Control of Neural Stem Cell Survival by Electroactive Polymer Substrates

Stem cell function is regulated by intrinsic as well as microenvironmental factors, including chemical and mechanical signals. Conducting polymer-based cell culture substrates provide a powerful tool to control both chemical and physical stimuli sensed by stem cells. Here we show that polypyrrole (PPy), a commonly used conducting polymer, can be tailored to modulate survival and maintenance of rat fetal neural stem cells (NSCs). NSCs cultured on PPy substrates containing different counter ions, dodecylbenzenesulfonate (DBS), tosylate (TsO), perchlorate (ClO4) and chloride (Cl), showed a distinct correlation between PPy counter ion and cell viability. Specifically, NSC viability was high on PPy(DBS) but low on PPy containing TsO, ClO4 and Cl. On PPy(DBS), NSC proliferation and differentiation was comparable to standard NSC culture on tissue culture polystyrene. Electrical reduction of PPy(DBS) created a switch for neural stem cell viability, with widespread cell death upon polymer reduction. Coating the PPy(DBS) films with a gel layer composed of a basement membrane matrix efficiently prevented loss of cell viability upon polymer reduction. Here we have defined conditions for the biocompatibility of PPy substrates with NSC culture, critical for the development of devices based on conducting polymers interfacing with NSCs

Multidimensional Atomic Force Microscopy: A Versatile Novel Technology for Nanopharmacology Research

Nanotechnology is giving us a glimpse into a nascent field of nanopharmacology that deals with pharmacological phenomena at molecular scale. This review presents our perspective on the use of scanning probe microscopy techniques with special emphasis to multidimensional atomic force microscopy (m-AFM) to explore this new field with a particular emphasis to define targets, design therapeutics, and track outcomes of molecular-scale pharmacological interactions. The approach will be to first discuss operating principles of m-AFM and provide representative examples of studies to understand human health and disease at the molecular level and then to address different strategies in defining target macromolecules, screening potential drug candidates, developing and characterizing of drug delivery systems, and monitoring target–drug interactions. Finally, we will discuss some future directions including AFM tip-based parallel sensors integrated with other high-throughput technologies which could be a powerful platform for drug discovery

Mapping of γ/δ T cells reveals Vδ2+ T cells resistance to senescence

Immune adaptation with aging is a major of health outcomes. Studies in humans have mainly focus on αβ T cells while γδ T cells have been neglected despite their role in immunosurveillance. We investigated the impact of aging on γδ T cell subsets phenotypes, functions, senescence and their molecular response to stress. Methods: Peripheral blood of young and old donors in Singapore have been used to assess the phenotype, functional capacity, proliferation capacity and gene expression of the various γδ T cell subsets. Peripheral blood mononuclear cells from apheresis cones and young donors have been used to characterize the telomere length, epigenetics profile and DNA damage response of the various γδ T cell subsets phenotype. Findings: Our data shows that peripheral Vδ2+ phenotype, functional capacity (cytokines, cytotoxicity, proliferation) and gene expression profile are specific when compared against all other αβ and γδ T cells in aging. Hallmarks of senescence including telomere length, epigenetic profile and DNA damage response of Vδ2+ also differs against all other αβ and γδ T cells. Interpretation: Our results highlight the differential impact of lifelong stress on γδ T cells subsets, and highlight possible mechanisms that enable Vδ2+ to be resistant to cellular aging. The new findings reinforce the concept that Vδ2+ have an “innate-like” behavior and are more resilient to the environment as compared to “adaptive-like” Vδ1+ T cells

