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Biomedical subjects

S Dyson

Publications and source records attributed to S Dyson.

At least 19 recordsLinked to original sources

Single cells can sense their position in a morphogen gradient.

Xenopus blastula cells show a morphogen-like response to activin by expressing different genes according to the concentration of activin to which they are exposed. To understand how cells recognize their position in a concentration gradient, it is essential to know whether each cell responds individually to activin concentration. An alternative idea, proposed by previous work, is that cells need to interact with their neighbours to generate a concentration-related response. To distinguish between these ideas, we have cultured blastula cells under conditions which provide different degrees of contact with other cells, allowing nil to maximum communication with their neighbours. The cultures include cells attached to fibronectin and cells resting unattached on an agarose base. The cultures also include cells that have no contact with any cell except their clonal progeny, cells that have lateral contact to neighbouring cells, and cells that are completely enveloped by other cells in a reaggregate. We have used RNase protection and in situ hybridization to assay the expression of the activin-responsive Xenopus genes Xbra, Xgsc, Xeomes, Xapod, Xchordin, Mix1, Xlim1 and Cerberus. We find no difference in gene expression between cells attached to fibronectin and those unattached on agarose. Most importantly, we find that cells respond to activin in a concentration-related way irrespective of their degree of contact with other cells. Therefore interaction among cells is not required for the interpretation of morphogen concentration, at least in the case of the early genes studied here. We conclude that isolated blastula cells can sense and respond individually to activin by expressing genes in a concentration-dependent way.

Activins↗

The interpretation of position in a morphogen gradient as revealed by occupancy of activin receptors.

Xenopus blastula cells activate different mesodermal genes as a concentration-dependent response to activin, which behaves like a morphogen. To understand how cells recognize morphogen concentration, we have bound naturally labeled activin to cells and related this to choice of gene activation. We find that the increasing occupancy of a single receptor type can cause cells to switch gene expression. Cells sense ligand concentration by the absolute number of occupied receptors per cell (100 and 300 molecules of bound activin induce Xbra and Xgsc, respectively, i.e., 2% and 6% of the total receptors) and not by a ratio of occupied to unoccupied receptors. The long duration of occupancy explains a previously described ratchet effect. Our results suggest a new concept of morphogen gradient formation and interpretation that is particularly well suited to the needs of early development.

Activin Receptors↗

Cooperation between the activin and Wnt pathways in the spatial control of organizer gene expression.

The normal expression pattern of the Wnt responsive homeobox gene Siamois is restricted to the dorso-vegetal region of the Xenopus embryo. Because the Wnt signaling pathway (via beta-catenin) is active on the entire dorsal side of the early embryo, we have asked why Siamois expression is not seen in the dorsal ectoderm. Only Wnt signaling, via activation of beta-catenin, can induce directly Siamois, and signaling via the SMAD1 (BMP2/4) or SMAD2 (activin/Vg-1) pathways cannot. We now directly show that the SMAD2 pathway can cooperate with the Wnt pathway to induce expression of Siamois much more strongly than the Wnt pathway alone, in normal embryos. We demonstrate the significance of this cooperation in normal embryos by blocking the SMAD2 signaling pathway with a dominant negative activin receptor. The activin dominant negative receptor blocks this cooperative effect and reduces the expression of Siamois by threefold in early embryos. Furthermore, we find that this cooperative relationship between the SMAD2 and Wnt pathways is reciprocal. Thus, in normal embryos, the Wnt pathway can enhance induction, by the SMAD 2 pathway, of the organizer genes Gsc and Chd but not the pan-mesodermal marker genes Xbra and Eomes. We conclude that the Wnt and SMAD2 signaling pathways cooperate to induce the expression of Spemann-organizer specific genes and so help to localize their spatial expression.

Activin Receptors↗

Equine botulism.

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Animals↗

Activin signalling has a necessary function in Xenopus early development.

