The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome.

X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X's gene content, gene expression, and evolution

SHORT-TERM RADIO VARIABILITY AND PARSEC-SCALE STRUCTURE IN A GAMMA-RAY NARROW-LINE SEYFERT 1 GALAXY 1H 0323+342

We made simultaneous single-dish and very long baseline interferometer (VLBI) observations of a narrow-line Seyfert 1 galaxy 1H 323+342, showing gamma-ray activity revealed by Fermi/Large Area Telescope observations. We found significant variation of the total flux density at 8 GHz on the timescale of one month by the single-dish monitoring. The total flux density varied by 5.5% in 32 days, which is comparable to the gamma-ray variability timescale, corresponding to the variability brightness temperature of 7.0 x 10(11) K. The source consists of central and southeastern components on the parsec (pc) scale. Only the flux of the central component decreased in the same way as the total flux density, indicating that the short-term radio variability, and probably the gamma-ray-emitting region, is associated with this component. From the VLBI observations, we obtained brightness temperatures of greater than (5.2 +/- 0.3) x 10(10) K and derived an equipartition Doppler factor of greater than 1.7, a variability Doppler factor of 2.2, and an 8 GHz radio power of 10(24.6) W Hz(-1). Combining them, we conclude that acceleration of radio jets and creation of high-energy particles are ongoing in the central engine and that the apparent very radio-loud feature of the source is due to the Doppler boosting effect, resulting in the intrinsic radio loudness being an order of magnitude smaller than the observed values. We also conclude that the pc-scale jet represents recurrent activity from the spectral fitting and the estimated kinematic age of pc- and kpc-scale extended components with different position angles

Short-term radio variability and parsec-scale structure in a gamma-ray narrow-line seyfert 1 galaxy 1H 0323+342

We made simultaneous single-dish and very long baseline interferometer (VLBI) observations of a narrow-line Seyfert 1 galaxy 1H 323+342, showing gamma-ray activity revealed by Fermi/Large Area Telescope observations. We found significant variation of the total flux density at 8 GHz on the timescale of one month by the single-dish monitoring. The total flux density varied by 5.5% in 32 days, which is comparable to the gamma-ray variability timescale, corresponding to the variability brightness temperature of 7.0 x 10(11) K. The source consists of central and southeastern components on the parsec (pc) scale. Only the flux of the central component decreased in the same way as the total flux density, indicating that the short-term radio variability, and probably the gamma-ray-emitting region, is associated with this component. From the VLBI observations, we obtained brightness temperatures of greater than (5.2 +/- 0.3) x 10(10) K and derived an equipartition Doppler factor of greater than 1.7, a variability Doppler factor of 2.2, and an 8 GHz radio power of 10(24.6) W Hz(-1). Combining them, we conclude that acceleration of radio jets and creation of high-energy particles are ongoing in the central engine and that the apparent very radio-loud feature of the source is due to the Doppler boosting effect, resulting in the intrinsic radio loudness being an order of magnitude smaller than the observed values. We also conclude that the pc-scale jet represents recurrent activity from the spectral fitting and the estimated kinematic age of pc- and kpc-scale extended components with different position angles

Acute and Subacute Toxicity In Vivo of Thermal-Sprayed Silver Containing Hydroxyapatite Coating in Rat Tibia

To reduce the incidence of implant-associated infection, we previously developed a novel coating technology using hydroxyapatite (HA) containing silver (Ag). This study examined in vivo acute and subacute toxicity associated with the Ag-HA coating in rat tibiae. Ten-week-old rats received implantation of HA-, 2% Ag-HA-, or 50% Ag-HA-coated titanium rods. Concentrations of silver in serum, brain, liver, kidneys, and spleen were measured in the acute phase (2–4 days after treatment) and subacute phase (4–12 weeks after treatment). Biochemical and histological examinations of those organs were also performed. Mean serum silver concentration peaked in the acute phase and then gradually decreased. Mean silver concentrations in all examined organs from the 2% Ag-HA coating groups showed no significant differences compared with the HA coating group. No significant differences in mean levels of glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, lactate dehydrogenase, creatinine, or blood urea nitrogen were seen between the three groups and controls. Histological examinations of all organs revealed no abnormal pathologic findings. No acute or subacute toxicity was seen in vivo for 2% Ag-HA coating or HA coating. Ag-HA coatings on implants may represent biologically safe antibacterial biomaterials and may be of value for reducing surgical-site infections related to implantation

Multiple ETS family proteins regulate PF4 gene expression by binding to the same ETS binding site.

In previous studies on the mechanism underlying megakaryocyte-specific gene expression, several ETS motifs were found in each megakaryocyte-specific gene promoter. Although these studies suggested that several ETS family proteins regulate megakaryocyte-specific gene expression, only a few ETS family proteins have been identified. Platelet factor 4 (PF4) is a megakaryocyte-specific gene and its promoter includes multiple ETS motifs. We had previously shown that ETS-1 binds to an ETS motif in the PF4 promoter. However, the functions of the other ETS motifs are still unclear. The goal of this study was to investigate a novel functional ETS motif in the PF4 promoter and identify proteins binding to the motif. In electrophoretic mobility shift assays and a chromatin immunoprecipitation assay, FLI-1, ELF-1, and GABP bound to the -51 ETS site. Expression of FLI-1, ELF-1, and GABP activated the PF4 promoter in HepG2 cells. Mutation of a -51 ETS site attenuated FLI-1-, ELF-1-, and GABP-mediated transactivation of the promoter. siRNA analysis demonstrated that FLI-1, ELF-1, and GABP regulate PF4 gene expression in HEL cells. Among these three proteins, only FLI-1 synergistically activated the promoter with GATA-1. In addition, only FLI-1 expression was increased during megakaryocytic differentiation. Finally, the importance of the -51 ETS site for the activation of the PF4 promoter during physiological megakaryocytic differentiation was confirmed by a novel reporter gene assay using in vitro ES cell differentiation system. Together, these data suggest that FLI-1, ELF-1, and GABP regulate PF4 gene expression through the -51 ETS site in megakaryocytes and implicate the differentiation stage-specific regulation of PF4 gene expression by multiple ETS factors