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1. Genomic characterization of DICER1-associated neoplasms uncovers molecular classes.

Author

Kommoss, F.K.F., Chong, A.S., Chong, A.L., Pfaff, E., Jones, D.T.W., Hiemcke-Jiwa, L.S., Kester, L.A., Flucke, U.E., Gessler, M., Schrimpf, D., Sahm, F., Clarke, B.A., Stewart, C.J.R., Wang, Yemin, Gilks, C.B., Kommoss, F., Huntsman, D.G., Schüller, U., Koelsche, C., Glenn McCluggage, W., Deimling, A. von, Foulkes, W.D., Kommoss, F.K.F., Chong, A.S., Chong, A.L., Pfaff, E., Jones, D.T.W., Hiemcke-Jiwa, L.S., Kester, L.A., Flucke, U.E., Gessler, M., Schrimpf, D., Sahm, F., Clarke, B.A., Stewart, C.J.R., Wang, Yemin, Gilks, C.B., Kommoss, F., Huntsman, D.G., Schüller, U., Koelsche, C., Glenn McCluggage, W., Deimling, A. von, and Foulkes, W.D.

Abstract

Item does not contain fulltext, DICER1 syndrome is a tumor predisposition syndrome that is associated with up to 30 different neoplastic lesions, usually affecting children and adolescents. Here we identify a group of mesenchymal tumors which is highly associated with DICER1 syndrome, and molecularly distinct from other DICER1-associated tumors. This group of DICER1-associated mesenchymal tumors encompasses multiple well-established clinicopathological tumor entities and can be further divided into three clinically meaningful classes designated "low-grade mesenchymal tumor with DICER1 alteration" (LGMT DICER1), "sarcoma with DICER1 alteration" (SARC DICER1), and primary intracranial sarcoma with DICER1 alteration (PIS DICER1). Our study not only provides a combined approach to classify DICER1-associated neoplasms for improved clinical management but also suggests a role for global hypomethylation and other recurrent molecular events in sarcomatous differentiation in mesenchymal tumors with DICER1 alteration. Our results will facilitate future investigations into prognostication and therapeutic approaches for affected patients.

Published
2023

4. Role for the Wilms Tumor Gene in Genital Development?

Author

Van Heyningen, V., Bickmore, W. A., Seawright, A., Fletcher, J. M., Maule, J., Fekete, G., Gessler, M., Bruns, G. A. P., Huerre-Jeanpierre, C., Junien, C., Williams, B. R. G., and Hastie, N. D.

Published
1990

5. Fifty years of clinical and research studies for childhood renal tumors within the International Society of Pediatric Oncology (SIOP)

Author

Graf, N., primary, Bergeron, C., additional, Brok, J., additional, de Camargo, B., additional, Chowdhury, T., additional, Furtwängler, R., additional, Gessler, M., additional, Godzinski, J., additional, Pritchard-Jones, K., additional, Ramirez-Villar, G.L., additional, Rübe, C., additional, Sandstedt, B., additional, Schenk, J.-P., additional, Spreafico, F., additional, Sudour-Bonnange, H., additional, van Tinteren, H., additional, Verschuur, A., additional, Vujanic, G., additional, and van den Heuvel-Eibrink, M.M., additional

Published
2021
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7. Sarcoma classification by DNA methylation profiling

