Real-time single-molecule imaging reveals a direct interaction between UvrC and UvrB on DNA tightropes

Nucleotide excision DNA repair is mechanistically conserved across all kingdoms of life. In prokaryotes, this multi-enzyme process requires six proteins: UvrA?D, DNA polymerase I and DNA ligase. To examine how UvrC locates the UvrB? DNA pre-incision complex at a site of damage, we have labeled UvrB and UvrC with different colored quantum dots and quantitatively observed their interactions with DNA tightropes under a variety of solution conditions using oblique angle fluorescence imaging. Alone, UvrC predominantly interacts statically with DNA at low salt. Surprisingly, however, UvrC and UvrB together in solution bind to form the previously unseen UvrBC complex on duplex DNA. This UvrBC complex is highly motile and engages in unbiased one-dimensional diffusion. To test whether UvrB makes direct contact with the DNA in the UvrBC?DNA complex, we investigated three UvrB mutants: Y96A, a b-hairpin deletion and D338N. These mutants affected the motile properties of the UvrBC complex, indicating that UvrB is in intimate contact with the DNA when bound to UvrC. Given the in vivo excess of UvrB and the abundance of UvrBC in our experiments, this newly identified complex is likely to be the predominant form of UvrC in the cell. © 2013 The Author(s)

Large-amplitude driving of a superconducting artificial atom: Interferometry, cooling, and amplitude spectroscopy

Superconducting persistent-current qubits are quantum-coherent artificial atoms with multiple, tunable energy levels. In the presence of large-amplitude harmonic excitation, the qubit state can be driven through one or more of the constituent energy-level avoided crossings. The resulting Landau-Zener-Stueckelberg (LZS) transitions mediate a rich array of quantum-coherent phenomena. We review here three experimental works based on LZS transitions: Mach-Zehnder-type interferometry between repeated LZS transitions, microwave-induced cooling, and amplitude spectroscopy. These experiments exhibit a remarkable agreement with theory, and are extensible to other solid-state and atomic qubit modalities. We anticipate they will find application to qubit state-preparation and control methods for quantum information science and technology.Comment: 13 pages, 5 figure

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The role of networks to overcome large-scale challenges in tomography : the non-clinical tomography users research network

Our ability to visualize and quantify the internal structures of objects via computed tomography (CT) has fundamentally transformed science. As tomographic tools have become more broadly accessible, researchers across diverse disciplines have embraced the ability to investigate the 3D structure-function relationships of an enormous array of items. Whether studying organismal biology, animal models for human health, iterative manufacturing techniques, experimental medical devices, engineering structures, geological and planetary samples, prehistoric artifacts, or fossilized organisms, computed tomography has led to extensive methodological and basic sciences advances and is now a core element in science, technology, engineering, and mathematics (STEM) research and outreach toolkits. Tomorrow's scientific progress is built upon today's innovations. In our data-rich world, this requires access not only to publications but also to supporting data. Reliance on proprietary technologies, combined with the varied objectives of diverse research groups, has resulted in a fragmented tomography-imaging landscape, one that is functional at the individual lab level yet lacks the standardization needed to support efficient and equitable exchange and reuse of data. Developing standards and pipelines for the creation of new and future data, which can also be applied to existing datasets is a challenge that becomes increasingly difficult as the amount and diversity of legacy data grows. Global networks of CT users have proved an effective approach to addressing this kind of multifaceted challenge across a range of fields. Here we describe ongoing efforts to address barriers to recently proposed FAIR (Findability, Accessibility, Interoperability, Reuse) and open science principles by assembling interested parties from research and education communities, industry, publishers, and data repositories to approach these issues jointly in a focused, efficient, and practical way. By outlining the benefits of networks, generally, and drawing on examples from efforts by the Non-Clinical Tomography Users Research Network (NoCTURN), specifically, we illustrate how standardization of data and metadata for reuse can foster interdisciplinary collaborations and create new opportunities for future-looking, large-scale data initiatives

Flexible Resources Key to Neighborhood Resilience for Children: A Scoping Review

Neighborhoods have been the focus of health researchers seeking to develop upstream strategies to mitigate downstream disease development. In recent years, neighborhoods have become a primary target in efforts to promote health and resilience following deleterious social conditions such as the climate crisis, extreme weather events, the global pandemic, and supply chain disruptions. Children are often the most vulnerable populations after experiencing unexpected shocks. To examine and describe conceptually the construct of Neighborhood Resilience, we conducted a comprehensive scoping review using the terms (“resilience” or “resiliency” or “resilient”) AND (“neighborhood”), utilizing MEDLINE (through PubMed) and CINAHL (through EBSCOhost) databases, to assess overall neighborhood themes that impact resilience. A total of 57 articles were extracted that met inclusion criteria. Extracted characteristics included study purpose, country of origin, key findings, environmental protective/risk factors. The analysis revealed a positive relationship between neighborhood resource density, neighborhood resiliency, and individual resiliency. This study reports the finding for studies with a population focus of pre-school age and school age children (1.5–18 years of age). Broadly, we identified that the primary goals regarding neighborhood resilience for childhood can be conceptualized as all activities and resources that (a) prevent trauma during childhood development and/or (b) mitigate or heal childhood trauma once it has occurred. This goal conceptually encompasses antecedents that increase protective factors and reduces risk factors for children and their families. This comprehensive look at the literature showed that a neighborhood’s ability to build, promote, and maintain resiliency is often largely dependent on the flexible resources (i.e., knowledge, money, power, prestige, and beneficial social connections) that are available