1,499 research outputs found
Detection of chromosome aberrations in the human interphase nucleus by visualization of specific target DNAs with radioactive and non-radioactive in situ hybridization techniques: diagnosis of trisomy 18 with probe L1.84
The localization of chromosome 18 in human interphase nuclei is demonstrated by use of radioactive and nonradioactive in situ hybridization techniques with a DNA clone designated L1.84. This clone represents a distinct subpopulation of the repetitive human alphoid DNA family, located in the centric region of chromosome 18. Under stringent hybridization conditions hybridization of L1.84 is restricted to chromosome 18 and reflects the number of these chromosomes present in the nuclei, namely, two in normal diploid human cells and three in nuclei from cells with trisomy 18. Under conditions of low stringency, cross-hybridization with other subpopulations of the alphoid DNA family occurs in the centromeric regions of the whole chromosome complement, and numerous hybridization sites are detected over interphase nuclei. Detection of chromosome-specific target DNAs by non-radioactive in situ hybridization with appropriate DNA probes cloned from individual chromosomal subregions presents a rapid means of identifying directly numerical or even structural chromosome aberrations in the interphase nucleus. Present limitations and future applications of interphase cytogenetics are discussed
Development and testing of an online community care platform for frail older adults in the Netherlands: a user-centred design
Background
Recent transitions in long-term care in the Netherlands have major consequences for community-dwelling older adults. A new paradigm expects them to manage and arrange their own care and support as much as possible. Technology can support this shift. A study has been conducted to explore the needs of community-dwelling frail older adults with regard to an online platform. An existing platform was subsequently modified, based upon these needs, resulting in an online community care platform (OCC-platform) comprising of care, health, and communication functions. The purpose of this platform was to support frail older adults in their independence and functioning, by stimulating self-care and providing reliable information, products and services.
Methods
The study used a User-Centred Design. The development processes involved the following steps: Step 1) Identification of the User Requirements. To assess the user requirements, direct observations (N = 3) and interviews (N = 14) were performed. Step 2) Modification of an Existing Online Platform. Based upon Step 1, available online platforms were explored to determine whether an existing useful product was available. Two companies collaborated in modifying such a platform; Step 3) Testing the Modified Platform. A total of 73 older adults were invited to test a prototype of the OCC-platform during 6 months, which comprised of two phases: (1) a training phase; and (2) a testing phase.
Results
An iterative process of modifications resulted in an interactive software concept on a Standard PC, containing 11 Functions. The Functions of ‘contacts’, ‘services’ and ‘messaging’, were by far, the most frequently used. The use was at its highest during the first 2 weeks of the testing and then its use steadily declined. The vast majority of the subjects (94%) were positive about the usability of the platform. Only a minority of the subjects (27%) indicated that the platform had added value for them.
Conclusion
The overall prospect was that an OCC-platform can contribute to the social participation and the self-management competencies of frail older adults, together with their social cohesion in the community. In order to validate these prospects, further research is needed on the characteristics and the impact of online platforms
Telomere disruption results in non-random formation of de novo dicentric chromosomes involving acrocentric human chromosomes
Copyright: © 2010 Stimpson et al.Genome rearrangement often produces chromosomes with two centromeres (dicentrics) that are inherently unstable because of bridge formation and breakage during cell division. However, mammalian dicentrics, and particularly those in humans, can be quite stable, usually because one centromere is functionally silenced. Molecular mechanisms of centromere inactivation are poorly understood since there are few systems to experimentally create dicentric human chromosomes. Here, we describe a human cell culture model that enriches for de novo dicentrics. We demonstrate that transient disruption of human telomere structure non-randomly produces dicentric fusions involving acrocentric chromosomes. The induced dicentrics vary in structure near fusion breakpoints and like naturally-occurring dicentrics, exhibit various inter-centromeric distances. Many functional dicentrics persist for months after formation. Even those with distantly spaced centromeres remain functionally dicentric for 20 cell generations. Other dicentrics within the population reflect centromere inactivation. In some cases, centromere inactivation occurs by an apparently epigenetic mechanism. In other dicentrics, the size of the alpha-satellite DNA array associated with CENP-A is reduced compared to the same array before dicentric formation. Extrachromosomal fragments that contained CENP-A often appear in the same cells as dicentrics. Some of these fragments are derived from the same alpha-satellite DNA array as inactivated centromeres. Our results indicate that dicentric human chromosomes undergo alternative fates after formation. Many retain two active centromeres and are stable through multiple cell divisions. Others undergo centromere inactivation. This event occurs within a broad temporal window and can involve deletion of chromatin that marks the locus as a site for CENP-A maintenance/replenishment.This work was supported by the Tumorzentrum Heidelberg/Mannheim grant (D.10026941)and by March of Dimes Research Foundation grant #1-FY06-377 and NIH R01 GM069514
Optical Biosensors Based on Semiconductor Nanostructures
