Arrest of mammalian fibroblasts in G1 in response to actin inhibition is dependent on retinoblastoma pocket proteins but not on p53

p53 and the retinoblastoma (RB) pocket proteins are central to the control of progression through the G1 phase of the cell cycle. The RB pocket protein family is downstream of p53 and controls S-phase entry. Disruption of actin assembly arrests nontransformed mammalian fibroblasts in G1. We show that this arrest requires intact RB pocket protein function, but surprisingly does not require p53. Thus, mammalian fibroblasts with normal pocket protein function reversibly arrest in G1 on exposure to actin inhibitors regardless of their p53 status. By contrast, pocket protein triple knockout mouse embryo fibroblasts and T antigen–transformed rat embryo fibroblasts lacking both p53 and RB pocket protein function do not arrest in G1. Fibroblasts are very sensitive to actin inhibition in G1 and arrest at drug concentrations that do not affect cell adhesion or cell cleavage. Interestingly, G1 arrest is accompanied by inhibition of surface ruffling and by induction of NF2/merlin. The combination of failure of G1 control and of tetraploid checkpoint control can cause RB pocket protein–suppressed cells to rapidly become aneuploid and die after exposure to actin inhibitors, whereas pocket protein–competent cells are spared. Our results thus establish that RB pocket proteins can be uniquely targeted for tumor chemotherapy

Tensile testing of cellulose based natural fibers for structural composite applications

A series of tensile tests were conducted on a Lloyd LRX tensile testing machine for numerous natural fibers deemed potential candidates for development in composite applications. The tensile tests were conducted on the fibers jute, kenaf, flax, abaca, sisal, hemp, and coir for samples exposed to moisture conditions of (1) room temperature and humidity, (2) 65% moisture content, (3) 90% moisture content, and (4) soaked fiber. These seven fibers were then tested for the four conditions and the mechanical properties of tensile strength, tensile strain to failure, and Young's modulus were calculated for the results. These results were then compared and verified with those from the literature, with some of the fibers showing distinctly promising potential. Additionally, a study on the effect of alkalization using 3% NaOH solution was carried out on flax, kenaf, abaca, and sisal to observe impact that this common fiber pre-treatment process has on fiber mechanical properties. The result of the investigation indicated that over treatment of natural fibers using NaOH could have a negative effect on the base fiber properties. It is consequently apparent that a treatment time of less than 10 min is sufficient to remove hemicelluloses and to give the optimum effect

The theory of quantum levitators

We develop a unified theory for clocks and gravimeters using the interferences of multiple atomic waves put in levitation by traveling light pulses. Inspired by optical methods, we exhibit a propagation invariant, which enables to derive analytically the wave function of the sample scattering on the light pulse sequence. A complete characterization of the device sensitivity with respect to frequency or to acceleration measurements is obtained. These results agree with previous numerical simulations and confirm the conjecture of sensitivity improvement through multiple atomic wave interferences. A realistic experimental implementation for such clock architecture is discussed.Comment: 11 pages, 6 Figures. Minor typos corrected. Final versio

Orbits for the Impatient: A Bayesian Rejection Sampling Method for Quickly Fitting the Orbits of Long-Period Exoplanets

We describe a Bayesian rejection sampling algorithm designed to efficiently compute posterior distributions of orbital elements for data covering short fractions of long-period exoplanet orbits. Our implementation of this method, Orbits for the Impatient (OFTI), converges up to several orders of magnitude faster than two implementations of MCMC in this regime. We illustrate the efficiency of our approach by showing that OFTI calculates accurate posteriors for all existing astrometry of the exoplanet 51 Eri b up to 100 times faster than a Metropolis-Hastings MCMC. We demonstrate the accuracy of OFTI by comparing our results for several orbiting systems with those of various MCMC implementations, finding the output posteriors to be identical within shot noise. We also describe how our algorithm was used to successfully predict the location of 51 Eri b six months in the future based on less than three months of astrometry. Finally, we apply OFTI to ten long-period exoplanets and brown dwarfs, all but one of which have been monitored over less than 3% of their orbits, producing fits to their orbits from astrometric records in the literature.Comment: 32 pages, 28 figures, Accepted to A

