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Integration of different sarcoma virus genomes into host DNA: evidence against tandem arrangement and for shared integration sites.

Cellular DNA of 50--54 S was extracted from chicken embryo cells doubly infected with two different avian sarcoma viruses and was analyzed by the infectious DNA assay. Approximately 80--90% of the transformed foci that were induced by this DNA were found to give rise to one kind of avian sarcoma virus only, indicating that most proviral genomes are not integrated in tandem. When the two infecting viruses were varied with respect to multiplicity or time of infection, the initial infecting virus or the virus of higher multiplicity of infection was recovered at higher frequency in foci produced by the extracted DNA. This observation suggests that existence of common integration sites for different avian sarcoma viruses. Cells uniformly infected with avian leukosis virus could be transformed by superinfection with an avian sarcoma virus from a different envelope subgroup. Infectious DNA recovered from such cells contained 3--10 50% infectious dose (ID50) units of leukosis virus per microgram but only 0.3--0.4 ID50 of sarcoma virus. DNA from cells infected with sarcoma virus alone contained 3 sarcoma virus ID50 per microgram. These results suggest that, even though a second virus integrates with lower efficiency into preinfected cells, there is not a complete block of integration sites by the first virus.

Animals↗

Hepatitis B virus integration in hepatocellular carcinoma DNA: duplication of cellular flanking sequences at the integration site.

The integrated form of hepatitis B virus (HBV) in the human hepatoma cell line huH2-2 and its cellular counterpart sequence have been cloned and analyzed. Blot hybridization analysis and nucleotide sequencing indicated that a single copy of the 1895-base-pair (bp) subgenomic region of HBV DNA, spanning from the middle of pre-S to the end of gene X, was integrated and flanked by the 12-bp directly repeating cellular sequences. A comparison of the sequencing data with that of the cellular counterpart DNA indicated the absence of deletion and rearrangement in the cellular flanking DNA following integration of the 1895-bp HBV DNA, except for generation of the 12-bp direct repeat at the virus-cell junction. A possible model for the mechanism of HBV integration is proposed.

Base Sequence↗

Site-specific integration of mycobacteriophage L5: integration-proficient vectors for Mycobacterium smegmatis, Mycobacterium tuberculosis, and bacille Calmette-Guérin.

Mycobacteriophage L5, a temperate phage of mycobacteria, integrates site-specifically into the Mycobacterium smegmatis chromosome. We have identified the int gene and attP site of L5, characterized the chromosomal attachment site (attB), and constructed plasmid vectors that efficiently transform M. smegmatis through stable site-specific integration of the plasmid into the bacterial genome. These integration-proficient plasmids also efficiently transform slow-growing mycobacteria such as the pathogen Mycobacterium tuberculosis and the vaccine strain bacille Calmette-Guérin (BCG). The ability to easily generate stable recombinants in these slow-growing mycobacteria without the requirement for continual selection is of particular importance for the construction of recombinant BCG vaccines and for the isolation and characterization of mycobacterial pathogenic determinants in animal model systems. Integration vectors of this type should be of general use in a number of additional bacterial systems where temperate phages have been identified.

Amino Acid Sequence↗

A novel integration signal that is composed of two transmembrane segments is required to integrate the Neurospora plasma membrane H(+)-ATPase into microsomes.

The Neurospora plasma membrane H(+)-ATPase belongs to a family of cation-motive porters called P-type ATPases. Putative transmembrane segments of these enzymes contain one or more charged residues. Conditions were determined by which a transmembrane segment with charged residues is integrated into its cognate membrane. We constructed fusion proteins flanked by the hydrophilic domains of the amino and carboxyl termini of the H(+)-ATPase that contained either one or two transmembrane segments. Neurospora in vitro translation system supplemented with homologous microsomes was programmed with RNA transcripts of these constructs. When transmembrane segment number one (M1) or number two (M2) of the H(+)-ATPase was engineered into the construct, the resultant protein did not integrate into microsomes. When M1 and M2 were placed in tandem, the resultant protein integrated into microsomes as judged by the criteria of resistance to extraction at pH 11.5 and protection from protease digestion. The integration event depended on ATP and GTP and on microsomal protein(s). We posited that membrane topology of the amino-terminal third of the H(+)-ATPase, and perhaps of other P-type ATPases is achieved by inserting transmembrane segments into membrane in pairs.

Amino Acid Sequence↗

Research data integrity: a result of an integrated information system.

