Aenny Catzenstein nee Gottschalk at her 80th birthday party with Patrick Matthiesen and Serge Donabedian; London.

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Franz Matthiesen outdoors with his second wife Katherina Früh outside of Franz's Carton Hill home; London.

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Aenny Catzenstein nee Gottschalk reading the "Israelitisches Wochenblatt"; Israel.

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Family and guests at Aenny Catzenstein nee Gottschalk's 80th birthday party; London.

Dinner scene with Franz Mattheisen left, daughter Susan Mattheisen next to him, next daughter Maren Matthiesen, his wife Olga Matthiesen at the end of the table. Beatrice Durand is facing the camera

Interior of Aenny Catzenstein nee Gottschalk's cottage during WW II; Ascona, Switzerland Architecture Residences Interiors

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Aenny Catzenstein nee Gottschalk (right) with unidentified woman; Ascona, Switzerland.

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Ara-Serge Donabedian with Beatrice and Francine Durand at Aenny Catzenstein's 80th birthday; London Portraits; Children

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Yael Bernkopf with her mother Ellen; Israel.

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Francine Durand on Aenny's 80th birthday; London Portraits Children

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Profile view of bust of Henriette Gottschalk nee Rothschild by Ellen Bernkopf (Colmar) nee Catzenstein.

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Franz Matthiesen and his mother Aenny Catzenstein nee Gottschalk; Oslo Court, London.

At the time Franz was ill with cancer but Aenny did not know.

Family and guests at Aenny Catzenstein nee Gottschalk's 80th birthday; London.

Front row l-r: Francine Durand, Beatrice Durand and Aenny Catzenstein, the boys are Ara-Serge Donabedian and Patrick Matthiesen and the adults are Susan Prior, Francis Matthiesen, Maren Matthiesen, Nino Fabri and Olga Matthiesen,

Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 x 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-kappaB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.

In vitro development of islets from human adult pancreatic tissues

Transplantation of isolated islets from cadaver pancreas is a promising possibility for the optimal treatment of type 1 diabetes. The lack of islets is a major problem. Here we have investigated the possibility of generating islets in tissue culture of human pancreatic cells. We first reproduced a previously reported method of in vitro generation of endocrine cells from human adult pancreatic tissue. By tracing the bromodeoxyuridine-labeled cells in differentiated islet buds, we found that the pancreatic progenitor cells represented a subpopulation of cytokeratin 19 (CK19)-positive ductal cells. Serum-free medium and Matrigel overlay were essential for the endocrine differentiation. We then examined the involvement of preexisting islet cells in islet neogenesis. About 6-10% of endocrine cells dedifferentiated and acquired a transitional phenotype by coexpressing CK19. Significant cell proliferation was only observed in CK19-positive cells, but not in chromogranin A-positive endocrine cells. The in vitro-derived human islets were morphologically and functionally immature when compared with normal islets. Their insulin mRNA levels were only 4-5% of that found in fresh human islets, and glucose-stimulated insulin release was 3 times lower than that of control islets. Moreover, some immature endocrine cells coexpressed insulin and glucagon. After transplantation in nude mice, the in vitro-generated islets became mature with one type of hormone per endocrine cell. In addition, we also found that also in both fresh islet transplants many cells coexpressed endocrine markers and ductal marker CK19 as a sign of ductal to endocrine cell transition. Finally, we studied the effects of clinically used immunosuppressive drugs on precursor cell proliferation and differentiation. Mycophenolate mofetil (MMF) severely hampered duct-cell proliferation, and significantly reduced the total DNA content indicating its antiproliferative effect on the precursors. Tacrolimus mainly affected differentiated beta cells by decreasing the insulin content per DNA as well as the proportion of insulin-positive cells. Sirolimus and daclizumab did not show any individual or synergistic side effects suggesting that these drugs are amenable for use in clinical islet transplantation. In summary, we confirm the capacity of endocrine differentiation from progenitors present in the adult human pancreas. The plasticity of differentiated cell types of human pancreas may be a potential mechanism of human pancreas regeneration. Ductal cell differentiation into endocrine cells in transplanted islets may be an important factor in sustaining the long-term function of islet transplants. The immunosuppressive protocol is likely to be an important determinant of long-term clinical islet graft function. Moreover, these results provide new information on the mechanisms of pancreatic islet regeneration and provide the basis for the development of new strategies for the treatment of insulin deficient diabetes mellitus.