Ionic interaction of the HIV-1 V3 domain with CCR5 and deregulation of T lymphocyte function

We have reported that the principal neutralizing domain of V3 of the HIV-1 gp120 induces an antigen-specific activation apoptosis of responding effector CD4+ T lymphocytes, a phenomenon inhibited by RANTES, an agonist of CCR5. Here, addressing the question of how a hypervariable region could induce such a selective reaction, we demonstrated that the magnitude of the activation phase was dependent on the number of basic amino acids present in the V3 peptide, an observation confirmed by using V3 peptides with appropriate basic amino acid substitutions. The relative position of the amino acids in the V3 peptide did not affect the biological phenomenon. Using surface plasmon resonance biosensor analysis, we also provided direct evidence of the influence of basic amino acids in the interaction between V3 and the amino terminal domain of CCR5. Sulphation of tyrosines in the CCR5 peptide was essential. Our results confirm gp120 modelling predictions and demonstrate simple molecular ionic interactions as capable of affecting key cell events, the wider biological implications of which need to be further explored.     

Identification of gene variants in NOS3, ET-1 and RAS that confer risk and protection against microangiopathy in type 2 diabetic obese subjects

The study aim was to investigate NOS3 VNTR, NOS3 G894T, EDN1 C8002T, ACE I/D, AGT M235T and AGTR1 A1166C in nonobese and obese T2DM patients, and their interaction with the incidence of microangiopathy. T2DM subjects (n = 250; 166 nonobese, and 84 obese) were genotyped for the gene variants by PCR/RFLP. The interaction of these polymorphisms with obesity and their contribution to microangiopathy were analyzed by multivariate regression analysis. A higher frequency of NOS3 4a allele was found in obese (P = 0.027) vs. nonobese subjects. ACE D (P = 0.009) and AGT 235T (P = 0.026) alleles were associated with the reduced risk of diabetic nephropathy in nonobese and obese patients, respectively. In obese subjects, NOS3 4a (P = 0.011) had a converse effect to NOS3 894T (P = 0.043), and EDN1 8002T (P = 0.035) on the prevalence of combined microangiopathy (neuropathy/retinopathy/nephropathy) vs. microangiopathy-negative subjects. The study indicates association of RAS variants with obesity and nephropathy, and an opposite effect of NOS3 VNTR and NOS3 G894T on the occurrence of combined microangiopathy.     

Functional Interactions between BM88/Cend1, Ran-Binding Protein M and Dyrk1B Kinase Affect Cyclin D1 Levels and Cell Cycle Progression/Exit in Mouse Neuroblastoma Cells

BM88/Cend1 is a neuronal-lineage specific modulator with a pivotal role in coordination of cell cycle exit and differentiation of neuronal precursors. In the current study we identified the signal transduction scaffolding protein Ran-binding protein M (RanBPM) as a BM88/Cend1 binding partner and showed that BM88/Cend1, RanBPM and the dual specificity tyrosine-phosphorylation regulated kinase 1B (Dyrk1B) are expressed in mouse brain as well as in cultured embryonic cortical neurons while RanBPM can form complexes with either of the two other proteins. To elucidate a potential mechanism involving BM88/Cend1, RanBPM and Dyrk1B in cell cycle progression/exit, we transiently co-expressed these proteins in mouse neuroblastoma Neuro 2a cells. We found that the BM88/Cend1-dependent or Dyrk1B-dependent down-regulation of cyclin D1 is reversed following their functional interaction with RanBPM. More specifically, functional interaction of RanBPM with either BM88/Cend1 or Dyrk1B stabilizes cyclin D1 in the nucleus and promotes 5-bromo-2''-deoxyuridine (BrdU) incorporation as a measure of enhanced cell proliferation. However, the RanBPM-dependent Dyrk1B cytosolic retention and degradation is reverted in the presence of Cend1 resulting in cyclin D1 destabilization. Co-expression of RanBPM with either BM88/Cend1 or Dyrk1B also had a negative effect on Neuro 2a cell differentiation. Our results suggest that functional interactions between BM88/Cend1, RanBPM and Dyrk1B affect the balance between cellular proliferation and differentiation in Neuro 2a cells and indicate that a potentially similar mechanism may influence cell cycle progression/exit and differentiation of neuronal precursors.     

