DRhoGEF2 Regulates Cellular Tension and Cell Pulsations in the Amnioserosa during Drosophila Dorsal Closure

Coordination of apical constriction in epithelial sheets is a fundamental process during embryogenesis. Here, we show that DRhoGEF2 is a key regulator of apical pulsation and constriction of amnioserosal cells during Drosophila dorsal closure. Amnioserosal cells mutant for DRhoGEF2 exhibit a consistent decrease in amnioserosa pulsations whereas overexpression of DRhoGEF2 in this tissue leads to an increase in the contraction time of pulsations. We probed the physical properties of the amnioserosa to show that the average tension in DRhoGEF2 mutant cells is lower than wild-type and that overexpression of DRhoGEF2 results in a tissue that is more solid-like than wild-type. We also observe that in the DRhoGEF2 overexpressing cells there is a dramatic increase of apical actomyosin coalescence that can contribute to the generation of more contractile forces, leading to amnioserosal cells with smaller apical surface than wild-type. Conversely, in DRhoGEF2 mutants, the apical actomyosin coalescence is impaired. These results identify DRhoGEF2 as an upstream regulator of the actomyosin contractile machinery that drives amnioserosa cells pulsations and apical constriction

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

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

PEG-Interferon for Chronic Phase CML - Still an Option in the Era of Imatinib?.

Abstract Objectives PEG-Interferon alpha 2b (PEG-IFN) is a new formulation of Interferon with a prolonged half-life and can therefore be given once weekly. It has shown efficacy in patients refractory or intolerant to IFN. Within a German multicenter study (SHG CMLIIIA) PEG-IFN (PEG-Intron, Essex) was used in our centre for patients with CML in first chronic phase. Methods: 17 patients with newly diagnosed bcr-abl positive CML in chronic phase were included in our centre as part of the CML IIIA study. Median age was 42 yrs (range 24 – 78 yrs). After initial cytoreduction with hydroxyurea patients received 3–6 μg/kg PEG-IFN subcutaneously once a week. One patient received additional cytarabine at a dose of 20 mg/m2 10 days per month. Results: After 3 months 13/17 patients had a complete hematological response, 3 had a partial hematological response, 1 patient had a hereditary thrombocytopenia and therefor did not fulfill hematological CR criteria. Cytogenetics/FISH after 6 months were available in 12 patients and showed 1 complete cytogenetic response, 3 partial cytogenetic responses, 5 minor cytogenetic reponses and no response in 3 patients. 9 patients remained on PEG-IFN for at least 12 months and showed 2 complete, 1 partial and 2 minor cytogenetic responses and no response in 4 patients. Thus the rate of major cytogenetic responses was 33% at 6 months and at 12 months. PEG-IFN treatment was stopped in 14 patients due IFN-intolerance (n=6), patient decision (n=1), blast crisis (n=2), accelerated phase (n=1) or cytogenetic non-response (n=4). Relevant toxicities included acute pancreatitis in 1 patient, a grand mal seizure in a patient with a history of subdural hematoma, exacerbation of supraventricular tachycardia in 1 patient, transient elevation of GPT in 1 patient and a local abscess at the injection site in 1 patient. All patients experienced fever and flu-like symptoms in the first 4 weeks which gradually improved. Conclusion: PEG-IFN at a dose of 3–6 μg/kg was effective in producing complete hematological remissions after 3 months in the majority of patients and showed major cytogenetic responses in one third of patients. However there was a considerable toxicity. Still 53% of patients were able to continue treatment for at least 12 months and 4 of these (44%) are in continuous partial or complete cytogenetic response. This response rate is comparable to the results for conventional IFN in combination with Ara-C from the recent IRIS study. However in the IRIS study only 10.8% remained on IFN compared to 53% in our cohort. For patients able to tolerate this treatment PEG-IFN appears to be a valid alternative to IFN+Ara-C or imatinib in chronic phase CML.</jats:p