Role of sirtuin 3 on mitochondrial dynamics in Huntington's disease striatal cells

Dissertação de mestrado em Genética Molecular

Inflammation-induced alteration of astrocyte mitochondrial dynamics requires autophagy for mitochondrial network maintenance.

Accumulating evidence suggests that changes in the metabolic signature of astrocytes underlie their response to neuroinflammation, but how proinflammatory stimuli induce these changes is poorly understood. By monitoring astrocytes following acute cortical injury, we identified a differential and region-specific remodeling of their mitochondrial network: while astrocytes within the penumbra of the lesion undergo mitochondrial elongation, those located in the core-the area invaded by proinflammatory cells-experience transient mitochondrial fragmentation. In brain slices, proinflammatory stimuli reproduced localized changes in mitochondrial dynamics, favoring fission over fusion. This effect was triggered by Drp1 phosphorylation and ultimately resulted in reduced respiratory capacity. Furthermore, maintenance of the mitochondrial architecture critically depended on the induction of autophagy. Deletion of Atg7, required for autophagosome formation, prevented the reestablishment of tubular mitochondria, leading to marked reactive oxygen species accumulation and cell death. Thus, our data reveal autophagy to be essential for regenerating astrocyte mitochondrial networks during inflammation.

Driven fragmentation of granular gases

The dynamics of homogeneously heated granular gases which fragment due to particle collisions is analyzed. We introduce a kinetic model which accounts for correlations induced at the grain collisions and analyze both the kinetics and relevant distribution functions these systems develop. The work combines analytical and numerical studies based on direct simulation Monte Carlo calculations. A broad family of fragmentation probabilities is considered, and its implications for the system kinetics are discussed. We show that generically these driven materials evolve asymptotically into a dynamical scaling regime. If the fragmentation probability tends to a constant, the grain number diverges at a finite time, leading to a shattering singularity. If the fragmentation probability vanishes, then the number of grains grows monotonously as a power law. We consider different homogeneous thermostats and show that the kinetics of these systems depends weakly on both the grain inelasticity and driving. We observe that fragmentation plays a relevant role in the shape of the velocity distribution of the particles. When the fragmentation is driven by local stochastic events, the longvelocity tail is essentially exponential independently of the heating frequency and the breaking rule. However, for a Lowe-Andersen thermostat, numerical evidence strongly supports the conjecture that the scaled velocity distribution follows a generalized exponential behavior f (c)~exp (−cⁿ), with n ≈1.2, regarding less the fragmentation mechanisms

Woody community dynamics in two fragments of "cerrado" stricto sensu over a seven-year period (1995-2002), MA, Brazil

This study was conducted in two fragments of "cerrado" stricto sensu in the Gerais de Balsas Colonization Project, located in southern Maranhão, Brazil. The objective was to evaluate the dynamics of the woody plant community, over seven years (1995-2002). Four transects of 160 × 20 m were monitored. All woody plants with a stem diameter > 3 cm, at 0.30 m above ground level, were recorded. In 1995, 983 and 1,177 stems were sampled in fragments 1 and 2, respectively; in 2002, 1057 and 1406 stems were sampled in the same fragments. In 1995, the Shannon diversity indices (H') were 3.07 and 3.33, in fragments 1 and 2, respectively, reaching their maximum value in 2002 of 3.11 and 3.35. The community of fragment 1 showed an increase of 7.5% in density and 4.4% in basal area between 1995 and 2002, while in fragment 2 there was an increment of 19.4% in density and 23.5% in basal area, over the same period. The annual increment in diameter was 0.13 cm year-1 and 0.17 cm year-1 in fragments 1 and 2, respectively. The mortality rate was 2.73% per year in fragment 1 and 4.88% per year in fragment 2, while the recruitment rate was 3.25% per year and 5.86% per year, respectively. The community presented high recruitment and mortality rates compared to the studies conducted in other sites, indicating a community that was highly dynamic in the period studied.

Femtosecond spectroscopy of molecular autoionization and fragmentation

Femtosecond laser pulses are applied to the study of the dynamics and the pathways of multiphoton-induced ionization, autoionization, and fragmentation of Na_2 in molecular-beam experiments. In particular, we report on first results obtained studying electronic autoionization (leading to Na_2{^+} + {e ^-}) and autoionization-induced fragmentation (leading to Na{^+} + Na + {e ^-}) of a bound doubly excited molecular state. The final continuum states are analyzed by photoelectron spectroscopy and by measuring the mass and the released kinetic energy of the corresponding ionic fragments with a time-of-flight arrangement.

