Effective stiffening of DNA due to nematic ordering causes DNA molecules packed in phage capsids to preferentially form torus knots

Observation that DNA molecules in bacteriophage capsids preferentially form torus type of knots provided a sensitive gauge to evaluate various models of DNA arrangement in phage heads. Only models resulting in a preponderance of torus knots could be considered as close to reality. Recent studies revealed that experimentally observed enrichment of torus knots can be qualitatively reproduced in numerical simulations that include a potential inducing nematic arrangement of tightly packed DNA molecules within phage capsids. Here, we investigate what aspects of the nematic arrangement are crucial for inducing formation of torus knots. Our results indicate that the effective stiffening of DNA by the nematic arrangement not only promotes knotting in general but is also the decisive factor in promoting formation of DNA torus knots in phage capsid

Monitoring the hydrothermal growth of cobalt spinel water oxidation catalysts - from preparative history to catalytic activity

The hydrothermal growth of cobalt oxide spinel (Co₃O₄) nanocrystals from cobalt acetate precursors was monitored with in situ powder X‐ray diffraction (PXRD) in combination with ex situ electron microscopy and vibrational spectroscopy. Kinetic data from in situ PXRD monitoring were analyzed using Sharp‐Hancock and Gualtieri approaches, which both clearly indicate a change of the growth mechanism for reaction temperatures above 185°C. This mechanistic transition goes hand in hand with morphology changes that notably influence the photocatalytic oxygen evolution activity. Complementary quenching investigations of conventional hydrothermal Co₃O₄ growth demonstrate that these insights derived from in situ PXRD data provide valuable synthetic guidelines for water oxidation catalyst production. Furthermore, the ex situ analyses of hydrothermal quenching experiments were essential to assess the influence of amorphous cobalt‐containing phases arising from the acetate precursor on the catalytic activity. Thereby, we illustrate how the efficient combination of a single in situ technique with ex situ analyses paves the way to optimize parameter‐sensitive hydrothermal production processes of key energy materials

Implementation and performance analysis of bridging Monte Carlo moves for off-lattice single chain polymers in globular states

Bridging algorithms are global Monte Carlo moves which allow for an efficient sampling of single polymer chains. In this manuscript we discuss the adaptation of three bridging algorithms from lattice to continuum models, and give details on the corrections to the acceptance rules which are required to fulfill detailed balance. For the first time we are able to compare the efficiency of the moves by analyzing the occurrence of knots in globular states. For a flexible homopolymer chain of length N=1000, independent configurations can be generated up to two orders of magnitude faster than with slithering snake moves.Comment: 12 pages, 5 figures, preprint submitted to computer physics communication

Response to sunitinib in combination with proton beam radiation in a patient with chondrosarcoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Chondrosarcoma is well-known to be primarily resistant to conventional radiation and chemotherapy.</p> <p>Case presentation</p> <p>We present the case of a 32-year-old Caucasian man with clear cell chondrosarcoma who presented with symptomatic recurrence in his pelvis and metastases to his skull and lungs. Our patient underwent systemic therapy with sunitinib and then consolidation with proton beam radiation to his symptomatic site. He achieved complete symptomatic relief with a significantly improved performance status and had an almost complete and durable metabolic response on fluorine-18-fluorodeoxyglucose positron emission tomography.</p> <p>Conclusions</p> <p>Our findings have important clinical implications and suggest novel clinical trials for this difficult to treat disease.</p

Impact of endorectal filling on interobserver variability of MRI based rectal primary tumor delineation

