Coral reef fish larvae show no evidence for map-based navigation after physical displacement

Millions of minute, newly hatched coral reef fish larvae get carried into the open ocean by highly complex and variable currents. To survive, they must return to a suitable reef habitat within a species-specific time. Strikingly, previous studies have demonstrated that return to home reefs is much more frequent than would be expected by chance. It has been shown that magnetic and sun compass orientation can help cardinalfish maintain their innate swimming direction but do they also have a navigational map to cope with unexpected displacements? If displaced settling-stage cardinalfish Ostorhinchus doederleini use positional information during their pelagic dispersal, we would expect them to re-orient toward their home reef. However, after physical displacement by 180 km, the fish showed a swimming direction indistinguishable from original directions near the capture site. This suggests that the tested fish rely on innate or learned compass directions and show no evidence for map-based navigation

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.Peer reviewe

Identification of the synaptic vesicle glycoprotein 2 receptor binding site in botulinum neurotoxin A

AbstractBotulinum neurotoxins (BoNTs) inhibit neurotransmitter release by hydrolysing SNARE proteins. The most important serotype BoNT/A employs the synaptic vesicle glycoprotein 2 (SV2) isoforms A-C as neuronal receptors. Here, we identified their binding site by blocking SV2 interaction using monoclonal antibodies with characterised epitopes within the cell binding domain (HC). The site is located on the backside of the conserved ganglioside binding pocket at the interface of the HCC and HCN subdomains. The dimension of the binding pocket was characterised in detail by site directed mutagenesis allowing the development of potent inhibitors as well as modifying receptor binding properties

Early-stage endometrial cancer, CTNNB1 mutations, and the relationship between lymphovascular space invasion and recurrence.

INTRODUCTION Women diagnosed with early-stage (FIGO 1) endometrial cancer, grade 1 and 2 can have a good prognosis. Most of these women can be treated successfully with a hysterectomy and bilateral salpingo-oophorectomy and without the additional adjuvant treatment that is accompanied by more risks for complications. However, when recurrence does occur, the consequences can be dire. Accurate decisions must therefore be made by surgeons to avoid either under- or over-treatment. Risk and patient stratification for tailoring treatment still need further improvement. Both histopathology and genetic variants could be integrated into the decision process if relevant factors were identified. MATERIAL AND METHODS Morphological features and the presence of selected genetic mutations in isolated malignant endometrial epithelial cells from these tumors were analyzed in a strictly defined cohort of FIGO 1, grade 1 and 2 low-risk endometrial cancer. Their presence in this cohort, their relationship to recurrence, and the association between histopathological features and mutations were determined. This analysis was performed using archival formalin-fixed paraffin-embedded tissue, complete re-evaluation of histopathological features, laser capture microdissection of epithelial cells, and a polymerase chain reaction-based mutational screening assay. RESULTS Twenty-one women with recurrence, after initial identification as low-risk endometrial cancer, were compared with 20 matched control women. The histological marker of lymphovascular invasion was significantly associated with recurrence. There was also a very high prevalence of mutations in CTNNB1 gene, occurring in 50% of this cohort. PTEN mutations were also observed in 27.8% of cases and PIK3CA mutations in 22.2%; none of these mutations were significantly related to recurrence. CONCLUSIONS This study supports the importance of lymphovascular space invasion to identify women with significant risk for recurrence in initially low-risk, early-stage endometrial cancer. It also identifies CTNNB1 as a significant mutation in early-stage disease, and although it may not represent a marker for recurrence its high prevalence in early stage disease could have relevance for both pathogenesis and early treatment

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 science. © The Author(s) 2019. Published by Oxford University Press