scholarly journals Abundance and localization of human UBE3A protein isoforms

2020 ◽  
Author(s):  
Carissa L. Sirois ◽  
Judy E. Bloom ◽  
James J. Fink ◽  
Dea Gorka ◽  
Steffen Keller ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Neurodevelopmental Disorder ◽  
Embryonic Stem ◽  
Protein Isoforms ◽  
Wild Type ◽  
Neuronal Function ◽  
Recent Case Study ◽  
The Individual ◽  
Human Isoforms

AbstractLoss of UBE3A expression, a gene regulated by genomic imprinting, causes Angelman Syndrome (AS), a rare neurodevelopmental disorder. The UBE3A gene encodes an E3 ubiquitin ligase with three known protein isoforms in humans. Studies in mouse suggest that the human isoforms may have differences in localization and neuronal function. A recent case study reported mild AS phenotypes in individuals lacking one specific isoform. Here we have used CRISPR/Cas9 to generate isogenic human embryonic stem cells (hESCs) that lack the individual protein isoforms. We demonstrate that isoform 1 accounts for the majority of UBE3A protein in hESCs and neurons. We also show that UBE3A predominantly localizes to the cytoplasm in both wild type and isoform-null cells. Finally, we show that neurons lacking isoform 1 display a less severe electrophysiological AS phenotype.

scholarly journals Abundance and localization of human UBE3A protein isoforms

2020 ◽  
Vol 29 (18) ◽  
pp. 3021-3031 ◽  
Author(s):  
Carissa L Sirois ◽  
Judy E Bloom ◽  
James J Fink ◽  
Dea Gorka ◽  
Steffen Keller ◽  
...  
Keyword(s):  
Neurodevelopmental Disorder ◽  
Embryonic Stem ◽  
Protein Isoforms ◽  
Wild Type ◽  
Neuronal Function ◽  
Ube3a Gene ◽  
Recent Case Study ◽  
The Individual ◽  
Human Isoforms

Abstract Loss of UBE3A expression, a gene regulated by genomic imprinting, causes Angelman syndrome (AS), a rare neurodevelopmental disorder. The UBE3A gene encodes an E3 ubiquitin ligase with three known protein isoforms in humans. Studies in mouse suggest that the human isoforms may have differences in localization and neuronal function. A recent case study reported mild AS phenotypes in individuals lacking one specific isoform. Here we have used CRISPR/Cas9 to generate isogenic human embryonic stem cells (hESCs) that lack the individual protein isoforms. We demonstrate that isoform 1 accounts for the majority of UBE3A protein in hESCs and neurons. We also show that UBE3A predominantly localizes to the cytoplasm in both wild type and isoform-null cells. Finally, we show that neurons lacking isoform 1 display a less severe electrophysiological AS phenotype.

scholarly journals Activin βC and βE Genes Are Not Essential for Mouse Liver Growth, Differentiation, and Regeneration

2000 ◽  
Vol 20 (16) ◽  
pp. 6127-6137 ◽  
Author(s):  
Anthony L. Lau ◽  
T. Rajendra Kumar ◽  
Katsuhiko Nishimori ◽  
Jeffrey Bonadio ◽  
Martin M. Matzuk
Keyword(s):  
Embryonic Development ◽  
Transforming Growth Factor ◽  
Serum Proteins ◽  
Embryonic Stem ◽  
Transforming Growth Factor Β ◽  
Wild Type ◽  
Rnase Protection ◽  
Liver Growth ◽  
Adult Mice ◽  
The Individual

