Tracking the Molecular Fingerprint of Head and Neck Cancer for Recurrence Detection in Liquid Biopsies

The 5-year relative survival for patients with head and neck cancer, the seventh most common form of cancer worldwide, was reported as 67% in developed countries in the second decade of the new millennium. Although surgery, radiotherapy, chemotherapy, or combined treatment often elicits an initial satisfactory response, relapses are frequently observed within two years. Current surveillance methods, including clinical exams and imaging evaluations, have not unambiguously demonstrated a survival benefit, most probably due to a lack of sensitivity in detecting very early recurrence. Recently, liquid biopsy monitoring of the molecular fingerprint of head and neck squamous cell carcinoma has been proposed and investigated as a strategy for longitudinal patient care. These innovative methods offer rapid, safe, and highly informative genetic analysis that can identify small tumors not yet visible by advanced imaging techniques, thus potentially shortening the time to treatment and improving survival outcomes. In this review, we provide insights into the available evidence that the molecular tumor fingerprint can be used in the surveillance of head and neck squamous cell carcinoma. Challenges to overcome, prior to clinical implementation, are also discussed.     

Shhedding New Light on the Role of Hedgehog Signaling in Corneal Wound Healing

The cornea, an anterior ocular tissue that notably serves to protect the eye from external insults and refract light, requires constant epithelium renewal and efficient healing following injury to maintain ocular homeostasis. Although several key cell populations and molecular pathways implicated in corneal wound healing have already been thoroughly investigated, insufficient/impaired or excessive corneal wound healing remains a major clinical issue in ophthalmology, and new avenues of research are still needed to further improve corneal wound healing. Because of its implication in numerous cellular/tissular homeostatic processes and oxidative stress, there is growing evidence of the role of Hedgehog signaling pathway in physiological and pathological corneal wound healing. Reviewing current scientific evidence, Hedgehog signaling and its effectors participate in corneal wound healing mainly at the level of the corneal and limbal epithelium, where Sonic Hedgehog-mediated signaling promotes limbal stem cell proliferation and corneal epithelial cell proliferation and migration following corneal injury. Hedgehog signaling could also participate in corneal epithelial barrier homeostasis and in pathological corneal healing such as corneal injury-related neovascularization. By gaining a better understanding of the role of this double-edged sword in physiological and pathological corneal wound healing, fascinating new research avenues and therapeutic strategies will undoubtedly emerge.     

A Single Bout of Ultra-Endurance Exercise Reveals Early Signs of Muscle Aging in Master Athletes

Middle-aged and master endurance athletes exhibit similar physical performance and long-term muscle adaptation to aerobic exercise. Nevertheless, we hypothesized that the short-term plasticity of the skeletal muscle might be distinctly altered for master athletes when they are challenged by a single bout of prolonged moderate-intensity exercise. Six middle-aged (37Y) and five older (50Y) master highly-trained athletes performed a 24-h treadmill run (24TR). Vastus lateralis muscle biopsies were collected before and after the run and assessed for proteomics, fiber morphometry, intramyocellular lipid droplets (LD), mitochondrial oxidative activity, extracellular matrix (ECM), and micro-vascularisation. Before 24TR, muscle fiber type morphometry, intramyocellular LD, oxidative activity, ECM and micro-vascularisation were similar between master and middle-aged runners. For 37Y runners, 24TR was associated with ECM thickening, increased capillary-to-fiber interface, and an 89% depletion of LD in type-I fibers. In contrast, for 50Y runners, 24TR did not alter ECM and capillarization and poorly depleted LDs. Moreover, an impaired succinate dehydrogenase activity and functional class scoring of proteomes suggested reduced oxidative phosphorylation post-24TR exclusively in 50Y muscle. Collectively, our data support that middle-aged and master endurance athletes exhibit distinct transient plasticity in response to a single bout of ultra-endurance exercise, which may constitute early signs of muscle aging for master athletes.     

The P2Y2 Receptor C-Terminal Tail Modulates but Is Dispensable for β-Arrestin Recruitment

The P2Y₂ receptor (P2Y₂R) is a G protein-coupled receptor that is activated by extracellular ATP and UTP, to a similar extent. This allows it to play roles in the cell’s response to the (increased) release of these nucleotides, e.g., in response to stress situations, including mechanical stress and oxygen deprivation. However, despite its involvement in important (patho)physiological processes, the intracellular signaling induced by the P2Y₂R remains incompletely described. Therefore, this study implemented a NanoBiT^® functional complementation assay to shed more light on the recruitment of β-arrestins (βarr1 and βarr2) upon receptor activation. More specifically, upon determination of the optimal configuration in this assay system, the effect of different (receptor) residues/regions on βarr recruitment to the receptor in response to ATP or UTP was estimated. To this end, the linker was shortened, the C-terminal tail was truncated, and phosphorylatable residues in the third intracellular loop of the receptor were mutated, in either singly or multiply adapted constructs. The results showed that none of the introduced adaptations entirely abolished the recruitment of either βarr, although EC₅₀ values differed and time-luminescence profiles appeared to be qualitatively altered. The results hint at the C-terminal tail modulating the interaction with βarr, while not being indispensable.     

