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PubMed2004

An ecological integrity index for littoral wetlands in agricultural catchments of semiarid mediterranean regions.

The main goal of the present study was to develop an ecological integrity index for littoral wetland management and conservation in semiarid Mediterranean areas that have been highly impacted by agriculture, including the selection of pressure and state indicators at landscape and wetlands scales that reflect the status, condition, and trends of wetlands ecosystems. We used a causality framework based on the relationship between pressure of anthropogenic activities and the ecological state of wetlands and their catchments, integrating environmental, biologic, economic, and social issues. From the application of 51 indicators in 7 littoral wetlands in the southeastern Iberian Peninsula, we selected 12 indicators (5 at catchment scale and 7 at wetland scale) to constitute the ecological integrity index proposed. The potential nitrogen export per area at catchment scale and the potential relative nitrogen export from the area surrounding the wetlands were the best pressure single predictors of state indicators with a causal relationship with environmental meaning. Wetlands in catchments with more agriculture had less ecological integrity than those in less impacted areas. A wide riparian zone in some wetlands acts as a buffer area, diminishing the effects of intensive agriculture. The index of ecological integrity developed here has a number of essential characteristics that make it a useful tool for ecosystem managers and decision-makers. The index can be used to (1) assess and control ecological integrity, (2) diagnose probable causes of ecological impairment, (3) establish criteria for protecting and restoring wetland ecosystems, and (4) integrate catchment management.

Abstracting and Indexing↗
PubMed2002

The effect of preceding sonar emission on temporal integration in the bat, Megaderma lyra.

The present study investigated whether and to which extent temporal integration in bats is influenced by echolocation behavior. One way to quantify temporal integration is to measure the detection threshold for a pair of short tone pips as a function of the temporal separation between the pips. To asses the effect of preceding sonar emission on temporal integration in the bat, Megaderma lyra, the detection thresholds of identical subjects were measured in a passive as well as in an active paradigm. In the passive paradigm, the presentation of the pip pairs was independent of the bats' sonar emissions; in the active paradigm, the presentation was triggered by the bats' sonar emissions. In both cases, the bats showed a very short integration time in the range of 100-200 micros. Moreover, the comparison of the active and passive results within each bat revealed no systematic differences in the two measuring paradigms. These results indicate that temporal integration is not influenced by echolocation. Simulations with a computer model of cochlear filtering based on measurements of M. lyra cochlear tuning suggest that the perceptual temporal integration is dominated by the integration of the cochlear filters.

Animals↗
PubMed2001

An Aspergillus nidulans uvsC null mutant is deficient in homologous DNA integration.

The Aspergillus nidulans uvsC gene was identified as a homolog of RAD51 and recA of Saccharomyces cerevisiae and Escherichia coli, respectively, whose role in genetic recombination and recombinational repair has been extensively studied. Like many other filamentous fungi, A. nidulans shows no bias towards either homologous or ectopic integration of exogenous DNA. Therefore it is a unique and useful organism for the study of the mechanisms of DNA integration. Homologous integration of a 1.7-kb argB gene was not detected in 50 transformants obtained from a uvsC null mutant. In contrast, the frequency of homologous integration in uvsC+ control strains varied from 41 to 86%. Another feature observed with the uvsC null mutant was that an increased number of transformants had undergone ectopic integrations at multiple sites in the genome. These results are consistent with the established function of Rad51/RecA, and further indicate the involvement of redundant pathways in integration of exogenous DNA. This study provides direct evidence for the involvement of uvsC in exogenous DNA integration and should contribute to the improvement of genetic manipulations in general, but particularly in fungi.

Aspergillus nidulans↗
PubMed2002

Developing an action plan for integrating sleep topics into the medical school curriculum.

