How the Listeria monocytogenes ActA protein converts actin polymerization into a motile force

The ActA protein is an essential determinant of pathogenicity that is responsible for the actin-based motility of Listeria monocytogenes in mammalian cells and cell-free extracts. ActA appears to control at least four functions that collectively lead to actin-based motility: (1) initiation of actin polymerization, (2) polarization of ActA function, (3) transformation of actin polymerization into a motile force and (4) acceleration of movement mediated by the host protein profilin.     

Interaction of human Arp2/3 complex and the Listeria monocytogenes ActA protein in actin filament nucleation

Actin filament assembly at the cell surface of the pathogenic bacterium Listeria monocytogenes requires the bacterial ActA surface protein and the host cell Arp2/3 complex. Purified Arp2/3 complex accelerated the nucleation of actin polymerization in vitro, but pure ActA had no effect. However, when combined, the Arp2/3 complex and ActA synergistically stimulated the nucleation of actin filaments. This mechanism of activating the host Arp2/3 complex at the L. monocytogenes surface may be similar to the strategy used by cells to control Arp2/3 complex activity and hence the spatial and temporal distribution of actin polymerization.     

Indirect Exciton–Phonon Dynamics in MoS2 Revealed by Ultrafast Electron Diffraction

Transition metal dichalcogenides layered nano-crystals are emerging as promising candidates for next-generation optoelectronic and quantum devices. In such systems, the interaction between excitonic states and atomic vibrations is crucial for many fundamental properties, such as carrier mobilities, quantum coherence loss, and heat dissipation. In particular, to fully exploit their valley-selective excitations, one has to understand the many-body exciton physics of zone-edge states. So far, theoretical and experimental studies have mainly focused on the exciton–phonon dynamics in high-energy direct excitons involving zone-center phonons. Here, ultrafast electron diffraction and ab initio calculations are used to investigate the many-body structural dynamics following nearly- resonant excitation of low-energy indirect excitons in MoS₂. By exploiting the large momentum carried by scattered electrons, the excitation of in-plane K- and Q- phonon modes are identified with 𝑬^′ symmetry as key for the stabilization of indirect excitons generated via near-infrared light at 1.55 eV, and light is shed on the role of phonon anharmonicity and the ensuing structural evolution of the MoS₂ crystal lattice. The results highlight the strong selectivity of phononic excitations directly associated with the specific indirect- exciton nature of the wavelength-dependent electronic transitions triggered in the system.     

Orthogonal variant moments features in image analysis

Moments are statistical measures used to obtain relevant information about a certain object under study (e.g., signals, images or waveforms), e.g., to describe the shape of an object to be recognized by a pattern recognition system. Invariant moments (e.g., the Hu invariant set) are a special kind of these statistical measures designed to remain constant after some transformations, such as object rotation, scaling, translation, or image illumination changes, in order to, e.g., improve the reliability of a pattern recognition system. The classical moment invariants methodology is based on the determination of a set of transformations (or perturbations) for which the system must remain unaltered. Although very well established, the classical moment invariants theory has been mainly used for processing single static images (i.e. snapshots) and the use of image moments to analyze images sequences or video, from a dynamic point of view, has not been sufficiently explored and is a subject of much interest nowadays. In this paper, we propose the use of variant moments as an alternative to the classical approach. This approach presents clear differences compared to the classical moment invariants approach, that in specific domains have important advantages. The difference between the classical invariant and the proposed variant approach is mainly (but not solely) conceptual: invariants are sensitive to any image change or perturbation for which they are not invariant, so any unexpected perturbation will affect the measurements (i.e. is subject to uncertainty); on the contrary, a variant moment is designed to be sensitive to a specific perturbation, i.e., to measure a transformation, not to be invariant to it, and thus if the specific perturbation occurs it will be measured; hence any unexpected disturbance will not affect the objective of the measurement confronting thus uncertainty. Furthermore, given the fact that the proposed variant moments are orthogonal (i.e. uncorrelated) it is possible to considerably reduce the total inherent uncertainty. The presented approach has been applied to interesting open problems in computer vision such as shape analysis, image segmentation, tracking object deformations and object motion tracking, obtaining encouraging results and proving the effectiveness of the proposed approach.     

Perceiving interpersonally-mediated risk in virtual environments

Using virtual reality (VR) to examine risky behavior that is mediated by interpersonal contact, such as agreeing to have sex, drink, or smoke with someone, offers particular promise and challenges. Social contextual stimuli that might trigger impulsive responses can be carefully controlled in virtual environments (VE), and yet manipulations of risk might be implausible to participants if they do not feel sufficiently immersed in the environment. The current study examined whether individuals can display adequate evidence of presence in a VE that involved potential interpersonally-induced risk: meeting a potential dating partner. Results offered some evidence for the potential of VR for the study of such interpersonal risk situations. Participants’ reaction to the scenario and risk-associated responses to the situation suggested that the embodied nature of virtual reality override the reality of the risk’s impossibility, allowing participants to experience adequate situational embedding, or presence.     

Analysis of the softening of heterophase aluminum alloys with a eutectic component

The effect of interparticle distance, volume fraction, and the average particle size of phases of eutectic origin in cold-rolled sheets of alloys of the Al-Ni, Al-Ni-Ce, Al-Mg-Si, and Al-Cu-Ce systems on strengthening and structural changes during heating at temperatures of 0.6?C0.8 T _m is investigated. The dependence of the intensity of softening on the particle parameters in the investigated alloys is established, and their ability to accelerate or retard recrystallization is analyzed using these results.     