Femtosecond probing of sodium cluster ion Na_n ^+ fragmentation

We report on the first femtosecond time-resolved experiments in cluster physics. The photofragmentation dynamics of small sodium cluster ions Na_n ^+ have been studied with pump-probe techniques. Ultrashort laser pulses of 60-fs duration are employed to photoionize the sodium clusters and to probe the photofragments. We find that the ejection of neutral dimer Na_2 and, observed for the first time, neutral trimer Na_3 photofragments occur on ultrashort time scales of 2.5 and 0.4 ps, respectively. This and the absence of cluster heating reveals that direct photoinduced fragmentation processes are important at short times rather than the statistical unimolecular decay.

Femtosecond time-resolved wave packet motion in molecular multiphoton ionization and fragmentation

The dynamics of molecular multiphoton ionization and fragmentation of a diatomic molecule (Na_2) have been studied in molecular beam experiments. Femtosecond laser pulses from an amplified colliding-pulse mode-locked (CPM) ring dye laser are employed to induce and probe the molecular transitions. The final continuum states are analyzed by photoelectron spectroscopy, by ion mass spectrometry and by measuring the kinetic energy of the formed ionic fragments. Pump-probe spectra employing 70-fs laser pulses have been measured to study the time dependence of molecular multiphoton ionization and fragmentation. The oscillatory structure of the transient spectra showing the dynamics on the femtosecond time scale can best be understood in terms of the motion of wave packets in bound molecular potentials. The transient Na_2^+ ionization and the transient Na^+ fragmentation spectra show that contributions from direct photoionization of a singly excited electronic state and from excitation and autoionization of a bound doubly excited molecular state determine the time evolution of molecular multiphoton ionization.

Femtosecond time-resolved molecular multiphoton ionization and fragmentation of Na_2

We present a comparison between experimental and theoretical results for pump/probe multiphoton ionizing transitions of the sodium dimer, initiated by femtosecond laser pulses. It is shown that the motion of vibrational wavepackets in two electronic states is probed simultaneously and their dynamics is reflected in the total Na^+_2 ion signal which is recorded as a function of the time delay between pump and probe pulse. The time dependent quantum calculations demonstrate that two ionization pathways leading to the same final states of the molecularion exist: one gives an oscillating contribution to the ion signal, the other yields a constant background. From additional measurements of the Na^+ -transient photofragmentation spectrum it is deduced that another ionization process leading to different final ionic states exists. The process includes the excitation of a doubly excitedbound Rydberg state. This conclusion is supported by the theoretical simulation.

Effects of roads, topography, and land use on forest cover dynamics in the Brazilian Atlantic Forest

Roads and topography can determine patterns of land use and distribution of forest cover, particularly in tropical regions. We evaluated how road density, land use, and topography affected forest fragmentation, deforestation and forest regrowth in a Brazilian Atlantic Forest region near the city of Sao Paulo. We mapped roads and land use/land cover for three years (1962, 1981 and 2000) from historical aerial photographs, and summarized the distribution of roads, land use/land cover and topography within a grid of 94 non-overlapping 100 ha squares. We used generalized least squares regression models for data analysis. Our models showed that forest fragmentation and deforestation depended on topography, land use and road density, whereas forest regrowth depended primarily on land use. However, the relationships between these variables and forest dynamics changed in the two studied periods; land use and slope were the strongest predictors from 1962 to 1981, and past (1962) road density and land use were the strongest predictors for the following period (1981-2000). Roads had the strongest relationship with deforestation and forest fragmentation when the expansions of agriculture and buildings were limited to already deforested areas, and when there was a rapid expansion of development, under influence of Sao Paulo city. Furthermore, the past(1962)road network was more important than the recent road network (1981) when explaining forest dynamics between 1981 and 2000, suggesting a long-term effect of roads. Roads are permanent scars on the landscape and facilitate deforestation and forest fragmentation due to increased accessibility and land valorization, which control land-use and land-cover dynamics. Topography directly affected deforestation, agriculture and road expansion, mainly between 1962 and 1981. Forest are thus in peril where there are more roads, and long-term conservation strategies should consider ways to mitigate roads as permanent landscape features and drivers facilitators of deforestation and forest fragmentation. (C) 2009 Elsevier B.V. All rights reserved.

