Curiosidades na nomenclatura mineralógica: Porpezita do Brasil

Na virada do século 19 para o século 20, especialmente nos primeiros anos do século 20, surgiu o nome Porpezita, imerso em livros de mineralogia, principalmente na Europa e em especial na literatura francesa. O termo foi atribuído à liga de ouro-paládio (Au, Pd). Amostras de Porpezita chegaram a Viena, em meados do século 19, provavelmente pelo mineralogista austríaco Pohl. Dizia-se que elas teriam chegado da província Porpez no Brasil. No entanto, essa capitania não existe e jamais existiu. O mineral recebeu seu nome provavelmente de uma desfiguração do nome do estado brasileiro de Goiás. Este artigo discute três possíveis razões para tal distorção, ou seja, de como Goiás virou Porpez e como Porpez deu seu nome ao mineral Porpezita. A IMA (International Mineralogical Association) não reconhece o nome; no entanto, ele não pode ser mais banido da literatura, particularmente da InterNet

Schuermann_Figure_4

Schuermann_Figure_4 - contains files demonstrating that the consecutive N-terminal truncation of HhC85S reverses the dominant negative phenotype. Supplemental folders contain confirming data obtained from independent driver lines en(2)-Gal4 and Hh_Gal4. Unimpaired multimerization as a prerequisite for direct contact with, and dominant-negative suppression of Hh activity are shown as excel-files. HhC85SD86-100 denotes a non-palmitoylated Hh variant that lacks inhibitory N-terminal peptide amino acids 86-100

Schuermann_Figure_3

Schuermann_Figure_3 - contains Excel-data on HhC85S multimerization and demonstrates that HhNC85S, a non-lipidated artificial Hh variant, does not act in dominant-negative manner. Contains Prize-Files to quantify unaffected wing patterning in three independently derived HhNC85S lines. The original wing patterns are shown in folders en>HhNC85S and ptc>HhNC85S

Data from: Proteolytic processing of palmitoylated Hedgehog peptides specifies the 3-4 intervein region of the Drosophila wing

Cell fate determination during development often requires morphogen transport from producing to distant responding cells. Hedgehog (Hh) morphogens present a challenge to this concept, as all Hhs are synthesized as terminally lipidated molecules that form insoluble clusters at the surface of producing cells. While several proposed Hh transport modes tie directly into these unusual properties, the crucial step of Hh relay from producing cells to receptors on remote responding cells remains unresolved. Using wing development in Drosophila melanogaster as a model, we show that Hh relay and direct patterning of the 3-4 intervein region strictly depend on proteolytic removal of lipidated N-terminal membrane anchors. Site-directed modification of the N-terminal Hh processing site selectively eliminated the entire 3-4 intervein region, and additional targeted removal of N-palmitate restored its formation. Hence, palmitoylated membrane anchors restrict morphogen spread until site-specific processing switches membrane-bound Hh into bioactive forms with specific patterning functions

Argonaute proteins are key determinants of RNAi efficacy, toxicity, and persistence in the adult mouse liver

shRNA overexpression from viral gene therapy vectors can trigger cytotoxicity leading to organ failure and lethality in mice and rats. This process likely involves saturation of endogenous cellular RNAi factors including exportin-5 (Xpo-5). Here, we have shown that Xpo-5 overexpression enhanced shRNA efficiency in the liver of adult mice but increased hepatotoxicity. We identified the 4 members of the human Argonaute (Ago) protein family as downstream factors involved in saturation of endogenous cellular RNAi, all of which were able to interact with shRNAs in cells and mice. In Ago/shRNA coexpression studies, Ago-2 (Slicer) was the primary rate-limiting determinant of both in vitro and in vivo RNAi efficacy, toxicity, and persistence. In adult mice, vector-based Ago-2/Xpo-5 coexpression enhanced U6-driven shRNA silencing of exogenous and endogenous hepatic targets, reduced hepatotoxicity, and extended RNAi stability by more than 3 months. Use of weaker RNA polymerase III promoters to minimize shRNA expression likewise alleviated in vivo toxicity and permitted greater than 95% persistent knockdown of hepatitis B virus and other transgenes in mouse liver for more than 1 year. Our studies substantiate that abundant small RNAs can overload the endogenous RNAi pathway and reveal possible strategies for reducing hepatotoxicity of short- and long-term clinical gene silencing in humans

Fate tracing of mature hepatocytes in mouse liver homeostasis and regeneration

Recent evidence has contradicted the prevailing view that homeostasis and regeneration of the adult liver are mediated by self duplication of lineage-restricted hepatocytes and biliary epithelial cells. These new data suggest that liver progenitor cells do not function solely as a backup system in chronic liver injury; rather, they also produce hepatocytes after acute injury and are in fact the main source of new hepatocytes during normal hepatocyte turnover. In addition, other evidence suggests that hepatocytes are capable of lineage conversion, acting as precursors of biliary epithelial cells during biliary injury. To test these concepts, we generated a hepatocyte fate-tracing model based on timed and specific Cre recombinase expression and marker gene activation in all hepatocytes of adult Rosa26 reporter mice with an adenoassociated viral vector. We found that newly formed hepatocytes derived from preexisting hepatocytes in the normal liver and that liver progenitor cells contributed minimally to acute hepatocyte regeneration. Further, we found no evidence that biliary injury induced conversion of hepatocytes into biliary epithelial cells. These results therefore restore the previously prevailing paradigms of liver homeostasis and regeneration. In addition, our new vector system will be a valuable tool for timed, efficient, and specific loop out of floxed sequences in hepatocytes

Schuermann_Figure_1

Schuermann_Figure_1 - contains Prism-File "angles between nearest neighbours" to quantify patterns of immunoggold-labelling of cell-surface associated large Hedgehog (Hh) morphogen clusters. Contains Folder "IEM of Shh on Bosc23" showing original IEM data. Contains PyMol file "apbs_olig_hh.pse" showing a modelled fly Hh pentamer using crystal lattice interactions observed in the human Sonic Hh crystal structure pdb3m1n as a template