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Article ; Online: Fluorogenic Chemical Probes for Wash-free Imaging of Cell Membrane Damage in Ferroptosis, Necrosis, and Axon Injury.

Mauker, Philipp / Beckmann, Daniela / Kitowski, Annabel / Heise, Constanze / Wientjens, Chantal / Davidson, Andrew J / Wanderoy, Simone / Fabre, Gabin / Harbauer, Angelika B / Wood, Will / Wilhelm, Christoph / Thorn-Seshold, Julia / Misgeld, Thomas / Kerschensteiner, Martin / Thorn-Seshold, Oliver

Journal of the American Chemical Society

2024

Abstract: Selectively labeling cells with damaged membranes is needed not only for identifying dead cells in culture, but also for imaging membrane barrier dysfunction in ... ...

Abstract	Selectively labeling cells with damaged membranes is needed not only for identifying dead cells in culture, but also for imaging membrane barrier dysfunction in pathologies
Language	English
Publishing date	2024-04-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/jacs.3c07662
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Article: Claudin tight junction proteins: novel aspects in paracellular transport.

Will, Constanze / Fromm, Michael / Müller, Dominik

Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis

2008 Volume 28, Issue 6, Page(s) 577–584

Abstract: Claudins are essential components of the intercellular tight junction and major determinants of paracellular solute fluxes across epithelia and endothelia. Many members of this family display a distinct charge or size specificity, whereas others render ... ...

Abstract	Claudins are essential components of the intercellular tight junction and major determinants of paracellular solute fluxes across epithelia and endothelia. Many members of this family display a distinct charge or size specificity, whereas others render the epithelium impermeable to transport. Due to intercellular localization, claudin-mediated transport processes are passive and driven by an electrochemical gradient. In epithelial tissues, claudins exhibit a temporal-spatial expression pattern corresponding with regional and local solute transport profiles. Whereas paracellular transport mechanisms in organs such as intestine and kidney have been extensively investigated, little is known about the molecular mechanisms determining solute transport in the peritoneum, and thus the determinants of peritoneal dialysis. Given the ubiquitous expression of claudins in endothelia and epithelia, it is predictable that claudins also contribute to pore formation and determination in the peritoneum, and that they are involved in solute flux. Therefore, we review the basic characteristics of claudin family members and their function as exemplified in renal tubular transport and give an outlook to what extent claudin family members might be of importance for solute reabsorption across the peritoneal membrane.
MeSH term(s)	Absorption ; Animals ; Claudin-1 ; Dialysis Solutions/metabolism ; Epithelium/metabolism ; Humans ; Kidney Tubules/physiology ; Loop of Henle/metabolism ; Membrane Proteins/genetics ; Membrane Proteins/physiology ; Peritoneal Dialysis ; Peritoneum/metabolism ; Tight Junctions/physiology
Chemical Substances	CLDN1 protein, human ; Claudin-1 ; Dialysis Solutions ; Membrane Proteins
Language	English
Publishing date	2008-10-27
Publishing country	United States
Document type	Comment ; Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	645010-6
ISSN	0896-8608
ISSN	0896-8608
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Book ; Online ; Thesis: Generierung und Charakterisierung Claudin 16 und Claudin 10 defizienter Mäuse

Will, Constanze [Verfasser] / Tzschentke, Barbara [Akademischer Betreuer] / Müller, Dominik [Akademischer Betreuer] / Fromm, Michael [Akademischer Betreuer]

2011

Author's details	Constanze Will. Gutachter: Barbara Tzschentke ; Dominik Müller ; Michael Fromm
Keywords	Biowissenschaften, Biologie ; Life Science, Biology
Subject code	sg570
Language	German
Publisher	Humboldt Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I
Publishing place	Berlin
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article: Evidence of initial success for China exiting COVID-19 social distancing policy after achieving containment.

Ainslie, Kylie E C / Walters, Caroline E / Fu, Han / Bhatia, Sangeeta / Wang, Haowei / Xi, Xiaoyue / Baguelin, Marc / Bhatt, Samir / Boonyasiri, Adhiratha / Boyd, Olivia / Cattarino, Lorenzo / Ciavarella, Constanze / Cucunuba, Zulma / Cuomo-Dannenburg, Gina / Dighe, Amy / Dorigatti, Ilaria / van Elsland, Sabine L / FitzJohn, Rich / Gaythorpe, Katy /

Wellcome open research

2020 Volume 5, Page(s) 81

Abstract: ... ...

