Mechano-sensing and cell migration: A 3D model approach

Cell migration is essential for tissue development in different physiological and pathological conditions. It is a complex process orchestrated by chemistry, biological factors, microstructure and surrounding mechanical properties. Focusing on the mechanical interactions, cells do not only exert forces on the matrix that surrounds them, but they also sense and react to mechanical cues in a process called mechano-sensing. Here, we hypothesize the involvement of mechano-sensing in the regulation of directional cell migration through a three-dimensional (3D) matrix. For this purpose, we develop a 3D numerical model of individual cell migration, which incorporates the mechano-sensing process of the cell as the main mechanism regulating its movement. Consistent with this hypothesis, we found that factors, such as substrate stiffness, boundary conditions and external forces, regulate specific and distinct cell movements

Other‐Sacrificing Options

I argue that you can be permitted to discount the interests of your adversaries even though doing so would be impartially suboptimal. This means that, in addition to the kinds of moral options that the literature traditionally recognises, there exist what I call other-sacrificing options. I explore the idea that you cannot discount the interests of your adversaries as much as you can favour the interests of your intimates; if this is correct, then there is an asymmetry between negative partiality toward your adversaries and positive partiality toward your intimates

Knowledge of Objective 'Oughts': Monotonicity and the New Miners Puzzle

In the classic Miners case, an agent subjectively ought to do what they know is objectively wrong. This case shows that the subjective and objective ‘oughts’ are somewhat independent. But there remains a powerful intuition that the guidance of objective ‘oughts’ is more authoritative—so long as we know what they tell us. We argue that this intuition must be given up in light of a monotonicity principle, which undercuts the rationale for saying that objective ‘oughts’ are an authoritative guide for agents and advisors

Post-Collision Interaction with Wannier electrons

A theory of the Post-Collision Interaction (PCI) is developed for the case when an electron atom impact results in creation of two low-energy Wannier electrons and an ion excited into an autoionizing state. The following autoionization decay exposes the Wannier pair to the influence of PCI resulting in variation of the shape of the line in the autoionization spectrum. An explicit dependence of the autoionization profile on the wave function of the Wannier pair is found. PCI provides an opportunity to study this wave function for a wide area of distancesComment: 33 pages, Latex, IOP style, and 3 figures fig1.ps, fig2.ps, fig3.p

MicroRNA delivery through nanoparticles

MicroRNAs (miRNAs) are attracting a growing interest in the scientific community due to their central role in the etiology of major diseases. On the other hand, nanoparticle carriers offer unprecedented opportunities for cell specific controlled delivery of miRNAs for therapeutic purposes. This review critically discusses the use of nanoparticles for the delivery of miRNA-based therapeutics in the treatment of cancer and neurodegenerative disorders and for tissue regeneration. A fresh perspective is presented on the design and characterization of nanocarriers to accelerate translation from basic research to clinical application of miRNA-nanoparticles. Main challenges in the engineering of miRNA-loaded nanoparticles are discussed, and key application examples are highlighted to underline their therapeutic potential for effective and personalized medicine

Temporal Effects of Cyclic Stretching on Distribution and Gene Expression of Integrin and Cytoskeleton by Ligament Fibroblasts In Vitro

Cyclic stretching is pivotal to maintenance of the ligaments. However, it is still not clear when ligament fibroblasts switch on expression of genes related to the mechanotransduction pathway in response to cyclic stretching. This in vitro study investigated, using ligament fibroblasts, the time-dependent changes in distribution and gene expression of β1 integrin, the cytoskeleton, and collagens after the application of 6% cyclic stretching at a frequency of 0.1 Hz for 3 hr on silicon membranes. We carried out confocal laser scanning microscopy to demonstrate changes in distribution of these components as well as quantitative real-time RT-PCR to quantify levels of these gene expression both during application of cyclic stretching and at 0, 2, 6, 12, and 18 hr after the termination of stretching. Control (unstretched) cells were used at each time point. Within 1 hr of the application of stretching, the fibroblasts and their actin stress fibers became aligned in a direction perpendicular to the major axis of stretch, whereas control (unstretched) cells were randomly distributed. In response to cyclic stretching, upregulation of actin at the mRNA level was first observed within 1 hr after the onset of stretching, while upregulation of β1 integrin and type I and type III collagens was observed between 2 and 12 hr after the termination of stretching. These results indicate that the fibroblasts quickly modify their morphology in response to cyclic stretching, and subsequently they upregulate the expression of genes related to the mechanotransduction pathway mainly during the resting period after the termination of stretching

Adalimumab for the treatment of fistulas in patients with Crohn’s disease

To evaluate the efficacy of adalimumab in the healing of draining fistulas in patients with active Crohn's disease (CD). A phase III, multicentre, randomised, double-blind, placebo controlled study with an open-label extension was conducted in 92 sites. A subgroup of adults with moderate to severely active CD (CD activity index 220-450) for >or=4 months who had draining fistulas at baseline. All patients received initial open-label adalimumab induction therapy (80 mg/40 mg at weeks 0/2). At week 4, all patients were randomly assigned to receive double-blind placebo or adalimumab 40 mg every other week or weekly to week 56 (irrespective of fistula status). Patients completing week 56 of therapy were then eligible to enroll in an open-label extension. Complete fistula healing/closure (assessed at every visit) was defined as no drainage, either spontaneous or with gentle compression. Of 854 patients enrolled, 117 had draining fistulas at both screening and baseline (70 randomly assigned to adalimumab and 47 to placebo). The mean number of draining fistulas per day was significantly decreased in adalimumab-treated patients compared with placebo-treated patients during the double-blind treatment period. Of all patients with healed fistulas at week 56 (both adalimumab and placebo groups), 90% (28/31) maintained healing following 1 year of open-label adalimumab therapy (observed analysis). In patients with active CD, adalimumab therapy was more effective than placebo for inducing fistula healing. Complete fistula healing was sustained for up to 2 years by most patients in an open-label extension tria

Atomistic modelling of large-scale metal film growth fronts

We present simulations of metallization morphologies under ionized sputter deposition conditions, obtained by a new theoretical approach. By means of molecular dynamics simulations using a carefully designed interaction potential, we analyze the surface adsorption, reflection, and etching reactions taking place during Al physical vapor deposition, and calculate their relative probability. These probabilities are then employed in a feature-scale cellular-automaton simulator, which produces calculated film morphologies in excellent agreement with scanning-electron-microscopy data on ionized sputter deposition.Comment: RevTeX 4 pages, 2 figure

The Early ANTP Gene Repertoire: Insights from the Placozoan Genome

The evolution of ANTP genes in the Metazoa has been the subject of conflicting hypotheses derived from full or partial gene sequences and genomic organization in higher animals. Whole genome sequences have recently filled in some crucial gaps for the basal metazoan phyla Cnidaria and Porifera. Here we analyze the complete genome of Trichoplax adhaerens, representing the basal metazoan phylum Placozoa, for its set of ANTP class genes. The Trichoplax genome encodes representatives of Hox/ParaHox-like, NKL, and extended Hox genes. This repertoire possibly mirrors the condition of a hypothetical cnidarian-bilaterian ancestor. The evolution of the cnidarian and bilaterian ANTP gene repertoires can be deduced by a limited number of cis-duplications of NKL and “extended Hox” genes and the presence of a single ancestral “ProtoHox” gene