The impact of fragmentation and density regulation on forest succession in the Atlantic rain forest

The Atlantic Rain Forest, an important biodiversity hot spot, has faced severe habitat loss since the last century which has resulted in a highly fragmented landscape with a large number of small forest patches (<100 ha). For conservation planning it is essential to understand how current and future forest regeneration depends on ecological processes, fragment size and the connection to the regional seed pool. We have investigated the following questions by applying the forest growth simulation model FORMIND to the situation of the Atlantic Forest in the state of Sao Paulo, SE Brazil: (1) which set of parameters describing the local regeneration and level of density regulation can reproduce the biomass distribution and stem density of an old growth forest in a reserve? (2) Which additional processes apart from those describing the dynamics of an old growth forest, drive forest succession of small isolated fragments? (3) Which role does external seed input play during succession? Therefore, more than 300 tree species have been classified into nine plant functional types (PFTs), which are characterized by maximum potential height and shade tolerance. We differentiate between two seed dispersal modes: (i) local dispersal, i.e. all seedlings originated from fertile trees within the simulated area and (ii) external seed rain. Local seed dispersal has been parameterized following the pattern oriented approach, using biomass estimates of old growth forest. We have found that moderate density regulation is essential to achieve coexistence for a broad range of regeneration parameters. Considering the expected uncertainty and variability in the regeneration processes it is important that the forest dynamics are robust to variations in the regeneration parameters. Furthermore, edge effects such as increased mortality at the border and external seed rain have been necessary to reproduce the patterns for small isolated fragments. Overall, simulated biomass is much lower in the fragments compared to the continuous forest, whereas shade tolerant species are affected most strongly by fragmentation. Our simulations can supplement empirical studies by extrapolating local knowledge on edge effects of fragments to larger temporal and spatial scales. In particular our results show the importance of external seed rain and therefore highlight the importance of structural connectivity between regenerating fragments and mature forest stands. (C) 2009 Elsevier B.V. All rights reserved.

Fragmentation drives tropical forest fragments to early successional states: A modelling study for Brazilian Atlantic forests

Land use leads to massive habitat destruction and fragmentation in tropical forests. Despite its global dimensions the effects of fragmentation on ecosystem dynamics are not well understood due to the complexity of the problem. We present a simulation analysis performed by the individual-based model FORMIND. The model was applied to the Brazilian Atlantic Forest, one of the world`s biodiversity hot spots, at the Plateau of Sao Paulo. This study investigates the long-term effects of fragmentation processes on structure and dynamics of different sized remnant tropical forest fragments (1-100 ha) at community and plant functional type (PFT) level. We disentangle the interplay of single effects of different key fragmentation processes (edge mortality, increased mortality of large trees, local seed loss and external seed rain) using simulation experiments in a full factorial design. Our analysis reveals that particularly small forest fragments below 25 ha suffer substantial structural changes, biomass and biodiversity loss in the long term. At community level biomass is reduced up to 60%. Two thirds of the mid- and late-successional species groups, especially shade-tolerant (late successional climax) species groups are prone of extinction in small fragments. The shade-tolerant species groups were most strongly affected; its tree number was reduced more than 60% mainly by increased edge mortality. This process proved to be the most powerful of those investigated, explaining alone more than 80% of the changes observed for this group. External seed rain was able to compensate approximately 30% of the observed fragmentation effects for shade-tolerant species. Our results suggest that tropical forest fragments will suffer strong structural changes in the long term, leading to tree species impoverishment. They may reach a new equilibrium with a substantially reduced subset of the initial species pool, and are driven towards an earlier successional state. The natural regeneration potential of a landscape scattered with forest fragments appears to be limited, as external seed rain is not able to fully compensate for the observed fragmentation-induced changes. Our findings suggest basic recommendations for the management of fragmented tropical forest landscapes. (C) 2011 Elsevier B.V. All rights reserved.

DYNAMICAL SCALING IN FRAGMENTATION

The dynamics of a fragmentation model is examined from the point of view of numerical simulation and rate equations. The model includes effects of temperature. The number n (s,t) of fragments of size s at time t is obtained and is found to obey the scaling form n(s,t) approximately s(-tau)t(omegasgamma e(-rhot) f(s/t(z)) where f(x) is a crossover function satisfying f(x) congruent-to 1 for x much less than and f(x) much less than 1 for x much greater than 1. The dependence of the critical exponents tau, omega, gamma and z on space dimensionality d is studied from d = 1 to 5. The result of the dynamics on fractal and nonfractal objects as well as on square and triangular lattices is also examined.

Forest destructuring as revealed by the temporal dynamics of fundamental species - Case study of Santa Genebra Forest in Brazil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)