Spindle Checkpoint Silencing: PP1 Tips the Balance

The spindle checkpoint is a mitotic surveillance mechanism that delays anaphase until all sister chromatids are correctly attached to microtubules from opposite poles. Recent studies reveal that protein kinase Aurora B is a key regulator of spindle checkpoint activation whereas protein phosphatase PP1 antagonizes Aurora B and induces checkpoint silencing. Chromosome biorientation stretches the kinetochores and spatially separates centromeric Aurora B from its kinetochore substrates, comprising several PP1-interacting proteins (PIPs). The ensuing dephosphorylation of these PIPs creates docking sites for the bulk recruitment of PP1 to the kinetochores. We propose that this tension-induced targeting of PP1 triggers checkpoint silencing by the dephosphorylation of kinetochore and checkpoint components, including Aurora B substrates. In addition, PP1 also directly inactivates a kinetochore-associated pool of Aurora B and silences checkpoint signaling by opposing the centromeric targeting of Aurora B

Cooperative binding of ApiAP2 transcription factors is crucial for the expression of virulence genes in Toxoplasma gondii

International audienceToxoplasma gondii virulence depends on the expression of factors packed into specific organelles such as rhoptry and microneme. Although virulence factor expression is tightly regulated, the molecular mechanisms controlling their regulation remain poorly understood. ApiAP2 are a family of conserved transcription factors (TFs) that play an important role in regulating gene expression in apicomplexan parasites. TgAP2XI-5 is able to bind to transcription-ally active promoters of genes expressed during the S/M phase of the cell cycle, such as virulence genes (rhoptries and micronemes genes). We identified proteins interacting with TgAP2XI-5 including a cell cycle-regulated ApiAP2 TF, TgAP2X-5. Using an inducible knock-down strategy and RNA-seq, we demonstrated that the level of expression of number of virulence factors transcripts is affected by the disruption of TgAP2X-5 expression. While TgAP2X-5 disruption has mild effect on parasite invasion, it leads to the strain avirulence in mice. To better understand the molecular mechanisms at stake, we investigated the binding of TgAP2XI-5 at promoters in the TgAP2X-5 mutant strain in a genome-wide assay. We show that disruption of TgAP2X-5 expression leads to defects in TgAP2XI-5 binding to multiple rhoptry gene promoters. Taken together, these data suggest a cooperative contribution of two ApiAP2 TF in the regulation of virulence genes in T. gondii

Integrated optimal design for power systems of more electrical aircraft

This paper proposes an optimal design approach that aims at coupling a set of design models with an optimization algorithm in order “to improve the integration” of electrical devices and systems embedded in more electrical aircraft. This approach has already been applied to relatively complex power conversion systems like an electrical air conditioning system (ECS) and its interest has been proved. But, elementary components and technologies can also benefit from this approach, and this will be shown on the example of a special magnetic device referred to as Intercell Transformer(ICT)

The su(2)_{-1/2} WZW model and the beta-gamma system

The bosonic beta-gamma ghost system has long been used in formal constructions of conformal field theory. It has become important in its own right in the last few years, as a building block of field theory approaches to disordered systems, and as a simple representative -- due in part to its underlying su(2)_{-1/2} structure -- of non-unitary conformal field theories. We provide in this paper the first complete, physical, analysis of this beta-gamma system, and uncover a number of striking features. We show in particular that the spectrum involves an infinite number of fields with arbitrarily large negative dimensions. These fields have their origin in a twisted sector of the theory, and have a direct relationship with spectrally flowed representations in the underlying su(2)_{-1/2} theory. We discuss the spectral flow in the context of the operator algebra and fusion rules, and provide a re-interpretation of the modular invariant consistent with the spectrum.Comment: 33 pages, 1 figure, LaTeX, v2: minor revision, references adde

Quantitative investigation of the effect of the extra-cerebral vasculature in diffuse optical imaging: a simulation study

Diffuse optical imaging (DOI) is a non invasive technique allowing the recovery of hemodynamic changes in the brain. Due to the diffusive nature of photon propagation in turbid media and the fact that cerebral tissues are located around 1.5 cm under the adult human scalp, DOI measurements are subject to partial volume errors. DOI measurements are also sensitive to large pial vessels because oxygenated and deoxygenated hemoglobin are the dominant chromophores in the near infrared window. In this study, the effect of the extra-cerebral vasculature in proximity of the sagittal sinus was investigated for its impact on DOI measurements simulated over the human adult visual cortex. Numerical Monte Carlo simulations were performed on two specific models of the human head derived from magnetic resonance imaging (MRI) scans. The first model included the extra-cerebral vasculature in which constant hemoglobin concentrations were assumed while the second did not. The screening effect of the vasculature was quantified by comparing recovered hemoglobin changes from each model for different optical arrays and regions of activation. A correction factor accounting for the difference between the recovered and the simulated hemoglobin changes was computed in each case. The results show that changes in hemoglobin concentration are better estimated when the extra-cerebral vasculature is modeled and the correction factors obtained in this case were at least 1.4-fold lower. The effect of the vasculature was also examined in a high-density diffuse optical tomography configuration. In this case, the difference between changes in hemoglobin concentration recovered with each model was reduced down to 10%