Author

Koelsche, C, Schrimpf, D, Stichel, D, Sill, M, Sahm, F, Reuss, DE, Blattner, M, Worst, B, Heilig, CE, Beck, K, Horak, P, Kreutzfeldt, S, Paff, E, Stark, S, Johann, P, Selt, F, Ecker, J, Sturm, D, Pajtler, K W, Reinhardt, A, Wefers, AK, Sievers, P, Ebrahimi, A, Suwala, A, Fernandez-Klett, F, Casalini, B, Korshunov, A, Hovestadt, V, Kommoss, FKF, Kriegsmann, M, Schick, M, Bewerunge-Hudler, M, Milde, T, Witt, O, Kulozik, AE, Kool, M, Romero-Perez, L, Grunewald, TGP, Kirchner, T, Wick, W, Platten, M, Unterberg, A, Uhl, M, Abdollahi, A, Debus, J, Lehner, B, Thomas, C, Hasselblatt, M, Paulus, W, Hartmann, C, Staszewski, O, Prinz, M, Hench, J, Frank, S, Versleijen-Jonkers, YMH, Weidema, ME, Mentzel, T, Griewank, K, Alava, E, Martin, JD, Gastearena, MAI, Chang, KTE, Low, SYY, Cuevas-Bourdier, A, Mittelbronn, M, Mynarek, M, Rutkowski, S, Schuller, U, Mautner, VF, Schittenhelm, J, Serrano, J, Snuderl, M, Buttner, R, Klingebiel, T, Buslei, R, Gessler, M, Wesseling, P, Dinjens, Winand, Brandner, S, Jaunmuktane, Z, Lyskjaer, I, Schirmacher, P, Stenzinger, A, Brors, B, Glimm, H, Heining, C, Tirado, OM, Sainz-Jaspeado, M, Mora, J, Alonso, J, del Muro, XG, Moran, S, Esteller, M, Benhamida, JK, Ladanyi, M, Wardelmann, E, Antonescu, C, Flanagan, A, Dirksen, U, Hohenberger, P, Baumhoer, D, Hartmann, W, Vokuhl, C, Flucke, U, Petersen, I, Mechtersheimer, G, Capper, D, Jones, DT, Frohling, S, Pfister, SM, von Deimling, A, Koelsche, C, Schrimpf, D, Stichel, D, Sill, M, Sahm, F, Reuss, DE, Blattner, M, Worst, B, Heilig, CE, Beck, K, Horak, P, Kreutzfeldt, S, Paff, E, Stark, S, Johann, P, Selt, F, Ecker, J, Sturm, D, Pajtler, K W, Reinhardt, A, Wefers, AK, Sievers, P, Ebrahimi, A, Suwala, A, Fernandez-Klett, F, Casalini, B, Korshunov, A, Hovestadt, V, Kommoss, FKF, Kriegsmann, M, Schick, M, Bewerunge-Hudler, M, Milde, T, Witt, O, Kulozik, AE, Kool, M, Romero-Perez, L, Grunewald, TGP, Kirchner, T, Wick, W, Platten, M, Unterberg, A, Uhl, M, Abdollahi, A, Debus, J, Lehner, B, Thomas, C, Hasselblatt, M, Paulus, W, Hartmann, C, Staszewski, O, Prinz, M, Hench, J, Frank, S, Versleijen-Jonkers, YMH, Weidema, ME, Mentzel, T, Griewank, K, Alava, E, Martin, JD, Gastearena, MAI, Chang, KTE, Low, SYY, Cuevas-Bourdier, A, Mittelbronn, M, Mynarek, M, Rutkowski, S, Schuller, U, Mautner, VF, Schittenhelm, J, Serrano, J, Snuderl, M, Buttner, R, Klingebiel, T, Buslei, R, Gessler, M, Wesseling, P, Dinjens, Winand, Brandner, S, Jaunmuktane, Z, Lyskjaer, I, Schirmacher, P, Stenzinger, A, Brors, B, Glimm, H, Heining, C, Tirado, OM, Sainz-Jaspeado, M, Mora, J, Alonso, J, del Muro, XG, Moran, S, Esteller, M, Benhamida, JK, Ladanyi, M, Wardelmann, E, Antonescu, C, Flanagan, A, Dirksen, U, Hohenberger, P, Baumhoer, D, Hartmann, W, Vokuhl, C, Flucke, U, Petersen, I, Mechtersheimer, G, Capper, D, Jones, DT, Frohling, S, Pfister, SM, and von Deimling, A

Abstract

Sarcomas are malignant soft tissue and bone tumours affecting adults, adolescents and children. They represent a morphologically heterogeneous class of tumours and some entities lack defining histopathological features. Therefore, the diagnosis of sarcomas is burdened with a high inter-observer variability and misclassification rate. Here, we demonstrate classification of soft tissue and bone tumours using a machine learning classifier algorithm based on array-generated DNA methylation data. This sarcoma classifier is trained using a dataset of 1077 methylation profiles from comprehensively pre-characterized cases comprising 62 tumour methylation classes constituting a broad range of soft tissue and bone sarcoma subtypes across the entire age spectrum. The performance is validated in a cohort of 428 sarcomatous tumours, of which 322 cases were classified by the sarcoma classifier. Our results demonstrate the potential of the DNA methylation-based sarcoma classification for research and future diagnostic applications.

Published
2021

11. 0613 / #917 Characteristics and Outcome of Pediatric Patients With Renal Cell Carcinoma Registered in International Society of Pediatric Oncology Renal Tumor Study Group 93-01 and 2001/UK-Import Databases

Author

Cancer, Onderzoek Beeld, Genetica Klinische Genetica, PMC Research, MS Radiologie, CDL Nanomedicine, PMC Medisch specialisten, Speerpunt, Zorg en O&O, Child Health, Van der Beek, J. N., Hol, J. A., Coulomb-L'Hermine, A., Graf, N., Van Tinteren, H., Pritchard-Jones, K., Houwing, M. E., DeKrijger, R. R., Vujanic, G. M., Dzhuma, K., Littooij, A. S., Ramirez-Villar, G. L., Murphy, D., Ray, S., Al-Saadi, R., Gessler, M., Godzinski, J., Ruebe, C., Collini, P., Verschuur, A. C., Frisk, T., Vokuhl, C., Hulsbergen-Van De Kaa, C. A., De Camargo, B., Sandstedt, B., Selle, B., Tytgat, G., Van den Heuvel-Eibrink, M. M., Cancer, Onderzoek Beeld, Genetica Klinische Genetica, PMC Research, MS Radiologie, CDL Nanomedicine, PMC Medisch specialisten, Speerpunt, Zorg en O&O, Child Health, Van der Beek, J. N., Hol, J. A., Coulomb-L'Hermine, A., Graf, N., Van Tinteren, H., Pritchard-Jones, K., Houwing, M. E., DeKrijger, R. R., Vujanic, G. M., Dzhuma, K., Littooij, A. S., Ramirez-Villar, G. L., Murphy, D., Ray, S., Al-Saadi, R., Gessler, M., Godzinski, J., Ruebe, C., Collini, P., Verschuur, A. C., Frisk, T., Vokuhl, C., Hulsbergen-Van De Kaa, C. A., De Camargo, B., Sandstedt, B., Selle, B., Tytgat, G., and Van den Heuvel-Eibrink, M. M.