Liquid biopsies come of age: towards implementation of circulating tumour DNA

Improvements in genomic and molecular methods are expanding the range of potential applications for circulating tumour DNA (ctDNA), both in a research setting and as a ‘liquid biopsy’ for cancer management. Proof-of-principle studies have demonstrated the translational potential of ctDNA for prognostication, molecular profiling and monitoring. The field is now in an exciting transitional period in which ctDNA analysis is beginning to be applied clinically, although there is still much to learn about the biology of cell-free DNA. This is an opportune time to appraise potential approaches to ctDNA analysis, and to consider their applications in personalized oncology and in cancer research.We would like to acknowledge the support of The University of Cambridge, Cancer Research UK (grant numbers A11906, A20240, A15601) (to N.R., J.D.B.), the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement n. 337905 (to N.R.), the Cambridge Experimental Cancer Medicine Centre, and Hutchison Whampoa Limited (to N.R.), AstraZeneca (to R.B., S.P.), the Cambridge Experimental Cancer Medicine Centre (ECMC) (to R.B., S.P.), and NIHR Biomedical Research Centre (BRC) (to R.B., S.P.). J.G.C. acknowledges clinical fellowship support from SEOM

Microstructural Characterization Of U-Nb-Zr, U-Mo-Nb, And U-Mo-Ti Alloys Via Electron Microscopy

Ternary uranium molybdenum alloys are being examined for use as dispersion and monolithic nuclear fuels in research and test reactors. In this study, three such ternary alloys, with compositions U-10Nb-4Zr, U-8Mo-3Nb, and U-7Mo-3Ti in wt.%, were examined using scanning electron microscopy (SEM), x-ray diffraction (XRD), and transmission electron microscopy (TEM) with high angle annular dark field (HAADF) imaging via scanning transmission electron microscopy (STEM). These alloys were homogenized at 950 °C for 96 h and were expected to be single-phase bcc-γ-U. However, upon examination, it was determined that despite homogenization, each of the alloys contained a small volume fraction precipitate phase. Through SEM and XRD, it was confirmed that the matrix retained the bcc-γ-U phase. TEM specimens were prepared using site-specific focused ion beam (FIB) in situ lift out (INLO) technique to include at least one precipitate from each alloy. By electron diffraction, the precipitate phases for the U-10Nb-4Zr, U-8Mo-3Nb, and U-7Mo-3Ti alloys were identified as bcc-(Nb,Zr), bcc-(Mo,Nb), and bcc-(Mo,Ti) solid solutions, respectively. The composition and phase information collected in this study was then used to construct ternary isotherms for each of these alloys at 950 °C. © 2010 ASM International

Phase Constituents Of Al-Rich U-Mo-Al Alloys Examined By Transmission Electron Microscopy

To supplement the understanding of diffusional interactions involving Al-rich region of the U-Mo-Al system, alloys with composition 85.7Al-11.44U-2.86Mo and 87.5Al-10U-2.5Mo in at.%, were examined to determine the equilibrium phase constituents at 500 °C. These alloys were triple arc-melted, homogenized at 500 °C for 200 h, and water-quenched to preserve the high temperature microstructure. X-ray diffraction, scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (XEDS), and transmission electron microscopy (TEM) with high angle annular dark field (HAADF) imaging via scanning transmission electron microscopy (STEM) were employed for the characterization. Alloy specimens for TEM/STEM were prepared using site-specific focused ion beam (FIB) in situ lift-out (INLO) technique. Despite the homogenization time and temperature, five different phases, namely fcc-Al solid solution, cubic-UAl3, orthorhombic-UAl4, hexagonal-U6Mo4Al43 and diamond cubic-UMo2Al20, were observed. Based on U-Al, U-Mo and Al-Mo binary phase diagrams, previously proposed U-Mo-Al isotherms, and the solidification microstructure of these alloys, the Al-rich region of the equilibrium ternary isotherm at 500 °C was constructed. The fcc-Al solid solution, orthorhombic-UAl4, and diamond cubic-UMo2Al20 which were determined to be the equilibrium phases in 85.7Al-11.44U-2.86Mo and 87.5Al-10U-2.5Mo alloys. © 2009 Elsevier B.V

Growth Kinetics Of Intermetallic Phases In U-Mo Vs. Al Alloy Diffusion Couples Annealed At 550°C

