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Biomedical subjects

P Monaghan

Publications and source records attributed to P Monaghan.

At least 37 records · Page 2Linked to original sources
PubMed2001

Implementing a community-based social marketing project to improve agricultural worker health.

The Together for Agricultural Safety project is a community-based social marketing project working to reduce the adverse health effects of pesticide exposure among fernery and nursery workers in Florida. In 3 years, the collaboration between university and community researchers has embodied many of the principles of community-based research while completing multiple stages of formative data collection required for a social marketing project. This hybrid approach to developing a health intervention for a minority community has been successful in its early stages because the community partners are organized, empowered, and motivated to execute research activities with the assistance of academic partners. However, this work has also been labor intensive and costly. This article describes the lessons learned by project partners and considers the limitations of this approach for agricultural health research.

Adult↗
PubMed2000

Developmental trade-offs and life histories: strategic allocation of resources in caddis flies.

Resource allocation trade-offs during development are potentially very important in the evolution of organism morphology and life-history strategy However, they have rarely been demonstrated empirically. To what extent the division of limited resources between growing organs is a consequence of particular developmental pathways or varies strategically in line with life-history predictions is unknown. It has been demonstrated in a number of holometabolous insects that altering the resources available at pupation changes the pattern of allocation to adult tissues, but this has not been examined in a life-history context. Using caddis flies (Trichoptera), we show here that the effect of depleted larval resources on the pattern of somatic and reproductive investment is not fixed but varies between species with different life-history patterns. In particular, we demonstrate that, in a long-lived species, thorax size is preserved, which contrasts with the pattern previously observed in a short-lived species. That the adult body can be differentially altered by the same resource depletion in the larvae demonstrates that the allocation of resources amongst body parts is not a consequence of fixed pathways during development. Rather, the allocation of resources during development can occur in a manner consistent with the minimization of the effects on adult fitness.

Animals↗
PubMed2000

Resource allocation between reproductive phases: the importance of thermal conditions in determining the cost of incubation.

Changes in the resources allocated to particular stages of reproduction are expected to influence allocation to, and performance in, subsequent reproductive stages. Experimental manipulation of individual investment patterns provides important evidence that such physiological trade-offs occur, and can highlight the key environmental variables that influence reproductive costs. By temporarily altering the thermal properties of starling nests, we reduced the energetic demand of first-clutch incubation, and examined the effect of this manipulation on performance during the same and the subsequent reproductive attempts. Compared with controls, starlings investing less in incubation were more successful in fledging young, and were more likely to hatch all their eggs if a subsequent reproductive attempt was made. Our results show that incubation demands can limit reproductive success, and that resources saved during incubation can be reallocated to later stages of the same reproductive attempt and to future reproductive attempts. This study also shows that small changes in thermal environment can affect breeding success by altering the energetic demands imposed on incubating parents, independently of the effect of temperature on other environmental variables such as food supply.

Animals↗
PubMed2000

Developmental expression and assembly of connexins into homomeric and heteromeric gap junction hemichannels in the mouse mammary gland.

During the development of the mammary gland, duct-lining epithelial cells progress through a program of expansive proliferation, followed by a terminal differentiation that allows for the biosynthesis and secretion of milk during lactation. The role of gap junction proteins, connexins, in the development and function of this secretory epithelium was investigated. Connexins, Cx26 and Cx32, were differentially expressed throughout pregnancy and lactation in alveolar cells. Cx26 poly-(A)(+) RNA and protein levels increased from early pregnancy, whereas Cx32 was detectable only during lactation. At this time, immunolocalization of connexins by confocal microscopy and immunogold labeling of high-pressure frozen freeze-substituted tissue showed that both connexins colocalized to the same junctional plaque. Analysis of gap junction hemichannels (connexons) isolated from lactating mammary gland plasma membranes by a rate-density centrifugation procedure, followed by immunoprecipitation and by size-exclusion chromatography, showed that Cx26 and Cx32 were organized as homomeric and heteromeric connexons. Structural diversity in the assembly of gap junction hemichannels demonstrated between pregnant and lactating mammary gland may account for differences in ionic and molecular signaling that may physiologically influence the onset and/or maintenance of the secretory phenotype of alveolar epithelial cells.

Animals↗
PubMed2000

Glutamic acid decarboxylase-positive neuronal cell bodies and terminals in the human cerebellar cortex.

The distribution of gamma-aminobutyric acid (GABA) in the human cerebellar cortex was studied using immunohistochemistry for glutamic acid decarboxylase (GAD), the enzyme that catalyses GABA synthesis. Observations by light microscopy revealed, in all layers of the cerebellar cortex, strong, punctate positivity for GAD, related to putative GABAergic nerve terminals, as well as a diffuse cytoplasmic immunoreactivity within neuronal cell bodies. GAD-positive nerve terminals were found in close relationship with the walls of the cerebellar cortex microvessels. Observations by electron microscopy revealed positive nerve terminals in contact with the astrocyte perivascular sheath of capillaries. GAD immunoreactivity was also detected within astroglial perivascular endfeet and endothelial cells. The findings provide further insights into the GABAergic synapses of the circuitry of the human cerebellar cortex. The detection of 'vascular' GAD immunoreactivities suggests that GABAergic mechanisms may regulate cerebellar microvessel function.

