Mitochondrial fusion is regulated by Reaper to modulate Drosophila programmed cell death.

In most multicellular organisms, the decision to undergo programmed cell death in response to cellular damage or developmental cues is typically transmitted through mitochondria. It has been suggested that an exception is the apoptotic pathway of Drosophila melanogaster, in which the role of mitochondria remains unclear. Although IAP antagonists in Drosophila such as Reaper, Hid and Grim may induce cell death without mitochondrial membrane permeabilization, it is surprising that all three localize to mitochondria. Moreover, induction of Reaper and Hid appears to result in mitochondrial fragmentation during Drosophila cell death. Most importantly, disruption of mitochondrial fission can inhibit Reaper and Hid-induced cell death, suggesting that alterations in mitochondrial dynamics can modulate cell death in fly cells. We report here that Drosophila Reaper can induce mitochondrial fragmentation by binding to and inhibiting the pro-fusion protein MFN2 and its Drosophila counterpart dMFN/Marf. Our in vitro and in vivo analyses reveal that dMFN overexpression can inhibit cell death induced by Reaper or γ-irradiation. In addition, knockdown of dMFN causes a striking loss of adult wing tissue and significant apoptosis in the developing wing discs. Our findings are consistent with a growing body of work describing a role for mitochondrial fission and fusion machinery in the decision of cells to die.

Characterization of cellular and molecular functions of the p21 -activated kinase, Shk1, in the fission yeast, Schizosaccharomyces pombe

The p21-activated kinase, Shk1, is an essential serine/threonine kinase required for normal cell polarity, proper mating response, and hyperosmotic stress response, in the fission yeast, Schizosaccharomyces pombe. This study has established a novel role for Shk1 as a microtubule regulator in fission yeast and, in addition, characterized a potential biological substrate of Shk1. Cells defective in Shk1 function were found to exhibit malformed interphase and mitotic microtubules, are hypersensitive to the microtubule disrupting drug thiabendazole (TBZ), and are cold sensitive for growth. Microtubule disruption by TBZ results in a significant reduction of Shk1 kinase activity, which is restored after cells are released from the drug, thus providing a correlation between Shk1 kinase activity and active microtubule polymerization. Consistent with a role for Shk1 as a microtubule regulator, GFP-Shk1 fusion proteins localize to interphase microtubules and mitotic microtubule spindles. Furthermore, loss of Tea1, a presumptive microtubule regulator in fission yeast, exacerbates the growth and microtubule defects of cells deficient in Shk1 function, and results in illicit Shk1 localization. Moreover, loss of the Cdc2 inhibitory kinase Wee1, which has been implicated as a mediator of the Shk1 pathway, leads to significant microtubule defects. Intriguingly, Wee1 protein levels are markedly reduced both by partial loss of Shk1 function and by treatment with TBZ. These results suggest that Shk1 is required for proper regulation of microtubule dynamics in fission yeast and may interact with Tea1 and Wee1 in this regulatory process. ^ To further understand Shk1 function in fission yeast, a yeast two-hybrid screen for proteins that interact with the Shk1 catalytic domain was performed. This screen led to the identification of a novel protein, Skb10 (for S&barbelow;hk1 k&barbelow;inase b&barbelow;inding protein 10). Coprecipitation experiments demonstrated that Skb10 associates with Shk1 in S. pombe cells. (Abstract shortened by UMI.) ^

A Comparison of different Uncertainty Activation Cross-Section Data Libraries and collapsed values for different neutron spectra: ADS, FISSION and FUSION

PART I:Cross-section uncertainties under differentneutron spectra. PART II: Processing uncertainty libraries

Coronal fluid-dynamics in laser fusion

The fluid-dynamics of the corona ejected by laser-fusion targets in the direct-drive approach (thermal radiation and atomic physics unimportant) is discussed. A two-fluid model involves inverse bremsstrahlung absorption, refraction, different ion and electron temperatures with energy exchange, different ion and electron velocities and magnetic field generation, and their effect on ion-electron friction and heat flux. Four dimensionless parameters determine coronal regimes for one-dimensional flows under uniform irradiation. One additional parameter is involved in two-dimensional problems,including the stability of one-dimensional flows, and the smoothing of nonuniform driving.

Simulating the remote handling of the blanket segments in DEMO fusion reactor with thermo-mechanical meshfree multibody dynamics

The present study shows a first approach to the simulation of the remote handling oper- ation which takes into account the thermal and flexible behavior of the blanket segments and its implications on the remote handling equipment, in order to validate and improve its design.