Evaluation of Silk Biomaterials in Combination with Extracellular Matrix Coatings for Bladder Tissue Engineering with Primary and Pluripotent Cells

Silk-based biomaterials in combination with extracellular matrix (ECM) coatings were assessed as templates for cell-seeded bladder tissue engineering approaches. Two structurally diverse groups of silk scaffolds were produced by a gel spinning process and consisted of either smooth, compact multi-laminates (Group 1) or rough, porous lamellar-like sheets (Group 2). Scaffolds alone or coated with collagen types I or IV or fibronectin were assessed independently for their ability to support attachment, proliferation, and differentiation of primary cell lines including human bladder smooth muscle cells (SMC) and urothelial cells as well as pluripotent cell populations, such as murine embryonic stem cells (ESC) and induced pluripotent stem (iPS) cells. AlamarBlue evaluations revealed that fibronectin-coated Group 2 scaffolds promoted the highest degree of primary SMC and urothelial cell attachment in comparison to uncoated Group 2 controls and all Group 1 scaffold variants. Real time RT-PCR and immunohistochemical (IHC) analyses demonstrated that both fibronectin-coated silk groups were permissive for SMC contractile differentiation as determined by significant upregulation of α-actin and SM22α mRNA and protein expression levels following TGFβ1 stimulation. Prominent expression of epithelial differentiation markers, cytokeratins, was observed in urothelial cells cultured on both control and fibronectin-coated groups following IHC analysis. Evaluation of silk matrices for ESC and iPS cell attachment by alamarBlue showed that fibronectin-coated Group 2 scaffolds promoted the highest levels in comparison to all other scaffold formulations. In addition, real time RT-PCR and IHC analyses showed that fibronectin-coated Group 2 scaffolds facilitated ESC and iPS cell differentiation toward both urothelial and smooth muscle lineages in response to all trans retinoic acid as assessed by induction of uroplakin and contractile gene and protein expression. These results demonstrate that silk scaffolds support primary and pluripotent cell responses pertinent to bladder tissue engineering and that scaffold morphology and fibronectin coatings influence these processes

Specificity of Anti-Tau Antibodies when Analyzing Mice Models of Alzheimer's Disease: Problems and Solutions

Aggregates of hyperphosphorylated tau protein are found in a group of diseases called tauopathies, which includes Alzheimer's disease. The causes and consequences of tau hyperphosphorylation are routinely investigated in laboratory animals. Mice are the models of choice as they are easily amenable to transgenic technology; consequently, their tau phosphorylation levels are frequently monitored by Western blotting using a panel of monoclonal/polyclonal anti-tau antibodies. Given that mouse secondary antibodies can recognize endogenous mouse immunoglobulins (Igs) and the possible lack of specificity with some polyclonal antibodies, non-specific signals are commonly observed. Here, we characterized the profiles of commonly used anti-tau antibodies in four different mouse models: non-transgenic mice, tau knock-out (TKO) mice, 3xTg-AD mice, and hypothermic mice, the latter a positive control for tau hyperphosphorylation. We identified 3 tau monoclonal antibody categories: type 1, characterized by high non-specificity (AT8, AT180, MC1, MC6, TG-3), type 2, demonstrating low non-specificity (AT270, CP13, CP27, Tau12, TG5), and type 3, with no non-specific signal (DA9, PHF-1, Tau1, Tau46). For polyclonal anti-tau antibodies, some displayed non-specificity (pS262, pS409) while others did not (pS199, pT205, pS396, pS404, pS422, A0024). With monoclonal antibodies, most of the interfering signal was due to endogenous Igs and could be eliminated by different techniques: i) using secondary antibodies designed to bind only non-denatured Igs, ii) preparation of a heat-stable fraction, iii) clearing Igs from the homogenates, and iv) using secondary antibodies that only bind the light chain of Igs. All of these techniques removed the non-specific signal; however, the first and the last methods were easier and more reliable. Overall, our study demonstrates a high risk of artefactual signal when performing Western blotting with routinely used anti-tau antibodies, and proposes several solutions to avoid non-specific results. We strongly recommend the use of negative (i.e., TKO) and positive (i.e., hypothermic) controls in all experiments

