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Living cells regulate the dynamics of developmental events through interconnected signaling systems that activate and deactivate inert precursors. This suggests that similarly, synthetic biomaterials could be designed to develop over time by using chemical reaction networks to regulate the availability of assembling components. Here we demonstrate how the sequential activation or deactivation of distinct DNA building blocks can be modularly coordinated to form distinct populations of self-assembling polymers using a transcriptional signaling cascade of synthetic genes. Our building blocks are DNA tiles that polymerize into nanotubes, and whose assembly can be controlled by RNA molecules produced by synthetic genes that target the tile interaction domains. To achieve different RNA production rates, we use a strategy based on promoter nicking and strand displacement. By changing the way the genes are cascaded and the RNA levels, we demonstrate that we can obtain spatially and temporally different outcomes in nanotube assembly, including random DNA polymers, block polymers, and as well as distinct autonomous formation and dissolution of distinct polymer populations. Our work demonstrates a way to construct autonomous supramolecular materials whose properties depend on the timing of molecular instructions for self-assembly, and can be immediately extended to a variety of other nucleic acid circuits and assemblies.

Inspiring New Science to Guide Healthcare in Turner Syndrome (InsighTS) Registry is a national, multicenter registry for individuals with Turner syndrome (TS) designed to collect and store validated longitudinal clinical data from a diverse cohort of patients with TS. Herein, we describe the rationale, design, and approach used to develop the InsighTS registry, as well as the demographics of the initial participants to illustrate the registrys diversity and future utility. Multiple stakeholder groups have been involved from project conceptualization through dissemination, ensuring the registry serves the priorities of the TS community. Key features of InsighTS include recruitment strategies to facilitate enrollment of participants that appropriately reflect the population of individuals with TS receiving care in the US, clarity of data ownership and sharing, and sustainability of this resource. The registry gathers clinical data on diagnosis, treatment, comorbidities, health care utilization, clinical practices, and quality of life with the goal of improving health outcomes for this population. Future directions include multiple patient-centered clinical-translational research projects that will use the InsighTS platform. This thorough and thoughtful planning will ensure InsighTS is a valuable and sustainable resource for the TS community for decades to come.

The US National Institute of Allergy and Infectious Diseases hosted a two-day virtual workshop on skin microbial communities and their interactions with the host immune system in health and disease. The aim of the workshop was to evaluate the current state of knowledge in the field and identify gaps, challenges, and future directions.

Electrochemical aptamer-based (EAB) sensors utilize the binding-induced conformational change of an electrode-attached, redox-reporter-modified aptamer to transduce target recognition into an easily measurable electrochemical output. Because this signal transduction mechanism is single-step and rapidly reversible, EAB sensors support high-frequency, real-time molecular measurements, and because it recapitulates the reagentless, conformation-linked signaling seen in vivo among naturally occurring receptors, EAB sensors are selective enough to work in the complex, time-varying environments found in the living body. The fabrication of EAB sensors, however, requires that their target-recognizing aptamer be modified such that (1) it undergoes the necessary binding-induced conformational change and (2) that the thermodynamics of this conformational switch are tuned to ensure that they reflect an acceptable trade-off between affinity and signal gain. That is, even if an as-selected aptamer achieves useful affinity and specificity, it may fail when adapted to the EAB platform because it lacks the binding-induced conformational change required to support EAB signaling. In this paper we reveal the spectroscopy-guided approaches we use to modify aptamers such that they support the necessary binding-induced conformational change. Specifically, using newly reported aptamers, we demonstrate the systematic design of EAB sensors achieving clinically and physiologically relevant specificity, limits of detection, and dynamic range against the targets methotrexate and tryptophan.

Current health emergencies have highlighted the need to have rapid, sensitive, and convenient platforms for the detection of specific antibodies. In response, we report here the design of an electrochemical DNA circuit that responds quantitatively to multiple specific antibodies. The approach employs synthetic antigen-conjugated nucleic acid strands that are rationally designed to induce a strand displacement reaction and release a redox reporter-modified strand upon the recognition of a specific target antibody. The approach is sensitive (low nanomolar detection limit), specific (no signal is observed in the presence of non-targeted antibodies), and selective (the platform can be employed in complex media, including 90% serum). The programmable nature of the strand displacement circuit makes it also versatile, and we demonstrate here the detection of five different antibodies, including three of which are clinically relevant. Using different redox reporters, we also show that the antibody-responsive circuit can be multiplexed and responds to different antibodies in the same solution without crosstalk.

A versatile platform for the one-step fluorescence detection of both monovalent and multivalent proteins has been developed. This system is based on a conformation-switching stem-loop DNA scaffold that presents a small-molecule, polypeptide, or nucleic-acid recognition element on each of its two stem strands. The steric strain associated with the binding of one (multivalent) or two (monovalent) target molecules to these elements opens the stem, enhancing the emission of an attached fluorophore/quencher pair. The sensors respond rapidly (

Turner syndrome, a congenital condition that affects ∼1/2,500 births, results from absence or structural alteration of the second sex chromosome. There has been substantial effort by numerous clinical and genetic research groups to delineate the clinical, pathophysiological, cytogenetic, and molecular features of this multisystem condition. Questions about the molecular-genetic and biological basis of many of the clinical features remain unanswered, and health care providers and families seek improved care for affected individuals. The inaugural "Turner Resource Network (TRN) Symposium" brought together individuals with Turner syndrome and their families, advocacy group leaders, clinicians, basic scientists, physician-scientists, trainees and other stakeholders with interest in the well-being of individuals and families living with the condition. The goal of this symposium was to establish a structure for a TRN that will be a patient-powered organization involving those living with Turner syndrome, their families, clinicians, and scientists. The TRN will identify basic and clinical questions that might be answered with registries, clinical trials, or through bench research to promote and advocate for best practices and improved care for individuals with Turner syndrome. The symposium concluded with the consensus that two rationales justify the creation of a TRN: inadequate attention has been paid to the health and psychosocial issues facing girls and women who live with Turner syndrome; investigations into the susceptibility to common disorders such as cardiovascular or autoimmune diseases caused by sex chromosome deficiencies will increase understanding of disease susceptibilities in the general population.

