Negative Cell Cycle Regulation and DNA Damage-inducible Phosphorylation of the BRCT Protein 53BP1

In a screen designed to discover suppressors of mitotic catastrophe, we identified the Xenopus ortholog of 53BP1 (X53BP1), a BRCT protein previously identified in humans through its ability to bind the p53 tumor suppressor. X53BP1 transcripts are highly expressed in ovaries, and the protein interacts with Xp53 throughout the cell cycle in embryonic extracts. However, no interaction between X53BP1 and Xp53 can be detected in somatic cells, suggesting that the association between the two proteins may be developmentally regulated. X53BP1 is modified via phosphorylation in a DNA damage-dependent manner that correlates with the dispersal of X53BP1 into multiple foci throughout the nucleus in somatic cells. Thus, X53BP1 can be classified as a novel participant in the DNA damage response pathway. We demonstrate that X53BP1 and its human ortholog can serve as good substrates in vitro as well as in vivo for the ATM kinase. Collectively, our results reveal that 53BP1 plays an important role in the checkpoint response to DNA damage, possibly in collaboration with ATM

Ceramic identity contributes to mechanical properties and osteoblast behavior on macroporous composite scaffolds.

Implants formed of metals, bioceramics, or polymers may provide an alternative to autografts for treating large bone defects. However, limitations to each material motivate the examination of composites to capitalize on the beneficial aspects of individual components and to address the need for conferring bioactive behavior to the polymer matrix. We hypothesized that the inclusion of different bioceramics in a ceramic-polymer composite would alter the physical properties of the implant and the cellular osteogenic response. To test this, composite scaffolds formed from poly(lactide-co-glycolide) (PLG) and either hydroxyapatite (HA), β-tricalcium phosphate (TCP), or bioactive glass (Bioglass 45S®, BG) were fabricated, and the physical properties of each scaffold were examined. We quantified cell proliferation by DNA content, osteogenic response of human osteoblasts (NHOsts) to composite scaffolds by alkaline phosphatase (ALP) activity, and changes in gene expression by qPCR. Compared to BG-PLG scaffolds, HA-PLG and TCP-PLG composite scaffolds possessed greater compressive moduli. NHOsts on BG-PLG substrates exhibited higher ALP activity than those on control, HA-, or TCP-PLG scaffolds after 21 days, and cells on composites exhibited a 3-fold increase in ALP activity between 7 and 21 days versus a minimal increase on control scaffolds. Compared to cells on PLG controls, RUNX2 expression in NHOsts on composite scaffolds was lower at both 7 and 21 days, while expression of genes encoding for bone matrix proteins (COL1A1 and SPARC) was higher on BG-PLG scaffolds at both time points. These data demonstrate the importance of selecting a ceramic when fabricating composites applied for bone healing

A two-layer shallow water model for bedload sediment transport: convergence to Saint-Venant-Exner model

A two-layer shallow water type model is proposed to describe bedload sediment transport. The upper layer is filled by water and the lower one by sediment. The key point falls on the definition of the friction laws between the two layers, which are a generalization of those introduced in Fern\'andez-Nieto et al. (ESAIM: M2AN, 51:115-145, 2017). This definition allows to apply properly the two-layer shallow water model for the case of intense and slow bedload sediment transport. Moreover, we prove that the two-layer model converges to a Saint-Venant-Exner system (SVE) including gravitational effects when the ratio between the hydrodynamic and morphodynamic time scales is small. The SVE with gravitational effects is a degenerated nonlinear parabolic system. This means that its numerical approximation is very expensive from a computational point of view, see for example T. Morales de Luna et al. (J. Sci. Comp., 48(1): 258-273, 2011). In this work, gravitational effects are introduced into the two-layer system without such extra computational cost. Finally, we also consider a generalization of the model that includes a non-hydrostatic pressure correction for the fluid layer and the boundary condition at the sediment surface. Numerical tests show that the model provides promising results and behave well in low transport rate regimes as well as in many other situations

Preliminary study on electrophysiological changes after cellular autograft in age-related macular degeneration

Background: Evolving atrophic macular degeneration represents at least 80% of all macular degenerations and is currently without a standardized care. Autologous fat transplantation (AFT) efficacy was demonstrated by several studies, since these cells are able to produce growth factors. The aim of the work was to demonstrate possible therapeutic effect of the joined suprachoroidal graft of adipocytes, adipose derived stem-cells (ADSCs) in tissue adipose’s stromal vascular fractions (SVF), and platelet rich plasma (PRP). Methods: Twelve eyes in 12 dry age macular degeneration (AMD) patients, aged 71.25 (SD ± 6.8) between 62 and 80 years, were analyzed. A complete ocular evaluation was performed using: best corrected visual acuity (BCVA), retinographic analysis, spectral-domain optical coherence tomography, microperimetry, computerized visual field, and standard electroretinogram (ERG). Each eye received a cell in graft between choroid and sclera by means of the variant second Limoli, grafting of mature fat cells and ADSCs in SVF enriched with PRP (LRRT). In order to test if the differences pre- and post-treatment were significant the Wilcoxon signed rank test has been performed. Results: Adverse effects were not reported in the patients. After surgery with LRRT the most significant increase in the ERG values was recorded by scotopic rod-ERG (answer coming from the rods), from 41.26 to 60.83 μVolts (µV) with an average increase of 47.44% highly significant (p<0.05). Moderately significant was the one recorded by scotopic maximal ERG (answer coming from the rods and cones), from 112.22 to 129.68 μV with an average increase of 15.56% (p<0.1). Conclusions: Cell-mediated therapy based on growth factors used appears interesting because it can improve the retinal functionality responses in the short term. The ERG could, therefore, be used to monitor the effect of cell-mediated regenerative therapies

On Loop Quantum Gravity Phenomenology and the Issue of Lorentz Invariance

A simple model is constructed which allows to compute modified dispersion relations with effects from loop quantum gravity. Different quantization choices can be realized and their effects on the order of corrections studied explicitly. A comparison with more involved semiclassical techniques shows that there is agreement even at a quantitative level. Furthermore, by contrasting Hamiltonian and Lagrangian descriptions we show that possible Lorentz symmetry violations may be blurred as an artifact of the approximation scheme. Whether this is the case in a purely Hamiltonian analysis can be resolved by an improvement in the effective semiclassical analysis.Comment: 16 pages, RevTeX