The Expression of microRNA and microRNA Clusters in the Aging Heart

Background: The microRNAs have been implicated in the process of cardiac development, cardiac hypertrophy, and heart failure. However, the impact of adult aging on cardiac expression of miRNA clusters, as well as both miRNA guide (miR) and passenger (miR*) strands has not been well established. Methods/Results: We explored the expression profile of both miR and miR * in the hearts of young adult versus old mice. We found that 65 miRNAs were differentially expressed in the old versus young adult hearts; approximately half of them were clustered miRNAs that were distributed in 11 miRNA clusters. Each miRNA cluster contained from 2 to as many as 71 miRNA genes. The majority of the clusters displayed similar expression, with most cluster members within a cluster being either increased or decreased together, suggesting that most clusters are likely to be regulated by a common signaling mechanism and that the combined expression of multiple miRNA genes in a cluster could pose an impact on a broad range of targets during aging. We also found age-related changes in the expression of miR*s. The expression of both miR and miR* correlated with that of pri-miRNA transcript over the time course from development and maturation through adult aging. Age-related changes in the expression of Ago1 and Ago2 proteins in the heart were also observed. Transfection assay revealed that both Ago1 and Ago2 synergistically induced miR-21 and miR-21 * when the mir-21 plasmid was co-transfected with either

Regulation of cardiac microRNAs by serum response factor

Serum response factor (SRF) regulates certain microRNAs that play a role in cardiac and skeletal muscle development. However, the role of SRF in the regulation of microRNA expression and microRNA biogenesis in cardiac hypertrophy has not been well established. In this report, we employed two distinct transgenic mouse models to study the impact of SRF on cardiac microRNA expression and microRNA biogenesis. Cardiac-specific overexpression of SRF (SRF-Tg) led to altered expression of a number of microRNAs. Interestingly, downregulation of miR-1, miR-133a and upregulation of miR-21 occurred by 7 days of age in these mice, long before the onset of cardiac hypertrophy, suggesting that SRF overexpression impacted the expression of microRNAs which contribute to cardiac hypertrophy. Reducing cardiac SRF level using the antisense-SRF transgenic approach (Anti-SRF-Tg) resulted in the expression of miR-1, miR-133a and miR-21 in the opposite direction. Furthermore, we observed that SRF regulates microRNA biogenesis, specifically the transcription of pri-microRNA, thereby affecting the mature microRNA level. The mir-21 promoter sequence is conserved among mouse, rat and human; one SRF binding site was found to be in the mir-21 proximal promoter region of all three species. The mir-21 gene is regulated by SRF and its cofactors, including myocardin and p49/Strap. Our study demonstrates that the downregulation of miR-1, miR-133a, and upregulation of miR-21 can be reversed by one single upstream regulator, SRF. These results may help to develop novel therapeutic interventions targeting microRNA biogenesis

MACK-IV, a new version of MACK: a program to calculate nuclear response functions from data in ENDF/B format

MACK-IV calculates nuclear response functions important to the neutronics analysis of nuclear and fusion systems. A central part of the code deals with the calculation of the nuclear response function for nuclear heating more commonly known as the kerma factor. Pointwise and multigroup neutron kerma factors, individual reactions, helium, hydrogen, and tritium production response functions are calculated from any basic nuclear data library in ENDF/B format. The program processes all reactions in the energy range of 0 to 20 MeV for fissionable and nonfissionable materials. The program also calculates the gamma production cross sections and the gamma production energy matrix. A built-in computational capability permits the code to calculate the cross sections in the resolved and unresolved resonance regions from resonance parameters in ENDF/B with an option for Doppler broadening. All energy pointwise and multigroup data calculated by the code can be punched, printed and/or written on tape files. Multigroup response functions (e.g., kerma factors, reaction cross sections, gas production, atomic displacements, etc.) can be outputted in the format of MACK-ACTIVITY-Table suitable for direct use with current neutron (and photon) transport codes