The toxicologic problems of today frequently require long-term, multidisciplinary experimentation involving large numbers of animals. In order to provide the extensive safety evaluation necessary to produce data that can be reasonably extrapolated to humans, automated research support systems have transcended the position of useful tools and have become an integral part of the total design of experimental protocols. For an automated information system to fully represent the reality of the experiment, it must be able to assure integrity, as well as provide for the storage, calculation, and retrieval of data values of the quality and quantity necessary for fulfilling protocol requirements. Guarantees against error and loss of data, in addition to flexibility and easy access, must be an inherent part of the system if the acceptance and condifence of the investigator are to be obtained. This paper discusses the criteria, philosophies, and benefits of integrated data systems that ensure integrity of toxicologic research support.

Computers↗

The effects of sensory integration therapy on nystagmus duration, equilibrium reactions and visual-motor integration in reading retarded children.

Previous research on the effects of sensory integration therapy on vestibular processing dysfunction has not used an appropriate control group design. Using a control group, this research investigated the effects of sensory integration therapy on nystagmus duration, equilibrium reactions and visual-motor integration in 26 children with reading retardation. The sample had average intelligence but showed depressed nystagmus duration, problems in equilibrium reactions and delays in visual-motor coordination. Sixty-six sessions of therapy did not significantly affect duration, equilibrium or visual-motor integration.

Child↗

Validation of three-dimensional cardiac image integration: use of integrated CT image into electroanatomic mapping system to perform catheter ablation of atrial fibrillation.

INTRODUCTION: Accurate visualization of the complex left atrial (LA) anatomy and the location of an ablation catheter within the chamber is important in the success and safety of ablation for atrial fibrillation (AF). We describe the integration of CT into an electroanatomic mapping (EAM) system and its validation in patients undergoing catheter ablation for AF. METHODS AND RESULTS: Thirty patients (59.2 +/- 8 years, 25 M) with paroxysmal (12) and persistent (18) AF underwent ablation using CT image integration into an electroanatomic mapping system. CT registration using the pulmonary veins as markers (landmark) was achieved with an error of 6.4 +/- 2.8 mm with repeat registration required in two patients. Registration of the CT by best fit to a electroanatomic geometry (surface) was achieved with an error of 2.3 +/- 0.4 mm. There was no significant difference in the regional LA registration error at superior (1.7 +/- 0.7 mm), inferior (2.2 +/- 1.4 mm), septal (1.7 +/- 0.8 mm), and lateral (1.7 +/- 0.7 mm, P = 0.13) sites. Cardiac rhythm at the time of CT did not have a significant effect on total or regional surface registration accuracy (mean total 2.5 +/- 0.3 in AF patients vs 2.3 +/- 0.5 in SR patients, P = 0.22). The integrated CT was used to guide the encirclement of the pulmonary veins (PV) in pairs with electrical isolation achieved by maintaining ablation along the ablation line in 58 of 60 PV pairs. Postprocedural PV angiography did not demonstrate significant stenosis. CONCLUSION: CT image integration into an EAM system was successfully performed in patients undergoing catheter ablation for AF. With a greater appreciation of the complex and variable nature of the PV and LA anatomy this new technology may improve the efficacy and safety of the procedure.

Atrial Fibrillation↗

Retroviral DNA integrated during infection by an integration-deficient mutant of murine leukemia virus is oligomeric.

Mutants with lesions engineered into the 3' region of the pol gene of murine leukemia virus (MLV), the region that encodes p40pol, have allowed us to define a function that is required for the normal integration of retroviral DNA. Two such mutants, MLV-SF1, which bears a single missense mutation (L. A. Donehower and H. E. Varmus, Proc. Natl. Acad. Sci. USA 81:6461-6465, 1984), and MLV-SF2, which has a frameshift mutation at the same site, have been used to explore the consequences of integration deficiencies. Pseudotypes that were formed with viral proteins supplied by these mutants and a replication-defective genome that carried a selectable genetic marker induced colony formation at least 100-fold less efficiently than did pseudotypes that were formed with proteins encoded by wild-type helper virus. Most of the proviruses from the mutant pseudotypes were manifestly aberrant when they were analyzed by mapping with restriction enzymes. Rare proviruses that appeared to be normal by restriction enzyme mapping were molecularly cloned and subjected to more detailed study. Two proviruses resulting from infection with the MLV-SF1 pseudotype were identical or nearly identical to wild-type MI V proviruses. Two base pairs were missing from the ends of the long terminal repeats at the host-viral junctions, and 4- or 5-base-pair duplications of host DNA flanked the proviruses. Thus, the missense mutant appears to retain a low level of normal integration activity. Four proviruses from cells that were infected with the MLV-SF2 pseudotype were flanked on both sides by viral DNA of either helper or vector origin, with a single long terminal repeat at each end of the intact vector DNA and with irregular junctions of viral and host DNAs. These results are most simply explained by the nonspecific integration of dimeric or trimeric forms of viral DNA, which may arise during infection by replicative or recombinational mechanisms.

