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Biomedical subjects

P Monaghan

Publications and source records attributed to P Monaghan.

At least 19 recordsLinked to original sources
PubMed1999

Experimental demonstration that offspring sex ratio varies with maternal condition.

Sex ratio theory predicts that, if prevailing ecological or social circumstances differentially influence the fitness benefits of offspring of each sex, parents should adjust their production accordingly to maximize fitness. For species in which sex is chromosomally determined, such as birds and mammals, a differential effect of maternal condition on the fitness of male and female young is one important route whereby selection is expected to favor a bias in the offspring sex ratio at birth or egg laying. However, despite its central place in sex allocation theory, this hypothesis has rarely been tested in wild populations. We manipulated maternal condition upward and downward in a sexually dimorphic wild bird and examined the effect on offspring survival and on offspring sex ratio. The survival to fledging of male, but not female, young was substantially reduced if they came from less well provisioned eggs produced by females in relatively poor condition. As female condition, and thereby her capacity to produce high quality eggs, declined, she progressively skewed the sex ratio of her eggs toward females; i.e., she produced more of the sex with the higher survival prospects. The decline in the survival of male offspring, and the sex ratio bias, was removed when maternal condition was enhanced. These results provide experimental evidence of an adaptive, facultative adjustment of sex ratio in response to changes in maternal condition in wild birds.

Adaptation, Biological↗
PubMed1999

The effect of clutch cooling rate on starling, Sturnus vulgaris, incubation strategy.

In avian species where only one parent incubates, that parent must divide its time between the mutually exclusive activities of incubation and foraging in such a way as to maintain both body condition and clutch temperature within certain limits. In a uniparental incubator, the starling, we experimentally reduced the rate at which unattended clutches of eggs cooled down and monitored the resulting changes in the parent's incubation strategy. Opposite to the predictions of standard models of time allocation during incubation, parents spent a much greater percentage of each 24-h period incubating when the rate of clutch cooling was reduced. Incubation bouts lasted significantly longer on experimental nests than on control nests, both during the daytime and overnight. Mean foraging bout duration did not differ between the two groups of nests. These results are consistent with the hypotheses that parental foraging success cues the end of a foraging bout, and that parental energy level cues the end of an incubation bout. However, most previous studies suggest that parents spend less time incubating when the rate of clutch cooling is slow. If parental energy level cues departure, these results can be explained only if the amount of time available for incubation is constrained in these cases by the time a parent must spend foraging in order to maintain body condition. Such parents should take more time away from incubation when the unattended clutch cools slowly, as this is when the cost of being absent is minimized. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed1999

Functional domains of the SYT and SYT-SSX synovial sarcoma translocation proteins and co-localization with the SNF protein BRM in the nucleus.

The t(X;18)(p11.2;q11.2) chromosomal translocation commonly found in synovial sarcomas fuses the SYT gene on chromosome 18 to either of two similar genes, SSX1 or SSX2, on the X chromosome. The SYT protein appears to act as a transcriptional co-activator and the SSX proteins as co-repressors. Here we have investigated the functional domains of the proteins. The SYT protein has a novel conserved 54 amino acid domain at the N-terminus of the protein (the SNH domain) which is found in proteins from a wide variety of species, and a C-terminal domain, rich in glutamine, proline, glycine and tyrosine (the QPGY domain), which contains the transcriptional activator sequences. Deletion of the SNH domain results in a more active transcriptional activator, suggesting that this domain acts as an inhibitor of the activation domain. The C-terminal SSX domain present in SYT-SSX translocation protein contributes a transcriptional repressor domain to the protein. Thus, the fusion protein has transcriptional activating and repressing domains. We demonstrate that the human homologue of the SNF2/Brahama protein BRM co-localizes with SYT and SYT-SSX in nuclear speckles, and also interacts with SYT and SYT-SSX proteins in vitro. This interaction may provide an explanation of how the SYT protein activates gene transcription.

Amino Acid Sequence↗
PubMed1999

Analysis of mice carrying targeted mutations of the glucocorticoid receptor gene argues against an essential role of glucocorticoid signalling for generating adrenal chromaffin cells.

