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Although the function of the BRCA1 gene has been extensively studied, the relationship between BRCA1 gene expression and tumor aggressiveness remains controversial in sporadic breast cancers. Because the BRCA1 protein is known to regulate estrogen signaling, we selected microarray data of ER+ breast cancers from the GEO public repository to resolve previous conflicting findings. The BRCA1 gene expression level in highly proliferative luminal B tumors was shown to be higher than that in luminal A tumors. Survival analysis using a cure model indicated that patients of early ER+ breast cancers with high BRCA1 expression developed rapid distant metastasis. In addition, the proliferation marker genes MKI67 and PCNA, which are characteristic of aggressive tumors, were also highly expressed in patients with high BRCA1 expression. The associations among high BRCA1 expression, high proliferation marker expression, and high risk of distant metastasis emerged in independent datasets, regardless of tamoxifen treatment. Tamoxifen therapy could improve the metastasis-free fraction of high BRCA1 expression patients. Our findings link BRCA1 expression with proliferation and possibly distant metastasis via the ER signaling pathway. We propose a testable hypothesis based on these consistent results and offer an interpretation for our reported associations. [ABSTRACT FROM AUTHOR]

Q-band continuos wave (QW) and pulsed electron-nuclear double resonance spectroscopy (ENDOR) were used to study the chloroperoxidase heme in situ following the inactivation with allylbenzene. Samples prepared in natural isotopic abundance, with N-labeled enzyme, and with allylbenzene labeled with 2H or 13C in specific vinylic positions were used. QW and ENDOR together with molecular modeling calculations determined the in situ structure of the alkene-modified heme.

EPR and ENDOR spectroscopic experiments at the X and Q microwave bands were performed to study Ni(sup I)F430, the putative active form of S-methyl coenzyme M reductase, and Ni(sup I)OEiBC, a nickel isobacteriochlorin used as a model for the tetrapyrrole cofactor F430. The results revealed two types of nitrogen ligands with different Ni(I) bonding characteristics due to their similarity with the pyrrole nitrogen of Cu(II)TPP and the imine nitrogen of Zn(II) imidazoles, respectively.

Background and Objective: In order to facilitate clinical research across multiple institutions, data harmonization is a critical requirement. Common data elements (CDEs) collect data uniformly, allowing data interoperability between research studies. However, structural limitations have hindered the application of CDEs. An advanced modeling structure is needed to rectify such limitations. The openEHR 2-level modeling approach has been widely implemented in the medical informatics domain. The aim of our study is to explore the feasibility of applying an openEHR approach to model the CDE concept.Materials and Methods: Using the National Institute of Neurological Disorders and Stroke General CDEs as material, we developed a semiautomatic mapping tool to assist domain experts mapping CDEs to existing openEHR archetypes in order to evaluate their coverage and to allow further analysis. In addition, we modeled a set of CDEs using the openEHR approach to evaluate the ability of archetypes to structurally represent any type of CDE content.Results: Among 184 CDEs, 28% (51) of the archetypes could be directly used to represent CDEs, while 53% (98) of the archetypes required further development (extension or specialization). A comprehensive comparison between CDEs and openEHR archetypes was conducted based on the lessons learnt from the practical modeling.Discussion: CDEs and archetypes have dissimilar modeling approaches, but the data structure of both models are essentially similar. This study proposes to develop a comprehensive structure to model CDE concepts instead of improving the structure of CED.Conclusion: The findings from this research show that the openEHR archetype has structural coverage for the CDEs, namely the openEHR archetype is able to represent the CDEs and meet the functional expectations of the CDEs. This work can be used as a reference when improving CDE structure using an advanced modeling approach. [ABSTRACT FROM AUTHOR]

Continuous-wave and 1H electron-nuclear double resonance spectroscopy identified the aqua ligand nature of the axial ligand of native low-spin chloroperoxidase (PO). The ligand has two major conformations. The identical nature of heme iron coordination sphere associated with CPO and cytochrome P-450(sub a) is proved using this scheme. The heme ligation structures have significant differences. Quadrupole coupling and 14N hyperfine coupling for these two enzyme are different due to out-of-planarity and/or heme ruffling.

Investigates nickel(I) form of cofactor F430(Ni1F430) of Methanobacterium thermoautotrophicum and of nickel(I) octaethylisobacteriochlorin(Ni1OEiBC) by electron paramagnetic resonance and electron nuclear double resonance spectroscopy. Preparation of Ni1F430 and Ni1OEiBC; Previous studies by x-ray spectroscopy.

Studies the 19F and 1,2H continuous-wave and pulsed electron nuclear double resonance (ENDOR) measurements of fluorometmyoglobin (MbF) frozen solutions. Probes of subtle structural features at the heme not directly accessible through X-ray methods; Deuterium isotope effect on the 19F coupling in the low-pH form; Hyperfine components derived from Zeeman effect.