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At least 919 records · Page 51Linked to original sources
PubMed2003

Sip, an integrase protein with excision, circularization and integration activities, defines a new family of mobile Staphylococcus aureus pathogenicity islands.

We report the complete sequence of Staphylococcal pathogenicity island bovine 2 (SaPIbov2), encoding the biofilm-associated protein Bap. SaPIbov2 contains 24 open reading frames, including sip, which encodes a functional staphylococcal integrase protein. SaPIbov2 is bordered by 18 bp direct repeats. The integration site into the chromosome lies at the 3' end of a gene encoding GMP synthase. SaPIbov2 has extensive similarity to previously described pathogenicity islands of Staphylococcus aureus. The principal difference is that toxin genes present in the other pathogenicity islands are exchanged for a transposon-like element that carries the bap gene and genes encoding an ABC transporter and a transposase. Also, SaPIbov2 can be excised to form a circular element and can integrate site-specifically and RecA-independently at a chromosomal att site in a Sip-dependent manner. This was demonstrated both in S. aureus and with plasmid substrates ectopically in Escherichia coli. Thus, SaPIbov2 encodes a functional recombinase of the integrase family that promotes element excision and insertion/integration. In addition, we demonstrated that the presence of SaPIbov2 facilitated the persistence of S. aureus in an intramammary gland infection model. Finally, different bovine isolates of S. aureus were found to carry islands related to SaPIbov2, suggesting the existence of a family of related pathogenicity islands.

Amino Acid Sequence↗
PubMed2003

Design and fabrication of a silica on silicon integrated optical biochip as a fluorescence microarray platform.

Previous research into the use of Flame Hydrolysis Deposition (FHD) of glasses in integrated optics has focused on the successful commercial exploitation of low cost optical devices within the field of telecommunications and optoelectronics. Recently we have sought to apply these fabrication technologies to the development of optical biochips, utilising their ability to be integrated with microfluidics as a 'Lab-on-a-chip' platform. In this paper, we carry this development forward by seeking to create a microarray of integrated optical sensing elements, addressed using a glass-polymer hybrid technology in which poly(dimethylsiloxane), PDMS, is used as an elastomeric packaging over-layer. In particular, we describe the wide range of modelling and microfabrication processes required for the successful manufacture, integration and packaging of such arrays. The integration of both optical and fluidic circuits in this device avoids precise alignment requirements and results in a compact, robust and reliable device. Finally, in this paper, we describe the implementation of a pumping system for delivering small amounts of fluid across the array together with an optical signal treatment.

Carbocyanines↗
PubMed2006

RegRNA: an integrated web server for identifying regulatory RNA motifs and elements.

Numerous regulatory structural motifs have been identified as playing essential roles in transcriptional and post-transcriptional regulation of gene expression. RegRNA is an integrated web server for identifying the homologs of regulatory RNA motifs and elements against an input mRNA sequence. Both sequence homologs and structural homologs of regulatory RNA motifs can be recognized. The regulatory RNA motifs supported in RegRNA are categorized into several classes: (i) motifs in mRNA 5'-untranslated region (5'-UTR) and 3'-UTR; (ii) motifs involved in mRNA splicing; (iii) motifs involved in transcriptional regulation; (iv) riboswitches; (v) splicing donor/acceptor sites; (vi) inverted repeats; and (vii) miRNA target sites. The experimentally validated regulatory RNA motifs are extracted from literature survey and several regulatory RNA motif databases, such as UTRdb, TRANSFAC, alternative splicing database (ASD) and miRBase. A variety of computational programs are integrated for identifying the homologs of the regulatory RNA motifs. An intuitive user interface is designed to facilitate the comprehensive annotation of user-submitted mRNA sequences. The RegRNA web server is now available at http://RegRNA.mbc.NCTU.edu.tw/.

Animals↗
PubMed1996

Germline transformation of Drosophila virilis with the transposable element mariner.