Published
2020

14. Lernen durch Lehren: Gruppenpuzzle erfolgreich gestalten [Bericht über Forschungsergebnisse]

Author

Hauser, S, Sippel, S, Backhaus, J, König, S, and Gessler, M

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Problemstellung/Ziele: Bei der kooperativen Lehrmethode Gruppenpuzzle findet sich jede/r Studierende/r sowohl in der Rolle des Lehrenden als auch des Lernenden [ref:1]. Wir zeigten bereits, dass sich die Lehrmethode Gruppenpuzzle eignet, um die aktive Beteiligung von Studierenden[zum vollständigen Text gelangen Sie über die oben angegebene URL], Jahrestagung der Gesellschaft für Medizinische Ausbildung (GMA)

Published
2018
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18. TRIM28 haploinsufficiency predisposes to Wilms tumor

Author

Diets, I.J., Hoyer, J., Ekici, A.B., Popp, B., Hoogerbrugge, N., Reijmersdal, S.V. van, Bhaskaran, R., Hadjihannas, M., Vasileiou, G., Thiel, C.T., Seven, D., Uebe, S., Ilencikova, D., Waanders, E., Mavinkurve-Groothuis, A.M.C., Roeleveld, N., Krijger, R.R. de, Wegert, J., Graf, N., Vokuhl, C., Agaimy, A., Gessler, M., Reis, A., Kuiper, R.P., Jongmans, M.C.J., Metzler, M., Diets, I.J., Hoyer, J., Ekici, A.B., Popp, B., Hoogerbrugge, N., Reijmersdal, S.V. van, Bhaskaran, R., Hadjihannas, M., Vasileiou, G., Thiel, C.T., Seven, D., Uebe, S., Ilencikova, D., Waanders, E., Mavinkurve-Groothuis, A.M.C., Roeleveld, N., Krijger, R.R. de, Wegert, J., Graf, N., Vokuhl, C., Agaimy, A., Gessler, M., Reis, A., Kuiper, R.P., Jongmans, M.C.J., and Metzler, M.

Abstract

Contains fulltext : 205528.pdf (publisher's version ) (Closed access), Two percent of patients with Wilms tumors have a positive family history. In many of these cases the genetic cause remains unresolved. By applying germline exome sequencing in two families with two affected individuals with Wilms tumors, we identified truncating mutations in TRIM28. Subsequent mutational screening of germline and tumor DNA of 269 children affected by Wilms tumor was performed, and revealed seven additional individuals with germline truncating mutations, and one individual with a somatic truncating mutation in TRIM28. TRIM28 encodes a complex scaffold protein involved in many different processes, including gene silencing, DNA repair and maintenance of genomic integrity. Expression studies on mRNA and protein level showed reduction of TRIM28, confirming a loss-of-function effect of the mutations identified. The tumors showed an epithelial-type histology that stained negative for TRIM28 by immunohistochemistry. The tumors were bilateral in six patients, and 10/11 tumors are accompanied by perilobar nephrogenic rests. Exome sequencing on eight tumor DNA samples from six individuals showed loss-of-heterozygosity (LOH) of the TRIM28-locus by mitotic recombination in seven tumors, suggesting that TRIM28 functions as a tumor suppressor gene in Wilms tumor development. Additionally, the tumors showed very few mutations in known Wilms tumor driver genes, suggesting that loss of TRIM28 is the main driver of tumorigenesis. In conclusion, we identified heterozygous germline truncating mutations in TRIM28 in 11 children with mainly epithelial-type Wilms tumors, which become homozygous in tumor tissue. These data establish TRIM28 as a novel Wilms tumor predisposition gene, acting as a tumor suppressor gene by LOH.

