17 research outputs found
Loss-of-function mutations in SLC30A8 protect against type 2 diabetes.
Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenLoss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ~150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels. Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P = 1.7 × 10(-6)), and non-diabetic Icelandic carriers of a frameshift variant (p.Lys34Serfs*50) demonstrated reduced glucose levels (-0.17 s.d., P = 4.6 × 10(-4)). The two most common protein-truncating variants (p.Arg138* and p.Lys34Serfs*50) individually associate with T2D protection and encode unstable ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc transport increases T2D risk, and phenotypic heterogeneity was observed in mouse Slc30a8 knockouts. In contrast, loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention.US National Institutes of Health (NIH) Training
5-T32-GM007748-33
Doris Duke Charitable Foundation
2006087
Fulbright Diabetes UK Fellowship
BDA 11/0004348
Broad Institute from Pfizer, Inc.
NIH
U01 DK085501
U01 DK085524
U01 DK085545
U01 DK085584
Swedish Research Council
Dnr 521-2010-3490
Dnr 349-2006-237
European Research Council (ERC)
GENETARGET T2D
GA269045
ENGAGE
2007-201413
CEED3
2008-223211
Sigrid Juselius Foundation
Folkh lsan Research Foundation
ERC
AdG 293574
Research Council of Norway
197064/V50
KG Jebsen Foundation
University of Bergen
Western Norway Health Authority
Lundbeck Foundation
Novo Nordisk Foundation
Wellcome Trust
WT098017
WT064890
WT090532
WT090367
WT098381
Uppsala University
Swedish Research Council and the Swedish Heart- Lung Foundation
Academy of Finland
124243
102318
123885
139635
Finnish Heart Foundation
Finnish Diabetes Foundation, Tekes
1510/31/06
Commission of the European Community
HEALTH-F2-2007-201681
Ministry of Education and Culture of Finland
European Commission Framework Programme 6 Integrated Project
LSHM-CT-2004-005272
City of Kuopio and Social Insurance Institution of Finland
Finnish Foundation for Cardiovascular Disease
NIH/NIDDK
U01-DK085545
National Heart, Lung, and Blood Institute (NHLBI)
National Institute on Minority Health and Health Disparities
N01 HC-95170
N01 HC-95171
N01 HC-95172
European Union Seventh Framework Programme, DIAPREPP
Swedish Child Diabetes Foundation (Barndiabetesfonden)
5U01DK085526
DK088389
U54HG003067
R01DK072193
R01DK062370
Z01HG000024info:eu-repo/grantAgreement/EC/FP7/20201
Making it your own by adapting it to what’s important to you”: Plurilingual Critical Literacies to promote L2 Japanese users’ sense of ownership of Japanese
The dichotomy between native speaker (NS) and non-native speaker (NNS) remains ubiquitous across different language-learning contexts despite increasing mobility and multilingualism of society. L2 Japanese learners in particular may find themselves positioned as subordinate to NSs because of the myth of Japan being a homogeneous nation of one race and one language. To help L2 Japanese students counter such positioning and gain a sense of ownership, we implemented “plurilingual critical literacies” in a Japanese language course in the U.S. Critical literacy aims to cultivate students’ awareness that power relationships are at play in language use, and plurilingual pedagogy valorizes students’ multilingual resources. Eleven high-intermediate-level Japanese students mobilized their linguistic and cultural resources to read and discuss authentic texts by transcultural or “culturally mobile” writers (Dagnino 2015). These writers expressed resistance to the status quo and made meaning creatively, as mediators between two languages and cultures. Reading, analyzing, and discussing texts by transcultural writers motivated students to counter ideologies of NS superiority, and to own Japanese in the ways that best suited their transcultural identities