Immunomodulatory Properties of Masticadienonic Acid and 3α-Hydroxy Masticadienoic Acid in Dendritic Cells

Dendritic cells are antigen-presenting cells, which identify and process pathogens to subsequently activate specific T lymphocytes. To regulate the immune responses, DCs have to mature by the recognition of TLR ligands, TNFα or IFNγ. These ligands have been used as adjuvants to activate DCs in situ or in vitro, with toxic effects. It has been shown that some molecules affect the immune system, e.g., Masticadienonic acid (MDA) and 3α-hydroxy masticadienoic acid (3α-OH MDA) triterpenes naturally occurring in several medicinal plants, since they activate the nitric oxide synthase in macrophages and induce T lymphocyte proliferation. The DCs maturation induced by MDA or 3a-OH MDA was determined by incubating these cells with MDA or 3α-OH MDA, and their phenotype was afterwards analyzed. The results showed that only 3α-OH MDA was able to induce DCs maturation. When mice with melanoma were inoculated with DCs/3α-OH MDA, a decreased tumor growth rate was observed along with an extended cell death area within tumors compared to mice treated with DCs incubated with MDA. In conclusion, it is proposed that 3α-OH MDA may be an immunostimulant molecule. Conversely, it is proposed that MDA may be a molecule with anti-inflammatory properties.     

Glass fragility and atomic ordering on the intermediate and extended range

The relation between the fragility of glass-forming systems, a parameter which describes many of their key physical characteristics, and atomic scale structure is investigated by using neutron diffraction to measure the topological and chemical ordering for germania, or GeO(2), which is an archetypal strong glass former. We find that the ordering for this and other tetrahedral network-forming glasses at distances greater than the nearest neighbor can be rationalized in terms of an interplay between the relative importance of two length scales. One of these is associated with an intermediate range, the other with an extended range and, with increasing glass fragility, it is the extended range ordering which dominates.     

Biophysical changes induced by cholesterol on phosphatidylcholine artificial biomembranes containing alamethicin oligomers

Cholesterol is an important constituent of eukaryotic cell membranes, whose interaction with phospholipids leads to a broad range of biological roles, such as: maintenance of proper fluidity, formation of raft domains, reduction of passive permeability of various chemical species through the bilayer (e.g., glucose, glycerol, K⁺, Na⁺ and Cl⁻ ions), and increased mechanical strength of the membrane. In this work we studied an interesting paradigm, as to whether cholesterol-containing phosphatidylcholine biomembranes influence the kinetics and transport features of alamethicin oligomers embedded into it. We demonstrate that moderate relative amounts of cholesterol increase the electrical conductance of various sub-conductance states of the alamethicin oligomer, caused probably by a non-monotonic change in the lumped dipole moment of the biomembrane. Our data suggest that biomembrane stiffness caused by cholesterol, visibly modifies the association-dissociation rates of alamethicin oligomerization in the biomembrane. Moreover, increasing concentrations of cholesterol seem to lead to more stable intermediate alamethicin oligomers. We show that in the presence of cholesterol, as the diameter of the alamethicin oligomer increases, so does the time of another monomer to get picked up. These results brings into focus the interesting issue of how oligomerization of proteins affects their interaction affinities for membrane-based lipids.     

Suppression of flavor symmetry breaking in B decay sum rules

While flavor symmetries are useful for studying hadronic B   decays, symmetry relations for amplitudes and decay rates are usually violated by first order symmetry breaking corrections. We point out two cases in which first order symmetry breaking is suppressed by a small ratio of amplitudes: (1) An isospin sum rule for four B→Kπ$B\to K\pi$ decays, where isospin breaking is shown to be negligible. (2) An SU(3)$\mathrm{SU}(3)$ sum rule for pairs of B→Kπ$B\to K\pi$ and B→Kη₈$B\to K{\eta }_8$, generalized to pairs of B→Kπ$B\to K\pi$, B→Kη$B\to K\eta$ and B→Kη^′$B\to K{\eta }^{\prime }$.     

Simultaneous estimation of attenuation and structure parameters of aggregated red blood cells from backscatter measurements

The analysis of the ultrasonic frequency-dependent backscatter coefficient of aggregating red blood cells reveals information about blood structural properties. The difficulty in applying this technique in vivo is due to the frequency-dependent attenuation caused by intervening tissue layers that distorts the spectral content of backscattering properties from blood microstructures. An optimization method is proposed to simultaneously estimate tissue attenuation and blood structure factor. With in vitro experiments, the method gave satisfactory estimates with relative errors below 22% for attenuations between 0.101 and 0.317 dBcmMHz, signal-to-noise ratios>28 dB and kR<2.7 (k being the wave number and R the aggregate radius).     

