Secreted cysteine proteases of the carcinogenic liver fluke, Opisthorchis viverrini: Regulation of cathepsin F activation by autocatalysis and trans-processing by cathepsin B

Opisthorchis viverrini is an important helminth pathogen of humans that is endemic in Thailand and Laos. Adult flukes reside within host bile ducts and feed on epithelial tissue and blood cells. Chronic opisthorchiasis is associated with severe hepatobiliary diseases such as cholangiocarcinoma. Here we report that adult O. viverrini secrete two major cysteine proteases: cathepsin F (Ov-CF-1) and cathepsin B1 (Ov-CB-1). Ov-CF-1 is secreted as an inactive zymogen that autocatalytically processes and activates to a mature enzyme at pH 4.5 via an intermolecular cleavage at the prosegment-mature domain junction. Ov-CB-1 is also secreted as a zymogen but, in contrast to Ov-CF-1, is fully active against peptide and macromolecular substrates despite retaining the N-terminal prosegment. The active Ov-CB-1 zymogen was capable of trans-activating Ov-CF-1 by proteolytic removal of its prosegment at pH 5.5, a pH at which the Ov-CF-1 zymogen cannot autocatalytically activate. Both cathepsins hydrolyse human haemoglobin but their combined action more efficiently degrades haemoglobin to smaller peptides than each enzyme alone. Ov-CF-1 degraded extracellular matrix proteins more effectively than Ov-CB-1 at physiological pH. We propose that Ov-CB-1 regulates Ov-CF-1 activity and that both enzymes work together to degrade host tissue contributing to the development of liver fluke-associated cholangiocarcinoma.

Dressing Plasmons in Particle-in-Cavity Architectures

Placing metallic nanoparticles inside cavities, rather than in dimers, greatly improves their plasmonic response. Such particle-in-cavity (PIC) hybrid architectures are shown to produce extremely strong field enhancement at the particle cavity junctions, arising from the cascaded focusing of large optical cross sections into small gaps. These simply constructed PIC structures produce the strongest field enhancement for coupled nanoparticles, up to 90% stronger than for a dimer. The coupling is found to follow a universal power law with particle surface separation, both for field enhancements and resonant wavelength shifts. Significantly enhanced Raman signals are experimentally observed for molecules adsorbed in such PIC structures, in quantitive agreement with theoretical calculations. PIC architectures may have important implications in many applications, such as reliable single molecule sensing and light harvesting in plasmonic photovoltaic devices.

Does conurbation affect the risk of poor mental health? A population based record linkage study

To determine if urban residence is associated with an increased risk of anxiety/depression independent of psychosocial stressors, concentrated disadvantage or selective migration between urban and rural areas, this population wide record-linkage study utilised data on receipt of prescription medication linked to area level indicators of conurbation and disadvantage. An urban/rural gradient in anxiolytic and antidepressant use was evident that was independent of variation in population composition. This gradient was most pronounced amongst disadvantaged areas. Migration into increasingly urban areas increased the likelihood of medication. These results suggest increasing conurbation is deleterious to mental health, especially amongst residents of deprived areas

Development of release methods for critically endangered freshwater pearl mussels (Margaritifera margaritifera)

Biodiversity loss is a global problem with freshwater bivalves considered amongst the most
endangered biota. The freshwater pearl mussel, Margaritifera margaritifera, is declining
throughout its range owing to habitat degradation and overexploitation. In most of its range,
populations are regarded as reproductively non-functional which has led to the development
of captive breeding programmes. A novel method of releasing M. margaritifera was trialled,
with captive-bred juveniles being released into the rivers caged in ‘mussels silos’ (protective
concrete domes with ventilation creating upwelling to ensure water through flow). We
released 240 juvenile mussels and survival and growth rates were monitored for 18 months
post-release for three size classes: A (13.01-20.00mm); B (10.01-13.00mm); and C (4.01-
10.00mm). We explicitly tested two experimental treatments; one where sediment was added
to each silo (allowing mussels to orientate and burrow) and one without sediment. Survival
by the end of the experiment at month 18 was significantly higher for the largest size class at
97% (though growth was lowest in this cohort), and lowest for the smallest size class at 61%
(though growth was highest in this cohort). Survival and growth were unaffected by the
experimental treatment suggesting that adding sediment offered no advantage. Growth was
positively correlated with both water temperature and the particle size of suspended solids
(both of which were collinear, peaking in summer). There are a large number of ex situ
breeding programmes for freshwater pearl mussels throughout Europe and our finding
suggest that the use of ‘mussel silos’ could be a useful tool to protecting juvenile mussels
allowing them to be released at a relatively early stage of development, minimising the risk of
domestication.