Sleep disorders are prevalent although they go unrecognized by clinicians, partially because of limited exposure to sleep medicine topics during medical school. Sleep topics can be integrated during both the preclinical and clinical years of the medical school curriculum by developing an integration strategy and action plan. Components of the action plan include examining the current medical school curriculum and the teaching infrastructure. Understanding curricular governance issues and how curriculum time is allocated will allow development of an effective integrative strategy. Sleep topics can be integrated into neuroscience, neuroanatomy, physiology, and behavioral science courses during the preclinical years. The sleep history and physical can be integrated into the physical diagnosis course. Sleep disorders can be introduced in clinical correlation courses. Integration strategies during the clinical years may include computer-based simulations. Careful assessment of the existing curriculum, curricular governance processes, and available educational resources will optimize the probability of successfully integrating sleep topics into the medical school curriculum.

Curriculum↗
PubMed1991

Skeletal integrity in premenopausal and postmenopausal women receiving long-term L-thyroxine therapy.

PURPOSE: The impact of long-term L-thyroxine replacement therapy on skeletal integrity is a growing concern because of the large number of women receiving thyroid hormone therapy. The purpose of this study was to examine the hypothesis that long-term L-thyroxine therapy in which the free thyroxine index (FT4I) is maintained within a physiologic range has minimal impact on vertebral or femoral bone mineral density in both premenopausal and postmenopausal women. PATIENTS AND METHODS: We measured hip integral and spinal trabecular and integral bone densities in 28 premenopausal and 28 postmenopausal women who had been receiving L-thyroxine therapy for a median of 12 and 15 years, respectively, and in whom therapy was titrated to keep the FT4I within the normal range. The relationship between bone density parameters and thyroid hormone status was examined using univariate and multivariate statistical methods. RESULTS: Seventy-nine percent of the premenopausal women and 86% of the postmenopausal women had FT4I values in the normal range at the time of bone density determination. Moreover, throughout the study's duration, the majority of annually measured values were in the normal range for more than 80% of subjects. Premenopausal women had slightly lower bone density than would be expected for age: -6.7% (z = -0.39 +/- 0.74 [mean +/- SD], p less than 0.01), -3.1% (z = -0.22 +/- 0.78, p = 0.15), and -5.1% (z = -0.36 +/- 0.74, p less than 0.02) for spinal trabecular, spinal integral, and hip integral bone density, respectively. Postmenopausal women likewise had slightly lower bone density values that were significant only at the hip: -0.2% (z = -0.01 +/- 1.01, p = 0.95), -1.0% (z = -0.05 +/- 1.11, p = 0.80), and -6.2% (z = -0.39 +/- 0.80, p less than 0.02) for spinal trabecular, spinal integral, and hip integral bone density, respectively. When patients with previously treated Graves' disease (n = 4 in each group) were eliminated, the differences in bone density at the hip were no longer seen. Correlation analysis revealed only weak and generally nonsignificant relationships between parameters of thyroid hormone status and bone density at any site in either subgroup. Results of multiple regression analysis among the pooled data of all subjects showed that age provided a consistently significant contribution (R2 = 0.18 to 0.66) to the variability in bone density at the spine and the hip, but parameters of thyroid hormone status did not. CONCLUSION: These data provide the first supportive evidence that long-term L-thyroxine therapy that maintains the FT4I in the physiologic range is associated with a statistically significant, but clinically minimal, decrement in spinal and hip bone density in both premenopausal and postmenopausal women. The decrement at the hip was entirely due to the inclusion of patients with treated Graves' diseases. Thus, the changes in bone density in women receiving long-term L-thyroxine therapy are minimal at most and should not be a contraindication to therapy.

Adult↗
PubMed1985

Numerical integration in the reconstruction of cardiac action potentials using Hodgkin-Huxley-type models.

