Hypoxia and oxidative stress in breast cancer: Hypoxia signalling pathways

Hypoxia-inducible factor-1 (HIF), which is centrally involved in physiological oxygen homeostasis, is also activated in the majority of tumours. Activation of HIF can occur through genetic mechanisms or as a result of hypoxia within the tumour microenvironment. In some cases HIF activation appears to be intimately linked to the proliferative stimulus itself. HIF affects patterns of gene expression and tumour growth, although precise effects vary between tumour types. Modulation of HIF activity, if correctly applied, may be therapeutically beneficial in tumour therapy

Determination and comparison of specific activity of the HIF-prolyl hydroxylases

AbstractHypoxia-inducible factor (HIF) is a transcriptional complex that is regulated by oxygen sensitive hydroxylation of its α subunits by the prolyl hydroxylases PHD1, 2 and 3. To better understand the role of these enzymes in directing cellular responses to hypoxia, we derived an assay to determine their specific activity in both native cell extracts and recombinant sources of enzyme. We show that all three are capable of high rates of catalysis, in the order PHD2=PHD3>PHD1, using substrate peptides derived from the C-terminal degradation domain of HIF-α subunits, and that each demonstrates similar and remarkable sensitivity to oxygen, commensurate with a common role in signaling hypoxia

Utility of interval kidney biopsy in ANCA-associated vasculitis

OBJECTIVES: ANCA-associated vasculitis (AAV) is a rare autoimmune disorder that commonly involves the kidney. Early identification of kidney involvement, assessing treatment-response and predicting outcome are important clinical challenges. Here, we assessed the potential utility of interval kidney biopsy in AAV. METHODS: In a tertiary referral centre with a dedicated vasculitis service, we identified patients with AAV who had undergone interval kidney biopsy, defined as a repeat kidney biopsy (following an initial biopsy showing active AAV) undertaken to determine the histological response in the kidney following induction immunosuppression. We analysed biochemical, histological and outcome data, including times to kidney failure and death for all patients. RESULTS: We identified 57 patients with AAV who underwent at least one interval kidney biopsy (59 interval biopsies in total; median time to interval biopsy ∼130 days). Of the 59 interval biopsies performed, 24 (41%) patients had clinically suspected active disease at time of biopsy which was confirmed histologically in only 42% of cases; 35 (59%) patients were in clinical disease-remission, and this was correct in 97% of cases. The clinician’s impression was incorrect in one in four patients. Hematuria at interval biopsy did not correlate with histological activity. Interval biopsy showed fewer acute lesions and more chronic damage compared with initial biopsy and led to immunosuppressive treatment-change in 75% (44/59) of patients. Clinical risk prediction tools tended to operate better using interval biopsy data. CONCLUSION: Interval kidney biopsy is useful for determining treatment-response and subsequent disease management in AAV. It may provide better prognostic information than initial kidney biopsy and should be considered for inclusion into future clinical trials and treatment protocols for patients with AAV

Effect of vessel wettability on the foamability of "ideal" surfactants and "real-world" beer heads

The ability to tailor the foaming properties of a solution by controlling its chemical composition is highly desirable and has been the subject of extensive research driven by a range of applications. However, the control of foams by varying the wettability of the foaming vessel has been less widely reported. This work investigates the effect of the wettability of the side walls of vessels used for the in situ generation of foam by shaking aqueous solutions of three different types of model surfactant systems (non-ionic, anionic and cationic surfactants) along with four different beers (Guinness Original, Banks’s Bitter, Bass No 1 and Harvest Pale). We found that hydrophilic vials increased the foamability only for the three model systems but increased foam stability for all foams except the model cationic system. We then compared stability of beer foams produced by shaking and pouring and demonstrated weak qualitative agreement between both foam methods. We also showed how wettability of the glass controls bubble nucleation for beers and champagne and used this effect to control exactly where bubbles form using simple wettability patterns

Mapping multi-dimensional variability in water stress strategies across temperate forests

Increasing water stress is emerging as a global phenomenon, and is anticipated to have a marked impact on forest function. The role of tree functional strategies is pivotal in regulating forest fitness and their ability to cope with water stress. However, how the functional strategies found at the tree or species level scale up to characterise forest communities and their variation across regions is not yet well-established. By combining eight water-stress-related functional traits with forest inventory data from the USA and Europe, we investigated the community-level trait coordination and the biogeographic patterns of trait associations for woody plants, and analysed the relationships between the trait associations and climate factors. We find that the trait associations at the community level are consistent with those found at the species level. Traits associated with acquisitive-conservative strategies forms one dimension of variation, while leaf turgor loss point, associated with stomatal water regulation strategy, loads along a second dimension. Surprisingly, spatial patterns of community-level trait association are better explained by temperature than by aridity, suggesting a temperature-driven adaptation. These findings provide a basis to build predictions of forest response under water stress, with particular potential to improve simulations of tree mortality and forest biomass accumulation in a changing climate

Search for Fractional Charges Produced in Heavy-Ion Collisions at 1.9 GeV/nucleon

An experiment was performed to capture fractionally charged particles produced in heavy-ion collisions and to concentrate them in samples suitable for analysis by various techniques. Two of the samples so produced have been searched, with use of an automated version of Millikan\u27s oil-drop apparatus. The beam was 56Fe at 1.9 GeV/nucleon, incident on a lead target. Less than one fractional charge per 1.0× 104 Fe-Pb collisions was found to be produced, and, with further assumptions, less than one per 2.0× 106 collisions