ultraviolet absorption spectroscopy. In this paper we present the results of our investigation into the use of this technique to probe the folding of quadruplex and triplex nanoswitches. We confirmed that four G-quartets were necessary for folding at sub-mM concentrations of potassium and found that the wrong choice of sequence for the linker between G-tracts could dramatically disrupt folding, presumably due to the presence of kinetic traps in the folding landscape. In the case of the triplex nanoswitch we examined, we found that the UV spectrum showed a small change in absorbance when a triplex was formed. We anticipate that our results will be of interest to researchers seeking to design DNA nanoswitches based on quadruplexes and triplexes
Integration of vanHAX downstream of a ribosomal RNA operon restores vancomycin resistance in a susceptible Enterococcus faecium strain
During the genomic characterisation of Enterococcus faecium strains (nâ=â39) collected in a haematology ward, we identified an isolate (OI25), which contained vanA-type vancomycin resistance genes but was phenotypically susceptible to vancomycin. OI25 could revert to resistance when cultured in the presence of vancomycin and was thus considered to be vancomycin-variable. Long-read sequencing was used to identify structural variations within the vancomycin resistance region of OI25 and to uncover its resistance reversion mechanism. We found that OI25 has a reduced ability to positively regulate expression of the vanHAX genes in the presence of vancomycin, which was associated with the insertion of an IS6-family element within the promoter region and the first 50âbp of the vanR gene. The vancomycin-resistant revertant isolates constitutively expressed vanHAX genes at levels up to 36,000-fold greater than OI25 via co-transcription with a ribosomal RNA operon. The vancomycin-resistant revertants did not exhibit a significant growth defect. During VRE outbreaks, attention should be paid to contemporaneous vancomycin-susceptible strains as these may carry silent vancomycin resistance genes that can be activated through genomic rearrangements
Dimensions and Global Twist of Single-Layer DNA Origami Measured by Small-Angle X-ray Scattering
The
rational design of complementary DNA sequences can be used
to create nanostructures that self-assemble with nanometer precision.
DNA nanostructures have been imaged by atomic force microscopy and
electron microscopy. Small-angle X-ray scattering (SAXS) provides
complementary structural information on the ensemble-averaged state
of DNA nanostructures in solution. Here we demonstrate that SAXS can
distinguish between different single-layer DNA origami tiles that
look identical when immobilized on a mica surface and imaged with
atomic force microscopy. We use SAXS to quantify the magnitude of
global twist of DNA origami tiles with different crossover periodicities:
these measurements highlight the extreme structural sensitivity of
single-layer origami to the location of strand crossovers. We also
use SAXS to quantify the distance between pairs of gold nanoparticles
tethered to specific locations on a DNA origami tile and use this
method to measure the overall dimensions and geometry of the DNA nanostructure
in solution. Finally, we use indirect Fourier methods, which have
long been used for the interpretation of SAXS data from biomolecules,
to measure the distance between DNA helix pairs in a DNA origami nanotube.
Together, these results provide important methodological advances
in the use of SAXS to analyze DNA nanostructures in solution and insights
into the structures of single-layer DNA origami
Menopausal Quality of Life: A RCT of Yoga, Exercise and Omega-3 Supplements
Objectiveâ
Determine efficacy of three non-hormonal therapies for improving menopause-
related quality of life (QOL) in women with vasomotor symptoms (VMS).
Methodsâ
12-week 3Ă2 randomized, controlled, factorial design trial. Peri- and postmenopausal
women, ages 40-62 years, were randomized to yoga (n=107), exercise (n=106), or usual activity
(n=142), and also randomized to double-blind comparison of omega-3 (n=177) or placebo (n=178)
capsules. Interventions: 1) weekly 90-minute yoga classes with daily at-home practice; 2)
individualized facility-based aerobic exercise training 3 times/week; and 3) 0.615 gram omega-3
supplement, 3 times/day. Outcomes: Menopausal Quality of Life Questionnaire (MENQOL) total
and domain (VMS, psychosocial, physical and sexual) scores.
Resultsâ
Among 355 randomized women, average age 54.7 years, 338 (95%) completed 12-
week assessments. Mean baseline VMS frequency was 7.6/day and mean baseline total MENQOL
score was 3.8 (range 1-8 from better to worse) with no between-group differences. For yoga
compared to usual activity, baseline to 12-week improvements were seen for MENQOL total -0.3
(95% CI -0.6 to 0.0, p=0.02), and VMS (p=0.02) and sexuality (p=0.03) domain scores. For
exercise and omega-3 compared to controls, improvements in baseline to 12-week total MENQOL
scores were not observed. Exercise showed benefit in the MENQOL physical domain score at 12-
weeks (p=0.02).
Conclusionâ
All women become menopausal and many seek medical advice on ways to
improve quality of life; little evidence-based information exists. We found, among healthy
sedentary menopausal women, yoga appears to improve menopausal QOL - the clinical
significance of our finding is uncertain due to modest effect
Canalization and developmental stability in the Brachyrrhine mouse
The semi-dominant Br mutation affects presphenoid growth, producing the facial retrognathism and globular neurocranial vault that characterize heterozygotes. We analysed the impact of this mutation on skull shape, comparing heterozygotes to wildtype mice, to determine if the effects are skull-wide or confined to the sphenoid region targeted by the mutation. In addition, we examined patterns of variability of shape for the skull as a whole and for three regions (basicranium, face and neurocranium). We found that the Br mice differed significantly from wildtype mice in skull shape in all three regions as well as in the shape of the skull as a whole. However, the significant increases in variance and fluctuating asymmetry were found only in the basicranium of mutant mice. These results suggest that the mutation has a significant effect on the underlying developmental architecture of the skull, which produces an increase in phenotypic variability that is localized to the anatomical region in which the mean phenotype is most dramatically affected. These results suggest that the same developmental mechanisms that produce the change in phenotypic mean also produce the change in variance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75710/1/j.1469-7580.2006.00527.x.pd
Adaptive Manufacturing for Healthcare During the COVID-19 Emergency and Beyond
During the COVID-19 pandemic, global health services have faced unprecedented demands. Many key workers in health and social care have experienced crippling shortages of personal protective equipment, and clinical engineers in hospitals have been severely stretched due to insufficient supplies of medical devices and equipment. Many engineers who normally work in other sectors have been redeployed to address the crisis, and they have rapidly improvised solutions to some of the challenges that emerged, using a combination of low-tech and cutting-edge methods. Much publicity has been given to efforts to design new ventilator systems and the production of 3D-printed face shields, but many other devices and systems have been developed or explored. This paper presents a description of efforts to reverse engineer or redesign critical parts, specifically a manifold for an anaesthesia station, a leak port, plasticware for COVID-19 testing, and a syringe pump lock box. The insights obtained from these projects were used to develop a product lifecycle management system based on Aras Innovator, which could with further work be deployed to facilitate future rapid response manufacturing of bespoke hardware for healthcare. The lessons learned could inform plans to exploit distributed manufacturing to secure back-up supply chains for future emergency situations. If applied generally, the concept of distributed manufacturing could give rise to â21st century cottage industriesâ or ânanofactories,â where high-tech goods are produced locally in small batches
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