Highlights d A single chromatin substrate is torsionally softer than a braided substrate d Thus, DNA supercoiling should primarily partition to the front of a replisome d Yeast topo II shows a strong preference for a single chromatin substrate d Thus, torsional mechanics and topoisomerase activity coordinate synergistically

The advent of nanophotonic evanescent field trapping and transport platforms has permitted increasingly complex single molecule and single cell studies on-chip. Here, we present the next generation of nanophotonic Standing Wave Array Traps (nSWATs) representing a streamlined CMOS fabrication process and compact biocompatible design. These devices utilize silicon nitride (Si3N4) waveguides, operate with a bio-friendly 1064 nm laser, allow for several watts of input power with minimal absorption and heating, and are protected by an anticorrosive layer for sustained on-chip microelectronics in aqueous salt buffers. In addition, due to Si3N4’s negligible nonlinear effects, these devices can generate high stiffness traps while resolving sub-nanometer displacements for each trapped particle. In contrast to traditional table-top counterparts, the stiffness of each trap in an nSWAT device scales linearly with input power and is independent of the number of trapping centers. Through a unique integration of micro-circuitry and photonics, the nSWAT can robustly trap, and controllably position, a large number of nanoparticles along the waveguide surface, operating in an all-optical, constant-force mode without need for active feedback. By reducing device fabrication cost, minimizing trapping laser specimen heating, increasing trapping force, and implementing commonly used trapping techniques, this new generation of nSWATs significantly advances the development of a high performance, low cost optical tweezers array laboratory on-chip.

Optical trapping is a powerful and widely used laboratory technique in the biological and materials sciences that enables rapid manipulation and measurement at the nanometer scale. However, expanding the analytical throughput of this technique beyond the serial capabilities of established single-trap microscopebased optical tweezers remains a current goal in the field. In recent years, advances in nanotechnology have been leveraged to create innovative optical trapping methods that increase the number of available optical traps and permit parallel manipulation and measurement of arrays of optically trapped targets. In particular, nanophotonic trapping holds significant promise for integration with other lab-on-a-chip technologies to yield compact, robust analytical devices. In this review, we highlight progress in nanophotonic manipulation and measurement, as well as the potential for implementing these on-chip functionalities in biological research and biomedical applications.

The E. coli single-stranded DNA binding (SSB) protein interacts with at least 17 different proteins, known as SSB-interacting proteins (SIPs), during DNA replication, repair, and recombination. The E. coli RecO protein is a recombination mediator protein functioning in complex with RecF and RecR proteins in the RecF pathway of homologous recombination. RecO has been shown to interact with the last 9 amino acids of the intrinsically disordered C-terminal tails of SSB (SSB-Ct). Although structures of RecOR complexes from organisms, such as D. Radiodurans and T. Tencongensis, have been determined, they differ in stoichiometry. Furthermore, structures of the E. coli RecOR complex are not yet available. We therefore investigated the assembly states of RecO and RecR, and RecOR complexes using analytical ultracentrifugation. We find that E. coli RecO is a stable monomer. Although E. coli RecR had previously been reported to form a dimer, we find that it is in a pH-dependent dimer-tetramer equilibrium. We also find that only the RecR tetramer and not the dimer binds RecO and that the SSB-C-terminal peptide destabilizes the RecOR 4 complex (supported by NIH GM030498 to TML).

Recent technological advances have introduced diverse engineered nanoparticles (ENPs) into our air, water, medicine, cosmetics, clothing, and food. However, the health and environmental effects of these increasingly common ENPs are still not well understood. In particular, potential neurological effects are one of the most poorly understood areas of nanoparticle toxicology (nanotoxicology), in that low-to-moderate neurotoxicity can be subtle and difficult to measure. Culturing primary neuron explants on planar microelectrode arrays (MEAs) has emerged as one of the most promising in vitro techniques with which to study neuro-nanotoxicology, as MEAs enable the fluorescent tracking of nanoparticles together with neuronal electrical activity recording at the submillisecond time scale, enabling the resolution of individual action potentials. Here we examine the dose-dependent neurotoxicity of dextran-coated iron oxide nanoparticles (dIONPs), a common type of functionalized ENP used in biomedical applications, on cultured primary neurons harvested from postnatal day 0–1 mouse brains. A range of dIONP concentrations (5–40 µg/ml) were added to neuron cultures, and cells were plated either onto well plates for live cell, fluorescent reactive oxidative species (ROS) and viability observations, or onto planar microelectrode arrays (MEAs) for electrophysiological measurements. Below 10 µg/ml, there were no dose-dependent cellular ROS increases or effects in MEA bursting behavior at sub-lethal dosages. However, above 20 µg/ml, cell death was obvious and widespread. Our findings demonstrate a significant dIONP toxicity in cultured neurons at concentrations previously reported to be safe for stem cells and other non-neuronal cell types.

