An adaptive finite element model for steerable needles

Biomechanics and Modeling in Mechanobiology - Penetration of a flexible and steerable needle into a soft target material is a complex problem to be modelled, involving several mechanical...     

Where do you come from; where do you go? Pluripotency,differentiation and malfunction of stem cells

The international conference 'Stem Cells in Development and Disease' took place in September 2011 at the Max-Delbrück-Center for Molecular Medicine (MDC) in Berlin. It brought together scientists working on different types of stem cell and covered the latest findings in stem cell biology, including the genetic and epigenetic mechanisms of reprogramming, maintenance of pluripotency and differentiation.     

Application of molecular dynamics DL_POLY codes to interfaces of inorganic materials

Three recent applications of the DL_POLY molecular dynamics code are described, which demonstrate the flexibility and viability of the code for extending our understanding of the structure, stability and reactivity of ceramics and minerals at the atomic level. The first is an investigation into differences in oxygen atom mobility in bulk and at the most stable {111} surface of ceria. The results show enhanced surface transport but that it is via subsurface oxygen. Secondly, we investigate how polychloro-dibenzo-pdioxins (PCDDs) molecules might adsorb on clay surfaces. The resulting adsorption energies show a clear relationship with chlorine content of the molecule. Finally, we apply DL_POLY to comparing the aggregation of magnesium oxide and calcium carbonate nanoparticles. We find that very small calcium carbonate nanoparticles are amorphous and their aggregation shows no preferred orientation in contrast to magnesium oxide, which remain highly crystalline and combine in a highly structural specific way.     

Ryanodine receptor activation by Ca v 1.2 is involved in dendritic cell major histocompatibility complex class II surface expression

Dendritic cells express the skeletal muscle ryanodine receptor (RyR1), yet little is known concerning its physiological role and activation mechanism. Here we show that dendritic cells also express the Ca(v)1.2 subunit of the L-type Ca(2+) channel and that release of intracellular Ca(2+) via RyR1 depends on the presence of extracellular Ca(2+) and is sensitive to ryanodine and nifedipine. Interestingly, RyR1 activation causes a very rapid increase in expression of major histocompatibility complex II molecules on the surface of dendritic cells, an effect that is also observed upon incubation of mouse BM12 dendritic cells with transgenic T cells whose T cell receptor is specific for the I-A(bm12) protein. Based on the present results, we suggest that activation of the RyR1 signaling cascade may be important in the early stages of infection, providing the immune system with a rapid mechanism to initiate an early response, facilitating the presentation of antigens to T cells by dendritic cells before their full maturation.     

Extended, relaxed, and condensed conformations of hyaluronan observed by atomic force microscopy

The conformation of the polysaccharide hyaluronan (HA) has been investigated by tapping mode atomic force microscopy in air. HA deposited on a prehydrated mica surface favored an extended conformation, attributed to molecular combing and inhibition of subsequent chain recoil by adhesion to the structured water layer covering the surface. HA deposited on freshly cleaved mica served as a defect in a partially structured water layer, and favored relaxed, weakly helical, coiled conformations. Intramolecularly condensed forms of HA were also observed, ranging from pearl necklace forms to thick rods. The condensation is attributed to weak adhesion to the mica surface, counterion-mediated attractive electrostatic interactions between polyelectrolytes, and hydration effects. Intermolecular association of both extended and condensed forms of HA was observed to result in the formation of networks and twisted fibers, in which the chain direction is not necessarily parallel to the fiber direction. Whereas the relaxed coil and partially condensed conformations of HA are relevant to the native structure of liquid connective tissues, fully condensed rods may be more relevant for HA tethered to a cell surface or intracellular HA, and fibrous forms may be relevant for HA subjected to shear flow in tight intercellular spaces or in protein-HA complexes.     

