Synergistic Coordination of Chromatin Torsional Mechanics and Topoisomerase Activity.

DNA replication in eukaryotes generates DNA supercoiling, which may intertwine (braid) daughter chromatin fibers to form precatenanes, posing topological challenges during chromosome segregation. The mechanisms that limit precatenane formation remain unclear. By making direct torque measurements, we demonstrate that the intrinsic mechanical properties of chromatin play a fundamental role in dictating precatenane formation and regulating chromatin topology. Whereas a single chromatin fiber is torsionally soft, a braided fiber is torsionally stiff, indicating that supercoiling on chromatin substrates is preferentially directed in front of the fork during replication. We further show that topoisomerase II relaxation displays a strong preference for a single chromatin fiber over a braided fiber. These results suggest a synergistic coordination-the mechanical properties of chromatin inherently suppress precatenane formation during replication elongation by driving DNA supercoiling ahead of the fork, where supercoiling is more efficiently removed by topoisomerase II. VIDEO ABSTRACT.

Biocompatible and High Stiffness Nanophotonic Trap Array for Precise and Versatile Manipulation.

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 biofriendly 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 subnanometer 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 microcircuitry 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.

Perceptions of social rigidity predict loneliness across the Japanese population.

Loneliness is associated with mental and physical health problems and elevated suicide risk, and is increasingly widespread in modern societies. However, identifying the primary factors underlying loneliness remains a major public health challenge. Historically, loneliness was thought to result from a lack of high-quality social connections, but broader cultural factors (e.g. social norms) are increasingly recognized to also influence loneliness. Here, we used a large-scale survey (N = 4977) to assess to what degree the loneliness epidemic in Japan is associated with traditional measures of social isolation (number of close friends), cultural factors (perceptions of social rigidity, as measured by relational mobility), and socioeconomic factors (e.g. income). We confirmed that a lack of close friends is a dominant factor underlying loneliness in Japan. We also found that perceptions of the social rigidity in one's environment was a major correlate of loneliness. Subjects who perceived lower levels of rigidity in their social environments felt significantly less lonely than those who perceived higher levels of social rigidity, though the association was weak in low income males. Thus, Japanese society and other high social rigidity cultures may need to reflect on the possibility that inflexible traditional norms of socialization are exacerbating loneliness.

Trust in Institutions, Not in Political Leaders, Determines Compliance in COVID-19 Prevention Measures within Societies across the Globe.

A core assumption often heard in public health discourse is that increasing trust in national political leaders is essential for securing public health compliance during crises such as the COVID-19 pandemic (2019-ongoing). However, studies of national government trust are typically too coarse-grained to differentiate between trust in institutions versus more interpersonal trust in political leaders. Here, we present multiscale trust measurements for twelve countries and territories across the West, Oceania and East Asia. These trust results were used to identify which specific domains of government and social trust were most crucial for securing public health compliance (frequency of mask wearing and social distancing) and understanding the reasons for following health measures (belief in effectiveness of public health measures). Through the use of linear regression and structural equation modeling, our cross-cultural survey-based analysis (N = 3369 subjects) revealed that higher trust in national and local public health institutions was a universally consistent predictor of public health compliance, while trust in national political leaders was not predictive of compliance across cultures and geographical regions. Institutional trust was mediated by multiple types of transparency, including providing rationale, securing public feedback, and honestly expressing uncertainty. These results highlight the importance of distinguishing between components of government trust, to better understand which entities the public gives the most attention to during crises.

Dextran-coated iron oxide nanoparticle-induced nanotoxicity in neuron cultures.

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.

Towards biological applications of nanophotonic tweezers.

Optical trapping (synonymous with optical tweezers) has become a core biophysical technique widely used for interrogating fundamental biological processes on size scales ranging from the single-molecule to the cellular level. Recent advances in nanotechnology have led to the development of 'nanophotonic tweezers,' an exciting new class of 'on-chip' optical traps. Here, we describe how nanophotonic tweezers are making optical trap technology more broadly accessible and bringing unique biosensing and manipulation capabilities to biological applications of optical trapping.

High Trap Stiffness Microcylinders for Nanophotonic Trapping.

Nanophotonic waveguides have enabled on-chip optical trap arrays for high-throughput manipulation and measurements. However, the realization of the full potential of these devices requires trapping enhancement for applications that need large trapping force. Here, we demonstrate a solution via fabrication of high refractive index cylindrical trapping particles. Using two different fabrication processes, a cleaving method and a novel lift-off method, we produced cylindrical silicon nitride (Si3N4) particles and characterized their trapping properties using the recently developed nanophotonic standing-wave array trap (nSWAT) platform. Relative to conventionally used polystyrene microspheres, the fabricated Si3N4 microcylinders attain an approximately 3- to 6-fold trap stiffness enhancement. Furthermore, both fabrication processes permit tunable microcylinder geometry, and the lift-off method also results in ultrasmooth surface termination of the ends of the microcylinders. These combined features make the Si3N4 microcylinders uniquely suited for a broad range of high-throughput, high-force, nanophotonic waveguide-based optical trapping applications.

Nanophotonic trapping: precise manipulation and measurement of biomolecular arrays.

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 microscope-based 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. WIREs Nanomed Nanobiotechnol 2018, 10:e1477. doi: 10.1002/wnan.1477 This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.