A comparison between traditional numerical integration methods and a new hybrid integration method for the reconstruction of action potential activity is presented, using a mathematical model of the cardiac Purkinje fiber (MNT model). It is shown that the hybrid integration method reduces importantly the overall computation time required for solving the Hodgkin-Huxley differential equations describing membrane electrical events. To accomplish this, the particular form of the gating variable equations is exploited to reformulate the step-by-step computation. In this way, the time increment can be made much larger compared with traditional methods when the membrane potential changes slowly. A mathematical analysis of the hybrid integration method is presented also, together with a numerical verification of its performance both for the propagated and nonpropagated membrane action potential. It is shown that the local error, that is the error arising at each integration step, and the cumulative integration error are strictly controlled by the membrane potential offset. Using the MNT model, the nonpropagated cardiac Purkinje action potential can be reconstructed in real time with an accuracy of 1% for the potential and 5% for the time of occurrence of its main features. In reconstructing propagated events, the hybrid integration method allows computation time savings by a factor of 10 or more compared to accurate Runge-Kutta schemes.

Action Potentials↗
PubMed1992

Effect of measurement interval on performance of the ST integral for the identification of three-vessel coronary disease.

Measurement of the ST integral has usually incorporated ST-segment depression integrated between the J point and 80 ms after the J point (J + 80). To assess the effect of varied onset and offset of ST measurement on performance of the ST integral for the identification of three-vessel coronary disease, the exercise electrocardiograms (ECGs) of 60 patients with angiographically proven coronary disease were analyzed using J point or J + 20 onsets and J + 60 or J + 80 offsets of ST integral calculation. Simple ST-segment depression of greater than 200 microV, measured at 60 ms after the J point, identified three-vessel disease with a specificity of 68% (17 out of 25 patients) and sensitivity of 69% (22 out of 35 patients). At a matched specificity of 68% (17 out of 25 patients), there was identical sensitivity (54%, 19 out of 35 patients) of ST integrals measured either from the J point to J + 80, from the J point to J + 60, or from J + 20 to J + 60. A trend toward increased sensitivity (60%, 21 out of 35 patients) when the ST integral was measured from J + 20 to J + 80 did not reach statistical significance, and comparison of receive operating characteristics (ROC) curves demonstrated that varying the onset and offset of ST-segment measurement had no significant effect on the overall performance of ST integral criteria for the detection of three-vessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Angiography↗
PubMed1987

A rare common integration site of proviruses of the mouse mammary tumor virus in P-type mammary tumors of mouse strain GR.

The mouse mammary tumor virus (MMTV) can induce mammary tumors in mice by proviral activation of the cellular oncogenes int-1 or int-2. Activation of these genes, however, is observed in only a few hormone- and pregnancy-dependent mammary tumors of the mouse strain GR. To study the possible involvement of other oncogenes we cloned three MMTV proviral-host fragments (MT 40, 42, and 53) from different mammary tumors of GR with a single acquired MMTV provirus. From a genomic library of normal mouse DNA we isolated phages with insert DNAs that covered 20-30 kb of the uninterrupted regions. Suitable probes devoid of repetitive DNA sequences were isolated in order to screen other mammary tumors for MMTV proviral integrations in these regions. Only two mammary tumors, MT 40 and 42, showed integration of extra MMTV proviruses within the same region. The integrations occurred only 60 bp apart. The other mammary tumors, however, did not contain MMTV proviral integrations in this region, nor in the MT 53 region. Using mouse-hamster somatic cell hybrid DNA, the MT 40/42 integration region was assigned to mouse chromosome 7, and the second region, MT 53, to chromosome 16. The two regions bear no homology to known cellular oncogenes. We did not observe any mRNA being expressed from these cloned segments either in tumors or in normal mammary glands. These findings indicate that plaque(P)-type mammary tumors in mouse strain GR do not originate from MMTV provirus insertions in a particularly favored integration region, but that there may be a variety of integration sites in these tumors.

Animals↗
PubMed1990

Analysis of the unoccupied site of an integrated human papillomavirus 16 sequence in a cervical carcinoma.

