Deformability and collision-induced reorientation enhance cell topotaxis in dense microenvironments.

In vivo, cells navigate through complex environments filled with obstacles such as other cells and the extracellular matrix. Recently, the term "topotaxis" has been introduced for navigation along topographic cues such as obstacle density gradients. Experimental and mathematical efforts have analyzed topotaxis of single cells in pillared grids with pillar density gradients.

Spatial and Temporal Modulation of Cell Instructive Cues in a Filamentous Supramolecular Biomaterial.

Supramolecular materials provide unique opportunities to mimic both the structure and mechanics of the biopolymer networks that compose the extracellular matrix. However, strategies to modify their filamentous structures in space and time in 3D cell culture to study cell behavior as encountered in development and disease are lacking. We herein disclose a multicomponent squaramide-based supramolecular material whose mechanics and bioactivity can be controlled by light through co-assembly of a 1,2-dithiolane (DT) monomer that forms disulfide cross-links.

Impact of neurite alignment on organelle motion.

Intracellular transport is pivotal for cell growth and survival. Malfunctions in this process have been associated with devastating neurodegenerative diseases, highlighting the need for a deeper understanding of the mechanisms involved. Here, we use an experimental methodology that leads neurites of differentiated PC12 cells into either one of two configurations: a one-dimensional configuration, where the neurites align along lines, or a two-dimensional configuration, where the neurites adopt a random orientation and shape on a flat substrate.

Squaramide-Based Supramolecular Materials Drive HepG2 Spheroid Differentiation.

A major challenge in the use of HepG2 cell culture models for drug toxicity screening is their lack of maturity in 2D culture. 3D culture in Matrigel promotes the formation of spheroids that express liver-relevant markers, yet they still lack various primary hepatocyte functions. Therefore, alternative matrices where chemical composition and materials properties are controlled to steer maturation of HepG2 spheroids remain desired.

A Two-Armed Probe for In-Cell DEER Measurements on Proteins*.

The application of double electron-electron resonance (DEER) with site-directed spin labeling (SDSL) to measure distances in proteins and protein complexes in living cells puts rigorous restraints on the spin-label. The linkage and paramagnetic centers need to resist the reducing conditions of the cell. Rigid attachment of the probe to the protein improves precision of the measured distances.

Photopatternable, Branched Polymer Hydrogels Based on Linear Macromonomers for 3D Cell Culture Applications.

Photochemical ligation strategies in hydrogel materials are crucial to model spatiotemporal phenomena that occur in the natural extracellular matrix. We here describe the use of cyclic 1,2-dithiolanes to cross-link with norbornene on linear poly(ethylene glycol) polymers through UV irradiation in a rapid and byproduct-free manner, resulting in branched macromolecular architectures and hydrogel materials from low-viscosity precursor solutions. Oscillatory rheology and NMR data indicate the one-pot formation of thioether and disulfide cross-links.

Topotaxis of active Brownian particles.

Recent experimental studies have demonstrated that cellular motion can be directed by topographical gradients, such as those resulting from spatial variations in the features of a micropatterned substrate. This phenomenon, known as topotaxis, has been extensively studied for topographical gradients at the subcellular scale, but can also occur in the presence of a spatially varying density of cell-sized features. Such a large-scale topotaxis has recently been observed in highly motile cells that persistently crawl within an array of obstacles with smoothly varying lattice spacing.

Stress-induced formation of cell wall-deficient cells in filamentous actinomycetes.

The cell wall is a shape-defining structure that envelopes almost all bacteria and protects them from environmental stresses. Bacteria can be forced to grow without a cell wall under certain conditions that interfere with cell wall synthesis, but the relevance of these wall-less cells (known as L-forms) is unclear. Here, we show that several species of filamentous actinomycetes have a natural ability to generate wall-deficient cells in response to hyperosmotic stress, which we call S-cells.

Grafting from a Hybrid DNA-Covalent Polymer by the Hybridization Chain Reaction.

