Subtle Recognition of 14-Base Pair DNA Sequences via Threading Polyintercalation

ABSTRACT: Small molecules that bind DNA in a sequence-specific manner could act as antibiotic, antiviral, or anticancer agents because of their potential ability to manipulate gene expression. Our laboratory has developed threading poly-intercalators based on 1,4,5,8-naphthalene diimide (NDI) units connected in a head-to-tail fashion by flexible peptide linkers. Previously, a threading tetraintercalator composed of alternating minor−major−minor groove-binding modules was shown to bind specifically to a 14 bp DNA sequence with a dissociation half-life of 16 days [Holman, G. G., et al. (2011) Nat. Chem. 3, 875−881]. Herein are described new NDI-based tetraintercalators with a different major groove-binding module and a reversed N to C directionality of one of the minor groove-binding modules. DNase I footprinting and kinetic analyses revealed that these new tetraintercalators are able to discriminate, by as much as 30-fold, 14 bp DNA binding sites that differ by 1 or 2 bp. Relative affinities were found to correlate strongly with dissociation rates, while overall C2 symmetry in the DNA-binding molecule appeared to contribute to enhanced association rates

On the interpretation of removable interactions: A survey of the field 33 years after Loftus

In a classic 1978 Memory &Cognition article, Geoff Loftus explained why noncrossover interactions are removable. These removable interactions are tied to the scale of measurement for the dependent variable and therefore do not allow unambiguous conclusions about latent psychological processes. In the present article, we present concrete examples of how this insight helps prevent experimental psychologists from drawing incorrect conclusions about the effects of forgetting and aging. In addition, we extend the Loftus classification scheme for interactions to include those on the cusp between removable and nonremovable. Finally, we use various methods (i.e., a study of citation histories, a questionnaire for psychology students and faculty members, an analysis of statistical textbooks, and a review of articles published in the 2008 issue of Psychology andAging) to show that experimental psychologists have remained generally unaware of the concept of removable interactions. We conclude that there is more to interactions in a 2 × 2 design than meets the eye

Understanding cyclic seismicity and ground deformation patterns at volcanoes: intriguing lessons from Tungurahua volcano, Ecuador

Cyclic seismicity and ground deformation patterns are observed on many volcanoes worldwide where seismic swarms and the tilt of the volcanic flanks provide sensitive tools to assess the state of volcanic activity. Ground deformation at active volcanoes is often interpreted as pressure changes in a magmatic reservoir, and tilt is simply translated accordingly into inflation and deflation of such a reservoir. Tilt data recorded by an instrument in the summit area of Tungurahua volcano in Ecuador, however, show an intriguing and unexpected behaviour on several occasions: prior to a Vulcanian explosion when a pressurisation of the system would be expected, the tilt signal declines significantly, hence indicating depressurisation. At the same time, seismicity increases drastically. Envisaging that such a pattern could carry the potential to forecast Vulcanian explosions on Tungurahua, we use numerical modelling and reproduce the observed tilt patterns in both space and time. We demonstrate that the tilt signal can be more easily explained as caused by shear stress due to viscous flow resistance, rather than by pressurization of the magmatic plumbing system. In general, our numerical models prove that if magma shear viscosity and ascent rate are high enough, the resulting shear stress is sufficient to generate a tilt signal as observed on Tungurahua. Furthermore, we address the interdependence of tilt and seismicity through shear stress partitioning and suggest that a joint interpretation of tilt and seismicity can shed new light on the eruption potential of silicic volcanoes

