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K Larkin

Publications and source records attributed to K Larkin.

13 recordsLinked to original sources
PubMed2001

In vivo co-localisation of MBNL protein with DMPK expanded-repeat transcripts.

Myotonic dystrophy (DM1) is the most common form of adult muscular dystrophy and is inherited as an autosomal dominant trait. The genetic basis of DM1 is the expansion of a CTG repeat in the 3' untranslated region of a protein kinase gene (DMPK). The molecular mechanism by which this expanded repeat produces the pathophysiology of DM1 remains unknown. Transcripts from the expanded allele accumulate as foci in the nucleus of DM1 cells and it has been suggested that these transcript foci sequester cellular proteins that are required for normal nuclear function. We have investigated the role of three RNA-binding proteins, CUG-BP, hnRNP C and MBNL, as possible sequestered factors. Using a combination of indirect immunofluorescence to detect endogenous proteins and overexpression of proteins with green fluorescent protein (GFP) tags we have shown that CUG-BP and hnRNP C do not co-localise with expanded repeat foci in DM1 cell lines. However, GFP-tagged MBNL does itself form foci in DM1 cell lines and co-localises with the foci of expanded repeat transcripts. GFP-tagged MBNL does not appear as foci in non-DM1 cell lines. This work provides further support for the involvement of MBNL in DM1.

3' Untranslated Regions↗
PubMed1999

Ventral cell rearrangements contribute to anterior-posterior axis lengthening between neurula and tailbud stages in Xenopus laevis.

Studies of morphogenesis in early Xenopus embryos have focused primarily on gastrulation and neurulation. Immediately following these stages is another period of intense morphogenetic activity, the neurula-to-tailbud transition. During this period the embryo is transformed from the spherical shape of the early stages into the long, thin shape of the tailbud stages. While gastrulation and neurulation depend largely on active cell rearrangement and cell shape changes in dorsal tissues, we find that the neurula-to-tailbud transition depends in part on activities of ventral cells. Ventral explants of neurula lengthen autonomously as much as the ventral sides of intact embryos, while dorsal explants lengthen less than the dorsal sides of intact embryos. Analyses of cell division, cell shapes, and cell rearrangement by transplantation of labeled cells and by time lapse recordings in live intact embryos concur that cell rearrangements in ventral mesoderm and ectoderm contribute to the autonomous anterior-posterior axis lengthening of ventral explants between neurula and tailbud stages.

Animals↗
PubMed1999

Microtubules are required for completion of cytokinesis in sea urchin eggs.

Completion of cytokinesis, abscission, has been studied little despite the intensive studies of the onset and contractile mechanism of the earlier phases of division. It has been well documented that microtubule (MT) disruption before furrow stimulation prevents furrowing, while MT disruption after furrow stimulation allows division to proceed. We have confirmed those findings using the MT inhibitors, nocodazole and demecolcine. In addition, we have found that MT disruption after furrow stimulation but before completion of division prevents abscission as evidenced by the observation that prospective daughter cells in MT-disrupted eggs maintain electrical continuity. Continued observation of eggs revealed that the furrow in MT-disrupted eggs did not result in abscission, but rather held steady until the time when controls underwent second cleavage, at which point the furrows regressed. These findings extend the recent reports that MTs are required for completion of division in mammalian tissue culture cells and frog eggs, to invertebrates, suggesting a common mechanism of abscission for animal cells.

Animals↗
PubMed1999

Development of a yeast-based assay system for monitoring microsatellite instability.

Simple sequence repeats (microsatellites) are found in all eukaryotic genomes. Instabilities within these sequences have been associated with several human disorders including Huntington's chorea and myotonic dystrophy. Further studies have identified links between microsatellite instability, faulty mismatch repair and certain human cancers, in particular a form of hereditary colorectal cancer. The assay system described here consists of a congenic set of yeast strains mutated in DNA replication and mismatch repair genes and assay plasmids with which it is possible to measure differences in microsatellite stability in the range of 5-850-fold. The development of this technology will allow monitoring of environmental and dietary influences on the genomic stability in the context of human disease.

Base Pair Mismatch↗
PubMed1999

Metal binding to the HIV nucleocapsid peptide.

Co(II) and Zn(II) binding constants have been measured for binding to the HIV-1 nucleocapsid N-terminal metal binding domain (residues 1-18), using competition titration methods and monitoring Co(II) binding by visible absorbance spectroscopy. Enthalpies for binding were directly measured by isothermal titration colorimetry. The results are compared with recent studies of related systems, including a study of Zn(II) binding by the full length protein.

Amino Acid Sequence↗
PubMed1998

Requirement for microtubules in new membrane formation during cytokinesis of Xenopus embryos.

