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Article ; Online: GLUT4 dispersal at the plasma membrane of adipocytes: a super-resolved journey.

Geiser, Angéline / Foylan, Shannan / Tinning, Peter W / Bryant, Nia J / Gould, Gwyn W

2023 Volume 43, Issue 10

Abstract: In adipose tissue, insulin stimulates glucose uptake by mediating the translocation of GLUT4 from intracellular vesicles to the plasma membrane. In 2010, insulin was revealed to also have a fundamental impact on the spatial distribution of GLUT4 within ... ...

Abstract	In adipose tissue, insulin stimulates glucose uptake by mediating the translocation of GLUT4 from intracellular vesicles to the plasma membrane. In 2010, insulin was revealed to also have a fundamental impact on the spatial distribution of GLUT4 within the plasma membrane, with the existence of two GLUT4 populations at the plasma membrane being defined: (1) as stationary clusters and (2) as diffusible monomers. In this model, in the absence of insulin, plasma membrane-fused GLUT4 are found to behave as clusters. These clusters are thought to arise from exocytic events that retain GLUT4 at their fusion sites; this has been proposed to function as an intermediate hub between GLUT4 exocytosis and re-internalisation. By contrast, insulin stimulation induces the dispersal of GLUT4 clusters into monomers and favours a distinct type of GLUT4-vesicle fusion event, known as fusion-with-release exocytosis. Here, we review how super-resolution microscopy approaches have allowed investigation of the characteristics of plasma membrane-fused GLUT4 and further discuss regulatory step(s) involved in the GLUT4 dispersal machinery, introducing the scaffold protein EFR3 which facilitates localisation of phosphatidylinositol 4-kinase type IIIα (PI4KIIIα) to the cell surface. We consider how dispersal may be linked to the control of transporter activity, consider whether macro-organisation may be a widely used phenomenon to control proteins within the plasma membrane, and speculate on the origin of different forms of GLUT4-vesicle exocytosis.
MeSH term(s)	Adipocytes/metabolism ; Cell Membrane/metabolism ; Adipose Tissue/metabolism ; Membrane Fusion ; Insulin/metabolism ; Glucose Transporter Type 4/metabolism
Chemical Substances	Insulin ; Glucose Transporter Type 4
Language	English
Publishing date	2023-10-04
Publishing country	England
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	764946-0
ISSN	1573-4935 ; 0144-8463
ISSN (online)	1573-4935
ISSN	0144-8463
DOI	10.1042/BSR20230946
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Article ; Online: Soft sensor for in-line quality control of turning processes based on non-destructive testing techniques and advanced data fusion

Böttger, David / González, Germán / Geiser, Alexander / Kempf, Daniel / Lanza, Gisela / Schulze, Volker / Wolter, Bernd

2024

Abstract: 197 ... 206 ... This study describes the systematic process of training, testing, and validating a soft sensor designed for quality control of a turning process on components made of AISI 4140 steel. The soft sensor allows product quality to be predicted and ...

Abstract	197 206 This study describes the systematic process of training, testing, and validating a soft sensor designed for quality control of a turning process on components made of AISI 4140 steel. The soft sensor allows product quality to be predicted and unfavorable surface conditions to be identified, in particular the appearance of a phenomenon known as "White Layer", often characterized in the case of AISI 4140 steel by an ultra-fine-grained microstructure (UFG). Basis of the soft sensor is a data fusion supported by non-destructive testing techniques (NDT), particularly micromagnetic methods (3MA). A critical part of this work is to address challenges such as lift-off compensation and in-process detection using 3MA. The application of machine-learning techniques, including Principal Component Analysis (PCA) and regression analysis, is detailed. These techniques result in robust models capable of detecting the occurrence of the White Layer phenomenon while minimizing the influence of measurement setup variations and process disturbances. In addition, the study demonstrates the integration of NDT into the machining process which drives the soft sensor and allows suitable adjustments of the process parameters. The data-driven soft sensor approach demonstrates a possible In-Line control system and discusses different control theories and their respective advantages and disadvantages. This system can effectively set targeted surface conditions in real time during the turning process. 18 2
Keywords	non-destructive testing techniques (NDT) ; Principal Component Analysis (PCA) ; quality control ; machine-learning techniques ; AISI 4140 steel ; DDC::600 Technik ; Medizin ; angewandte Wissenschaften
Subject code	670
Language	English
Publishing country	de
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Benchmarking Thiolate-Driven Photoswitching of Cyanine Dyes.

