Evidence for cross rift structural controls on deformation and seismicity at a continental rift caldera

In continental rifts structural heterogeneities, such as pre-existing faults and foliations, are thought to influence shallow crustal processes, particularly the formation of rift faults, magma reservoirs and surface volcanism. We focus on the Corbetti caldera, in the southern central Main Ethiopian Rift. We measure the surface deformation between 22nd June 2007 and 25th March 2009 using ALOS and ENVISAT SAR interferograms and observe a semi-circular pattern of deformation bounded by a sharp linear feature cross-cutting the caldera, coincident with the caldera long axis. The signal reverses in sign but is not seasonal: from June to December 2007 the region south of this structure moves upwards 3 cm relative to the north, while from December 2007 until November 2008 it subsides by 2 cm. Comparison of data taken from two different satellite look directions show that the displacement is primarily vertical. We discuss potential mechanisms and conclude that this deformation is associated with pressure changes within a shallow (<1 km) fault-bounded hydrothermal reservoir prior to the onset of a phase of caldera-wide uplift. Analysis of the distribution of post-caldera vents and cones inside the caldera shows their locations are statistically consistent with this fault structure, indicating that the fault has also controlled the migration of magma from a reservoir to the surface over tens of thousands of years. Spatial patterns of seismicity are consistent with a cross-rift structure that extents outside the caldera and to a depth of ∼30 km, and patterns of seismic anisotropy suggests stress partitioning occurs across the structure. We discuss the possible nature of this structure, and conclude that it is most likely associated with the Goba–Bonga lineament, which cross-cuts and pre-dates the current rift. Our observations show that pre-rift structures play an important role in magma transport and shallow hydrothermal processes, and therefore they should not be neglected when discussing these processes

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

The Role of E2 Affinity in Ubiquitination by the Anaphase-Promoting Complex

The anaphase-promoting complex/cyclosome (APC/C) is a large, multi-subunit E3 ubiquitin ligase that governs key mitotic events in eukaryotes. The APC/C catalyzes the transfer of ubiquitin from an E2 ubiquitin-conjugating enzyme to a protein substrate, building polyubiquitin signals that mark substrates for destruction by the proteasome. In yeast, the APC/C collaborates with two E2s, Ubc4 and Ubc1: APC/CUbc4 catalyzes the attachment of the initial ubiquitin to the substrate, while APC/CUbc1 elongates ubiquitin chains. Both E2s seem to interact with the same site on the APC/C, and it is not clear how their competing activities collaborate to generate a polyubiquitin chain that is sufficient for proteosomal recognition. We hypothesized that E2 synergy requires a finely tuned balance of the affinities of the two E2 proteins for the APC/C, allowing E2s to alternate on the APC/C. In this work, we uncovered new insights into this problem by studying the role of a C-terminal ubiquitin-associated (UBA) domain in Ubc1. Deletion of the UBA domain decreased the length of polyubiquitin chains and increased the concentration of Ubc1 required for half-maximal APC/C activity in vitro. Surprisingly, the stimulatory effect of the UBA domain does not depend on previous initiation of a ubiquitin chain on the substrate, suggesting that the UBA domain does not promote polyubiquitination by interacting with ubiquitin on a substrate. Instead, deletion of the UBA domain reduced Ubc1 binding to the APC/C. Finally, deletion of the UBA domain from Ubc1 decreased its ability to compete with Ubc4 and reduced polyubiquitin chain length, while attachment of the UBA domain to Ubc4 increased its ability to compete with Ubc1 and reduced polyubiquitin chain length. Thus, the extra affinity provided by the UBA domain of Ubc1 ensures efficient polyubiquitination of substrate by balancing Ubc1 affinity with that of Ubc4, resulting in an efficient collaboration between the two E2s

An E2 Accessory Domain Increases Affinity for the Anaphase-promoting Complex and Ensures E2 Competition*

The anaphase-promoting complex/cyclosome (APC/C) is a member of the RING family of E3 ubiquitin ligases, which promote ubiquitin transfer from an E2 ubiquitin-conjugating enzyme to a substrate. In budding yeast, the APC/C collaborates with two E2s, Ubc4 and Ubc1, to promote the initiation and elongation, respectively, of polyubiquitin chains on the substrate. Ubc4 and Ubc1 are thought to compete for the same site on the APC/C, but it is not clear how their affinities are balanced. Here, we demonstrate that a C-terminal ubiquitin-associated (UBA) domain enhances the affinity of Ubc1 for the APC/C. Deletion of the UBA domain reduced apparent APC/C affinity for Ubc1 and decreased polyubiquitin chain length. Surprisingly, the positive effect of the UBA domain was not due to an interaction with the acceptor ubiquitin attached to the APC/C substrate or the donor ubiquitin attached to Ubc1 itself. Instead, our evidence suggests that the UBA domain binds to a site on the APC/C core, thereby increasing Ubc1 affinity and enhancing its ability to compete with Ubc4. The UBA domain is required for normal Ubc1 function and E2 competition in vivo. Thus, the UBA domain of Ubc1 ensures efficient polyubiquitination of substrate by balancing Ubc1 affinity with that of Ubc4

Injury-induced inflammatory signaling and hematopoiesis in Drosophila.