We have previously cloned and analyzed the structure of a type 16 human papillomavirus (HPV16) integration in a primary cervical carcinoma tissue, M50 (Choo et al., J. Virol. 62, 1659-1666, 1988). We found that specific nucleotide sequences within the HPV16 genome influenced the genomic organization of the integrated viral genome. Using the viral-cellular junctions of the M50 DNA as probes, we have now cloned the unoccupied site from a human genomic library. Mapping analysis showed that a deletion of about 1.1 kilobase pairs (kb) had occurred at the integration site of M50. Sequencing of the integration junctions of the unoccupied site and comparison with the viral sequence has revealed short regions of sequence homology between the viral and the cellular genomes at both junctions. Our results are consistent with a mechanism of integration of the HPV16 sequences in the M50 carcinoma involving illegitimate recombination events using short patches of homologous sequences between the two heterologous genomes for anchorage and as guides for crossover. Preferred topoisomerase I cleavage sites and alternating purine and pyrimidine bases, which favor the formation of Z-DNA, could also be identified at the integration regions, supporting a proposed role for the topoisomerase I enzyme in the illegitimate recombination in the viral integration process.

Attachment Sites, Microbiological↗
PubMed1996

Contour integration with colour and luminance contrast.

In this study, we consider how colour contrast can be used to integrate form and how it interacts with luminance contrast in the task. The performance of form integration was assessed by measuring the detection of a winding "contour" of aligned gabor elements embedded in a background of randomly oriented gabors, using both luminance and isoluminant (red/green) contrast. Performance on the task improves with gabor element contrast, and identical performance for colour and luminance contour detection is achieved at high screen contrasts, showing that colour is able to support a complex form integration task. In a second experiment, we investigate whether colour and luminance contrast can be combined in contour integration by measuring the detection of a path with alternating isoluminant colour and luminance elements. We find that contour detection uses both colour and luminance information cooperatively, but performance is much poorer than would be expected from a single common contour integration process which fails to distinguish the two types of contrast. This suggests that there are specific contour integration processes for colour and luminance. In a third experiment, we measure the effects of variations in colour and luminance contrast on contour detection using elements that combine colour and luminance contrast. We find that varying the colour contrast of elements tends to worsen the detection of a luminance contour, as do luminance contrast variations for colour contour detection. These results suggest no special role for colour in integrating contours, and are discussed with regard to their ecological significance.

Algorithms↗
PubMed1978

Sites of integration of infectious DNA of avian reticuloendotheliosis viruses in different avian cellular DNAs.

The pattern of integration for the infectious DNA of two avian reticuloendotheliosis viruses whose DNA is not inactivated by digestion with the restriction endonuclease, Eco RI was determined. High molecular weight DNA from infected chicken, turkey and pheasant cells was digested with Eco RI, electrophoresed through agarose gels and assayed for infectivity. The same patterns of integration of infectious viral DNA were found for these species of avian cells infected at high or low multiplicities with two reticuloendotheliosis viruses. There were multiple sites of integration in acutely infected cells with concomitant cell death. There was a single site of integration in chronically infected cells with no cell death. There were more integrated infectious viral DNA molecules per cell in acutely infected cells than in chronically infected cells. These results are consistent with the hypotheses that the cell death in the acute phase of infection is a result of the integration of the infectious viral DNA at multiple sites, and that only those cells survive that have the infectious viral DNA integrated exclusively at the single site.

Cell Line↗
PubMed1987

Correct integration of retroviral DNA in vitro.

We have developed a cell-free system for studying the integration of retroviral DNA. In our assay, amber mutations in a bacteriophage lambda genome that serves as the target for integration are suppressed by integration of an MLV derivative that carries the E. coli supF gene. The structure of the reaction products is that expected from an authentic MLV integration reaction. Linear viral DNA from the cytoplasm of infected cells serves as a precursor, though not necessarily the immediate precursor, to the provirus integrated in vitro. The viral DNA in the infected cell appears to be tightly associated with the enzymatic machinery required for its integration. Supercoiling, chromatin structure, transcription, and replication are not required of the target DNA. Since no high-energy cofactor is necessary, the DNA breakage and joining steps in the integration reaction are probably coupled.