Herdly, Lucas / Tinning, Peter W / Geiser, Angéline / Taylor, Holly / Gould, Gwyn W / van de Linde, Sebastian

The journal of physical chemistry. B

2023 Volume 127, Issue 3, Page(s) 732–741

Abstract: Carbocyanines are among the best performing dyes in single-molecule localization microscopy (SMLM), but their performance critically relies on optimized photoswitching buffers. Here, we study the versatile role of thiols in cyanine photoswitching at ... ...

Abstract	Carbocyanines are among the best performing dyes in single-molecule localization microscopy (SMLM), but their performance critically relies on optimized photoswitching buffers. Here, we study the versatile role of thiols in cyanine photoswitching at varying intensities generated in a single acquisition by a microelectromechanical systems (MEMS) mirror placed in the excitation path. The key metrics we have analyzed as a function of the thiolate concentration are photon budget, on-state and off-state lifetimes and the corresponding impact on image resolution. We show that thiolate acts as a concentration bandpass filter for the maximum achievable resolution and determine a minimum of ∼1 mM is necessary to facilitate SMLM measurements. We also identify a concentration bandwidth of 1-16 mM in which the photoswitching performance can be balanced between high molecular brightness and high off-time to on-time ratios. Furthermore, we monitor the performance of the popular oxygen scavenger system based on glucose and glucose oxidase over time and show simple measures to avoid acidification during prolonged measurements. Finally, the impact of buffer settings is quantitatively tested on the distribution of the glucose transporter protein 4 within the plasma membrane of adipocytes. Our work provides a general strategy for achieving optimal resolution in SMLM with relevance for the development of novel buffers and dyes.
MeSH term(s)	Benchmarking ; Fluorescent Dyes ; Carbocyanines ; Single Molecule Imaging/methods ; Quinolines
Chemical Substances	Fluorescent Dyes ; Carbocyanines ; Quinolines
Language	English
Publishing date	2023-01-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1520-5207
ISSN (online)	1520-5207
DOI	10.1021/acs.jpcb.2c06872
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Article ; Online: GLUT4 translocation and dispersal operate in multiple cell types and are negatively correlated with cell size in adipocytes.

Koester, Anna M / Geiser, Angéline / Bowman, Peter R T / van de Linde, Sebastian / Gadegaard, Nikolaj / Bryant, Nia J / Gould, Gwyn W

Scientific reports

2022 Volume 12, Issue 1, Page(s) 20535

Abstract: The regulated translocation of the glucose transporter, GLUT4, to the surface of adipocytes and muscle is a key action of insulin. This is underpinned by the delivery and fusion of GLUT4-containing vesicles with the plasma membrane. Recent studies have ... ...

Abstract	The regulated translocation of the glucose transporter, GLUT4, to the surface of adipocytes and muscle is a key action of insulin. This is underpinned by the delivery and fusion of GLUT4-containing vesicles with the plasma membrane. Recent studies have revealed that a further action of insulin is to mediate the dispersal of GLUT4 molecules away from the site of GLUT4 vesicle fusion with the plasma membrane. Although shown in adipocytes, whether insulin-stimulated dispersal occurs in other cells and/or is exhibited by other proteins remains a matter of debate. Here we show that insulin stimulates GLUT4 dispersal in the plasma membrane of adipocytes, induced pluripotent stem cell-derived cardiomyocytes and HeLa cells, suggesting that this phenomenon is specific to GLUT4 expressed in all cell types. By contrast, insulin-stimulated dispersal of TfR was not observed in HeLa cells, suggesting that the mechanism may be unique to GLUT4. Consistent with dispersal being an important physiological mechanism, we observed that insulin-stimulated GLUT4 dispersal is reduced under conditions of insulin resistance. Adipocytes of different sizes have been shown to exhibit distinct metabolic properties: larger adipocytes exhibit reduced insulin-stimulated glucose transport compared to smaller cells. Here we show that both GLUT4 delivery to the plasma membrane and GLUT4 dispersal are reduced in larger adipocytes, supporting the hypothesis that larger adipocytes are refractory to insulin challenge compared to their smaller counterparts, even within a supposedly homogeneous population of cells.
MeSH term(s)	Humans ; HeLa Cells ; Adipocytes ; Cell Size ; Insulin/pharmacology ; Translocation, Genetic ; Myocytes, Cardiac
Chemical Substances	Insulin
Language	English
Publishing date	2022-11-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-24736-y
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Article ; Online: Innovations in nanotechnology for water treatment

Gehrke I / Geiser A / Somborn-Schulz A

Nanotechnology, Science and Applications, Vol 2015, Iss default, Pp 1-

2015 Volume 17

Abstract: Ilka Gehrke, Andreas Geiser, Annette Somborn-SchulzFraunhofer Institute for Environmental, Safety and Energy Technology UMSICHT, Oberhausen, GermanyAbstract: Important challenges in the global water situation, mainly resulting from worldwide population ... ...