BACKGROUND: Inhaled nitric oxide (INO) is used in infants as a therapy for elevated pulmonary vascular resistance. When INO is delivered at low tidal volumes, displayed inspiratory and expiratory volumes vary widely. We hypothesize that volume is removed by the sampling line during the ventilation cycle, and this results in a net volume loss at low tidal volumes. This study aimed to measure the volumes delivered and to assess the accuracy of displayed ventilator values using a test lung. METHODS: A test lung was connected to a ventilator and an INO delivery system. All tests were performed with stable mode settings across volumes of 18, 30, 42, and 60 mL. Flow measured with a pneumotachometer attached between the test lung and the circuit assessed the percent error between inspiratory and expiratory volumes measured by the pneumotachometer measured and displayed on the ventilator under various INO/sample line conditions to determine where and how much volume was being displaced. RESULTS: Displayed and measured inspiratory volumes had small variations between the INO/sample line conditions and baseline. However, expiratory volumes, with the sample line connected, exhibited large percent error values that increased (-14, -20, -27, and -34) as tidal volume decreased (60, 42, 30, and 18 mL) and error was significantly larger compared to baseline in all tidal volumes (P < .01) with and without INO delivery. CONCLUSIONS: We concluded that inspiratory volumes were not affected by INO delivery, but additional removal of volume in the expiratory phase of the breath cycle by the sampling line results in a large error in the displayed expiratory volume. [ABSTRACT FROM AUTHOR]

The article focuses on connected learning theory which create deeper learning opportunities. Topics discussed include support of libraries for connected learning with out-of-school programming and teen librarians; the use of variety of free software in the programs and teen programs in the connected learning model at Cuyahoga County Public Library.

Biologic scaffolds composed of extracellular matrix are commonly used in a variety of surgical procedures. The Food and Drug Administration typically regulates biologic scaffolds as medical devices, thus requiring terminal sterilization prior to clinical use. However, to date, no consensus exists for the most effective yet minimally destructive sterilization protocol for biologic scaffold materials. The objective of the present study was to characterize the effect of ethylene oxide, gamma irradiation and electron beam (e-beam) irradiation on the material properties and the elicited in vivo remodeling response of a porcine dermal biologic scaffold. Outcome measures included biochemical, structural, and mechanical properties as well as cytocompatibility in vitro. In vivo evaluation utilized a rodent model to examine the host response to the materials following 7, 14, and 35 days. The host response to each experimental group was determined by quantitative histologic methods and by immunolabeling for macrophage polarization (M1/M2). In vitro results show that increasing irradiation dosage resulted in a dose dependent decrease in mechanical properties compared to untreated controls. Ethylene oxide-treated porcine dermal ECM resulted in decreased DNA content, extractable total protein, and bFGF content compared to untreated controls. All ETO treated, gamma irradiated, and e-beam irradiated samples had similar cytocompatibility scores in vitro. However, in vivo results showed that increasing dosages of e-beam and gamma irradiation elicited an increased rate of degradation of the biologic scaffold material following 35 days. Statement of Significance The FDA typically regulates biologic scaffolds derived from mammalian tissues as medical devices, thus requiring terminal sterilization prior to clinical use. However, there is little data and no consensus for the most effective yet minimally destructive sterilization protocol for such materials. The present study characterized the effect of common sterilization methods: ethylene oxide, gamma irradiation and electron beam irradiation on the material properties and the elicited in vivo remodeling response of a porcine dermal biologic scaffold. The results of the study will aid in the meaningful selection of sterilization methods for biologic scaffold materials. [ABSTRACT FROM AUTHOR]

Purpose: CT radiation exposure has come under increasing scrutiny because of dramatically increased utilization. Multiphase CT studies (repeated scanning before and after contrast injection) are a potentially important, overlooked source of medically unnecessary radiation because of the dose-multiplier effect of extra phases. The purpose of this study was to determine the frequency of unindicated multiphase scanning and resultant excess radiation exposure in a sample referral population. Methods: Abdominal and pelvic CT examinations (n = 500) performed at outside institutions submitted for tertiary interpretation were retrospectively reviewed for (1) the appropriateness of each phase on the basis of clinical indication and ACR Appropriateness Criteria® and (2) per phase and total radiation effective dose. Results: A total of 978 phases were performed in 500 patients; 52.8% (264 of 500) received phases that were not supported by ACR criteria. Overall, 35.8% of phases (350 of 978) were unindicated, most commonly being delayed imaging (272 of 350). The mean overall total radiation effective dose per patient was 25.8 mSv (95% confidence interval, 24.2-27.5 mSv). The mean effective dose for unindicated phases was 13.1 mSv (95% confidence interval, 12.3-14.0 mSv), resulting in a mean excess effective dose of 16.8 mSv (95% confidence interval, 15.5-18.3 mSv) per patient. Unindicated radiation constituted 33.3% of the total radiation effective dose in this population. Radiation effective doses exceeding 50 mSv were found in 21.2% of patients (106 of 500). Conclusions: The results of this study suggest that a large proportion of patients undergoing abdominal and pelvic CT scanning receive unindicated additional phases that add substantial excess radiation dose with no associated clinical benefit. [ABSTRACT FROM AUTHOR]