Animals↗

Integrative physiology: some texts and methods of integrative study.

The development of the integrative dimensions of physiology will require texts and forms of study that differ from those to which we have become accustomed in the areas of specialization. The following two types of texts lie at the heart of integrative study: framework statements and case histories. Framework statements are scientific aphorisms that summarize integrative insights; ordered chains of these statements form conceptual frameworks that stimulate integrative dialogue and thought. Case histories are stories that portray the events in the life of a living being, generally human. The nature of these texts, how framework statements are created, and methods of how texts of this kind may be used in group dialogues are discussed.

Communication↗

Imitate to integrate: reviewing the pathway for B chromosome integration in Trypoxylon (Trypargilum) albitarse (Hymenoptera, Sphecidae).

B chromosomes are genomic "intruders" normally characterized by their total dispensability counteracted by a variety of drive mechanisms, which assures their presence regardless of their harmful effects on the host genome. From an evolutionary standpoint, the relationship between standard (A) and B chromosomes can go through different pathways, from an everlasting arms race to a cordial B integration. Examples underlying the first situation are fairly common; B integration, however, has been more a theoretical than a practical possibility. The B chromosome in the haplodiploid solitary wasp Trypoxylon albitarse is probably the first example of a "mimetic" B, which is being integrated into the A genome by limiting itself to one B per haploid genome, the same dosage as the A chromosomes. Here we review some of the findings underlying this hypothesis and discuss the T. albitarse B strategy as a possible mechanism for B chromosome integration as a regular member of the chromosome complement in haplodiploid organisms.

Animals↗

Democratic integration: self-organized integration of adaptive cues.

Sensory integration or sensor fusion -- the integration of information from different modalities, cues, or sensors -- is among the most fundamental problems of perception in biological and artificial systems. We propose a new architecture for adaptively integrating different cues in a self-organized manner. In Democratic Integration different cues agree on a result, and each cue adapts toward the result agreed on. In particular, discordant cues are quickly suppressed and recalibrated, while cues having been consistent with the result in the recent past are given a higher weight in the future. The architecture is tested in a face tracking scenario. Experiments show its robustness with respect to sudden changes in the environment as long as the changes disrupt only a minority of cues at the same time, although all cues may be disrupted at one time or another.

Contrast Sensitivity↗

Integration tutorials and seminars: examining the integration of academic and fieldwork learning by student occupational therapists.

This paper, the second of two companion papers, describes a collaborative research study conducted by academic and fieldwork educators of an undergraduate educational programme in occupational therapy. The study examined the perception of student occupational therapists' ability to integrate and apply academic and theoretical knowledge in fieldwork education sites following the introduction of Integration Tutorials and Seminars to the curriculum. The literature review supports the need to develop educational strategies to improve this integration process. The qualitative research design consisted of guided interviews with preceptors and students during two consecutive fieldwork education experiences. Inductive data analysis revealed three themes that contribute to understanding students' ability to integrate academic learning during their fieldwork education: the fieldwork learning environment; preceptor influence on student learning; and the student learning process over time. The discussion section raises implications for academic and fieldwork education approaches.

Adult↗

Microglial integrity is maintained by erythropoietin through integration of Akt and its substrates of glycogen synthase kinase-3beta, beta-catenin, and nuclear factor-kappaB.

Recognized as a robust cytoprotectant for multiple tissues of the hematopoietic, vascular, cardiac, and nervous systems, erythropoietin (EPO) also is considered to be an attractive therapeutic candidate to modulate inflammatory cell function and survival during neurodegenerative disorders. To this end, microglia of the central nervous system serve a complex function not only to dispense of foreign organisms and injured cells of the brain, but also to foster tissue repair and reorganization during neuronal and vascular cell insults. We therefore examined the ability of EPO to modulate microglial cell survival and the underlying signal transduction pathways that govern microglial integrity during oxygen-glucose deprivation (OGD)--induced oxidative stress. We demonstrate in the microglial cell line EOC 2 that EPO provides direct microglial protection against early and late apoptotic programs of membrane phosphatidylserine exposure and genomic DNA degradation. Furthermore, expression and activation of Akt1 is vital to the cytoprotective capacity of EPO, since pharmacological inhibition of the PI 3-K pathway or gene silencing of Akt1 expression eliminates the ability of EPO to protect microglial cells. Through Akt1 dependent mechanisms that can be abrogated through the gene silencing of Akt1, maintenance of microglial cell integrity during OGD by EPO is closely integrated with the phosphorylation and inhibition of glycogen synthase kinase-3beta activity as well as the intracellular trafficking of beta-catenin and nuclear factor-kappaB. Further work that continues to elucidate the ability of EPO to target the intricate pathways that determine inflammatory cell function and integrity may lay the ground work for new therapeutic avenues for neurodegenerative disease.