Molecular mechanisms underlying the generation of distinct cell phenotypes is a key issue in developmental biology. A major paradigm of determination of neural cell fate concerns the development of sympathetic neurones and neuroendocrine chromaffin cells from a common sympathoadrenal (SA) progenitor cell. Two decades of in vitro experiments have suggested an essential role of glucocorticoid receptor (GR)-mediated signalling in generating chromaffin cells. Targeted mutation of the GR should consequently abolish chromaffin cells. The present analysis of mice lacking GR gene product demonstrates that animals have normal numbers of adrenal chromaffin cells. Moreover, there are no differences in terms of apoptosis and proliferation or in expression of several markers (e.g. GAP43, acetylcholinesterase, adhesion molecule L1) of chromaffin cells in GR-deficient and wild-type mice. However, GR mutant mice lack the adrenaline-synthesizing enzyme PNMT and secretogranin II. Chromaffin cells of GR-deficient mice exhibit the typical ultrastructural features of this cell phenotype, including the large chromaffin granules that distinguish them from sympathetic neurones. Peripherin, an intermediate filament of sympathetic neurones, is undetectable in chromaffin cells of GR mutants. Finally, when stimulated with nerve growth factor in vitro, identical proportions of chromaffin cells from GR-deficient and wild-type mice extend neuritic processes. We conclude that important phenotypic features of chromaffin cells that distinguish them from sympathetic neurones develop normally in the absence of GR-mediated signalling. Most importantly, chromaffin cells in GR-deficient mice do not convert to a neuronal phenotype. These data strongly suggest that the dogma of an essential role of glucocorticoid signalling for the development of chromaffin cells must be abandoned.

Adrenal Glands↗
PubMed1998

Glucose transporter GLUT1 localization in human foetus telencephalon.

The endothelial cells of the mature cerebral microvessels, provided with barrier devices (blood-brain barrier, BBB), selectively express the glucose transporter isoform 1 (GLUT1). Presence and localization of the GLUT1 were studied by immunogold silver staining (IGSS) labelling on ultrathin sections of foetal human telencephalon tissue embedded in Lowicryl HM20 according to the progressive lowering of temperature (PLT) method. In the microvascular endothelial cells of the human telencephalon GLUT1 molecules are detected at the 12th gestational week and their expression is increased at the 18th week. In both ages, the transporter is mainly localized on the ablumenal and lateral endothelial cell membranes, and at 18 weeks a greater number of GLUT1 antigenic sites are also seen at the lumenal membrane. Our findings demonstrate both the expression and subcellular localization of GLUT1 be developmentally regulated and suggest an early functioning of the BBB-GLUT1 transporter in the developing human brain.

Blood-Brain Barrier↗
PubMed1998

Processing of palindromes in neglect dyslexia.

We report an investigation into the processing of symmetrical lexical stimuli by a patient with moderate visual neglect. This subject's neglect dyslexia was significantly less pronounced when presented with symmetrical lexical stimuli (palindromes) than with matched non-symmetrical words. We discuss the hypothesis that symmetry facilitates processing.

Arteriovenous Malformations↗
PubMed1998

Avian diving, respiratory physiology and the marginal value theorem.

Behavioural studies of diving birds have reported that the ratio of dive duration to the duration of the subsequent period on the surface displays a characteristic relation to dive duration. For short dives, the dive to surface ratio increases with dive duration, whereafter the relation peaks, and for longer dives decreases with increasing dive duration. Such a relationship is not a general prediction of existing marginal value models which have been used to predict optimal diving behaviour. This may be because the smooth curve used to describe the oxygen gain rate of individuals after surfacing is not a good reflection of the respiratory physiology of birds. Here we argue that on physiological grounds, the oxygen gain curve for avian divers will not be smooth, but will have two distinct regions (representing oxygen recovery in the respiratory tract, and in haemoglobin and myoglobin, respectively). Modifying two of the classical diving models by incorporating such a kinked curve causes them to predict the humped relationship between dive to surface ratio and dive duration under many circumstances. We also present data on the duration of dives and surface periods from three species of diving seabirds: the shag, Phalacrocorax aristotelis, the black guillemot, Cepphus grylle and the common guillemot, Uria aalge. All three species showed a humped relationship for dive to surface ratio as a function of dive duration. In line with the predictions of our model, when oxygen stores on surfacing were greatly depleted, the dive to surface ratio peaked at short dive durations. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed1998

Differential expression of type XIV collagen/undulin by human mammary gland intralobular and interlobular fibroblasts.