Nucleic acid-polymer conjugates are an attractive class of materials endowed with tunable and responsive character. Herein, we exploit the dynamic character of nucleic acids in the preparation of hybrid DNA-covalent polymers with extendable grafts by the hybridization chain reaction. Addition of DNA hairpins to an initiator DNA-dextran graft copolymer resulted in the growth of the DNA grafts as evidenced by various characterization techniques over several length scales.

Performing SELEX experiments in silico.

Due to the sequence-dependent nature of the elasticity of DNA, many protein-DNA complexes and other systems in which DNA molecules must be deformed have preferences for the type of DNA sequence they interact with. SELEX (Systematic Evolution of Ligands by EXponential enrichment) experiments and similar sequence selection experiments have been used extensively to examine the (indirect readout) sequence preferences of, e.g.

Site-specific association between distal aortic pulse wave velocity and peripheral arterial stenosis severity: a prospective cardiovascular magnetic resonance study.

Background: Vascular disease expression in one location may not be representative for disease severity in other vascular territories, however, strong correlation between disease expression and severity within the same vascular segment may be expected. Therefore, we hypothesized that aortic stiffening is more strongly associated with disease expression in a vascular territory directly linked to that aortic segment rather than in a more remote segment. We prospectively compared the association between aortic wall stiffness, expressed by pulse wave velocity (PWV), sampled in the distal aorta, with the severity of peripheral arterial occlusive disease (PAOD) as compared to atherosclerotic markers sampled in remote vascular territories such as PWV in the proximal aorta and the normalized wall index (NWI), representing the vessel wall thickness, of the left common carotid artery.

Cardiovascular effects after low-dose exposure and radiotherapy: what research is needed?

The authors of this report met at the Head Quarter of the International Atomic Energy Agency (IAEA) in Vienna, Austria, on 2-4 July 2012, for intensive discussions of an abundance of original publications on new epidemiological studies on cardiovascular effects after low-dose exposure and radiotherapy and radiobiological experiments as well as several comprehensive reviews that were published since the previous meeting by experts sponsored by the IAEA in June 2006. The data necessitated a re-evaluation of the situation with special emphasis on the consequences current experimental and clinical data may have for clinical oncology/radiotherapy and radiobiological research. The authors jointly arrived at the conclusions and recommendations presented here.

An international survey of tissue banking: a preliminary report.

International Atomic Energy Agency is currently carrying out a survey on the tissue banking activities from the tissue banking organisations worldwide. The purpose of the survey is to establish regional and global overview of the current tissue banking activities and practices in order to assist the International Atomic Energy Agency to provide further guidance about the use of radiation technology to sterilise tissues as well as to promote better collaboration between the regional tissue banking associations. The survey is an on-going exercise and the preliminary data is presented here.

IAEA activities related to radiation biology and health effects of radiation.

The IAEA is involved in capacity building with regard to the radiobiological sciences in its member states through its technical cooperation programme. Research projects/programmes are normally carried out within the framework of coordinated research projects (CRPs). Under this programme, two CRPs have been approved which are relevant to nuclear/radiation accidents: (1) stem cell therapeutics to modify radiation-induced damage to normal tissue, and (2) strengthening biological dosimetry in IAEA member states.

International Conference on Advances in Radiation Oncology (ICARO): outcomes of an IAEA meeting.

The IAEA held the International Conference on Advances in Radiation Oncology (ICARO) in Vienna on 27-29 April 2009. The Conference dealt with the issues and requirements posed by the transition from conventional radiotherapy to advanced modern technologies, including staffing, training, treatment planning and delivery, quality assurance (QA) and the optimal use of available resources. The current role of advanced technologies (defined as 3-dimensional and/or image guided treatment with photons or particles) in current clinical practice and future scenarios were discussed.

The anatomy of the thoracic spinal canal investigated with magnetic resonance imaging (MRI).