Assessment of the teledial gas-cooled transmuter concept

The application of four gas-turbine, modular helium cooled reactors and an accelerator unit (GT/AD-MHR) has been proposed for burning transuranics recycled from LWR waste. The recycled LWR discharged transuranics encapsulated in TRISO coated particles are first loaded into the outer thermal spectrum zone of the GT/AD-MHR for burning in the critical mode for about three years. Previously burned fuel is in a central fast zone. In the fourth year, the same unit is configured as an accelerator-driven system, containing a centrally located spallation target. The three-year, thermal-zone burned fuel and the inner fast-zone fuel from the critical mode operation are used in this subcritical cycle, and remain in their respective zones. At the end of this one-year subcritical irradiation, the outer thermal-zone fuel is reconstituted and used as fast-zone fuel in another critical mode operation. As the fuel in the fast-zone has reached its end of life it is discharged, with very low transuranics content. The critical mode operation is staggered, and each GT/AD-MGR unit undergoes the subcritical burn in one out of four year. The physics performance of the GT/AD-MHR has been evaluated using independent deterministic and Monte Carlo codes and the results of the study are presented in the current paper. A companion paper discussing the verification of the codes is also presented at this meeting. Single-batch and three-batch fuel loading schemes for the GT/AD-MHR have been evaluated using the REBUS-3/DIF3D fuel cycle code, to determine the feasibility of achieving very high burnup without exceeding reactivity and power density limits. The reactor physics of the GT-MHR is complicated by the presence of the low-lying plutonium and Er-167 resonances (0.2--1.1 eV) and by the fact that the neutron spectrum has a low-energy peak about this energy range. This peak can change depending on the core state or material loading. The location of the peak and the direction of the spectral shift greatly affect both the resonance fission and capture rates and dictate the core or element criticality state and the magnitude and sign of reactivity coefficients. For these reasons, 23-energy-group, burnup-dependent microscopic cross sections are employed in the REBUS-3/DIF3D model used for evaluating the system. These cross sections were generated with the DRAGON codes using ENDF/B-VI data

Activation characteristics of different steel alloys proposed for near-term fusion reactors

Analyses have been made for different structural alloys proposed for the International Thermonuclear Experimental Reactor (ITER). Candidate alloys include austenitic steels stabilized with nickel (NiSS) or manganese (MnSS). The radioactivity, the decay heat, and the waste disposal rating of each alloy have been calculated for the inboard shield of the ITER design option utilizing water cooled solid breeder blanket. The results show, for the 55 cm inboard shield and after 3 MW.yr/m2 fluence, that the long term activation problems, e.g., radioactive waste, of the MnSS are much less than that of the NiSS. All the MnSS alloys considered are qualified as Class C or better low level waste. Most of the NiSS alloys are not qualified for near surface burial. However, the short term decay heat generation rate for the MnSS is much higher than that of the NiSS. 6 refs., 8 figs., 2 tabs

Radioactive Isotope Production for Medical Applications Using Kharkov Electron Driven Subcritical Assembly Facility.

Kharkov Institute of Physics and Technology (KIPT) of Ukraine has a plan to construct an accelerator driven subcritical assembly. The main functions of the subcritical assembly are the medical isotope production, neutron thereby, and the support of the Ukraine nuclear industry. Reactor physics experiments and material research will be carried out using the capabilities of this facility. The United States of America and Ukraine have started collaboration activity for developing a conceptual design for this facility with low enrichment uranium (LEU) fuel. Different conceptual designs are being developed based on the facility mission and the engineering requirements including nuclear physics, neutronics, heat transfer, thermal hydraulics, structure, and material issues. Different fuel designs with LEU and reflector materials are considered in the design process. Safety, reliability, and environmental considerations are included in the facility conceptual design. The facility is configured to accommodate future design improvements and upgrades. This report is a part of the Argonne National Laboratory Activity within this collaboration for developing and characterizing the subcritical assembly conceptual design. In this study, the medical isotope production function of the Kharkov facility is defined. First, a review was carried out to identify the medical isotopes and its medical use. Then a preliminary assessment was performed without including the self-shielding effect of the irradiated samples. Finally, more detailed investigation was carried out including the self-shielding effect, which defined the sample size and irradiation location for producing each medical isotope. In the first part, the reaction rates were calculated as the multiplication of the cross section with the unperturbed neutron flux of the facility. Over fifty isotopes were considered and all transmutation channels are used including (n,{gamma}), (n,2n), (n,p), and ({gamma},n). In the second part, the parent isotopes with high reaction rate were explicitly modeled in the calculations. For the nuclides with a very high capture microscopic cross section, such as iridium, rhenium, and samarium, their specific activities are reduced by a factor of 30 when the self-shielding effect is included. Four irradiation locations were considered in the analyses to maximize the medical isotope production rate. The results show the self-shield effect reduces the specific activity values and changes the irradiation location for obtaining the maximum possible specific activity. The axial and radial distributions of the specific activity were used to define the irradiation sample size for producing each isotope

