First Author: Ophir Keret
All Authors: Keret O
Journal Title: The Israel Medical Association journal : IMAJ
Abstract: Synthetic bioiogy is a ,relatively new fieild of bologlcal research and development that focases on the engineering of genetic molecular machlnes wIth a specific predefined function. Plainly put the newly engineered organism functions as a machine. It can process information. manufature, heal and even diagnose. We just have to engineer It to do so. The famous quote "Biology Is the nanotechnology that works" is currently being put to the test on a worldwide scale. The application of these machines Is theoretically boundless. In laboratories worldwide synthetic biology technologies are being rationally designed to assist in diagnosis or disrupt disease mechnisms. In the not too distant future they are expected to reach the clinical setting. This new field should be distinguished from classic genetic engineering. The latter researches naturalfy found DNA segments via cloning. It is weakly associated with engineering. Synthetic biology focuses on the engineering of molecular biological machines for the benefit of mankind. This is done via synthetic (computer printed) DNA sequences, man-designed or altered in silico. In this article I will briefly introduce synthetic biology, elaborate on the BiobrickFoundation as an independent fast-growing synthetic biology-sharing movement, and report on selected developing applications for medicine.
Authors: Barzegari A, Saei AA
Abstract: The severe need for constructing replacement tissues in organ transplanta-tion has necessitated the development of tissue engineering approaches and bioreactors that can bring these approaches to reality. The inherent limitations of conventional bioreactors in generating realistic tissue constructs led to the devise of the microgravity tissue engineering that uses Rotating Wall Vessel (RWV) bioreactors initially developed by NASA.In this review article, we intend to highlight some major advances and accomplishments in the rapidly-growing field of tissue engineering that could not be achieved without using microgravity.Research is now focused on assembly of 3 dimensional (3D) tissue fragments from various cell types in human body such as chon-drocytes, osteoblasts, embryonic and mesenchymal stem cells, hepatocytes and pancreas islet cells. Hepatocytes cultured under microgravity are now being used in extracorporeal bioartificial liver devices. Tissue constructs can be used not only in organ replacement therapy, but also in pharmaco-toxicology and food safety assessment. 3D models of vari-ous cancers may be used in studying cancer development and biology or in high-throughput screening of anticancer drug candidates. Finally, 3D heterogeneous assemblies from cancer/immune cells provide models for immunotherapy of cancer.Tissue engineering in (simulated) microgravity has been one of the stunning impacts of space research on biomedical sciences and their applications on earth.
Authors: Daggett T, Greenshields IR
Abstract: The current trend in medical image acquisition is towards the generation of image datasets which are massively large, either because they exhibit fine x, y, or z resolution, are volumetric, are multispectral, or a combination of all of the preceding. Such images pose a significant computational challenge in their analysis, not only in terms of data throughput, but also in terms of platform costs and simplicity. In this paper we describe the role of a cluster of workstations together with two quite different application programming interfaces (APIs) in the quantitative analysis of anatomic image data from the visible human project using an MRF-Gibbs classification algorithm. We describe the typical architecture of a cluster computer, two API options and the parallelization of the MRF-Gibbs procedure for the cluster. Finally, we show speedup results obtained on the cluster and sample classifications of visible human data.
Authors: Schulz S, Kumar A, Bittner T
Abstract: Mereological relations such as part-of and its inverse has-part are fundamental to the description of the structure of living organisms. Whereas classical mereology focuses on individual entities, mereological relations in biomedical ontologies are generally asserted between classes of individuals. In general, this practice leaves some basic issues unanswered: type constraints of mereological relations, e.g., concerning artifacts and biological entities, the relation between parthood and time, inferred parts and wholes as well as a delimitation of parthood against spatial inclusion. Furthermore, mereological relations can be asserted not only between physical objects but also between biological processes and medical procedures. We analyze these ambiguities and make suggestions for a standardization of mereological relations in biomedical ontologies.
