175 research outputs found
Primary ciliary dyskinesia (Siewert's/Kartagener's syndrome): respiratory symptoms and psycho-social impact
No full textAlthough the pathophysiological defect in primary ciliary dyskinesia (PCD; Siewert's/Kartagener's syndrome) is now well characterised, there are few studies of the impact of the condition upon health function, particularly in later life. This study assesses the health impact of the condition in a large group of patients. In addition, it assesses the similarity in age of diagnosis, symptoms and problems of those with situs inversus (PCD-SI) and those with situs solitus (PCD-SS)
Motile and non-motile cilia in human pathology: from function to phenotypes
No full textCiliopathies are inherited human disorders caused by both motile and non-motile cilia dysfunction that form an important and rapidly expanding disease category. Ciliopathies are complex conditions to diagnose, being multisystem disorders characterized by extensive genetic heterogeneity and clinical variability with high levels of lethality. There is marked phenotypic overlap among distinct ciliopathy syndromes that presents a major challenge for their recognition, diagnosis, and clinical management, in addition to posing an on-going task to develop the most appropriate family counselling. The impact of next-generation sequencing and high-throughput technologies in the last decade has significantly improved our understanding of the biological basis of ciliopathy disorders, enhancing our ability to determine the possible reasons for the extensive overlap in their symptoms and genetic aetiologies. Here, we review the diverse functions of cilia in human health and disease and discuss a growing shift away from the classical clinical definitions of ciliopathy syndromes to a more functional categorization. This approach arises from our improved understanding of this unique organelle, revealed through new genetic and cell biological insights into the discrete functioning of subcompartments of the cilium (basal body, transition zone, intraflagellar transport, motility). Mutations affecting these distinct ciliary protein modules can confer different genetic diseases and new clinical classifications are possible to define, according to the nature and extent of organ involvement. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd
Opportunities and Challenges for Molecular Understanding of Ciliopathies–The 100,000 Genomes Project
No full textCilia are highly specialized cellular organelles that serve multiple functions in human
development and health. Their central importance in the body is demonstrated by the
occurrence of a diverse range of developmental disorders that arise from defects of cilia
structure and function, caused by a range of different inherited mutations found in more
than 150 different genes. Genetic analysis has rapidly advanced our understanding of
the cell biological basis of ciliopathies over the past two decades, with more recent
technological advances in genomics rapidly accelerating this progress. The 100,000
Genomes Project was launched in 2012 in the UK to improve diagnosis and future
care for individuals affected by rare diseases like ciliopathies, through whole genome
sequencing (WGS). In this review we discuss the potential promise and medical impact
of WGS for ciliopathies and report on current progress of the 100,000 Genomes Project,
reviewing the medical, technical and ethical challenges and opportunities that new, large
scale initiatives such as this can offer
Person
No full textThis record was harvested from a previous catalogue system and will be withdrawn in 2025. Information in this record may be superseded or incomplete. Visit this record in UMA's new catalogue at: https://archives.library.unimelb.edu.au/nodes/view/58827Naomi Haldane was born in 1897 and after a brief career as a nurse married G.R. Mitchison who after distinguished war service became a long time Labor Minister and Peer. While raising five children, Naomi Mitchison became a successful author of historical fiction, was a committed political activist and travelled extensively to the Soviet Union, the Deep South in America and Botswana. In 1978 she attended the Adelaide Arts Festival Writer's Week and while in Australia she travelled widely and wrote articles for the Australian and British press. Lady Mitchison's publications include "The Conquered", "We Have Been Warned" and the "Bull Calves"
Naomi Mitchison\u27s Spring Queen: A Not So Archetypical Monarch
No full textGrowing up in a politically and socially active household, Scottish author Naomi Mitchison (1897-1998) was a polymath. She had a curious mind and a great capacity to express her knowledge about science and society in her literary works. Her fantasy novel The Corn King and the Spring Queen (1931) takes us back to a mythical past, typical of the returning to roots and folklore of the Scottish Renaissance. However, she subverts the roles traditionally associated with men and women as she advocates for sexual freedom and illustrates the symbolic connection between the female body and the earth.La autora escocesa Naomi Mitchison (1897-1998) creció en un entorno política y socialmente activo. Fue una mujer muy polifacética, de mente inquieta y con una gran capacidad para plasmar sus conocimientos sobre ciencia y sociedad en sus obras. En la novela fantástica de 1931 El Rey Maíz y la Reina Primavera, nos transporta a un pasado mítico propio del retorno a las raíces y el folklore del Renacimiento Escocés. Sin embargo, subvierte los roles tradicionalmente asociados a hombres y mujeres mientras aboga por la libertad sexual e ilustra la simbólica relación entre cuerpo femenino y tierra