Abstract	Ilka Gehrke, Andreas Geiser, Annette Somborn-SchulzFraunhofer Institute for Environmental, Safety and Energy Technology UMSICHT, Oberhausen, GermanyAbstract: Important challenges in the global water situation, mainly resulting from worldwide population growth and climate change, require novel innovative water technologies in order to ensure a supply of drinking water and reduce global water pollution. Against this background, the adaptation of highly advanced nanotechnology to traditional process engineering offers new opportunities in technological developments for advanced water and wastewater technology processes. Here, an overview of recent advances in nanotechnologies for water and wastewater treatment processes is provided, including nanobased materials, such as nanoadsorbents, nanometals, nanomembranes, and photocatalysts. The beneficial properties of these materials as well as technical barriers when compared with conventional processes are reported. The state of commercialization is presented and an outlook on further research opportunities is given for each type of nanobased material and process. In addition to the promising technological enhancements, the limitations of nanotechnology for water applications, such as laws and regulations as well as potential health risks, are summarized. The legal framework according to nanoengineered materials and processes that are used for water and wastewater treatment is considered for European countries and for the USA.Keywords: nanotechnology, water technology, nanoadsorbents, nanometals, nanomembranes, photocatalysis
Keywords	Chemical technology ; TP1-1185 ; Science ; Q
Subject code	690
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Dove Medical Press
Document type	Article ; Online
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Article ; Online: EFR3 and phosphatidylinositol 4-kinase IIIα regulate insulin-stimulated glucose transport and GLUT4 dispersal in 3T3-L1 adipocytes.

Koester, Anna M / Geiser, Angéline / Laidlaw, Kamilla M E / Morris, Silke / Cutiongco, Marie F A / Stirrat, Laura / Gadegaard, Nikolaj / Boles, Eckhard / Black, Hannah L / Bryant, Nia J / Gould, Gwyn W

Bioscience reports

2022 Volume 42, Issue 7

Abstract: Insulin stimulates glucose transport in muscle and adipocytes. This is achieved by regulated delivery of intracellular glucose transporter (GLUT4)-containing vesicles to the plasma membrane where they dock and fuse, resulting in increased cell surface ... ...

Abstract	Insulin stimulates glucose transport in muscle and adipocytes. This is achieved by regulated delivery of intracellular glucose transporter (GLUT4)-containing vesicles to the plasma membrane where they dock and fuse, resulting in increased cell surface GLUT4 levels. Recent work identified a potential further regulatory step, in which insulin increases the dispersal of GLUT4 in the plasma membrane away from the sites of vesicle fusion. EFR3 is a scaffold protein that facilitates localization of phosphatidylinositol 4-kinase type IIIα to the cell surface. Here we show that knockdown of EFR3 or phosphatidylinositol 4-kinase type IIIα impairs insulin-stimulated glucose transport in adipocytes. Using direct stochastic reconstruction microscopy, we also show that EFR3 knockdown impairs insulin stimulated GLUT4 dispersal in the plasma membrane. We propose that EFR3 plays a previously unidentified role in controlling insulin-stimulated glucose transport by facilitating dispersal of GLUT4 within the plasma membrane.
MeSH term(s)	1-Phosphatidylinositol 4-Kinase/metabolism ; 3T3-L1 Cells ; Adipocytes/metabolism ; Animals ; Biological Transport ; Cell Membrane/metabolism ; Glucose/metabolism ; Glucose Transport Proteins, Facilitative/metabolism ; Glucose Transporter Type 4/genetics ; Glucose Transporter Type 4/metabolism ; Insulin/metabolism ; Insulin/pharmacology ; Mice
Chemical Substances	Glucose Transport Proteins, Facilitative ; Glucose Transporter Type 4 ; Insulin ; 1-Phosphatidylinositol 4-Kinase (EC 2.7.1.67) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2022-06-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	764946-0
ISSN	1573-4935 ; 0144-8463
ISSN (online)	1573-4935
ISSN	0144-8463
DOI	10.1042/BSR20221181
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Article: Innovations in nanotechnology for water treatment.

