Fractography of poly(: N -isopropylacrylamide) hydrogel networks crosslinked with mechanofluorophores using confocal laser scanning microscopy

Due to their soft and brittle nature, the mechanical characterization of polymer hydrogels is a difficult task employing traditional testing equipment. Here, we endowed poly(N-isopropyl acrylamide) (PNIPAAm) hydrogel networks with Diels-Alder adducts of π-extended anthracenes as mechanofluorophore crosslinkers. After swelling the networks with varying amounts of water and subjecting them to force, we visualized the subsequent fluorescence caused by covalent bond scission with confocal laser scanning microscopy (CLSM) and related the intensities to the macroscopic fracture mechanics and the elastic moduli recorded with traditional uniaxial compression. The sensitivity of the mechanofluorophores allowed the analysis of low levels of mechanical stress produced via a hand-induced needle-puncturing process and, thus, is an alternative to conventional force application methods. The detection and precise localization of covalent bond scission via CLSM helps elucidating the interrelationship between molecular structure and the macroscopic properties of chemically crosslinked polymeric hydrogels. We believe that this micro-scale mechanophore-assisted fractography can establish a new paradigm for the mechanical analysis of soft matter in fields covering traditional polymer and life sciences. © 2019 The Royal Society of Chemistry

Protective Efficacy of Individual CD8+ T Cell Specificities in Chronic Viral Infection.

Specific CD8(+) T cells (CTLs) play an important role in resolving protracted infection with hepatitis B and C virus in humans and lymphocytic choriomeningitis virus (LCMV) in mice. The contribution of individual CTL specificities to chronic virus control, as well as epitope-specific patterns in timing and persistence of antiviral selection pressure, remain, however, incompletely defined. To monitor and characterize the antiviral efficacy of individual CTL specificities throughout the course of chronic infection, we coinoculated mice with a mixture of wild-type LCMV and genetically engineered CTL epitope-deficient mutant virus. A quantitative longitudinal assessment of viral competition revealed that mice continuously exerted CTL selection pressure on the persisting virus population. The timing of selection pressure characterized individual epitope specificities, and its magnitude varied considerably between individual mice. This longitudinal assessment of "antiviral efficacy" provides a novel parameter to characterize CTL responses in chronic viral infection. It demonstrates remarkable perseverance of all antiviral CTL specificities studied, thus raising hope for therapeutic vaccination in the treatment of persistent viral diseases

EUHASS: The European Haemophilia Safety Surveillance system

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Anoctamin 6 differs from VRAC and VSOAC but is involved in apoptosis and supports volume regulation in the presence of Ca²⁺

Anoctamin 6 (ANO6), also known as TMEM16F, has been shown to be a calcium-activated anion channel with delayed calcium activation. The cellular function of ANO6 is under debate, and different groups have come to different conclusions about ANO6’s physiological role. Although it is now quite well established that ANO6 is distinct from the volume-regulated anion channel, it is still unclear whether ANO6 or other anoctamins can be activated by cell swelling. In this study, we suggest that ANO1, ANO6, and ANO10 do not contribute to the volume-activated current in ANO-overexpressing HEK293 cells. Furthermore, knock-down of ANO6 in Ehrlich ascites tumor cells (EATC) and Ehrlich–Lettre ascites (ELA) did not decrease but instead significantly increased swelling-activated membrane currents. Knock-down of ANO6 in EATC did not reduce regulatory volume decrease (RVD) in the absence of extracellular calcium, whereas it significantly reduced RVD in the presence of calcium. Interestingly, we found that knock-down of ANO6 in ELA cells resulted in a decrease in cisplatin-induced caspase-3 activity, confirming earlier findings that ANO6 is involved in apoptosis. Finally, knock-down of ANO1 and ANO6 did not affect the volume-sensitive release of taurine in ELA cells. Thus, our data provide evidence that ANO6 cannot be activated directly by cell swelling unless Ca(2+) is present. We also conclude that ANO6 carries a current during RVD, provided extracellular calcium is present. Thus, swelling activation of ANO6 requires the presence of free calcium

Mapping cell-in-cell structures in oral squamous cell carcinoma

Cell-in-cell (CIC) structures contribute to tumor aggressiveness and poor prognosis in oral squamous cell carcinoma (OSCC). In vitro 3D models may contribute to the understanding of the underlying molecular mechanisms of these events. We employed a spheroid model to study the CIC structures in OSCC. Spheroids were obtained from OSCC (HSC3) and cancer-associated fibroblast (CAF) lines using the Nanoshuttle-PLTM bioprinting system (Greiner Bio-One). Spheroid form, size, and reproducibility were evaluated over time (EvosTM XL; ImageJ version 1.8). Slides were assembled, stained (hematoxylin and eosin), and scanned (Axio Imager Z2/VSLIDE) using the OlyVIA System (Olympus Life Science) and ImageJ software (NIH) for cellular morphology and tumor zone formation (hypoxia and/or proliferative zones) analysis. CIC occurrence, complexity, and morphology were assessed considering the spheroid regions. Well-formed spheroids were observed within 6 h of incubation, showing the morphological aspects of the tumor microenvironment, such as hypoxic (core) and proliferative zone (periphery) formation. CIC structures were found in both homotypic and heterotypic groups, predominantly in the proliferative zone of the mixed HSC3/CAF spheroids. “Complex cannibalism” events were also noted. These results showcase the potential of this model in further studies on CIC morphology, formation, and relationship with tumor prognosis