Immunolocalisation of type XIV collagen/undulin in the human mammary gland revealed greater deposition in the interlobular stroma than in the intralobular stroma. The interlobular stroma is located between the breast lobules and their associated intralobular stroma. Fibroblasts isolated from the interlobular stroma synthesised 3- to 5-fold more type XIV collagen/undulin than intralobular fibroblasts, but synthesised type I and type IV collagens in similar amounts. The differential expression of type XIV collagen/undulin was maintained with passage in culture. The results suggest a role for type XIV collagen/undulin in stabilising dense collagen fibrils. The maintenance of two types of structurally distinct stromas may be important during developmental processes in the mammary gland.

Breast↗
PubMed1998

Comparison of four techniques for monitoring the setting kinetics of gypsum.

STATEMENT OF PROBLEM: Setting time of gypsum depends on the method of measurement. PURPOSE: In this study, four methods for ascertaining the setting time of gypsum were compared. MATERIAL AND METHODS: Gypsum setting was evaluated with Gillmore needles, setting expansion, scanning electron microscopy, and x-ray diffraction. Both die stone (Vel-Mix) and fast-setting dental stone (Snap-Stone) were investigated. By using Gillmore needles, both initial set and final set were recorded. Setting expansion was monitored until equilibrium was achieved. For scanning electron microscopy, samples of mixed stone were immersed into liquid nitrogen to stop the reaction. The water was subsequently removed by freeze-drying. Samples were then examined in a scanning electron microscope. For x-ray diffraction, the percentages of dihydrate and hemihydrate crystals were monitored every 1.5 minutes. RESULTS: Setting times for the fast-setting type III stone and for the regular-setting type IV stone were approximately 3 and 10 minutes, respectively, with the Gillmore needle indentation tests; 10 and 20 minutes with scanning electron microscopy; and 20 and 60 minutes with x-ray diffraction. CONCLUSION: Scanning electron microscopy, setting expansion, and x-ray diffraction indicated changes that occurred at times after a clinically relevant set was obtained in the gypsum setting reaction.

Calcium Sulfate↗
PubMed1998

High-pressure freezing for immunocytochemistry.

Ultrastructural immunocytochemistry requires that minimal damage to antigens is imposed by the processing methods. Immersion fixation in cross-linking fixatives with their potential to damage antigens is not an ideal approach and rapid freezing as an alternative sample-stabilization step has a number of advantages. Rapid freezing at ambient pressure restricts the thickness of well-frozen material obtainable to approximately 15 microm or less. In contrast, high-pressure freezing has been demonstrated to provide ice-crystal-artefact-free freezing of samples up to 200 microm in thickness. There have been few reports of high-pressure freezing for immunocytochemical studies and there is no consensus on the choice of post-freezing sample preparation. A range of freeze-substitution time and temperature protocols were compared with improved tissue architecture as the primary goal, but also to compare ease of resin-embedding, polymerization and immunocytochemical labelling. Freeze-substitution in acetone containing 2% osmium tetroxide followed by epoxy-resin embedding at room temperature gave optimum morphology. Freeze-substitution in methanol was completed within 18 h and in tetrahydrofuran within 48 h but the cellular morphology of the Lowicryl-embedded samples was not as good as when samples were substituted in pure acetone. Acetone freeze-substitution was slow, taking at least 6 days to complete, and gave blocks which were difficult to embed in Lowicryl HM20. Careful handling of frozen samples avoiding rapid temperature changes reduced apparent ice-crystal damage in sections of embedded material. Thus a slow warm-up to freeze-substitution temperature and a long substitution time in acetone gave the best results in terms of freezing quality and cellular morphology. No clear differences emerged between the different freeze-substitution media from immunocytochemical labelling experiments.

Animals↗
PubMed1998

The cross-over effect in unilateral neglect. Modelling detailed data in the line-bisection task.

The line-bisection task is the standard assessment of unilateral visual neglect. It supplies one effect, the crossover effect, that challenges models of neglect: in left neglect, the rightward displacement of the midpoint of the line becomes a left displacement for small lines. We review the various attempts to account for the cross-over effect, before describing a computational model of performance in the line-bisection task that produces a cross-over effect quite naturally in its damaged state. The model trades on aspects of several current theories of neglect, including independent attentional processing in the two hemispheres, each of which possesses an attentional gradient in which the contralateral field is accentuated. We assume a small residual noise, along the same gradient, in the damaged hemisphere. When lesioned to simulate right hemisphere damage, the model produces line bisections similar to human performance, in terms of the relationship with line length, a variable cross-over point for the smaller lines, and an amelioration of performance with leftside, but not rightside cueing.

Animals↗
PubMed1997

An immunohistochemical and morphometric study on astrocytes and microvasculature in the human cerebral cortex.

