Acute Oak Decline (AOD) is a new condition affecting both species of native oak, Quercus robur and Quercus petraea, in Great Britain. The decline is characterised by a distinctive set of externally visible stem symptoms; bark cracks that “weep” dark exudate are found above necrotic lesions in the inner bark. Emergence holes of the buprestid beetle, Agrilus biguttatus are often also seen on the stems of oak within affected woodlands. This investigation assesses the extent to which the external symptoms of these two agents co-occur and reveals the spatial and temporal patterns present in affected woodland. Annual monitoring in eight affected woodlands showed that stem bleeding and emergence holes frequently occur on the same trees, with new emergence holes significantly more likely to occur when trees already have stem bleeds. Trials with coloured prism traps confirm A. biguttatus was present at all experimental sites. Beetle emergence is linked primarily to a few heavily declining trees, indicating that susceptibility may vary between hosts and that those with reduced health may be predisposed to AOD. Stem bleeds occur on trees in close proximity to the locations of trees with exit holes. Full article

Blinding cataract is a significant effect of canine diabetes with 75% of animals affected two years after diagnosis. Lens opacification occurs primarily through the generation of sorbitol, a sugar alcohol, through the action of aldose reductase (AR). The osmotic effect of sorbitol draws water into the lens, causing opacification. Inhibition of AR should thus prevent the generation of cataracts. A topical AR inhibitor has been shown to have this effect, as has the commercially available neutraceutical OcuGLO, containing the AR inhibitor alpha lipoic acid (ALA) together with other plant-based antioxidants. Here a comparison is made between the number of diabetic dogs developing cataracts when given oral ALA alone and those given a mix containing ascorbic acid and tocopherol. Animals given ALA developed significantly fewer lens opacities than those given conventional antioxidants. Cataracts which formed occurred at a significantly greater duration after the commencement of treatment than those on the antioxidant mix. Although this is a small study conducted over a short period, the significant benefit of ALA in diabetic dogs is a reason to evaluate these effects in larger trials. As AR is involved in diabetic retinopathy and neuropathy, this enzyme inhibitor may be worthy of evaluation in preventing these conditions in human diabetics also. Full article

New Zealand blackcurrant (NZBC) extract has been shown to enhance high-intensity intermittent treadmill running. We examined the effects of NZBC extract during the Loughborough Intermittent Shuttle Test (LIST) which involves 5 × 15 min blocks with intermittent 15-m maximal sprints, interspersed by moderate and high-intensity running to simulate team sport activity, and a subsequent run to exhaustion. Thirteen males (age: 22 ± 1 year, $\dot{V}{O}_{2\text{max}}$ : 50 ± 5 mL·kg⁻¹·min⁻¹) participated in three indoor sessions (T: 24 ± 3 °C, humidity: 52% ± 9%). In the first session, a multistage fitness test was completed to determine peak running speed and estimate $\dot{V}{O}_{2\text{max}}$ . Participants consumed NZBC extract in capsules (300 mg·day⁻¹ CurraNZ™) or placebo (PL) (300 mg·day⁻¹ microcrystalline cellulose M102) for seven days in a double-blind, randomized, cross-over design (wash-out at least seven days). NZBC extract did not affect average 15-m sprint times in each block. NZBC reduced slowing of the fastest sprint between block 1 and 5 (PL: 0.12 ± 0.07 s; NZBC: 0.06 ± 0.12 s; p < 0.05). NZBC extract had no effect on heart rate, vertical jump power, lactate and time to exhaustion (PL: 13.44 ± 8.09 min, NZBC: 15.78 ± 9.40 min, p > 0.05). However, eight participants had higher running times to exhaustion when consuming NZBC extract. New Zealand blackcurrant extract may enhance performance in team sports with repeated maximal sprints. Full article

Convincing evidence has emerged demonstrating that impairment of mitochondrial function is critically important in regulating alveolar epithelial cell (AEC) programmed cell death (apoptosis) that may contribute to aging-related lung diseases, such as idiopathic pulmonary fibrosis (IPF) and asbestosis (pulmonary fibrosis following asbestos exposure). The mammalian mitochondrial DNA (mtDNA) encodes for 13 proteins, including several essential for oxidative phosphorylation. We review the evidence implicating that oxidative stress-induced mtDNA damage promotes AEC apoptosis and pulmonary fibrosis. We focus on the emerging role for AEC mtDNA damage repair by 8-oxoguanine DNA glycosylase (OGG1) and mitochondrial aconitase (ACO-2) in maintaining mtDNA integrity which is important in preventing AEC apoptosis and asbestos-induced pulmonary fibrosis in a murine model. We then review recent studies linking the sirtuin (SIRT) family members, especially SIRT3, to mitochondrial integrity and mtDNA damage repair and aging. We present a conceptual model of how SIRTs modulate reactive oxygen species (ROS)-driven mitochondrial metabolism that may be important for their tumor suppressor function. The emerging insights into the pathobiology underlying AEC mtDNA damage and apoptosis is suggesting novel therapeutic targets that may prove useful for the management of age-related diseases, including pulmonary fibrosis and lung cancer. Full article

