138 research outputs found
Whose 'New Vision' for adult social care? Involving service users and unpaid carers in policy research
No full textA perspective on inversin
No full textOver the past 5 years, there has been increasing evidence for the role of primary (9+0) cilia in renal physiology and in establishing the left–right axis. The cilia in the renal tract are immotile and thought to have a sensory function. Cilia at the murine embryonic node have a vortical movement that sets up a leftward flow. Inversin, the protein defective in the inv mouse and in patients with type-2 nephronophthisis, localizes to both renal and node primary cilia. However, we present evidence that it is also expressed before the node forms and that its subcellular localization in renal tubular cells is not confined to the cilia. Its role in both the pathway determining left–right axis and renal function remains to be elucidated
The left-right determinant inversin has highly conserved ankyrin repeat and IQ domains and interacts with calmodulin
No full textAll vertebrates have a left-right body axis with invariant asymmetries of the heart and the positions of the abdominal viscera. Major advances have recently been made in defining molecular components of the pathway specifying the vertebrate left-right axis, but our knowledge of the early determinants is extremely limited. In the inv mouse the left-right axis is consistently reversed, unlike other vertebrate mutants where randomisation of situs is apparent. The gene disrupted in this mouse encodes a 1062-amino-acid protein, inversin. We previously reported 16 tandem ankyrin repeats, spanning amino acids 13-557, and two putative nuclear localisation sequences, but otherwise the sequence offered few clues to the possible function. In order to identify regions likely to be functionally important, we have identified and characterised orthologous sequences in several species, including chick, Xenopus and zebrafish. Sequence comparisons show strong conservation of the ankyrin repeat region and also a lysine-rich domain spanning amino acids 558-604. Further analysis identified a highly conserved IQ calmodulin-binding domain in the latter region and another such domain in an otherwise poorly conserved C-terminal region. A yeast two-hybrid screen identified calmodulin in one third of the positive clones, and we confirmed this interaction by immunoprecipitation
Molecular genetics of X-linked immunodeficiency disorders
No full textEight disorders of the immune system have been described which
are inherited as X-linked recessive conditions. The aim of this study
has been to improve predictive testing in X-linked agammaglobulinaemia
(XLA) and X-linked severe combined immunodeficiency (XSCID) and to
investigate the underlying defect in XSCID.Precise genetic localisation is essential for accurate predictive
testing and in order to develop strategies to clone the genes. Before
disease localisation can be improved it is necessary to clarify the
order of a number of probes within the region of interest. Fourteen
genetic markers assigned to the X chromosome between the
pericentromeric region and Xq22 were ordered by family studies and
deletion mapping. Pulsed field gel electrophoresis was used to make a
physical map of the markers linked to XLA.Knowledge of the order of these anonymous DNA probes led to
finding addditional linked probes for both diseases. This makes
predictive testing possible in more families.There are X-linked and autosomal recessive forms of severe
combined immunodeficiency. This has caused difficulties in counselling
couples who have an affected male child and where there is no previous
family history of the disease. In this study it has been shown that
female carriers of the X-linked disorder have non-random use of the X
chromosome in T lymphocytes. This provides a means of distinguishing
between the autosomal and X-linked forms which enables more accurate
genetic counselling.XSCID has been mapped to Xqll-ql3 using DNA markers which detect
polymorphic variation (de Saint Basile et al, 1987). No recombinations
have been observed between the disease locus and the anonymous DNA
probe cpX289. In this study the PGK1 locus was also shown to be
closely linked to the disease. Using both of these linked markers
predictive tests can be offered to 65% of families.The probe pSPT/PGK which detects a polymorphism at the PGK1 locus
can also be used to investigate X chromosome usage. In females who are
heterozygous for the polymorphism detected by this probe, carrier
detection and assignment of phase can be carried out in the same
procedure. This is a unique situation and is particularly useful when
the proband could carry a new mutation or when there are no males
available who can be used to assign linkage phase.It has been thought that XSCID results from a defect in a T
lymphocyte specific gene because the phenotype is predominantly a lack
of T lymphocytes and because host B lymphocytes produce functional
antibody following transplantation and engraftment of T lymphocytes.
Finding a non-random pattern of X chromosome usage in a mature cell
population implies that the defective gene is expressed in that cell
type and this technique was used to investigate gene expression. Nonrandom
X chromosome usage was found in T lymphocytes, B lymphocytes,
monocytes and granulocytes. The pattern of expression suggests that
the underlying defect in XSCID is in a general metabolic pathway
rather than a pathway specific to lymphocytes
The genetics and pathogenesis of haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura
No full text
A Nonsense Mutation in the IKBKG Gene in Mares with Incontinentia Pigmenti.
No full textEctodermal dysplasias (EDs) are a large and heterogeneous group of hereditary disorders characterized by abnormalities in structures of ectodermal origin. Incontinentia pigmenti (IP) is an ED characterized by skin lesions evolving over time, as well as dental, nail, and ocular abnormalities. Due to X-linked dominant inheritance IP symptoms can only be seen in female individuals while affected males die during development in utero. We observed a family of horses, in which several mares developed signs of a skin disorder reminiscent of human IP. Cutaneous manifestations in affected horses included the development of pruritic, exudative lesions soon after birth. These developed into wart-like lesions and areas of alopecia with occasional wooly hair re-growth. Affected horses also had streaks of darker and lighter coat coloration from birth. The observation that only females were affected together with a high number of spontaneous abortions suggested an X-linked dominant mechanism of transmission. Using next generation sequencing we sequenced the whole genome of one affected mare. We analyzed the sequence data for non-synonymous variants in candidate genes and found a heterozygous nonsense variant in the X-chromosomal IKBKG gene (c.184C>T; p.Arg62*). Mutations in IKBKG were previously reported to cause IP in humans and the homologous p.Arg62* variant has already been observed in a human IP patient. The comparative data thus strongly suggest that this is also the causative variant for the observed IP in horses. To our knowledge this is the first large animal model for IP
The instant expert: plastics, processing and properties
No full text"Plastics - they are everywhere." The first sentence of this book hints at the problem it seeks to address. The shear diversity of plastics materials has led to their use in products as varied as disposable packaging, life-saving medical devices, giant wind-turbine blades and tiny electronic components. Their prices and properties vary as widely, and they can be moulded, extruded, blown, formed, and shaped in many other ways. Traditionally made from petrochemicals, designers can now also choose from a range of natural materials. Performance will depend on chemical constitution, but also on the selection of processing aids and property modifiers which can be added to the basic material. For years, people have asked for a simple book to help them understand this complex subject. This is that book! Managers, sales personnel, industry newcomers, designers and end-users are all confronted with a bewildering range of technology and terminology by their colleagues, customers and suppliers. The Instant Expert: Plastics, Processing and Properties provides clear descriptions of the wide range of plastic materials, and explanations of the basic shaping and finishing processes. The author also talks about materials properties and testing, and provides some simple examples of why particular plastics are used in common or more challenging applications. Common abbreviations are explained. Readable from cover-to-cover, or easily referred to when questions arise, this book will be indispensible
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