No abstract

Biological and artificial intelligence (AI) are often defined by their capacity to achieve a hierarchy of short-term and long-term goals that require incorporating information over time and space at both local and global scales. More advanced forms of this capacity involve the adaptive modulation of integration across scales, which resolve computational inefficiency and explore-exploit dilemmas at the same time. Research in neuroscience and AI have both made progress towards understanding architectures that achieve this. Insight into biological computations come from phenomena such as decision inertia, habit formation, information search, risky choices and foraging. Across these domains, the brain is equipped with mechanisms (such as the dorsal anterior cingulate and dorsolateral prefrontal cortex) that can represent and modulate across scales, both with top-down control processes and by local to global consolidation as information progresses from sensory to prefrontal areas. Paralleling these biological architectures, progress in AI is marked by innovations in dynamic multiscale modulation, moving from recurrent and convolutional neural networks—with fixed scalings—to attention, transformers, dynamic convolutions, and consciousness priors—which modulate scale to input and increase scale breadth. The use and development of these multiscale innovations in robotic agents, game AI, and natural language processing (NLP) are pushing the boundaries of AI achievements. By juxtaposing biological and artificial intelligence, the present work underscores the critical importance of multiscale processing to general intelligence, as well as highlighting innovations and differences between the future of biological and artificial intelligence.

The advent of nanophotonic evanescent field trapping and transport platforms has permitted increasingly complex single molecule and single cell studies on-chip. Here, we present the next generation of nanophotonic Standing Wave Array Traps (nSWATs) representing a streamlined CMOS fabrication process and compact biocompatible design. These devices utilize silicon nitride (Si 3 N 4 ) waveguides, operate with a bio-friendly 1064 nm laser, allow for several watts of input power with minimal absorption and heating, and are protected by an anticorrosive layer for sustained on-chip microelectronics in aqueous salt buffers. In addition, due to Si 3 N 4 's negligible nonlinear effects, these devices can generate high stiffness traps while resolving sub-nanometer displacements for each trapped particle. In contrast to traditional table-top counterparts, the stiffness of each trap in an nSWAT device scales linearly with input power and is independent of the number of trapping centers. Through a unique integration of micro-circuitry and photonics, the nSWAT can robustly trap, and controllably position, a large number of nanoparticles along the waveguide surface, operating in an all-optical, constant-force mode without need for active feedback. By reducing device fabrication cost, minimizing trapping laser specimen heating, increasing trapping force, and implementing commonly used trapping techniques, this new generation of nSWATs significantly advances the development of a high performance, low cost optical tweezers array laboratory on-chip. Graphical Abstract Author ContributionsThe manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. F.Y. and R.B. designed and fabricated the devices. J.T.I., F.Y., and J.L.K. upgraded the nanophotonics measurement setup and F.Y. carried out measurements. M.S. obtained some preliminary data on some of the experiments. F.Y., R.B, and M.D.W. drafted the manuscript and all authors edited the manuscript. M.D.W. provided overall guidance on experimental designs and measurements.Supporting Information. Fabrication protocol for Si 3 N 4 nSWAT device, Data acquisition and analysis methods, Si 3 N 4 waveguide loss measurement, microheater calibration curve, modulation speed measurement of the Ni microheater, 3D full-wave electromagnetic simulations, kymograph of long range transport of trapped bead array, stiffness measurements using three different methods, spatial resolution measurement of trap movement, cross-talk among different traps, and simultaneous trap stiffness calibration for an array of trapped beads. This material is available free of charge via the Internet at http://pubs.acs.org. Optical trapping utilizes the gradient forces of an electromagnetic field to trap and manipulate small dielectric particles. 1-9 A traditional free-space optical trap is a sensitive tool generated by a tightly focused laser beam using table-top optics. These traps can generate piconewtons (pN) of force and detect nanomete...