Vacuole Fusion Regulated by Protein Phosphatase 2C in Fission Yeast

The gene ptc4+ encodes one of four type 2C protein phosphatases (PP2C) in the fission yeast Schizosaccharomyces pombe. Deletion of ptc4+ is not lethal; however, Δptc4 cells grow slowly in defined minimal medium and undergo premature growth arrest in response to nitrogen starvation. Interestingly, Δptc4 cells are unable to fuse vacuoles in response to hypotonic stress or nutrient starvation. Conversely, Ptc4 overexpression appears to induce vacuole fusion. These findings reveal a hitherto unrecognized function of type 2C protein phosphatases: regulation of vacuole fusion. Ptc4 localizes in vacuole membranes, which suggests that Ptc4 regulates vacuole fusion by dephosphorylation of one or more proteins in the vacuole membrane. Vacuole function is required for the process of autophagy that is induced by nutrient starvation; thus, the vacuole defect of Δptc4 cells might explain why these cells undergo premature growth arrest in response to nitrogen starvation.

Dynamics of Centromeres during Metaphase–Anaphase Transition in Fission Yeast: Dis1 Is Implicated in Force Balance in Metaphase Bipolar Spindle

In higher eukaryotic cells, the spindle forms along with chromosome condensation in mitotic prophase. In metaphase, chromosomes are aligned on the spindle with sister kinetochores facing toward the opposite poles. In anaphase A, sister chromatids separate from each other without spindle extension, whereas spindle elongation takes place during anaphase B. We have critically examined whether such mitotic stages also occur in a lower eukaryote, Schizosaccharomyces pombe. Using the green fluorescent protein tagging technique, early mitotic to late anaphase events were observed in living fission yeast cells. S. pombe has three phases in spindle dynamics, spindle formation (phase 1), constant spindle length (phase 2), and spindle extension (phase 3). Sister centromere separation (anaphase A) rapidly occurred at the end of phase 2. The centromere showed dynamic movements throughout phase 2 as it moved back and forth and was transiently split in two before its separation, suggesting that the centromere was positioned in a bioriented manner toward the poles at metaphase. Microtubule-associating Dis1 was required for the occurrence of constant spindle length and centromere movement in phase 2. Normal transition from phase 2 to 3 needed DNA topoisomerase II and Cut1 but not Cut14. The duration of each phase was highly dependent on temperature.

Feasibility study of a fission-suppressed Tokamak fusion breeder /

"UCID-20154"--Cover.

Remote Ischemic Conditioning Influences Mitochondrial Dynamics

International audience

Fusion of in-vehicle sensor data to develop Intelligent Driver Training System (IDTS)

The over represented number of novice drivers involved in crashes is alarming. Driver training is one of the interventions aimed at mitigating the number of crashes that involve young drivers. To our knowledge, Advanced Driver Assistance Systems (ADAS) have never been comprehensively used in designing an intelligent driver training system. Currently, there is a need to develop and evaluate ADAS that could assess driving competencies. The aim is to develop an unsupervised system called Intelligent Driver Training System (IDTS) that analyzes crash risks in a given driving situation. In order to design a comprehensive IDTS, data is collected from the Driver, Vehicle and Environment (DVE), synchronized and analyzed. The first implementation phase of this intelligent driver training system deals with synchronizing multiple variables acquired from DVE. RTMaps is used to collect and synchronize data like GPS, vehicle dynamics and driver head movement. After the data synchronization, maneuvers are segmented out as right turn, left turn and overtake. Each maneuver is composed of several individual tasks that are necessary to be performed in a sequential manner. This paper focuses on turn maneuvers. Some of the tasks required in the analysis of ‘turn’ maneuver are: detect the start and end of the turn, detect the indicator status change, check if the indicator was turned on within a safe distance and check the lane keeping during the turn maneuver. This paper proposes a fusion and analysis of heterogeneous data, mainly involved in driving, to determine the risk factor of particular maneuvers within the drive. It also explains the segmentation and risk analysis of the turn maneuver in a drive.

GPS fault detection with IMU and aircraft dynamics

Approaches with Vertical Guidance (APV) can provide greater safety and cost savings to general aviation through accurate GPS horizontal and vertical navigation. However, GPS needs augmentation to achieve APV fault detection requirements. Aircraft Based Augmentation Systems (ABAS) fuse GPS with additional sensors at the aircraft. Typical ABAS designs assume high-quality inertial sensors with Kalman filters but these are too expensive for general aviation. Instead of using high-quality (and expensive) sensors, the purpose of this paper is to investigate augmenting GPS with a low-quality MEMS IMU and Aircraft Dynamic Model (ADM). The IMU and ADM are fused together using a multiple model fusion strategy in a bank of Extended Kalman Filters (EKF) with the Normalized Solution Separation (NSS) fault detection scheme. A tightly-coupled configuration with GPS is used and frequent GPS updates are applied to the IMU and ADM to compensate for their errors. Based upon a simulated APV approach, the performance of this architecture in detecting a GPS ramp fault is investigated showing a performance improvement over a GPS-only “snapshot” implementation of the NSS method. The effect of fusing the IMU with the ADM is evaluated by comparing a GPS-IMU-ADM EKF with a GPS-IMU EKF where a small improvement in protection levels is shown.