42 research outputs found
Expression of DNAJB12 or DNAJB14 causes coordinate invasion of the nucleus by membranes associated with a novel nuclear pore structure.
No full textDNAJB12 and DNAJB14 are transmembrane proteins in the endoplasmic reticulum (ER) that serve as co-chaperones for Hsc70/Hsp70 heat shock proteins. We demonstrate that over-expression of DNAJB12 or DNAJB14 causes the formation of elaborate membranous structures within cell nuclei, which we designate DJANGOS for DNAJ-associated nuclear globular structures. DJANGOS contain DNAJB12, DNAJB14, Hsc70 and markers of the ER lumen and ER and nuclear membranes. Strikingly, they are evenly distributed underneath the nuclear envelope and are of uniform size in any one nucleus. DJANGOS are composed primarily of single-walled membrane tubes and sheets that connect to the nuclear envelope via a unique configuration of membranes, in which the nuclear pore complex appears anchored exclusively to the outer nuclear membrane, allowing both the inner and outer nuclear membranes to flow past the circumference of the nuclear pore complex into the nucleus. DJANGOS break down rapidly during cell division and reform synchronously in the daughter cell nuclei, demonstrating that they are dynamic structures that undergo coordinate formation and dissolution. Genetic studies showed that the chaperone activity of DNAJ/Hsc70 is required for the formation of DJANGOS. Further analysis of these structures will provide insight into nuclear pore formation and function, activities of molecular chaperones, and mechanisms that maintain membrane identity
BiP and multiple DNAJ molecular chaperones in the endoplasmic reticulum are required for efficient simian virus 40 infection
No full textSimian virus 40 (SV40) is a nonenveloped DNA virus that traffics through the endoplasmic reticulum (ER) en route to the nucleus, but the mechanisms of capsid disassembly and ER exit are poorly understood. We conducted an unbiased RNA interference screen to identify cellular genes required for SV40 infection. SV40 infection was specifically inhibited by up to 50-fold by knockdown of four different DNAJ molecular cochaperones or by inhibition of BiP, the Hsp70 partner of DNAJB11. These proteins were not required for the initiation of capsid disassembly, but knockdown markedly inhibited SV40 exit from the ER. In addition, BiP formed a complex with SV40 capsids in the ER in a DNAJB11-dependent fashion. These experiments identify five new cellular proteins required for SV40 infection and suggest that the binding of BiP to the capsid is required for ER exit. Further studies of these proteins will provide insight into the molecular mechanisms of polyomavirus infection and ER function.Edward C. Goodwin, Alex Lipovsky, Takamasa Inoue, Thomas G. Magaldi, Anne P. B. Edwards, Kristin E. Y. Van Goor, Adrienne W. Paton, James C. Paton, Walter J. Atwood, Billy Tsai, and Daniel DiMai
Activation of a Metabolic Gene Regulatory Network Downstream of mTOR Complex 1
No full textAberrant activation of the mammalian target of rapamycin complex 1 (mTORC1) is a common molecular event in a variety of pathological settings, including genetic tumor syndromes, cancer, and obesity. However, the cell-intrinsic consequences of mTORC1 activation remain poorly defined. Through a combination of unbiased genomic, metabolomic, and bioinformatic approaches, we demonstrate that mTORC1 activation is sufficient to stimulate specific metabolic pathways, including glycolysis, the oxidative arm of the pentose phosphate pathway, and de novo lipid biosynthesis. This is achieved through the activation of a transcriptional program affecting metabolic gene targets of hypoxia-inducible factor (HIF1α) and sterol regulatory element-binding protein (SREBP1 and SREBP2). We find that SREBP1 and 2 promote proliferation downstream of mTORC1, and the activation of these transcription factors is mediated by S6K1. Therefore, in addition to promoting protein synthesis, mTORC1 activates specific bioenergetic and anabolic cellular processes that are likely to contribute to human physiology and disease
Assessment of risk to infrastructure from permafrost degradation and a changing climate, Ross River
No full text"Northern Canadian communities are at the forefront of climate change. Permafrost thaw is one of the major threats that they face. Many communities, particularly those within the discontinuous permafrost zone, have ground temperatures just below 0ºC. This makes them particularly susceptible to permafrost thaw under a changing climate. Permafrost thaw and the resulting ground shifting and changes in hydrology in these areas may have broad-reaching consequences for people's ability to travel on the land and on roads, access to traditional food sources, and stability of infrastructure, among other things. This report focuses on the effect of permafrost thaw on the stability of buildings operated by Government of Yukon in Ross River, a small community in south-central Yukon" -- from Introduction
LGBTQ issues of the right to asylum and the refugee status
No full textCHARLES UNIVERSITY FACULTY OF SOCIAL SCIENCES Institute of political sciences LGBTQ issues of the right to asylum and the refugee status Master thesis 2019 Jon Landaluze Aurre Author: Jon Landaluze Aurre Supervisor: JUDr. Milan Lipovsky, Ph.D. Study programme: MAIN Academic Year: 2018/2019 Bibliographic note LANDALUZE, Jon. (2019) LGBTQ issues of the right to asylum and the refugee status. Master thesis. Charles University, Faculty of Social Sciences. Institute of Political Science. Supervisor: JUDr. Milan Lipovsky, Ph.D. Abstract Here we find a thesis on the topic of refugee protection and the specific area of LGBTQ applicants. This is a topic that still nowadays is important to analyze, since the acceptation and evolution of these specific cases is something that evolves throughout the present times. The objective of it is to first define the refugee definition and to see if the definition that is given is actually interpreted in the way that it protects this group of people worldwide. It then goes to analyze the European interpretation of the topic and the issues that usually arise when making decisions about international protection of the applicants, concluding with the problems that actually happen and the possible solutions to avoid them. Keywords Refugees, Asylum, LGBTQ, Persecution, International..