In this study, astrocytes and microvessels of the human cerebral cortex were analysed morphometrically with the aim of acquiring quantitative information on the glio-vascular relationships, considered to be of great importance in the formation and functioning of the blood-brain barrier. Immunohistochemistry for the astrocytic marker, glial fibrillary acidic protein, was used with a computerized image analysis system. The brain tissue was embedded using the progressive lowering of temperature method, and the image analyser was applied to semithin sections subjected to immunogold-silver staining and viewed by epipolarization microscopy. The results show that, in the human cerebral cortex, astrocytes cover 11.4% of the cortex area and that their perivascular processes are nearly as extensive as the vascular bed (0.8% versus 1.72% of the cortex area). These processes form a virtually continuous sheath around the vascular walls, only 11% of the vessel perimeter lacking this astrocytic glia covering. The present results, compared with previous unpublished data obtained by conventional immunocytochemical procedures on wax sections, indicate that low-temperature methods combined with gold-silver immunolabelling on semithin sections significantly improve the detection of immunoreactivity and the performance of the image analyser.

Astrocytes↗
PubMed1997

Glucose transporter GLUT1 in human brain microvessels revealed by ultrastructural immunocytochemistry.

The brain glucose transporter GLUT1 is a transmembrane glycoprotein belonging to the glucose carrier family comprising five isoforms characterized by different functional properties and tissue specificity. Biochemical and immunohistochemical analyses have demonstrated that GLUT isoform 1 is localised within the brain microvascular endothelium, where it controls glucose uptake through the blood-brain barrier (BBB). In this study the expression of GLUT1 was analysed by means of light and electron immunocytochemistry in the adult human cerebellar cortex. The glucose transporter is strongly expressed in cerebellum microvessels, and is localised not only within endothelial cells but also in microvascular pericytes. Moreover, some glial expression of GLUT1 was observed in the neutrophil and in perivascular glial sheaths. The observations demonstrate that different cellular types are involved in the control of brain glucose homeostasis by GLUT1 expression at the BBB site, and support the postulated highly specialised role of brain microvascular pericytes.

Adult↗
PubMed1996

Gap junction distribution and connexin expression in human breast.

Expression of the gap junction proteins (connexins) in human breast epithelium was studied in vivo and in vitro. A panel of sequence-specific anti-peptide antibodies was used to examine four connexin (Cx) isoforms by indirect immunofluorescence labeling. Antibodies to Cx43 readily detected gap junctions between the basal cells in major ducts, but less so within lobular/alveolar structures. Cx26 immunoreactivity was less abundant in beast epithelium but was observed between the luminal cells in major ducts and to a lesser extent in lobular/alveolar structures. Ultrastructural studies of normal human breast showed gap junctions between basal cells in ducts and lobules, but not between luminal cells or between luminal and basal cells. Immunomagnetically separated luminal and basal cells were grown in vitro. Basal cells expressed Cx43 at cell-cell attachment points whereas luminal cells showed only small amounts of immunolabeling with the Cx26 antibody which was generally not associated with the cell borders. Microinjection of Lucifer yellow into cultured luminal or basal cells indicated that basal cells have high levels of gap junctional communication, but dye transfer between luminal cells was difficult to detect by transfer of Lucifer yellow. Western blot analysis of purified luminal and basal cells indicated the presence of mainly Cx43 in both cell types. Polymerase chain reaction analysis of breast mRNA identified message for CX43 and to a lesser extent for Cx26; Cx32 was not detected in human breast, although it was present in mouse mammary gland. mRNA extracted from cloned cultures of human luminal and basal cells contained message for Cx43 and Cx26 in both cell types.

Animals↗
PubMed1996

Connexin expression and gap junctions in the mammary gland.

Gap junctional communication plays a vital role in embryogenesis, cell differentiation and the co-ordination of tissue responses. Gap junctions are formed by a family of closely-related proteins called connexins which show tissue-specific patterns of expression. The role of gap junctions in the mammary gland remains unclear. The lumena of mammary gland ducts are lined by luminal cells with an outer layer of basal cells. In rodents, the luminal cells express connexin26 only during pregnancy and lactation and the basal cells, in some reports, express connexin43. In the normal human breast the basal cells express connexin43, although human mammary epithelial cells in vitro have been reported to express both connexin26 and connexin43. Analysis of connexin expression at the molecular level is now bringing new insights into the structure and function of gap junctions in a range of normal and pathological cell systems.

Animals↗