Aged↗
PubMed2000

Eye-fixation behavior, lexical storage, and visual word recognition in a split processing model.

Some of the implications of a model of visual word recognition in which processing is conditioned by the anatomical splitting of the visual field between the two hemispheres of the brain are explored. The authors investigate the optimal processing of visually presented words within such an architecture, and, for a realistically sized lexicon of English, characterize a computationally optimal fixation point in reading. They demonstrate that this approach motivates a range of behavior observed in reading isolated words and text, including the optimal viewing position and its relationship with the preferred viewing location, the failure to fixate smaller words, asymmetries in hemisphere-specific processing, and the priority given to the exterior letters of words. The authors also show that split architectures facilitate the uptake of all the letter-position information necessary for efficient word recognition and that this information may be less specific than is normally assumed. A split model of word recognition captures a range of behavior in reading that is greater than that covered by existing models of visual word recognition.

Brain↗
PubMed2000

Recombinant rinderpest vaccines expressing membrane-anchored proteins as genetic markers: evidence of exclusion of marker protein from the virus envelope.

Rinderpest virus (RPV) causes a severe disease of cattle resulting in serious economic losses in parts of the developing world. Effective control and elimination of this disease require a genetically marked rinderpest vaccine that allows serological differentiation between animals that have been vaccinated against rinderpest and those which have recovered from natural infection. We have constructed two modified cDNA clones of the vaccine strain RNA genome of the virus, with the coding sequence of either a receptor site mutant form of the influenza virus hemagglutinin (HA) gene or a membrane-anchored form of the green fluorescent protein (GFP) gene (ANC-GFP), inserted as a potential genetic marker. Infectious recombinant virus was rescued in cell culture from both constructs. The RPVINS-HA and RPVANC-GFP viruses were designed to express either the HA or ANC-GFP protein on the surface of virus-infected cells with the aim of stimulating a strong humoral antibody response to the marker protein. In vitro studies showed that the marker proteins were expressed on the surface of virus-infected cells, although to different extents, but neither was incorporated into the envelope of the virus particles. RPVINS-HA- or RPVANC-GFP-vaccinated cattle produced normal levels of humoral anti-RPV antibodies and significant levels of anti-HA or anti-GFP antibodies, respectively. Both viruses were effective in stimulating protective immunity against RPV and antibody responses to the marker protein in all animals when tested in a cattle vaccination trial.

Animals↗
PubMed2000

Immunolocalization of collagen types II and III in single fibrils of human articular cartilage.

Type II and III fibrillar collagens were localized by immunogold electron microscopy in resin sections of human femoral articular cartilage taken from the upper radial zone in specimens from patients with osteoarthritis. Tissue samples stabilized by high-pressure cryofixation were processed by freeze-substitution, either in acetone containing osmium or in methanol without chemical fixatives, before embedding in epoxy or Lowicryl resin, respectively. Ultrastructural preservation was superior with osmium-acetone, although it was not possible to localize collagens by this method. In contrast, in tissue prepared by low-temperature methods without chemical fixation, collagens were successfully localized with mono- or polyclonal antibodies to the helical (Types II and III) and amino-propeptide (Type III procollagen) domains of the molecule. Dual localization using secondary antibodies labeled with 5- or 10-nm gold particles demonstrated the presence of Types II and III collagen associated within single periodic banded fibrils. Collagen fibrils in articular cartilage are understood to be heteropolymers mainly of Types II, IX, and XI collagen. Our observations provide further evidence for the complexity of these assemblies, with the potential for interactions between at least 11 distinct collagen types as well as several noncollagenous components of the extracellular matrix.

Cartilage, Articular↗
PubMed2000

Comparison of thymidylate synthase (TS) protein up-regulation after exposure to TS inhibitors in normal and tumor cell lines and tissues.

Thymidylate synthase (TS) is an important target for cancer chemotherapy. However, several mechanisms of resistance to TS inhibitors have been described. One mechanism that may be relevant to short-term exposure to TS inhibitors occurs as a result of disruption of the autoregulatory loop, which allows TS to control its own translation. This disruption leads to up-regulation of TS protein and is generally thought to decrease efficacy. This study has investigated TS protein up-regulation using a range of TS inhibitors in both tumor and nonmalignant cell lines in vitro and in vivo. Up-regulation of TS protein showed a time-, dose-, and cell-type-specific response to treatment with ZD9331. This response was observed in W1L2 cells treated for 24 h at equitoxic doses of raltitrexed (6-fold), ZD9331 (10-fold), fluorouracil (5-fold), LY231514 (7-fold), AG337 (7-fold), and BW1843U89 (3-fold). Up-regulation was observed over a range of doses. Elevation of TS protein only persisted up to 12 h after removal of drug. The extent of induction does not depend on basal TS levels. Nontransformed human fibroblasts showed significantly greater up-regulation of TS protein than tumor cells exposed to an equitoxic dose of ZD9331. In vivo experiments using the L5178Y thymidine kinase -/- mouse lymphoma implanted into DBA2 mice also showed greater up-regulation of TS protein in normal intestinal epithelial cells compared with tumor cells. These results confirm that TS up-regulation is a common feature of TS inhibition in tumor cells and that it may occur to a greater extent in normal tissues, although the clinical implications of these findings remain to be determined.

Analysis of Variance↗
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↗