1-Phenyl-1H-naphtho­[1,2-e][1,3]oxazin-3(2H)-one

In the title compound, C18H13NO2, the naphthalene (r.m.s. deviation = 0.025 Å) and benzaldehyde (r.m.s. deviation = 0.006 Å) groups are oriented at a dihedral angle of 89.48 (4)°. The oxazine group is oriented at dihedral angles of 13.36 (4) and 85.08 (5)°, respectively, with respect to the naphthalene and benzaldehyde fragments. In the crystal, inversion dimers linked by pairs of C—H⋯O hydrogen bonds generate R 2 2(8) loops. The dimers are linked into [010] chains via N—H⋯O hydrogen bonds. Weak C—H⋯π links and aromatic π–π stacking between the centroids of the naphthalene phenyl rings [centroid–centroid separation = 3.5977 (8) Å] help to consolidate the packing

Effects of Different Substituents on the Crystal Structures and Antimicrobial Activities of Six Ag(I) Quinoline Compounds

The syntheses and single crystal X-ray structures of [Ag(5-nitroquinoline)(2)]NO3 (1), [Ag(8-nitroquinoline)(2)]NO3 center dot H2O (2), [Ag(6-methoxy-8-nitroquinoline)(NO3)](n) (3), [Ag(3-quinolinecarbonitrile)(NO3)](n) (4), [Ag(3-quinolinecarbonitrile)(2)]NO3 (5), and [Ag(6-quinolinecarboxylic acid)(2)]NO3 (6) are described. As an alternative to solution chemistry, solid-state grinding could be used to prepare compounds 1 and 3, but the preparation of 4 and 5 in this way failed. The Ag(I) ions in the monomeric compounds 1, 2, 5, and 6 are coordinated to two ligands via the nitrogen atoms of the quinoline rings, thereby forming a distorted linear coordination geometry with Ag-N bond distances of 2.142(2)-2.336(2) angstrom and N-Ag-N bond angles of 163.62(13)degrees-172.25(13)degrees. The 1D coordination polymers 3 and 4 contain Ag(I) centers coordinating one ligand and two bridging nitrate groups, thereby forming a distorted trigonal planar coordination geometry with Ag-N bond distances of 2.2700(14) and 2.224(5) angstrom, Ag-O bond distances of 2.261(4)-2.536(5) angstrom, and N-Ag-O bond angles of 115.23(5)degrees-155.56(5)degrees. Hirshfeld surface analyses of compounds 1-6 are presented as d(norm) and curvedness maps. The d(norm) maps show different interaction sites around the Ag(I) ions, i.e., Ag center dot center dot center dot Ag interactions and possible O-H center dot center dot center dot O, C-H center dot center dot center dot O, C-H center dot center dot center dot N, and C-H center dot center dot center dot C hydrogen bonds. Curvedness maps are a good way of visualizing pi-pi tacking interactions between molecules. The antimicrobial activities of compounds 1, 2, and 6 were screened against 15 different multidrug-resistant strains of bacteria isolated from diabetic foot ulcers and compared to the antimicrobial activities of the clinically used silver sulfadiazine (SS). Compound 2 showed activity similar to SS against this set of test organisms, being active against all strains and having slightly better average silver efficiency than SS (5 vs 6 mu g Ag/mL). Against the standard nonresistant bacterial strains of Staphylococcus aureus, Pseudomonas aeruginosa, Proteus mirabilis, and Streptococcus pyogenes, compound 1 performed better than silver nitrate, with an average MIC of 6 mu g Ag/mL versus 18 mu g Ag/mL for the reference AgNO3. Electrospray ionization mass spectrometry (ESI-MS) analyses of compounds 3 and 6 in DMSO/MeOH confirm the two-coordinated Ag+ complexes in solution, and the results of the H-1 NMR titrations of DMSO solutions of 5-nitroquinoline and 8-nitroquinoline with AgNO3 in DMSO suggest that 5-nitroquinoline is more strongly coordinated to the silver ion