Gehrke, Ilka / Geiser, Andreas / Somborn-Schulz, Annette

Nanotechnology, science and applications

2015 Volume 8, Page(s) 1–17

Abstract: Important challenges in the global water situation, mainly resulting from worldwide population growth and climate change, require novel innovative water technologies in order to ensure a supply of drinking water and reduce global water pollution. Against ...

Abstract	Important challenges in the global water situation, mainly resulting from worldwide population growth and climate change, require novel innovative water technologies in order to ensure a supply of drinking water and reduce global water pollution. Against this background, the adaptation of highly advanced nanotechnology to traditional process engineering offers new opportunities in technological developments for advanced water and wastewater technology processes. Here, an overview of recent advances in nanotechnologies for water and wastewater treatment processes is provided, including nanobased materials, such as nanoadsorbents, nanometals, nanomembranes, and photocatalysts. The beneficial properties of these materials as well as technical barriers when compared with conventional processes are reported. The state of commercialization is presented and an outlook on further research opportunities is given for each type of nanobased material and process. In addition to the promising technological enhancements, the limitations of nanotechnology for water applications, such as laws and regulations as well as potential health risks, are summarized. The legal framework according to nanoengineered materials and processes that are used for water and wastewater treatment is considered for European countries and for the USA.
Language	English
Publishing date	2015-01-06
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	2494782-9
ISSN	1177-8903
ISSN	1177-8903
DOI	10.2147/NSA.S43773
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Article ; Online: Knockout of syntaxin-4 in 3T3-L1 adipocytes reveals new insight into GLUT4 trafficking and adiponectin secretion.

Black, Hannah L / Livingstone, Rachel / Mastick, Cynthia C / Al Tobi, Mohammed / Taylor, Holly / Geiser, Angéline / Stirrat, Laura / Kioumourtzoglou, Dimitrios / Petrie, John R / Boyle, James G / Bryant, Nia J / Gould, Gwyn W

Journal of cell science

2022 Volume 135, Issue 1

Abstract: Adipocytes are key to metabolic regulation, exhibiting insulin-stimulated glucose transport that is underpinned by the insulin-stimulated delivery of glucose transporter type 4 (SLC2A4, also known and hereafter referred to as GLUT4)-containing vesicles ... ...

Abstract	Adipocytes are key to metabolic regulation, exhibiting insulin-stimulated glucose transport that is underpinned by the insulin-stimulated delivery of glucose transporter type 4 (SLC2A4, also known and hereafter referred to as GLUT4)-containing vesicles to the plasma membrane where they dock and fuse, and increase cell surface GLUT4 levels. Adipocytokines, such as adiponectin, are secreted via a similar mechanism. We used genome editing to knock out syntaxin-4, a protein reported to mediate fusion between GLUT4-containing vesicles and the plasma membrane in 3T3-L1 adipocytes. Syntaxin-4 knockout reduced insulin-stimulated glucose transport and adiponectin secretion by ∼50% and reduced GLUT4 levels. Ectopic expression of haemagglutinin (HA)-tagged GLUT4 conjugated to GFP showed that syntaxin-4-knockout cells retain significant GLUT4 translocation capacity, demonstrating that syntaxin-4 is dispensable for insulin-stimulated GLUT4 translocation. Analysis of recycling kinetics revealed only a modest reduction in the exocytic rate of GLUT4 in knockout cells, and little effect on endocytosis. These analyses demonstrate that syntaxin-4 is not always rate limiting for GLUT4 delivery to the cell surface. In sum, we show that syntaxin-4 knockout results in reduced insulin-stimulated glucose transport, depletion of cellular GLUT4 levels and inhibition of adiponectin secretion but has only modest effects on the translocation capacity of the cells. This article has an associated First Person interview with Hannah L. Black and Rachel Livingstone, joint first authors of the paper.
MeSH term(s)	3T3 Cells ; 3T3-L1 Cells ; Adipocytes/metabolism ; Adiponectin/genetics ; Animals ; Cell Membrane/metabolism ; Glucose Transporter Type 4/genetics ; Humans ; Insulin/metabolism ; Mice ; Qa-SNARE Proteins/genetics
Chemical Substances	Adiponectin ; Glucose Transporter Type 4 ; Insulin ; Qa-SNARE Proteins ; Stx4a protein, mouse
Language	English
Publishing date	2022-01-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
DOI	10.1242/jcs.258375
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Zs.A 1200: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 14: Show issues

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Article ; Online: Pharmacological Evaluation of a Pegylated Urocortin-1 Peptide in Experimental Autoimmune Disease Models.

