Alx1, a member of the Cart1/Alx3/Alx4 subfamily of Paired-class homeodomain proteins, is an essential component of the gene network controlling skeletogenic fate specification in the sea urchin embryo

In the sea urchin embryo, the large micromeres and their progeny function as a critical signaling center and execute a complex morphogenetic program. We have identified a new and essential component of the gene network that controls large micromere specification, the homeodomain protein Alx1. Alx1 is expressed exclusively by cells of the large micromere lineage beginning in the first interphase after the large micromeres are born. Morpholino studies demonstrate that Alx1 is essential at an early stage of specification and controls downstream genes required for epithelial-mesenchymal transition and biomineralization. Expression of Alx1 is cell autonomous and regulated maternally through ß-catenin and its downstream effector, Pmar1. Alx1 expression can be activated in other cell lineages at much later stages of development, however, through a regulative pathway of skeletogenesis that is responsive to cell signaling. The Alx1 protein is highly conserved among euechinoid sea urchins and is closely related to the Cart1/Alx3/Alx4 family of vertebrate homeodomain proteins. In vertebrates, these proteins regulate the formation of skeletal elements of the limbs, face and neck. Our findings suggest that the ancestral deuterostome had a population of biomineral-forming mesenchyme cells that expressed an Alx1-like protein

Graphical methods, kinematic and finite element analysis of the premilcuore masonry bridge

This paper presents the results of static and seismic vulnerability analyses performed on a single-span masonry bridge located in Northern Italy. The structure, dated back to the 17th century, is a bridge with single-span of about 16 meters and height of 8 meters, built with rubble and irregular masonry. A preliminary static analysis was performed on the bridge through traditional graphic approaches such as the Méry's rule and the Durand-Claye's method. Afterwards, a kinematic non-linear analysis was executed once the collapse mechanism under horizontal earthquake-type actions was identified. Finally, a static finite element analysis with brick elements was performed to state the seismic vulnerability of the bridge, by changing its mechanical properties to evaluate their influence on the structural response. Collapse load factors have been also computed considering non-uniform gravitational loads and horizontal settlements at the bridge foundations

Finite dimensional corrections to mean field in a short-range p-spin glassy model

In this work we discuss a short range version of the $p$-spin model. The model is provided with a parameter that allows to control the crossover with the mean field behaviour. We detect a discrepancy between the perturbative approach and numerical simulation. We attribute it to non-perturbative effects due to the finite probability that each particular realization of the disorder allows for the formation of regions where the system is less frustrated and locally freezes at a higher temperature.Comment: 18 pages, 5 figures, submitted to Phys Rev

Nod2 Deficiency in mice is Associated with Microbiota Variation Favouring the Expansion of mucosal CD4+ LAP+ Regulatory Cells

Nucleotide-binding Oligomerization Domain-2 (NOD2) mutations are associated with an increased risk to develop Crohn's Disease. In previous studies, we have shown that Nod2-/- mice manifest increased proportion of Lamina Propria (LP) CD4+ LAP+ Foxp3- regulatory cells, when compared with Nod2+/+ mice, while CD4+ Foxp3 + regulatory cells were not affected. Here, we investigated the Nod2 gut microbiota, by 16S rRNA pyrosequencing, at steady state and after TNBS-colitis induction in mice reared separately or in cohousing, correlating the microbial profiles with LP regulatory T cells proportion and tissue cytokines content. We found that enrichment of Rikenella and Alistipes (Rikenellaceae) in Nod2-/- mice at 8 weeks of age reared separately was associated with increased proportion of CD4+ LAP+ Foxp3- cells and less severe TNBS-colitis. In co-housed mice the acquisition of Rickenellaceae by Nod2+/+ mice was associated with increased CD4+ LAP+ Foxp3- proportion and less severe colitis. Severe colitis was associated with enrichment of gram-negative pathobionts (Escherichia and Enterococcus), while less severe colitis with protective bacteria (Barnesiella, Odoribacter and Clostridium IV). Environmental factors acting on genetic background with different outcomes according to their impact on microbiota, predispose in different ways to inflammation. These results open a new scenario for therapeutic attempt to re-establish eubiosis in Inflammatory Bowel Disease patients with NOD2 polymorphisms

Light-cone fluctuations and the renormalized stress tensor of a massless scalar field

We investigate the effects of light-cone fluctuations over the renormalized vacuum expectation value of the stress-energy tensor of a real massless minimally coupled scalar field defined in a ($d+1$)-dimensional flat space-time with topology ${\cal R}\times {\cal S}^d$. For modeling the influence of light-cone fluctuations over the quantum field, we consider a random Klein-Gordon equation. We study the case of centered Gaussian processes. After taking into account all the realizations of the random processes, we present the correction caused by random fluctuations. The averaged renormalized vacuum expectation value of the stress-energy associated with the scalar field is presented

Zero-point energy of massless scalar fields in the presence of soft and semihard boundaries in D dimensions

The renormalized energy density of a massless scalar field defined in a D-dimensional flat spacetime is computed in the presence of "soft" and "semihard" boundaries, modeled by some smoothly increasing potential functions. The sign of the renormalized energy densities for these different confining situations is investigated. The dependence of this energy on $D$ for the cases of "hard" and "soft/semihard" boundaries are compared.Comment: 36 pages, LaTeX, 4 figure

Accelerated detectors in Dirac vacuum: the effects of horizon fluctuations

We consider an Unruh-DeWitt detector interacting with a massless Dirac field. Assuming that the detector is moving along an hyperbolic trajectory, we modeled the effects of fluctuations in the event horizon using a Dirac equation with random coefficients. First, we develop the perturbation theory for the fermionic field in a random media. Further we evaluate corrections due to the randomness in the response function associated to different model detectors.Comment: 19 pages, 1 figur

Complex spatio-temporal structure of the Holocene Thermal Maximum

Inconsistencies between Holocene climate reconstructions and numerical model simulations question the robustness of climate models and proxy temperature records. Climate reconstructions suggest an early-middle Holocene Thermal Maximum (HTM) followed by gradual cooling, whereas climate models indicate continuous warming. This discrepancy either implies seasonal biases in proxy-based climate reconstructions, or that the climate model sensitivity to forcings and feedbacks needs to be reevaluated. Here, we analyze a global database of Holocene paleotemperature records to investigate the spatiotemporal structure of the HTM. Continental proxy records at mid and high latitudes of the Northern Hemisphere portray a “classic” HTM (8–4 ka). In contrast, marine proxy records from the same latitudes reveal an earlier HTM (11–7ka), while a clear temperature anomaly is missing in the tropics. The results indicate a heterogeneous response to climate forcing and highlight the lack of globally synchronous HTM