Binary control of enzymatic cleavage of DNA origami by structural antideterminants

Controlling DNA nanostructure interaction with protein is essential in developing nanodevices with programmable function, reactivity, and stability for biological and medical applications. Here, we show that the sequence-specific action of restriction endonucleases towards sharp triangular or rectangular DNA origami exhibits a novel, binary 'on/off' behaviour, as canonical recognition sites are either essentially fully reactive, or strongly resistant to enzymatic cutting. Moreover, introduction of structural defects in the sharp triangle can activate an otherwise unreactive site, with a site-to-defect distance of ∼50 nm. We argue that site reactivity is dependent upon programmable, mechanical coupling in the two-dimensional DNA origami, with specific structural elements, including DNA nicks and branches proximal to the sites that can function as negative(anti) determinants of reactivity. Empirically modelling the constraints to DNA degrees of freedom associated with each recognition site in the sharp triangle can rationalize the pattern of suppressed reactivity towards nine restriction endonucleases, in substantial agreement with the experimental results. These results provide a basis for a predictive understanding of structure-reactivity correlates of specific DNA nanostructures, which will allow a better understanding of the behaviour of nucleic acids under nanoscale confinement, as well as in the rational design of functional nanodevices based on self-assembling nucleic acids

Science Enabling Exploration: Using LRO to Prepare for Future Missions

Discoveries from LRO have transformed our understanding of the Moon, but LRO's instruments were originally designed to collect the measurements required to enable future lunar surface exploration. A high lunar exploration priority is the collection of new samples and their return to Earth for comprehensive analysis. The importance of sample return from South Pole-Aitken is well-established [Jolliff et al., this conference], but there are numerous other locations where sample return will yield important advances in planetary science. Using new LRO data, we have defined an achievability envelope based on the physical characteristics of successful lunar landing sites. Those results were then used to define 1km x 1km regions of interest where sample return could be executed, including: the basalt flows in Oceanus Procellarum (22.1N, 53.9W), the Gruithuisen Domes (36.1N, 39.7W), the Dewar cryptomare (2.2S, 166.8E), the Aristarchus pyroclastic deposit (24.8N, 48.5W), the Sulpicius Gallus formation (19.9N, 10.3E), the Sinus Aestuum pyroclastic deposit (5.2N, 9.2W), the Compton-Belkovich volcanic complex (61.5N, 99.9E), the Ina Irregular Mare Patch (18.7N, 5.3E), and the Marius Hills volcanic complex (13.4N, 55.9W). All of these locations represent safe landing sites where sample returns are needed to advance our understanding of the evolution of the lunar interior and the timescales of lunar volcanism. If LRO is still active when any future mission reaches the surface, LRO's capability to rapidly place surface activities into broader geologic context will provide operational advantages. LRO remains a unique strategic asset that continues to address the needs of future missions

Building on the Cornerstone: Destinations for Nearside Sample Return

Discoveries from LRO (Lunar Reconnaissance Orbiter) have transformed our knowledge of the Moon, but LRO's instruments were originally designed to collect the measurements required to enable future lunar surface exploration. Compelling science questions and critical resources make the Moon a key destination for future human and robotic exploration. Lunar surface exploration, including rovers and other landed missions, must be part of a balanced planetary science and exploration portfolio. Among the highest planetary exploration priorities is the collection of new samples and their return to Earth for more comprehensive analysis than can be done in-situ. The Moon is the closest and most accessible location to address key science questions through targeted sample return. The Moon is the only other planet from which we have contextualized samples, yet critical issues need to be addressed: we lack important details of the Moon's early and recent geologic history, the full compositional and age ranges of its crust, and its bulk composition

Identifying and Characterizing Impact Melt Outcrops in the Nectaris Basin

The Nectaris Basin is an 820-km diameter, multi-ring impact basin located on the near side of the Moon. Nectaris is a defining stratigraphic horizon based on relationships between ejecta units, giving its name to the Nectarian epoch of lunar history. Lunar basin chronology based on higher resolution LRO imagery and topography, while assigning some important basins like Serenitatis to pre-Nectarian time, were generally consistent with those previously derived. Based on this stratigraphy, at least 11 large basins formed in the time between Nectaris and Imbrium. The absolute age of Nectaris, therefore, is a crucial marker in the lunar time-stratigraphic sequence for understanding the impact flux on the Moon, and by extension, the entire inner solar system. For several decades, workers have attempted to constrain the age of the Nectaris basin through radiometric dating of lunar samples. However, there is little agreement on which samples in our collection represent Nectaris, if any, and what the correct radiometric age of such samples is. The importance of the age of Nectaris goes far beyond assigning a stratigraphic marker to lunar chronology. Several dynamical models use Nectaris as their pin date, so that this date becomes crucial in understanding the time-correlated effects in the rest of the solar system. The importance of the Nectaris basin age, coupled with its nearside, mid-latitude location, make remnants of the impact-melt sheet an attractive target for a future mission, either for in-situ dating or for sample return. We have started exploring this possibility. We have begun a consortium data-analysis effort bringing multiple datasets and analysis methods to bear on these putative impact-melt deposits to characterize their extent, elemental composition and mineralogy, maturity and geologic setting, and to identify potential landing sites that meet both operational safety and science requirements

