164,275 research outputs found
Miro o mar, Morais no grande tabuleiro?
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Comunicação e Expressão. Programa de Pós-Graduação em Literatura.Esta pesquisa tem como objeto de estudo a obra A coroa no reino das possibilidades, do escritor catarinense Miro Morais e pretende realizar o entrecruzamento entre a corrente filosófica existencialista e a história veiculada no romance, cujo tema principal é comum e pertinente: a busca incessante da liberdade. Inicialmente investiga-se a trajetória literária do autor, seu estilo ficcional, temática e sua recepção na crítica literária. A seguir, percorre-se a história, temas e principais pensadores da filosofia existencialista, vertente filosófica que se propalava nos meios intelectuais na época em que o romance foi escrito. Logo, reconhece-se a forte influência que essa corrente de pensamento exerceu na poética literatura de Miro Morais, que numa escrita lúdica e lúcida leva o leitor a refletir sobre a vida, a liberdade e o sentido da existência
Miro proteins and their role in mitochondrial transfer in cancer and beyond
No full textMitochondria are organelles essential for tumor cell proliferation and metastasis. Although their main cellular function, generation of energy in the form of ATP is dispensable for cancer cells, their capability to drive their adaptation to stress originating from tumor microenvironment makes them a plausible therapeutic target. Recent research has revealed that cancer cells with damaged oxidative phosphorylation import healthy (functional) mitochondria from surrounding stromal cells to drive pyrimidine synthesis and cell proliferation. Furthermore, it has been shown that energetically competent mitochondria are fundamental for tumor cell migration, invasion and metastasis. The spatial positioning and transport of mitochondria involves Miro proteins from a subfamily of small GTPases, localized in outer mitochondrial membrane. Miro proteins are involved in the structure of the MICOS complex, connecting outer and inner-mitochondrial membrane; in mitochondria-ER communication; Ca(2+) metabolism; and in the recycling of damaged organelles via mitophagy. The most important role of Miro is regulation of mitochondrial movement and distribution within (and between) cells, acting as an adaptor linking organelles to cytoskeleton-associated motor proteins. In this review, we discuss the function of Miro proteins in various modes of intercellular mitochondrial transfer, emphasizing the structure and dynamics of tunneling nanotubes, the most common transfer modality. We summarize the evidence for and propose possible roles of Miro proteins in nanotube-mediated transfer as well as in cancer cell migration and metastasis, both processes being tightly connected to cytoskeleton-driven mitochondrial movement and positioning
[Report to Chief J. E. Curry, by an unknown author #1]
No full textReport to Chief J. E. Curry, by an unknown author. The report contains a list of officers who gave depositions to the United States Attorney
[Report to Chief J. E. Curry, by an unknown author #2]
No full textReport to Chief J. E. Curry, by an unknown author. The report contains a list of officers who gave depositions to the United States Attorney
Insight into the regulation of mitochondrial motility in the processes of S2R+ cells by endogenous Miro and Split-Miro.
