Molecular flexibility of citrus pectins by combined sedimentation and viscosity analysis

The flexibility/rigidity of pectins plays an important part in their structure-function relationship and therefore on their commercial applications in the food and biomedical industries. Earlier studies based on sedimentation analysis in the ultracentrifuge have focused on molecular weight distributions and qualitative and semi-quantitative descriptions based on power law and Wales-van Holde treatments of conformation in terms of "extended" conformations [Harding, S. E., Berth, G., Ball, A., Mitchell, J.R., & Garcìa de la Torre, J. (1991). The molecular weight distribution and conformation of citrus pectins in solution studied by hydrodynamics. Carbohydrate Polymers, 168, 1-15; Morris, G. A., Foster, T. J., & Harding, S.E. (2000). The effect of degree of esterification on the hydrodynamic properties of citrus pectin. Food Hydrocolloids, 14, 227-235]. In the present study, four pectins of low degree of esterification 17-27% and one of high degree of esterification (70%) were characterised in aqueous solution (0.1 M NaCl) in terms of intrinsic viscosity [η], sedimentation coefficient (s°20,w) and weight average molar mass (Mw). Solution conformation/flexibility was estimated qualitatively using the conformation zoning method [Pavlov, G.M., Rowe, A.J., & Harding, S.E. (1997). Conformation zoning of large molecules using the analytical ultracentrifuge. Trends in Analytical Chemistry, 16, 401-405] and quantitatively (persistence length Lp) using the traditional Bohdanecky and Yamakawa-Fujii relations combined together by minimisation of a target function. Sedimentation conformation zoning showed an extended coil (Type C) conformation and persistence lengths all within the range Lp=10-13 nm (for a fixed mass per unit length)

Molecular analysis of hepatitis C virus infection in Bulgarian injecting drug users

Intravenous drug users constitute a group at risk for hepatitis C virus (HCV) infection. Today, no data are available on the molecular epidemiology of HCV in Bulgaria despite the fact that in recent years the incidence of acute hepatitis C infection among Bulgarian intravenous drug users increased sixfold and about 2/3 of them developed a chronic infection. The aim of this study was to determine the circulation of hepatitis C genotypes among drug users and to study the evolution and transmission history of the virus by molecular clock and Bayesian methods, respectively. Sequencing of NS5B gene showed that the genotype 3a was the most prevalent type among intravenous drug users. In the Bayesian tree, the 3a subtypes grouped in one main clade with one small cluster well statistically supported. The root of the tree was dated back to the year 1836, and the main clade from Bulgaria was dated 1960. The effective number of infections remained constant until about years 1950s, growing exponentially from the 1960s to the 1990s, reaching a plateau in the years 2000. The not significant intermixing with isolates from other countries may suggest a segregated circulation of the epidemic between 1940s and 1980s. The plateau reached by the epidemic in the early 2000s may indicate the partial success of the new preventive policies adopted in Bulgaria. J. Med. Virol. 83:1565-1570, 2011. © 2011 Wiley-Liss, Inc

The effect of cryopreservation in liquid nitrogen on the viability of flax seeds

Background. A promising technique for preserving plant genetic resources is cryopreservation of seeds in liquid nitrogen at –196°C. The lack of information on cryopreservation of flax seeds and on the effect of liquid nitrogen on their viability makes this work relevant for the conservation of valuable flax germplasm.Materials and methods. Seeds of the fiber flax cultivar ‘Orshansky 2’ were used in the experiment. The experiment was carried out in 2 replications; each of them included 6 options. In options 1 and 2, the seeds were stored in paper bags at room temperature (1 – control, seeds without treatment; 2 – treated with a biodegradable polymer of 3-hydroxybutyric acid [P(3GB)]). In options 3, 4, 5 and 6, the seeds were stored in liquid nitrogen without treatment and with P(3GB) treatment (in 3 and 4 in gauze packaging, and in 5 and 6 in laminated foil bags).Results. Laboratory-based germination energy and viability of control seeds were the same in all options of the experiment (99%), and field viability averaged 83%. The lowest germination energy, laboratory-based and field germination capacity were observed after storage in laminated bags, without P(3HB) processing: option 5. stage II (79%); option 5, stage III (74%), and with P(3HB): processing: option 6, stage II (78%); option 6, stage III (82%). A two-factor analysis of variance showed that liquid nitrogen had significant effect on laboratory germination energy, field germination capacity, laboratory germination energy and capacity after 6 months of storage at room temperature: the effect size was 42, 11, 31, and 24%, respectively, while treatment with P(3HB) had no significant effect on any of the options of the experiment with its application.Conclusion. Flax seeds tolerated direct immersion in liquid nitrogen (t = –196°C) best of all in gauze packaging. The biodegradable polymer P(3HB) did not produce a significant effect on seed viability in any option

