Flexible electronic substrates to deliver electromechanical stimuli to regenerative cardiac patches

After myocardial infarction, the stressed environment may cause negative cardiac remodeling. An emerging treatment option, engineered cardiac patches can be mechanically conditioned to increase alignment or electrically stimulated to enable anisotropic conduction. While proper integration with native tissue may require both stimuli, very few studies have applied both simultaneously, and only to extracted tissues. To demonstrate feasibility, a rigid electrode prototype was constructed to incorporate electrical stimulation into a commercially available mechanical conditioning system. Electrodes were assembled to fit the system’s geometry, and parameters were optimized to mimic the human heart rate. Previously, a study used 5-Azacytidine (5-Aza) to differentiate mesenchymal stem cells (MSCs) toward cardiac lineage, which was used here for proof-of-concept testing. Unexpectedly, MSCs treated with 5-Aza and electrically stimulated showed a decrease in cardiac marker troponin and an increase in MSC surface marker gene expression. In this setup, current from rigid electrodes passes through the media; however, under physiologically relevant conditions, electrical signals should propagate directly through cardiomyocytes. Therefore, a method to apply electromechanical stimulation to individual cells was explored in a point source stimulation platform. Electroconductive adhesive (ECA), a composite of silver and polydimethylsiloxane, was used to fabricate flexible elastic microelectrode arrays that provided positive and negative voltage sources to individual cells. Devices were not cytotoxic before applying an electric field; however, applied current caused electrolysis of media and cytotoxicity, even using current stimulation parameters lower than those in published studies. These findings suggest ECA electrochemical properties need more characterization and alternative materials for microelectrodes

Insight into the structure-property relationship of UO2_{2} nanoparticles

Highly crystalline UO$_{2}$ nanoparticles (NPs) with sizes of 2–3 nm were produced by fast chemical deposition of uranium(IV) under reducing conditions at pH 8–11. The particles were then characterized by microscopy and spectroscopy techniques including high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), high-energy resolution fluorescence detection (HERFD) X-ray absorption spectroscopy at the U M$_{4}$ edge and extended X-ray absorption fine structure (EXAFS) spectroscopy at the U L$_{3}$ edge. The results of this investigation show that despite U(IV) being the dominant oxidation state of the freshly prepared UO$_{2}$ NPs, they oxidize to U$_{4}$O$_{9}$ with time and under the X-ray beam, indicating the high reactivity of U(IV) under these conditions. Moreover, it was found that the oxidation process of NPs is accompanied by their growth in size to 6 nm. We highlight here the major differences and similarities of the UO$_{2}$ NP properties to PuO$_{2}$, ThO$_{2}$ and CeO$_{2}$ NPs

Dynamic loading of human engineered heart tissue enhances contractile function and drives a desmosome-linked disease phenotype

The role that mechanical forces play in shaping the structure and function of the heart is critical to understanding heart formation and the etiology of disease but is challenging to study in patients. Engineered heart tissues (EHTs) incorporating human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes have the potential to provide insight into these adaptive and maladaptive changes. However, most EHT systems cannot model both preload (stretch during chamber filling) and afterload (pressure the heart must work against to eject blood). Here, we have developed a new dynamic EHT (dyn-EHT) model that enables us to tune preload and have unconstrained contractile shortening of >10%. To do this, three-dimensional (3D) EHTs were integrated with an elastic polydimethylsiloxane strip providing mechanical preload and afterload in addition to enabling contractile force measurements based on strip bending. Our results demonstrated that dynamic loading improves the function of wild-type EHTs on the basis of the magnitude of the applied force, leading to improved alignment, conduction velocity, and contractility. For disease modeling, we used hiPSC-derived cardiomyocytes from a patient with arrhythmogenic cardiomyopathy due to mutations in the desmoplakin gene. We demonstrated that manifestation of this desmosome-linked disease state required dyn-EHT conditioning and that it could not be induced using 2D or standard 3D EHT approaches. Thus, a dynamic loading strategy is necessary to provoke the disease phenotype of diastolic lengthening, reduction of desmosome counts, and reduced contractility, which are related to primary end points of clinical disease, such as chamber thinning and reduced cardiac output

