A proteolytic memory element based on the integrating function of the neuron.
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The Ta (transcribed, subset a) subfamily of L1 LINEs (long interspersed elements) is characterized by a 3-bp ACA sequence in the 3' untranslated region and contains approximately 520 members in the human genome. Here, we have extracted 468 Ta L1Hs (L1 human specific) elements from the draft human genomic sequence and screened individual elements using polymerase-chain-reaction (PCR) assays to determine their phylogenetic origin and levels of human genomic diversity. One hundred twenty-four of the elements amenable to complete sequence analysis were full length ( approximately 6 kb) and have apparently escaped any 5' truncation. Forty-four of these full-length elements have two intact open reading frames and may be capable of retrotransposition. Sequence analysis of the Ta L1 elements showed a low level of nucleotide divergence with an estimated age of 1.99 million years, suggesting that expansion of the L1 Ta subfamily occurred after the divergence of humans and African apes. A total of 262 Ta L1 elements were screened with PCR-based assays to determine their phylogenetic origin and the level of human genomic variation associated with each element. All of the Ta L1 elements analyzed by PCR were absent from the orthologous positions in nonhuman primate genomes, except for a single element (L1HS72) that was also present in the common (Pan troglodytes) and pygmy (P. paniscus) chimpanzee genomes. Sequence analysis revealed that this single exception is the product of a gene conversion event involving an older preexisting L1 element. One hundred fifteen (45%) of the Ta L1 elements were polymorphic with respect to insertion presence or absence and will serve as identical-by-descent markers for the study of human evolution.
A tracheary element (TE) is a typical example of a cell type that undergoes programmed cell death in the developmental processes of vascular plants. The loss of the selective permeability of the tonoplast, which corresponds to tonoplast disintegration, occurred after the cells commenced secondary wall thickening and played a pivotal role in the programmed cell death of TEs in a zinnia (Zinnia elegans L.) cell culture. A search for events specifically associated with the TE vacuole provided an important clue to the understanding of the cell death mechanism. The transport of fluorescein, a fluorescent organic anion, across the tonoplast declined drastically in differentiating TEs. The capacity of the vacuole to accumulate the probe was also impaired. Treatment with probenecid, an inhibitor of organic anion transport, caused rapid cell death of TEs and led to the ultimate disruption of the vacuole even in other types of cultured cells. These changes in vacuolar properties during TE development were suppressed by cycloheximide. Specific mRNA accumulation in cells cultured in a TE differentiation-inductive condition was abolished by probenecid. These results suggest that a change in vacuolar membrane permeability promotes programmed cell death in TEs.
Despite advances in female developmental theory since the 1970s, there remains a lingering tendency to stereotype and polarize gender identity. The key to this puzzle may be found in the legacy of early libido theory, which offers an unintegratable solution for women. This is because in order for a woman to claim femininity according to this early theory, her masculine trends in development must be repudiated and "overcome." A contemporary theory based on primary femininity suggests that this early theoretical "either/or" dilemma puts forward a developmentally immature solution. The analysis of a thirty-year-old woman, and a commentary contrasting "old" and "newer" ways of thinking on the part of the analyst, demonstrate that an interweaving pattern of paternal identifications and male body representations, together with the female body image and female identifications, is necessary to create a mature gender identity portrait. The female body representation and maternal identifications may indeed be enhanced by male internalizations, as happened in this particular instance.
We describe a method in which holograms can be produced by calculation from images captured by integral photography (IP). We present a basic algorithm obtained by simulating IP reconstruction, in which conditions are set so as not to cause aliasing in the holograms after the calculations. To reduce the calculation load, we also propose a way to limit the range of calculation considering the distribution of light and a way to shift the optical field on the exit plane of microlenses in a lens array. Finally, by optical experiments, we confirm that three-dimensional images can be reconstructed from holograms calculated from an integral photograph of a real object captured with an IP camera.
The previous discussions obviously lend credibility to the construct of concurrent integrated UR-QR management. DRG prospective payment obviously accelerates the need for coordinated interdepartmental UR-QR management so that managers are in positions to control the units of service. The value of concurrent integrated UR-QA management is patent in supporting the institutional mission of fiscal solvency under DRG prospective payment. However, very few acute care facilities have such programs in place; the rule is to departmentalize the components of UR and QR at the expense of efficiency, cost-effectiveness and problem resolution.