Helium in superstrong magnetic fields

We investigate the helium atom embedded in a superstrong magnetic field gamma=100-10000 au. All effects due to the finite nuclear mass for vanishing pseudomomentum are taken into account. The influence and the magnitude of the different finite mass effects are analyzed and discussed. Within our full configuration interaction approach calculations are performed for the magnetic quantum numbers M=0,-1,-2,-3, singlet and triplet states, as well as positive and negative z parities. Up to six excited states for each symmetry are studied. With increasing field strength the number of bound states decreases rapidly and we remain with a comparatively small number of bound states for gamma=10^4 au within the symmetries investigated here.Comment: 16 pages, including 14 eps figures, submitted to Phys. Rev.

Tailoring spontaneous infrared emission of HgTe quantum dots with laser-printed plasmonic arrays.

Chemically synthesized near-infrared to mid-infrared (IR) colloidal quantum dots (QDs) offer a promising platform for the realization of devices including emitters, detectors, security, and sensor systems. However, at longer wavelengths, the quantum yield of such QDs decreases as the radiative emission rate drops following Fermi's golden rule, while non-radiative recombination channels compete with light emission. Control over the radiative and non-radiative channels of the IR-emitting QDs is crucially important to improve the performance of IR-range devices. Here, we demonstrate strong enhancement of the spontaneous emission rate of near- to mid-IR HgTe QDs coupled to periodically arranged plasmonic nanoantennas, in the form of nanobumps, produced on the surface of glass-supported Au films via ablation-free direct femtosecond laser printing. The enhancement is achieved by simultaneous radiative coupling of the emission that spectrally matches the first-order lattice resonance of the arrays, as well as more efficient photoluminescence excitation provided by coupling of the pump radiation to the local surface plasmon resonances of the isolated nanoantennas. Moreover, coupling of the HgTe QDs to the lattice plasmons reduces the influence of non-radiative decay losses mediated by the formation of polarons formed between QD surface-trapped carriers and the IR absorption bands of dodecanethiol used as a ligand on the QDs, allowing us to improve the shape of the emission spectrum through a reduction in the spectral dip related to this ligand coupling. Considering the ease of the chemical synthesis and processing of the HgTe QDs combined with the scalability of the direct laser fabrication of nanoantennas with tailored plasmonic responses, our results provide an important step towards the design of IR-range devices for various applications

ISO-1 Binding to the Tautomerase Active Site of MIF Inhibits Its Pro-inflammatory Activity and Increases Survival in Severe Sepsis

MIF is a proinflammatory cytokine that has been implicated in the pathogenesis of sepsis, arthritis, and other inflammatory diseases. Antibodies against MIF are effective in experimental models of inflammation, and there is interest in strategies to inhibit its deleterious cytokine activities. Here we identify a mechanism of inhibiting MIF pro-inflammatory activities by targeting MIF tautomerase activity. We designed small molecules to inhibit this tautomerase activity; a lead molecule, "ISO-1 ((S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester)," significantly inhibits the cytokine activity in vitro. Moreover, ISO-1 inhibits tumor necrosis factor release from macrophages isolated from LPStreated wild type mice but has no effect on cytokine release from MIFdeficient macrophages. The therapeutic importance of the MIF inhibition by ISO-1 is demonstrated by the significant protection from sepsis, induced by cecal ligation and puncture in a clinically relevant time frame. These results identify ISO-1 as the first small molecule inhibitor of MIF proinflammatory activities with therapeutic implications and indicate the potential of the MIF active site as a novel target for therapeutic interventions in human sepsis