Published
2019

19. Lernen durch Lehren: Gruppenpuzzle versus Referate im Biochemieseminar

Author

Hauser, S, Backhaus, J, König, S, and Gessler, M

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Hintergrund und Fragestellung: Die aktive Eigenbeteiligung von Studierenden in Seminaren beschränkt sich oft auf das Halten von Referaten. Die Zuhörer bleiben dabei meist in einer passiven Rolle, was deren Lernprozess erschwert. Bei der kooperativen Lehrmethode Gruppenpuzzle [ref:1][zum vollständigen Text gelangen Sie über die oben angegebene URL], Gemeinsame Jahrestagung der Gesellschaft für Medizinische Ausbildung (GMA) und des Arbeitskreises zur Weiterentwicklung der Lehre in der Zahnmedizin (AKWLZ)

Published
2017
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21. Untersuchungen zur epiduralen Opiatanalgesie

Author

Rust, M., Gessler, M., Zieglgänsberger, W., Egbert, R., Struppler, A., Bergmann, H., editor, Brückner, J. B., editor, Henschel, W. F., editor, Peter, K., editor, Gemperle, M., editor, Mayrhofer, O., editor, and Brückner, Jürgen B., editor

Published
1982
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24. Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death

Author

Bezzina, C, Barc, J, Mizusawa, Y, Remme, C, Gourraud, J, Simonet, F, Verkerk, A, Schwartz, P, Crotti, L, Dagradi, F, Guicheney, P, Fressart, V, Leenhardt, A, Antzelevitch, C, Bartkowiak, S, Borggrefe, M, Schimpf, R, Schulze-Bahr, E, Zumhagen, S, Behr, E, Bastiaenen, R, Tfelt-Hansen, J, Olesen, M, Kääb, S, Beckmann, B, Weeke, P, Watanabe, H, Endo, N, Minamino, T, Horie, M, Ohno, S, Hasegawa, K, Makita, N, Nogami, A, Shimizu, W, Aiba, T, Froguel, P, Balkau, B, Lantieri, O, Torchio, M, Wiese, C, Weber, D, Wolswinkel, R, Coronel, R, Boukens, B, Bézieau, S, Charpentier, E, Chatel, S, Despres, A, Gros, F, Kyndt, F, Lecointe, S, Lindenbaum, P, Portero, V, Violleau, J, Gessler, M, Tan, H, Roden, D, Christoffels, V, Le Marec, H, Wilde, A, Probst, V, Schott, J, Dina, C, Redon, R, Bezzina CR., Barc J., Mizusawa Y., Remme CA., Gourraud JB., Simonet F., Verkerk AO., Schwartz PJ., Crotti L., Dagradi F., Guicheney P., Fressart V., Leenhardt A., Antzelevitch C., Bartkowiak S., Borggrefe M., Schimpf R., Schulze-Bahr E., Zumhagen S., Behr ER., Bastiaenen R., Tfelt-Hansen J., Olesen MS., Kääb S., Beckmann BM., Weeke P., Watanabe H., Endo N., Minamino T., Horie M., Ohno S., Hasegawa K., Makita N., Nogami A., Shimizu W., Aiba T., Froguel P., Balkau B., Lantieri O., Torchio M., Wiese C., Weber D., Wolswinkel R., Coronel R., Boukens BJ., Bézieau S., Charpentier E., Chatel S., Despres A., Gros F., Kyndt F., Lecointe S., Lindenbaum P., Portero V., Violleau J., Gessler M., Tan HL., Roden DM., Christoffels VM., Le Marec H., Wilde AA., Probst V., Schott JJ., Dina C., Redon R., Bezzina, C, Barc, J, Mizusawa, Y, Remme, C, Gourraud, J, Simonet, F, Verkerk, A, Schwartz, P, Crotti, L, Dagradi, F, Guicheney, P, Fressart, V, Leenhardt, A, Antzelevitch, C, Bartkowiak, S, Borggrefe, M, Schimpf, R, Schulze-Bahr, E, Zumhagen, S, Behr, E, Bastiaenen, R, Tfelt-Hansen, J, Olesen, M, Kääb, S, Beckmann, B, Weeke, P, Watanabe, H, Endo, N, Minamino, T, Horie, M, Ohno, S, Hasegawa, K, Makita, N, Nogami, A, Shimizu, W, Aiba, T, Froguel, P, Balkau, B, Lantieri, O, Torchio, M, Wiese, C, Weber, D, Wolswinkel, R, Coronel, R, Boukens, B, Bézieau, S, Charpentier, E, Chatel, S, Despres, A, Gros, F, Kyndt, F, Lecointe, S, Lindenbaum, P, Portero, V, Violleau, J, Gessler, M, Tan, H, Roden, D, Christoffels, V, Le Marec, H, Wilde, A, Probst, V, Schott, J, Dina, C, Redon, R, Bezzina CR., Barc J., Mizusawa Y., Remme CA., Gourraud JB., Simonet F., Verkerk AO., Schwartz PJ., Crotti L., Dagradi F., Guicheney P., Fressart V., Leenhardt A., Antzelevitch C., Bartkowiak S., Borggrefe M., Schimpf R., Schulze-Bahr E., Zumhagen S., Behr ER., Bastiaenen R., Tfelt-Hansen J., Olesen MS., Kääb S., Beckmann BM., Weeke P., Watanabe H., Endo N., Minamino T., Horie M., Ohno S., Hasegawa K., Makita N., Nogami A., Shimizu W., Aiba T., Froguel P., Balkau B., Lantieri O., Torchio M., Wiese C., Weber D., Wolswinkel R., Coronel R., Boukens BJ., Bézieau S., Charpentier E., Chatel S., Despres A., Gros F., Kyndt F., Lecointe S., Lindenbaum P., Portero V., Violleau J., Gessler M., Tan HL., Roden DM., Christoffels VM., Le Marec H., Wilde AA., Probst V., Schott JJ., Dina C., and Redon R.

