36 research outputs found
Reliability and normative values for the foot mobility magnitude: a composite measure of vertical and medial-lateral mobility of the midfoot
Background: A study was conducted to determine the reliability and minimal detectable change for a new composite measure of the vertical and medial-lateral mobility of the midfoot called the foot mobility magnitude
Creation of an Open-Access, Mutation-Defined Fibroblast Resource for Neurological Disease Research
Our understanding of the molecular mechanisms of many neurological disorders has been greatly enhanced by the discovery of mutations in genes linked to familial forms of these diseases. These have facilitated the generation of cell and animal models that can be used to understand the underlying molecular pathology. Recently, there has been a surge of interest in the use of patient-derived cells, due to the development of induced pluripotent stem cells and their subsequent differentiation into neurons and glia. Access to patient cell lines carrying the relevant mutations is a limiting factor for many centres wishing to pursue this research. We have therefore generated an open-access collection of fibroblast lines from patients carrying mutations linked to neurological disease. These cell lines have been deposited in the National Institute for Neurological Disorders and Stroke (NINDS) Repository at the Coriell Institute for Medical Research and can be requested by any research group for use in in vitro disease modelling. There are currently 71 mutation-defined cell lines available for request from a wide range of neurological disorders and this collection will be continually expanded. This represents a significant resource that will advance the use of patient cells as disease models by the scientific community
Creation of an Open-Access, Mutation-Defined Fibroblast Resource for Neurological Disease Research
Our understanding of the molecular mechanisms of many neurological disorders has been greatly enhanced by the discovery of mutations in genes linked to familial forms of these diseases. These have facilitated the generation of cell and animal models that can be used to understand the underlying molecular pathology. Recently, there has been a surge of interest in the use of patient-derived cells, due to the development of induced pluripotent stem cells and their subsequent differentiation into neurons and glia. Access to patient cell lines carrying the relevant mutations is a limiting factor for many centres wishing to pursue this research. We have therefore generated an open-access collection of fibroblast lines from patients carrying mutations linked to neurological disease. These cell lines have been deposited in the National Institute for Neurological Disorders and Stroke (NINDS) Repository at the Coriell Institute for Medical Research and can be requested by any research group for use in in vitro disease modelling. There are currently 71 mutation-defined cell lines available for request from a wide range of neurological disorders and this collection will be continually expanded. This represents a significant resource that will advance the use of patient cells as disease models by the scientific community
Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis
Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p
The effectiveness of interventions to increase physical activity among young girls: A meta-analysis
Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe
Silk in European and American Trade before 1783: A commodity of commerce or a frivolous luxury?
This outline is taken from ray as yet unpublished book on The English Silk Industry 1700-1825, and especially from the chapters on raw silk and the distribution of the woven material. In addition, I have widened the scope for this talk to discuss the subject more generally. In terms of general economic history the quantities of silk produced and sold are minuscule but there are a lot of instructive points to be made which are of general importance - as well as some very pretty objects. The latter are documents in the French sense as well as works of art - a point that many people have heard me make only too often. One aspect which I shall state now and, no doubt, several more times in different ways is that we must understand for what a particular fibre was used and how that use may change. Since for all clothing and furnishing there were, effectively, four fibres this should seem self-evident but it does not always seem to be. On the other hand, statistics compiled in a period when in no sense were they compiled scientifically or objectively I prefer to treat with great caution. They can point research in a useful direction but not much more. The Customs compiled yearly statistics of imports and exports in the Port Books now in the Public Record Office in London [1], They used the great pound, however, and an out of date Book of Rates. So what ? The statistics did tell me to which countries English silks were exported and which were the most important markets, of which more anon.
Sources of raw silk: The Harp
Even at this first stage an appreciation of the real object is of great importance. The silk for the warp had to be of higher quality than that for the weft since it took the strain of the loom in weaving. Not every country which grew silk could produce a suitable quality. In the 17th-18th century there were two main sources. The first was China and it was imported into Europe with other goods by the English, French and Dutch East India Companies. The quality was usually excellent but it arrived spasmodically [2] making it difficult for silkmen and weavers alike. The second and more important source was Piedmont , an easy market for Lyon in the second half of the 17th century but as the English industry expanded competition in Piedmont between the French and English grew increasingly tense - and the price rose . Raw silk was also exported from Spain in the first half of the 18th century but it is not clear whether it was intended for the warp or the weft. Some silk was exported already thrown as organzine [3]. The pressure of demand led both countries to look for other sources in the 18th century. The English tried growing silk in Georgia and South Carolina but although the climate was suitable slave labour was not. [4] The white mulberry cannot be grown in Northern Europe as a commercial enterprise. Whether or not the myth is true that James I of England encouraged the planting of mulberries is irrelevant because what grows nicely in England is the red mulberry , delicious for humans but not for silk worms. The French were much more practical and began to grow silk in Provence where both labour and climate were suitable. This did not entirely satisfy their needs but reduced French dependence on Piedmont
L'organisation du commerce des soieries en France et en Angleterre au XVIIIe siècle d'après un livre de commissions lyonnais conservé au Victoria & Albert Museum de Londres
Rothstein (Natalie). — The organisation of the silk fabric commerce in France and in England in the Eighteenth Century, taken from a book of commissions in Lyon, conserved in Victoria & Albert Museum in London.
Analyzing an anonymous book of commissions from Lyon, conserved in the Victoria & Albert Muséum Collections in London, allows a comparison of French and English methods of commerce in the middle of the Eighteenth Century. The author's main thrust is to explore the paths that he provides, in order to fully understand the reality of working methods in Lyon, known essentially, until then, through payments. By identifying, in the album, a sample of a silk fabric woven in Lyon, the author is able to attribute other silk fragments to firms in Lyon. He is also led to ask a certain number of questions : were silk fabrics in Lyon specialized fabrics as certain indications seem to suggest ? Were the weavers specialized weavers also ? What were their relations with the commission agents ?...
Le Monde alpin et rhodanien, 2-3e trimestres 1991, Les filières de
la soie lyonnaise, pp. 85 à 92.Rothstein (Natalie). — L'organisation du commerce des soiries en France et en Angleterre au XVIIIe siècle d'après un livre de commissions lyonnais conservé au Victoria & Albert Museum de Londres.
L'analyse d'un livre de commissions anonyme d'origine lyonnaise, conservé dans les collections du Victoria & Albert Muséum de Londres, permet une comparaison des méthodes de vente françaises et anglaises au milieu du XVIIIe siècle. L'auteur s'attache plus particulièrement à explorer les pistes qu'il fournit pour appréhender la réalité des méthodes de travail à Lyon, connues jusqu'alors essentiellement à travers les règlements. A partir de l'identification, dans l'album, de l'échantillon d'une soierie tissée à Lyon, l'auteur attribue d'autres fragments de tissu à des maisons lyonnaises et est amenée à poser un certain nombre de questions : les maisons de soieries lyonnaises étaient-elles spécialisées, comme certains indices permettent de le croire ? Les tisseurs l'étaient-ils aussi ? Quelles étaient leurs relations avec les commissionnaires ? ...
Le Monde alpin et rhodanien, 2-3e trimestres 1991, Les filières de
la soie lyonnaise, pp. 85 à 92.Rothstein Natalie. L'organisation du commerce des soieries en France et en Angleterre au XVIIIe siècle d'après un livre de commissions lyonnais conservé au Victoria & Albert Museum de Londres. In: Le Monde alpin et rhodanien. Revue régionale d'ethnologie, n°2-3/1991. Les filières de la soie lyonnaise, sous la direction de Florence Charpigny . pp. 85-92