Enhanced in vivo osteogenesis by nanocarrier-fused bone morphogenetic protein-4

Purpose: Bone defects and nonunions are major clinical skeletal problems. Growth factors are commonly used to promote bone regeneration; however, the clinical impact is limited because the factors do not last long at a given site. The introduction of tissue engineering aimed to deter the diffusion of these factors is a promising therapeutic strategy. The purpose of the present study was to evaluate the in vivo osteogenic capability of an engineered bone morphogenetic protein-4 (BMP4) fusion protein. Methods: BMP4 was fused with a nanosized carrier, collagen-binding domain (CBD), derived from fibronectin. The stability of the CBD-BMP4 fusion protein was examined in vitro and in vivo. Osteogenic effects of CBD-BMP4 were evaluated by computer tomography after intramedullary injection without a collagen-sponge scaffold. Recombinant BMP-4, CBD, or vehicle were used as controls. Expressions of bone-related genes and growth factors were compared among the groups. Osteogenesis induced by CBD-BMP4, BMP4, and CBD was also assessed in a bone-defect model. Results: In vitro, CBD-BMP4 was retained in a collagen gel for at least 7 days while BMP4 alone was released within 3 hours. In vivo, CBD-BMP4 remained at the given site for at least 2 weeks, both with or without a collagen-sponge scaffold, while BMP4 disappeared from the site within 3 days after injection. CBD-BMP4 induced better bone formation than BMP4 did alone, CBD alone, and vehicle after the intramedullary injection into the mouse femur. -Bone-related genes and growth factors were expressed at higher levels in CBD-BMP4-treated mice than in all other groups, including BMP4-treated mice. Finally, CBD-BMP4 potentiated more bone formation than did controls, including BMP4 alone, when applied to cranial bone defects without a collagen scaffold. Conclusion: Altogether, nanocarrier-CBD enhanced the retention of BMP4 in the bone, thereby promoting augmented osteogenic responses in the absence of a scaffold. These results suggest that CBD-BMP4 may be clinically useful in facilitating bone formation

Logical Operation Based Literature Association with Genes and its application, PosMed.

PosMed prioritizes candidate genes for positional cloning by employing our original database search engine GRASE, which uses an inferential process similar to an artificial neural network comprising documental neurons (or 'documentrons') that represent each document contained in databases such as MEDLINE and OMIM (Yoshida, _et al_. 2009, Makita, _et al_. 2009). PosMed immediately ranks the candidate genes by connecting phenotypic keywords to the genes through connections representing gene–gene interactions other biological relationships, such as metabolite–gene, mutant mouse–gene, drug–gene, disease–gene, and protein–protein interactions, ortholog data, and gene–literature connections.

To make proper relationships between genes and literature, we manually curate queries, which are defined by logical operation rules, against MEDLINE. For example, to detect a set of MEDLINE documents for the AT1G03880 gene in _A. thaliana_, we applied the following logical query: (‘AT1G03880’ OR ‘CRU2’ OR ‘CRB’ OR ‘CRUCIFERIN 2' OR ‘CRUCIFERIN B’) AND (‘Arabidopsis’) NOT (‘chloroplast RNA binding’). Curators refined these queries in mouse, rice and _A. thaliana_. For human and rat genes, we use mouse curation results via ortholog genes in PosMed.

PosMed is available at "http://omicspace.riken.jp/PosMed":http://omicspace.riken.jp/PosMed

References:
Yoshida Y, et al. _Nucleic Acids Res_. 37(Web Server issue):W147-52. 2009. 
Makita Y, et al. _Plant Cell Physiol_. 2009 Jul;50(7):1249-59.
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Extracting and Mathematical Identifying Form of Stationary Noise in X-ray Images

Image noise may prevent proper diagnostic X-ray imaging. This study is aimed at developing new noise rejection methods using a mathematical model that describes the form of X-ray image noise. Stationary noise is one type of noise found in X-ray images. Stationary noise is nonstochastic and appears independent of the radiographic factors. In this paper, we verify methods for identifying stationary noise using a polynomial regression model, and extracting such noise from X-ray images obtained from a CR system. The results of this study demonstrate that stationary noise can be extracted with high precision using a particular low-pass filter frequency. We found that a regression model for greater than second-degree polynomials can be applied for roughly identifying stationary noise. However, the fitting accuracy of the regression curve is not significantly improved in terms of the amount of multiplication required when increasing the degree of the polynomial regression model

Residual mitral regurgitation after repair for posterior leaflet prolapse- Importance of preoperative anterior leaflet tethering

Background Carpentier's techniques for degenerative posterior mitral leaflet prolapse have been established with excellent long‐term results reported. However, residual mitral regurgitation ( MR ) occasionally occurs even after a straightforward repair, though the involved mechanisms are not fully understood. We sought to identify specific preoperative echocardiographic findings associated with residual MR after a posterior mitral leaflet repair. Methods and Results We retrospectively studied 117 consecutive patients who underwent a primary mitral valve repair for isolated posterior mitral leaflet prolapse including a preoperative 3‐dimensional transesophageal echocardiography examination. Twelve had residual MR after the initial repair, of whom 7 required a corrective second pump run, 4 underwent conversion to mitral valve replacement, and 1 developed moderate MR within 1 month. Their preoperative parameters were compared with those of 105 patients who had an uneventful mitral valve repair. There were no hospital deaths. Multivariate analysis identified preoperative anterior mitral leaflet tethering angle as a significant predictor for residual MR (odds ratio, 6.82; 95% confidence interval, 1.8–33.8; P =0.0049). Receiver operator characteristics curve analysis revealed a cut‐off value of 24.3° (area under the curve, 0.77), indicating that anterior mitral leaflet angle predicts residual MR . In multivariate regression analysis, smaller anteroposterior mitral annular diameter ( P &lt;0.001) and lower left ventricular ejection fraction ( P =0.002) were significantly associated with higher anterior mitral leaflet angle, whereas left ventricular and left atrial dimension had no significant correlation. Conclusions Anterior mitral leaflet tethering in cases of posterior mitral leaflet prolapse has an adverse impact on early results following mitral valve repair. The findings of preoperative 3‐dimensional transesophageal echocardiography are important for consideration of a careful surgical strategy. </jats:sec

Experimentalstudy on porouscurrentcollectors of PEMelectrolyzers

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