A new multicompartmental reaction-diffusion modeling method links transient membrane attachment of E. coli MinE to E-ring formation

Many important cellular processes are regulated by reaction-diffusion (RD) of molecules that takes place both in the cytoplasm and on the membrane. To model and analyze such multicompartmental processes, we developed a lattice-based Monte Carlo method, Spatiocyte that supports RD in volume and surface compartments at single molecule resolution. Stochasticity in RD and the excluded volume effect brought by intracellular molecular crowding, both of which can significantly affect RD and thus, cellular processes, are also supported. We verified the method by comparing simulation results of diffusion, irreversible and reversible reactions with the predicted analytical and best available numerical solutions. Moreover, to directly compare the localization patterns of molecules in fluorescence microscopy images with simulation, we devised a visualization method that mimics the microphotography process by showing the trajectory of simulated molecules averaged according to the camera exposure time. In the rod-shaped bacterium _Escherichia coli_, the division site is suppressed at the cell poles by periodic pole-to-pole oscillations of the Min proteins (MinC, MinD and MinE) arising from carefully orchestrated RD in both cytoplasm and membrane compartments. Using Spatiocyte we could model and reproduce the _in vivo_ MinDE localization dynamics by accounting for the established properties of MinE. Our results suggest that the MinE ring, which is essential in preventing polar septation, is largely composed of MinE that is transiently attached to the membrane independently after recruited by MinD. Overall, Spatiocyte allows simulation and visualization of complex spatial and reaction-diffusion mediated cellular processes in volumes and surfaces. As we showed, it can potentially provide mechanistic insights otherwise difficult to obtain experimentally

Inferring introduction routes of invasive species using approximate Bayesian computation on microsatellite data

Determining the routes of introduction provides not only information about the history of an invasion process, but also information about the origin and construction of the genetic composition of the invading population. It remains difficult, however, to infer introduction routes from molecular data because of a lack of appropriate methods. We evaluate here the use of an approximate Bayesian computation (ABC) method for estimating the probabilities of introduction routes of invasive populations based on microsatellite data. We considered the crucial case of a single source population from which two invasive populations originated either serially from a single introduction event or from two independent introduction events. Using simulated datasets, we found that the method gave correct inferences and was robust to many erroneous beliefs. The method was also more efficient than traditional methods based on raw values of statistics such as assignment likelihood or pairwise F(ST). We illustrate some of the features of our ABC method, using real microsatellite datasets obtained for invasive populations of the western corn rootworm, Diabrotica virgifera virgifera. Most computations were performed with the DIYABC program (http://www1.montpellier.inra.fr/CBGP/diyabc/)