Animals↗
PubMedDate not supplied

Effect of DNA damage on stable transformation of mammalian cells with integrative and episomal plasmids.

The efficiency of stable transformation of human cells by integrative (non-replicating) plasmids carrying a selectable gene has been shown to be markedly enhanced by the introduction into the plasmid DNA of bulky damage, such as cyclobutane pyrimidine dimers or psoralen photoadducts. Enhanced transformation (ET) occurs in all human cells tested, including DNA repair-deficient cells from the hereditary syndrome xeroderma pigmentosum, but significantly less, if at all, in rodent cells. ET has been observed with a variety of integrative plasmid constructs, suggesting the generality of the phenomenon; as expected, ET is due to an increase in the number of cells carrying integrated plasmid sequences. In contrast to integrative plasmids, stable transformation by episomal (autonomously replicating) plasmids derived from the Epstein-Barr virus is only depressed by the introduction of photoproducts; furthermore, pronounced inactivation of transformation mediated by episomal plasmids becomes apparent in xeroderma pigmentosum cells. Altogether, these results suggest that DNA damage increases the probability of stable insertion of heterologous non-replicating DNA into human chromosomes. Moreover, the differential sensitivity to DNA damage of human cell transformation mediated by integrative versus episomal plasmids suggests caution in using such assay to measure host cell reactivation capacity; processing of DNA damage in mammalian cells might differ significantly between intra- versus extra-chromosomal DNA. Since ET may be induced by damage outside the selectable gene carried on integrative plasmids, we propose a model that involves local disruption of chromatin structure by helix-distorting DNA lesions flanking actively transcribed sequences; alternatively, reorganization of such altered DNA structure might be favored by the presence of topoisomerase-like activities in the proximity of active genes. Because ET can also be induced by DNA damage to the recipient cells, it is speculated that similar mechanism(s) might be involved in the generation of other types of non-homologous DNA recombination in damaged human chromosomes, including oncogenic cell transformation mediated by integrative DNA viruses.

Animals↗
PubMed1995

Vestibular integrators in the oculomotor system.

The interstitial nucleus of Cajal (INC) and the nucleus prepositus hypoglossi (nph) are key elements in the vertical and horizontal oculomotor neural integrators, respectively. In this article, we attempt to develop possible circuits for these vestibular integrators by synthesizing recent information on the properties and connections of neurons involved in the integration process. We also examine how the cerebellar flocculus could play a role in the vertical integrator and vestibulo-ocular reflex (VOR) as well as in the modulation and plasticity of the VOR. We suggest that the circuitry for the vertical integrator involves the cerebellar flocculus in addition to the already proposed circuits distributed between the INC and the vestibular nuclei. The horizontal vestibular integrator is also distributed and seems to be characterized by functional compartmentalization. Both integrators play a wider role than simply transforming velocity-coded signals into position commands and may be pivotal in the short- and long-term modulation of the various oculomotor subsystems.

Animals↗
PubMed1986

Patterns of integration of exogenous DNA sequences transfected into mammalian cells of primate and rodent origin.

We studied the cotransfer and cointegration of several genes transfected into four cell lines of primate origin. Mouse thymidine-kinase-negative LM cells, which had been extensively studied previously, were used as a reference. We found that in monkey kidney Vero cells, on average between 3.5 and 6.0 kb of plasmid sequences was integrated per clone, while in the murine LM cell line, 9-186 kb of exogenous DNA was integrated per clone. Transformed Vero clones which had integrated more than 6 kb of DNA did not integrate larger DNA fragments in a second transformation assay than had the parental Vero cells. We found that the efficiency of gene cointegration is similar in Vero, HeLa and GM4312A cells, the latter being deficient in the repair of UV-induced damage. The human hepatocarcinoma Hep G2 cells integrated on the average 2 kb more exogenous DNA than the three other primate cell lines, which resulted in a 4-5 times higher efficiency of gene cointegration. Plasmid penetration and persistence in a free state between 24 h and two weeks after transfection was similar in Vero and LM cells. No major post-integration DNA rearrangement could be demonstrated after the isolation of Vero clones. These observations correlate the low efficiency of gene cointegration in some primate cell lines with a genomic recombination step or with rearrangements taking place during early cell divisions following integration.