Trace element content in human milk during lactation of preterm newborns

The present study has been finalized to perform the content of Zn, Cu, Cr, Se, Mn, F, Mo, Ni, and B in the preterm human milk over 21 d of lactation. Trace element (TE) contents were analyzed by inductively coupled plasma atomic emission spectroscopy (ICP-MS), and median concentrations of Zn, Cu, Cr, Se, Mn, and F observed in preterm milk did not demonstrate significant differences in comparison to levels shown in term milk. A statistical significant difference (p<0.05) has been found among Mo, Ni, and B content in preterm milk for every stage of lactation. TE content of infant blood founded concentrations of Mo in preterm babies significantly (p<0.01) lower than in term offsprings. Similar values of other TE content were obtained in blood of preterm, and term newborns. These findings point to the need for a considerable reassessment of the existing dietary recommendation for Mo content in infant feeding.     

Propionyl-L-carnitine reduces proliferation and potentiates Bax-related apoptosis of aortic intimal smooth muscle cells by modulating nuclear factor-kappaB activity

Propionyl-l-carnitine (PLC) has been introduced among the therapeutic approaches of peripheral arterial disease, and more recently, an increase of intimal cell apoptosis has been demonstrated to contribute to its effectiveness in rabbit carotid postinjury myointimal hyperplasia prevention. How PLC mediates these effects on vascular smooth muscle cells (SMCs) remains poorly understood. We investigated the role of NF-kappaB in PLC-induced arterial remodeling. In vivo, daily PLC treatment 15 days after injury resulted in a reduction of relative rat aortic intimal volume, an increase of apoptosis, Bax up-regulation without changing the Bcl-2 level, and a reduction of NF-kappaB, vascular cell adhesion molecule-1, monocyte chemotactic protein-1, and survivin in myointimal thickening compared with controls. In the presence of 10% serum, a reduced G(1) --> S phase progression preceded PLC-induced intimal cell apoptosis; in 0.1% serum cultures, in a dose-dependent manner, PLC rapidly induced intimal cell apoptosis and reduced p65, p50, IAP-1, and IAP-2 expression. Inhibiting NF-kappaB activation through SN50 increased apoptotic rate and Bax expression in intimal but not in medial SMCs, and successive PLC treatment failed to induce a further increase in apoptotic rate. Bax antisense oligodeoxynucleotide reduced PLC-induced intimal cell apoptosis and cytochrome c release. The PLC-induced attenuation of NF-kappaB activity in intimal cells was also due to the increase of IkappaB-alpha bioavailability, as the result of a parallel induction of IkappaB-alpha synthesis and reduction of phosphorylation and degradation. Collectively, these findings document that NF-kappaB activity inhibition contributes to PLC-induced proliferative arrest and Bax-related apoptosis of intimal SMCs.     

TGF-beta signaling is essential for joint morphogenesis

Despite its clinical significance, joint morphogenesis is still an obscure process. In this study, we determine the role of transforming growth factor beta (TGF-beta) signaling in mice lacking the TGF-beta type II receptor gene (Tgfbr2) in their limbs (Tgfbr2(PRX-1KO)). In Tgfbr2(PRX-1KO) mice, the loss of TGF-beta responsiveness resulted in the absence of interphalangeal joints. The Tgfbr2(Prx1KO) joint phenotype is similar to that in patients with symphalangism (SYM1-OMIM185800). By generating a Tgfbr2-green fluorescent protein-beta-GEO-bacterial artificial chromosome beta-galactosidase reporter transgenic mouse and by in situ hybridization and immunofluorescence, we determined that Tgfbr2 is highly and specifically expressed in developing joints. We demonstrated that in Tgfbr2(PRX-1KO) mice, the failure of joint interzone development resulted from an aberrant persistence of differentiated chondrocytes and failure of Jagged-1 expression. We found that TGF-beta receptor II signaling regulates Noggin, Wnt9a, and growth and differentiation factor-5 joint morphogenic gene expressions. In Tgfbr2(PRX-1KO) growth plates adjacent to interphalangeal joints, Indian hedgehog expression is increased, whereas Collagen 10 expression decreased. We propose a model for joint development in which TGF-beta signaling represents a means of entry to initiate the process.