ABSTRACT The liver is an essential organ that produces several serum proteins, stores vital nutrients, and detoxifies many carcinogenic and xenobiotic compounds. Various growth factors positively regulate liver growth, but only a few negative regulators are known. Among the latter are the transforming growth factor β (TGF-β) superfamily members TGF-β1 and activin A. To study the function of novel activin family members, we have cloned and generated mice deficient in the activin βC and βE genes. Expression analyses demonstrated that these novel genes are liver specific in adult mice. Here, we show by RNase protection that activin βC transcripts are present in the liver beginning at embryonic day 11.5 (E11.5) whereas activin βE expression is detected starting from E17.5. Gene targeting in embryonic stem cells was used to generate mice with null mutations in either the individual activin βC and βE genes or both genes. In contrast to the structurally related activin βA and βB subunits, which are necessary for embryonic development and pituitary follicle-stimulating hormone homeostasis, mice deficient in activin βC and βE were viable, survived to adulthood, and demonstrated no reproductive abnormalities. Although activin βC and βE mRNAs are abundantly expressed in the liver of wild-type mice, the single and double mutants did not show any defects in liver development and function. Furthermore, in the homozygous mutant mice, liver regeneration after >70% partial hepatectomy was comparable to that in wild-type mice. Our results suggest that activin βC and βE are not essential for either embryonic development or liver function.

The Development of Language-Training Programs for Postrubella Hearing-Impaired Children

1973 ◽  
Vol 38 (1) ◽  
pp. 15-24 ◽  
Author(s):  
Linda Lynch ◽  
Annette Tobin
Keyword(s):  
Hearing Impaired ◽  
Treatment Programs ◽  
Individual Treatment ◽  
Target Behaviors ◽  
Systematic Fashion ◽  
Development Of Language ◽  
The Individual ◽  
Impaired Children ◽  
Hearing Impaired Children

This paper presents the procedures developed and used in the individual treatment programs for a group of preschool, postrubella, hearing-impaired children. A case study illustrates the systematic fashion in which the clinician plans programs for each child on the basis of the child’s progress at any given time during the program. The clinician’s decisions are discussed relevant to (1) the choice of a mode(s) for the child and the teacher, (2) the basis for selecting specific target behaviors, (3) the progress of each program, and (4) the implications for future programming.

‘A Routh O’ Auld Nick-Nackets’ – the antiquarian collection of John Rae

2015 ◽  
Vol 36-37 (1) ◽  
pp. 163-183
Author(s):  
Paul Taylor
Keyword(s):  
United States ◽  
Nineteenth Century ◽  
Social Context ◽  
Moral Education ◽  
The United States ◽  
Representative Case ◽  
National Museums ◽  
The Individual ◽  
The University

John Rae, a Scottish antiquarian collector and spirit merchant, played a highly prominent role in the local natural history societies and exhibitions of nineteenth-century Aberdeen. While he modestly described his collection of archaeological lithics and other artefacts, principally drawn from Aberdeenshire but including some items from as far afield as the United States, as a mere ‘routh o’ auld nick-nackets' (abundance of old knick-knacks), a contemporary singled it out as ‘the best known in private hands' (Daily Free Press 4/5/91). After Rae's death, Glasgow Museums, National Museums Scotland, the University of Aberdeen Museum and the Pitt Rivers Museum in Oxford, as well as numerous individual private collectors, purchased items from the collection. Making use of historical and archive materials to explore the individual biography of Rae and his collection, this article examines how Rae's collecting and other antiquarian activities represent and mirror wider developments in both the ‘amateur’ antiquarianism carried out by Rae and his fellow collectors for reasons of self-improvement and moral education, and the ‘professional’ antiquarianism of the museums which purchased his artefacts. Considered in its wider nineteenth-century context, this is a representative case study of the early development of archaeology in the wider intellectual, scientific and social context of the era.

Drowning in negativism, self-hate, doubt, madness: Linguistic insights into Sylvia Plath’s experience of depression

2015 ◽  
Vol 11 (1) ◽  
pp. 41-54 ◽  
Author(s):  
Zsófia Demjén
Keyword(s):  
Lived Experience ◽  
Medical Humanities ◽  
Sylvia Plath ◽  
Individual Experience ◽  
Qualitative And Quantitative ◽  
The World ◽  
The Individual ◽  
Linguistic Methods ◽  
Linguistic Approach