An important goal in molecular genetics has been to identify a transposable element that might serve as an efficient transformation vector in diverse species of insects. The transposable element mariner occurs naturally in a wide variety of insects. Although virtually all mariner elements are nonfunctional, the Mos1 element isolated from Drosophila mauritiana is functional. Mos1 was injected into the pole-cell region of embryos of D. virilis, which last shared a common ancestor with D. mauritiana 40 million years ago. Mos1 PCR fragments were detected in several pools of DNA from progeny of injected animals, and backcross lines were established. Because G0 lines were pooled, possibly only one transformation event was actually obtained, yielding a minimum frequency of 4%. Mos1 segregated in a Mendelian fashion, demonstrating chromosomal integration. The copy number increased by spontaneous mobilization. In situ hybridization confirmed multiple polymorphic locations of Mos1. Integration results in a characteristic 2-bp TA duplication. One Mos1 element integrated into a tandem array of 370-bp repeats. Some copies may have integrated into heterochromatin, as evidenced by their ability to support PCR amplification despite absence of a signal in Southern and in situ hybridization.

Animals↗
PubMed2006

The concept of risk and responsible conduct of research.

Assessment of risk is one of the key issues in the field of responsible conduct of research which covers discourses of research ethics and research integrity. The principle of minimizing risks and balancing of risks and benefits is one of the main requirements of research ethics. In addition, the content of informed consent that is another fundamental principle of research ethics derives from the assessment of risks and benefits related to a particular research project. Risk assessment also plays a crucial role in methodological design of the research project. This is an important point where research ethics and research integrity discourses overlap. Firstly, because the choice of a control group (e.g., placebo control) is a key ethical issue related to the protection of the research subjects' interests. Secondly, because the quality of the research data, that is one of the key elements of research integrity, is closely connected to the choice of research methodology as well. The problem of biased interpretation or manipulation of risk related features of biomedical research should also be taken into account. Despite the importance of the concept of risk to the field of biomedical research, its relevance has not yet attracted a sufficient attention in the responsible conduct of research debate.

Biomedical Research↗
PubMed1994

Competition for DNA steroid response elements as a possible mechanism for neuroendocrine integration.

For the analysis of a simple steroid-dependent mating behavior, careful response definition, complete neural circuit delineation and placement of estrogen-responsive cells within this circuit have been accomplished. Molecular studies of two relevant genes have emphasized DNA/RNA hybridization assays and DNA binding techniques. For both the rat preproenkephalin gene and the gene for the progesterone receptor, a strong induction by estrogen, tissue specificity of expression and a sex difference in regulation are prominent phenomena. On the rat preproenkephalin promoter, estrogen (ER) and thyroid receptors may compete for a DNA binding site. Likewise, progesterone (PR) and glucocorticoid receptors may compete for the same sites. On the rat PR gene, interactions between ER and AP-1 binding proteins are of special interest. Such interactions could underlay competitions and synergies between steroid hormones and neurally signalled events in the environment.

Animals↗
PubMed2003

Integration of CT, CAD system and finite element method to investigate interfacial stresses of resin-bonded prosthesis.

The question of whether prosthesis/abutment tooth interface debonding is associated with inappropriate occlusal force is investigated in this study. A new modeling approach was employed to perform the interfacial stress analyses. Solid models of resin-bonded (RB) prosthesis and abutment teeth were constructed by stacking serious section contours that were obtained from CT images. A 3-D finite element (FE) model of RB prosthesis/abutment teeth was generated in a CAD system after assembling and meshing procedures. An in-house program was developed to combine the FE package (ANSYS) to calculate the interfacial (normal and shear) stresses at the prosthesis/molar interface with the bonding and debonding conditions. After 10 different occlusal force(s) evaluations, three initial opening gaps at the distal margin of the retainer were assumed to examine the possible interface debonding mechanism under the worst loading case. The results indicated that a more accurate FE model of the posterior RB prosthesis/abutments could be generated through combining several computer-aided techniques. The maximum interfacial stresses were obtained when the occlusal force was applied on the buccal slope of the distolingual cusp of the molar. For interface debonding simulations, peak normal and shear stresses were found near the debonding areas and stress values increased gradually with small to large initial opening gaps. From these results, prosthesis/abutment tooth interfacial fatigue damage might arise or accelerate the interface to debond under adequate bonding or initial gap opening conditions after long-term repeated inappropriate occlusal force actions.