Heuer, Josef G / Meyer, Catalina M / Baker, Hana E / Geiser, Andrea / Lucchesi, Jonathan / Xu, Daniel / Hamang, Matthew / Martin, Jennifer A / Hu, Charlie / Roth, Kenneth D / Thirunavukkarasu, Kannan / Alsina-Fernandez, Jorge / Ma, Yanfei L

The Journal of pharmacology and experimental therapeutics

2022 Volume 382, Issue 3, Page(s) 287–298

Abstract: Urocortin-1 (UCN1) is a member of the corticotropin releasing hormone (CRH) family of peptides that acts through CRH-receptor 1 (CRHR1) and CRH-receptor 2 (CRHR2). UCN1 can induce the adrenocorticotropin hormone and downstream glucocorticoids through ... ...

Abstract	Urocortin-1 (UCN1) is a member of the corticotropin releasing hormone (CRH) family of peptides that acts through CRH-receptor 1 (CRHR1) and CRH-receptor 2 (CRHR2). UCN1 can induce the adrenocorticotropin hormone and downstream glucocorticoids through CRHR1 and promote beneficial metabolic effects through CRHR2. UCN1 has a short half-life and has been shown to improve experimental autoimmune disease. A pegylated UCN1 peptide (PEG-hUCN1) was generated to extend half-life and was tested in multiple experimental autoimmune disease models and in healthy mice to determine effects on corticosterone induction, autoimmune disease, and glucocorticoid induced adverse effects. Cardiovascular effects were also assessed by telemetry. PEG-hUCN1 demonstrated a dose dependent 4-6-fold elevation of serum corticosterone and significantly improved autoimmune disease comparable to prednisolone in several experimental models. In healthy mice, PEG-hUCN1 showed less adverse effects compared with corticosterone treatment. PEG-hUCN1 peptide induced an initial 30% reduction in blood pressure that was followed by a gradual and sustained 30% increase in blood pressure at the highest dose. Additionally, an adeno-associated viral 8 (AAV8) UCN1 was used to assess adverse effects of chronic elevation of UCN1 in wild type and CRHR2 knockout mice. Chronic UCN1 expression by an AAV8 approach in wild type and CRHR2 knockout mice demonstrated an important role of CRHR2 in countering the adverse metabolic effects of elevated corticosterone from UCN1. Our findings demonstrate that PEG-hUCN1 shows profound effects in treating autoimmune disease with an improved safety profile relative to corticosterone and that CRHR2 activity is important in metabolic regulation. SIGNIFICANCE STATEMENT: This study reports the generation and characterization of a pegylated UCN1 peptide and the role of CRHR2 in UCN1-induced metabolic effects. The potency/selectivity, pharmacokinetic properties, pharmacodynamic effects, and efficacy in four autoimmune models and safety profiles are presented. This pegylated UCN1 shows potential for treating autoimmune diseases with reduced adverse effects compared to corticosterone treatment. Continuous exposure to UCN1 through an AAV8 approach demonstrates some glucocorticoid mediated adverse metabolic effects that are exacerbated in the absence of the CRHR2 receptor.
MeSH term(s)	Animals ; Autoimmune Diseases/drug therapy ; Corticosterone ; Corticotropin-Releasing Hormone/metabolism ; Corticotropin-Releasing Hormone/pharmacology ; Glucocorticoids ; Mice ; Mice, Knockout ; Models, Theoretical ; Polyethylene Glycols/pharmacology ; Receptors, Corticotropin-Releasing Hormone/metabolism ; Urocortins/metabolism ; Urocortins/pharmacology
Chemical Substances	Glucocorticoids ; Receptors, Corticotropin-Releasing Hormone ; Urocortins ; Polyethylene Glycols (3WJQ0SDW1A) ; Corticotropin-Releasing Hormone (9015-71-8) ; Corticosterone (W980KJ009P)
Language	English
Publishing date	2022-06-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	3106-9
ISSN	1521-0103 ; 0022-3565
ISSN (online)	1521-0103
ISSN	0022-3565
DOI	10.1124/jpet.122.001151
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Book: Social exclusion and conflict transformation in Nepal: women, Dalit and ethnic groups

Geiser, Alexandra

FAST country risk profile Nepal

(Working paper / Swisspeace ; 2005,5)

2005

Author's details	Alexandra Geiser
Series title	Working paper / Swisspeace ; 2005,5
Language	English ; German ; French
Size	40 S
Publisher	Swisspeace
Publishing place	Bern
Document type	Book
Note	Zsfassung. engl., dt., und franz.
ISBN	3908230624 ; 9783908230625
Database	Former special subject collection: coastal and deep sea fishing

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