To formulate an alginate dental impression material with virucidal properties, experimental alginate dental impression materials were developed and the formulations adjusted in order to study the effect on pH profiles during setting. Commercially available materials served as a comparison. Eight experimental materials were tested for antiviral activity against Herpes Simplex Virus type 1 (HSV-1). Changing the amount of magnesium oxide (MgO) used in the experimental formulations had a marked effect on pH. Increasing MgO concentration corresponded with increased pH values. All experimental materials brought about viral log reductions ranging between 0.5 and 4.0 over a period of 4 h. The material with the lowest pH was the most effective. The current work highlights the very important role of MgO in controlling pH profiles. This knowledge has been applied to the formulation of experimental alginates; where materials with pH values of approximately 4.2–4.4 are able to achieve a significant log reduction when assayed against HSV-1. Full article

A novel multi-axial bioreactor was designed and developed to deliver combinations of the following dynamic mechanical stimulation conditions: hydrostatic pressure, pulsatile perfusion flow and uniaxial compression in order to mimic in vivo conditions. This mechanical arrangement simultaneously allows triaxial stimulation and characterization of mechanical properties of samples, in particular simulating the conditions experienced by the nucleus pulposus in vivo. A series of initial experiments were performed on this prototype system using consistent, commercially-available, three dimensional scaffolds in combination with human dermal fibroblasts. Our results show that while such bioreactors hold much promise in tissue engineering of desired organs, achieving the right combination of mechanical stimuli and other conditions required in order to enhance the final properties of the cell-scaffold systems is challenging. Full article

We examine a rod piston-rotaxane system, where the positions of several mobile rings on the axle are controlled by an external force acting on one of the rings. This allows us to access the translational entropy of the rings. For a simple rotaxane molecule with an axle that has uniform ring-axle interactions along its length, the molecule behaves like a miniature piston filled with a one-dimensional ideal gas. We then examine the effect of two stripes on the axle, having different ring-axle interactions with the mobile rings, so that one section is of high energy (repulsive) for the rings and another section is of lower energy (or attractive). This kind of rotaxane can exhibit rapid changes in displacement or force, and in particular, this molecule can exhibit a yield stress in which the piston suddenly compresses under a small increase in the applied force. Full article

Multiple drug resistance (MDR) in Mycobacterium tuberculosis (mTB), the causative agent for tuberculosis (TB), has led to increased use of second-line drugs, including ethionamide (ETA). ETA is a prodrug bioactivated by mycobacterial and mammalian flavin-containing monooxygenases (FMOs). FMO2 is the major isoform in the lungs of most mammals, including primates. In humans a polymorphism exists in the expression of FMO2. FMO2.2 (truncated, inactive) protein is produced by the common allele, while the ancestral allele, encoding active FMO2.1, has been documented only in individuals of African and Hispanic origin, at an incidence of up to 50% and 7%, respectively. We hypothesized that FMO2 variability in TB-infected individuals would yield differences in concentrations and ratios of ETA prodrug and metabolites. In this study we assessed the impact of the FMO2 genetic polymorphism on the pharmacokinetics of ETA after administration of a single oral dose of ETA (125 mg/kg) to wild type and triple Fmo1/2/4-null mice, measuring levels of prodrug vs. metabolites in plasma collected from 0 to 3.5 h post-gavage. All mice metabolized ETA to ETA S-oxide (ETASO) and 2-ethyl-4-amidopyridine (ETAA). Wild type mice had higher plasma concentrations of metabolites than of parent compound (p = 0.001). In contrast, Fmo1/2/4-null mice had higher plasma concentrations of parent compound than of metabolites (p = 0.0001). Thus, the human FMO2 genotype could impact the therapeutic efficacy and/or toxicity of ETA. Full article

Detailed crystal structures and ¹H-NMR characteristics of some alkylaminephthalimides, including dendritic polyphthalimides, are reported. These investigations were undertaken in order to obtain a better understanding of the relationship between solid-state supramolecular interactions, their persistence in solution and associated dynamics of magnetically hypersensitive phthalimide aromatic AA'BB'-AA'XX' proton NMR resonances. Some alkylamine phthalimides feature folded molecular geometries, which we attribute to n-π interactions among proximal amine-phthalimide sites; those alkylamine-phthalimides that have no possibility for such interactions feature fully extended phthalimide functionalities. Accordingly, alkylamine phthalimide compounds with folded solid-state geometries feature solvent and temperature dependent hypersensitive AA'BB'-AA'XX' ¹H-NMR line profiles, which we attribute to the n-π interactions. Luminescence of Eu³⁺(⁵D0) and Tb³⁺(⁵D₄) states show well defined metal ion environments in their complexes with dendritic phthalimides, as well as relatively weak phthalimide-lanthanide(III) interactions. Full article