The Science of Stem Cell Biobanking: Investing in the Future

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Systematic Chromosomal Analysis of Cultured Mouse Neural Stem Cell Lines

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Shear-Velocity Structure and Dynamics Beneath the Sicily Channel and Surrounding Regions of the Central Mediterranean Inferred From Seismic Surface Waves

The evolution of the Sicily Channel Rift Zone (SCRZ) is thought to accommodate the regional tectonic stresses of the Calabrian subduction system. Much of the observations we have today are either limited to the surface or to the upper crust or deeper from regional seismic tomography, missing important details about the lithospheric structure and dynamics. It is unclear whether the rifting is passive from far-field extensional stresses or active from mantle upwelling beneath. We measure Rayleigh-and Love-wave phase velocities from ambient seismic noise and invert for 3-D shear-velocity and radial anisotropic models. Variations in crustal S-velocities coincide with topographic and tectonic features. The Tyrrhenian Sea has a ∼10 km thin crust, followed by the SCRZ (∼20 km). The thickest crust is beneath the Apennine-Maghrebian Mountains (∼55 km). Areas experiencing extension and intraplate volcanism have positive crustal radial anisotropy (VSH > VSV); areas experiencing compression and subduction-related volcanism have negative anisotropy. The crustal anisotropy across the Channel shows the extent of the extension. Beneath the Tyrrhenian Sea, we find very low sub-Moho S-velocities. In contrast, the SCRZ has a thin mantle lithosphere underlain by a low-velocity zone. The lithosphere-asthenosphere boundary rises from 60 km depth beneath Tunisia to ∼33 km beneath the SCRZ. Negative radial anisotropy in the upper mantle beneath the SCRZ is consistent with vertical mantle flow. We hypothesize a more active mantle upwelling beneath the rift than previously thought from an interplay between poloidal and toroidal fluxes related to the Calabrian slab, which in turn produces uplift at the surface and induces volcanism

Cx36 makes channels coupling human pancreatic β-cells, and correlates with insulin expression

Previous studies have documented that the insulin-producing β-cells of laboratory rodents are coupled by gap junction channels made solely of the connexin36 (Cx36) protein, and have shown that loss of this protein desynchronizes β-cells, leading to secretory defects reminiscent of those observed in type 2 diabetes. Since human islets differ in several respects from those of laboratory rodents, we have now screened human pancreas, and islets isolated thereof, for expression of a variety of connexin genes, tested whether the cognate proteins form functional channels for islet cell exchanges, and assessed whether this expression changes with β-cell function in islets of control and type 2 diabetics. Here, we show that (i) different connexin isoforms are differentially distributed in the exocrine and endocrine parts of the human pancreas; (ii) human islets express at the transcript level different connexin isoforms; (iii) the membrane of β-cells harbors detectable levels of gap junctions made of Cx36; (iv) this protein is concentrated in lipid raft domains of the β-cell membrane where it forms gap junctions; (v) Cx36 channels allow for the preferential exchange of cationic molecules between human β-cells; (vi) the levels of Cx36 mRNA correlated with the expression of the insulin gene in the islets of both control and type 2 diabetics. The data show that Cx36 is a native protein of human pancreatic islets, which mediates the coupling of the insulin-producing β-cells, and contributes to control β-cell function by modulating gene expressio

Cx36 makes channels coupling human pancreatic β-cells, and correlates with insulin expression

Previous studies have documented that the insulin-producing beta-cells of laboratory rodents are coupled by gap junction channels made solely of the connexin36 (Cx36) protein, and have shown that loss of this protein desynchronizes beta-cells, leading to secretory defects reminiscent of those observed in type 2 diabetes. Since human islets differ in several respects from those of laboratory rodents, we have now screened human pancreas, and islets isolated thereof, for expression of a variety of connexin genes, tested whether the cognate proteins form functional channels for islet cell exchanges, and assessed whether this expression changes with beta-cell function in islets of control and type 2 diabetics. Here, we show that (i) different connexin isoforms are differentially distributed in the exocrine and endocrine parts of the human pancreas; (ii) human islets express at the transcript level different connexin isoforms; (iii) the membrane of beta-cells harbors detectable levels of gap junctions made of Cx36; (iv) this protein is concentrated in lipid raft domains of the beta-cell membrane where it forms gap junctions; (v) Cx36 channels allow for the preferential exchange of cationic molecules between human beta-cells; (vi) the levels of Cx36 mRNA correlated with the expression of the insulin gene in the islets of both control and type 2 diabetics. The data show that Cx36 is a native protein of human pancreatic islets, which mediates the coupling of the insulin-producing beta-cells, and contributes to control beta-cell function by modulating gene expression.The Swiss National Science Foundation (310000-122430 to P.Me), the Juvenile Diabetes Research Foundation (1-2005-1084 to V.C., 1-2007-158 to P.Me), the National Institute of Health (DK55183 to V.C.), the European Union (FP6-Integrated Project EuroDia LSHM-CT-2006-518153 to P.Ma; FP-7 BETAIMAGE 222980 to P.Me), Novo Nordisk (to P.Me) and The Larry L. Hillblom Foundation (to V.C.). Image analysis was performed at The National Center for Microscopy and Imaging Research (NIH grant RR4050 to M. Ellisman). Fresh human islets were provided by the Cell Isolation and Transplantation Cente

