Expression of hMLH1 and hMSH2 proteins in ameloblastomas and tooth germs.

BACKGROUND: Mismatch repair proteins (MMRPs) are a group of nuclear enzymes that participate in the repair of base mismatches that occur during DNA replication in all proliferating cells. The most studied MMRPs are hMSH2 and hMLH1, which are known to be highly expressed in normal tissues. A loss of MMRPs leads to the accumulation of DNA replication errors in proliferating cells. Ki-67 is a biomarker regarded to be the gold-standard tool for determining cell proliferation by immunohistochemical methods. The aim of this study was to investigate the immunohistochemical expression of hMLH1, hMSH2 and Ki-67 proteins in ameloblastomas and tooth germs, to contribute to the understanding of the development of this odontogenic neoplasm. MATERIAL AND METHODS: Immunohistochemical assays to determine the presence of proteins hMSH2, hMLH1 and Ki-67 were performed in 80 ameloblastomas (40 solid and 40 unicystic) and five tooth germs. RESULTS: Unicystic ameloblastomas showed higher MMRP expression (hMLH1: 62.5 ± 43.4; hMSH2: 83.3 ± 47.8) than did solid ameloblastomas (hMLH1: 59.4 ± 13.5; hMSH2: 75.8 ± 40.2). Additionally, the cell proliferation index assessed by Ki-67 was inversely proportional to the expression of MMRP. Comparison between tooth germs and ameloblastoma revealed significantly higher expression of hMLH1, hMSH2 and Ki-67 in tooth germs (p=0.02). CONCLUSIONS: The differences of MMRP and Ki-67 immunoexpression between ameloblastomas and tooth germ suggest that alterations in the MMRP mechanisms could participate in the biological behavior of ameloblastomas.

Paving the way to nanoionics: atomic origin of barriers for ionic transport through interfaces.

The blocking of ion transport at interfaces strongly limits the performance of electrochemical nanodevices for energy applications. The barrier is believed to arise from space-charge regions generated by mobile ions by analogy to semiconductor junctions. Here we show that something different is at play by studying ion transport in a bicrystal of yttria (9% mol) stabilized zirconia (YSZ), an emblematic oxide ion conductor. Aberration-corrected scanning transmission electron microscopy (STEM) provides structure and composition at atomic resolution, with the sensitivity to directly reveal the oxygen ion profile. We find that Y segregates to the grain boundary at Zr sites, together with a depletion of oxygen that is confined to a small length scale of around 0.5 nm. Contrary to the main thesis of the space-charge model, there exists no evidence of a long-range O vacancy depletion layer. Combining ion transport measurements across a single grain boundary by nanoscale electrochemical strain microscopy (ESM), broadband dielectric spectroscopy measurements, and density functional calculations, we show that grain-boundary-induced electronic states act as acceptors, resulting in a negatively charged core. Besides the possible effect of the modified chemical bonding, this negative charge gives rise to an additional barrier for ion transport at the grain boundary.

Relaxation pathway confinement in glassy dynamics.

We compute for an archetypical glass-forming system the excess of particle mobility distributions over the corresponding distribution of dynamic propensity, a quantity that measures the tendency of the particles to be mobile and reflects the local structural constraints. This enables us to demonstrate that, on supercooling, the dynamical trajectory in search for a relaxation event must deal with an increasing confinement of relaxation pathways. This "entropic funnel" of relaxation pathways built upon a restricted set of mobile particles is also made evident from the decay and further collapse of the associated Shannon entropy.

Aggregation and adsorption behavior of low concentration aqueous solutions of hexadecyltrimethylammonium ortho, meta, and parafluorobenzoate.

The aggregation properties of 2-, 3-, and 4-fluorobenzoic acids (2FBA, 3FBA, and 4FBA, respectively) and their salts with hexadecyltrimethylammonium cations (HTA2FB, HTA3FB, and HTA4FB) in water were studied with a battery of techniques. Their activity at the air/solution interface has been also studied. The position of the fluorine atom in the acid affected the solubility, adsorption, and aggregation in the pure acids solutions. The 4FBA is less water soluble, more hydrophobic, and has the lower critical aggregation concentration of the three isomers. The behavior of the HTA2FB compound in aqueous solution is different from that of HTA3FB and HTA4FB. The critical micelle concentration, critical concentration for sphere-to-rod-like micelle transition, and Krafft point of HTA3FB and HTA4FB are lower than those of the other surfactant but their surface activities are higher. The differences between the HTA2FB and the other two surfactants have been explained on the basis of the regular solution theory of mixed micelles and in light of the analysis of the hydration shell of the acids through molecular dynamic simulations. The results of the present work suggest that the different behaviors are due to a combination of different dehydration tendencies and the steric possibility of inclusion of the counterions in the micelle palisade layer. The formation of rod-like micelles by HTA2FB, while the tetradecyltrimethylammonium 2-fluorobenzoate only forms spherical aggregates, is explained on the basis of the packing parameter. The mentioned factors are complementary to others presented in literature. These conditions may be used in the rational design of micelles by means of molecular dynamics simulations, reducing the trial-and-error approach used to date.