Authors: Al-Zaidan L, El Ruz RA, Malki AM
Abstract: Metformin is a commonly prescribed antihyperglycemic drug, and has been investigated in vivo and in vitro for its effect to improve the comorbidity of diabetes and various types of cancers. Several studies investigated the therapeutic mechanisms of metformin on cancer cells, but the exact mechanism of metformin's effect on the proteomic pathways of cancer cells is yet to be further investigated. The main objective of our research line is to discover safe and alternative therapeutic options for breast cancer, we aimed in this study to design a novel "bottom up proteomics workflow" in which proteins were first broken into peptides to reveal their identity, then the proteomes were precisely evaluated using spectrometry analysis. In our study, metformin suppressed cell proliferation and induced apoptosis in human breast carcinoma cell line MCF-7 with minimal toxicity to normal breast epithelial cells MCF-10. Metformin induced apoptosis by arresting cells in G1 phase as evaluated by flow cytometric analysis. Moreover, The G1 phase arrest for the MCF-7 has been confirmed by increased expression levels of p21 and reduction in cyclin D1 level. Additionally, metformin increased the expression levels of p53, Bax, Bad while it reduced expression levels of Akt, Bcl-2, and Mdm2. The study employed a serviceable strategy that investigates metformin-dependent changes in the proteome using a literature-derived network. The protein extracts of the treated and untreated cell lines were analyzed employing proteomic approaches; the findings conveyed a proposed mechanism of the effectual tactics of metformin on breast cancer cells. Metformin proposed an antibreast cancer effect through the examination of the proteomic pathways upon the MCF-7 and MCF-10A exposure to the drug. Our findings proposed prolific proteomic changes that revealed the therapeutic mechanisms of metformin on breast cancer cells upon their exposure. In conclusion, the reported proteomic pathways lead to increase the understanding of breast cancer prognosis and permit future studies to examine the effect of metformin on the proteomic pathways against other types of cancers. Finally, it suggests the possibility to develop further therapeutic generations of metformin with increased anticancer effect through targeting specific proteomes.
Authors: Kazanci M, Cohn D, Marom G, Ben-Bassat H
Abstract: Three different compositions of butene-ethylene copolymer composites reinforced by polyethylene fibers and produced by filament winding are potentially suitable for biomedical applications. This study examines the effect of various processing and finishing conditions and of sterilization on the extent and composition of surface oxidation. An XPS analysis revealed only insignificant differences between the various treatments, while fibroblast cell attachment tests indicated good attachment with no signs of cytotoxity or cell degeneration for any of the materials.
Authors: Yu K, Chen L, Zhao J, Li S, Dai Y, Huang Q, Yu Z
Abstract: In this study 5, 10 and 15% ?-Ca(3)(PO(4))(2)/Mg-Zn composites were prepared through powder metallurgy methods, and their corrosion behavior and mechanical properties were studied in simulated body fluid (SBF) at 37°C. The 10% ?-Ca(3)(PO(4))(2)/Mg-Zn composite was selected for cytocompatibility assessment and in vivo biodegradation testing. The results identified the ?-Mg, MgZn and ?-Ca(3)(PO(4))(2) phases in these sintered composites. The density and elastic modulus of the ?-Ca(3)(PO(4))(2)/Mg-6% Zn composite match those of natural bone, and the strength is approximately double that of natural bone. The 10% ?-Ca(3)(PO(4))(2)/Mg-6% Zn composites exhibit good corrosion resistance, as determined by a 30 day immersion test and electrochemical measurements in SBF at 37°C. The 10% ?-Ca(3)(PO(4))(2)/Mg-6% Zn composite is safe for cellular applications, with a cytotoxicity grade of ?0-1 against L929 cells in in vitro testing. The ?-Ca(3)(PO(4))(2)/Mg-6% Zn composite also exhibits good biocompatibility with the tissue and the important visceral organs the heart, kidney and liver of experimental rabbits. The composite has a suitable degradation rate and improves the concrescence of a pre-broken bone. The corrosion products, such as Mg(OH)(2) and Ca(5)(PO(4))(6)(OH)(2), can improve the biocompatibility of the ?-Ca(3)(PO(4))(2)/Mg-Zn composite.
Authors: McCrary SV, Anderson CB, Jakovljevic J, Khan T, McCullough LB, Wray NP, Brody BA
Abstract: Conflicts of interest pose a threat to the integrity of scientific research. The current regulations of the U.S. Public Health Service and the National Science Foundation require that medical schools and other research institutions report the existence of conflicts of interest to the funding agency but allow the institutions to manage conflicts internally. The regulations do not specify how to do so.We surveyed all medical schools (127) and other research institutions (170) that received more than $5 million in total grants annually from the National Institutes of Health or the National Science Foundation; 48 journals in basic science and clinical medicine; and 17 federal agencies in order to analyze their policies on conflicts of interest.Of the 297 institutions, 250 (84 percent) responded by March 2000, as did 47 of the 48 journals and 16 of the 17 federal agencies. Fifteen of the 250 institutions (6 percent)--5 medical schools and 10 other research institutions--reported that they had no policy on conflicts of interest. Among the institutions that had policies, there was marked variation in the definition and management of conflicts. Ninety-one percent had policies that adhered to the federal threshold for disclosure ($10,000 in annual income or equity in a relevant company or 5 percent ownership), and 9 percent had policies that exceeded the federal guidelines. Only 8 percent had policies requiring disclosure to funding agencies, only 7 percent had such policies regarding journals, and only 1 percent had policies requiring the disclosure of information to the relevant institutional review boards or to research subjects. Twenty journals (43 percent) reported that they had policies requiring disclosure of conflicts of interest. Only four federal agencies had policies that explicitly addressed conflicts of interest in extramural research, and all but one of the agencies relied primarily on institutional discretion.There is substantial variation among policies on conflicts of interest at medical schools and other research institutions. This variation, combined with the fact that many scientific journals and funding agencies do not require disclosure of conflicts of interest, suggests that the current standards may not be adequate to maintain a high level of scientific integrity.
