Seed sequence polymorphism rs2168518 and allele-specific target gene regulation of hsa-miR-4513

Acknowledgements We thank Lisa Michaelis and Dr Karolina Plößl (Institute of Human Genetics, University of Regensburg) for excellent technical help and thorough proofreading of the manuscript, respectively. We thank Marina Sauer and Franz-Stephan Attenkofer (Institute of Human Genetics, University of Regensburg) for their support in generating the luciferase reporter vectors. Conflict of Interest statement. The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Funding German Research Foundation (GR5065/1-1 to F.G.); and the Helmut Ecker Foundation (Ingolstadt, Germany) (no. 05/17 to B.H.F.W).Peer reviewedPublisher PD

Aldosterone does not require angiotensin II to activate NCC through a WNK4–SPAK–dependent pathway

We and others have recently shown that angiotensin II can activate the sodium chloride cotransporter (NCC) through a WNK4–SPAK-dependent pathway. Because WNK4 was previously shown to be a negative regulator of NCC, it has been postulated that angiotensin II converts WNK4 to a positive regulator. Here, we ask whether aldosterone requires angiotensin II to activate NCC and if their effects are additive. To do so, we infused vehicle or aldosterone in adrenalectomized rats that also received the angiotensin receptor blocker losartan. In the presence of losartan, aldosterone was still capable of increasing total and phosphorylated NCC twofold to threefold. The kinases WNK4 and SPAK also increased with aldosterone and losartan. A dose-dependent relationship between aldosterone and NCC, SPAK, and WNK4 was identified, suggesting that these are aldosterone-sensitive proteins. As more functional evidence of increased NCC activity, we showed that rats receiving aldosterone and losartan had a significantly greater natriuretic response to hydrochlorothiazide than rats receiving losartan only. To study whether angiotensin II could have an additive effect, rats receiving aldosterone with losartan were compared with rats receiving aldosterone only. Rats receiving aldosterone only retained more sodium and had twofold to fourfold increase in phosphorylated NCC. Together, our results demonstrate that aldosterone does not require angiotensin II to activate NCC and that WNK4 appears to act as a positive regulator in this pathway. The additive effect of angiotensin II may favor electroneutral sodium reabsorption during hypovolemia and may contribute to hypertension in diseases with an activated renin–angiotensin–aldosterone system

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

UNESCO Welterbe Schweizer Alpen Jungfrau-Aletsch: Eine Werkstatt für den Geographieunterricht Sekundarstufe II

Die Werkstatt UNESCO Welterbe Schweizer Alpen Jungfrau-Aletsch fördert die Auseinandersetzung mit den Themen Ökonomie, Ökologie und Gesellschaft in der Welterbe-Region und deren Talschaften

Comparative study of impaction and sedimentation in an aerosol chamber using defined fungal spore and bacterial concentrations

<div><p>Biocontamination control is a very significant part of the manufacturing process of sterile drugs. Sterility is frequently monitored by active or passive air sampling measurements, but there are no specific rules as to how this is to be done. This study tested air sampling methods of active impaction and passive sedimentation under standardized conditions. <i>Aspergillus niger</i> (<i>A</i>. <i>niger</i>) and <i>Staphylococcus aureus</i> (<i>S</i>. <i>aureus</i>) were selected in this experiment to examine parallels, correlations and differences between the two methods. The results show that the number of colony forming units per plate (CFU/plate) was higher for <i>A</i>. <i>niger</i> in the active method, whereas for <i>S</i>. <i>aureus</i> it was higher in the sedimentation method. A high correlation coefficient was found between the impaction and sedimentation methods for <i>A</i>. <i>niger</i>. For <i>S</i>. <i>aureus</i>, depending on the culture media used and the time for passive air sampling, a larger number of CFU/plate was found than in active air sampling. This study concludes that active and passive air sampling can be used for monitoring the air in clean rooms. For fungal spore detection, the impaction is more efficient, as it is possible to sample a higher volume of air in a shorter period of time, whereas the optimal measurement methods for <i>S</i>. <i>aureus</i> depend on a number of factors.</p></div

Impaction measurements (n = 30) of <i>A</i>. <i>niger</i> and <i>S</i>. <i>aureus</i> with mean values in CFU/ml (test suspension) and CFU/plate.

<p>Impaction measurements (n = 30) of <i>A</i>. <i>niger</i> and <i>S</i>. <i>aureus</i> with mean values in CFU/ml (test suspension) and CFU/plate.</p

Correlation coefficient (r) of impaction and sedimentation for <i>A</i>. <i>niger</i> and <i>S</i>. <i>aureus</i>.

<p>Correlation coefficient (r) of impaction and sedimentation for <i>A</i>. <i>niger</i> and <i>S</i>. <i>aureus</i>.</p

Ratio of impaction and sedimentation for <i>A</i>. <i>niger</i> and <i>S</i>. <i>aureus</i>.

<p>Ratio of impaction and sedimentation for <i>A</i>. <i>niger</i> and <i>S</i>. <i>aureus</i>.</p

Recovery of <i>S</i>. <i>aureus</i> concentration on CNA-agar.

<p>Recovery of <i>S</i>. <i>aureus</i> concentration on CNA-agar.</p