Politics and the problem of speaking for others in the work of Naomi Mitchison
No full textThis thesis focuses on the political influences that shaped the life and writing of Naomi Mitchison (1897-1999). Mitchison was a polymath who published extensively in a wide range of genres, and whose left-wing political interests informed many of her works. I explore the view that in her roles as author and social activist she aimed to represent 'the people who have not spoken yet' (Calder 1997: ix), and I interrogate the potential difficulties in representing those marginal voices.;Examining texts from the 1910s through to the 1970s, this thesis traces Mitchison's political development to show how her socialist outlook emerged, shifted and directly responded to socio-historical contexts throughout the twentieth century. An evaluation of her extensive corpus, including fictional and non-fictional texts, archival material and unpublished letters, will be employed to show how she repeatedly campaigned, examined and documented the political and social issues of her time. Her role as an author not only enabled her to represent silenced groups, but also provided an opportunity to write through and explore her own, often contradictory, stance.;Drawing upon theoretical frameworks, including Linda Alcoff's 'The Problem of Speaking for Others', I contend that throughout Mitchison's career she repeatedly seeks to 'know' and explain others, and justify her right to speak for them. Mitchison's endeavours were grounded in altruism, but she was consciously aware of her paradoxical position as a privileged upper-middle-class author and socialist champion, and her writing pivots around this contradictory struggle. In representing marginal groups, she aimed to give agency to those who had been silenced, but her works also served to validate her place as spokesperson for such groups.This thesis focuses on the political influences that shaped the life and writing of Naomi Mitchison (1897-1999). Mitchison was a polymath who published extensively in a wide range of genres, and whose left-wing political interests informed many of her works. I explore the view that in her roles as author and social activist she aimed to represent 'the people who have not spoken yet' (Calder 1997: ix), and I interrogate the potential difficulties in representing those marginal voices.;Examining texts from the 1910s through to the 1970s, this thesis traces Mitchison's political development to show how her socialist outlook emerged, shifted and directly responded to socio-historical contexts throughout the twentieth century. An evaluation of her extensive corpus, including fictional and non-fictional texts, archival material and unpublished letters, will be employed to show how she repeatedly campaigned, examined and documented the political and social issues of her time. Her role as an author not only enabled her to represent silenced groups, but also provided an opportunity to write through and explore her own, often contradictory, stance.;Drawing upon theoretical frameworks, including Linda Alcoff's 'The Problem of Speaking for Others', I contend that throughout Mitchison's career she repeatedly seeks to 'know' and explain others, and justify her right to speak for them. Mitchison's endeavours were grounded in altruism, but she was consciously aware of her paradoxical position as a privileged upper-middle-class author and socialist champion, and her writing pivots around this contradictory struggle. In representing marginal groups, she aimed to give agency to those who had been silenced, but her works also served to validate her place as spokesperson for such groups
Held together by words : 'The Bull Calves' and the Scottish fiction of Naomi Mitchison
No full textNaomi Mitchison (1897-1999) was an accomplished Scottish author noted for her historical fiction. Her literary career was prolific and lengthy, moving through several phases. From the early 1930s through the 1960s, Mitchison wrote primarily Scottish works. Whether in setting, characterisation, or concern, her literature during these years was for the Scottish people. In this reader’s estimation, Mitchison’s greatest contribution to the Scottish literary world was her ability to write engaging story while constructively recreating strong national mythos and setting forth models of healthy, loyal communities. Mitchison first is artist; therefore, any social agenda she embraces finds expression in art (whether these concerns be socialism, feminism, education, the arts, agricultural practices, or fishing, to name a few). This thesis will trace the themes in her earlier and later periods of the Scottish phase of her literary art, with The Bull Calves as focal point not only of this study, but also of the Scottish period of her writing. Exploration of the early works (1930s-40s) and the later works (1950s-60s and the later Early in Orcadia) will highlight themes that recur throughout her literary career. While not new to her particularly Scottish works, recurring themes take on new significance in light of Mitchison’s political involvement with the Labour Party and her local Community of Carradale. Mikhail Bakhtin’s study of narratology acknowledges the inherent political nature of language, and how the lexical range of characters within a text signifies particular class, occupation, religious and/or political propensity. When examining The Bull Calves, Bakhtinian method will be applied to the text, illustrating Mitchison’s utilisation of the facets of language to refract meaning within the text.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