Abstract	Background
Keywords	covid19
Language	English
Publishing date	2020-10-01
Publishing country	England
Document type	Journal Article
ISSN	2398-502X
ISSN	2398-502X
DOI	10.12688/wellcomeopenres.15843.2
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Article: HPV typing and CGH analysis for the differentiation of primary and metastatic squamous cell carcinomas of the aerodigestive tract.

Will, Constanze / Schewe, Christiane / Schluns, Karsten / Petersen, Iver

Cellular oncology : the official journal of the International Society for Cellular Oncology

2001 Volume 28, Issue 3, Page(s) 97–105

Abstract: Human papilloma virus (HPV) typing and Comparative Genomic Hybridisation (CGH) analysis can be used in the classification of multiple tumours of the aerodigestive tract for the differentiation between secondary malignancy versus metastasis. We present 3 ... ...

Abstract	Human papilloma virus (HPV) typing and Comparative Genomic Hybridisation (CGH) analysis can be used in the classification of multiple tumours of the aerodigestive tract for the differentiation between secondary malignancy versus metastasis. We present 3 exemplary cases of patients with multiple squamous cell carcinomas, localised within the head and neck region, cervical lymph node and the lung. In two patients, HPV typing identified HPV type 16 in the tonsillar carcinomas and the corresponding cervical lymph node and lung carcinoma indicating that the latter were metastatic spreads. In case 1, CGH confirmed the clonal relationship. Case two showed a peculiar syncytial growth pattern with lymphocytic infiltration which may constitute a potential morphological marker for HPV infection. In case three, a vallecular carcinoma was HPV negative while a lung cancer was positive for HPV type 6 indicating two independent primary tumours. Our case triplet illustrates the variability of HPV infection in squamous cell cancer of the aerodigestive tract and power as well as limitations of morphology, HPV typing and tumour genetics in the classification of multiple tumours.
MeSH term(s)	Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/pathology ; Carcinoma, Squamous Cell/virology ; DNA, Viral/analysis ; DNA, Viral/genetics ; Female ; Genome, Human/genetics ; Head and Neck Neoplasms/genetics ; Head and Neck Neoplasms/pathology ; Head and Neck Neoplasms/virology ; Human papillomavirus 16/genetics ; Human papillomavirus 6/genetics ; Humans ; Lung Neoplasms/genetics ; Lung Neoplasms/secondary ; Lung Neoplasms/virology ; Male ; Middle Aged ; Nucleic Acid Hybridization/methods ; Papillomaviridae/classification ; Papillomaviridae/genetics ; Papillomavirus Infections/genetics ; Papillomavirus Infections/pathology ; Papillomavirus Infections/virology ; Tonsillar Neoplasms/genetics ; Tonsillar Neoplasms/pathology ; Tonsillar Neoplasms/virology
Chemical Substances	DNA, Viral
Language	English
Publishing date	2001-01-10
Publishing country	Netherlands
Document type	Case Reports ; Comparative Study ; Journal Article
ZDB-ID	2157351-7
ISSN	1875-8606 ; 1570-5870
ISSN (online)	1875-8606
ISSN	1570-5870
DOI	10.1155/2006/619539
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Article ; Online: Deletion of claudin-10 (Cldn10) in the thick ascending limb impairs paracellular sodium permeability and leads to hypermagnesemia and nephrocalcinosis.

Breiderhoff, Tilman / Himmerkus, Nina / Stuiver, Marchel / Mutig, Kerim / Will, Constanze / Meij, Iwan C / Bachmann, Sebastian / Bleich, Markus / Willnow, Thomas E / Müller, Dominik

Proceedings of the National Academy of Sciences of the United States of America

2012 Volume 109, Issue 35, Page(s) 14241–14246

Abstract: In the kidney, tight junction proteins contribute to segment specific selectivity and permeability of paracellular ion transport. In the thick ascending limb (TAL) of Henle's loop, chloride is reabsorbed transcellularly, whereas sodium reabsorption takes ...