Abstract

Brugada syndrome is a rare cardiac arrhythmia disorder, causally related to SCN5A mutations in around 20% of cases. Through a genome-wide association study of 312 individuals with Brugada syndrome and 1,115 controls, we detected 2 significant association signals at the SCN10A locus (rs10428132) and near the HEY2 gene (rs9388451). Independent replication confirmed both signals (meta-analyses: rs10428132, P = 1.0 × 10 -68; rs9388451, P = 5.1 × 10 -17) and identified one additional signal in SCN5A (at 3p21; rs11708996, P = 1.0 × 10 -14). The cumulative effect of the three loci on disease susceptibility was unexpectedly large (P trend = 6.1 × 10 -81). The association signals at SCN5A-SCN10A demonstrate that genetic polymorphisms modulating cardiac conduction can also influence susceptibility to cardiac arrhythmia. The implication of association with HEY2, supported by new evidence that Hey2 regulates cardiac electrical activity, shows that Brugada syndrome may originate from altered transcriptional programming during cardiac development. Altogether, our findings indicate that common genetic variation can have a strong impact on the predisposition to rare diseases

Published
2013

26. Biotransformation und Detoxifizierung in der Leber

Author

Schartl, M, Gessler, M, von Eckardstein, A, Schartl, M ( M ), Gessler, M ( M ), von Eckardstein, A ( A ), Stieger, B, Arand, Michael; https://orcid.org/0000-0003-2413-3177, Schartl, M, Gessler, M, von Eckardstein, A, Schartl, M ( M ), Gessler, M ( M ), von Eckardstein, A ( A ), Stieger, B, and Arand, Michael; https://orcid.org/0000-0003-2413-3177

Published
2009

27. Lipidtransport und Regulation des Lipidstoffwechsels

Author

Schartl, M, Gessler, M, von Eckardstein, A, Schartl, M ( M ), Gessler, M ( M ), von Eckardstein, A ( A ), Luley, C, Schartl, M, Gessler, M, von Eckardstein, A, Schartl, M ( M ), Gessler, M ( M ), von Eckardstein, A ( A ), and Luley, C

Published
2009

28. Lipidstoffwechsel: Einführung, Acylfette und Triglyceride

Author

Schartl, M, Gessler, M, von Eckardstein, A, Schartl, M ( M ), Gessler, M ( M ), von Eckardstein, A ( A ), Luley, C, Schartl, M, Gessler, M, von Eckardstein, A, Schartl, M ( M ), Gessler, M ( M ), von Eckardstein, A ( A ), and Luley, C

Published
2009

29. Hormone

Author

Schartl, M, Gessler, M, von Eckardstein, A, Schartl, M ( M ), Gessler, M ( M ), von Eckardstein, A ( A ), Hersberger, M; https://orcid.org/0000-0002-4472-329X, von Eckardstein, S, Schartl, M, Gessler, M, von Eckardstein, A, Schartl, M ( M ), Gessler, M ( M ), von Eckardstein, A ( A ), Hersberger, M; https://orcid.org/0000-0002-4472-329X, and von Eckardstein, S

Published
2009

30. HeyL: A New Mammalian Mediator of Notch Signaling

Author

Steidl, C., Knobeloch, K. P., Leimeister, C., Maier, M., and Gessler, M.

Subjects
Mammals -- Genetic aspects, Developmental genetics -- Research, Biological sciences
Abstract

Delta-Notch signaling affects the implementation of differentiation, proliferation, and apoptotic programs influencing organ formation and morphogenesis. We have identified three mammalian genes, Hey1, Hey2, and HeyL, which possess high similarity to the Drosophila Notch-target genes hairy and the Enhancer of split complex genes. In situ hybridization revealed a distinct expression pattern of HeyL during neurogenesis, somitogenesis, blood vessel formation, and development of other organs. GFP fusion as well as direct antibody staining showed a nuclear localization of the HeyL protein. Notch-dependent expression was confirmed by HeyL promoter studies as well as HeyL expression analysis in Delta-like 1 (Dll1) and Notch1 knockout mice and in Notch1-overexpressing mice. For functional analysis of HeyL the exons 2 to 4, encoding the bHLH domain, were replaced with a lacZ cassette. HeyL expression sites, as shown by in situ hybridization, could be confirmed by [Beta]-Gal staining of whole-mount knockout mouse embryos. In adult mouse organs lacZ expression was detected in the capillary blood vessels especially of the lung, heart, and brain. Knockout mice from the F2 backcross generation are born at expected Mendelian ratio and appear healthy and fertile. Further characterization of these mice as well as generation of double knockout mice is currently under way.

