The Journal of the Friends' Historical Society vol. 1 No. 3

1. Notices. 2. Notes and Queries. 3. First Publishers of Truth. 4. Edmund Peckover's Travels in North America and Barbados. 5. Quaker or Common Beggars. 6. County Tipperary Friends Records I. 7. The Quaker Family of Owen III. 8. Inscriptions in Friends' Burial Ground, Bowcroft, near Sheffield. 9. Notes on Friends in South of Scotland II. 10. Editors Proposals. 11. Samuel Bownas to James Wilson, 1751. 12. Friends' Library, Philadelphia, Pennsylvania. 13. Friends' Historical Society of America. 14. Friends' Reference Library. 15. Awbrey of Brecknockshire. 16. Paragraph of the Will of John Rutty, 1770. 17. Third List of Members. 18. Index to Volume 1

The Journal of the Friends' Historical Society vol. 5 No. 1

1. Notices. 2. Notes and Queries. 3. The Westmorland and Swaledale Seekers in 1651. 4. Extracts from the Minute Book of the Sufferings of Friends in Mansfield. 5. Reminiscences of the Friends' Meeting, Manchester. 6. Women Ministers stopped by Highwaymen. 7. Presentations of Quakers in Episcopal Visitations, 1662-1679. 8. Elisha Bates. 9. Keye-Worsley Marriage Certificate, 1666. 10. Thomas Areskine, Brewer, of Edinburgh. 11. Meeting Records. 12. A Glimpse of Ancient Friends in Dorset I. 13. Distribution of Literature in Cornwall, 1734. 14. William White, M.D. F.R.S. of York. 15. Friends in Barbadoes. 16. Some Quaker Teachers in 1736. 17. Friends in Current Literature. 18. Editors' Note. 19. Anecdote of Obed Cook, Schoolmaster. 20. Early Quaker Booksellers of York

TWEAK-FN14 signaling induces lysosomal degradation of a cIAP1–TRAF2 complex to sensitize tumor cells to TNFα

Synthetic inhibitor of apoptosis (IAP) antagonists induce degradation of IAP proteins such as cellular IAP1 (cIAP1), activate nuclear factor κB (NF-κB) signaling, and sensitize cells to tumor necrosis factor α (TNFα). The physiological relevance of these discoveries to cIAP1 function remains undetermined. We show that upon ligand binding, the TNF superfamily receptor FN14 recruits a cIAP1–Tnf receptor-associated factor 2 (TRAF2) complex. Unlike IAP antagonists that cause rapid proteasomal degradation of cIAP1, signaling by FN14 promotes the lysosomal degradation of cIAP1–TRAF2 in a cIAP1-dependent manner. TNF-like weak inducer of apoptosis (TWEAK)/FN14 signaling nevertheless promotes the same noncanonical NF-κB signaling elicited by IAP antagonists and, in sensitive cells, the same autocrine TNFα-induced death occurs. TWEAK-induced loss of the cIAP1–TRAF2 complex sensitizes immortalized and minimally passaged tumor cells to TNFα-induced death, whereas primary cells remain resistant. Conversely, cIAP1–TRAF2 complex overexpression limits FN14 signaling and protects tumor cells from TWEAK-induced TNFα sensitization. Lysosomal degradation of cIAP1–TRAF2 by TWEAK/FN14 therefore critically alters the balance of life/death signals emanating from TNF-R1 in immortalized cells

Challenges and Opportunities in the Hydrologic Sciences

This is the Table of Contents and Introduction of a Report published as Hornberger, G. M., E. Bernhardt, W. E. Dietrich, D. Entekhabi, G. E. Fogg, E. Foufoula-Georgiou, W. J. Gutowski, W. B. Lyons, K. W. Potter, S. W. Tyler, H. J. Vaux, C. J. Vorosmarty, C. Welty, C. A. Woodhouse, C. Zheng, Challenges and Opportunities in the Hydrologic Sciences. 2012: Water Science and Technology Board, Division on Earth and Life Studies, National Academy of Sciences, Washington, DC. 173 pp. Posted with permission.</p

The role of the mucin-glycan foraging Ruminococcus gnavus in the communication between the gut and the brain

Ruminococcus gnavus is a prevalent member of the human gut microbiota, which is over-represented in inflammatory bowel disease and neurological disorders. We previously showed that the ability of R. gnavus to forage on mucins is strain-dependent and associated with sialic acid metabolism. Here, we showed that mice monocolonized with R. gnavus ATCC 29149 (Rg-mice) display changes in major sialic acid derivatives in their cecum content, blood, and brain, which is accompanied by a significant decrease in the percentage of sialylated residues in intestinal mucins relative to germ-free (GF) mice. Changes in metabolites associated with brain function such as tryptamine, indolacetate, and trimethylamine N-oxide were also detected in the cecal content of Rg-mice when compared to GF mice. Next, we investigated the effect of R. gnavus monocolonization on hippocampus cell proliferation and behavior. We observed a significant decrease of PSA-NCAM immunoreactive granule cells in the dentate gyrus (DG) of Rg-mice as compared to GF mice and recruitment of phagocytic microglia in the vicinity. Behavioral assessments suggested an improvement of the spatial working memory in Rg-mice but no change in other cognitive functions. These results were also supported by a significant upregulation of genes involved in proliferation and neuroplasticity. Collectively, these data provide first insights into how R. gnavus metabolites may influence brain regulation and function through modulation of granule cell development and synaptic plasticity in the adult hippocampus. This work has implications for further understanding the mechanisms underpinning the role of R. gnavus in neurological disorders

Determining Signalling Nodes for Apoptosis by a Genetic High-Throughput Screen

With the ever-increasing information emerging from the various sequencing and gene annotation projects, there is an urgent need to elucidate the cellular functions of the newly discovered genes. The genetically regulated cell suicide of apoptosis is especially suitable for such endeavours as it is governed by a vast number of factors.We have set up a high-throughput screen in 96-well microtiter plates for genes that induce apoptosis upon their individual transfection into human cells. Upon screening approximately 100,000 cDNA clones we determined 74 genes that initiate this cellular suicide programme. A thorough bioinformatics analysis of these genes revealed that 91% are novel apoptosis regulators. Careful sequence analysis and functional annotation showed that the apoptosis factors exhibit a distinct functional distribution that distinguishes the cell death process from other signalling pathways. While only a minority of classic signal transducers were determined, a substantial number of the genes fall into the transporter- and enzyme-category. The apoptosis factors are distributed throughout all cellular organelles and many signalling circuits, but one distinct signalling pathway connects at least some of the isolated genes. Comparisons with microarray data suggest that several genes are dysregulated in specific types of cancers and degenerative diseases.Many unknown genes for cell death were revealed through our screen, supporting the enormous complexity of cell death regulation. Our results will serve as a repository for other researchers working with genomics data related to apoptosis or for those seeking to reveal novel signalling pathways for cell suicide