Melting ice triggers Himalayan flood warning.
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Biomedical subjects
Publications and source records attributed to N McDowell.
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In early development much of the cellular diversity and pattern formation of the embryo is believed to be set up by morphogens. However, for many morphogens, including members of the TGF-beta superfamily, the mechanism(s) by which they reach distant cells is unknown. We have used immunofluorescence to detect, at single cell resolution, a morphogen gradient formed across vertebrate tissue. The TGF-beta ligand is distributed in a gradient visible up to 7 cell diameters (about 150-200 microm) from its source, and is detectable only in the extracellular space. This morphogen gradient is functional, since we demonstrate activation of a high response gene (Xeomes) and a low-response gene (Xbra) at different distances from the TGF-beta source. Expression of the high affinity type II TGF-beta receptor is necessary for detection of the gradient, but the shape of the gradient formed only depends in part on the spatial variation in the amount of receptor. Finally, we demonstrate that the molecular processes that participate in forming this functional morphogen gradient are temperature independent, since the gradient forms to a similar extent whether the cells are maintained at 4 degrees C or 23 degrees C. In contrast, TGF-beta1 internalisation by cells of the Xenopus embryo is a temperature-dependent process. Our results thus suggest that neither vesicular transcytosis nor other active processes contribute to a significant extent to the formation of the morphogen gradient we observe. We conclude that, in the model system used here, a functional morphogen gradient can be formed within a few hours by a mechanism of passive diffusion.
Activin, a member of the Transforming Growth Factor beta (TGF-beta) superfamily, can behave as a morphogen in cells of the early Xenopus embryo by inducing a range of mesodermal genes in a concentration-dependent manner. This review examines the behaviour of activin as it forms a morphogen gradient. It also discusses how a cell can perceive its position in a concentration gradient in order to activate appropriate mesodermal gene responses.
OBJECTIVE: To examine the promotion of physical activity by general practitioners (GPs) and practice nurses (PNs). METHODS: A questionnaire that examined the types of barriers and the levels of their influence as well as stage of change for activity promotion and for personal behaviour was mailed to 846 subjects. RESULTS: The return rate exceeded 70% in each group with a high proportion (69%) of GPs and PNs reporting that they regularly promote physical activity with their patients. GPs were less likely to regularly promote physical activity with their patients if they indicated lack of time as a barrier (odds ratio (OR) = 0.73, 95% confidence interval (CI) 0.58 to 0.93) or lack of incentives (OR = 0.74, 95% CI 0.59 to 0.94), and more likely to promote exercise if they themselves were regular exercisers (OR = 3.19, 95% CI 1.96 to 5.18). However, for PNs longer consultation times (by 1.5 to 2 minutes) had a higher likelihood of producing regular promotion of activity (OR = 1.61, 95% CI 1.02 to 1.62). For PNs personal physical activity stage was the strongest significant predictor of promotion level, but with a stronger effect (OR = 4.77, 95% CI 1.48 to 15.35) than in the GPs. CONCLUSION: The main finding is that GPs in the action or maintenance stage of changing their own physical activity are three times more likely to regularly promote the same behaviour in their patients than those in the other stages; for PNs the same difference quadruples the likelihood of them promoting physical activity. Professional readiness to change is influenced by known system barriers in GPs, and not in PNs, but is more strongly predicted by personal physical activity behaviour in both groups.
BACKGROUND: Activin has strong mesoderm-inducing properties in the early Xenopus embryo, and has a long-range signalling activity that activates genes in cells distant from a source in a concentration-dependent way. It has not yet been established what mechanism of signal transmission accounts for this and other examples of long-range signalling in vertebrates. Nor is it known whether activin itself acts on distant cells or whether other kinds of molecules are used for long-range signalling. Here we have used a well characterised model system, involving animal caps of Xenopus blastulae treated with activin or transforming growth factor beta, to analyze some fundamental properties of long-range signalling and of the formation of a morphogen gradient. RESULTS: We find that cells distant from the source of activin require functional activin receptors to activate Xbrachyury, a result suggesting that activin itself acts directly on distant cells and that other secondary signalling molecules are not required. We also find that the signals can be transmitted across a tissue that cannot respond to it; this argues against a relay process. We provide direct evidence that labelled activin forms a concentration gradient emanating from its source and extending to the distant cells that express Xbrachyury. Lastly, we show that there is no inherent polarity in the responding tissue that influences either the direction or rate of signalling. CONCLUSIONS: The long-range signalling mechanism by which activin initiates the transcription of genes in a concentration-dependent manner depends on a process of rapid diffusion and the establishment of an activin gradient across the tissue. It cannot be explained by a relay or wave propagation mechanism. Activin itself is the signalling molecule to which distant cells respond.
OBJECTIVE: To investigate what factors may influence practice nurses to promote physical activity. METHODS: Postal questionnaires were sent to all practice nurses in the county of Avon, UK in 1994. Specifically, the questionnaire survey explored whether patient, provider, and practice factors influenced practice nurses promotion behaviour. In addition, the stages of change model was used to measure current levels of promoting behaviour. RESULTS: A response rate of 80.9% was achieved. Over 80% of the sample reported currently promoting physical activity to some degree. "Promoting" nurses more frequently followed up all (new, established or targeted) patients' activity progress when compared with "restricted promoting" nurses (P < 0.05). Nurses who engaged in regular exercise were more likely to encourage physical activity as a treatment than "irregularly active" nurses (P < 0.05) for five of six clinical groups with the single exception of people with diabetes. CONCLUSIONS: This study shows that the two stage measures (activity promotion and personal behaviour) of the health care professional are associated with important differences in patient and practice factors for physical activity promotion. Further investigations into the content and quality of delivery are required before planning strategies to develop physical activity in the general practice.
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