Published
2001

31. Functional Characterization of the Hey bHLH Gene Family

Author

Gessler, M., Knobeloch, K., Schumacher, N., Amann, K., Golenhofen, N., and Leimeister, C.

Subjects
Developmental genetics -- Research, Vertebrates -- Genetic aspects, Gene expression -- Research, Biological sciences
Abstract

The vertebrate Hey genes (Hey1, Hey2, HeyL) constitute a family of hairy- and Enhancer-of-split-related bHLH genes. Related genes were detected in other vertebrates species like chicken, Xenopus, and fish. Hey genes are dynamically expressed during mouse development with an emphasis on somitogenesis, neurogenesis, and cardiovascular morphogenesis. Hey genes can homodimerize or heterodimerize with related bHLH factors in the nucleus and function as Notch-regulated transcriptional repressors similar to Hes genes. A distinct E-box has been identified as the preferred target, but Hey target genes have yet to be identified. The zebrafish gridlock gene (Hey2) is involved in aortic development. To elucidate the role of mammalian Hey genes knockout mice were generated. Complete loss of Hey1 or HeyL did not lead to any obvious developmental defects. Despite the intriguing oscillating expression of Hey2 in the presomitic mesoderm no alterations of somitogenesis in Hey2 knockout animals were seen. However, Hey2 loss resulted in very high postnatal lethality likely due to cardiac problems. Gross changes in heart size and shape are seen postnatally. Histological and morphometric analysis suggests massive hypertrophy with activated myocytes, a concomittant loss of contractile elements, and functional impairment. A subset of knockout mice is able to compensate for this after prolonged wasting periods. The molecular basis is currently being investigated by comparison of global expression patterns. In situ hybridization of several cardiac marker genes did not yet reveal substantial deregulation of gene expression.

Published
2001

32. Hey genes form a novel family of Notch target genes with Hey2 as an independent component of the somitogenesis clock

Author

Gessler, M., Maier, M., Steidl, C., Fischer, A., Dale, K., Pourquie, O., and Leimeister, C.

Subjects
Gene expression -- Physiological aspects, Vertebrates -- Genetic aspects, Somite -- Genetic aspects, Developmental genetics -- Research, Biological sciences
Abstract

Hey genes (Hey1, Hey2, HeyL) form a new subfamily of hairy-related bHLH genes that is distinct from the known vertebrate Hes or Her genes. Sequence comparison predicts Hey proteins to function as transcriptional repressors, while critical changes in the basic region and the C-terminus suggest unique interaction properties. The HeyL protein localises to the nucleus as expected and all Hey proteins can form homo- and heterodimers, but they also interact with a subset of the ubiquitous class A bHLH proteins. Binding site selection experiments with Hey1 identified a subset of E-box sequences that is also recognised by the other Hey proteins. Analysis of the mouse and human genomic loci showed a 5 exon structure and suggested a number of candidate diseases/mutants, most of which could be excluded, however. Promoter studies revealed a Notch-dependent expression of Hey genes that greatly expands the number of developmentally interesting Notch targets beyond Hes1/5. Hey genes are dynamically expressed in multiple tissues during mouse development with an emphasis on somitogenesis, neurogenesis and cardiovascular morphogenesis. Detailed analysis of chick somitogenesis revealed a rhythmic expression of Hey2 in the presomitic mesoderm that resembles the oscillating pattern of c-hairy1 expression. Direct interaction between Hey proteins and c-hairy1 suggests that they form a dynamic and combinatorial system of bHLH factors involved in somite formation and patterning.