Abstract	In the kidney, tight junction proteins contribute to segment specific selectivity and permeability of paracellular ion transport. In the thick ascending limb (TAL) of Henle's loop, chloride is reabsorbed transcellularly, whereas sodium reabsorption takes transcellular and paracellular routes. TAL salt transport maintains the concentrating ability of the kidney and generates a transepithelial voltage that drives the reabsorption of calcium and magnesium. Thus, functionality of TAL ion transport depends strongly on the properties of the paracellular pathway. To elucidate the role of the tight junction protein claudin-10 in TAL function, we generated mice with a deletion of Cldn10 in this segment. We show that claudin-10 determines paracellular sodium permeability, and that its loss leads to hypermagnesemia and nephrocalcinosis. In isolated perfused TAL tubules of claudin-10-deficient mice, paracellular permeability of sodium is decreased, and the relative permeability of calcium and magnesium is increased. Moreover, furosemide-inhibitable transepithelial voltage is increased, leading to a shift from paracellular sodium transport to paracellular hyperabsorption of calcium and magnesium. These data identify claudin-10 as a key factor in control of cation selectivity and transport in the TAL, and deficiency in this pathway as a cause of nephrocalcinosis.
MeSH term(s)	Animals ; Biological Transport/genetics ; Biological Transport/physiology ; Calcium/metabolism ; Claudins/genetics ; Claudins/metabolism ; Drinking/physiology ; Embryonic Stem Cells/physiology ; Gene Deletion ; Homeostasis/genetics ; Homeostasis/physiology ; Loop of Henle/metabolism ; Magnesium/blood ; Metabolic Diseases/genetics ; Metabolic Diseases/metabolism ; Metabolic Diseases/physiopathology ; Mice ; Mice, Knockout ; Nephrocalcinosis/genetics ; Nephrocalcinosis/metabolism ; Nephrocalcinosis/physiopathology ; Phenotype ; Sodium/metabolism ; Water Deprivation/physiology
Chemical Substances	Claudins ; claudin 10 ; Sodium (9NEZ333N27) ; Magnesium (I38ZP9992A) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2012-08-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1203834109
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Article ; Online: Evidence of initial success for China exiting COVID-19 social distancing policy after achieving containment [version 2; peer review

Kylie E. C. Ainslie / Caroline E. Walters / Han Fu / Sangeeta Bhatia / Haowei Wang / Xiaoyue Xi / Marc Baguelin / Samir Bhatt / Adhiratha Boonyasiri / Olivia Boyd / Lorenzo Cattarino / Constanze Ciavarella / Zulma Cucunuba / Gina Cuomo-Dannenburg / Amy Dighe / Ilaria Dorigatti / Sabine L van Elsland / Rich FitzJohn / Katy Gaythorpe /

Wellcome Open Research, Vol

2 approved]

2020 Volume 5

Abstract: Background: The COVID-19 epidemic was declared a Global Pandemic by WHO on 11 March 2020. By 24 March 2020, over 440,000 cases and almost 20,000 deaths had been reported worldwide. In response to the fast-growing epidemic, which began in the Chinese city ...

Abstract	Background: The COVID-19 epidemic was declared a Global Pandemic by WHO on 11 March 2020. By 24 March 2020, over 440,000 cases and almost 20,000 deaths had been reported worldwide. In response to the fast-growing epidemic, which began in the Chinese city of Wuhan, Hubei, China imposed strict social distancing in Wuhan on 23 January 2020 followed closely by similar measures in other provinces. These interventions have impacted economic productivity in China, and the ability of the Chinese economy to resume without restarting the epidemic was not clear. Methods: Using daily reported cases from mainland China and Hong Kong SAR, we estimated transmissibility over time and compared it to daily within-city movement, as a proxy for economic activity. Results: Initially, within-city movement and transmission were very strongly correlated in the five mainland provinces most affected by the epidemic and Beijing. However, that correlation decreased rapidly after the initial sharp fall in transmissibility. In general, towards the end of the study period, the correlation was no longer apparent, despite substantial increases in within-city movement. A similar analysis for Hong Kong shows that intermediate levels of local activity were maintained while avoiding a large outbreak. At the very end of the study period, when China began to experience the re-introduction of a small number of cases from Europe and the United States, there is an apparent up-tick in transmission. Conclusions: Although these results do not preclude future substantial increases in incidence, they suggest that after very intense social distancing (which resulted in containment), China successfully exited its lockdown to some degree. Elsewhere, movement data are being used as proxies for economic activity to assess the impact of interventions. The results presented here illustrate how the eventual decorrelation between transmission and movement is likely a key feature of successful COVID-19 exit strategies.
Keywords	Medicine ; R ; Science ; Q ; covid19
Subject code	950
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	Wellcome
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Evidence of initial success for China exiting COVID-19 social distancing policy after achieving containment [version 1; peer review