Animals↗

Partial cross-validation of low correlation for scores on the Test of Visual-Motor Integration and the Beery-Buktenica Developmental Test of Visual-Motor Integration.

The aim of this study was to further investigate the correlation between a well established test, the Beery-Buktenica Developmental Test of Visual-Motor Integration and a new copying test, the Test of Visual-Motor Integration. For scores on the tests of 71 children from a public school in Italy, the correlation is .34, which is consistent with earlier evidence and indicates that the Test of Visual-Motor Integration is not a substitute for the Beery-Buktenica Developmental Test of Visual-Motor Integration.

Child↗

Integrating integrated laboratory information into health care delivery systems.

Attention to integration of laboratory data and its integration into clinical processes and enterprises can help make the laboratory's work a more integral part of clinical practice. The resulting integration holds great potential for improving the quality and effectiveness of care and adding to the clinical value of the laboratory work.

Clinical Laboratory Information Systems↗

[Application of numeric integration in waveform morphology of visual evoked potentials in optic nerve diseases. Numeric integration method].

PURPOSE: Presentation of new waveform analysis of pattern and flash visual evoked potentials (VEPs) in patients with optic neuropathy. MATERIAL AND METHODS: The study involved 48 patients with acute optic neuritis (2nd group), 60 patients with demyelinating (3rd group), 32 patients with compressive (4th group), 24 patients with nonarteritic anterior ischemic optic neuropathy (5th group) and 32 healthy subjects (1st group). Using computer system UTAS E-1000 (pattern and flash stimulation) the VEPs tests were performed. Amplitude, latency of 8 VEP components, 4 gradients, mean waveform and 16 areas of numeric integrals were calculated. Results were analysed with the use of AN-STAT software. RESULTS: Statistical difference recorded under pattern stimulation was obtained in latency of 3rd, 4th, 5th components of VEP in comparing 3th and 4th groups, as well as amplitude of 3rd waveform, second gradient, areas of integrals between cursors number 2 and 4 in comparing 3rd and 5th groups (p < 0.001). Statistical difference recorded under flash stimulation was obtained in latency of 4th component in comparing 2nd and 5th groups, in amplitude of 7th waveform, areas of integrals covering 160 and 224, 224 and 256 ms, between cursors number 2 and 4 in comparing 4th and 5th groups, as well as in a range of areas of integrals covering 160 and 192 ms in comparing 4th and 5th groups (p < 0.001). CONCLUSION: Results prove clinical potency of the presented new comprehensive method in analysis of VEP in optic nerve diseases.

Acute Disease↗

[Genetic study of plasmid integration into yeast chromosomes. V. Mapping of integration sites for the plasmid pYF91].

The data on mapping the episomal plasmid integration sites in yeast chromosomes I, III, IV, V, VII, XV are presented. In addition to the integration site at leu2 of chromosome III localized earlier, 6 more loci containing apparently the homologous yeast transposons, with a copy in a plasmid, were defined. The fact of plasmid integration was proved by colony hybridization technique with the pBR322 probe. The plasmid DNA segregation (the ratio 2:2) and its linkage to pLEU2 plasmid marker gene were observed in hybrids of all integrants studied.

Chromosome Mapping↗

Integrated school health services. American Academy of Pediatrics Task Force on Integrated school Health Services.

When integrated school health services are implemented according to an assessment of community needs and resources, and with adequate attention to quality assurance and evaluation, they may be a way to expand access to health care services for underserved populations. They can also become a coordinated extension of an ongoing medical care home. This approach may be an effective vehicle for integrating psychosocial care and education with medical care. Pediatricians practicing in public and private sectors should become actively involved in any community effort to develop an integrated school health services initiative. The well-designed integrated health services program, when coupled with comprehensive school health education, could significantly advance the state of health of the nation's children, youth, and families.

Adolescent↗