Published
2000

34. Moderatorenbericht Der Stellenwert der intrapartualen Kardiotokographie. Ein Beitrag zur Effizienz der Methode

Author

Bolte, A., De Haan, R., Mastricht, Hamacher, K., Hochuli, E., Junge, H. D., Würzburg, Rüttgers, H., Link, G., Jensen, A., Hohmann, M., Künzel, W., Jensen, A., Künzel, W., Paulick, R., Kastendieck, E., Wernze, H., Liedtke, B., Inthraphuvasak, J., Merz, E., Schmitt, W., Kurz, C. S., Huch, R., Huch, A., Kurz, C. S., Huch, R., Huch, A., Schmidt, S., Langner, K., Dudenhausen, J. W., Saling, E., Wernicke, K., Gauwerky, J., Holting, T., Matthis, P., Härdle, W., Kubli, F., Goeschen, K., Kersting, A., Saling, E., Prill, H. J., Klöck, F. -K., Harms, E., Klöpper, A., Goecke, C., Scheidt-Oepen, U., Bauer, O., Berle, P., Ponnath, H., Willers, H., Müller, R., Schneider, J., Gerlach, H., Genz, H. -J., Schuhmann, R., Hertel, H., Granitzka, S., Rothhammer, A., Hartmann, G., Parache, J., Garcia Hernandez, J. A., Gonzalez Gonzalez, N. L., Gonzalez Miranda, F., Valero, J., Santisimo, J. L., Warnecke, H. H., Graeff, H., Selbmann, H. K., Praec-Mursci, V., Adam, D., Gloning, K. P., Jänicke, F., Zander, J., Pluta, M., Dudenhausen, J. W., Heyner, C., Gesche, J., Saling, E., Beck, A., Vutuc, C., Kunze, M., Rust, M., Egbert, R., Gessler, M., Johannigmann, J., Kolb, E., Struppler, A., Zieglgänsberger, W., Rust, M., Weindl, A., Fabinger, R., Martin, K., Schüßler, B., Knitza, R., Alloussie, S., Hägele, D., Berg, D., Fuchs, I., Arnold, H., Schneider-Affeld, F., Müller-Holve, W., Fabinger, R., Martin, K., Schüßler, B., Knitza, R., Alloussie, S., Hägele, D., Berg, D., Fuchs, I., and Arnold, H.

Published
1983
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36. Biochemie und Molekularbiologie des Menschen

Author

Schartl, M, Gessler, M, von Eckardstein, A, and University of Zurich

Subjects
540 Chemistry, 610 Medicine & health, textbook, 10038 Institute of Clinical Chemistry
Published
2009

40. School industry partnerships: An innovative strategy for vocational education

Author

Gessler, M, Deitmer, L, Manning, S, Watters, Jim, Hay, Steven, Dempster, Neil, Pillay, Hitendra, Gessler, M, Deitmer, L, Manning, S, Watters, Jim, Hay, Steven, Dempster, Neil, and Pillay, Hitendra

Abstract

One of the challenges confronting contemporary education internationally is to ensure that students are provided with opportunities to make informed choices about future careers and to acquire the capacity to transition into these careers. Schools need to manage their curricula, teacher capacity, timetables, and diversity of student populations by offering pathways that are seen as engaging and meaningful to life beyond schooling. Traditionally, education in the senior years has privileged those students who intend to progress to advanced studies at university or in other professional careers. In more recent times, in response the need for more sophisticated technical knowledge in the trades and a growing skills shortages in these fields, schools have paid more attention to vocational education. It has been argued that the vocational aspect of the school curriculum is less well understood and poorly implemented in comparison with the traditional academic curricula. One attempt to address this issue is through the establishment of school-industry partnerships. This paper explores the process of knowledge transfer between industry and schools in these partnerships. The paper theorises how knowledge that is valued and foundational in workplace employment can inform school curricula and pedagogical practices. The paper draws on theories of organisational knowledge, workplace learning and experiential learning to explore strategies that enhance school-to-employment transition outcomes.

Published
2013

43. Inorganic-organic polymers with barrier properties for water vapor, oxygen and flavors

Author

Amberg-Schwab, Sabine, Hoffmann, M., Bader, H., Gessler, M., and Publica

Subjects
Kaschiermittel, Wasserdampfsperre, anorganisch-organische Copolymere, Barrierebeschichtung, Aromabarriere, Werkstoff, Barrierematerial, Sauerstoffbarriere
Abstract

With a new kind of barrier coating material, inorganic-organic polymers, it is possible to obtain high-barrier properties with respect to the permeation rates of oxygen, water vapor and volatile organic compounds. The hybrid polymers are accessible via the sol-gel technique. The inorganic network is formed as a result of controlled hydrolysis and condensation of alkoxysilanes, organoalkoxysilanes, acrylosysilanes or metal alcoholates. The organic network results from subsequent thermal or UV-induced polymerization of organo-functional groups. Due to the control of the inorganic and organic network densities and the insertion of specific functional groups to control the polarity of the resulting material, it was possible to develop high-barrier coatings with excellent adhesion properties on a wide variety of polymer films. These high-barrier coatings are also suitable as adhesives which can be used in laminates. The properties of the processable multilayer structures are preserved to a much higher extent than with other comparable, commercially available materials even under high mechanical and thermal stress and storage in humidity.

Published
1998

44. Genome-Wide Association Analysis Identifies 3 Common Variants Predisposing to Brugada Syndrome, a Rare Disease with High Risk of Sudden Cardiac Death

Author

Barc, J., primary, Bezzina, C., additional, Mizusawa, Y., additional, Remme, C., additional, Gourraud, J., additional, Verkerk, A., additional, Schwartz, P., additional, Guicheney, P., additional, Antzelevitch, C., additional, Schulze-Bahr, E., additional, Behr, E., additional, Tfelt-Hanson, J., additional, Kaab, S., additional, Watanabe, H., additional, Horie, M., additional, Makita, N., additional, Shimizu, W., additional, Roden, D., additional, Christoffels, V., additional, Gessler, M., additional, Wilde, A., additional, Probst, V., additional, Schott, J., additional, Dina, C., additional, and Redon, R., additional

Published
2013
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45. Combined loss of Hey1 and HeyL causes congenital heart defects because of impaired epithelial to mesenchymal transition.