Boundary renormalisation group flows of unitary superconformal minimal models

In this paper we investigate renormalisation group flows of supersymmetric minimal models generated by the boundary perturbing field (\hat G_{-1/2}\phi_{1,3}). Performing the Truncated Conformal Space Approach analysis the emerging pattern of the flow structure is consistent with the theoretical expectations. According to the results, this pattern can be naturally extended to those cases for which the existing predictions are uncertain.Comment: A more detailed analysis is presented. (29 pages, 16 figures

Characterization of a nuclear pore protein sheds light on the roles and composition of the Toxoplasma gondii nuclear pore complex

International audienceThe nuclear pore is a key structure in eukaryotes regulating nuclear-cytoplasmic transport as well as a wide range of cellular processes. Here, we report the characterization of the first Toxoplasma gondii nuclear pore protein, named TgNup302, which appears to be the orthologue of the mammalian Nup98-96 protein. We produced a conditional knock-down mutant that expresses TgNup302 under the control of an inducible tetracycline-regulated promoter. Under ATc treatment, a substantial decrease of TgNup302 protein in inducible knock-down (iKD) parasites was observed, causing a delay in parasite proliferation. Moreover, the nuclear protein TgENO2 was trapped in the cytoplasm of ATc-treated mutants, suggesting that TgNup302 is involved in nuclear transport. Fluorescence in situ hybridization revealed that TgNup302 is essential for 18S RNA export from the nucleus to the cytoplasm, while global mRNA export remains unchanged. Using an affinity tag purification combined with mass spectrometry, we identified additional components of the nuclear pore complex, including proteins potentially interacting with chromatin. Furthermore, reverse immunoprecipitation confirmed their interaction with TgNup302, and structured illuminated microscopy confirmed the NPC localization of some of the TgNup302-interacting proteins. Intriguingly, facilitates chromatin transcription complex (FACT) components were identified, suggesting the existence of an NPC-chromatin interaction in T. gondii. Identification of TgNup302-interacting proteins also provides the first glimpse at the NPC structure in Apicomplexa, suggesting a structural conservation of the NPC components between distant eukaryotes

Comments on nonunitary conformal field theories

As is well-known, nonunitary RCFTs are distinguished from unitary ones in a number of ways, two of which are that the vacuum 0 doesn't have minimal conformal weight, and that the vacuum column of the modular S matrix isn't positive. However there is another primary field, call it o, which has minimal weight and has positive S column. We find that often there is a precise and useful relationship, which we call the Galois shuffle, between primary o and the vacuum; among other things this can explain why (like the vacuum) its multiplicity in the full RCFT should be 1. As examples we consider the minimal WSU(N) models. We conclude with some comments on fractional level admissible representations of affine algebras. As an immediate consequence of our analysis, we get the classification of an infinite family of nonunitary WSU(3) minimal models in the bulk.Comment: 24 page

Association between Statin Use and Balance in Older Adults

ABSTRACT: Background: Several medications have been associated with an increased risk of balance deficits and greater likelihood to sustain a fall, representing a large health and economic issue. Statins are regularly prescribed to prevent strokes and heart attacks, but their impact on balance is unknown. The aim of this paper was to determine whether statin use is associated with poorer balance performances in older adults. Methods: All participants, one group taking statins (n = 34), and the other group not taking statins (n = 31), completed a balance assessment with their eyes closed and their eyes opened on a MatScan Pressure Sensing Mat. Center of Pressure (CoP) velocity, peak-to-peak distance, and standard deviation were collected in both anteroposterior (AP) and mediolateral (ML) directions. Multiple linear regression analyses were performed for each balance outcome, testing the statin use status as a predictor and controlling for appropriate factors including participants characteristics, lipid profile, and cardiovascular disease. Results: After controlling for confounding factors, statin use significantly predicted both CoP ML-Amplitude (beta = 0.638, p = 0.004) and ML-Velocity (beta = 0.653, p = 0.002) in the eyes-opened condition. Conclusions: The present study detected a negative association between statin use and balance control in the ML direction, suggesting that caution should be taken when prescribing statins in older adults, as this could decrease ML stability and ultimately increase fall and fracture risks