This paper demonstrates how a range of linguistic methods can be harnessed in pursuit of a deeper understanding of the ‘lived experience’ of psychological disorders. It argues that such methods should be applied more in medical contexts, especially in medical humanities. Key extracts from The Unabridged Journals of Sylvia Plath are examined, as a case study of the experience of depression. Combinations of qualitative and quantitative linguistic methods, and inter- and intra-textual comparisons are used to consider distinctive patterns in the use of metaphor, personal pronouns and (the semantics of) verbs, as well as other relevant aspects of language. Qualitative techniques provide in-depth insights, while quantitative corpus methods make the analyses more robust and ensure the breadth necessary to gain insights into the individual experience. Depression emerges as a highly complex and sometimes potentially contradictory experience for Plath, involving both a sense of apathy and inner turmoil. It involves a sense of a split self, trapped in a state that one cannot overcome, and intense self-focus, a turning in on oneself and a view of the world that is both more negative and more polarized than the norm. It is argued that a linguistic approach is useful beyond this specific case.

THE ROLE OF EDUCATION ON DISASTER PREPAREDNESS CASE STUDY OF 2012 INDIAN OCEAN EARTHQUAKES ON THAILAND’S

2018 ◽  
Author(s):  
Raya Muttarak ◽  
Wiraporn Pothisiri
Keyword(s):  
Indian Ocean ◽  
Emergency Preparedness ◽  
Disaster Preparedness ◽  
Formal Education ◽  
Disaster Experience ◽  
Individual Household ◽  
The Indian Ocean ◽  
The Individual

In this paper we investigate how well residents of the Andaman coast in Phang Nga province, Thailand, are prepared for earthquakes and tsunami. It is hypothesized that formal education can promote disaster preparedness because education enhances individual cognitive and learning skills, as well as access to information. A survey was conducted of 557 households in the areas that received tsunami warnings following the Indian Ocean earthquakes on 11 April 2012. Interviews were carried out during the period of numerous aftershocks, which put residents in the region on high alert. The respondents were asked what emergency preparedness measures they had taken following the 11 April earthquakes. Using the partial proportional odds model, the paper investigates determinants of personal disaster preparedness measured as the number of preparedness actions taken. Controlling for village effects, we find that formal education, measured at the individual, household, and community levels, has a positive relationship with taking preparedness measures. For the survey group without past disaster experience, the education level of household members is positively related to disaster preparedness. The findings also show that disaster related training is most effective for individuals with high educational attainment. Furthermore, living in a community with a higher proportion of women who have at least a secondary education increases the likelihood of disaster preparedness. In conclusion, we found that formal education can increase disaster preparedness and reduce vulnerability to natural hazards.

Breaking the Shackles of Gender Stereotyping to Create New Norms: The Case of Zimbabwean Migrant Women in Mthatha Town

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Sanction Madambi
Keyword(s):  
South Africa ◽  
Gender Stereotyping ◽  
Personal Agency ◽  
Migrant Women ◽  
Host Countries ◽  
Qualitative Research Design ◽  
Norms And Values ◽  
Recent Case Study ◽  
Traditional Approaches

The migration of Zimbabweans into South Africa is shaped by several factors and processes. Traditionally, the decision to migrate was mostly based on family considerations (where gender stereotypic roles were a priority), although in some cases the migrants exercised individualism and personal agency. This led to migration trends that were male dominated. Current Zimbabwean migration trends reflect large volumes of women as the socio-economic crisis forces them to leave their country. These migrant women encounter a myriad of challenges in their host countries. This paper explores Zimbabwean women’s migration to the town of Mthatha in South Africa, highlighting their challenges and the strategies they employ to overcome these, as found in a recent case study. Applying a qualitative research design and using questionnaires and interviews to gather data from the 100 purposively sampled women, the study found that many Zimbabwean migrant women in Mthatha encountered numerous challenges. They lacked the required documents to live and work in South Africa, experienced exploitation and marriage constraints, and had broken ties with their families back in Zimbabwe. According to the study, these women managed to navigate these challenges, rising above the stereotypic norms and values that used to label them as non-productive citizens to superheroes who were supporting their families and the country’s economy—thus breaking the shackles of gender stereotyping to create new norms. These findings underline the importance of shifting from the traditional approaches to women migration and pursuing perspectives that present migration as a critical component of the process of social change and development to all migrants.

Sign in / Sign up

Export Citation Format

Share Document