The SPARC Toroidal Field Model Coil Program

The SPARC Toroidal Field Model Coil (TFMC) Program was a three-year effort between 2018 and 2021 that developed novel Rare Earth Yttrium Barium Copper Oxide (REBCO) superconductor technologies and then successfully utilized these technologies to design, build, and test a first-in-class, high-field (~20 T), representative-scale (~3 m) superconducting toroidal field coil. With the principal objective of demonstrating mature, large-scale, REBCO magnets, the project was executed jointly by the MIT Plasma Science and Fusion Center (PSFC) and Commonwealth Fusion Systems (CFS). The TFMC achieved its programmatic goal of experimentally demonstrating a large-scale high-field REBCO magnet, achieving 20.1 T peak field-on-conductor with 40.5 kA of terminal current, 815 kN/m of Lorentz loading on the REBCO stacks, and almost 1 GPa of mechanical stress accommodated by the structural case. Fifteen internal demountable pancake-to-pancake joints operated in the 0.5 to 2.0 nOhm range at 20 K and in magnetic fields up to 12 T. The DC and AC electromagnetic performance of the magnet, predicted by new advances in high-fidelity computational models, was confirmed in two test campaigns while the massively parallel, single-pass, pressure-vessel style coolant scheme capable of large heat removal was validated. The REBCO current lead and feeder system was experimentally qualified up to 50 kA, and the crycooler based cryogenic system provided 600 W of cooling power at 20 K with mass flow rates up to 70 g/s at a maximum design pressure of 20 bar-a for the test campaigns. Finally, the feasibility of using passive, self-protection against a quench in a fusion-scale NI TF coil was experimentally assessed with an intentional open-circuit quench at 31.5 kA terminal current.Comment: 17 pages 9 figures, overview paper and the first of a six-part series of papers covering the TFMC Progra

Degradation of tetracycline, sulfamethazine, and tylosin in soil from prairie strips and row crops in Iowa

The livestock industry in the United States relies on antibiotics for disease prevention and treatment. As a result, antibiotic-laden manure is frequently applied to farmland to recycle nutrients. In the soil environment, antibiotics may accumulate and create selective pressure for antibiotic resistance in bacteria or travel to nearby water resources. This in vitro incubation study evaluated whether prairie buffer strips on farmland enhance degradation of three antibiotics—tetracycline, sulfamethazine, and tylosin—compared with degradation in soil from row crops adjacent to the strips. Soil from prairie strips of varying establishment ages and adjacent row crops were evaluated from three central Iowa sampling locations. Antibiotics mixed with swine manure slurry were added to soils at a starting concentration (10 μg kg–1) that reflects common veterinary antibiotic concentrations in soil and runoff after manure application. Antibiotic concentrations were quantified at six time points throughout a 72-d incubation period and fit to a first-order model to calculate decay rate constants and half-lives. The mean half-life for tetracycline was 0.54 d longer in prairie strip soil than row crop soil, whereas sulfamethazine and tylosin demonstrated no significant difference in persistence in strip or crop soil. Time since the establishment of the prairie strip did not affect antibiotic persistence. Concentrations of each antibiotic decreased to near-background levels throughout the incubation period. This study suggests that prairie strips do not consistently enhance antibiotic degradation in farm fields, but that antibiotics are unlikely to persist throughout the growing season in soil under strip or crop management.This article is published as Iverson, Alyssa N., Thomas B. Moorman, Michelle L. Soupir, and Amy J. Morrow. "Degradation of tetracycline, sulfamethazine, and tylosin in soil from prairie strips and row crops in Iowa." Agrosystems, Geosciences & Environment 5, no. 1 (2022): e20224. DOI: 10.1002/agg2.20224. Copyright 2022 The Author(s). Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0). Posted with permission

Multiple Genotypes of Influenza B Virus Circulated between 1979 and 2003

The segmented genome of influenza B virus allows exchange of gene segments between cocirculating strains. Through this process of reassortment, diversity is generated by the mixing of genes between viruses that differ in one or more gene segments. Phylogenetic and evolutionary analyses of all 11 genes of 31 influenza B viruses isolated from 1979 to 2003 were used to study the evolution of whole genomes. All 11 genes diverged into two new lineages prior to 1987. All genes except the NS1 gene were undergoing linear evolution, although the rate of evolution and the degree to which nucleotide changes translated into amino acid changes varied between lineages and by gene. Frequent reassortment generated 14 different genotypes distinct from the gene constellation of viruses circulating prior to 1979. Multiple genotypes cocirculated in some locations, and a sequence of reassortment events over time could not be established. The surprising diversity of the viruses, unrestricted mixing of lineages, and lack of evidence for coevolution of gene segments do not support the hypothesis that the reassortment process is driven by selection for functional differences