Profiling Insulin Like Factor 3 (INSL3) Signaling in Human Osteoblasts

Abstract BACKGROUND: Young men with mutations in the gene for the INSL3 receptor (Relaxin family peptide 2, RXFP2) are at risk of reduced bone mass and osteoporosis. Consistent with the human phenotype, bone analyses of Rxfp2(-/-) mice showed decreased bone volume, alterations of the trabecular bone, reduced mineralizing surface, bone formation, and osteoclast surface. The aim of this study was to elucidate the INSL3/RXFP2 signaling pathways and targets in human osteoblasts. METHODOLOGY/PRINCIPAL FINDINGS: Alkaline phosphatase (ALP) production, protein phosphorylation, intracellular calcium, gene expression, and mineralization studies have been performed. INSL3 induced a significant increase in ALP production, and Western blot and ELISA analyses of multiple intracellular signaling pathway molecules and their phosphorylation status revealed that the MAPK was the major pathway influenced by INSL3, whereas it does not modify intracellular calcium concentration. Quantitative Real Time PCR and Western blotting showed that INSL3 regulates the expression of different osteoblast markers. Alizarin red-S staining confirmed that INSL3-stimulated osteoblasts are fully differentiated and able to mineralize the extracellular matrix. CONCLUSIONS/SIGNIFICANCE: Together with previous findings, this study demonstrates that the INSL3/RXFP2 system is involved in bone metabolism by acting on the MAPK cascade and stimulating transcription of important genes of osteoblast maturation/differentiation and osteoclastogenesis

Trapping in irradiated p-on-n silicon sensors at fluences anticipated at the HL-LHC outer tracker

The degradation of signal in silicon sensors is studied under conditions expected at the CERN High-Luminosity LHC. 200 $\mu$m thick n-type silicon sensors are irradiated with protons of different energies to fluences of up to $3 \cdot 10^{15}$ neq/cm$^2$. Pulsed red laser light with a wavelength of 672 nm is used to generate electron-hole pairs in the sensors. The induced signals are used to determine the charge collection efficiencies separately for electrons and holes drifting through the sensor. The effective trapping rates are extracted by comparing the results to simulation. The electric field is simulated using Synopsys device simulation assuming two effective defects. The generation and drift of charge carriers are simulated in an independent simulation based on PixelAV. The effective trapping rates are determined from the measured charge collection efficiencies and the simulated and measured time-resolved current pulses are compared. The effective trapping rates determined for both electrons and holes are about 50% smaller than those obtained using standard extrapolations of studies at low fluences and suggests an improved tracker performance over initial expectations

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

Structure of bryozoan communities in an Antarctic glacial fjord (Admiralty Bay, South Shetlands)

Bryozoans are among the most important groups of the Southern Ocean benthic macrofauna, both in terms of species richness and abundance. However, there is a considerable lack of ecological research focused on their distribution patterns and species richness on smaller scale, especially in the soft bottom habitats of Antarctic glacial fjords. The aim of this study was to describe those patterns in the Admiralty Bay. Forty-nine Van Veen grab samples were collected at the depth range from 15 to 265 m, in the summer season of 1979/1980, at three sites distributed along the main axis of the fjord. Among 53 identified species of bryozoans, 32 were recorded in the Admiralty Bay for the first time. The most common and abundant species were Himantozoum antarcticum, Inversiula nutrix and Nematoflustra flagellata. Genera such as Arachnopusia, Cellarinella and Osthimosia were the most speciose taxa. It was demonstrated that depth was important for the distribution of the bryozoans. More than half of the recorded species were found only below 70 m. An influence of glacial disturbance was reflected in the dominance structure of colony growth-forms. The inner region of the fjord was dominated almost entirely by encrusting species, while the diversity of bryozoan growth-forms in less disturbed areas was much higher. In those sites the highest percentage of branched, tuft like species represented by buguliform and flustriform zoaria was observed.The study was supported by a grant of Polish Ministry of Science and Higher Education No. 51/N-IPY/2007/0 as well as Census of Antarctic Marine Life Project. Krzysztof Pabis was also partially supported by University of Lodz internal funds. This research was also supported by the Polish Geological Institute-National Research Institute during the realization of the project numbered 40.2900.0903.18.0 titled “Bryozoan assemblage of Admiralty Bay—richness, diversity and abundance.” Urszula Hara is deeply grateful to Leszek Giro (Micro-area Analyses Laboratory at the Polish Geological Institute-National Research Institute, Warsaw), for providing SEM assistance during the project. We also want to thank two anonymous reviewers for their suggestions that helped us improve this article. Thanks are also due to Magdalena Błażewicz-Paszkowycz for language correction and polishing the final version of the manuscript