This study examined the growth kinetics of intermetallic phases that develop in solid-to-solid diffusion couples assembled with U-7, 10 and 12wt.%Mo vs. Al alloys (Al, Al-2wt.%Si, Al-5wt.%Si, 4043 and 6061) after a diffusion anneal at 550°C for 24 hours. Based on interdiffusion microstructure and integrated interdiffusion coefficients, the addition of Si into the Al matrix alloy was observed to significantly reduce the growth rate of the intermetallic layer that primarily consisted of (U,Mo)Al4 phase. Growth rate of the (U,Mo)Al4 intermetallic layer also increases slightly with Mo content; however, it was not significant compared to the effect of alloying Si into Al alloys. Growth kinetics of (U,Mo)Al4 intermetallic layer appear highly sensitive to composition of U-Mo fuel alloy and Al cladding alloys, and must be an important criteria in alloy development/selection for optimum fuel performance with due consideration for composition-dependent multicomponent interdiffusion

Interdiffusion And Reaction Between Uranium And Iron

The simultaneous effect of a vertical AC electric field and rotation on the onset of thermal convective instability in a horizontal rotating dielectric fluid layer is studied by performing linear stability analysis. The lower and upper boundaries of the fluid layer are considered to be either rigid or free and either isothermal or insulated to temperature perturbations. The resulting eigenvalue problem is solved exactly for free-free isothermal boundaries. It is observed that the oscillatory convection is not a preferred mode of instability for dielectric fluids and the necessary conditions for its occurrence are independent of applied vertical AC electric field. For the other combinations of velocity and temperature boundary conditions, the problem is solved numerically using the Galerkin method. The similarities and differences between the results of isothermal and insulated boundaries are highlighted. It is noted that the effect of increasing AC electric Rayleigh number is to increase the transfer of heat more effectively and hence to hasten the onset of convection. To the contrary, the effect of rotation is to delay the electrothermal convection for a fixed type of boundary conditions. Although the rigid-rigid boundaries enhance the stability when compared to rigid-free and free-free boundaries up to moderate values of Taylor number, the situation is reversed at high Taylor number domain. This trend depends on the temperature boundary conditions as well. © 2012 Elsevier Ltd. All rights reserved

Prenatal cerebral imaging features of a new syndromic entity related to KIAA1109

Our goal was to describe and illustrate prenatal cerebral imaging features of the most severe form of a new syndromic entity related to KIAA1109 pathogenic variants based on a retrospective multicentric study of seven cases. All cases demonstrated a similar complex severe cerebral malformative pattern. This pattern included, within the supratentorial space, major cerebral parenchymal thinning with a lissencephalic cortical pattern, voluminous germinal matrices, severe ventriculomegaly, and corpus callosum agenesis. Within the infra-tentorial space, cerebellar hypoplasia was associated with characteristic brainstem dysgenesis including elongation of the pons, as well as a variable degree of kinking of the brainstem. This cerebral pattern, which was suggestive of the more severe phenotypes related to disrupting variants of tubulin-encoding genes, was associated in all cases with clubfoot and/or arthrogryposis, and in most cases with cardiac and ophthalmologic anomalies. In all cases, exome sequencing led to the identification of KIAA1109 pathogenic variants

Prenatal cerebral imaging features of a new syndromic entity related to KIAA1109 pathogenic variants mimicking tubulinopathy.

Our goal was to describe and illustrate prenatal cerebral imaging features of the most severe form of a new syndromic entity related to KIAA1109 pathogenic variants based on a retrospective multicentric study of seven cases. All cases demonstrated a similar complex severe cerebral malformative pattern. This pattern included, within the supratentorial space, major cerebral parenchymal thinning with a lissencephalic cortical pattern, voluminous germinal matrices, severe ventriculomegaly, and corpus callosum agenesis. Within the infra-tentorial space, cerebellar hypoplasia was associated with characteristic brainstem dysgenesis including elongation of the pons, as well as a variable degree of kinking of the brainstem. This cerebral pattern, which was suggestive of the more severe phenotypes related to disrupting variants of tubulin-encoding genes, was associated in all cases with clubfoot and/or arthrogryposis, and in most cases with cardiac and ophthalmologic anomalies. In all cases, exome sequencing led to the identification of KIAA1109 pathogenic variants