Transcriptional regulation of androgen receptor gene expression in Sertoli cells and other cell types

Cooperative actions of FSH and androgens on initiation, maintenance, and restoration of spermatogenesis have been described. In the present experiments the regulatory effects of FSH on androgen receptor (AR) gene expression in Sertoli cells were studied. In immature rats injection of FSH (1 microgram/g BW, ip) resulted in a rapid down-regulation of testicular AR mRNA expression (4 h), followed by recovery to the control level (10 h). Using cultured immature Sertoli cells, a similar transient effect on AR mRNA expression was observed after the addition of FSH (500 ng/ml) or (Bu)2cAMP (0.5 mM). Cycloheximide treatment of the cells did not prevent the rapid FSH-induced down-regulation of AR mRNA expression, indicating that de novo protein synthesis is not required for this effect. Furthermore, using a transcriptional run-on assay, no marked decrease in the rate of AR gene transcription was found upon treatment of the cultured Sertoli cells with FSH for 2 or 4 h. This demonstrates that the short term effect of FSH or AR mRNA expression reflects a change in mRNA stability. The AR protein level was not markedly affected by the transient decrease in AR mRNA expression. When immature Sertoli cells were incubated with FSH for longer time periods (24-72 h), both AR mRNA and protein expression were increased. In Sertoli cells isolated from 15-day-old rats, this increase was higher (mRNA, 2- to 3-fold; protein, 2-fold) than in Sertoli cell

Threeâ dimensional imaging of shear bands in bulk metallic glass composites

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134811/1/jmi12443_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134811/2/jmi12443.pd

Allosteric inhibition of carnosinase (CN1) by inducing a conformational shift

In humans, low serum carnosinase (CN1) activity protects patients with type 2 diabetes from diabetic nephropathy. We now characterized the interaction of thiol-containing compounds with CN1 cysteine residue at position 102, which is important for CN1 activity. Reduced glutathione (GSH), N-acetylcysteine and cysteine (3.2 \uc2\ub1 0.4, 2.0 \uc2\ub1 0.3, 1.6 \uc2\ub1 0.2 \uc2\ub5mol/mg/h/mM; p <.05) lowered dose-dependently recombinant CN1 (rCN1) efficiency (5.2 \uc2\ub1 0.2 \uc2\ub5mol/mg/h/mM) and normalized increased CN1 activity renal tissue samples of diabetic mice. Inhibition was allosteric. Substitution of rCN1 cysteine residues at position 102 (Mut1C102S) and 229 (Mut2C229S) revealed that only cysteine-102 is influenced by cysteinylation. Molecular dynamic simulation confirmed a conformational rearrangement of negatively charged residues surrounding the zinc ions causing a partial shift of the carnosine ammonium head and resulting in a less effective pose of the substrate within the catalytic cavity and decreased activity. Cysteine-compounds influence the dynamic behaviour of CN1 and therefore present a promising option for the treatment of diabetes

Can We Identify Sources of Fine Particles Responsible for Exercise-Induced Ischemia on Days with Elevated Air Pollution? The ULTRA Study

Epidemiologic studies have shown that ambient particulate matter (PM) has adverse effects on cardiovascular health. Effective mitigation of the health effects requires identification of the most harmful PM sources. The objective of our study was to evaluate relative effects of fine PM [aerodynamic diameter ≤ 2.5 μm (PM(2.5))] from different sources on exercise-induced ischemia. We collected daily outdoor PM(2.5) samples between autumn 1998 and spring 1999 in Helsinki, Finland. The mass of PM(2.5) was apportioned between five sources. Forty-five elderly nonsmoking persons with stable coronary heart disease visited a clinic biweekly for submaximal exercise testing, during which the occurrence of ST segment depressions was recorded. Levels of PM(2.5) originating from local traffic and long-range transport were associated with ST segment depressions > 0.1 mV, with odds ratios at 2-day lag of 1.53 [95% confidence interval (CI), 1.19–1.97] and 1.11 (95% CI, 1.02–1.20) per 1 μg/m(3), respectively. In multipollutant models, where we used indicator elements for sources instead of source-specific PM(2.5), only absorbance (elemental carbon), an indicator of local traffic and other combustion, was associated with ST segment depressions. Our results suggest that the PM fraction originating from combustion processes, notably traffic, exacerbates ischemic heart diseases associated with PM mass