Modeling bread baking with focus on overall deformation and local porosity evolution

A two dimensional model of bread baking was developed including, for the first time, the dependence of dough viscosity on both temperature and moisture content, the carbon dioxide dissolved from liquid water together with gas generation from yeast at the beginning of baking and the shrinkage due to dough drying. Particular attention was paid to experimental validation of both overall and local variables such as local temperature, overall mass loss, and local moisture content, overall CO₂ released into the oven, and overall deformation and local expansion or shrinkage. Sensitivity studies on generation of carbon dioxide, gravity, and shrinkage are presented to discuss their influences on bread geometry, porosity (reflecting the alveolar structure) and gas pressure. © 2016 American Institute of Chemical Engineers AIChE J, 62: 3847–3863, 2016     

Catalytic olefin polymerisation at short times: Studies using specially adapted reactors

Despite the fact that the very early stages (several tens of seconds) of catalysed olefin polymerisation processes appear negligibly short with respect to the residence time of most industrial reactors, they are critical in terms of catalyst activation, obtaining good particle morphology, and avoiding irreparable problems caused by particle overheating. The different types of reactors that have been used over the course of the past few years are discussed in this feature article. It is shown that despite the difficulties encountered in finding the perfect experimental tool for this purpose, different configurations of stopped flow reactors can be used successfully to explore different aspects of what happens to the catalyst (supported and molecular) during these critical moments of polymerisation. © 2012 Canadian Society for Chemical Engineering     

Dielectric features of two grades of bi‐oriented isotactic polypropylene

The dielectric properties of two grades of bi‐oriented isotactic polypropylene were studied with a variety of techniques: breakdown field measurements, dielectric spectroscopy, thermally stimulated depolarization currents (Is), and direct‐current (dc) conduction I values. Standard polypropylene (STPP) and high‐crystallinity polypropylene (HCPP) films were investigated. Measurements were carried out over a wide temperature range (?150°C/+125°C). The breakdown fields in both materials showed a very small difference. On the other hand, the dielectric losses and dc conduction I values were significantly lower in HCPP. Both materials showed a decrease in the dielectric loss versus temperature in the range 20–90°C; this is favorable for application in alternating‐current power capacitors. The analysis of the dc I value allowed us to find evidence of two main conduction mechanisms: (1) below 80°C in both materials, a hopping mechanism due to the motion of electrons occurred in the amorphous phase, and (2) above 80°C, ionic conduction occurred in HCPP, and hopping conduction occurred in STPP. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42224.     

Dietary intakes and food sources of fatty acids for Belgian women, focused on n-6 and n-3 polyunsaturated fatty acids

The intake of fat, saturated and monounsaturated FA (SFA and MUFA), and omega-6 and omega-3 PUFA has been estimated in 641 Belgian women (age 18-39 y). Their food intake was recorded using a 2-d food diary. The PUFA included were linoleic (LA), alpha-linolenic (LNA), arachidonic (AA), eicosapentaeonoic (EPA), docosapentaenoic (DPA) and docosahexaenoic (DHA) acids. The mean total fat intake corresponded to 34.3% of total energy intake (E). The mean intake of the FA groups corresponded to 13.7%, 13.1%, and 6.0% of E, for SFA, MUFA, and PUFA, respectively. The mean intake of LA was 5.3% of E and of LNA was 0.6% of E, with a mean LA/LNA ratio of 8.7. The mean intake of AA was 0.03% of E. The mean intake of EPA, DPA, and DHA was 0.4%, 0.01%, and 0.06% of E, respectively. According to the Belgian recommendations, the total fat and SFA intake was too high for about three-quarters of the population. The mean LA and overall n-6 PUFA intake corresponded with the recommendation, with part of the population exceeding the upper level. Conversely, the population showed a large deficit for LNA and n-3 PUFA. The major food source for LA and LNA was fats and oils, followed by cereal products. The main sources of long-chain PUFA were fish and seafood, and meat, poultry, and eggs. From a public health perspective, it seems desirable to tackle the problem of low n-3 PUFA intake.     

Binding Mode and Structure–Activity Relationships around Direct Inhibitors of the Nrf2–Keap1 Complex

An X‐ray crystal structure of Kelch‐like ECH‐associated protein (Keap1) co‐crystallised with (1S,2R)‐2‐[(1S)‐1‐[(1,3‐dioxo‐2,3‐dihydro‐1H‐isoindol‐2‐yl)methyl]‐1,2,3,4‐tetrahydroisoquinolin‐2‐carbonyl]cyclohexane‐1‐carboxylic acid (compound (S,R,S)‐ 1 a ) was obtained. This X‐ray crystal structure provides breakthrough experimental evidence for the true binding mode of the hit compound (S,R,S)‐ 1 a , as the ligand orientation was found to differ from that of the initial docking model, which was available at the start of the project. Crystallographic elucidation of this binding mode helped to focus and drive the drug design process more effectively and efficiently.     

The busbar system for Wendelstein 7-X prepared for assembly and operational loads

Forschungszentrum Jülich has taken over the design, manufacturing and assembly of the superconducting busbar system for the stellarator Wendelstein 7-X. This includes the busbars itself, the support structure consisting of supports and clamps, and the joints for electrical and hydraulic connection of the busbars and coil terminals. Apart from providing the required electrical connection scheme, the busbar system has to be designed for relevant electrical and mechanical loads. Numerous interfaces and geometric boundary conditions define the confined space to accommodate the busbars and their support elements. This article describes how the individual challenges to engineering have been met in the course of the project. This includes design concepts and the method for iterative design of supports with respect to the individual load distribution caused by the supports itself.