NOTCH PRODUCES A DEREGULATION OF CXCR4/SDF-1A CHEMOKINE SIGNALING IN MULTIPLE MYELOMA CELLS

Notch deregulation occurs in several solid and hematopoietic tumors. Recently, Notch receptor oncogenic role has been shown to be critical in multiple myeloma (MM) which frequently displays over-expression of the Notch ligand, Jagged2. MM is a malignant disorder in which the tumor microenvironment plays a critical role: in this contest, Ig-secreting plasma cells accumulate in the bone marrow where they interacts with stroma and BM cells. The cross-talk between MM cells and BM milieu activates signaling such as chemokines and their receptors (CRs) pathways that mediate growth, survival and migration of MM cells, cell-adhesion-mediated drug resistance (CAM-DR) and finally bone lesions trough hyper-stimulation of osteoclasts (OCLs) activity. In our study we took advantage of a panel of MM and bone marrow stromal (BMSC) cell lines and investigated the effects of the Notch signaling withdrawal on MM cell and several chemokine systems. Inhibition of Notch activity, obtained by treatment with gamma-secretase inhibitor (GSI) or Jagged 1 and 2 knock-down indicated that Notch down-regulation hampers MM cell growth, arresting cell cycle progression and inducing increase of apoptosis. Moreover the effects of Notch inhibition on the expression of a number of CRs and correspondent ligands which display a relevant role in MM were investigated: mRNA and protein expression of CXCR4 and SDF-1 were under Notch control. Functional consequences of Notch inhibition were analyzed: GSI XII inhibits SDF1-dependent chemotaxis and proliferation of MM cells. Afterwards, the role of Notch in the MM cells relationship with the BM microenvironment was investigated trough co-culture assays. Our results show that Notch is able to control the cross-talk between MM and BMSCs trough the modulation of SDF-1 and other soluble factors produced by stroma, initiating in this way, a surviving loop. Thus, Notch pathway is able to modulate the MM cell proliferation, apoptosis and migration by directly deregulating the CXCR4/SDF-1 axis activity and the cross-talk between MM cells and BMSCs

Enamel Erosion Reduction through Coupled Sodium Fluoride and Laser Treatments before Exposition in an Acid Environment: An In Vitro Randomized Control SEM Morphometric Analysis

(1) Background: Erosive lesions of dental enamel are steadily increasing owing to both the availability of exogenous acid and the production of endogenous acid. The aim of this study was to investigate the erosion-inhibiting potential of a diode laser irradiation and topical application of fluoride used alone or in combination on the enamel surface of extracted teeth before exposure to an acidic solution. (2) Methods: The four axial enamel surfaces of 40 healthy molars were used for four study groups: (A) no treatment; (B) application of fluoride gel for 120 s; (O) a diode laser application for 120 s; and (X) a combined laser/fluoride for 120 s. Each enamel surface was examined by SEM (scanning electron microscopy). (3) Results: At 700× magnification, it was possible to detect the enamel prisms of the test area of groups A, B, and O, while no structures such as enamel prisms were highlighted for group X because they were covered by an amorphous layer. The mean number of prisms ×1000 µm2 was 7.2 units with an SD of 0.72 for group A, 8 units with an SD of 0.96 for group B, and 4.8 units with a SD of 0.4 for group O. Student’s t-test showed no significant difference between group A and B with a p = 0.054. Group O showed a significant reduction of prims ×1000 µm2 compared with group A (p = 0.0027) and group B (p = 0.0009). Student’s t-test showed no significant difference between groups A and B with a p = 0.054. Group O showed a significant reduction of prims density with respect to group A (p = 0.0027) and group B (p = 0.0009). (4) Conclusions: This amorphous layer might be correlated with the effect of laser on enamel, which reduces both water and carbonate ion; increases the crystallinity of hydroxyapatite, and improves the mechanical properties of enamel; which is responsible for greater protection expressed by the enamel of group X against acid attacks

CONTAINER LOCALISATION AND MASS ESTIMATION WITH AN RGB-D CAMERA

In the research area of human-robot interactions, the automatic estimation of the mass of a container manipulated by a person leveraging only visual information is a challenging task. The main challenges consist of occlusions, different filling materials and lighting conditions. The mass of an object constitutes key information for the robot to correctly regulate the force required to grasp the container. We propose a single RGB-D camera-based method to locate a manipulated container and estimate its empty mass i.e., independently of the presence of the content. The method first automatically selects a number of candidate containers based on the distance with the fixed frontal view, then averages the mass predictions of a lightweight model to provide the final estimation. Results on the CORSMAL Containers Manipulation dataset show that the proposed method estimates empty container mass obtaining a score of 71.08% under different lighting or filling conditions

Bioresorption control and biological response of magnesium alloy az31 coated with poly-β-hydroxybutyrate