Biomechanical Phenomena↗
PubMed1999

Forward problem solution of electromagnetic source imaging using a new BEM formulation with high-order elements.

Representations of the active cell populations on the cortical surface via electric and magnetic measurements are known as electromagnetic source images (EMSIs) of the human brain. Numerical solution of the potential and magnetic fields for a given electrical source distribution in the human brain is an essential part of electromagnetic source imaging. In this study, the performance of the boundary element method (BEM) is explored with different surface element types. A new BEM formulation is derived that makes use of isoparametric linear, quadratic or cubic elements. The surface integration is performed with Gauss quadrature. The potential fields are solved assuming a concentric three-shell model of the human head for a tangential dipole at different locations. In order to achieve 2% accuracy in potential solutions, the number of quadratic elements is of the order of hundreds. However, with linear elements, this number is of the order of ten thousand. The relative difference measures (RDMs) are obtained for the numerical models that use different element types. The numerical models that employ quadratic and cubic element types provide superior performance over linear elements in terms of accuracy in solutions. Assuming a homogeneous sphere model of the head, the RDMs are also obtained for the three components (radial and tangential) of the magnetic fields. The RDMs obtained for the tangential fields are, in general, much higher than those obtained for the radial fields. Both quadratic and cubic elements provide superior performance compared with linear elements for a wide range of dipole locations.

Algorithms↗
PubMed2001

Solving the forward problem in electrical impedance tomography for the human head using IDEAS (integrated design engineering analysis software), a finite element modelling tool.

If electrical impedance tomography is to be used as a clinical tool, the image reconstruction algorithms must yield accurate images of impedance changes. One of the keys to producing an accurate reconstructed image is the inclusion of prior information regarding the physical geometry of the object. To achieve this, many researchers have created tools for solving the forward problem by means of finite element methods (FEMs). These tools are limited, allowing only a set number of meshes to be produced from the geometric information of the object. There is a clear need for geometrical accurate FEM models to improve the quality of the reconstructed images. We present a commercial tool called IDEAS, which can be used to create FEM meshes for these models. The application of this tool is demonstrated by using segmented data from the human head to model impedance changes inside the head.

Algorithms↗
PubMed2003

A synthetic analysis of the Saccharomyces cerevisiae stress sensor Mid2p, and identification of a Mid2p-interacting protein, Zeo1p, that modulates the PKC1-MPK1 cell integrity pathway.

Mid2p is a plasma membrane protein that functions in Saccharomyces cerevisiae as a sensor of cell wall stress, activating the PKC1-MPK1 cell integrity pathway via the small GTPase Rho1p during exposure to mating pheromone, calcofluor white, and heat. To examine Mid2p signalling, a global synthetic interaction analysis of a mid2 mutant was performed; this identified 11 interacting genes. These include WSC1 and ROM2, upstream elements in cell integrity pathway signalling, and FKS1 and SMI1, required for 1,3-beta-glucan synthesis. These synthetic interactions indicate that the Wsc1p sensor acts through Rom2p to activate the Fks1p glucan synthase in a Mid2p-independent way. To further explore Mid2p signalling a two-hybrid screen was done using the cytoplasmic tail of Mid2p; this identified ZEO1 (YOL109w), encoding a 12 kDa peripheral membrane protein that localizes to the plasma membrane. Disruption of ZEO1 leads to resistance to calcofluor white and to a Mid2p-dependent constitutive phosphorylation of Mpk1p, supporting a role for Zeo1p in the cell integrity pathway. Consistent with this, zeo1-deficient cells suppress the growth defect of mutants in the Rho1p GDP-GTP exchange factor Rom2p, while exacerbating the growth defect of sac7delta mutants at 37 degrees C. In contrast, mid2delta mutants have opposing effects to zeo1delta mutants, being synthetically lethal with rom2delta, and suppressing an 18 degrees C growth defect of sac7delta, while overexpression of MID2 rescues a rom2delta 37 degrees C growth defect. Thus, MID2 and ZEO1 appear to play reciprocal roles in the modulation of the yeast PKC1-MPK1 cell integrity pathway.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Elements and strategies of an effective provider integration strategy.