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Tn916 is a broad host range tetracycline resistance conjugative transposon. In most bacteria, this element enters the bacterial genome at multiple sites. However, in Clostridium difficile, the element has a strong hot spot when introduced by filter mating from Bacillus subtilis. In this work, the DNA sequence of the preferred insertion site (att916) was obtained. An environmental isolate of C. difficile was also discovered which contained an element indistinguishable from Tn916, Tn916CD. Tn916CD was found integrated at att916.
The ninja element, originally isolated from an unstable white mutant strain white-milky (w(mky)) of Drosophila simulans, is a member of the retrotransposon family with long terminal repeats (LTRs). We show that ninja is present in high copy numbers in the w(mky)-derivative sublines white-chocolate (w(cho)) and white-persimmonl (w(psm1)), in a low copy number in another derivative subline white-milky 3 (w(mky3)), and in only a few copies in a wild type strain. We have cloned the ninja elements from these sublines and examined their structures. Most of the elements cloned (38 out of 41 independent clones) from w(cho) were full length. In contrast, only 9 of 23 independent clones from w(mky3) were full length. We hypothesize that ninja elements were integrated and lost frequently in the w(mky) strain and its derivative genomes, and that a rapid decrease in numbers of the ninja element was caused not by an increased rate of loss but by a reduction of integration of full length ninja elements in w(mky3). Each defective element had a unique deletion and/or an insertion except for the three from w(mky3), which had exactly the same 81-bp deletion in each of the 5' and 3' LTRs. The 5' and 3' ends of the deletion appeared to represent sequences similar to those of Drosophila consensussplicing sites. Ectopic splicing may have produced these defective ninja elements.
Development of the finite-element-based Integrated Groundwater and Surface-Water Model (IGSM) began in the 1970s. Its popularity grew in the early 1990s with its application to California's Central Valley Groundwater Surface-Water Model in support of the Central Valley Project Improvement Act. Since that time, IGSM has been applied by federal, state, and local agencies to model a number of major basins in California. Our review of the recently released version 5.0 of IGSM reveals a solution methodology that deviates from established solution techniques, potentially compromising its reliability under many circumstances. One difficulty occurs because of the semi-explicit time discretization used. Combined with the fixed monthly time step of IGSM, this approach can prevent applications from accurately converging when using parameter values typically found in nature. Additionally, IGSM fails to properly couple and simultaneously solve ground water and surface water models with appropriate mass balance and head convergence under the reasonable conditions considered herein. As a result, IGSM-predicted streamflow is error prone, and errors could exceed 100%. IGSM does not inform the user that there may be a convergence problem with the solution, but instead generally reports good mass balance. Although our review touches on only a few aspects of the code, which exceeds 17,000 lines, our experience is that similar problems arise in other parts of IGSM. Review and examples demonstrate the potential consequences of using the solution methods in IGSM for the prediction, planning, and management of water resources, and provide perspective on the roles of standards and code validation in ground water modeling.
The ubiquity of mobile elements in mammalian genomes poses considerable challenges for the maintenance of genome integrity. The predisposition of mobile elements towards participation in genomic rearrangements is largely a consequence of their interspersed homologous nature. As tracts of nonallelic sequence homology, they have the potential to interact in a disruptive manner during both meiotic recombination and DNA repair processes, resulting in genomic alterations ranging from deletions and duplications to large-scale chromosomal rearrangements. Although the deleterious effects of transposable element (TE) insertion events have been extensively documented, it is arguably through post-insertion genomic instability that they pose the greatest hazard to their host genomes. Despite the periodic generation of important evolutionary innovations, genomic alterations involving TE sequences are far more frequently neutral or deleterious in nature. The potentially negative consequences of this instability are perhaps best illustrated by the >25 human genetic diseases that are attributable to TE-mediated rearrangements. Some of these rearrangements, such as those involving the MLL locus in leukemia and the LDL receptor in familial hypercholesterolemia, represent recurrent mutations that have independently arisen multiple times in human populations. While TE-instability has been a potent force in shaping eukaryotic genomes and a significant source of genetic disease, much concerning the mechanisms governing the frequency and variety of these events remains to be clarified. Here we survey the current state of knowledge regarding the mechanisms underlying mobile element-based genetic instability in mammals. Compared to simpler eukaryotic systems, mammalian cells appear to have several modifications to their DNA-repair ensemble that allow them to better cope with the large amount of interspersed homology that has been generated by TEs. In addition to the disruptive potential of nonallelic sequence homology, we also consider recent evidence suggesting that the endonuclease products of TEs may also play a key role in instigating mammalian genomic instability.
