Srg3 (SWI3-related gene product) is a mouse homolog of yeast SWI3, Drosophila melanogaster MOIRA (also named MOR/BAP155), and human BAF155 and is known as a core subunit of SWI/SNF complex. This complex is involved in the chromatin remodeling required for the regulation of transcriptional processes associated with development, cellular differentiation, and proliferation. We generated mice with a null mutation in the Srg3 locus to examine its function in vivo. Homozygous mutants develop in the early implantation stage but undergo rapid degeneration thereafter. An in vitro outgrowth study revealed that mutant blastocysts hatch, adhere, and form a layer of trophoblast giant cells, but the inner cell mass degenerates after prolonged culture. Interestingly, about 20% of heterozygous mutant embryos display defects in brain development with abnormal organization of the brain, a condition known as exencephaly. Histological examination suggests that exencephaly is caused by the failure in neural fold elevation, resulting in severe brain malformation. Our findings demonstrate that Srg3 is essential for early embryogenesis and plays an important role in the brain development of mice.

Pseudomonas aeruginosa is a ubiquitous environmental bacterium whose major catalase (KatA) is highly stable, extracellularly present, and required for full virulence as well as for peroxide resistance in planktonic and biofilm states. Here, we dismantled the function of P. aeruginosa KatA (KatA Pa ) by comparing its properties with those of two evolutionarily related (clade 3 monofunctional) catalases from Bacillus subtilis (KatA Bs ) and Streptomyces coelicolor (CatA Sc ). We switched the coding region for KatA Pa with those for KatA Bs and CatA Sc , expressed the catalases under the potential katA-regulatory elements in a P. aeruginosa PA14 katA mutant, and verified their comparable protein levels by Western blot analysis. The activities of KatA Bs and CatA Sc , however, were less than 40% of the KatA Pa activity, suggestive of the difference in intrinsic catalatic activity or efficiency for posttranslational activity modulation in P. aeruginosa. Furthermore, KatA Bs and CatA Sc were relatively susceptible to proteinase K, whereas KatA Pa was highly stable upon proteinase K treatment. As well, KatA Bs and CatA Sc were undetectable in the extracellular milieu. Nevertheless, katA Bs and catA Sc fully rescued the peroxide sensitivity and osmosensitivity of the katA mutant, respectively. Both catalase genes rescued the attenuated virulence of the katA mutant in mouse acute infection and Drosophila melanogaster models. However, the peroxide susceptibility of the katA mutant in a biofilm growth state was rescued by neither katA Bs nor catA Sc . Based on these results, we propose that the P. aeruginosa KatA is highly stable compared to the two major catalases from gram-positive bacteria and that its unique properties involving metastability and extracellular presence may contribute to the peroxide resistance of P. aeruginosa biofilm and presumably to chronic infections.

Background-Maximal hyperemia is a prerequisite for the accurate measurement of fractional flow reserve (FFR).Although continuous infusion of adenosine via the femoral vein is considered to be the gold standard, this requires an additional invasive procedure for femoral vein access and is difficult to use during transradial coronary catheterization. We performed this prospective study to evaluate the feasibility and efficacy of peripheral intravenous infusion of adenosine for FFR measurement. Methods and Results-Seventy-one patients were prospectively enrolled, and FFR was measured using a 0.014-inch coronary pressure wire. Hyperemic efficacy of adenosine was compared among intracoronary bolus injection and continuous IV infusion (140 g/min/kg) via the femoral and via the forearm vein. In 20 patients, hyperemic mean transit time and index of microcirculatory resistance were also measured. Mean FFR after bolus administration of adenosine was 0.81Ϯ0.

We used a list of genes enriched in each of 21 stem cell subpopulations, and their upstream genomic sequences. The LVM-based study allowed us to uncover the regulatory modules for each stem cell cluster, e.g. GABP and E2F for the proliferation phase, and Ap2alpha and Ap2gamma for the quiescence phase. Furthermore, the identities of the stem cell clusters were well revealed by the constituent genes that were directly targeted by the modules. Consequently, our analytical framework was demonstrated to be useful through a detailed case study of stem cell differentiation and can be applied to problems with similar characteristics.