No full text(A) Representative western blots of Miro from total lysates of control and Miro RNAi-treated S2R+ cells. (B) Duty cycle analysis describes the average time mitochondria spend moving anterogradely, retrogradely, or pausing. For each parameter, all mitochondrial values from each cell were averaged and compared between control and Miro dsRNA condition using a multiple Student’s t tests. Number of mitochondria analysed are in brackets from 29 (Ctrl dsRNA) and 36 (Miro dsRNA) cells, respectively, from 2 independent experiments. (C) Run velocities of short and long runs in control dsRNA-treated S2R+ cells showing that Miro-dependent long runs are significantly more processive than the short, Miro-independent runs (Fig 2C). Number of runs analysed are in brackets, from 2 independent experiments. Mann–Whitney test. (D) Split-Miro interacts with Milton in S2R+ cells. Cells were transfected with Split-Miro or Control (as shown in E) and the total cell lysates immunoprecipitated using GFP-beads to pull down EGFP-tagged Split-Miro C-terminus. Immunoprecipitates were blotted and probed with anti-GFP antibody (to detect Split-Miro C-terminus), anti-Miro antibody (to detect Split-Miro N-terminus), and an anti-Milton antibody. Inputs are total lysates (25 μg protein). (E) Cartoon showing Split-Miro and Control constructs with the GFP and Miro antibodies used for immunoprecipitation and western blotting in (D). (F) Representative kymographs of mitochondrial transport in the processes of S2R+ cells transfected with mCherry-tagged Zdk1-MiroC (Control), mCherry-Miro (wt-Miro), and mCherry-Split-Miro (Split-Miro). Scale bars: 2 μm (distance) and 5 seconds (time). G) Distribution of mitochondria run lengths in the processes of S2R+ cells, transfected with control, wt-Miro, and Split-Miro, as shown in F. N = number of mitochondrial runs. One-way ANOVA with Tukey’s post hoc test. (H) Duty cycle analysis describing the average time mitochondria spend moving anterogradely, retrogradely, or pausing in control, wt-Miro, and Split-Miro–transfected cells, relative to (F). For each parameter, all mitochondrial values per cell were averaged and compared by one-way ANOVA followed by Tukey’s post hoc test. Number of mitochondria are in brackets from 16 (control), 15 (wt-Miro), and 15 (Split-Miro) cells, respectively, from 3 independent experiments. (I) S2R+ cells transfected with wt-Miro and Split-Miro were imaged for 1 minute with a 561-nm laser, to capture the mCherry signal, followed by 1-minute imaging with 488-nm blue light, to capture the EGFP signal after Split-Miro photocleavage (relative to Fig 2E). Number of mitochondria are in brackets from 11 (wt-Miro) and 17 (Split-Miro) cells, from 3 independent experiments. Data are shown as mean ± SEM. Kolmogorov–Smirnov test showed no statistical difference between groups. (J) Distribution of mitochondrial run lengths in the anterograde direction in the processes of S2R+ cells, during the first and seventh minute of time-lapse imaging with blue light in cells transfected with wt-Miro or Split-Miro. N = number of runs. Mann–Whitney test showed no statistical difference between groups. (K) Run velocities for long processive anterograde and retrograde runs in S2R+ cells transfected with Split-Miro and Miro dsRNA (which targets endogenous Miro) and imaged by time-lapse for 7 minutes under blue light. Circles, number of runs, from 2 independent experiments. Mann–Whitney test shows no difference between first and seventh minutes of imaging, with the velocities remaining high compared to nontransfected condition (e.g., Figs 2H and S2C). This result shows that the velocities of the processive mitochondria, augmented as a consequence of Split-Miro overexpression, remain elevated even after reduction of endogenous Miro, suggesting Miro is not necessary for maintaining mitochondrial velocities. * p p p S1 Data. (TIF)</p
Advanced Mathematical Methods for Collaborative Robotics
No full textGracia Calandin, LI.; Perez-Vidal, C.; Valls-Miro, J. (2018). Advanced mathematical methods for collaborative robotics. Mathematical Problems in Engineering. 2018. https://doi.org/10.1155/2018/1605817S201
Doctor of Philosophy