Enantioanalysis of Pipecolic Acid with Stochastic and Potentiometric Microsensors

Stochastic and potentiometric microsensors based on porphyrins and polymeric surfactants such as polysodium N‐undecanoyl‐ l ‐leucylvanilate and polysodium 相似文献   

Evidence for cellular uptake of recombinant hepatitis C virus non-enveloped capsid-like particles

Although the hepatitis C virus (HCV) is an enveloped virus, naked nucleocapsids have been reported in the serum of infected patients, and most recently novel HCV subgenomes with deletions of the envelope proteins have been identified. However the significance of these findings remains unclear. In this study, we used the baculovirus expression system to generate recombinant HCV capsid-like particles, and investigated their possible interactions with cells. We show that expression of HCV core in insect cells can sufficiently direct the formation of capsid-like particles in the absence of the HCV envelope glycoproteins and of the 5' untranslated region. By confocal microscopy analysis, we provide evidence that the naked capsid-like particles could be uptaken by human hepatoma cells. Moreover, our findings suggest that they have the potential to produce cell-signaling effects.     

A rare all-Mn decametallic cage from distorted face-sharing cubes

The preparation and crystal structure of a decametallic Mn^II carboxylate cluster containing neutral 2-pyridinealdoxime, (py)C(H)NOH, and its anion, (py)C(H)NO⁻, is reported. The reaction between Mn(O₂CPh)₂ · 2H₂O and (py)C(H)NOH in CH₂Cl₂, in the presence of NH₄PF₆, produces the complex [Mn₁₀(O₂CPh)₁₂{(py)C(H)CNO}₆{(py)C(H)NOH}₂](PF₆)₂ · 2.6CH₂Cl₂ · 1.3H₂O (1 · 2.6CH₂Cl₂ · 1.3H₂O) in good yield. The cationic complex consists of ten Mn^II ions assembled together by four η¹:η¹:η³:μ₄ and two η¹:η¹:η²:μ₃ oximato(−1) ligands, and four η¹:η²:μ₃ ligands to form an unprecedented core, where R = PhCO and R′ = (py)C(H)N. Peripheral ligation is provided by a combination of bridging benzoates and chelating (py)C(H)NOH ligands. Dc magnetic susceptibility studies reveal the presence of dominant antiferromagnetic interactions leading to a spin ground-state of S_T = 0. A survey of the ternary reaction system is attempted with comparisons to previously reported complexes.     

Sorption Behavior of Cesium in Two Greek Soils: Effects of Cs Initial Concentration,Clay Mineralogy,and Particle-size Fraction

The characteristics of Cs sorption behavior in two soils (soil 1 and soil 2) with nearly the same clay content and exhangeable K concentration, but with different clay mineralogy, were studied by the quantification of the distribution coefficient (k_d). It was observed that as the initial Cs concentration increased from 4 to 50 mg L^?1, the k_d values decreased in both soils, suggesting a progressive saturation of Cs available sorption sites. However, the presence of expansible 2:1 phyllosilicates minerals in the clay fraction of soil 2 maintained a high Cs sorption ability for this soil, even at high Cs concentrations. The experimental data were also fitted to the Freundlich isotherm and the results showed that parameters of the Freundlich equation could be used to estimate the degree of Cs sorption and the nature of the available sorption sites. For the studied soils, the k_f and the k_d values followed a similar trend and the n Freundlich constant values provided a reliable indicator for the soils’ clay mineralogy. The removal of the sand fraction enhanced Cs sorption in both soils and the absence of sorbed Cs ions on the quartz minerals, as observed by the SEM analysis, additionally supported the effect of particle-size fraction on Cs sorption.