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A Meredith

Publications and source records attributed to A Meredith.

11 recordsLinked to original sources

Negative autoregulation of Mash1 expression in CNS development.

Mash1, a neural-specific bHLH transcription factor, is essential for the formation of multiple CNS and PNS neural lineages. Transcription from the Mash1 locus is elevated in mice null for Mash1, suggesting that MASH1 normally acts to repress its own transcription. This activity is contrary to the positive autoregulation of other proneural bHLH proteins. To investigate the mechanisms involved in this process, sequences flanking the Mash1 gene were tested for the ability to mediate negative autoregulation. A Mash1/lacZ transgene containing 36 kb of cis-regulatory sequence exhibits an increase in lacZ expression in the Mash1 mutant background, which phenocopies the observation of transcriptional autoregulation at the endogenous Mash1 locus. Using Mash1/lacZ lines with progressively less cis-acting sequence, autoregulatory responsive elements were demonstrated to colocalize with a previously characterized 1.2-kb CNS enhancer. Mutations of E-box sites within this enhancer did not result in an apparent loss of autoregulation, suggesting that MASH1 does not directly repress its own transcription. Interestingly, these mutations did not indicate any underlying positive auto- or cross-regulation of Mash1. Furthermore, the loss of autoregulation in the Mash1 mutant background is reminiscent of a loss of lateral inhibitory signaling. However, mutations in HES consensus sites, the likely purveyors of Notch-mediated lateral inhibition, do not support a role for these sites in negative autoregulation. We hypothesize that MASH1 normally inhibits its own expression indirectly, possibly through a HES-mediated repression of positive regulators or through novel HES binding sites.

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Exotic pets.

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Animals↗

Respiratory syncytial virus-associated bronchopneumonia in a young chimpanzee.

A fatal bronchopneumonia in a captive, 14-month-old female chimpanzee (Pan troglodytes) is reported. Clinical, necropsy and histopathological findings, together with immunofluorescence and virus isolation studies implicated respiratory syncytial virus as the causative agent. The probable pathogenesis is discussed.

Animals↗

Is birth weight determined genetically?

Birthweight correlations were analysed among 505 intergenerational pairs of first births to women aged 18-25 identified from a large obstetric data bank. After standardisation for fetal sex, maternal height, gestational age, and proteinuric pre-eclampsia residual correlations of between 0.1402 and 0.1725 were found, suggesting only a small genetic effect. It is concluded that genetic factors play only a small part in determining birth weight.

Adolescent↗

Some studies of maternal and infant lead exposure in Glasgow.

In two studies in the city of Glasgow, 236 mothers and their newly born infants and 117 mothers and their 6-weeks old children's environmental lead exposure were examined. In both studies blood lead concentrations were found to correlate significantly with the cube root of the domestic water lead concentrations. In the first study, multiple regression analyses of maternal blood lead and cord blood lead concentrations on other variables showed a significant negative correlation with gestational age. It was also noted that there was an annual fluctuation in maternal blood lead concentration with highest values in the autumn. In the second study, similar relationships were found. Although there was no association between blood lead and sex, age, place of birth or feeding method, as in the previous study, a significant association between social class and blood lead was found. This could be explained on the basis of the significant correlation between water lead and social class. In those mothers who breast fed, breast milk lead concentrations were found to correlate significantly with blood lead concentrations where breast milk lead was around one tenth of blood lead concentration. These studies emphasise the importance of water lead in the economy of environmental lead exposure to mothers and their unborn and newly born infants.

Adolescent↗

Methods for the study of lung metabolism.

The recognition of the non-respiratory functions of the lung has led to an increased interest in pulmonary metabolism. The practical methods used to study metabolism in other tissues have all been applied to the investigation of lung metabolism. Methods fall into two groups: those used in vivo and those used in vitro after disrupting the organ or isolating it from other tissues and perfusing its circulation. Some of the methods used in vitro disturb the tissue environment in such a way as to introduce experimental artifacts which make the interpretation of results difficult. There are advantages to the use of the isolated perfused organ technique which, although it has been established for many years, has recently been improved. This method lends itself particularly well to studies of the intermediary metabolism and uptake of drugs by lung tissue. These improvements are described and the application to pulmonary drug uptake is illustrated by reference to the drug mexiletine. The relative advantages of the various methods and their applications are discussed.

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Correct coordination of neuronal differentiation events in ventral forebrain requires the bHLH factor MASH1.

MASH1 is a bHLH transcription factor specifically expressed in the developing nervous system that has an essential role in the formation of multiple neuronal lineages in the peripheral and central nervous systems. Here we demonstrate the requirement for MASH1 for normal development of ventral forebrain structures. MASH1 is expressed at high levels in the ventral telencephalon and specific regions within the ventral diencepharon. In the absence of MASH1, tissue morphology, proliferation, and gene expression within these forebrain regions is disrupted. The decreased incorporation of BrdU in the neuro-epithelium and the enlargement of the ventricles demonstrate a reduction in cell proliferation. A loss of anatomically distinct lateral and medial ganglionic eminences, and a disruption of axons traversing this region, indicate abnormalities in cell-type specification. The aberrant expression of Tuj-1, a marker of neuronal differentiation in the neuroepithelium, and Dlx, a marker of regional cell identity, in the ventricular zone in the MASH1 mutant brains suggest coordination of differentiation events is disrupted. In addition, the involvement of MASH1 in lateral inhibition processes that affect the development of these forebrain regions is implicated. Taken together, an essential role for MASH1 in the coordination of events required for correct cell-type specification and timing of differentiation during neural development in ventral forebrain regions is demonstrated.

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