The first signalling event in Xenopus development is the mesoderm-forming (or Nieuwkoop) induction, starting three hours after fertilization [1]. Two prime candidates for the molecule that mediates this signalling are activin [2] and Vg1 [3], both members of the transforming growth factor beta (TGFbeta) family. Because genetic methods are not available for amphibian studies, 'dominant-negative' truncated receptors have been used in studying signalling molecules such as the receptors for fibroblast and platelet-derived growth factors (FGF and PDGF) [4] [5]. The truncated receptors bind to, and prevent signalling from, endogenous receptors. Activin is a potent mesoderm inducer in vitro, and the severe phenotype obtained using a dominant-negative activin receptor in Xenopus [6], coupled with evidence from fish [7], suggested that activin is essential for development. However, a dominant-negative receptor for activin blocked the activity of other TGFbeta family members in Xenopus, most notably Vg1 [8], and activin 'knock-out' mice are essentially wild-type in phenotype [7]; these two findings cast doubt on the idea of a function for activin in early development. We have designed a new receptor construct which can selectively block the function of activin but not of Vg1, and we have used it to show that activin has an essential role in vivo in Xenopus early development. We conclude that activin, or a close relative that has yet to be described, is required for normal development.

Activin Receptors↗

Midwives' knowledge of haemoglobinopathies.

A good working knowledge of haemoglobinopathies is essential if midwives are to provide an equitable service. Almost half of the respondents had received no training in this area. Where training had been received, it was usually during basic midwifery education. Few had received haemoglobinopathies training since qualification as a midwife. Training was linked with higher knowledge levels, especially concerning patterns of inheritance of haemoglobinopathies. Further training sessions were linked with a further rise in knowledge levels. Respondents taught by haemoglobinopathies counsellors had higher knowledge levels than those taught by midwife teachers or doctors.

Anemia, Sickle Cell↗

Whooping-cough vaccination: historical, social and political controversies.

New acellular whooping cough vaccines may have the effect of leading us to forget that infectious diseases such as whooping cough have declined in the context of particular historical, social conditions and persist in the context of particular types of social inequalities. The debates over the existence of damage from whole-cell whooping cough vaccine, and the respective risks of the vaccine and the disease are still unresolved owing to methodological limitations of studies on both sides of the argument. One-sided health 'education' campaigns on whooping cough vaccine have questionable ethics, and suppression of dissenting views is counterproductive. Health professionals and parents have a right to know the political context of the debate.

Ethics, Medical↗

Practical management of superficial digital flexor tendinitis in the performance horse.

The authors of this section represent a broad range of practice experience with horses that perform in rigorous and varied sport competitions. Each breed and performance application represent unique challenges of diagnosis and uncompromising demands on rehabilitated tendon injuries. This article will serve to guide, stimulate, and encourage veterinarians to apply scientific criteria to the evaluation of tendinitis therapy in the years to come so that we can arrive at a more valid consensus as to the "best" means of tendon and ligament injury management.

Animals↗

Thalassaemia. Part 3 of 3. Counselling and community education.

In two previous articles, Simon Dyson, Verna Davis, and Raheya Rahman described the basic facts about thalassaemia and also considered the outcome of a preliminary survey establishing levels of awareness among community groups in one area. In this, the concluding article in the series, they look at the particular issues raised in thalassaemia counselling work and consider one approach to community education on the issue.

Genetic Counseling↗

Thalassaemia: 1 of 3. Establishing basic awareness.

Thalassaemia has until recently received little attention and consequently is not widely understood by health professionals, write Simon Dyson, Verna Davis and Rafeya Rahman. In the first of three articles they describe the illness and its treatment and the potential role for health visitors in supporting children with the condition and their families. They conclude with a brief questionnaire to test thalassaemia-awareness levels.

Blood Transfusion↗

Thalassaemia: 2 of 3. Current community knowledge.

In this second of three articles Simon Dyson, Verna Davis and Rafeya Rahman describe a study carried out in Manchester for the sickle-cell anaemia and thalassaemia centre to gauge the extent of community awareness about thalassaemia, the likely level of demand for further information and how that information might most usefully be given.

Health Knowledge, Attitudes, Practice↗

Clinical and radiographic features, treatment and outcome in 15 horses with fracture of the medial aspect of the patella.

A sagittal fracture of the medial aspect of the patella was identified in 15 horses, 2 of which had been kicked and 12 of which had hit a fixed fence while jumping. Eight horses showed concurrent fragmentation of the base of the patella, and 2 had sustained a concurrent fracture of the distal end of the lateral trochlear ridge of the femur. A cranioproximal-craniodistal oblique radiographic view was essential to identify the site of the medial patellar fracture and to determine its configuration. Fourteen horses were treated by surgical removal of the medial patellar fracture fragment(s). Of 12 horses (83%) without evidence of pre-existing degenerative joint disease, 10 were treated successfully with return to full athletic function.

Animals↗