No full textdissertationMitochondrial movement is a conserved cellular process observed in all eukaryotes, ranging from single-celled organisms to multicellular organisms. The distribution of mitochondria in most eukaryotes is dictated by the subcellular need for adenosine triphosphate (ATP) and intracellular calcium buffering. This is most apparent in polarized eukaryotic cells, like budding yeast and mammalian neurons. Perturbances in mitochondrial movement in polarized cells can impact cell division, function, and even survival. In fact, there are a growing number of neurodegenerative diseases linked to mitochondrial distribution defects. Guanine triphosphatase (GTPase) EF-hand protein of mitochondria or mitochondrial Rho GTPase (Gem1/Miro) proteins are the only known mitochondrial surface receptors implicated in mitochondrial movement. Although Gem1/Miro proteins are conserved from yeast to human, the molecular mechanism for mitochondrial movement is not apparently well conserved. Gem1, the yeast homologue of mammalian Miro, is implicated in actin-based mitochondrial movement. However, to date, there is no clear evidence that it is associated with motor proteins. Interestingly, both Gem1 and Miro are found at mitochondrial-endoplasmic reticulum (ER) contact sites and it is possible that mitochondria are moved by "hitching a ride" with the ER. The first part of this dissertation will focus on a yeast mitochondrial-ER connection and test whether mitochondrial movement in yeast can be mediated through these contact sites. Miro, the mammalian homologue of Gem1, on the other hand, forms a complex with motor proteins to move mitochondria along microtubules. The molecular function of mammalian Miro has been extensively studied in flies and mammalian cell culture. However, our understanding of the cellular and physiological consequences of disrupted mitochondrial motility in mammals is lacking. The latter part of this dissertation will focus on experiments that will test the in vivo function of Miro1 in neuronal maintenance and neurodegeneration. This dissertation will provide a detailed cellular and physiological analysis of Gem1/Miro-mediated mitochondrial movement using two model organisms, Saccharomyces cerevisiae and Mus Musculus. Chapter 2 will show that Gem1 is not required for mitochondrial-ER connections and that mitochondrial movement does not require a specific type of mitochondrial-ER connection found in yeast. Chapter 3 will provide the first direct evidence demonstrating that Miro1 is neuroprotective and that loss of Miro1 in neurons results in neurodegenerative phenotypes similar to human Motor Neuron Disease
Tactile Feedback for Artery Detection in Minimally Invasive Robotic Surgery –Preliminary Results of a New Approach
No full textMinimally invasive robotic surgery (MIRS) entails
total absence of haptic feedback due to the spatial separation
of patient and surgeon. In conventional surgery, however,
palpation to detect superficial arteries by a slight pulsation is
an important, commonly applied, and security-relevant procedure.
Therefore, an ultrasound based unidirectional sensor for
MIRS was developed feeding back kinesthetic impulses to the
surgeon-sided haptic input device
Shared structural features of Miro binding control mitochondrial homeostasis
No full textMiro proteins are universally conserved mitochondrial calcium-binding GTPases that regulate a multitude of mitochondrial processes, including transport, clearance, and lipid trafficking. The exact role of Miro in these functions is unclear but involves binding to a variety of client proteins. How this binding is operated at the molecular level and whether and how it is important for mitochondrial health, however, remains unknown. Here, we show that known Miro interactors—namely, CENPF, Trak, and MYO19—all use a similar short motif to bind the same structural element: a highly conserved hydrophobic pocket in the first calcium-binding domain of Miro. Using these Miro-binding motifs, we identified direct interactors de novo, including MTFR1/2/1L, the lipid transporters Mdm34 and VPS13D, and the ubiquitin E3-ligase Parkin. Given the shared binding mechanism of these functionally diverse clients and its conservation across eukaryotes, we propose that Miro is a universal mitochondrial adaptor coordinating mitochondrial health
Identification of Miro as a mitochondrial receptor for myosin XIX
No full textABSTRACTMitochondrial distribution in cells is critical for cellular function and proper inheritance during cell division. In mammalian cells, mitochondria are transported predominantly along microtubules by kinesin and dynein and along actin filaments by myosin. Myosin XIX (Myo19) associates with the outer mitochondrial membrane, but no specific receptor has been identified. Using proximity BioID labeling, we identified Miro-1 and Miro-2 as potential binding partners of Myo19. Interaction studies show that Miro-1 binds to a C-terminal fragment of the Myo19 tail region and that Miro recruits the Myo19 tail in vivo. This recruitment is regulated by the nucleotide-state of the N-terminal Rho-like GTPase domain of Miro. Notably, Myo19 protein stability in cells depends on its association with Miro. Finally, Myo19 regulates the subcellular distribution of mitochondria. Downregulation, as well as overexpression, of Myo19 induces perinuclear collapse of mitochondria, phenocopying the loss of kinesin KIF5 or its mitochondrial receptor Miro. These results suggest that Miro coordinates microtubule- and actin-based mitochondrial movement.</jats:p
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