Nutrition and colony investment in Solenopsis invicta workers

Dissertação de Mestrado em Biologia Celular e Molecular, apresentada ao Departamento de Ciências da Vida Da Faculdade de Ciências e Tecnologia da Universidade de Coimbra.A proteína Tau é responsável pela ligação e estabilização dos microtúbulos (MT) no citoesqueleto, sendo fundamental na função neuronal. A atividade desta proteína pode ser regulada por modificações pós-translacionais, como a fosforilação, que promovem a separação dos microtúbulos. A alteração na conformação da Tau provocada por uma deficiente regulação, como a híper-fosforilação, causa destabilização dos MT e agregação da mesma em filamentos helicoidais emparelhados e tranças neurofibrilares. Estas estruturas são uma das principais características na doença de Alzheimer (AD), e o seu processo de formação pode representar um dos principais motivos que leva a morte celular nas Tauopatias, inclusivamente AD e outras patologias neurodegenerativas. Nos últimos anos, recursos têm sido empregues na descoberta de novas estratégias que permitam diminuir a formação ou diminuam a quantidade de agregados da Tau dentro das células. Estudos recentes identificaram a indução da autofagia através da rapamicina como um dos potenciais alvos no aumento da remoção de agregados proteicos associados a doenças neurodegenerativas, melhorando também a esperança de vida em ratos e outros modelos. Recentemente, o nosso laboratório desenvolveu um modelo celular baseado no trabalho de Guo e Lee (2011) que mimetiza a agregação intracelular da Tau depois de induzida a expressão de uma forma mutada desta proteína seguido do seeding com fibrilas K18:P301L pré-agregadas. Neste estudo, foi possível demonstrar como a utilização destes modelos permite identificar novos compostos com atividade nas vias de redução da Tau. Curiosamente estas moléculas foram responsáveis pelo desenvolvimento de um fenótipo vesicular que identificámos como sendo lisossomas, derivados de um possível estímulo na via endócitica. As alterações na morfologia sub-celular foram acompanhadas por modificações em marcadores de autofagia, sem aumento no fluxo autofágico. Estes dados sugerem que o aumento na degradação de proteínas e estruturas por autofagia poderão ter origem em efeitos colaterais de outras vias em detrimento do estímulo direto. Para além disso, testamos uma série de moléculas com atividade reconhecida e validadas para induzir autofagia ou bloquear a degradação no lisossoma. Foi demonstrado que no nosso modelo, a ativação da autofagia não é responsável pela remoção de agregados. Por outro lado, provámos que os lisossomas são extremamente importantes da degradação de agregados da Tau. Por fim, usámos o fator de transcrição EB (TFEB) para aumentar a biogénese de lisossomas e a autofagia. Células transfectadas com este fator apresentaram menos agregados de Tau e um aumento na viabilidade celular. Quando considerados em conjunto, estes resultados demonstram que a biogénese de lisossomas seguida por estímulos na autofagia podem ser mais importantes do que a ativação da autofagia por si só. Concluindo, com este projeto foi não só possível identificar os mecanismos dos compostos responsáveis pela degradação dos agregados de Tau, como também foi possível validar o TFEB como um potencial novo alvo na descoberta de novos fármacos.Tau protein is responsible for binding and stabilizing microtubules (MT) in the cytoskeleton, thus supporting neuronal function. This protein activity can be regulated by post-translation modifications, such as phosphorylation, which promotes MT detachment. Tau misfolding provoked by abnormal regulation, like hyperphosphorilation, causes MT destabilization and Tau aggregation into paired helical filaments (PHF) and neurofibrillary tangles (NFTs). These structures are one of the main hallmarks in Alzheimer’s disease (AD), and its formation process may represent the principal motive for cell death in many Tauopathies, including AD and other neurodegenerative disorders. Over the last years, great efforts have been placed to find new strategies to either diminish the build-up or decrease the amount of aggregated Tau inside cells. Recent studies have identified induction of autophagy through rapamycin as a potential target in increasing the clearance of aggregated proteins associated with neurodegenerative diseases, as well as ameliorating life expectancy in rats and other animal models. Recently, our lab developed a cellular model based on the work by Guo and Lee (2011) that mimics the intracellular aggregation of Tau after overexpression of a mutated form of this protein and seeding with pre-aggregated K18:P301L fibrils. In this study, we have taken advantage of the developed model to discover new compounds active in Tau reduction pathways. Interestingly these molecules were responsible for the development of a vesicular phenotype that we identified as lysosomes due to a possible stimulation of the endocytic pathway. The change of the sub cellular morphology was followed by changes in autophagy markers, with no increase in the autophagic flux. This suggests an increment in the degradation of proteins and structures by autophagy as a collateral result from the activation of other pathways rather than a direct stimulus. Furthermore, we have tested a series of molecules with known and validated activity to induce autophagy or disable degradation via the lysosome. We showed that at least in our model, autophagy activation is not responsible for the clearance of aggregates. On the other hand, we have proven that lysosomes play a critical role in Tau aggregates degradation. Finally, we have used the transcription factor EB (TFEB) to intensify lysosomal biogenesis and autophagy. Cells transfected with this transcription factor had less Tau aggregates and cell viability was slightly increased. When considered together, these results show that lysosomal biogenesis followed by autophagy stimulation may be more important for clearance of Tau aggregates than autophagy by itself. In conclusion, we have not only determined the mechanisms targeted by the compounds responsible for the degradation of Tau aggregates, but also validated TFEB as a potential new target for drug discovery

Electronic Coherence Dephasing in Excitonic Molecular Complexes: Role of Markov and Secular Approximations

We compare four different types of equations of motion for reduced density matrix of a system of molecular excitons interacting with thermodynamic bath. All four equations are of second order in the linear system-bath interaction Hamiltonian, with different approximations applied in their derivation. In particular we compare time-nonlocal equations obtained from so-called Nakajima-Zwanzig identity and the time-local equations resulting from the partial ordering prescription of the cummulant expansion. In each of these equations we alternatively apply secular approximation to decouple population and coherence dynamics from each other. We focus on the dynamics of intraband electronic coherences of the excitonic system which can be traced by coherent two-dimensional spectroscopy. We discuss the applicability of the four relaxation theories to simulations of population and coherence dynamics, and identify features of the two-dimensional coherent spectrum that allow us to distinguish time-nonlocal effects.Comment: 14 pages, 8 figure

Widespread range expansions shape latitudinal variation in insect thermal limits

I thank the authors of previous studies on global variation in insect thermal tolerances who have generously provided open access use of their data sets.Peer reviewedPostprin

Inselect: Automating the Digitization of Natural History Collections

Copyright: © 2015 Hudson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns