Lamin B1 is a component of the nuclear lamina and plays a critical role in maintaining nuclear architecture, regulating gene expression and modulating chromatin positioning. We have previously shown that LMNB1 gene duplications cause autosomal dominant leukodystrophy (ADLD), a fatal adult onset demyelinating disease. The mechanisms by which increased LMNB1 levels cause ADLD are unclear. To address this, we used a transgenic mouse model where Lamin B1 overexpression is targeted to oligodendrocytes. These mice showed severe vacuolar degeneration of the spinal cord white matter together with marked astrogliosis, microglial infiltration, and secondary axonal damage. Oligodendrocytes in the transgenic mice revealed alterations in histone modifications favoring a transcriptionally repressed state. Chromatin changes were accompanied by reduced expression of genes involved in lipid synthesis pathways, many of which are known to play important roles in myelin regulation and are preferentially expressed in oligodendrocytes. Decreased lipogenic gene expression resulted in a significant reduction in multiple classes of lipids involved in myelin formation. Many of these gene expression changes and lipid alterations were observed even before the onset of the phenotype, suggesting a causal role. Our findings establish, for the first time, a link between LMNB1 and lipid synthesis in oligodendrocytes, and provide a mechanistic framework to explain the age dependence and white matter involvement of the disease phenotype. These results have implications for disease pathogenesis and may also shed light on the regulation of lipid synthesis pathways in myelin maintenance and turnover.
Key words: chromatin; demyelination; gene expression; inflammation; Lamin B1; lipid
Significance StatementAutosomal dominant leukodystrophy (ADLD) is fatal neurological disorder caused by increased levels of the nuclear protein, Lamin B1. The disease is characterized by an age-dependent loss of myelin, the fatty sheath that covers nerve fibers. We have studied a mouse model where Lamin B1 level are increased in oligodendrocytes, the cell type that produces myelin in the CNS. We demonstrate that destruction of myelin in the spinal cord is responsible for the degenerative phenotype in our mouse model. We show that this degeneration is mediated by reduced expression of lipid synthesis genes and the subsequent reduction in myelin enriched lipids. These findings provide a mechanistic framework to explain the age dependence and tissue specificity of the ADLD disease phenotype.
Recent developments of the Velocity Gradient Technique (VGT) show that the velocity gradients provide a reliable tracing of magnetic field direction in turbulent plasmas. In this paper, we explore the ability of velocity gradients to measure the magnetization of interstellar medium. We demonstrate that the distribution of velocity gradient orientations provides a reliable estimation of the magnetization of the media. In particular, we determine the relation between Alfvenic Mach number M A in the range of M A ∈ [0.2, 1.7] and properties of the velocity gradient distribution, namely, with the dispersion of velocity gradient orientation as well as with the peak to base ratio of the amplitudes. We apply our technique for a selected GALFA-HI region and find the results consistent with the expected behavior of M A . Using 3D MHD simulations we successfully compare the results with our new measure of magnetization that is based on the dispersion of starlight polarization. We demonstrate that, combined with the velocity dispersion along the line of sight direction, our technique is capable to delivering the magnetic field strength. The new technique opens a way to measure magnetization using other gradient measures such as synchrotron intensity gradients (SIGs) and synchrotron polarization gradients (SPGs).
TR, Rosengart MR, Tsung A. Calcium/ calmodulin-dependent protein kinase IV limits organ damage in hepatic ischemia-reperfusion injury through induction of autophagy.
We develop an unprecedented 3D pulsed chaos lidar system for potential intelligent machinery applications. Benefited from the random nature of the chaos, conventional CW chaos lidars already possess excellent anti-jamming and anti-interference capabilities and have no range ambiguity. In our system, we further employ self-homodyning and time gating to generate a pulsed homodyned chaos to boost the energy-utilization efficiency. Compared to the original chaos, we show that the pulsed homodyned chaos improves the detection SNR by more than 20 dB. With a sampling rate of just 1.25 GS/s that has a native sampling spacing of 12 cm, we successfully achieve millimeter-level accuracy and precision in ranging. Compared with two commercial lidars tested side-by-side, namely the pulsed Spectroscan and the random-modulation continuous-wave Lidar-lite, the pulsed chaos lidar that is in compliance with the class-1 eye-safe regulation shows significantly better precision and a much longer detection range up to 100 m. Moreover, by employing a 2-axis MEMS mirror for active laser scanning, we also demonstrate real-time 3D imaging with errors of less than 4 mm in depth.
Electromagnetic absorption and subsequent heating of nanoparticle solutions and simple NaCl ionic solutions is examined for biomedical applications in the radiofrequency range at 13.56 MHz. It is shown via both theory and experiment that for in vitro measurements the shape of the solution container plays a major role in absorption and heating.
Magnetohydrodynamic(MHD) turbulence displays velocity anisotropies which reflect the direction of the magnetic field. This anisotropy has led to the development of a number of statistical techniques for studying magnetic fields in the interstellar medium. In this paper, we review and compare three techniques that use radio position-position-velocity data for determining magnetic field strength and morphology : the correlation function anisotropy (CFA), Principal Component Analysis of Anisotropies (PCAA), and the more recent Velocity Gradient Technique (VGT). We compare these three techniques and suggest improvements to the CFA and PCAA techniques to increase their accuracy and versatility. In particular, we suggest and successfully implement a much faster way of calculating non-periodic correlation functions for the CFA. We discuss possible improvements to the current implementation of the PCAA. We show the advantages of the VGT in terms of magnetic field tracing and stress the complementary nature with the other two techniques.
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