In this study, the Voronoi tessellation method has been used to design novel bone like three dimension (3D) porous scaffolds. The Voronoi method has been processed with computer design software to ...obtain 3D virtual isotropic porous interconnected models, exactly matching the main histomorphometric indices of trabecular bone (trabecular thickness, trabecular separation, trabecular number, bone volume to total volume ratio, bone surface to bone volume ratio, etc.). These bone like models have been further computed for mechanical (elastic modulus) and fluid mass transport (permeability) properties. The results show that the final properties of the scaffolds can be controlled during their microstructure and histomorphometric initial design stage. It is also shown that final properties can be tuned during the design stage to exactly match those of trabecular natural bone. Moreover, identical total porosity models can be designed with quite different specific bone surface area and thus, this specific microstructural feature can be used to favour cell adhesion, migration and, ultimately, new bone apposition (i.e. osteoconduction). Once the virtual models are fully characterized and optimized, these can be easily 3D printed by additive manufacturing and/or stereolitography technologies.
The significance of this article goes far beyond the specific objectives on which it is focussed. In fact, it shows, in a guided way, the entire novel process that can be followed to design graded porous implants, whatever its external shape and geometry, but internally tuned to the exact histomorphometric indices needed to match natural human tissues microstructures and, consequently, their mechanical and fluid properties, among others. The significance is even more relevant nowadays thanks to the available new computing and design software that is easily linked to the 3D printing new technologies. It is this transversality, at the frontier of different disciplines, the main characteristic that gives this article a high scientific impact and interest to a broaden audience.
We study the time scales associated with diffusion processes that take place on multiplex networks, i.e., on a set of networks linked through interconnected layers. To this end, we propose the ...construction of a supra-laplacian matrix, which consists of a dimensional lifting of the laplacian matrix of each layer of the multiplex network. We use perturbative analysis to reveal analytically the structure of eigenvectors and eigenvalues of the complete network in terms of the spectral properties of the individual layers. The spectrum of the supra-laplacian allows us to understand the physics of diffusionlike processes on top of multiplex networks.
The Arp2/3 complex regulates endocytosis, sorting, and trafficking, yet the Arp2/3-stimulating factors orchestrating these distinct events remain ill defined. WASH (Wiskott-Aldrich Syndrome Protein ...and SCAR Homolog) is an Arp2/3 activator with unknown function that was duplicated during primate evolution. We demonstrate that WASH associates with tubulin and localizes to early endosomal subdomains, which are enriched in Arp2/3, F-actin, and retromer components. Although WASH localized with activated receptors, it was not essential for endocytosis. However, WASH did regulate retromer-mediated retrograde CI-MPR trafficking, which required its association with endosomes, Arp2/3-directed F-actin regulation, and tubulin interaction. Moreover, WASH exists in a multiprotein complex containing FAM21, which links WASH to endosomes and is required for WASH-dependent retromer-mediated sorting. Significantly, without WASH, retromer tubulation was exaggerated, supporting a model wherein WASH links retromer-mediated cargo containing tubules to microtubules for Golgi-directed trafficking and generates F-actin-driven force for tubule scission.
Certification of quantum nonlocality plays a central role in practical applications like device-independent quantum cryptography and random number generation protocols. These applications entail the ...challenging problem of certifying quantum nonlocality, something that is hard to achieve when the target quantum state is only weakly entangled, or when the source of errors is high, e.g. when photons propagate through the atmosphere or a long optical fiber. Here we introduce a technique to find a Bell inequality with the largest possible gap between the quantum prediction and the classical local hidden variable limit for a given set of measurement frequencies. Our method represents an efficient strategy to certify quantum nonlocal correlations from experimental data without requiring extra measurements, in the sense that there is no Bell inequality with a larger gap than the one provided. Furthermore, we also reduce the photodetector efficiency required to close the detection loophole. We illustrate our technique by improving the detection of quantum nonlocality from experimental data obtained with weakly entangled photons.
During arbuscular mycorrhizal (AM) symbiosis, the plant gains access to phosphate (Pi) and nitrogen delivered by its fungal symbiont. Transfer of mineral nutrients occurs at the interface between ...branched hyphae called arbuscules and root cortical cells. In Medicago truncatula, a Pi transporter, PT4, is required for symbiotic Pi transport, and in pt4, symbiotic Pi transport fails, arbuscules degenerate prematurely, and the symbiosis is not maintained. Premature arbuscule degeneration (PAD) is suppressed when pt4 mutants are nitrogen-deprived, possibly the result of compensation by PT8, a second AM-induced Pi transporter. However, PAD is also suppressed in nitrogen-starved pt4 pt8 double mutants, negating this hypothesis and furthermore indicating that in this condition, neither of these symbiotic Pi transporters is required for symbiosis. In M. truncatula, three AMT2 family ammonium transporters are induced during AM symbiosis. To test the hypothesis that suppression of PAD involves AMT2 transporters, we analyzed double and triple Pi and ammonium transporter mutants. ATM2;3 but not AMT2;4 was required for suppression of PAD in pt4, while AMT2;4, but not AMT2;3, complemented growth of a yeast ammonium transporter mutant. In summary, arbuscule life span is influenced by PT4 and ATM2;3, and their relative importance varies with the nitrogen status of the plant.