Regardless of the outcome of the debate in our nation's capitol, a health care revolution is sweeping the nation. In fact, if the debate lasts much longer, policy makers will be playing catch-up and responding to policies already in place in the trenches. Everywhere we turn as health care leaders, there is evidence of major change on the horizon. Reimbursement methodologies are undergoing radical alteration, traditionally stable institutions are being challenged, new organizational models are evolving, the types and roles of providers best suited to provide care are being questioned, and consumer expectations are being heightened. One of the basic strategies that is receiving attention throughout the country as a response to all this change relates to the development of integrated delivery organizations (IDO), integrated delivery systems (IDS), or integrated delivery networks (lDN). This article discusses these emerging systems in terms of health care reform, describes the rationale for their creation, and provides some strategies for their successful development.

Group Practice↗
PubMed1999

[Lessons from health education for HIV/AIDS prevention: theoretical elements for the construction of a new integrated practice].

There is an evident contrast between health education practices and theoretical reflection concerning them as models. Health education practices have undergone considerable development in terms of strategies, methods, and modalities, while theoretical models have remained deficient, reductionist, fragmentary, and focused on behavior rather than social practices. Major problems include individualism, asymmetrical "teacher-student" relationships, students as passive objects of practices, lack of social and cultural contextualism, and excessive focus on factual behavior. We propose a praxis based on ten levels of integration regarding different human dimensions: 1) complexity requires interdisciplinarity; 2) holism; 3) combined perceptual and expressive dimensions in a integrated language; 4) framing of practices in real contexts; 5) realization of the continuity between the individual and collective realms; 6) symmetrical, dialogic and active educational practice; 7) integration of both intellectual-cognitive and affective-volitional processes; 8) risks as vulnerabilities of social groups that are capable of organization; 9) use of imagination in role-playing games; 10) recognition of others and diversity. Political aspects of education are emphasized as promoting citizenship and social change.

Acquired Immunodeficiency Syndrome↗
PubMed1985

[Cis-active function of plasmid R 57 resolving co-integrates formed during transposition of ISI-elements].

The mechanism of pBR322 plasmid mobilization in the cells of Escherichia coli K-12 recA by conjugative factor R57 was studied. It was shown that mobilization of pB322 is achieved by formation of unstable IS1-mediated cointegrates with R57. In the rec+ E. coli strains cointegrates resolved with formation of pBR322:IS1 plasmids. In the recA bacteria the cointegrates dissociated to pBR:IS1, as well as to other insertion derivatives of pBR322. Some of the latter contain Tn9-like sequence, i.e. a transposon flanked by direct repeats of IS1. The subsequent transposition of IS1 from pBR-. IS1 to pBR3.1 plasmid (Aps deletion derivative of RP1) leads to formation of stable cointegrates incapable of dissociating even in the presence of coresident plasmid R57. It is suggested that R57 encodes the cys-acting function providing recA-independent recombination between direct repeats of IS1.

Ampicillin↗
PubMed1994

[Preparation and primary genetic analysis of Drosophila melanogaster transformants line w'lz(b)/XXywf, containing mini-white genes, integrated in the genome during P-element-dependent transformation].

Transformation of Drosophila melanogaster using P-element-based vectors yielded 129 sublines, which carried mini-white gene copies in the different genome regions. Dependence of mini-white gene expression on the location, gene dosage, and sex of the transformed individuals was analyzed. The mutation lzb was shown to suppress mini-white gene expression, the degree of suppression depending on the location and dosage of the mini-white gene.

ATP-Binding Cassette Transporters↗
PubMed1993

Activation of c-mos oncogene by integration of an endogenous long terminal repeat element during transfection of genomic DNA from mouse skin tumor cells.