Background: Online adaptive MR-guided radiotherapy allows for the reduction of safety margins in dose escalated treatment of rectal tumors. With the use of smaller margins, precise tumor delineation becomes more critical. In the present study we investigated the impact of rectal ultrasound gel filling on interobserver variability in delineation of primary rectal tumor volumes. Methods: Six patients with locally advanced rectal cancer were scanned on a 1.5 T MRI-Linac without (MRI_e) and with application of 100 cc of ultrasound gel transanally (MRI_f). Eight international radiation oncologists expert in the treatment of gastrointestinal cancers delineated the gross tumor volume (GTV) on both MRI scans. MRI_f scans were provided to the participating centers after MRI_e scans had been returned. Interobserver variability was analyzed by either comparing the observers’ delineations with a reference delineation (approach 1) and by building all possible pairs between observers (approach 2). Dice Similarity Index (DICE) and 95 % Hausdorff-Distance (95 %HD) were calculated. Results: Rectal ultrasound gel filling was well tolerated by all patients. Overall, interobserver agreement was superior in MRI_f scans based on median DICE (0.81 vs 0.74, p < 0.005 for approach 1 and 0.76 vs 0.64, p < 0.0001 for approach 2) and 95 %HD (6.9 mm vs 4.2 mm for approach 1, p = 0.04 and 8.9 mm vs 6.1 mm, p = 0.04 for approach 2). Delineated median tumor volumes and inter-quartile ranges were 26.99 cc [18.01–50.34 cc] in MRI_e and 44.20 [19.72–61.59 cc] in MRI_f scans respectively, p = 0.012. Conclusions: Although limited by the small number of patients, in this study the application of rectal ultrasound gel resulted in higher interobserver agreement in rectal GTV delineation. The endorectal gel filling might be a useful tool for future dose escalation strategies

Targeted p120-Catenin Ablation Disrupts Dental Enamel Development

Dental enamel development occurs in stages. The ameloblast cell layer is adjacent to, and is responsible for, enamel formation. When rodent pre-ameloblasts become tall columnar secretory-stage ameloblasts, they secrete enamel matrix proteins, and the ameloblasts start moving in rows that slide by one another. This movement is necessary to form the characteristic decussating enamel prism pattern. Thus, a dynamic system of intercellular interactions is required for proper enamel development. Cadherins are components of the adherens junction (AJ), and they span the cell membrane to mediate attachment to adjacent cells. p120 stabilizes cadherins by preventing their internalization and degradation. So, we asked if p120-mediated cadherin stability is important for dental enamel formation. Targeted p120 ablation in the mouse enamel organ had a striking effect. Secretory stage ameloblasts detached from surrounding tissues, lost polarity, flattened, and ameloblast E- and N-cadherin expression became undetectable by immunostaining. The enamel itself was poorly mineralized and appeared to be composed of a thin layer of merged spheres that abraded from the tooth. Significantly, p120 mosaic mouse teeth were capable of forming normal enamel demonstrating that the enamel defects were not a secondary effect of p120 ablation. Surprisingly, blood-filled sinusoids developed in random locations around the developing teeth. This has not been observed in other p120-ablated tissues and may be due to altered p120-mediated cell signaling. These data reveal a critical role for p120 in tooth and dental enamel development and are consistent with p120 directing the attachment and detachment of the secretory stage ameloblasts as they move in rows

HEATR2 Plays a Conserved Role in Assembly of the Ciliary Motile Apparatus

Cilia are highly conserved microtubule-based structures that perform a variety of sensory and motility functions during development and adult homeostasis. In humans, defects specifically affecting motile cilia lead to chronic airway infections, infertility and laterality defects in the genetically heterogeneous disorder Primary Ciliary Dyskinesia (PCD). Using the comparatively simple Drosophila system, in which mechanosensory neurons possess modified motile cilia, we employed a recently elucidated cilia transcriptional RFX-FOX code to identify novel PCD candidate genes. Here, we report characterization of CG31320/HEATR2, which plays a conserved critical role in forming the axonemal dynein arms required for ciliary motility in both flies and humans. Inner and outer arm dyneins are absent from axonemes of CG31320 mutant flies and from PCD individuals with a novel splice-acceptor HEATR2 mutation. Functional conservation of closely arranged RFX-FOX binding sites upstream of HEATR2 orthologues may drive higher cytoplasmic expression of HEATR2 during early motile ciliogenesis. Immunoprecipitation reveals HEATR2 interacts with DNAI2, but not HSP70 or HSP90, distinguishing it from the client/chaperone functions described for other cytoplasmic proteins required for dynein arm assembly such as DNAAF1-4. These data implicate CG31320/HEATR2 in a growing intracellular pre-assembly and transport network that is necessary to deliver functional dynein machinery to the ciliary compartment for integration into the motile axoneme