In cleaving Xenopus eggs, exposure to nocodazole or cold shock prevents the addition of new plasma membrane to the cleavage plane and causes furrows to recede, suggesting a specific role for microtubules in cytokinesis. Whole-mount confocal immunocytochemistry reveals a ring of radially arranged, acetylated microtubule bundles at the base of all advancing cleavage furrows, from the first cleavage through the midblastula stage. We hypothesize that this novel microtubular structure is involved in transporting maternal stores of membrane in the subcortex to a site of membrane addition near the leading edge of the furrow.

Acetylation↗
PubMed1997

Five newly established oesophageal carcinoma cell lines: phenotypic and immunological characterization.

The derivation of permanent cell lines from 40 resected oesophageal carcinomas has been attempted. Five long-term lines have been established from three adenocarcinomas, one mixed carcinoma and one squamous carcinoma. Molecular and cellular analyses have been carried out on the lines and clones derived from them. Karyotype analysis indicates genetic variation among the clones. HLA-A, -B and -C is expressed constitutively, but not HLA-DR. ICAM-1-expressing phenotypes may have arisen during adaptation to long-term culture. All lines are capable of response to interferon-gamma (IFN-gamma) and all produce transforming growth factor beta 1 (TGF-beta 1). Two lines are resistant to the inhibitory growth effects of the latter, possibly contributing to malignancy. It is anticipated that these lines, originating from histologically different carcinomas, will provide a valuable, continuous resource for the investigation and treatment of these aggressive tumours.

Animals↗
PubMed1996

Regulative development of Xenopus laevis in microgravity.

To test whether gravity is required for normal amphibian development, Xenopus laevis females were induced to ovulate aboard the orbiting Space Shuttle. Eggs were fertilized in vitro, and although early embryonic stages showed some abnormalities, the embryos were able to regulate and produce nearly normal larvae. These results demonstrate for the first time that a vertebrate can ovulate in the virtual absence of gravity, and that the eggs can develop to a free-living stage.

Animals↗
PubMed1993

Emotional and cardiovascular responses to adults' angry behavior and to challenging tasks in children of hypertensive and normotensive parents.

Cardiovascular, overt-motor, and verbal-reported responses to interadult emotional expressions, including anger, and to challenging task situations were examined in a sample of 49 10-14-year-old children of hypertensive (EH) and normotensive parents (NT). Sons of EH parents showed greater systolic blood pressure reactivity to interadult anger and to the digit span task than sons of NT parents. A consistent pattern was not found for girls. Marital distress and overt maternal anger expression predicted verbal-reported and overt-motor responses to interadult anger. Family history of EH and sex did not predict these responses. Implications include (a) heightened systolic blood pressure response to stress may be found in sons of EH parents before they are diagnosed to have EH disorders, (b) relations between family history of EH and cardiovascular response may be sex moderated, and (c) vulnerability to stress may be related to specific familial histories and backgrounds.

Adaptation, Psychological↗
PubMed1988

Competence and stress in school children: the moderating effects of individual and family qualities.

This study examined the associations of stress exposure to various aspects of school-based competence in a normative sample of 205 children aged 8-13. Potential moderators of these relations, including child attributes of sex and IQ and environmental attributes of socioeconomic status (SES) and family qualities, were also studied. Stress exposure was indexed by a life event questionnaire. Competence was assessed by teacher ratings, peer assessments and school record data. Family attributes were derived from a set of rating scales completed by interviewers after 6 hours of interviews with a parent. Results suggest that the relations of stress exposure to competence vary as a function of individual differences as well as the competence criterion. Disadvantaged children, with lower IQ and SES, and less positive family qualities, were generally less competent and more likely to be disruptive at high stress levels. Advantaged children were more competent, and with stress positively engaged in school, but were not likely to be disruptive. Boys were less socially competent than girls and, when stress was high, appeared to be less protected by positive family qualities. Causal hypotheses for future research in this area are discussed.

Achievement↗
PubMedDate not supplied

Myotonic dystrophy--a multigene disorder.

Myotonic dystrophy (DM1) is the most common form of adult muscular dystrophy with an estimated incidence of 1/8000 births. The mutation responsible for this condition is an expanded CTG repeat within the 3' untranslated region of the protein kinase gene DMPK. Strong nucleosome positioning signals created by this expanded repeat cause a reduction in gene expression within the region. This "field effect" is further confounded by the retention of DMPK expansion containing transcripts, which acquire a toxic gain of function. Thus, the various manifestations exhibited by DM1 patients can be explained as a result of gene silencing, nuclear retention and sequestration of nuclear factors by the CUG containing transcript.

Homeodomain Proteins↗