A short proof of Gowers’ lower bound for the regularity lemma

A celebrated result of Gowers states that for every ?>0 there is a graph G such that every ?-regular partition of G (in the sense of Szemerédi’s regularity lemma) has order given by a tower of exponents of height polynomial in 1/?. In this note we give a new proof of this result that uses a construction and proof of correctness that are significantly simpler and shorter.     

Radical–anion coupling through reagent design: hydroxylation of aryl halides

The design and development of an oxime-based hydroxylation reagent, which can chemoselectively convert aryl halides (X = F, Cl, Br, I) into phenols under operationally simple, transition-metal-free conditions is described. Key to the success of this approach was the identification of a reducing oxime anion which can interact and couple with open-shell aryl radicals. Experimental and computational studies support the proposed radical-nucleophilic substitution chain mechanism.

The design and development of an oxime-based hydroxylation reagent, which can chemoselectively convert aryl halides (X = F, Cl, Br, I) into phenols under operationally simple, transition-metal-free conditions is described.     

Structural basis for specific, high-affinity tetracycline binding by an in vitro evolved aptamer and artificial riboswitch

The tetracycline aptamer is an in vitro selected RNA that binds to the antibiotic with the highest known affinity of an artificial RNA for a small molecule (Kd approximately 0.8 nM). It is one of few aptamers known to be capable of modulating gene expression in vivo. The 2.2 A resolution cocrystal structure of the aptamer reveals a pseudoknot-like fold formed by tertiary interactions between an 11 nucleotide loop and the minor groove of an irregular helix. Tetracycline binds within this interface as a magnesium ion chelate. The structure, together with previous biochemical and biophysical data, indicates that the aptamer undergoes localized folding concomitant with tetracycline binding. The three-helix junction, h-shaped architecture of this artificial RNA is more complex than those of most aptamers and is reminiscent of the structures of some natural riboswitches.     

Exchange frequency in replica exchange molecular dynamics

The effect of the exchange-attempt frequency on sampling efficiency is studied in replica exchange molecular dynamics (REMD). We show that sampling efficiency increases with increasing exchange-attempt frequency. This conclusion is contrary to a commonly expressed view in REMD. Five peptides (1-21 residues long) are studied with a spectrum of exchange-attempt rates. Convergence rates are gauged by comparing ensemble properties between fixed length test REMD simulations and longer reference simulations. To show the fundamental correlation between exchange frequency and convergence time, a simple model is designed and studied, displaying the same basic behavior of much more complex systems.     

Vibrational analysis of amino acids and short peptides in hydrated media. 3. Successive KL repeats induce highly stable beta-strands capable of forming non-H-bonded aggregates

Circular dichroism (CD) and Raman scattering were applied to the aqueous solution of minimalist LK peptides constructed with successive KL repeats leading to the following generic primary sequence: (KL)nK. Three peptides of this family, a 3-mer (n=1), a 9-mer (n=4), and a 15-mer (n=7), are analyzed in this report. Raman spectra of the 3-mer (KLK, a random chain) and its labile-hydrogen deuterated species yield a set of interesting information for analyzing longer peptides of this series. Although the CD spectrum of the 9-mer (KLKLKLKLK) reveals a signal traditionally assigned to a random structure, the corresponding Raman spectrum allows finding a mixture of conformations in solution, adopting predominantly beta-type structures. This fact proves the utility of Raman spectroscopy to eliminate eventual ambiguity concerning conformational assignments in peptides based only on the use of CD technique. Finally, the 15-mer (KLKLKLKLKLKLKLK) gives rise to CD and Raman spectra clearly assignable to a beta-type structure. On the basis of all the observed results on the 15-mer, we can confirm that this peptide may exist as isolated beta-strands at low concentration (sub-micromolar), flat-oriented at the air/water interface, whereas at high concentrations (millimolar), non-H-bonded immersible aggregates might be formed. A hypothetical model for these beta-strand aggregates could be proposed as stabilized by an interior hydrophobic core and a hydrophilic external face, formed by leucine and lysine side chains, respectively.