LGBTQ důvody pro azyl a uprchlický status
No full textCHARLES UNIVERSITY FACULTY OF SOCIAL SCIENCES Institute of political sciences LGBTQ issues of the right to asylum and the refugee status Master thesis 2019 Jon Landaluze Aurre Author: Jon Landaluze Aurre Supervisor: JUDr. Milan Lipovsky, Ph.D. Study programme: MAIN Academic Year: 2018/2019 Bibliographic note LANDALUZE, Jon. (2019) LGBTQ issues of the right to asylum and the refugee status. Master thesis. Charles University, Faculty of Social Sciences. Institute of Political Science. Supervisor: JUDr. Milan Lipovsky, Ph.D. Abstract Here we find a thesis on the topic of refugee protection and the specific area of LGBTQ applicants. This is a topic that still nowadays is important to analyze, since the acceptation and evolution of these specific cases is something that evolves throughout the present times. The objective of it is to first define the refugee definition and to see if the definition that is given is actually interpreted in the way that it protects this group of people worldwide. It then goes to analyze the European interpretation of the topic and the issues that usually arise when making decisions about international protection of the applicants, concluding with the problems that actually happen and the possible solutions to avoid them. Keywords Refugees, Asylum, LGBTQ, Persecution, International...Department of International RelationsKatedra mezinárodních vztahůFakulta sociálních vědFaculty of Social Science
Faro landscape hazards: Geoscience mapping for climate change adaptation planning
No full textThis report outlines the landscape hazards mapping project the Northern Climate ExChange and its partners conducted for Faro, Yukon. The report and accompanying maps can be used to support climate change adaptation planning.
Climate change is a significant challenge for northern communities, where the impacts of a warming climate are already having considerable effects (Huntington and Weller, 2005). Many people living in small, isolated communities in northern Yukon are concerned about climate-related risks in their regions. Because adverse impacts are a reality, it is important to implement measures to reduce or moderate the negative effects of climate change – in other words, to implement climate change adaptation strategies.technical reportPublishedclimate changeSurficial GeologyPermafrostlandslideslandscape hazardshydrologyGeomorphologyGeological Hazardsgeohazard
Faro Landscape Hazards: Geoscience mapping for climate change adaptation planning
No full textClimate change is a significant challenge for northern communities, where the impacts of a warming climate are already having considerable effects (Huntington and Weller, 2005). Many people living in small, isolated communities in northern Yukon are concerned about climate-related risks in their regions. Because adverse impacts are a reality, it is important to implement measures to reduce or moderate the negative effects of climate change – in other words, to implement climate change adaptation strategies.Peer reviewedFinal article publishe
Ross River landscape hazards: Geoscience mapping for climate change adaptation planning
No full textThis report outlines the landscape hazards mapping project the Northern Climate ExChange and its partners conducted for Ross River, Yukon. The report and accompanying maps can be used to support climate change adaptation planning.
Climate change is a significant challenge for northern communities, where the impacts of a warming climate are already having considerable effects (Huntington and Weller, 2005). Many people living in small, isolated communities in northern Yukon are concerned about climate-related risks in their regions. Because adverse impacts are a reality, it is important to implement measures to reduce or moderate the negative effects of climate change – in other words, to implement climate change adaptation strategies.technical reportPublishedclimate changeSurficial GeologyRoss RiverPermafrostlandslideslandscape hazardshydrologyGeomorphologyGeological Hazardsgeohazard
Ross River landscape hazards: Geoscience mapping for climate change adaptation planning
No full textClimate change is a significant challenge for northern communities, where the impacts of a warming climate are already having considerable effects (Huntington and Weller, 2005). Many people living in small, isolated communities in northern Yukon are concerned about climate-related risks in their regions. Because adverse impacts are a reality, it is important to implement measures to reduce or moderate the negative effects of climate change – in other words, to implement climate change adaptation strategies.Peer reviewedFinal article publishe