To study integration of the human LINE-1 retrotransposon (L1) in vivo, we developed a transgenic mouse model of L1 retrotransposition that displays de novo somatic L1 insertions at a high frequency, occasionally several insertions per mouse. We mapped 3' integration sites of 51 insertions by Thermal Asymmetric Interlaced PCR (TAIL-PCR). Analysis of integration locations revealed a broad genomic distribution with a modest preference for intergenic regions. We characterized the complete structures of 33 de novo retrotransposition events. Our results highlight the large number of highly truncated L1s, as over 52% (27/51) of total integrants were <1/3 the length of a full-length element. New integrants carry all structural characteristics typical of genomic L1s, including a number with inversions, deletions, and 5'-end microhomologies to the target DNA sequence. Notably, at least 13% (7/51) of all insertions contain a short stretch of extra nucleotides at their 5' end, which we postulate result from template-jumping by the L1-encoded reverse transcriptase. We propose a unified model of L1 integration that explains all of the characteristic features of L1 retrotransposition, such as 5' truncations, inversions, extra nucleotide additions, and 5' boundary and inversion point microhomologies.
Variation in the use of clinical resources, outcomes, costs, access to health care and quality is a well recognized, ever present feature of health care. It is a phenomenon that affects all sectors of the health care delivery process and is important to clinicians, administrators and patients. As a phenomenon variation can be appropriate or inappropriate and the elimination of inappropriate variation is a fundamental principal behind continuous quality improvement in health care. The primary tools for the management of variation exists within the electronic medical record (EMR). The EMR utilizes the existing and evolving information storage technologies (data repositories) and information management tools (applications), to integrate the elements within this long-term data storage. Through this integration the EMR systems are able to provide knowledge representation in differing formats to the decision-makers and this will facilitate more accurate and appropriate decision-making with subsequent improvements in health care delivery.
Micromonospora carbonacea var. africana ATCC 39149 contains a temperate bacteriophage, pMLP1, that is present both as a replicative element and integrated into the chromosome. Sequence analysis of a 4.4 kb KpnI fragment revealed pMLP1 att/int functions consisting of an integrase, an excisionase and the phage attachment site (attP). Plasmids pSPRH840 and pSPRH910, containing the pMLP1 att/int region, were introduced into Micromonospora spp. by conjugation from Escherichia coli. Sequence analysis of DNA flanking the integration site confirmed site-specific integration into a tRNAHis gene in the chromosome. The pMLP1 attP element and chromosomal bacterial attachment (attB) site contain a 24 bp region of sequence identity located at the 3' end of the tRNA. Integration of pMLP1-based plasmids in M. carbonacea var. africana caused a loss of the pMLP1 phage. Placement of an additional attB site into the chromosome allowed integration of pSPRH840 into the alternate attB site. Plasmids containing the site-specific att/int functions of pMLP1 can be used to integrate genes into the chromosome.
The isolation of sequences flanking integrated transposable elements is an important step in gene tagging strategies. We have demonstrated that sequences flanking transposons integrated into complex genomes can be simply and rapidly obtained using the polymerase chain reaction. Amplification of such sequences was established in a model system, a transgenic tobacco plant carrying a single Ac element, and successfully applied to the cloning of a specific Spm element from a maize line carrying multiple Spm hybridizing sequences. The described utilization of methylation sensitive restriction enzymes (including those with degenerate recognition sequences) in the generation of templates for amplification will simplify the cloning and mapping of genomic sequences adjacent to transposable elements.