Loss of \u3ci\u3eActa2\u3c/i\u3e in Cardiac Fibroblasts Does Not Prevent the Myofibroblast Differentiation or Affect the Cardiac Repair After Myocardial Infarction

In response to myocardial infarction (MI), quiescent cardiac fibroblasts differentiate into myofibroblasts mediating tissue repair. One of the most widely accepted markers of myofibroblast differentiation is the expression of Acta2 which encodes smooth muscle alpha-actin (SMαA) that is assembled into stress fibers. However, the requirement of Acta2/SMαA in the myofibroblast differentiation of cardiac fibroblasts and its role in post-MI cardiac repair remained unknown. To answer these questions, we generated a tamoxifen-inducible cardiac fibroblast-specific Acta2 knockout mouse line. Surprisingly, mice that lacked Acta2 in cardiac fibroblasts had a normal post-MI survival rate. Moreover, Acta2 deletion did not affect the function or histology of infarcted hearts. No difference was detected in the proliferation, migration, or contractility between WT and Acta2-null cardiac myofibroblasts. Acta2-null cardiac myofibroblasts had a normal total filamentous actin level and total actin level. Acta2 deletion caused a significant compensatory increase in the transcription level of non-Acta2 actin isoforms, especially Actg2 and Acta1. Moreover, in myofibroblasts, the transcription levels of cytoplasmic actin isoforms were significantly higher than those of muscle actin isoforms. In addition, we found that myocardin-related transcription factor-A is critical for myofibroblast differentiation but is not required for the compensatory effects of non-Acta2 isoforms. In conclusion, the Acta2 deletion does not prevent the myofibroblast differentiation of cardiac fibroblasts or affect the post-MI cardiac repair, and the increased expression and stress fiber formation of non-SMαA actin isoforms and the functional redundancy between actin isoforms are able to compensate for the loss of Acta2 in cardiac myofibroblasts

Broken symmetry states and divergent resistance in suspended bilayer graphene

Graphene [1] and its bilayer have generated tremendous excitement in the physics community due to their unique electronic properties [2]. The intrinsic physics of these materials, however, is partially masked by disorder, which can arise from various sources such as ripples [3] or charged impurities [4]. Recent improvements in quality have been achieved by suspending graphene flakes [5,6], yielding samples with very high mobilities and little charge inhomogeneity. Here we report the fabrication of suspended bilayer graphene devices with very little disorder. We observe fully developed quantized Hall states at magnetic fields of 0.2 T, as well as broken symmetry states at intermediate filling factors $\nu = 0$, $\pm 1$, $\pm 2$ and $\pm 3$. The devices exhibit extremely high resistance in the $\nu = 0$ state that grows with magnetic field and scales as magnetic field divided by temperature. This resistance is predominantly affected by the perpendicular component of the applied field, indicating that the broken symmetry states arise from many-body interactions.Comment: 23 pages, including 4 figures and supplementary information; accepted to Nature Physic

Infection and genotype remodel the entire soybean transcriptome

<p>Abstract</p> <p>Background</p> <p>High throughput methods, such as high density oligonucleotide microarray measurements of mRNA levels, are popular and critical to genome scale analysis and systems biology. However understanding the results of these analyses and in particular understanding the very wide range of levels of transcriptional changes observed is still a significant challenge. Many researchers still use an arbitrary cut off such as two-fold in order to identify changes that may be biologically significant. We have used a very large-scale microarray experiment involving 72 biological replicates to analyze the response of soybean plants to infection by the pathogen <it>Phytophthora sojae </it>and to analyze transcriptional modulation as a result of genotypic variation.</p> <p>Results</p> <p>With the unprecedented level of statistical sensitivity provided by the high degree of replication, we show unambiguously that almost the entire plant genome (97 to 99% of all detectable genes) undergoes transcriptional modulation in response to infection and genetic variation. The majority of the transcriptional differences are less than two-fold in magnitude. We show that low amplitude modulation of gene expression (less than two-fold changes) is highly statistically significant and consistent across biological replicates, even for modulations of less than 20%. Our results are consistent through two different normalization methods and two different statistical analysis procedures.</p> <p>Conclusion</p> <p>Our findings demonstrate that the entire plant genome undergoes transcriptional modulation in response to infection and genetic variation. The pervasive low-magnitude remodeling of the transcriptome may be an integral component of physiological adaptation in soybean, and in all eukaryotes.</p

Bosonic Fractionalisation Transitions

At finite density, charge in holographic systems can be sourced either by explicit matter sources in the bulk or by bulk horizons. In this paper we find bosonic solutions of both types, breaking a global U(1) symmetry in the former case and leaving it unbroken in the latter. Using a minimal bottom-up model we exhibit phase transitions between the two cases, under the influence of a relevant operator in the dual field theory. We also embed solutions and transitions of this type in M-theory, where, holding the theory at constant chemical potential, the cohesive phase is connected to a neutral phase of Schr\"odinger type via a z=2 QCP.Comment: references added. minor changes. version published in JHE

How close can one approach the Dirac point in graphene experimentally?

