The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo

Human lymphatic filariasis is a major tropical disease transmitted through mosquito vectors which take up microfilarial larvae from the blood of infected subjects. Microfilariae are produced by long-lived adult parasites, which also release a suite of excretory-secretory products that have recently been subject to in-depth proteomic analysis. Surprisingly, the most abundant secreted protein of adult Brugia malayi is triose phosphate isomerase (TPI), a glycolytic enzyme usually associated with the cytosol. We now show that while TPI is a prominent target of the antibody response to infection, there is little antibody-mediated inhibition of catalytic activity by polyclonal sera. We generated a panel of twenty-three anti-TPI monoclonal antibodies and found only two were able to block TPI enzymatic activity. Immunisation of jirds with B. malayi TPI, or mice with the homologous protein from the rodent filaria Litomosoides sigmodontis, failed to induce neutralising antibodies or protective immunity. In contrast, passive transfer of neutralising monoclonal antibody to mice prior to implantation with adult B. malayi resulted in 60–70% reductions in microfilarial levels in vivo and both oocyte and microfilarial production by individual adult females. The loss of fecundity was accompanied by reduced IFNγ expression by CD4+ T cells and a higher proportion of macrophages at the site of infection. Thus, enzymatically active TPI plays an important role in the transmission cycle of B. malayi filarial parasites and is identified as a potential target for immunological and pharmacological intervention against filarial infections

Foraging for foundations in decision neuroscience: insights from ethology

Modern decision neuroscience offers a powerful and broad account of human behaviour using computational techniques that link psychological and neuroscientific approaches to the ways that individuals can generate near-optimal choices in complex controlled environments. However, until recently, relatively little attention has been paid to the extent to which the structure of experimental environments relates to natural scenarios, and the survival problems that individuals have evolved to solve. This situation not only risks leaving decision-theoretic accounts ungrounded but also makes various aspects of the solutions, such as hard-wired or Pavlovian policies, difficult to interpret in the natural world. Here, we suggest importing concepts, paradigms and approaches from the fields of ethology and behavioural ecology, which concentrate on the contextual and functional correlates of decisions made about foraging and escape and address these lacunae

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

Effects of spiked metals on the MSW anaerobic digestion

This study aimed to investigate the effects of eight metals on the anaerobic digestion of the organic fraction of municipal solid waste (OFMSW) in bioreactors. Anaerobic bioreactors containing 200?mL MSW mixed completely with 200?mL sludge seeding. Ca and K (0, 1000, 2000 and 6000?mg?L?1) and Cr, Ni, Zn, Co, Mo and W (0, 5, 50 and 100?mg?L?1) of various dose were added to anaerobic bioreactors to examine their anaerobic digestion performance. Results showed that except K and Zn, Ca (~728 to ~1461?mg?L?1), Cr (~0.0022 to ~0.0212?mg?L?1), Ni (~0.801 to ~5.362?mg?L?1), Co (~0.148 to ~0.580?mg?L?1), Mo (~0.044 to ~52.94?mg?L?1) and W (~0.658 to ~40.39?mg?L?1) had the potential to enhance the biogas production. On the other hand, except Mo and W, inhibitory concentrations IC50 of Ca, K, Cr, Ni, Zn and Co were found to be ~3252, ~2097, ~0.124, ~7.239, ~0.482, ~8.625?mg?L?1, respectively. Eight spiked metals showed that they were adsorbed by MSW to a different extent resulting in different liquid metals levels and potential stimulation and inhibition on MSW anaerobic digestion. These results were discussed and compared to results from literature