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Abstract Accurate positioning of the mitotic spindle within the rounded cell body is critical to physiological maintenance. Mitotic cells encounter confinement from neighboring cells or the extracellular matrix (ECM), which can cause rotation of mitotic spindles and tilting of the metaphase plate (MP). To understand the effect of confinement on mitosis by fibers (ECM confinement), we use flexible ECM-mimicking nanofibers that allow natural rounding of the cell body while confining it to differing levels. Rounded mitotic bodies are anchored in place by actin retraction fibers (RFs) originating from adhesions on fibers. We discover that the extent of confinement influences RF organization in 3D, forming triangular and band-like patterns on the cell cortex under low and high confinement, respectively. Our mechanistic analysis reveals that the patterning of RFs on the cell cortex is the primary driver of the MP rotation. A stochastic Monte Carlo simulation of the centrosome, chromosome, membrane interactions, and 3D arrangement of RFs recovers MP tilting trends observed experimentally. Under high ECM confinement, the fibers can mechanically pinch the cortex, causing the MP to have localized deformations at contact sites with fibers. Interestingly, high ECM confinement leads to low and high MP tilts, which we mechanistically show to depend upon the extent of cortical deformation, RF patterning, and MP position. We identify that cortical deformation and RFs work in tandem to limit MP tilt, while asymmetric positioning of MP leads to high tilts. Overall, we provide fundamental insights into how mitosis may proceed in ECM-confining microenvironments in vivo. 

This design-based research study describes the instructional design process, benefits, and lessons learned in providing District Science Coordinators (DSCs) with differentiated professional development. Two cohorts of DSCs participated in a two-year professional development (PD) program (12 in Cohort 1 and 11 in Cohort 2) that met synchronously once per month and assigned asynchronous modules to DSCs based on a pre-assessment performance. DSCs provided feedback for each module and the entire program through surveys and interviews. DSCs’ engagement in the program was also tracked through the differentiated modules. DSCs’ responses indicated that the PD program provided them with a community of practice and the knowledge, skills, and confidence to advocate for science education. Lessons learned throughout the process included that DSCs needed intermediate deadlines, modules needed to be divided into smaller topics, and more consistent feedback should be provided throughout the implementation. This study provides practical suggestions for designing differentiated PD programs for educators and offers a possible format to help create communities of practice for educators. 

Low-income families often live in low-upward-mobility neighborhoods. We study why by using a randomized trial with housing voucher recipients that provided information, financial support, and customized search assistance to move to high-opportunity neighborhoods. The treatment increased the fraction moving to high-upward-mobility areas from 15 to 53 percent. A second trial reveals this treatment effect is driven primarily by customized search assistance. Qualitative interviews show that the intervention relaxed bandwidth constraints and addressed family-specific needs. Our findings imply many low-income families do not have strong preferences to stay in low-opportunity areas and that barriers in housing search significantly increase residential segregation by income. 

During mitosis, kinetochore–microtubule attachments are monitored by a molecular surveillance system known as the spindle assembly checkpoint. The prevailing model posits that dynein evicts checkpoint proteins (e.g., Mad1, Mad2) from stably attached kinetochores by transporting them away from kinetochores, thus contributing to checkpoint silencing. However, the mechanism by which dynein performs this function, and its precise role in checkpoint silencing remain unresolved. Here, we find that dynein’s role in checkpoint silencing is restricted to evicting checkpoint effectors from the fibrous corona, and not the outer kinetochore. Dynein evicts these molecules from the corona in a manner that does not require stable, end-on microtubule attachments. Thus, by disassembling the corona through indiscriminate microtubule encounters, dynein primes the checkpoint signaling apparatus so it can respond to stable end-on microtubule attachments and permit cells to progress through mitosis. Accordingly, we find that dynein function in checkpoint silencing becomes largely dispensable in cells in which checkpoint effectors are excluded from the corona. 

DNA origami nanostructures (DOs) are promising tools for applications including drug delivery, biosensing, detecting biomolecules, and probing chromatin substructures. Targeting these nanodevices to mammalian cell nuclei could provide impactful approaches for probing, visualizing, and controlling biomolecular processes within live cells. We present an approach to deliver DOs into live-cell nuclei. We show that these DOs do not undergo detectable structural degradation in cell culture media or cell extracts for 24 hours. To deliver DOs into the nuclei of human U2OS cells, we conjugated 30-nanometer DO nanorods with an antibody raised against a nuclear factor, specifically the largest subunit of RNA polymerase II (Pol II). We find that DOs remain structurally intact in cells for 24 hours, including inside the nucleus. We demonstrate that electroporated anti–Pol II antibody–conjugated DOs are piggybacked into nuclei and exhibit subdiffusive motion inside the nucleus. Our results establish interfacing DOs with a nuclear factor as an effective method to deliver nanodevices into live-cell nuclei. 

This archived Paleoclimatology Study is available from the NOAA National Centers for Environmental Information (NCEI), under the World Data Service (WDS) for Paleoclimatology. The associated NCEI study type is Lake. The data include parameters of paleolimnology (hydrogen isotopes) with a geographic location of Peru. The time period coverage is from 42395 to -59 in calendar years before present (BP). See metadata information for parameter and study location details. Please cite this study when using the data. 

Abstract Many experimental and computational efforts have sought to understand DNA origami folding, but the time and length scales of this process pose significant challenges. Here, we present a mesoscopic model that uses a switchable force field to capture the behavior of single- and double-stranded DNA motifs and transitions between them, allowing us to simulate the folding of DNA origami up to several kilobases in size. Brownian dynamics simulations of small structures reveal a hierarchical folding process involving zipping into a partially folded precursor followed by crystallization into the final structure. We elucidate the effects of various design choices on folding order and kinetics. Larger structures are found to exhibit heterogeneous staple incorporation kinetics and frequent trapping in metastable states, as opposed to more accessible structures which exhibit first-order kinetics and virtually defect-free folding. This model opens an avenue to better understand and design DNA nanostructures for improved yield and folding performance.