Mucosa-like differentiation of head and neck cancer cells is inducible and drives the epigenetic loss of cell malignancy.

Head and neck squamous cell carcinoma (HNSCC) is a highly malignant disease with high death rates that have remained substantially unaltered for decades. Therefore, new treatment approaches are urgently needed. Human papillomavirus-negative tumors harbor areas of terminally differentiated tissue that are characterized by cornification.

Multiobjective Optimization of Rotodynamic Blood Pumps: The Use Case of a Cavopulmonary Assist Device.

Comprehensive optimization of rotodynamic blood pumps (RBPs) requires the consideration of three partially conflicting objectives: size, hemocompatibility, and motor efficiency. Optimizing these individual objectives independently, the potential of multiobjective optimizations often remains untapped. This study aimed at the multiobjective optimization of an RBP for cavopulmonary support accounting for all three objectives simultaneously.

Characterization of Bacterial Transcriptional Regulatory Networks in through Genome-Wide In Vitro Run-Off Transcription/RNA-seq (ROSE).

The global characterization of transcriptional regulatory networks almost exclusively uses in vivo conditions, thereby providing a snapshot on multiple regulatory interactions at the same time. To complement these approaches, we developed and applied a method for characterizing bacterial promoters genome-wide by in vitro transcription coupled to transcriptome sequencing specific for native 5'-ends of transcripts. This method, called ROSE (run-off transcription/RNA-sequencing), only requires chromosomal DNA, ribonucleotides, RNA polymerase (RNAP) core enzyme, and a specific sigma factor, recognizing the corresponding promoters, which have to be analyzed.

Primary head and neck cancer cell cultures are susceptible to proliferation of Epstein-Barr virus infected lymphocytes.

Background: New concepts for a more effective anti-cancer therapy are urgently needed. Experimental flaws represent a major counter player of this development and lead to inaccurate and unreproducible data as well as unsuccessful translation of research approaches into clinics. In a previous study we have created epithelial cell cultures from head and neck squamous cell carcinoma (HNSCC) tissue.

Evolutionary Transition in the Regulation of Vertebrate Pronephros Development: A New Role for Retinoic Acid.

The anterior-posterior (AP) axis in chordates is regulated by a conserved set of genes and signaling pathways, including genes and retinoic acid (RA), which play well-characterized roles in the organization of the chordate body plan. The intermediate mesoderm (IM), which gives rise to all vertebrate kidneys, is an example of a tissue that differentiates sequentially along this axis. Yet, the conservation of the spatiotemporal regulation of the IM across vertebrates remains poorly understood.

Purification of a GalNAc-cluster-conjugated oligonucleotide by reversed-phase twin-column continuous chromatography.

Multicolumn Countercurrent Solvent Gradient Purification (MCSGP) is a continuous chromatography technique used to maximize purification yields compared to traditional batch purification methods. Here we apply MCSGP for the reversed phase purification of a N-acetylgalactosamine (GalNAc)-cluster-conjugated DNA-LNA gapmer oligonucleotide therapeutic using a twin-column chromatography system. Based on a batch process as a starting point, MCSGP was designed, optimized and compared with the batch process regarding process performance and scale-up requirements.

Classification of three corynebacterial strains isolated from a small paddock in North Rhine-Westphalia: proposal of sp. nov., sp. nov. and sp. nov.

Three novel corynebacterial species were isolated from soil sampled at a paddock in Vilsendorf, North Rhine-Westphalia, Germany. The strains were coccoid or irregular rod-shaped, catalase-positive and pale white to yellow-orange in colour. By whole genome sequencing and comparison of the 16S rRNA genes as well as the whole genome structure, it was shown that all three strains represent novel species of the family , order , class .

Evaluation of treatment effects in patients with endometrial cancer and POLE mutations: An individual patient data meta-analysis.

Background: Endometrial cancers (ECs) with somatic mutations in DNA polymerase epsilon (POLE) are characterized by unfavorable pathological features, which prompt adjuvant treatment. Paradoxically, women with POLE-mutated EC have outstanding clinical outcomes, and this raises concerns of overtreatment. The authors investigated whether favorable outcomes were independent of treatment.

