NMR characterization of copper and lipid interactions of the C2B domain of synaptotagmin I—relevance to the non-classical secretion of the human acidic fibroblast growth factor (hFGF-1)

Human fibroblast growth factor (hFGF-1) is a ∼ 17 kDa heparin binding cytokine. It lacks the conventional hydrophobic N-terminal signal sequence and is secreted through non-classical secretion routes. Under stress, hFGF-1 is released as a multiprotein complex consisting of hFGF-1, S100A13 (a calcium binding protein), and p40 synaptotagmin (Syt1). Copper (Cu²⁺) is shown to be required for the formation of the multiprotein hFGF-1 release complex (Landriscina et al. ,2001; Di Serio et al., 2008). Syt1, containing the lipid binding C2B domain, is believed to play an important role in the eventual export of the hFGF-1 across the lipid bilayer. In this study, we characterize Cu²⁺ and lipid interactions of the C2B domain of Syt1 using multidimensional NMR spectroscopy. The results highlight how Cu²⁺ appears to stabilize the protein bound to pS vesicles. Cu²⁺ and lipid binding interface mapped using 2D ¹H-¹⁵N heteronuclear single quantum coherence experiments reveal that residues in β-strand I contributes to the unique Cu²⁺ binding site in the C2B domain. In the absence of metal ions, residues located in Loop II and β-strand IV contribute to binding to unilamelar pS vesicles. In the presence of Cu²⁺, additional residues located in Loops I and III appear to stabilize the protein-lipid interactions. The results of this study provide valuable information towards understanding the molecular mechanism of the Cu²⁺-induced non-classical secretion of hFGF-1.     

Energy Confinement in Self-Organized Tokamak Plasma (without Transport Barriers)

Plasma Physics Reports - The phenomenon of improved energy confinement during radiative cooling at the plasma edge was studied experimentally in the T-10 tokamak. It was shown that the effect is...     

Length-weight relationship of fish species captured around an artificial offshore reef (northern Rio de Janeiro,Brazil)

The present work provides length-weight relationships (LWRs) for fish species captured around artificial offshore reef deployed 5 km from Guaxindiba Port, northern Rio de Janeiro, Brazil. The fish were captured during two sampling periods each year between 1996 and 2017 using bottom gill nets (25 m_length × 3 m_depth; 30 mm mesh). The fish were kept on ice and the biometric data, including total length (cm) and total wet weight (g) were determined in the laboratory. A total of 16 species belonging to 10 families were analyzed with Sciaenidae being the species richest family (5 spp) in the samples. The new value of LWRs for Sphyraena guachancho and new maximum sizes recorded for seven species highlight the scarcity of information on biological aspects of South America coastal fishes. These LWRs should assist fisheries scientist and managers to complement their further studies of population parameters to improve management decisions.     

Cytotoxic Effects of the Selective Ligands of Membrane Progesterone Receptors in Human Pancreatic Adenocarcinoma Cells BxPC3

Biochemistry (Moscow) - Progesterone and its synthetic analogues act on cells through different types of receptors, affecting proliferation and apoptosis. These compounds exert their effect through...     

The Skeletal System as an Additional Storage System for Iodine Isotopes

Biophysics - Using the gamma-spectrometric method we found that the radioactive isotope 125I, when entering the body of a rat, actively accumulated not only in the thyroid gland, but also in the...     

An evolution-based high-fidelity method of epistasis measurement: Theory and application to influenza

Linkage effects in a multi-locus population strongly influence its evolution. The models based on the traveling wave approach enable us to predict the average speed of evolution and the statistics of phylogeny. However, predicting statistically the evolution of specific sites and pairs of sites in the multi-locus context remains a mathematical challenge. In particular, the effects of epistasis, the interaction of gene regions contributing to phenotype, is difficult to predict theoretically and detect experimentally in sequence data. A large number of false-positive interactions arises from stochastic linkage effects and indirect interactions, which mask true epistatic interactions. Here we develop a proof-of-principle method to filter out false-positive interactions. We start by demonstrating that the averaging of haplotype frequencies over multiple independent populations is necessary but not sufficient for epistatic detection, because it still leaves high numbers of false-positive interactions. To compensate for the residual stochastic noise, we develop a three-way haplotype method isolating true interactions. The fidelity of the method is confirmed analytically and on simulated genetic sequences evolved with a known epistatic network. The method is then applied to a large sequence database of neurominidase protein of influenza A H1N1 obtained from various geographic locations to infer the epistatic network responsible for the difference between the pre-pandemic virus and the pandemic strain of 2009. These results present a simple and reliable technique to measure epistatic interactions of any sign from sequence data.     

Molecular Beacon DNA Probes with Fluorescein Bifluorophore

Russian Journal of Bioorganic Chemistry - An azido-derivative of a fluorescein bifluorophore was obtained and used for the synthesis of “molecular beacon”-type oligonucleotide...     

Formation of an internal transport barrier and magnetohydrodynamic activity in experiments with the controlled density of rational magnetic surfaces in the T-10 Tokamak

Results are presented from experiments on the formation of an internal electron transport barrier near the q = 1.5 rational surface in the T-10 tokamak. The experiments were carried out in the regime with off-axis electron cyclotron resonance (ECR) heating followed by a fast plasma current ramp-up. After suppressing sawtooth oscillations by off-axis ECR heating, an internal transport barrier began to form near the q = 1.5 rational surface. In the phase of the current ramp-up, the quality of the transport barrier improved; as a result, the plasma energy confinement time increased 2–2.5 times. The intentionally produced flattening of the profile of the safety factor q(r) insignificantly affected magnetohydrodynamic activity in the plasma column in spite of the theoretical possibility of formation of substantial m/n = 3/2 and 2/1 magnetic islands. Conditions are discussed under which the flattening of the profile of the safety factor q near low-order rational surfaces leads to the formation of either an internal transport barrier or the development of an island magnetic structure induced by tearing modes.