Authors: Ishihara M, Kishimoto S, Takikawa M, Hattori H, Nakamura S, Shimizu M
Abstract: Low molecular weight heparin (LMWH)/protamine (P) nano/micro particles (N/MPs) (LMWH/P N/MPs) were applied as carriers for heparin-binding growth factors (GFs) and for adhesive cells including adipose-derived stromal cells (ADSCs) and bone marrow-derived mesenchymal stem cells (BMSCs). A mixture of LMWH and P yields a dispersion of N/MPs (100 nm-3 ?m in diameter). LMWH/P N/MPs can be immobilized onto cell surfaces or extracellular matrix, control the release, activate GFs and protect various GFs. Furthermore, LMWH/P N/MPs can also bind to adhesive cell surfaces, inducing cells and LMWH/P N/MPs-aggregate formation. Those aggregates substantially promoted cellular viability, and induced vascularization and fibrous tissue formation in vivo. The LMWH/P N/MPs, in combination with ADSCs or BMSCs, are effective cell-carriers and are potential promising novel therapeutic agents for inducing vascularization and fibrous tissue formation in ischemic disease by transplantation of the ADSCs and LMWH/P N/MPs-aggregates. LMWH/P N/MPs can also bind to tissue culture plates and adsorb exogenous GFs or GFs from those cells. The LMWH/P N/MPs-coated matrix in the presence of GFs may provide novel biomaterials that can control cellular activity such as growth and differentiation. Furthermore, three-dimensional (3D) cultures of cells including ADSCs and BMSCs using plasma-medium gel with LMWH/P N/MPs exhibited efficient cell proliferation. Thus, LMWH/P N/MPs are an adequate carrier both for GFs and for stromal cells such as ADSCs and BMSCs, and are a functional coating matrix for their cultures.
Authors: Marquet G, Mosser J, Burgun A
Abstract: The process of aligning ontologies comprises two major steps: i) mapping concepts and ii) characterizing the relations between the concepts. In this paper, we present an alignment method based on a hybrid approach that reuses the UMLS knowledge base and aims at identifying patterns to characterize the relations. The proposed method consist in four steps: 1) exact matching, 2) searching for terms from one ontology that are included in terms from the other ontology, 3) identifying direct relations through the UMLS and 4) extracting syntactico-semantic patterns to infer novel alignments. This method has been applied to aligning the Human Disease ontology and the Mouse Pathology ontology resulting in 48 exact matches and 3,697 pairs of concepts for which one term is included in a term from the other ontology. 1,270 alignments are present in the UMLS. Among these, 903 are characterized by a semantic attribute. Based on these alignments, a study of the syntactic patterns has been done. Not surprisingly, the distribution of the different syntactic patterns is not sufficient to discriminate the different types of relationships found in the UMLS alignments. We have used the semantic categorization of the concepts provided by the UMLS to extract syntactico-semantic patterns. 87 novel alignments based on 6 syntactico-semantic patterns associated with isa and has associated morphology have been inferred.
Authors: Paladini F, Pollini M, Sannino A, Ambrosio L
Abstract: The interest in nanotechnology and the growing concern for the antibiotic resistance demonstrated by many microorganisms have recently stimulated many efforts in designing innovative biomaterials and substrates with antibacterial properties. Among the implemented strategies to control the incidence of infections associated with the use of biomedical device and implants, interesting routes are represented by the incorporation of bactericidal agents onto the surface of biomaterials for the prevention of bacterial adhesion and biofilm growth. Natural products and particularly bioactive metals such as silver, copper and zinc represent an interesting alternative for the development of advanced biomaterials with antimicrobial properties. This review presents an overview of recent progress in the modification of biomaterials as well as the most attractive techniques for the deposition of antimicrobial coatings on different substrates for biomedical application. Moreover, some research activities and results achieved by the authors in the development of antibacterial materials are also presented and discussed.