Recent studies indicate that, similar to other covalent modifications, histone lysine methylation is subject to enzyme-catalysed reversion. So far, LSD1 (also known as AOF2) and the jumonji C (JmjC)-domain-containing proteins have been shown to possess histone demethylase activity. LSD1 catalyses removal of H3K4me2/H3K4me1 through a flavin-adenine-dinucleotide-dependent oxidation reaction. In contrast, JmjC-domain-containing proteins remove methyl groups from histones through a hydroxylation reaction that requires alpha-ketoglutarate and Fe(II) as cofactors. Although an increasing number of histone demethylases have been identified and biochemically characterized, their biological functions, particularly in the context of an animal model, are poorly characterized. Here we use a loss-of-function approach to demonstrate that the mouse H3K9me2/1-specific demethylase JHDM2A (JmjC-domain-containing histone demethylase 2A, also known as JMJD1A) is essential for spermatogenesis. We show that Jhdm2a-deficient mice exhibit post-meiotic chromatin condensation defects, and that JHDM2A directly binds to and controls the expression of transition nuclear protein 1 (Tnp1) and protamine 1 (Prm1) genes, the products of which are required for packaging and condensation of sperm chromatin. Thus, our work uncovers a role for JHDM2A in spermatogenesis and reveals transition nuclear protein and protamine genes as direct targets of JHDM2A.

A noninvasive tissue current measurement technique and its use in measuring a nonuniform current density are described. This current density image is created by measuring the magnetic field arising from these currents and taking its curl. These magnetic fields are proportional to the phase component of a complex magnetic resonance image. Measurements of all three components of a quasistatic nonuniform current density in a phantom are described. Expected current density calculations from a numerical solution for the magnetic field which was created by the phantom are presented for comparison. The results of a numerical simulation of the experiment, which used this field solution and which included the effects of slice selection and sampling, are also presented. The experimental and simulated results are quantitatively compared. It is concluded that the principle source of systematic error was the finite slice thickness, which causes blurring of boundaries.

Dentin Matrix Protein 1 (Dmp1) was originally identified from dentin. However, its expression and function in vivo are not clear. To clarify these two issues, we have generated mice carrying a truncated Dmp1 gene by using gene targeting to replace exon 6 with a lacZ gene. Northern blot analysis shows the expected 5.8-kb Dmp1-lacZ fusion transcript and loss of the wild-type 2.8-kb Dmp1 transcript, confirmed by a lack of immunostaining for the protein. Using heterozygous animals, we demonstrate that Dmp1 is specific for mineralized tissues. Not previously shown, Dmp1 is also expressed in pulp cells. Dmp1-deficient embryos and newborns display no apparent gross abnormal phenotype, although there are a modest expansion of the hypertrophic chondrocyte zone and a modest increase in the long bone diameter. This suggests that DMP1 is not essential for early mouse skeletal or dental development.

No abstract

No abstract

Background-The local environment of delivered mesenchymal stem cells (MSCs) may affect their ultimate phenotype.MR fluoroscopy has the potential to guide intramyocardial MSC injection to desirable targets, such as the border between infarcted and normal tissue. We tested the ability to (1) identify infarcts, (2) navigate injection catheters to preselected targets, (3) inject safely even into fresh infarcts, and (4) confirm injection success immediately. Methods and Results-A 1.5-T MRI scanner was customized for interventional use, with rapid imaging, independent color highlighting of catheter channels, multiple-slice 3D rendering, catheter-only viewing mode, and infarct-enhanced imaging. MRI receiver coils were incorporated into guiding catheters and injection needles. These devices were tested for heating and used for targeted MSC delivery. In infarcted pigs, myocardium was targeted by MR fluoroscopy. Infarct-enhanced imaging included both saturation preparation MRI after intravenous gadolinium and wall motion. Porcine MSCs were MRI-labeled with iron-fluorescent particles. Catheter navigation and multiple cell injections were performed entirely with MR fluoroscopy at 8 frames/s with 1.7ϫ3.3ϫ8-mm voxels. Infarct-enhanced MR fluoroscopy permitted excellent delineation of infarct borders. All injections were safely and successfully delivered to their preselected targets, including infarct borders. Iron-fluorescent particle-labeled MSCs were readily visible on delivery in vivo and post mortem. Conclusions-Precise

Magnetic resonance imaging is an inherently signal-to-noise-starved technique that limits the spatial resolution, diagnostic image quality and results in typically long acquisition times that are prone to motion artefacts. This limitation is exacerbated when receive coils have poor fit due to lack of flexibility or need for padding for patient comfort. Here, we report a new approach that uses printing for fabricating receive coils. Our approach enables highly flexible, extremely lightweight conforming devices. We show that these devices exhibit similar to higher signal-to-noise ratio than conventional ones, in clinical scenarios when coils could be displaced more than 18 mm away from the body. In addition, we provide detailed material properties and components performance analysis. Prototype arrays are incorporated within infant blankets for in vivo studies. This work presents the first fully functional, printed coils for 1.5- and 3-T clinical scanners.

Purpose Elongated conductors, such as pacemaker leads, neurostimulator leads, and conductive guidewires used for interventional procedures, can couple to the MRI radiofrequency (RF) transmit field, potentially causing dangerous tissue heating. The purpose of this work is to demonstrate the feasibility of using parallel transmit to control induced RF currents in elongated conductors, thereby reducing the RF heating hazard. Methods Phantom experiments were performed on a four-channel parallel transmit system at 1.5T. Parallel transmit “null mode” excitations that induce minimal wire current were designed using coupling measurements derived from axial B1+ maps. The resulting current reduction performance was evaluated with B1+ maps, current sensor measurements, and fluoroptic temperature probe measurements. Results Null mode excitations reduced the maximum coupling mode current by factors ranging from 2–80. For the straight wire experiment, a current null imposed at a single wire location was sufficient to reduce tip heating below detectable levels. For longer insertion lengths and a curved geometry, imposing current nulls at two wire locations resulted in more distributed current reduction along the wire length. Conclusion Parallel transmit can be used to create excitations that induce minimal RF current in elongated conductors, thereby decreasing the RF heating risk, while still allowing visualization of the surrounding volume.