Beneficial and Sexually Dimorphic Response to Combined HDAC Inhibitor Valproate and AMPK/SIRT1 Pathway Activator Resveratrol in the Treatment of ALS Mice

Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disorder. There is no cure and current treatments fail to slow the progression of the disease. Epigenetic modulation in the acetylation state of NF-kB RelA and the histone 3 (H3) protein, involved in the development of neurodegeneration, is a drugable target for the class-I histone deacetylases (HDAC) inhibitors, entinostat or valproate, and the AMP-activated kinase (AMPK)-sirtuin 1 pathway activator, resveratrol. In this study, we demonstrated that the combination of valproate and resveratrol can restore the normal acetylation state of RelA in the SOD1(G93A) murine model of ALS, in order to obtain the neuroprotective form of NF-kB. We also investigated the sexually dimorphic development of the disease, as well as the sex-sensibility to the treatment administered. We showed that the combined drugs, which rescued AMPK activation, RelA and the histone 3 acetylation state, reduced the motor deficit and the disease pathology associated with motor neuron loss and microglial reactivity, Brain-Derived Neurotrophic Factor (BDNF) and B-cell lymphoma-extra large (Bcl-xL) level decline. Specifically, vehicle-administered males showed earlier onset and slower progression of the disease when compared to females. The treatment, administered at 50 days of life, postponed the time of onset in the male by 22 days, but not in a significant way in females. Nevertheless, in females, the drugs significantly reduced symptom severity of the later phase of the disease and prolonged the mice’s survival. Only minor beneficial effects were produced in the latter stage in males. Overall, this study shows a beneficial and sexually dimorphic response to valproate and resveratrol treatment in ALS mice.     

Role of NEU3 Overexpression in the Prediction of Efficacy of EGFR-Targeted Therapies in Colon Cancer Cell Lines

The epidermal growth factor receptor (EGFR), through the MAP kinase and PI3K-Akt-mTOR axis, plays a pivotal role in colorectal cancer (CRC) pathogenesis. The membrane-associated NEU3 sialidase interacts with and desialylates EGFR by promoting its dimerization and downstream effectors’ activation. Among the targeted therapies against EGFR, the monoclonal antibody cetuximab is active only in a subgroup of patients not carrying mutations in the MAP kinase pathway. In order to better understand the EGFR-NEU3 interplay and the mechanisms of pharmacological resistance, we investigated the role of NEU3 deregulation in cetuximab-treated CRC cell lines transiently transfected with NEU3 using Western blot analysis. Our results indicate that NEU3 overexpression can enhance EGFR activation only if EGFR is overexpressed, indicating the existence of a threshold for NEU3-mediated EGFR activation. This enhancement mainly leads to the constitutive activation of the MAP kinase pathway. Consequently, we suggest that the evaluation of NEU3 expression cannot entirely substitute the evaluation of EGFR because EGFR-negative cases cannot be stimulated by NEU3. Furthermore, NEU3-mediated hyperactivation of EGFR is counterbalanced by the administration of cetuximab, hypothesizing that a combined treatment of NEU3- and EGFR-targeted therapies may represent a valid option for CRC patients, which must be investigated in the future.     

Determination of horizontal permeability from the elliptical flow of horizontal wells using conventional analysis

Besides the regular four flow regimes normally seen during a pressure test of horizontal wells, it is possible, under special circumstances, to observe such additional flow regimes as spherical, hemi-radial, linear (reservoir channel) and elliptical. The last flow regime is characterized by a slope of 0.36 of the pressure derivative curve and occurs between the early linear flow and the pseudo-radial flow periods. This may have been overlooked in horizontal well test analysis, because it is often masked by the other flow regimes, unless the conditions are just right.The elliptical flow regime has been previously mentioned by very few researchers, Issaka et al. [Issaka, M.B., Zaoral, K., Ambastha, A.K. and Mattar, L., 2000: “Determination of Horizontal Permeability Anisotropy from Horizontal Well Tests,” SPE Saudi Arabia Section Technical Symposium, Dhahran, Saudi Arabia, 21–23 October.], Chacon et al. [Chacon, A., Djebrouni, A. and Tiab, D., 2004. “Determining the Average Reservoir Pressure from Vertical and Horizontal Well Test Analysis Using Tiab's Direct Synthesis Technique”. SPE 88619, Proceedings, SPE Asia Pacific Oil & Gas Conf. & Exhibition, Perth, Australia, 18–20 October.] and Escobar et al. [Escobar, F.H., Munoz, O.F., and Sepulveda, J.A., 2004. “Horizontal Permeability Determination from the Elliptical Flow Regime for Horizontal Wells”. CT&F — Ciencia, Tecnología y Futuro. Vol. 2 Num. 5. p. 83–95. Dec.]. A methodology for its characterization has been also introduced using the pressure derivative concept and TDS technique [Escobar, F.H., Munoz, O.F., and Sepulveda, J.A., 2004. “Horizontal Permeability Determination from the Elliptical Flow Regime for Horizontal Wells”. CT&F — Ciencia, Tecnología y Futuro. Vol. 2 Num. 5. p. 83–95. Dec.]. However, conventional analysis for the characterization of this has not yet been reported in the literature. This flow regime is very useful to estimate the horizontal permeability, especially, when the pseudo-radial flow is very short or unclear, or simply, when it is desired to verify that estimation.In this paper, equations for the estimation of the horizontal permeability and elliptical skin factor are developed for both gas and oil horizontal wells, so that the mentioned parameters can be estimated, respectively, from the slope and intercept of linear plot of pressure versus time to the power 0.36. The equations were successfully tested with two field examples previously worked in the literature.