Forebrain Cholinergic Signaling Regulates Innate Immune Responses and Inflammation

The brain regulates physiological functions integral to survival. However, the insight into brain neuronal regulation of peripheral immune function and the neuromediator systems and pathways involved remains limited. Here, utilizing selective genetic and pharmacological approaches, we studied the role of forebrain cholinergic signaling in the regulation of peripheral immune function and inflammation. Forebrain-selective genetic ablation of acetylcholine release and vagotomy abolished the suppression of serum TNF by the centrally-acting cholinergic drug galantamine in murine endotoxemia. Selective stimulation of acetylcholine action on the M1 muscarinic acetylcholine receptor (M1 mAChR) by central administration of the positive allosteric modulator benzyl quinolone carboxylic acid (BQCA) suppressed serum TNF (TNF alpha) levels in murine endotoxemia. This effect was recapitulated by peripheral administration of the compound. BQCA also improved survival in murine endotoxemia and these effects were abolished in M1 mAChR knockout (KO) mice. Selective optogenetic stimulation of basal forebrain cholinergic neurons innervating brain regions with abundant M1 mAChR localization reduced serum TNF in endotoxemic mice. These findings reveal that forebrain cholinergic neurons regulate innate immune responses and inflammation, suggesting the possibility that in diseases associated with cholinergic dysfunction, including Alzheimer\u27s disease this anti-inflammatory regulation can be impaired. These results also suggest novel anti-inflammatory approaches based on targeting forebrain cholinergic signaling in sepsis and other disorders characterized by immune dysregulation

First IXPE Observations of the Accreting X-ray Pulsar Her X-1

Theoretical models for the X-ray emission of accretion-powered pulsars predict a high degree and a strong spin-phase dependence of the X-ray polarization. Using observations of the Imaging X-ray Polarimetry Explorer of the accreting pulsar Her X-1, we were able to test these predictions for the first time ever

Mismatch Repair–Independent Increase in Spontaneous Mutagenesis in Yeast Lacking Non-Essential Subunits of DNA Polymerase ε

Yeast DNA polymerase ε (Pol ε) is a highly accurate and processive enzyme that participates in nuclear DNA replication of the leading strand template. In addition to a large subunit (Pol2) harboring the polymerase and proofreading exonuclease active sites, Pol ε also has one essential subunit (Dpb2) and two smaller, non-essential subunits (Dpb3 and Dpb4) whose functions are not fully understood. To probe the functions of Dpb3 and Dpb4, here we investigate the consequences of their absence on the biochemical properties of Pol ε in vitro and on genome stability in vivo. The fidelity of DNA synthesis in vitro by purified Pol2/Dpb2, i.e. lacking Dpb3 and Dpb4, is comparable to the four-subunit Pol ε holoenzyme. Nonetheless, deletion of DPB3 and DPB4 elevates spontaneous frameshift and base substitution rates in vivo, to the same extent as the loss of Pol ε proofreading activity in a pol2-4 strain. In contrast to pol2-4, however, the dpb3Δdpb4Δ does not lead to a synergistic increase of mutation rates with defects in DNA mismatch repair. The increased mutation rate in dpb3Δdpb4Δ strains is partly dependent on REV3, as well as the proofreading capacity of Pol δ. Finally, biochemical studies demonstrate that the absence of Dpb3 and Dpb4 destabilizes the interaction between Pol ε and the template DNA during processive DNA synthesis and during processive 3′ to 5′exonucleolytic degradation of DNA. Collectively, these data suggest a model wherein Dpb3 and Dpb4 do not directly influence replication fidelity per se, but rather contribute to normal replication fork progression. In their absence, a defective replisome may more frequently leave gaps on the leading strand that are eventually filled by Pol ζ or Pol δ, in a post-replication process that generates errors not corrected by the DNA mismatch repair system