Investigating the Morphology and Mechanics of Biogenic Hierarchical Materials at and below Micrometer Scale

Investigating and understanding the intrinsic material properties of biogenic materials, which have evolved over millions of years into admirable structures with difficult to mimic hierarchical levels, holds the potential of replacing trial-and-error-based materials optimization in our efforts to make synthetic materials of similarly advanced complexity and properties. An excellent example is biogenic silica which is found in the exoskeleton of unicellular photosynthetic algae termed diatoms. Because of the complex micro-and nanostructures found in their exoskeleton, deter-mining the intrinsic mechanical properties of biosilica in diatoms has only partly been accomplished. Here, a general method is presented in which a combination of in situ deformation tests inside an SEM with a realistic 3D model of the frustule of diatom Craspedostauros sp. (C. sp.) obtained by electron tomography, alongside finite element method (FEM) simulations, enables quantification of the Young’s modulus (E = 2.3 ± 0.1 GPa) of this biogenic hierarchical silica. The workflow presented can be readily extended to other diatom species, biominerals, or even synthetic hierarchical materials.</p

A longitudinal investigation of repressive coping and ageing

This is an Accepted Manuscript of an article published by Taylor & Francis in Aging & Mental Health on October 2016, available online: http://www.tandfonline.com/doi/full/10.1080/13607863.2015.1060941.Two studies investigated the possibility that repressive coping is more prevalent in older adults and that this represents a developmental progression rather than a cohort effect. Study 1 examined repressive coping and mental health cross-sectionally in young and old adults. Study 2 examined whether there was a developmental progression of repressive coping prevalence rates in a longitudinal sample of older adults.Peer reviewedFinal Accepted Versio

Impact of a Prior Cancer Diagnosis on Quality of Care and Survival Following Acute Myocardial Infarction: Retrospective Population-Based Cohort Study in England

BACKGROUND: An increasing proportion of patients with cancer experience acute myocardial infarction (AMI). We investigated differences in quality of AMI care and survival between patients with and without previous cancer diagnoses. METHODS: A retrospective cohort study using Virtual Cardio-Oncology Research Initiative data. Patients aged 40+ years hospitalized in England with AMI between January 2010 and March 2018 were assessed, ascertaining previous cancers diagnosed within 15 years. Multivariable regression was used to assess effects of cancer diagnosis, time, stage, and site on international quality indicators and mortality. RESULTS: Of 512388 patients with AMI (mean age, 69.3 years; 33.5% women), 42187 (8.2%) had previous cancers. Patients with cancer had significantly lower use of ACE (angiotensin-converting enzyme) inhibitors/angiotensin receptor blockers (mean percentage point decrease [mppd], 2.6% [95% CI, 1.8–3.4]) and lower overall composite care (mppd, 1.2% [95% CI, 0.9–1.6]). Poorer quality indicator attainment was observed in patients with cancer diagnosed in the last year (mppd, 1.4% [95% CI, 1.8–1.0]), with later stage disease (mppd, 2.5% [95% CI, 3.3–1.4]), and with lung cancer (mppd, 2.2% [95% CI, 3.0–1.3]). Twelve-month all-cause survival was 90.5% in noncancer controls and 86.3% in adjusted counterfactual controls. Differences in post-AMI survival were driven by cancer-related deaths. Modeling improving quality indicator attainment to noncancer patient levels showed modest 12-month survival benefits (lung cancer, 0.6%; other cancers, 0.3%). CONCLUSIONS: Measures of quality of AMI care are poorer in patients with cancer, with lower use of secondary prevention medications. Findings are primarily driven by differences in age and comorbidities between cancer and noncancer populations and attenuated after adjustment. The largest impact was observed in recent cancer diagnoses (<1 year) and lung cancer. Further investigation will determine whether differences reflect appropriate management according to cancer prognosis or whether opportunities to improve AMI outcomes in patients with cancer exist

Photonic band gaps in materials with triply periodic surfaces and related tubular structures

We calculate the photonic band gap of triply periodic bicontinuous cubic structures and of tubular structures constructed from the skeletal graphs of triply periodic minimal surfaces. The effect of the symmetry and topology of the periodic dielectric structures on the existence and the characteristics of the gaps is discussed. We find that the C(I2-Y**) structure with Ia3d symmetry, a symmetry which is often seen in experimentally realized bicontinuous structures, has a photonic band gap with interesting characteristics. For a dielectric contrast of 11.9 the largest gap is approximately 20% for a volume fraction of the high dielectric material of 25%. The midgap frequency is a factor of 1.5 higher than the one for the (tubular) D and G structures