Kylie E C Ainslie / Caroline E. Walters / Han Fu / Sangeeta Bhatia / Haowei Wang / Xiaoyue Xi / Marc Baguelin / Samir Bhatt / Adhiratha Boonyasiri / Olivia Boyd / Lorenzo Cattarino / Constanze Ciavarella / Zulma Cucunuba / Gina Cuomo-Dannenburg / Amy Dighe / Ilaria Dorigatti / Sabine L van Elsland / Rich FitzJohn / Katy Gaythorpe /

Wellcome Open Research, Vol

2 approved]

2020 Volume 5

Abstract	Background: The COVID-19 epidemic was declared a Global Pandemic by WHO on 11 March 2020. By 24 March 2020, over 440,000 cases and almost 20,000 deaths had been reported worldwide. In response to the fast-growing epidemic, which began in the Chinese city of Wuhan, Hubei, China imposed strict social distancing in Wuhan on 23 January 2020 followed closely by similar measures in other provinces. These interventions have impacted economic productivity in China, and the ability of the Chinese economy to resume without restarting the epidemic was not clear. Methods: Using daily reported cases from mainland China and Hong Kong SAR, we estimated transmissibility over time and compared it to daily within-city movement, as a proxy for economic activity. Results: Initially, within-city movement and transmission were very strongly correlated in the five mainland provinces most affected by the epidemic and Beijing. However, that correlation decreased rapidly after the initial sharp fall in transmissibility. In general, towards the end of the study period, the correlation was no longer apparent, despite substantial increases in within-city movement. A similar analysis for Hong Kong shows that intermediate levels of local activity were maintained while avoiding a large outbreak. At the very end of the study period, when China began to experience the re-introduction of a small number of cases from Europe and the United States, there is an apparent up-tick in transmission. Conclusions: Although these results do not preclude future substantial increases in incidence, they suggest that after very intense social distancing (which resulted in containment), China successfully exited its lockdown to some degree. Elsewhere, movement data are being used as proxies for economic activity to assess the impact of interventions. The results presented here illustrate how the eventual decorrelation between transmission and movement is likely a key feature of successful COVID-19 exit strategies.
Keywords	Medicine ; R ; Science ; Q
Subject code	950
Language	English
Publishing date	2020-04-01T00:00:00Z
Publisher	Wellcome
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Targeted deletion of murine Cldn16 identifies extra- and intrarenal compensatory mechanisms of Ca2+ and Mg2+ wasting.

Will, Constanze / Breiderhoff, Tilman / Thumfart, Julia / Stuiver, Marchel / Kopplin, Kathrin / Sommer, Kerstin / Günzel, Dorothee / Querfeld, Uwe / Meij, Iwan C / Shan, Qixian / Bleich, Markus / Willnow, Thomas E / Müller, Dominik

American journal of physiology. Renal physiology

2010 Volume 298, Issue 5, Page(s) F1152–61

Abstract: Claudin-16 (CLDN16) is critical for renal paracellular epithelial transport of Ca(2+) and Mg(2+) in the thick ascending loop of Henle. To gain novel insights into the role of CLDN16 in renal Ca(2+) and Mg(2+) homeostasis and the pathological mechanisms ... ...