The increasing availability of semiconductor-based nanostructures with novel and unique properties has sparked widespread interest in their use in the field of biosensing. The precise control over the size, shape and composition of these nanostructures leads to the accurate control of their physico-chemical properties and overall behavior. Furthermore, modifications can be made to the nanostructures to better suit their integration with biological systems, leading to such interesting properties as enhanced aqueous solubility, biocompatibility or bio-recognition. In the present work, the most significant applications of semiconductor nanostructures in the field of optical biosensing will be reviewed. In particular, the use of quantum dots as fluorescent bioprobes, which is the most widely used application, will be discussed. In addition, the use of some other nanometric structures in the field of biosensing, including porous semiconductors and photonic crystals, will be presented
Modeling the clonal heterogeneity of stem cells
Recent experimental studies suggest that tissue stem cell pools are composed of functionally diverse clones. Metapopulation models in ecology concentrate on collections of populations and their role in stabilizing coexistence and maintaining selected genetic or epigenetic variation. Such models are characterized by expansion and extinction of spatially distributed populations. We develop a mathematical framework derived from the multispecies metapopulation model of Tilman et al (1994) to study the dynamics of heterogeneous stem cell metapopulations. In addition to normal stem cells, the model can be applied to cancer cell populations and their response to treatment. In our model disturbances may lead to expansion or contraction of cells with distinct properties, reflecting proliferation, apoptosis, and clonal competition. We first present closed-form expressions for the basic model which defines clonal dynamics in the presence of exogenous global disturbances. We then extend the model to include disturbances which are periodic and which may affect clones differently. Within the model framework, we propose a method to devise an optimal strategy of treatments to regulate expansion, contraction, or mutual maintenance of cells with specific properties
Large Tandem, Higher Order Repeats and Regularly Dispersed Repeat Units Contribute Substantially to Divergence Between Human and Chimpanzee Y Chromosomes
Comparison of human and chimpanzee genomes has received much attention,
because of paramount role for understanding evolutionary step distinguishing us
from our closest living relative. In order to contribute to insight into Y
chromosome evolutionary history, we study and compare tandems, higher order
repeats (HORs), and regularly dispersed repeats in human and chimpanzee Y
chromosome contigs, using robust Global Repeat Map algorithm. We find a new
type of long-range acceleration, human-accelerated HOR regions. In peripheral
domains of 35mer human alphoid HORs, we find riddled features with ten
additional repeat monomers. In chimpanzee, we identify 30mer alphoid HOR. We
construct alphoid HOR schemes showing significant human-chimpanzee difference,
revealing rapid evolution after human-chimpanzee separation. We identify and
analyze over 20 large repeat units, most of them reported here for the first
time as: chimpanzee and human ~1.6 kb 3mer secondary repeat unit (SRU) and
~23.5 kb tertiary repeat unit (~0.55 kb primary repeat unit, PRU); human 10848,
15775, 20309, 60910, and 72140 bp PRUs; human 3mer SRU (~2.4 kb PRU); 715mer
and 1123mer SRUs (5mer PRU); chimpanzee 5096, 10762, 10853, 60523 bp PRUs; and
chimpanzee 64624 bp SRU (10853 bp PRU). We show that substantial
human-chimpanzee differences are concentrated in large repeat structures, at
the level of as much as ~70% divergence, sizably exceeding previous numerical
estimates for some selected noncoding sequences. Smeared over the whole
sequenced assembly (25 Mb) this gives ~14% human--chimpanzee divergence. This
is significantly higher estimate of divergence between human and chimpanzee
than previous estimates.Comment: 22 pages, 7 figures, 12 tables. Published in Journal of Molecular
Evolutio
An RNA Polymerase III-Dependent Heterochromatin Barrier at Fission Yeast Centromere 1
Heterochromatin formation involves the nucleation and spreading of structural and epigenetic features along the chromatin fiber. Chromatin barriers and associated proteins counteract the spreading of heterochromatin, thereby restricting it to specific regions of the genome. We have performed gene expression studies and chromatin immunoprecipitation on strains in which native centromere sequences have been mutated to study the mechanism by which a tRNAAlanine gene barrier (cen1 tDNAAla) blocks the spread of pericentromeric heterochromatin at the centromere of chromosome 1 (cen1) in the fission yeast, Schizosaccharomyces pombe. Within the centromere, barrier activity is a general property of tDNAs and, unlike previously characterized barriers, requires the association of both transcription factor IIIC and RNA Polymerase III. Although the cen1 tDNAAla gene is actively transcribed, barrier activity is independent of transcriptional orientation. These findings provide experimental evidence for the involvement of a fully assembled RNA polymerase III transcription complex in defining independent structural and functional domains at a eukaryotic centromere
Automatic Detection of Cyberbullying in Social Media Text
While social media offer great communication opportunities, they also
increase the vulnerability of young people to threatening situations online.
Recent studies report that cyberbullying constitutes a growing problem among
youngsters. Successful prevention depends on the adequate detection of
potentially harmful messages and the information overload on the Web requires
intelligent systems to identify potential risks automatically. The focus of
this paper is on automatic cyberbullying detection in social media text by
modelling posts written by bullies, victims, and bystanders of online bullying.
We describe the collection and fine-grained annotation of a training corpus for
English and Dutch and perform a series of binary classification experiments to
determine the feasibility of automatic cyberbullying detection. We make use of
linear support vector machines exploiting a rich feature set and investigate
which information sources contribute the most for this particular task.
Experiments on a holdout test set reveal promising results for the detection of
cyberbullying-related posts. After optimisation of the hyperparameters, the
classifier yields an F1-score of 64% and 61% for English and Dutch
respectively, and considerably outperforms baseline systems based on keywords
and word unigrams.Comment: 21 pages, 9 tables, under revie
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