Animals↗
PubMed1987

Excision and integration of a self-transmissible replicon of Streptomyces ambofaciens.

When Streptomyces ambofaciens OSF was crossed with the plasmid-free Streptomyces lividans TK24, almost all S. lividans exconjugants contained the free 11.1-kb plasmid pOS1. Southern hybridizations showed that pOS1 was derived from the integrated copy of previously recognized plasmid pSAM2 present in strain OSF. A shorter derivative of pOS1 was constructed carrying the tsr gene in a non-essential region, and this pOS7 plasmid was used in transformation experiments with protoplasts of S. ambofaciens ATCC23877 (containing pSAM2 only as an integrated sequence) and S. ambofaciens DSM40697 (devoid of pSAM2-related forms). In both cases, some clones carrying pOS7 in an integrated state were found. Integration into strain ATCC23877 was into the pre-existing integrated copy of pSAM2. In contrast, plasmid pOS7 integrated through specific plasmidic and chromosomal sites into strain DSM40697. Thus it is probable that pSAM2 integrates by interaction between preferred regions of the plasmid and host genomes.

Animals↗
PubMed1990

Preferential integration of the Ad5/SV40 hybrid virus at the highly recombinogenic human chromosomal site 1p36.

Human fibroblasts transformed with an adenovirus-5/simian virus 40 recombinant construct (Ad5/SV40) were analyzed to determine the chromosomal site(s) of virus integration. This was firstly done by in situ hybridization using metaphase and prometaphase chromosomes and 125I-labeled Ad5 DNA. Out of seven transformed cell lines (six of clonal origin and one uncloned), six were proven to have integrated the viral genome at the short- or the long-subtelomeric regions of autosome 1, two regions known to include chromosomal modification sites induced by acute infection with Ad12. Characterization of the integration sites was carried out by restriction analysis. Transformed cell lines with the same major chromosomal integration site were found to have the viral genome inserted in restriction fragments of different size, indicating that viral integration has occurred at different sites within a relatively small chromosomal region. Molecular studies carried out on one of the transformed cell lines (H13.1) gave an independent confirmation of the viral integration at the subterminal region of autosome 1 short arm. Nucleotide sequencing at this cellular-viral junction has shown that the virus has integrated within tandemly repeated Alu-like elements and that the cellular flanking sequences have several homologies with variable number of tandem repeats core sequences. Many possible open reading frames were identified in the DNA segment adjacent to the Alu-like elements.

Adenoviruses, Human↗
PubMed1992

Kluyveromyces lactis rDNA as a target for multiple integration by homologous recombination.

Gene targeting to a single chromosomal locus has been extensively used in Saccharomyces cerevisiae. In this study, we have analyzed targeting of a repetitive sequence, the 25S rDNA gene, to the chromosomal rDNA cluster of Kluyveromyces lactis by the use of a replacement vector. We have obtained K. lactis transformants carrying multiple copies of the replacement cassette inserted into the rDNA chromosomal locus. Analysis of several transformants has shown that the number of integrated copies could range from 4 to 40. Moreover, the distribution of integration sites within the rDNA locus was found to differ in most transformants. Single-copy integration at multiple sites, rather than multicopy integration at a very limited number of sites, was found to be the most frequent event. Also, in most transformants, integration sites were distributed at random as well as in an orderly fashion, i.e., in contiguous or alternate rDNA repeats, suggesting that amplification of the integrated sequences, rather than multiple integration events, may account for the copy number of insertions.

Blotting, Northern↗