Suchergebnisse

Semaphorin 3A (Sema3A) is a cell-secreted protein that participates in the axonal guidance pathways. Sema3A acts as a canonical repulsive axon guidance molecule, inhibiting CNS regenerative axonal growth and propagation. Therefore, interfering with Sema3A signaling is proposed as a therapeutic target for achieving functional recovery after CNS injuries. It has been shown that Sema3A adheres to the proteoglycan component of the extracellular matrix (ECM) and selectively binds to heparin and chondroitin sulfate-E (CS-E) glycosaminoglycans (GAGs). We hypothesize that the biologically relevant interaction between Sema3A and GAGs takes place at Sema3A C-terminal polybasic region (SCT). The aims of this study were to characterize the interaction of the whole Sema3A C-terminal polybasic region (Sema3A 725–771) with GAGs and to investigate the disruption of this interaction by small molecules. Recombinant Sema3A basic domain was produced and we used a combination of biophysical techniques (NMR, SPR, and heparin affinity chromatography) to gain insight into the interaction of the Sema3A C-terminal domain with GAGs. The results demonstrate that SCT is an intrinsically disordered region, which confirms that SCT binds to GAGs and helps to identify the specific residues involved in the interaction. NMR studies, supported by molecular dynamics simulations, show that a new peptoid molecule (CSIC02) may disrupt the interaction between SCT and heparin. Our structural study paves the way toward the design of new molecules targeting these protein–GAG interactions with potential therapeutic applications. ; This work was funded by the European Union Seventh Framework Programme (FP7/2007–2013) under Project VISION, grant No. 304884, the Spanish Ministry of Science and Innovation/Spanish Research Agency (MCI/AEI/FEDER, RTI2018–096182-B-I00) and AGAUR (2017 SGR 208). ; Peer reviewed

Volume III of National Accounts of OECD Countries comprises Volume IIIa - Financial Accounts - Flows and Volume IIIb - Financial Balance Sheets - Stocks . In both volumes, data, based on the System of National Accounts (SNA 1993), are expressed in national currency (in euros for euro area countries). Volume IIIa covers financial accounts of OECD countries and includes financial transactions (both net acquisition of financial assets and net incurrence of liabilities), by institutional sector (non-financial corporations, financial corporations, general government, households and non-profit insti

"11 December 1978." ; Shipping list no.: 89-483-P. ; "Reprint which includes current pages from changes 1 and 2." ; Cover title. ; Includes bibliographical references. ; Mode of access: Internet. ; 14