Background
Fish is one of the most allergenic foods. While clinical cross‐reactivity among different fishes is a widely accepted feature of fish allergy, associations with other food allergies are ...not well understood. This study aims at analyzing the relevance of clinical cross‐reactivity between fish and chicken meat in patients with allergy to chicken meat without sensitization to hen's eggs.
Methods
Patients with food allergy to fish and chicken meat (n = 29) or chicken meat only (n = 7) were recruited. IgE‐reactive chicken proteins were identified (Edman, MS analysis) and quantified (ELISA). Allergens were used in IgE ELISA and skin testing.
Results
Chicken parvalbumin and two new allergens, aldolase and enolase, were identified at 12, 40, and 50 kDa, respectively. They were recognized by sIgE of 61%, 75%, and 83% of all patient sera which were in the majority of the cases positive for the fish homologues as well. Fish and chicken meat allergens were highly cross‐reactive while high inhibition rates with fish or chicken allergens correlated with the patients' primary sensitization to fish or chicken. In cooked or roasted foods, enolase and aldolase were detectable in chicken breast while parvalbumin was detectable in chicken legs and wings.
Conclusions
Fish and chicken meat are cross‐reactive foods; both fish‐allergic and chicken meat‐allergic patients might be at risk of developing a food allergy to chicken meat or to fish, respectively. This clinical phenomenon is proposed to be termed ‘fish–chicken syndrome’ with cross‐reactive allergens involved being parvalbumins, enolases, and aldolases.
Endosomal protein trafficking is an essential cellular process that is deregulated in several diseases and targeted by pathogens. Here, we describe a role for ubiquitination in this process. We find ...that the E3 RING ubiquitin ligase, MAGE-L2-TRIM27, localizes to endosomes through interactions with the retromer complex. Knockdown of MAGE-L2-TRIM27 or the Ube2O E2 ubiquitin-conjugating enzyme significantly impaired retromer-mediated transport. We further demonstrate that MAGE-L2-TRIM27 ubiquitin ligase activity is required for nucleation of endosomal F-actin by the WASH regulatory complex, a known regulator of retromer-mediated transport. Mechanistic studies showed that MAGE-L2-TRIM27 facilitates K63-linked ubiquitination of WASH K220. Significantly, disruption of WASH ubiquitination impaired endosomal F-actin nucleation and retromer-dependent transport. These findings provide a cellular and molecular function for MAGE-L2-TRIM27 in retrograde transport, including an unappreciated role of K63-linked ubiquitination and identification of an activating signal of the WASH regulatory complex.
Display omitted
► MAGE-L2-TRIM27 E3 ubiquitin ligase localizes to retromer-positive endosomes ► Retrograde transport requires MAGE-L2-TRIM27, Ube2O, and K63-ubiquitination ► MAGE-L2-TRIM27, Ube2O, and K63-ubiquitination facilitate endosomal actin nucleation ► WASH is activated by K63-linked ubiquitination of WASH K220 by MAGE-L2-TRIM27
The E3 ubiquitin ligase MAGE-L2-TRIM27 associates with the retromer complex and promotes F-actin nucleation via ubiquitination of the WASH complex. This regulation is critical for retrograde endosomal trafficking.
We present Chandra and Very Large Array observations of GW170817 at ∼521-743 days post-merger, and a homogeneous analysis of the entire Chandra data set. We find that the late-time nonthermal ...emission follows the expected evolution of an off-axis relativistic jet, with a steep temporal decay F ∝ t − 1.95 0.15 and power-law spectrum F ∝ − 0.575 0.007 . We present a new method to constrain the merger environment density based on diffuse X-ray emission from hot plasma in the host galaxy and find n ≤ 9.6 × 10 − 3 cm − 3 . This measurement is independent from inferences based on jet afterglow modeling and allows us to partially solve for model degeneracies. The updated best-fitting model parameters with this density constraint are a fireball kinetic energy E 0 = 1.5 − 1.1 + 3.6 × 10 49 erg ( E iso = 2.1 − 1.5 + 6.4 × 10 52 erg ) and jet opening angle θ 0 = 5.9 − 0.7 + 1.0 deg with characteristic Lorentz factor Γ j = 163 − 43 + 23 , expanding in a low-density medium with n 0 = 2.5 − 1.9 + 4.1 × 10 − 3 cm − 3 and viewed θ obs = 30.4 − 3.4 + 4.0 deg off-axis. The synchrotron emission originates from a power-law distribution of electrons with index p = 2.15 − 0.02 + 0.01 . The shock microphysics parameters are constrained to ϵ e = 0.18 − 0.13 + 0.30 and ϵ B = 2.3 − 2.2 + 16.0 × 10 − 3 . Furthermore, we investigate the presence of X-ray flares and find no statistically significant evidence of ≥2.5 of temporal variability at any time. Finally, we use our observations to constrain the properties of synchrotron emission from the deceleration of the fastest kilonova ejecta with energy E k KN ∝ ( Γ β ) − into the environment, finding that shallow stratification indexes ≤ 6 are disfavored. Future radio and X-ray observations will refine our inferences on the fastest kilonova ejecta properties.
PDF