The above question is frequently asked by theorists who are interested in graphene as a model system, especially in context of relativistic quantum physics. We offer an experimental answer by describing electron transport in suspended devices with carrier mobilities of several 10^6 cm^2V^-1s^-1 and with the onset of Landau quantization occurring in fields below 5 mT. The observed charge inhomogeneity is as low as \approx10^8 cm^-2, allowing a neutral state with a few charge carriers per entire micron-scale device. Above liquid helium temperatures, the electronic properties of such devices are intrinsic, being governed by thermal excitations only. This yields that the Dirac point can be approached within 1 meV, a limit currently set by the remaining charge inhomogeneity. No sign of an insulating state is observed down to 1 K, which establishes the upper limit on a possible bandgap

Biomimetic, Mild Chemical Synthesis of CdTe-GSH Quantum Dots with Improved Biocompatibility

Multiple applications of nanotechnology, especially those involving highly fluorescent nanoparticles (NPs) or quantum dots (QDs) have stimulated the research to develop simple, rapid and environmentally friendly protocols for synthesizing NPs exhibiting novel properties and increased biocompatibility

Spatially modulated instabilities of geometries with hyperscaling violation

We perform a study of possible instabilities of the infrared AdS(2) x R-2 region of solutions to Einstein-Maxwell-dilaton systems which exhibit an intermediate regime of hyperscaling violation and Lifshitz scaling. Focusing on solutions that are magnetically charged, we probe the response of the system to spatially modulated fluctuations, and identify regions of parameter space in which the infrared AdS(2) geometry is unstable to perturbations. The conditions for the existence of instabilities translate to restrictions on the structure of the gauge kinetic function and scalar potential. In turn, these can lead to restrictions on the dynamical critical exponent z and on the amount of hyperscaling violation theta. Our analysis thus provides further evidence for the notion that the true ground state of 'scaling' solutions with hyperscaling violation may be spatially modulated phases

Lineage-specific dynamic and pre-established enhancer–promoter contacts cooperate in terminal differentiation

Chromosome conformation is an important feature of metazoan gene regulation; however, enhancer–promoter contact remodeling during cellular differentiation remains poorly understood. To address this, genome-wide promoter capture Hi-C (CHi-C) was performed during epidermal differentiation. Two classes of enhancer–promoter contacts associated with differentiation-induced genes were identified. The first class ('gained') increased in contact strength during differentiation in concert with enhancer acquisition of the H3K27ac activation mark. The second class ('stable') were pre-established in undifferentiated cells, with enhancers constitutively marked by H3K27ac. The stable class was associated with the canonical conformation regulator cohesin, whereas the gained class was not, implying distinct mechanisms of contact formation and regulation. Analysis of stable enhancers identified a new, essential role for a constitutively expressed, lineage-restricted ETS-family transcription factor, EHF, in epidermal differentiation. Furthermore, neither class of contacts was observed in pluripotent cells, suggesting that lineage-specific chromatin structure is established in tissue progenitor cells and is further remodeled in terminal differentiation

Policy Experimentation and Innovation as a Response to Complexity in China’s Management of Health Reforms

There are increasing criticisms of dominant models for scaling up health systems in developing countries and a recognition that approaches are needed that better take into account the complexity of health interventions. Since Reform and Opening in the late 1970s, Chinese government has managed complex, rapid and intersecting reforms across many policy areas. As with reforms in other policy areas, reform of the health system has been through a process of trial and error. There is increasing understanding of the importance of policy experimentation and innovation in many of China’s reforms; this article argues that these processes have been important in rebuilding China’s health system. While China’s current system still has many problems, progress is being made in developing a functioning system able to ensure broad population access. The article analyses Chinese thinking on policy experimentation and innovation and their use in management of complex reforms. It argues that China’s management of reform allows space for policy tailoring and innovation by sub-national governments under a broad agreement over the ends of reform, and that shared understandings of policy innovation, alongside informational infrastructures for the systemic propagation and codification of useful practices, provide a framework for managing change in complex environments and under conditions of uncertainty in which ‘what works’ is not knowable in advance. The article situates China’s use of experimentation and innovation in management of health system reform in relation to recent literature which applies complex systems thinking to global health, and concludes that there are lessons to be learnt from China’s approaches to managing complexity in development of health systems for the benefit of the poor

Large Scale Searches for Brown Dwarfs and Free-Floating Planets

Searches of large scale surveys have resulted in the discovery of over 1000 brown dwarfs in the Solar neighbourhood. In this chapter we review the progress in finding brown dwarfs in large datasets, highlighting the key science goals, and summarising the surveys that have contributed most significantly to the current sample.Comment: Accepted to appear in the Handbook of Exoplanets (Springer); Editors: Hans J. Deeg & Juan Antonio Belmont