Abstract	Claudin-16 (CLDN16) is critical for renal paracellular epithelial transport of Ca(2+) and Mg(2+) in the thick ascending loop of Henle. To gain novel insights into the role of CLDN16 in renal Ca(2+) and Mg(2+) homeostasis and the pathological mechanisms underlying a human disease associated with CLDN16 dysfunction [familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), OMIM 248250], we generated a mouse model of CLDN16 deficiency. Similar to patients, CLDN16-deficient mice displayed hypercalciuria and hypomagnesemia. Contrary to FHHNC patients, nephrocalcinosis was absent in our model, indicating the existence of compensatory pathways in ion handling in this model. In line with the renal loss of Ca(2+), compensatory mechanisms like parathyroid hormone and 1,25(OH)(2)D(3) were significantly elevated. Also, gene expression profiling revealed transcriptional upregulation of several Ca(2+) and Mg(2+) transport systems including Trpv5, Trpm6, and calbindin-D9k. Induced gene expression was also seen for the transcripts of two putative Mg(2+) transport proteins, Cnnm2 and Atp13a4. Moreover, urinary pH was significantly lower when compared with wild-type mice. Taken together, our findings demonstrate that loss of CLDN16 activity leads to specific alterations in Ca(2+) and Mg(2+) homeostasis and that CLDN16-deficient mice represent a useful model to further elucidate pathways involved in renal Ca(2+) and Mg(2+) handling.
MeSH term(s)	Adenosine Triphosphatases/metabolism ; Animals ; Biological Transport/physiology ; Calcium/metabolism ; Cation Transport Proteins/metabolism ; Claudins/deficiency ; Claudins/genetics ; Claudins/metabolism ; Disease Models, Animal ; Gene Deletion ; Homeostasis/physiology ; Hypercalciuria/metabolism ; Hypercalciuria/physiopathology ; Magnesium/metabolism ; Membrane Transport Proteins ; Mice ; Mice, Knockout ; Nephrocalcinosis/metabolism ; Nephrocalcinosis/physiopathology ; Renal Tubular Transport, Inborn Errors/metabolism ; Renal Tubular Transport, Inborn Errors/physiopathology ; Signal Transduction/physiology
Chemical Substances	Cation Transport Proteins ; Claudins ; Cnnm2 protein, mouse ; Membrane Transport Proteins ; claudin 16 ; Adenosine Triphosphatases (EC 3.6.1.-) ; ATP13A4 protein, mouse (EC 3.6.1.3) ; Magnesium (I38ZP9992A) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2010-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00499.2009
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Article ; Online: Evidence of initial success for China exiting COVID-19 social distancing policy after achieving containment

Ainslie, Kylie E C / Walters, Caroline E. / Fu, Han / Bhatia, Sangeeta / Wang, Haowei / Xi, Xiaoyue / Baguelin, Marc / Bhatt, Samir / Boonyasiri, Adhiratha / Boyd, Olivia / Cattarino, Lorenzo / Ciavarella, Constanze / Cucunuba, Zulma / Cuomo-Dannenburg, Gina / Dighe, Amy / Dorigatti, Ilaria / van Elsland, Sabine L / FitzJohn, Rich / Gaythorpe, Katy /

Wellcome Open Res

Abstract	Background: The COVID-19 epidemic was declared a Global Pandemic by WHO on 11 March 2020. By 24 March 2020, over 440,000 cases and almost 20,000 deaths had been reported worldwide. In response to the fast-growing epidemic, which began in the Chinese city of Wuhan, Hubei, China imposed strict social distancing in Wuhan on 23 January 2020 followed closely by similar measures in other provinces. These interventions have impacted economic productivity in China, and the ability of the Chinese economy to resume without restarting the epidemic was not clear. Methods: Using daily reported cases from mainland China and Hong Kong SAR, we estimated transmissibility over time and compared it to daily within-city movement, as a proxy for economic activity. Results: Initially, within-city movement and transmission were very strongly correlated in the five mainland provinces most affected by the epidemic and Beijing. However, that correlation decreased rapidly after the initial sharp fall in transmissibility. In general, towards the end of the study period, the correlation was no longer apparent, despite substantial increases in within-city movement. A similar analysis for Hong Kong shows that intermediate levels of local activity were maintained while avoiding a large outbreak. At the very end of the study period, when China began to experience the re-introduction of a small number of cases from Europe and the United States, there is an apparent up-tick in transmission. Conclusions: Although these results do not preclude future substantial increases in incidence, they suggest that after very intense social distancing (which resulted in containment), China successfully exited its lockdown to some degree. Elsewhere, movement data are being used as proxies for economic activity to assess the impact of interventions. The results presented here illustrate how the eventual decorrelation between transmission and movement is likely a key feature of successful COVID-19 exit strategies.
Keywords	covid19
Publisher	PMC; WHO
Document type	Article ; Online
DOI	10.12688/wellcomeopenres.15843.1
Database	COVID19

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