Bringing "The Moth" to Light: A Planet-Sculpting Scenario for the HD 61005 Debris Disk

The HD 61005 debris disk ("The Moth") stands out from the growing collection of spatially resolved circumstellar disks by virtue of its unusual swept-back morphology, brightness asymmetries, and dust ring offset. Despite several suggestions for the physical mechanisms creating these features, no definitive answer has been found. In this work, we demonstrate the plausibility of a scenario in which the disk material is shaped dynamically by an eccentric, inclined planet. We present new Keck NIRC2 scattered-light angular differential imaging of the disk at 1.2-2.3 microns that further constrains its outer morphology (projected separations of 27-135 AU). We also present complementary Gemini Planet Imager 1.6 micron total intensity and polarized light detections that probe down to projected separations less than 10 AU. To test our planet-sculpting hypothesis, we employed secular perturbation theory to construct parent body and dust distributions that informed scattered-light models. We found that this method produced models with morphological and photometric features similar to those seen in the data, supporting the premise of a planet-perturbed disk. Briefly, our results indicate a disk parent body population with a semimajor axis of 40-52 AU and an interior planet with an eccentricity of at least 0.2. Many permutations of planet mass and semimajor axis are allowed, ranging from an Earth mass at 35 AU to a Jupiter mass at 5 AU.Comment: Accepted to AJ; added Figure 5 and minor text edit

Periodontal regeneration risk assessment in the treatment of intrabony defects.

BACKGROUND: Regenerative approaches performed in periodontics seems to be efficient in treating intrabony defects. There are, however, many factors that may affect the predictability of the regenerative procedures. The present article aimed to propose a new risk assessment tool for treating periodontal intrabony defects by regenerative therapy. METHODS: Different variables that could affect the success of a regenerative procedure were considered based on their impact on (i) the wound healing potential, promoting wound stability, cells, and angiogenesis, or (ii) the ability to clean the root surface and maintain an optimal plaque control or (iii) aesthetics (risk for gingival recession). RESULTS: The risk assessment variables were divided into a patient, tooth, defect, and operator level. Patient-related factors included medical conditions such as diabetes, smoking habit, plaque control, compliance with supportive care, and expectations. Tooth-related factors included prognosis, traumatic occlusal forces or mobility, endodontic status, root surface topography, soft tissue anatomy, and gingival phenotype. Defect-associated factors included local anatomy (number of residual bone walls, width, and depth), furcation involvement, cleansability, and number of sides of the root involved. Operator-related factors should not be neglected and included the clinician\u27s level of experience, the presence of environmental stress factors, and the use of checklists in the daily routine. CONCLUSIONS: Using a risk assessment comprised of patient-, tooth-, defect- and operator-level factors can aid the clinician in identifying challenging characteristics and in the treatment decision process

Constraints on the architecture of the HD 95086 planetary system with the Gemini Planet Imager

We present astrometric monitoring of the young exoplanet HD 95086 b obtained with the Gemini Planet Imager between 2013 and 2016. A small but significant position angle change is detected at constant separation; the orbital motion is confirmed with literature measurements. Efficient Monte Carlo techniques place preliminary constraints on the orbital parameters of HD 95086 b. With 68% confidence, a semimajor axis of 61.7^{+20.7}_{-8.4} au and an inclination of 153.0^{+9.7}_{-13.5} deg are favored, with eccentricity less than 0.21. Under the assumption of a co-planar planet-disk system, the periastron of HD 95086 b is beyond 51 au with 68% confidence. Therefore HD 95086 b cannot carve the entire gap inferred from the measured infrared excess in the SED of HD 95086. We use our sensitivity to additional planets to discuss specific scenarios presented in the literature to explain the geometry of the debris belts. We suggest that either two planets on moderately eccentric orbits or three to four planets with inhomogeneous masses and orbital properties are possible. The sensitivity to additional planetary companions within the observations presented in this study can be used to help further constrain future dynamical simulations of the planet-disk system.Comment: Accepted for publication in ApJ