Electrical stimulation using conductive polymer polypyrrole promotes differentiation of human neural stem cells: a biocompatible platform for translational neural tissue engineering

Conductive polymers (CPs) are organic materials that hold great promise for biomedicine. Potential applications include in vitro or implantable electrodes for excitable cell recording and stimulation, and conductive scaffolds for cell support and tissue engineering. Here we demonstrate the utility of electroactive CP Polypyrrole (PPy) containing the anionic dopant dodecylbenzenesulfonate (DBS) to differentiate novel clinically relevant human neural stem cells (hNSCs). Electrical stimulation of PPy(DBS) induced hNSCs to predominantly β-III Tubulin (Tuj1) expressing neurons, with lower induction of glial fibrillary acidic protein (GFAP) expressing glial cells. In addition, stimulated cultures comprised nodes or clusters of neurons with longer neurites and greater branching than unstimulated cultures. Cell clusters showed a similar spatial distribution to regions of higher conductivity on the film surface. Our findings support the use of electrical stimulation to promote neuronal induction and the biocompatibility of PPy(DBS) with hNSCs, and opens up the possibility of identifying novel mechanisms of fate determination of differentiating human stem cells for advanced in vitro modelling, translational drug discovery and regenerative medicine

Wet-Spun Trojan Horse Cell Constructs for Engineering Muscle

Engineering of 3D regenerative skeletal muscle tissue constructs (skMTCs) using hydrogels containing muscle precursor cells (MPCs) is of potential benefit for repairing Volumetric Muscle Loss (VML) arising from trauma (e.g., road/industrial accident, war injury) or for restoration of functional muscle mass in disease (e.g., Muscular Dystrophy, muscle atrophy). Additive Biofabrication (AdBiofab) technologies make possible fabrication of 3D regenerative skMTCs that can be tailored to specific delivery requirements of VML or functional muscle restoration. Whilst 3D printing is useful for printing constructs of many tissue types, the necessity of a balanced compromise between cell type, required construct size and material/fabrication process cyto-compatibility can make the choice of 3D printing a secondary alternative to other biofabrication methods such as wet-spinning. Alternatively, wet-spinning is more amenable to formation of fibers rather than (small) layered 3D-Printed constructs. This study describes the fabrication of biosynthetic alginate fibers containing MPCs and their use for delivery of dystrophin-expressing cells to dystrophic muscle in the mdx mouse model of Duchenne Muscular Dystrophy (DMD) compared to poly(DL-lactic-co-glycolic acid) copolymer (PLA:PLGA) topically-seeded with myoblasts. In addition, this study introduces a novel method by which to create 3D layered wet-spun alginate skMTCs for bulk mass delivery of MPCs to VML lesions. As such, this work introduces the concept of “Trojan Horse” Fiber MTCs (TH-fMTCs) and 3d Mesh-MTCs (TH-mMTCs) for delivery of regenerative MPCs to diseased and damaged muscle, respectively

The impact of sequencing depth on the inferred taxonomic composition and AMR gene content of metagenomic samples

Shotgun metagenomics is increasingly used to characterise microbial communities, particularly for the investigation of antimicrobial resistance (AMR) in different animal and environmental contexts. There are many different approaches for inferring the taxonomic composition and AMR gene content of complex community samples from shotgun metagenomic data, but there has been little work establishing the optimum sequencing depth, data processing and analysis methods for these samples. In this study we used shotgun metagenomics and sequencing of cultured isolates from the same samples to address these issues. We sampled three potential environmental AMR gene reservoirs (pig caeca, river sediment, effluent) and sequenced samples with shotgun metagenomics at high depth (~ 200 million reads per sample). Alongside this, we cultured single-colony isolates of Enterobacteriaceae from the same samples and used hybrid sequencing (short- and long-reads) to create high- quality assemblies for comparison to the metagenomic data. To automate data processing, we developed an open- source software pipeline, ‘ResPipe’

US and European Household Debt and Credit Constraints

This paper uses micro data from four OECD countries (the United States, Spain, Italy, and the Netherlands), to assess the determinants of household debt holding and to investigate whether or not credit constraints are important for household debt holding. We extend the existing literature in important ways. First, we present comparative evidence for four countries at the micro level, where we rely on household panel data for two countries; we are thus able to control for unobserved heterogeneity via individual household effects and to track changes in household behaviour over time. Second, by making data across countries as comparable as possible, we can explore the importance of the differences in institutional settings for debt incidence, debt outstanding and credit constraints. We also explore the implications for debt holding from consumption models, including a numerically solved precautionary savings model. We find that inter-country differences are substantial and remain even after controlling for a host of observable characteristics. This points to institutional differences between the countries being important

ISSCR standards for the use of human stem cells in basic research.