Molecular Subtype Not Immune Response Drives Outcomes in Endometrial Carcinoma.

Purpose: Tumors with high mutation load are thought to engender stronger immune responses, which in turn promote prolonged patient survival. To investigate this, we assessed tumor-infiltrating lymphocytes (TILs) and immunosuppressive factors across the 4 molecular subtypes of endometrial cancer, which have characteristic mutation rates ranging from low to ultra-high.

Experimental Design: A total of 460 endometrial cancers were stratified by ProMisE (Proactive Molecular Risk Classifier in Endometrial cancer) into 4 molecular subtypes: mismatch repair-deficient (MMRd), mutant (POLE), p53 abnormal (p53abn), and p53 wild-type (p53wt).

Effect of N- and C-terminal functional groups on the stability of collagen triple helices.

The effect of charged versus neutral N- and C-termini on the stability of the collagen triple helix was examined. Thermal denaturation studies at different pH with collagen model peptides showed that an ammonium group at the N-terminus destabilizes the triple helix more than a carboxylate at the C-terminus. A neutral carboxylic acid stabilizes the triple helix more than an amido moiety at the C-terminus.

NAOMInova: Interactive Geometric Analysis of Noncovalent Interactions in Macromolecular Structures.

Noncovalent interactions play an important role in macromolecular complexes. The assessment of molecular interactions is often based on knowledge derived from statistics on structural data. Within the last years, the available data in the Brookhaven Protein Data Bank has increased dramatically, quantitatively as well as qualitatively.

Comparison of boron-assisted oxime and hydrazone formations leads to the discovery of a fluorogenic variant.

We use kinetic data, photophysical properties, and mechanistic analyses to compare recently developed high-rate constant oxime and hydrazone formations. We show that when Schiff base formation between aldehydes and arylhydrazines is carried out with an appropriately positioned boron atom, then aromatic B-N heterocycles form irreversibly. These consist of an extended aromatic structure amenable to the tailoring of specific properties such as reaction rate and fluorescence.

Boronic acids facilitate rapid oxime condensations at neutral pH.

We report here the discovery and development of boron-assisted oxime formation as a powerful connective reaction for chemical biology. Oximes proximal to boronic acids form in neutral aqueous buffer with rate constants of more than 10 M s, the largest to date for any oxime condensation. Boron's dynamic coordination chemistry confers an adaptability that seems to aid a number of elementary steps in the oxime condensation.

Dialdehydes lead to exceptionally fast bioconjugations at neutral pH by virtue of a cyclic intermediate.

One of the open challenges in chemical biology is to identify reactions that proceed with large rate constants at neutral pH values. As shown here, dialdehydes react with O-alkylhydroxylamines at rates of 500 M(-1) s(-1) at neutral pH values in the absence of catalysts. The key to these conjugations is an unusually stable cyclic intermediate, which ultimately undergoes dehydration to yield an oxime.

Barriers to orthopaedic practice--why surgeons do not put into practice what they have learned in educational events.

Background: All orthopaedic and trauma surgeons attend educational events throughout their careers. Many surgeons find that when they return to practice they are unable to put into effect those things that they have learned.

Methods: This study focussed on 708 surgeons from 2 different cultural backgrounds (developed and developing world) who attended 7 separate trauma Educational events.

A cognitive perspective on technology enhanced learning in medical training: great opportunities, pitfalls and challenges.

As new technology becomes available and is used for educational purposes, educators often take existing training and simply transcribe it into the new technological medium. However, when technology drives e-learning rather than the learner and the learning, and when it uses designs and approaches that were not originally built for e-learning, then often technology does not enhance the learning (it may even be detrimental to it). The success of e-learning depends on it being 'brain friendly', on engaging the learners from an understanding of how the cognitive system works.

Universal newborn hearing screening: a 27-month experience in the French region of Champagne-Ardenne.

Objectives: This article reports the creation of a Universal Newborn Hearing Screening (UNHS) program in a French region, Champagne-Ardenne, and the results of its first 27 months.

Materials And Methods: We introduced a UNHS program in all the Champagne-Ardenne maternities in order to screen all newborns in the region. We used a two-step strategy.