An activated c-mos oncogene was identified in a transformed clone of golden hamster embryo cells transfected with DNA extracted from cells cultured from a UV-induced mouse skin tumor. Southern blot hybridization with a v-mos oncogene probe showed that the mos oncogene was amplified in the primary and secondary transformed cells but not in the original tumor cells. Expression of the mos oncogene was very high in the primary and secondary transformants, but mos mRNA was undetectable in the original tumor cells. A genomic DNA fragment containing the activated mos oncogene was cloned and sequenced. The upstream mouse sequence of the mos oncogene, which functions as the transcription terminator, was lost and replaced by a mouse endogenous long terminal repeat (LTR) element that provides the promoter sequence, resulting in high expression of the gene. The rearrangement apparently occurred during transfection, since the polymerase chain reaction (PCR) product encompassing the junction region was present in the primary and secondary transformants but not in the original tumor cells. The LTR element is likely to have been amplified during the skin tumor development caused by UV irradiation. Southern blot hybridization showed that the copy number of LTR in the tumor cells was significantly higher than that in normal skin cells. The amplification of the LTR in the cells may have increased the chance of recombination between the LTR and c-mos gene during the DNA transfection.

Animals↗
PubMed2002

An implementation framework for household and community integrated management of childhood illness.

This paper describes the development and recent history of the third component of the Integrated Management of Childhood Illness (IMCI) strategy, improving household and community practices (HH/C IMCI). An implementation framework for this third component, developed through review of experiences of non-governmental organizations (NGOs) working in community-based child health and nutrition programmes, is then presented. This Framework responds to demand from NGOs and their partners for a description of the different categories of community-level activities necessary for the implementation of a comprehensive child health and nutrition programme. These categories of activities facilitate the systematic cataloguing, synthesis and coordination of organizational activities and experience. It also serves as a reference tool for improving communication of related community child health activities, and a guide for designing appropriate behaviour change strategies. The Framework was endorsed by participants in an international workshop held in Baltimore, Maryland in January 2001, and specified three linked elements that are integral to HH/C IMCI, supported by a multi-sectoral platform that addresses constraints communities face in adopting practices that promote health and nutrition. The three programmatic Elements critical to HH/C IMCI programmes are (1). improving partnerships between health facilities or services and the communities they serve; (2). increasing appropriate and accessible care and information from community-based providers; and (3). integrating promotion of key family practices critical for child health and nutrition. The Framework presented in this paper is an ideal tool for describing, sharing and coordinating efforts in the field, and is purposely descriptive rather than prescriptive.

Child↗
PubMed2002

Specificity in DNA recognition by phage integrases.

The lambda-related (lambdoid) coliphages are related to one another by frequent natural recombination and maintain a high level of functional polymorphism for several activities of the phages. Arguments are presented that the polymorphism of the integration module results from selection (presumably frequency-dependent) for new (not improved) specificities of site recognition. Analysis of phages lambda and HK022 by Weisberg and collaborators previously showed that changes in five noncontiguous amino acids could switch site recognition specificity. Phage 21 and defective element e14, which integrate at the same site, differ in recognition specificity for both core and arm sites. In vitro assays of e14 and 21 insertion and excision confirm this conclusion. Inhibition by ds arm site oligonucleotides defines the sequence specificity more precisely.

Bacteriophage lambda↗
PubMed1997

Pathogenicity islands of virulent bacteria: structure, function and impact on microbial evolution.

Virulence genes of pathogenic bacteria, which code for toxins, adhesins, invasins or other virulence factors, may be located on transmissible genetic elements such as transposons, plasmids or bacteriophages. In addition, such genes may be part of particular regions on the bacterial chromosomes, termed 'pathogenicity islands' (Pais). Pathogenicity islands are found in Gram-negative as well as in Gram-positive bacteria. They are present in the genome of pathogenic strains of a given species but absent or only rarely present in those of non-pathogenic variants of the same or related species. They comprise large DNA regions (up to 200 kb of DNA) and often carry more than one virulence gene, the G + C contents of which often differ from those of the remaining bacterial genome. In most cases, Pais are flanked by specific DNA sequences, such as direct repeats or insertion sequence (IS) elements. In addition, Pais of certain bacteria (e,g. uropathogenic Escherichia coli, Yersinia spp., Helicobacter pylori) have the tendency to delete with high frequencies or may undergo duplications and amplifications. Pais are often associated with tRNA loci, which may represent target sites for the chromosomal integration of these elements. Bacteriophage attachment sites and cryptic genes on Pais, which are homologous to phage integrase genes, plasmid origins of replication of IS elements, indicate that these particular genetic elements were previously able to spread among bacterial populations by horizontal gene transfer, a process known to contribute to microbial evolution.

Biological Evolution↗