Background-The effects of left ventricular (LV) loading conditions on LV dyssynchrony have not been elucidated. We modified LV loading conditions to reveal their effects on echocardiography-derived LV dyssynchrony index (LVdys) in patients with documented nonischemic dilated cardiomyopathy. Methods and Results-Thirty-seven patients were consecutively enrolled. After baseline measurements, pneumatic compression of the lower extremities (Pcom) was used to increase LV afterload. Subsequently, sublingual nitroglycerin (SL-NG) was administered to modify preload. Conventional echocardiographic parameters, LVdys (by speckle-tracking radial strain analysis) and LV end-systolic wall stress (LV-ESWS), were calculated under each condition. LVdys-6 (defined as the maximal difference in time-to-peak radial strain between 6 myocardial segments) and LV-ESWS increased under Pcom (for LVdys-6, 159Ϯ117 at baseline versus 239Ϯ140 ms under Pcom, PϽ0.05; for LV-ESWS, 191Ϯ63 versus 228Ϯ80 g/m 2 , PϽ0.05) After SL-NG application, both parameters decreased significantly (for LVdys-6, 239Ϯ140 under Pcom versus 147Ϯ103 ms after SL-NG, PϽ0.05; for LV-ESWS, 228Ϯ80 under Pcom versus 189Ϯ67 g/m 2 after SL-NG, PϽ0.05). When the presence of LV dyssynchrony was defined as the absolute difference in time-to-peak radial strain between the anteroseptal and posterior segments (LVdys-2), the results were unchanged. Using 130 ms as a cutoff value, the proportion of patients with LV dyssynchrony changed significantly (29.7% at baseline, 45.9% under Pcom, and 35.1% after SL-NG). When the presence of LV dyssynchrony was defined as standard deviation of the time to peak radial strain for 6 segments (LVdys-SD), the results were same. LVdys and LV-ESWS showed a modest but significant association with each other (rϭ0.47, PϽ0.001 for LVdys-6; rϭ0.41, PϽ0.001 for LVdys-2; rϭ0.46, PϽ0.001 for LVdys-SD). Conclusions-To the best of our knowledge, the present study provides the first evidence of a significant association between LVdys and LV loading status, reflective of a dynamic nature of LVdys. Accordingly, LV loading conditions should be taken into account when echocardiographic LVdys is used for clinical decision-making of selecting candidates for cardiac resynchronization therapy or when it is used as a surrogate marker of prognosis. (Circ Cardiovasc Imaging. 2010;3:272-281.)

Abstract-Background: HIV and HCV infections are both characterized by increased oxidative stress. Information on the magnitude of this increase and its consequences in HIV/HCV co-infection and viral replication is limited. We investigated the relationship between oxidative stress and HIV-progression in HIV/HCV co-infected and HIV mono-infected adults.Methods: 106 HIV/HCV co-infected and 115 HIV mono-infected participants provided demographic information and blood to determine 8-oxo-dG and percent oxidized glutathione.

Immature double-positive thymocytes are sensitive to glucocorticoid (GC)-induced apoptosis, whereas mature single-positive T cells are relatively resistant. Thymocytes seem to acquire resistance to GCs during differentiation into mature single-positive thymocytes. However, detailed knowledge concerning what determines the sensitivity of thymocytes to GCs and how GC sensitivity is regulated in thymocytes during development is lacking. We have previously reported that the murine SRG3 gene (for SWI3-related gene) is required for GC-induced apoptosis in a thymoma cell line. Herein, we provide results suggesting that the expression level of SRG3 protein determines the GC sensitivity of T cells in mice. SRG3 associates with the GC receptor in the thymus, but rarely in the periphery. Transgenic overexpression of the SRG3 protein in peripheral T cells induces the formation of the complex and renders the cells sensitive to GC-induced apoptosis. Our results also show that blocking the formation of the SRG3-GC receptor complex with a dominant negative mutant form of SRG3 decreases GC sensitivity in thymoma cells. In addition, mice overexpressing the SRG3 protein appear to be much more susceptible to stress-induced deletion of peripheral T cells than normal mice, which may result in an immunosuppressive state in an animal.

Bupleurum falcatum, which belongs to the family Apiaceae, has long been applied for curative treatments, especially as a liver tonic, in herbal medicine. The chloroplast (cp) genome has been an ideal model to perform the evolutionary and comparative studies because of its highly conserved features and simple structure. The Apiaceae family is taxonomically close to the Araliaceae family and there have been numerous complete chloroplast genome sequences reported in the Araliaceae family, while little is known about the Apiaceae family. In this study, the complete sequence of the B. falcatum chloroplast genome was obtained. The full-length of the cp genome is 155,989 nucleotides with a 37.66% overall guanine-cytosine (GC) content and shows a quadripartite structure composed of three nomenclatural regions: a large single-copy (LSC) region, a small single-copy (SSC) region, and a pair of inverted repeat (IR) regions. The genome occupancy is 85,912-bp, 17,517-bp, and 26,280-bp for LSC, SSC, and IR, respectively. B. falcatum was shown to contain 111 unique genes (78 for protein-coding, 29 for tRNAs, and four for rRNAs, respectively) on its chloroplast genome. Genic comparison found that B. falcatum has no pseudogenes and has two gene losses, accD in the LSC and ycf15 in the IRs. A total of 55 unique tandem repeat sequences were detected in the B. falcatum cp genome. This report is the first to describe the complete chloroplast genome sequence in B. falcatum and will open up further avenues of research to understand the evolutionary panorama and the chloroplast genome conformation in related plant species.