History of Medicine #22: Send in the Clones? Naomi Mitchison (née Haldane)’s Musing on Reproduction, Breeding, Feminism, Socialism and Eugenics from the 1920s to the 1970s
No full textIn this seminar Lesley Hall investigates the relationship between feminism and eugenics through the fascinating lens of Naomi Mitchison’s fiction. JBS Haldane’s sister, and very much situated at the centre of the eugenic and literary movements of her time, Naomi Mitchison was a prolific author writing path braking historical fiction amongst other works before turning to Science Fiction. Scrutinizing her personal and political lives, this seminar focuses on three of Mitchison’s postwar works in relation to perceptions of breeding and reproduction, namely Memoirs of a Spacewomen (1962), Solution 3 (1975), and Not by Bread Alone (1983). This seminar took place at Oxford Brookes University on 13 November 2012
A high prevalence CCDC103 p.His154Pro mutation causing primary ciliary dyskinesia disrupts protein oligomerisation and is associated with normal diagnostic investigations
No full textRATIONALE: Primary ciliary dyskinesia is a genetically heterogeneous inherited condition characterised by progressive lung disease arising from abnormal cilia function. Approximately half of patients have situs inversus. The estimated prevalence of primary ciliary dyskinesia in the UK South Asian population is 1:2265. Early, accurate diagnosis is key to implementing appropriate management but clinical diagnostic tests can be equivocal.
OBJECTIVES: To determine the importance of genetic screening for primary ciliary dyskinesia in a UK South Asian population with a typical clinical phenotype, where standard testing is inconclusive.
METHODS: Next-generation sequencing was used to screen 86 South Asian patients who had a clinical history consistent with primary ciliary dyskinesia. The effect of a CCDC103 p.His154Pro missense variant compared with other dynein arm-associated gene mutations on diagnostic/phenotypic variability was tested. CCDC103 p.His154Pro variant pathogenicity was assessed by oligomerisation assay.
RESULT: Sixteen of 86 (19%) patients carried a homozygous CCDC103 p.His154Pro mutation which was found to disrupt protein oligomerisation. Variable diagnostic test results were obtained including normal nasal nitric oxide levels, normal ciliary beat pattern and frequency and a spectrum of partial and normal dynein arm retention. Fifteen (94%) patients or their sibling(s) had situs inversus suggesting CCDC103 p.His154Pro patients without situs inversus are missed.
CONCLUSIONS: The CCDC103 p.His154Pro mutation is more prevalent than previously thought in the South Asian community and causes primary ciliary dyskinesia that can be difficult to diagnose using pathology-based clinical tests. Genetic testing is critical when there is a strong clinical phenotype with inconclusive standard diagnostic tests
Colloid osmotic parameterization and measurement of subcellular crowding
No full text© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Mitchison, T. J. (2019). Colloid osmotic parameterization and measurement of subcellular crowding. Molecular Biology of the Cell, 30(2), (2019): 173-180, doi:10.1091/mbc.E18-09-0549.Crowding of the subcellular environment by macromolecules is thought to promote protein aggregation and phase separation. A challenge is how to parameterize the degree of crowding of the cell interior or artificial solutions that is relevant to these reactions. Here I review colloid osmotic pressure as a crowding metric. This pressure is generated by solutions of macromolecules in contact with pores that are permeable to water and ions but not macromolecules. It generates depletion forces that push macromolecules together in crowded solutions and thus promotes aggregation and phase separation. I discuss measurements of colloid osmotic pressure inside cells using the nucleus, the cytoplasmic gel, and fluorescence resonant energy transfer (FRET) biosensors as osmometers, which return a range of values from 1 to 20 kPa. I argue for a low value, 1–2 kPa, in frog eggs and perhaps more generally. This value is close to the linear range on concentration–pressure curves and is thus not crowded from an osmotic perspective. I discuss the implications of a low crowding pressure inside cells for phase separation biology, buffer design, and proteome evolution. I also discuss a pressure–tension model for nuclear shape, where colloid osmotic pressure generated by nuclear protein import inflates the nucleus.This article was prompted by lively discussions at the Marine Biological Laboratory (MBL) Physiology Course, Woods Hole, MA. I particularly thank Annie Pipathsouk (University of California, San Franscico) and Charlotte Strandkvist (Harvard Medical School) for experimental work in frog egg extract; James Pelletier (MIT), Tony Hyman (MPI Dresden), and Rob Phillips (Cal. Tech.) for discussions; and Nikon for microscopy support at MBL. T.J.M. is supported by National Institute of General Medical Sciences 39565
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