The origins and spread of domestic horses from the Western Eurasian steppes

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: All collapsed and paired-end sequence data for samples sequenced in this study are available in compressed fastq format through the European Nucleotide Archive under accession number PRJEB44430, together with rescaled and trimmed bam sequence alignments against both the nuclear and mitochondrial horse reference genomes. Previously published ancient data used in this study are available under accession numbers PRJEB7537, PRJEB10098, PRJEB10854, PRJEB22390 and PRJEB31613, and detailed in Supplementary Table 1. The genomes of ten modern horses, publicly available, were also accessed as indicated in their corresponding original publications57,61,85-87.NOTE: see the published version available via the DOI in this record for the full list of authorsDomestication of horses fundamentally transformed long-range mobility and warfare. However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling at Botai, Central Asia around 3500 BC. Other longstanding candidate regions for horse domestication, such as Iberia and Anatolia, have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 BC, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 BC driving the spread of Indo-European languages. This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium BC Sintashta culture

Ten millennia of hepatitis B virus evolution

Hepatitis B virus (HBV) has been infecting humans for millennia and remains a global health problem, but its past diversity and dispersal routes are largely unknown. We generated HBV genomic data from 137 Eurasians and Native Americans dated between ~10,500 and ~400 years ago. We date the most recent common ancestor of all HBV lineages to between ~20,000 and 12,000 years ago, with the virus present in European and South American hunter-gatherers during the early Holocene. After the European Neolithic transition, Mesolithic HBV strains were replaced by a lineage likely disseminated by early farmers that prevailed throughout western Eurasia for ~4000 years, declining around the end of the 2nd millennium BCE. The only remnant of this prehistoric HBV diversity is the rare genotype G, which appears to have reemerged during the HIV pandemic

Organ-on-e-Chip: 3D Self-Rolled Biosensor Array for Electrical Interrogations of Electrogenic Spheroids

Cell-cell communication plays a pivotal role in the coordination and function of biological systems. Three-dimensional (3D) cellular constructs provide venues to explore cellular communication for tissue development and drug discovery, as their 3D architecture mimics native in vivo microenvironments. Cellular electrophysiology (EP) is a prevalent signaling paradigm for studying electroactive cells. Currently, electrophysiological studies do not provide direct, multisite, simultaneous investigation of tissues in 3D. In this thesis, a controlled 3D assembly of biosensors was achieved via self-rolling. The 3D self-rolled biosensor arrays (3D-SR-BAs) were fabricated with customized geometries, designed to tightly interface 3D cellular constructs of varied sizes. The geometric arrangement of the sensors on the array provided a high spatial resolution in such a way that the electrical signal from individual cells can be recorded. 3D-SR-BA platform was shown to accommodate different sensor types: active field-effect transistors and passive microelectrodes. 3D-SR-BAs were interfaced with a few models of 3D-cultured constructs: human cardiac spheroids, human cardiac tissues, and rat cortical spheroids. The arrays provided continuous and stable multiplexed recordings of extracellular potentials with high sensitivity and spatiotemporal resolution, supported with simultaneous calcium imaging. The approach established in this work enabled EP investigation and monitoring of the complex signal transduction in 3D cardiac constructs. Additionally, the platform was sensitive enough to detect single-neuron and network activity in cortical spheroids. 3D-SR-BAs developed in this thesis provide a novel and versatile technology toward an organ-on-an-electronic-chip (organ-on-e-chip) platform for studying EP of 3D constructs in both healthy and diseased states. This platform can be further used in long-term EP studies to investigate and advance engineered tissue maturation, as well as develop and test therapeutics for personalized medicine

Sorption of radionuclides onto minerals: Experiments and modelling

Sorption of various radionuclides such as Cs(I), Eu(III)/Am(III), Np(V), U(VI) and others onto iron oxide (goethite, hematite) and clay minerals (montmorillonite, kaolinite) was studied at wide experimental range (pH ionic strength, total radionuclides concentrations). In all case athermodynamic model for describing sorption onto studied minerals was built and successfully applied for all experiments. The required constants were calculated or verified from published data. For modelling sorption in mineral assemblages Component Additivity (CA) approach was successfully applied

The Technique to Test the Software Prototype of One-Way Data Gateway

The purpose of the article was to investigate the interaction between a data source, a data sink and a oneway data gateway. The main steps are as follows: development of the one-way data gateway architecture and the data communication protocol, design of software data transfer prototype and investigation of its properties. The main result of the research was the technique to reduce a performance penalty

Mutual impact of reservoir sands and acidic liquid radioactive waste

The work is devoted to the study of the behavior of long-lived alpha-emitting radionuclides (Pu, Am, U, Np) under the conditions of injection of acidic liquid radioactive waste into a sandy rock reservoir bed. Different mineral phases of initial reservoir sands, secondary minerals formed when interacting with waste solutions, as well as phases precipitating from the waste solution are considered in terms of their retention properties towards to actinides