ArhGAP9, a novel MAP kinase docking protein, inhibits Erk and p38 activation through WW domain binding

We have identified human ArhGAP9 as a novel MAP kinase docking protein that interacts with Erk2 and p38α through complementarily charged residues in the WW domain of ArhGAP9 and the CD domains of Erk2 and p38α. This interaction sequesters the MAP kinases in their inactive states through displacement of MAP kinase kinases targeting the same sites. While over-expression of wild type ArhGAP9 caused MAP kinase activation by the epidermal growth factor receptor (EGFR) to be suppressed and preserved the actin stress fibres in quiescent Swiss 3T3 fibroblasts, over-expression of an ArhGAP9 mutant defective in MAP kinase binding restored EGFR-induced MAP kinase activation and resulted in significant disruption of the stress fibres, consistent with the role of Erk activation in disassembly of actin stress fibres. The interaction between ArhGAP9 and the MAP kinases represents a novel mechanism of cross-talk between Rho GTPase and MAP kinase signaling

Respiratory viral pathogens among Singapore military servicemen 2009 - 2012: Epidemiology and clinical characteristics

10.1186/1471-2334-14-204BMC Infectious Diseases141-BIDM

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

GaN-on-Silicon integration technology

This work presents our recent progress on addressing two major challenges to realizing GaN-Silicon integration namely epitaxial growth of GaN-on-Silicon and CMOS-compatible process. We have successfully demonstrated 0.3-μm gate-length GaN HEMTs on 8-inch Si(111) substrate with fT of 28GHz and fmax of of 64GHz. These device performances are comparable to our reported devices fabricated on 4-inch Si substrate. We have also developed a GaN HEMT process with CMOS-compatible non-gold metal scheme. Excellent ohmic contacts (Rc=0.24 Ω-mm) with smooth surface morphology have been achieved which are comparable to those using conventional III-V gold-based ohmic contacts. 0.15-μm gate-length GaN HEMTs fabricated with this process achieved fT and fmax of 51 GHz and 50GHz respectively. The 5nm-thick AlGaN barrier HEMT exhibited three terminal OFF-state breakdown voltage (BVgd) of 83 V. Our results demonstrate the feasibility of realizing CMOS-compatible high performance GaN HEMTs on 8-inch silicon substrates for future GaN-on-Si integration

Expression of the Homeobox Genes OTX2 and OTX1 in the Early Developing Human Brain

In rodents, the Otx2 gene is expressed in the diencephalon, mesencephalon, and cerebellum and is crucial for the development of these brain regions. Together with Otx1, Otx2 is known to cooperate with other genes to develop the caudal forebrain and, further, Otx1 is also involved in differentiation of young neurons of the deeper cortical layers. We have studied the spatial and temporal expression of the two homeobox genes OTX2 and OTX1 in human fetal brains from 7 to 14 weeks postconception by in situ hybridization and immunohistochemistry. OTX2 was expressed in the diencephalon, mesencephalon, and choroid plexus, with a minor expression in the basal telencephalon. The expression of OTX2 in the hippocampal anlage was strong, with no expression in the adjacent neocortex. Contrarily, the OTX1 expression was predominantly located in the proliferative zones of the neocortex. At later stages, the OTX2 protein was found in the subcommissural organ, pineal gland, and cerebellum. The early expression of OTX2 and OTX1 in proliferative cell layers of the human fetal brain supports the concept that these homeobox genes are important in neuronal cell development and differentiation: OTX1 primarily in the neocortex, and OTX2 in the archicortex, diencephalon, rostral brain stem, and cerebellum. (J Histochem Cytochem 58:669–678, 2010