Emergence of the mitochondrial reticulum from fission and fusion dynamics

Mitochondria form a dynamic tubular reticulum within eukaryotic cells. Currently, quantitative understanding of its morphological characteristics is largely absent, despite major progress in deciphering the molecular fission and fusion machineries shaping its structure. Here we address the principles of formation and the large-scale organization of the cell-wide network of mitochondria. On the basis of experimentally determined structural features we establish the tip-to-tip and tip-to-side fission and fusion events as dominant reactions in the motility of this organelle. Subsequently, we introduce a graph-based model of the chondriome able to encompass its inherent variability in a single framework. Using both mean-field deterministic and explicit stochastic mathematical methods we establish a relationship between the chondriome structural network characteristics and underlying kinetic rate parameters. The computational analysis indicates that mitochondrial networks exhibit a percolation threshold. Intrinsic morphological instability of the mitochondrial reticulum resulting from its vicinity to the percolation transition is proposed as a novel mechanism that can be utilized by cells for optimizing their functional competence via dynamic remodeling of the chondriome. The detailed size distribution of the network components predicted by the dynamic graph representation introduces a relationship between chondriome characteristics and cell function. It forms a basis for understanding the architecture of mitochondria as a cell-wide but inhomogeneous organelle. Analysis of the reticulum adaptive configuration offers a direct clarification for its impact on numerous physiological processes strongly dependent on mitochondrial dynamics and organization, such as efficiency of cellular metabolism, tissue differentiation and aging

Formins Determine the Functional Properties of Actin Filaments in Yeast

The actin cytoskeleton executes a broad range of essential functions within a living cell. The dynamic nature of the actin polymer is modulated to facilitate specific cellular processes at discrete locations by actin-binding proteins (ABPs), including the formins and tropomyosins (Tms). Formins nucleate actin polymers, while Tms are conserved dimeric proteins that form polymers along the length of actin filaments. Cells possess different Tm isoforms, each capable of differentially regulating the dynamic and func- tional properties of the actin polymer. However, the mecha- nism by which a particular Tm localizes to a specific actin polymer is unknown. Here we show that specific formin family members dictate which Tm isoform will associate with a particular actin filament to modulate its dynamic and functional properties at specific cellular locations. Exchanging the localization of the fission yeast formins For3 and Cdc12 results in an exchange in localizations of Tm forms on actin polymers. This nucleator-driven switch in filament composition is reflected in a switch in actin dynamics, together with a corresponding change in the filament’s ability to regulate ABPs and myosin motor activity. These data establish a role for formins in dictating which specific Tm variant will associate with a growing actin filament and therefore specify the functional capacity of the actin filaments that they create

Fission-Fragment Mass Distribution and Particle Evaporation at low Energies

Fusion-fission dynamics is investigated with a special emphasis on fusion reactions at low energy for which shell effects and pairing correlations can play a crucial role leading in particular to multi-modal fission. To follow the dynamical evolution of an excited and rotating nucleus we solve a 2-dimensional Langevin equation taking explicitly light-particle evaporation into account. The confrontation theory-experiment is demonstrated to give interesting information on the model presented, its qualities as well as its shortcomings.Comment: 19 pages, latex, 24 eps-figure

Cathodal Occipital tDCS is unable to modulate The Sound Induced Flash Illusion in migraine

Migraine is a highly disabling disease characterized by recurrent pain.Despite an intensive effort, mechanisms of migraine pathophysiology, still represent an unsolved issue. Evidences from both animals and humans studies suggest that migraine is characterized by hyperresponsivity or hyperexcitability of sensory cortices, especially the visual cortex. This phenomenon, in turn, may affect multisensory processing. Indeed, migraineurs present with an abnormal, reduced, perception of the Sound-induced Flash Illusion (SiFI), a crossmodal illusion that relies on optimal integration of visual and auditory stimuli by the occipital visual cortex. Decreasing visual cortical excitability with transcranial direct current stimulation (tDCS) can increase the SiFI in healthy subjects. Moving from these issues , we applied cathodal tDCS over the visual cortex of migraineurs, with and without aura, in order to decrease cortical excitability and thus physiologically restoring the perception of a reliable SiFI. Differently from our expectations tDCS was unable to reliably modulate SiFI in migraine. The chronic, relatively excessive, visual cortex hyperexcitability, , featuring the migraineur brain, may render tDCS ineffective for restoring multisensory processing in this disease

Contribution to fusion research from IAEA coordinated research projects and joint experiments

The paper presents objectives and activities of IAEA Coordinated Research Projects 'Conceptual development of steady-state compact fusion neutron sources' and 'Utilisation of a network of small magnetic confinement fusion devices for mainstream fusion research'. The background and main projects of the CRP on FNS are described in detail, as this is a new activity at IAEA. Recent activities of the second CRP, which continues activities of previous CRPs, are overviewed

An experimental survey of the production of alpha decaying heavy elements in the reactions of 238^{238}U +232^{232}Th at 7.5-6.1 MeV/nucleon

The production of alpha particle decaying heavy nuclei in reactions of 7.5-6.1 MeV/nucleon $^{238}$U +$^{232}$Th has been explored using an in-beam detection array composed of YAP scintillators and gas ionization chamber-Si telescopes. Comparisons of alpha energies and half-lives for the observed products with those of the previously known isotopes and with theoretically predicted values indicate the observation of a number of previously unreported alpha emitters. Alpha particle decay energies reaching as high as 12 MeV are observed. Many of these are expected to be from decay of previously unseen relatively neutron rich products. While the contributions of isomeric states require further exploration and specific isotope identifications need to be made, the production of heavy isotopes with quite high atomic numbers is suggested by the data.Comment: 12 pages, 12 figure