Author

Fischer, A., Steidl, C., Wagner, T.U., Lang, E., Jakob, P.M., Friedl, P.H.A., Knobeloch, K.P., Gessler, M., Fischer, A., Steidl, C., Wagner, T.U., Lang, E., Jakob, P.M., Friedl, P.H.A., Knobeloch, K.P., and Gessler, M.

Abstract

Contains fulltext : 51945.pdf (publisher's version ) (Closed access), Congenital heart defects affect almost 1% of human newborns. Recently, mutations in Notch ligands and receptors have been found to cause a variety of heart defects in rodents and humans. However, the molecular effects downstream of Notch are still poorly understood. Here we report that combined inactivation of Hey1 and HeyL, two primary target genes of Notch, causes severe heart malformations, including membranous ventricular septal defects and dysplastic atrioventricular and pulmonary valves. These defects lead to congestive cardiac failure with high lethality. We found both genes to be coexpressed with Notch1, Notch2 and the Notch ligand Jagged1 in the endocardium of the atrioventricular canal, representing the primary source of mesenchymal cells forming membraneous septum and valves. Atrioventricular explants from Hey1/HeyL deficient mice exhibited impaired epithelial to mesenchymal transition. Although epithelial to mesenchymal transition was initiated regularly, full transformation into mesenchymal cells failed. This was accompanied by reduced levels of matrix metalloproteinase-2 expression and reduced cell density in endocardial cushions in vivo. We further show that loss of Hey2 leads to very similar deficiencies, whereas a Notch1 null mutation completely abolishes epithelial to mesenchymal transition. Thus, the Hey gene family shows overlap in controlling Notch induced endocardial epithelial to mesenchymal transition, a process critical for valve and septum formation.

Published
2007

46. Transparente, flexible Hochbarrierefolien durch Kombination von aufgedampften, anorganischen Schichten mit anorganisch-organischen Hybridpolymeren

Author

Gessler, M., Bader, H., Hoffmann, M., Amberg-Schwab, S., and Publica

Subjects
oxygen permeability, Verbundfolie, polymer, Wasserdampfdurchlässigkeit, barrier properties, Kaschierung, lamination, coating, Sauerstoffdurchlässigkeit, Sperreigenschaft, Beschichtung, water vapour permeability
Abstract

Depending on the carrier material, inorganic-organic hybrid polymers lower the oxygen- and water vapour permeabiltiy by the factor 500 and 3 respectively. By coating SiOx vapour-deposited films, both the oxygen- and also the water vapour high-barrier range is reached. With the use of ORMOCERES as barrier-laminating adhesives, the laminating composites show improved interlayer adhesion- and oxygen barrier properties compared with commercially available laminating adhesives. In combination with SiOx vapour-deposited films, one obtains transparent, high-barrier composites with excellent interlayer adhesion and stability vis-a-vis mechanical stress and sterilization.

Published
1997

47. Oberflächenmodifikation von BOPP-Folien

Author

Bader, H., Gessler, M., Rodler, N., and Publica

Subjects
adhesion, electron beam deposition, Schiffchenverdampfung, Excimer-UV-Strahlung, Haftung, boat type evaporation, Elektronenstrahlbedampfung, UV-excimer irridation, permeation, Vorbehandlung, permeability, pretreatment
Abstract

Polyolefine bereiten aufgrund ihrer unpolaren Oberfläche Schwierigkeiten beim Bedrucken, Verkleben, Beschichten oder Bedampfen. Durch Bestrahlung mit UV-Licht im Vakuum läßt sich die Oberflächenspannung gezielt erhöhen.

Published
1997

48. Report of the Fifth International Workshop on Human Chromosome 11 Mapping 1996

Author

Shows, T. B., Alders, M., Bennett, S., Burbee, D., Cartwright, P., Chandrasekharappa, S., Cooper, P., Courseaux, A., Davies, C., Devignes, M. D., Devilee, P., Elliott, R., Evans, G., Fantes, J., Garner, H., Gaudray, P., Gerhard, D. S., Gessler, M., Higgins, M., Hummerich, H., James, M., Lagercrantz, J., Litt, M., Little, P., Mannens, M., Munroe, D., Nowak, N., O'Brien, S., Parker, N., Perlin, M., Reid, L., Richard, C., Sawicki, M., Swallow, D., Thakker, R., van Heyningen, V., van Schothorst, E., Vorechovsky, I., Wadelius, C., Weber, B., Zabel, B., and Other departments

Published
1996

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