Magnesium and its alloys are not normally used as bioresorbable temporary implants due to their high and uncontrolled degradation rate in a physiological liquid environment. The improvement of corrosion resistance to simulated body fluids (SBF) of a magnesium alloy (AZ31) coated with poly-β-hydroxybutyrate (PHB) was investigated. Scanning electron microscopy, Fourier transform infrared spectrometer, and contact angle measurements were used to characterize surface morphology, material composition, and wettability, respectively. pH modification of the SBF corroding medium, mass of Mg2+ ions released, weight loss of the samples exposed to the SBF solution, and electrochemical experiments were used to describe the corrosion process and its kinetics. The material’s biocompatibility was described by evaluating the effect of corrosion by products collected in the SBF equilibrating solution on hemolysis ratio, cytotoxicity, nitric oxide (NO), and total antioxidant capacity (T-AOC). The results showed that the PHB coating can diffusively control the degradation rate of magnesium alloy, improving its biocompatibility: the hemolysis rate of materials was lower than 5%, while in vitro human umbilical vein endothelial cell (HUVEC) compatibility experiments showed that PHB-coated Mg alloy promoted cell proliferation and had no effect on the NO content and that the T-AOC was enhanced compared with the normal group and bare AZ31 alloy. PHB-coated AZ31 magnesium alloy extraction fluids have a less toxic behavior due to the lower concentration of corrosion byproducts deriving from the diffusion control exerted by the PHB coating films both from the metal surface to the solution and vice versa. These findings provide more reference value for the selection of such systems as tunable bioresorbable prosthetic materials

Critical behaviour of the stochastic Wilson-Cowan model

Spontaneous brain activity is characterized by bursts and avalanche-like dynamics, with scale-free features typical of critical behaviour. The stochastic version of the celebrated Wilson- Cowan model has been widely studied as a system of spiking neurons reproducing non-trivial features of the neural activity, from avalanche dynamics to oscillatory behaviours. However, to what extent such phenomena are related to the presence of a genuine critical point remains elusive. Here we address this central issue, providing analytical results in the linear approximation and extensive numerical analysis. In particular, we present results supporting the existence of a bona fide critical point, where a second-order-like phase transition occurs, characterized by scale-free avalanche dynamics, scaling with the system size and a diverging relaxation time-scale. Moreover, our study shows that the observed critical behaviour falls within the universality class of the mean-field branching process, where the exponents of the avalanche size and duration distributions are, respectively, 3/2 and 2. We also provide an accurate analysis of the system behaviour as a function of the total number of neurons, focusing on the time correlation functions of the firing rate in a wide range of the parameter space

Mixed-ethnicity face shape and attractiveness in humans

Many studies show agreement within and between populations and cultures for general judgments of facial attractiveness. Studies that have examined the attractiveness of specific traits have also highlighted cross-cultural differences for factors such as symmetry, averageness, and masculinity. One trait that should be preferred across cultures is heterozygosity. Indeed, several studies suggest that mixed ethnicity, in terms of appearing to possess a mixture of traits from different human population groups, may be found attractive, which could reflect preferences for heterozygosity. We examined preferences for manipulated face shape associated with different populations in both Europeans (Britain) and Africans (Guinea-Bissau). We found that mixed-ethnicity face shapes were more attractive than enhanced single-ethnicity face shape across both populations. These results are consistent with evolutionary theories suggesting individuals should prefer heterozygosity in partners because facial cues to mixed-ethnicity are likely to indicate diverse genes compared to cues that indicate a face belongs to a single particular culture or population

Hunter-Gatherer Color Naming Provides New Insight into the Evolution of Color Terms

SummaryMost people name the myriad colors in the environment using between two and about a dozen color terms [1], with great variation within and between languages [2]. Investigators generally agree that color lexicons evolve from fewer terms to more terms, as technology advances and color communication becomes increasingly important [3]. However, little is understood about the color naming systems at the least technologically advanced end of the continuum. The Hadza people of Tanzania are nomadic hunter-gatherers who live a subsistence lifestyle that was common before the advent of agriculture (see Supplemental Experimental Procedures, section I; [4]), suggesting that the Hadzane language should be at an early stage of color lexicon evolution. When Hadza, Somali, and US informants named 23 color samples, Hadza informants named only the black, white, and red samples with perfect consensus. Otherwise, they used low-consensus terms or responded “don’t know.” However, even low-consensus color terms grouped test colors into lexical categories that aligned with those found in other world languages [5]. Furthermore, information-theoretic analysis showed that color communication efficiency within the Hadza, Somali, and US language communities falls on the same continuum as other world languages. Thus, the structure of color categories is in place in Hadzane, even though words for many of the categories are not in general use. These results suggest that even very simple color lexicons include precursors of many color categories but that these categories are initially represented in a diverse and distributed fashion