Switching-On Survival and Repair Response Programs in Islet Transplants by Bone Marrow–Derived Vasculogenic Cells

OBJECTIVE—Vascular progenitors of bone marrow origin participate to neovascularization at sites of wound healing and transplantation. We hypothesized that the biological purpose of this bone marrow–derived vascular component is to contribute angiogenic and survival functions distinct from those provided by the local tissue-derived vasculature

Endothelium-Derived Netrin-4 Supports Pancreatic Epithelial Cell Adhesion and Differentiation through Integrins α2β1 and α3β1

BACKGROUND: Netrins have been extensively studied in the developing central nervous system as pathfinding guidance cues, and more recently in non-neural tissues where they mediate cell adhesion, migration and differentiation. Netrin-4, a distant relative of Netrins 1-3, has been proposed to affect cell fate determination in developing epithelia, though receptors mediating these functions have yet to be identified. METHODOLOGY/PRINCIPAL FINDINGS: Using human embryonic pancreatic cells as a model of developing epithelium, here we report that Netrin-4 is abundantly expressed in vascular endothelial cells and pancreatic ductal cells, and supports epithelial cell adhesion through integrins α2β1 and α3β1. Interestingly, we find that Netrin-4 recognition by embryonic pancreatic cells through integrins α2β1 and α3β1 promotes insulin and glucagon gene expression. In addition, full genome microarray analysis revealed that fetal pancreatic cell adhesion to Netrin-4 causes a prominent down-regulation of cyclins and up-regulation of negative regulators of the cell cycle. Consistent with these results, a number of other genes whose activities have been linked to developmental decisions and/or cellular differentiation are up-regulated. CONCLUSIONS/SIGNIFICANCE: Given the recognized function of blood vessels in epithelial tissue morphogenesis, our results provide a mechanism by which endothelial-derived Netrin-4 may function as a pro-differentiation cue for adjacent developing pancreatic cell populations expressing adhesion receptors α2β1 and α3β1 integrins

Numerical Modelling of Local Cladding-Structure Interaction

As highlighted by many recent earthquakes, including the Darfield earthquake in New Zealand (2010), damage to non-structural components contributes significantly to the overall earthquake damage and costs. Understanding the interaction between a structure and its non-structural components is critical in order to reduce the damage to non-structural components during an earthquake event. This paper presents a numerical investigation into the local interaction between cladding systems and moment resisting frames utilizing lumped plasticity models of the cladding connections based on a two-dimensional finite element model. The research is part of a larger coordinated research programme which aims to reduce the damage to all non-structural components during earthquake events. The modelling exemplifies the different failure mechanisms that can result due to cladding-structure interaction. Results confirm that common design methods which neglect cladding interaction are inaccurate. The authors intend to continue the research to successively develop improved and innovative low damage cladding-moment resisting frame systems. They also aim to produce simple design tools that provide easy inclusion of the effects of cladding-frame interaction to the seismic response

Numerical Study on the Seismic Interaction Between 2D Seismic Resisting Frames and Claddings

Damage to non-structural components during recent earthquake events, such as the Darfield earthquake in New Zealand (2010) have confirmed the need to better address the interaction between a structure and its non-structural components. This paper aims to numerically investigate the seismic behaviour of a typical newly designed reinforced concrete multi-storey frame building with and without the interaction due to cladding panels. This interaction is investigated by means of non-linear static and dynamic analyses for common typologies of cladding systems. A seismic risk assessment analysis is also presented in order to develop fragility functions based on damage limit states for cladding connection. These are used for assessing the probability of damage of cladding systems after earthquake events of varying intensity. Results confirm the high influence of cladding systems upon the seismic performance of multi-storey buildings. Also revealed is the significant variation in possible levels of cladding damage throughout a building. Further investigations are going to be developed, refining the use of fragility functions associated to innovative low damage cladding solutions

Ground penetrating radar survey of a prehistoric site in southern Italy

In this paper, we present and discuss the results of a ground penetrating radar (GPR) study carried out in an area of southern Italy where a karst cave with prehistoric remains was found. The aim of the study involved the imaging of the subsurface stratigraphy, both inside and outside the cave, in order to assist archaeologists in an excavation programme. The survey grid comprised 18 intersecting GPR profiles. Problems associated with the use of the GPR within a cave environment are highlighted and the data processing sequence designed to extract useful geo-archaeological signatures is described. Interpretation of the radar sections was controlled by the excavation of two trenches (inside and outside the cave), allowing detailed outlining the complex stratigraphy and the reconstruction of Palaeolithic and Neolithic subsurface horizons