Vascular endothelial growth factor signaling in development and disease

Vascular endothelial growth factors (VEGFs) are best known for their involvement in orchestrating the development and maintenance of the blood and lymphatic vascular systems. VEGFs are secreted by a variety of cells and they bind to their cognate tyrosine kinase VEGF receptors (VEGFRs) in endothelial cells to elicit various downstream effects. In recent years, there has been tremendous progress in elucidating different VEGF/VEGFR signaling functions in both the blood and lymphatic vascular systems. Here, and in the accompanying poster, we present key elements of the VEGF/VEGFR pathway and highlight the classical and newly discovered functions of VEGF signaling in blood and lymphatic vessel development and pathology.Peer reviewe

Phylogeography of the ant Myrmica rubra and its inquiline social parasite

Peer reviewe

Efficient activation of the lymphangiogenic growth factor VEGF-C requires the C-terminal domain of VEGF-C and the N-terminal domain of CCBE1

Peer reviewe

Methods and Apparatus for Data Security in Mobile Ad Hoc Networks

Systems and techniques for key management in mobile ad hoc networks are described. Pseudonyms are defined for group members of mobile ad hoc networks such that a pseudonym in a message can be deterministically identified with the sending device only by the sending device and the message recipient. Key management for a group is performed by a group manager, and key management may include key renewal and revocation. Key renewal is performed by a group manager, with the group manager using a set of couple pseudonyms, including a couple pseudonym between the manger and each group member. Key renewal employs a renewal key used to encrypt the updated group key, and the group manager updates the group key be transmitting a message to each group member in proximity, with the message being identified using the couple pseudonym of the manager and the group member

Perilaku Berbahasa Santri Pondok Modern Gontor Pudahoa

AbstrakPerilaku Berbahasa Santri Gontor Pudahoa menarik dan unik. Spirit yang inginditelusuri penulis adalah kesadaran, kesetiaan dan tanggung jawab santri dalammemelihara bahasa Arab, bahasa Inggris, bahasa Indonesia dan bahasa daerah.Pengumpulan data menggunakan teknik pengamatan, wawancara mendalam, danpenelusuran dokumen. Penelitian menghasilkan temuan, di Gontor Pudahoapenggunaan bahasa disesuaikan dengan kehendak kurikulum berdasarkan tingkatkepentingannya. Penonjolan ciri khas Gontor terlihat sangat kentara padapenggunaan bahasa Arab dan Inggris dalam berbagai ranah. Pemilihan bahasadipengaruhi factor santri, guru dan lingkungan, kendati dalam banyak peristiwakebahasaan santri cenderung mentransfer unsur bahasa pertamanya. Penelitian inimenemukan pengaruh pandangan keagamaan santri terhadap perilaku bahasanya.Penggunaan bahasa Arab untuk memuliakan Al-Qur’an, meninggikan agama danmembangun peradaban Islam, bahasa Inggris untuk komunikasi internasional danpengembangan ilmu pengetahuan umum, pilihan bahasa Indonesia sebagai wujudpengabdian kepada Negara, dan bahasa daerah sebagai bentuk bakti dan rasahormat kepada orang tua/keluarga. Muncul kesadaran dan pandangan positifsantri juga terhadap bahasa Jepang, Mandarin dan Korea.Kata Kunci: Perilaku Berbahasa Santri, Pesantren Gontor, Pudaho

Finnish Forest Sector Economic Outlook 2018–2019. Executive Summary

The executive summary is a translation of the summary of the Finnish original publication, and is based on information available in early October 2018. Available at: http://urn.fi/URN:ISBN:978-952-326-628-5 Year 2018 will be a major economic peak in the Finnish forest sector. Forest industries’ production and export volumes are growing, industrial roundwood fellings are increasing, stumpage prices are rising, and operating profit in non-industrial private forestry is improving. Current cyclical peak is driven by growing world economy, which has increased the demand for forest industry products. Political decisions, such as restrictions on the import and use of recycled fibre and the closures of polluting mills in China, have contributed to the development of Finnish forest exports. In 2019, the growth in the world economy is expected to slow down. Uncertainty in export markets for forest industry products is maintained by, e.g. the Brexit and problems related to the accumulating debts in China and Italy. Despite the slowdown in the global economic growth, the Finnish forest sector is not expected to face a strong downturn. In 2019, the growth in production and export volumes of forest industry products will slow down for most products and the upward trend in export prices will level off. With regard to market pulp, the export price will decrease from the record high level of 2018.201

Transcription factor PROX1 suppresses Notch pathway activation via the nucleosome remodeling and deacetylase complex in colorectal cancer stem-like cells

The homeobox transcription factor PROX1 is induced by high Wnt/ß-catenin activity in intestinal adenomas and colorectal cancer (CRC), where it promotes tumor progression. Here we report that in LGR5+ CRC cells, PROX1 suppresses the Notch pathway, which is essential for cell fate in intestinal stem cells. Pharmacological inhibition of Notch in ex vivo 3D organoid cultures from transgenic mouse intestinal adenoma models increased Prox1 expression and the number of PROX1-positive cells. Notch inhibition led to increased proliferation of the PROX1-positive CRC cells but did not affect their ability to give rise to PROX1-negative secretory cells. Conversely, PROX1 deletion increased Notch target gene expression and NOTCH1 promoter activity, indicating reciprocal regulation between PROX1 and the Notch pathway in CRC. PROX1 interacted with the nucleosome remodeling and deacetylase (NuRD) complex to suppress the Notch pathway. Thus, our data suggests that PROX1 and Notch suppress each other and that PROX1-mediated suppression of Notch mediates its stem cell function in CRC

Genetic Variants of VEGFA and FLT4 Are Determinants of Survival in Renal Cell Carcinoma Patients Treated with Sorafenib

Molecular markers of sorafenib efficacy in patients with metastatic renal cell carcinoma (mRCC) are not available. The purpose of this study was to discover genetic markers of survival in patients with mRCC treated with sorafenib. Germline variants from 56 genes were genotyped in 295 patients with mRCC. Variant-overall survival (OS) associations were tested in multivariate regression models. Mechanistic studies were conducted to validate clinical associations. VEGFA rs1885657, ITGAV rs3816375, and WWOX rs8047917 (sorafenib arm), and FLT4 rs307826 and VEGFA rs3024987 (sorafenib and placebo arms combined) were associated with shorter OS. FLT4 rs307826 increased VEGFR-3 phosphorylation, membrane trafficking, and receptor activation. VEGFA rs1885657 and rs58159269 increased transcriptional activity of the constructs containing these variants in endothelial and RCC cell lines, and VEGFA rs58159269 increased endothelial cell proliferation and tube formation. FLT4 rs307826 and VEGFA rs58159269 led to reduced sorafenib cytotoxicity. Genetic variation in VEGFA and FLT4 could affect survival in sorafenib-treated patients with mRCC. These markers should be examined in additional malignancies treated with sorafenib and in other angiogenesis inhibitors used in mRCC. Significance: Clinical and mechanistic data identify germline genetic variants in VEGFA and FLT4 as markers of survival in patients with metastatic renal cell carcinoma.Peer reviewe