Structural and dynamical aspects of water in contact with a hydrophobic surface.

By means of molecular dynamics simulations we study the structure and dynamics of water molecules in contact with a model hydrophobic surface: a planar graphene-like layer. The analysis of the distributions of a local structural index indicates that the water molecules proximal to the graphene layer are considerably more structured than the rest and, thus, than the bulk. This structuring effect is lost in a few angstroms and is basically independent of temperature for a range studied comprising parts of both the normal liquid and supercooled states (240K to 320K). In turn, such structured water molecules present a dynamics that is slower than the bulk, as a consequence of their improved interactions with their first neighbors.

Determining the heterogeneity in time of the dynamics within a slowly relaxing region of a supercooled liquid: Role of sharp relaxation events.

Supercooled liquids have been shown to be dynamically heterogeneous with different regions of the system presenting dynamics that vary from each other even by orders of magnitude. Computer simulations have confirmed such a picture by detecting that the mobile particles in model glass formers are not homogeneously distributed within the system but arranged in clusters. More recently, the dynamics of small systems has been characterized by demonstrating that their structural relaxation is not homogeneous in time, in the sense that it does not evolve gradually but it is signed by rapid bursts of mobility characterized by relative compact clusters of mobile particles. These events (which have been named d clusters) are fast and sparse and trigger the transitions the system experiences between metabasins (MB) of its potential-energy surface. The MB residence times are much larger than the time scales of occurrence of the d clusters, and it has been suggested that the events that occur within them scarcely contribute to the structural relaxation of the system. Thus, the picture of glassy relaxation that emerges would indicate that at any time a supercooled liquid may present different spatial regions, each one characterized by different structural relaxation times. In turn, each of such regions would not relax smoothly or gradually but by means of sporadic sharp relaxation events. Here, we assess for a model glass former the relative relevance of the MB exploration events and of the d clusters both in small systems and within regions of large systems, to show that the structural relaxation at the region level is indeed extremely heterogeneous in time and utterly governed by the latter.

Connections between structural jamming, local metabasin features, and relaxation dynamics in a supercooled glassy liquid.

Dynamics in glass-forming liquids in the supercooled regime vary considerably from one point of the sample to another suggesting the existence of regions with different degrees of jamming. In fact, the existence of relatively compact regions with particles with an enhanced propensity for motion has been detected in model glassy systems. In turn, the structural relaxation has been shown to be accomplished by means of a series of fast transitions between metabasins in the potential energy landscape involving the collective motion of a substantial number of particles arranged in relatively compact clusters (democratic clusters or d clusters). In this work we shall complete this picture by identifying the connections between local structural jamming, metabasin confining strength, and d clusters. Thus we shall demonstrate that the degree of jamming of the local structure dictates the confining strength of the local metabasin and that the local high propensity regions and the d clusters are not only similar in nature but that they share a significant amount of particles.

Reproducibility of dynamical heterogeneities and metabasin dynamics in glass forming liquids: the influence of structure on dynamics.

The discovery that the propensity for particle motion in a supercooled liquid is completely determined by the initial structure pointed to the existence of a causal link between structure and dynamics in glassy systems. Here we demonstrate that this underlying influence of structure is only local in time, fading out beyond the metabasin lifetime much before the relaxation time. Thus, our results reveal the irreproducibility of metabasin dynamics and support the scenario of a random walk on metabasins for the long time diffusion.

Activated dynamics and timescale separation within the landscape paradigm: signature of complexity, diversity and glassiness.

The landscape paradigm has become a widespread picture within the realm of complex systems. Complex systems include a great variety of systems, ranging from glasses to biopolymers, which display a common dynamical behavior. Within this framework, the dynamics of a such a system can be envisioned as the search it performs on its (potential energy) landscape. This approach rests on the belief that the relaxation behavior depends only on generic features, irrespective of specific details and lies on the validity of a timescale separation scenario computationally corroborated but not properly validated yet form first principles. In this work we shall show that the prevalence of activated dynamics over other kinds of mechanisms determines the emergence of complex dynamical behavior. Thus, complexity and diversity are not intrinsic properties of a system but depend on the kind of exploration of the landscape. We shall focus mainly on an ample generic context (complex hierarchical systems which have been used as models of glasses, spin glasses and biopolymers) and a specific one (model glass formers). For the last case we shall be able to reveal (in mechanistic terms) the microscopic rationale for the occurrence of timescale separation. Furthermore, we shall explore the connections between these two up to now mostly unrelated contexts and the relation to a variational principle, and we shall reveal the conditions for the applicability of the landscape approach.