Viruses: incredible nanomachines. New advances with filamentous phages

During recent decades, bacteriophages have been at the cutting edge of new developments in molecular biology, biophysics, and, more recently, bionanotechnology. In particular filamentous viruses, for example bacteriophage M13, have a virion architecture that enables precision building of ordered and defect-free two and three-dimensional structures on a nanometre scale. This could not have been possible without detailed knowledge of coat protein structure and dynamics during the virus reproduction cycle. The results of the spectroscopic studies conducted in our group compellingly demonstrate a critical role of membrane embedment of the protein both during infectious entry of the virus into the host cell and during assembly of the new virion in the host membrane. The protein is effectively embedded in the membrane by a strong C-terminal interfacial anchor, which together with a simple tilt mechanism and a subtle structural adjustment of the extreme end of its N terminus provides favourable thermodynamical association of the protein in the lipid bilayer. This basic physicochemical rule cannot be violated and any new bionanotechnology that will emerge from bacteriophage M13 should take this into account

Population genomics of marine zooplankton

Author Posting. © The Author(s), 2017. This is the author's version of the work. It is posted here for personal use, not for redistribution. The definitive version was published in Bucklin, Ann et al. "Population Genomics of Marine Zooplankton." Population Genomics: Marine Organisms. Ed. Om P. Rajora and Marjorie Oleksiak. Springer, 2018. doi:10.1007/13836_2017_9.The exceptionally large population size and cosmopolitan biogeographic distribution that distinguish many – but not all – marine zooplankton species generate similarly exceptional patterns of population genetic and genomic diversity and structure. The phylogenetic diversity of zooplankton has slowed the application of population genomic approaches, due to lack of genomic resources for closelyrelated species and diversity of genomic architecture, including highly-replicated genomes of many crustaceans. Use of numerous genomic markers, especially single nucleotide polymorphisms (SNPs), is transforming our ability to analyze population genetics and connectivity of marine zooplankton, and providing new understanding and different answers than earlier analyses, which typically used mitochondrial DNA and microsatellite markers. Population genomic approaches have confirmed that, despite high dispersal potential, many zooplankton species exhibit genetic structuring among geographic populations, especially at large ocean-basin scales, and have revealed patterns and pathways of population connectivity that do not always track ocean circulation. Genomic and transcriptomic resources are critically needed to allow further examination of micro-evolution and local adaptation, including identification of genes that show evidence of selection. These new tools will also enable further examination of the significance of small-scale genetic heterogeneity of marine zooplankton, to discriminate genetic “noise” in large and patchy populations from local adaptation to environmental conditions and change.Support was provided by the US National Science Foundation to AB and RJO (PLR-1044982) and to RJO (MCB-1613856); support to IS and MC was provided by Nord University (Norway)

Profiling of dynamics in protein–lipid–water systems: a time-resolved fluorescence study of a model membrane protein with the label BADAN at specific membrane depths

Profiles of lipid-water bilayer dynamics were determined from picosecond time-resolved fluorescence spectra of membrane-embedded BADAN-labeled M13 coat protein. For this purpose, the protein was labeled at seven key positions. This places the label at well-defined locations from the water phase to the center of the hydrophobic acyl chain region of a phospholipid model membrane, providing us with a nanoscale ruler to map membranes. Analysis of the time-resolved fluorescence spectroscopic data provides the characteristic time constant for the twisting motion of the BADAN label, which is sensitive to the local flexibility of the protein–lipid environment. In addition, we obtain information about the mobility of water molecules at the membrane–water interface. The results provide an unprecedented nanoscale profiling of the dynamics and distribution of water in membrane systems. This information gives clear evidence that the actual barrier of membranes for ions and aqueous solvents is located at the region of carbonyl groups of the acyl chains

Shape variability of the central sulcus in the developing brain: a longitudinal descriptive and predictive study in preterm infants

Despite growing evidence of links between sulcation and function in the adult brain, the folding dynamics, occurring mostly before normal-term-birth, is vastly unknown. Looking into the development of cortical sulci in infants can give us keys to address fundamental questions: what is the sulcal shape variability in the developing brain? When are the shape features encoded? How are these morphological parameters related to further functional development? In this study, we aimed to investigate the shape variability of the developing central sulcus, which is the frontier between the primary somatosensory and motor cortices. We studied a cohort of 71 extremely preterm infants scanned twice using MRI - once around 30 weeks post-menstrual age (w PMA) and once at term-equivalent age, around 40w PMA -, in order to quantify the sulcus's shape variability using manifold learning, regardless of age-group or hemisphere. We then used these shape descriptors to evaluate the sulcus's variability at both ages and to assess hemispheric and age-group specificities. This led us to propose a description of ten shape features capturing the variability in the central sulcus of preterm infants. Our results suggested that most of these features (8/10) are encoded as early as 30w PMA. We unprecedentedly observed hemispheric asymmetries at both ages, and the one captured at term-equivalent age seems to correspond with the asymmetry pattern previously reported in adults. We further trained classifiers in order to explore the predictive value of these shape features on manual performance at 5 years of age (handedness and fine motor outcome). The central sulcus's shape alone showed a limited but relevant predictive capacity in both cases. The study of sulcal shape features during early neurodevelopment may participate to a better comprehension of the complex links between morphological and functional organization of the developing brain