The laboratory culture of human stem cells seeks to capture a cellular state as an in vitro surrogate of a biological system. For the results and outputs from this research to be accurate, meaningful, and durable, standards that ensure reproducibility and reliability of the data should be applied. Although such standards have been previously proposed for repositories and distribution centers, no widely accepted best practices exist for laboratory research with human pluripotent and tissue stem cells. To fill that void, the International Society for Stem Cell Research has developed a set of recommendations, including reporting criteria, for scientists in basic research laboratories. These criteria are designed to be technically and financially feasible and, when implemented, enhance the reproducibility and rigor of stem cell research

Corporate Social Responsibility (CSR) in Asia: a seven-country study of CSR web site reporting

This article addresses four hypotheses: (a) that corporate social responsibility (CSR) in Asia is not homogeneous but varies among countries, (b) that the variation is explained by stages of development, (c) that globalization enhances the adoption of CSR in Asia, and (d) that national business systems structure the profile of multinational corporations’ CSR. These hypotheses are investigated through analysis of Web site reporting of 50 companies in seven Asian countries: India, Indonesia, Malaysia, the Philippines, South Korea, Singapore, and Thailand. The article concludes that CSR does vary considerably among Asian countries but that this variation is not explained by development but by factors in the respective national business systems. It also concludes that multinational companies are more likely to adopt CSR than those operating solely in their home country but that the profile of their CSR tends to reflect the profile of the country of operation rather than the country of origin

A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer's disease risk and increased TREML1 and TREM2 brain gene expression

Introduction: We hypothesized that common Alzheimer's disease (AD)-associated variants within the triggering receptor expressed on myeloid (TREM) gene cluster influence disease through gene expression. Methods: Expression microarrays on temporal cortex and cerebellum from ∼400 neuropathologically diagnosed subjects and two independent RNAseq replication cohorts were used for expression quantitative trait locus analysis. Results: A variant within a DNase hypersensitive site 5′ of TREM2, rs9357347-C, associates with reduced AD risk and increased TREML1 and TREM2 levels (uncorrected P = 6.3 × 10−3 and 4.6 × 10−2, respectively). Meta-analysis on expression quantitative trait locus results from three independent data sets (n = 1006) confirmed these associations (uncorrected P = 3.4 × 10−2 and 3.5 × 10−3, Bonferroni-corrected P = 6.7 × 10−2 and 7.1 × 10−3, respectively). Discussion: Our findings point to rs9357347 as a functional regulatory variant that contributes to a protective effect observed at the TREM locus in the International Genomics of Alzheimer's Project genome-wide association study meta-analysis and suggest concomitant increase in TREML1 and TREM2 brain levels as a potential mechanism for protection from AD

Niche and local geography shape the pangenome of wastewater- and livestock-associated Enterobacteriaceae

Escherichia coli and other Enterobacteriaceae are diverse species with “open” pangenomes, where genes move intra- and interspecies via horizontal gene transfer. However, most analyses focus on clinical isolates. The pangenome dynamics of natural populations remain understudied, despite their suggested role as reservoirs for antimicrobial resistance (AMR) genes. Here, we analyze near-complete genomes for 827 Enterobacteriaceae (553 Escherichia and 274 non-Escherichia spp.) with 2292 circularized plasmids in total, collected from 19 locations (livestock farms and wastewater treatment works in the United Kingdom) within a 30-km radius at three time points over a year. We find different dynamics for chromosomal and plasmid-borne genes. Plasmids have a higher burden of AMR genes and insertion sequences, and AMR-gene-carrying plasmids show evidence of being under stronger selective pressure. Environmental niche and local geography both play a role in shaping plasmid dynamics. Our results highlight the importance of local strategies for controlling the spread of AMR

Overcoming leakage in scalable quantum error correction

Leakage of quantum information out of computational states into higher energy states represents a major challenge in the pursuit of quantum error correction (QEC). In a QEC circuit, leakage builds over time and spreads through multi-qubit interactions. This leads to correlated errors that degrade the exponential suppression of logical error with scale, challenging the feasibility of QEC as a path towards fault-tolerant quantum computation. Here, we demonstrate the execution of a distance-3 surface code and distance-21 bit-flip code on a Sycamore quantum processor where leakage is removed from all qubits in each cycle. This shortens the lifetime of leakage and curtails its ability to spread and induce correlated errors. We report a ten-fold reduction in steady-state leakage population on the data qubits encoding the logical state and an average leakage population of less than $1 \times 10^{-3}$ throughout the entire device. The leakage removal process itself efficiently returns leakage population back to the computational basis, and adding it to a code circuit prevents leakage from inducing correlated error across cycles, restoring a fundamental assumption of QEC. With this demonstration that leakage can be contained, we resolve a key challenge for practical QEC at scale.Comment: Main text: 7 pages, 5 figure