Background And Objectives: Anesthesiologists are reluctant to consider higher levels for spinal anesthesia, largely due to direct threats to the spinal cord. The goal of this study is to investigate, with magnetic resonance imaging (MRI), the distances between the relevant structures of the spinal canal (spinal cord, thecal tissue, etc.) to determine modal anatomical positions for neuraxial anesthesia.

Residual late radiation damage in mouse stromal tissue assessed by the tumor bed effect.

Irradiation of murine subcutaneous stroma before implantation of tumor cells leads to retarded tumor growth. This effect is called Tumor Bed Effect (TBE) and can be used to assess the sensitivity of stromal tissue to radiation. We tested the ability of stromal tissue to recover from X-ray-induced damage as a function of the time interval between X-irradiation and implantation of tumor cells over a period of 195 days.

Effects of hyperthermia on the central nervous system: what was learnt from animal studies?

Animal studies show that nervous tissue is sensitive to heat. Although inter-species variations may play a role, the data indicate that the maximum heat dose without obvious complications after localized hyperthermia in regions of the central nervous system (CNS) lies in the range of 40-60 min at 42-42.5 degrees C or 10-30 min at 43 degrees C.

X-ray imaging and the skin: radiation biology, patient dosimetry and observed effects.

A wide variety of radiation-induced deterministic skin effects have been observed after X-ray guided interventions ranging from mild effects, such as transient erythema or temporary epilation, to severe effects, such as desquamation and necrosis. Radiation biologists have identified, in addition to absorbed dose to the skin, other factors that strongly influence the type and severity of a skin reaction, including exposure-related factors (dose rate, fractionation, the size of the exposed area and its site), biological factors (age, oxygen status, capillary density, hormonal status and genetic factors) and ethnic differences. A peak entrance skin dose of 2 Gy is an arbitrary, but pragmatic, threshold for radiation-induced skin effects after X-ray guided interventions.

Influence of mast cells on structural and functional manifestations of radiation-induced heart disease.

Radiation-induced heart disease (RIHD), characterized by accelerated atherosclerosis and adverse tissue remodeling, is a serious sequelae after radiotherapy of thoracic and chest wall tumors. Adverse cardiac remodeling in RIHD and other cardiac disorders is frequently accompanied by mast cell hyperplasia, suggesting that mast cells may affect the development of cardiac fibrosis. This study used a mast cell-deficient rat model to define the role of mast cells in RIHD.

Microarray analysis of gene expression profiles of cardiac myocytes and fibroblasts after mechanical stress, ionising or ultraviolet radiation.

Background: During excessive pressure or volume overload, cardiac cells are subjected to increased mechanical stress (MS). We set out to investigate how the stress response of cardiac cells to MS can be compared to genotoxic stresses induced by DNA damaging agents. We chose for this purpose to use ionising radiation (IR), which during mediastinal radiotherapy can result in cardiac tissue remodelling and diminished heart function, and ultraviolet radiation (UV) that in contrast to IR induces high concentrations of DNA replication- and transcription-blocking lesions.

Histopathology of ventricles, coronary arteries and mast cell accumulation in transverse and longitudinal sections of the rat heart after irradiation.

The aim of the study was to compare cross sections with longitudinal sections in histopathological examination of the rat heart after irradiation, to find the most optimal method for the detection of cardiac radiation injuries. For this purpose, rats were irradiated locally on the heart with a single dose of 0 or 20 Gy. At different time points after irradiation, hearts were perfused and cut into longitudinal or cross sections.

Effects of hyperthermia on the peripheral nervous system: a review.

The present paper overviews the current knowledge about effects of hyperthermia at temperatures used in clinical oncology on the peripheral nervous system. From the experimental studies it may be concluded that the heat sensitivity of the nerve is determined by the sensitivity of the nerve vasculature. These studies show that in order to avoid induction of severe neuropathy, application of heat to the peripheral nerves should not be in excess of doses of 30 min at 44 degrees C or equivalent.