Pulsar timing arrays and the challenge of massive black hole binary astrophysics

Pulsar timing arrays (PTAs) are designed to detect gravitational waves (GWs) at nHz frequencies. The expected dominant signal is given by the superposition of all waves emitted by the cosmological population of supermassive black hole (SMBH) binaries. Such superposition creates an incoherent stochastic background, on top of which particularly bright or nearby sources might be individually resolved. In this contribution I describe the properties of the expected GW signal, highlighting its dependence on the overall binary population, the relation between SMBHs and their hosts, and their coupling with the stellar and gaseous environment. I describe the status of current PTA efforts, and prospect of future detection and SMBH binary astrophysics.Comment: 18 pages, 4 figures. To appear in the Proceedings of the 2014 Sant Cugat Forum on Astrophysics. Astrophysics and Space Science Proceedings, ed. C.Sopuerta (Berlin: Springer-Verlag

How are management fashions institutionalized? The role of institutional work

We explore how transitory management fashions become institutionalized. Based on the concepts of institutional entrepreneurship and institutional work, we postulate that fashionable management practices acquire permanence when they are anchored within fieldwide institutions. The building of such institutions requires various types of institutional work, including political work, technical work and cultural work. Based on a review of the empirical literature on various management fashions, we identify the actors engaging in these different types of works, and their skills. Our results suggest that the institutionalization effect is stronger if more types of institutional work are deployed and if the skill sets of the involved actors vary. We also argue that institutional construction in the case of management fashions is likely to take the form of decentralized `partaking' rather than being led by a single dominant institutional entrepreneur. We conclude with implications for the study of management fashions and the role of agency in institutionalization

Associations between PM2.5 and Heart Rate Variability Are Modified by Particle Composition and Beta-Blocker Use in Patients with Coronary Heart Disease

BACKGROUND: It has been hypothesized that ambient particulate air pollution is able to modify the autonomic nervous control of the heart, measured as heart rate variability (HRV). Previously we reported heterogeneous associations between particulate matter with aerodynamic diameter < 2.5 mu m (PM2.5) and HRV across three study centers. OBJECTIVE: We evaluated whether exposure misclassification, effect modification by medication, or differences in particle composition could explain die inconsistencies. METHODS: Subjects with coronary heart disease visited clinics biweekly in Amsterdam, the Netherlands; Erfurt, Germany; and Helsinki, Finland for 6-8 months. The standard deviation (SD) of NN intervals on an electrocardiogram (ECG; SDNN) and high frequency (HF) power of HRV was measured with ambulatory ECG during paced breathing. Outdoor levels of PM2.5 were measured at a central site. In Amsterdam and Helsinki, indoor and personal PM2.5 were measured during the 24 hr preceding the clinic visit. PM2.5 was apportioned between sources using principal component analyses. We analyzed associations of indoor/personal PM2.5 elements of PM2.5 and source-specific PM2.5 With HRV using linear regression. RESULTS: Indoor and personal PM2.5 were not associated with HRV. Increased outdoor PM2.5 was associated with decreased SDNN and HF at lags of 2 and 3 days only among persons not using beta-blocker medication. Traffic-related PM2.5 was associated with decreased SDNN, and long-range transported PM2.5 with decreased SDNN and HF, most strongly among persons not using beta blockers. Indicators for PM2.5 from traffic and long-range transport were also associated with decreased HRV. CONCLUSIONS: Our results suggest that differences in the composition of particles, beta-blocker use, and obesity of study subjects may explain some inconsistencies among previous studies on HRV

The structures and biological activities of the lipo-oligosaccharide nodulation signals produced by type I and II strains of Bradyrhizobium japonicum

Bradyrhizobium japonicum produces lipo-oligosaccharide signal molecules that induce deformation of root hairs and meristematic activity on soybeans. B. japonicum USDA135 (a Type I strain) produces modified chitin pentasaccharide molecules with either a terminal N-C16:0- or N-C18:1-glucosamine with and without an O-acetyl group at C-6 and with 2-O-methylfucose linked to C-6 of the reducing N-acetylglucosamine. An additional molecule has N-C16:1-glucosamine and no O-acetyl group. All of these molecules cause root hair deformation on Vicia sativa and Glycine soja. The C18:1-containing molecules were tested and found to induce meristem formation on G. soja. USDA61 (a Type II strain) produces eight additional molecules. Five have a carbamoyl group on the terminal N-acylglucosamine. Six have chitin tetrasaccharide backbones. Three have a terminal N-acyl-N-methylglucosaminosyl residue. In four molecules, the reducing-end N-acetylglucosamine is glycosidically linked to glycerol and has a branching fucosyl, rather than a 2-O-methylfucosyl, residue. One molecule has a terminal N-acylglucosamine that has both acetyl and carbamoyl groups (one each).Plant science