Inflammatory response in Drosophila to sterile (axenic) injury in embryos and adults has received some attention in recent years, and most concentrate on the events at the injury site. Here we focus on the effect sterile injury has on the hematopoietic organ, the lymph gland, and the circulating blood cells in the larva, the developmental stage at which major events of hematopoiesis are evident. In mammals, injury activates Toll-like receptor/NF-κB signaling in macrophages, which then express and secrete secondary, proinflammatory cytokines. In Drosophila larvae, distal puncture injury of the body wall epidermis causes a rapid activation of Toll and Jun kinase (JNK) signaling throughout the hematopoietic system and the differentiation of a unique blood cell type, the lamellocyte. Furthermore, we find that Toll and JNK signaling are coupled in their activation. Secondary to this Toll/JNK response, a cytokine, Upd3, is induced as a Toll pathway transcriptional target, which then promotes JAK/STAT signaling within the blood cells. Toll and JAK/STAT signaling are required for the emergence of the injury-induced lamellocytes. This is akin to the derivation of specialized macrophages in mammalian systems. Upstream, at the injury site, a Duox- and peroxide-dependent signal causes the activation of the proteases Grass and SPE, needed for the activation of the Toll-ligand Spz, but microbial sensors or the proteases most closely associated with them during septic injury are not involved in the axenic inflammatory response

Drosophila as a Genetic Model for Hematopoiesis.

In this FlyBook chapter, we present a survey of the current literature on the development of the hematopoietic system in Drosophila The Drosophila blood system consists entirely of cells that function in innate immunity, tissue integrity, wound healing, and various forms of stress response, and are therefore functionally similar to myeloid cells in mammals. The primary cell types are specialized for phagocytic, melanization, and encapsulation functions. As in mammalian systems, multiple sites of hematopoiesis are evident in Drosophila and the mechanisms involved in this process employ many of the same molecular strategies that exemplify blood development in humans. Drosophila blood progenitors respond to internal and external stress by coopting developmental pathways that involve both local and systemic signals. An important goal of these Drosophila studies is to develop the tools and mechanisms critical to further our understanding of human hematopoiesis during homeostasis and dysfunction

Additional file 1: of Quantitative framework for ordered degradation of APC/C substrates

Supplementary Figures. Figure S1. Ordered degradation of APC/C substrates. Figure S2. Determination of the time of degradation onset. Figure S3. Mechanisms that determine substrate degradation timing all change degradation onset. Figure S4. Ordinary differential equations for analysis of substrate degradation in the one-substrate model. Figure S5. APC/CCdc20 levels in the cell are lower than those of its substrates. Figure S6. Including deubiquitination in the model further limits the parameter space that generates a good delay in degradation onset and a fast rate of degradation. Figure S7. Changing k d influences T95 when not all APC/CCdc20 is bound to the substrate. Figure S8. Effects of doubling the concentration of C on T95 of S. (PDF 5283 kb

Paths and pathways that generate cell-type heterogeneity and developmental progression in hematopoiesis.

Mechanistic studies of Drosophila lymph gland hematopoiesis are limited by the availability of cell-type-specific markers. Using a combination of bulk RNA-Seq of FACS-sorted cells, single-cell RNA-Seq, and genetic dissection, we identify new blood cell subpopulations along a developmental trajectory with multiple paths to mature cell types. This provides functional insights into key developmental processes and signaling pathways. We highlight metabolism as a driver of development, show that graded Pointed expression allows distinct roles in successive developmental steps, and that mature crystal cells specifically express an alternate isoform of Hypoxia-inducible factor (Hif/Sima). Mechanistically, the Musashi-regulated protein Numb facilitates Sima-dependent non-canonical, and inhibits canonical, Notch signaling. Broadly, we find that prior to making a fate choice, a progenitor selects between alternative, biologically relevant, transitory states allowing smooth transitions reflective of combinatorial expressions rather than stepwise binary decisions. Increasingly, this view is gaining support in mammalian hematopoiesis

An E2 Accessory Domain Increases Affinity for the Anaphase-promoting Complex and Ensures E2 Competition

The anaphase-promoting complex/cyclosome (APC/C) is a member of the RING family of E3 ubiquitin ligases, which promote ubiquitin transfer from an E2 ubiquitin-conjugating enzyme to a substrate. In budding yeast, the APC/C collaborates with two E2s, Ubc4 and Ubc1, to promote the initiation and elongation, respectively, of polyubiquitin chains on the substrate. Ubc4 and Ubc1 are thought to compete for the same site on the APC/C, but it is not clear how their affinities are balanced. Here, we demonstrate that a C-terminal ubiquitin-associated (UBA) domain enhances the affinity of Ubc1 for the APC/C. Deletion of the UBA domain reduced apparent APC/C affinity for Ubc1 and decreased polyubiquitin chain length. Surprisingly, the positive effect of the UBA domain was not due to an interaction with the acceptor ubiquitin attached to the APC/C substrate or the donor ubiquitin attached to Ubc1 itself. Instead, our evidence suggests that the UBA domain binds to a site on the APC/C core, thereby increasing Ubc1 affinity and enhancing its ability to compete with Ubc4. The UBA domain is required for normal Ubc1 function and E2 competition in vivo. Thus, the UBA domain of Ubc1 ensures efficient polyubiquitination of substrate by balancing Ubc1 affinity with that of Ubc4